Anda di halaman 1dari 1417

Arranged by:

Dr. Fouad Shamsan

The contents is according to:

Bailey's Head and Neck Surgery - Otolaryngology (2001)

Cumming's Otolaryngology - Head and Neck Surgery (1999)

The arrangement is according to :

Bailey's Head and Neck Surgery - Otolaryngology (2006)


Table of Contents
I Basic Science & General Medicine:
1- Antimicrobial Therapy …………………………………………………………………………………………..1
2- Microbiology, Infections, & Antibiotic Therapy……………………………………………………..4
3- Degenerative & Idiopathic Diseases………………………………………………………………………7
4- Connective Tissue Diseases…………………………………………………………………………………14
5- Granulomatous Diseases of Head & Neck…………………………………………………………..17
6- Geriatric Otolaryngology…………………………………………………………………………………..…25
7- Headache & Facial Pain……………………………………………………………………………………….28
8- Manifestation of AIDS…………………………………………………………………………………………31
9- Principle Of Surgery (POS) 69 Notes………………………………………………………………..…35
10- Pathology Review ……………………………………………………………………………………………….40
11- Selected Pharmacopia………………………………………………………………………………………..49
12- POS Systemic Response to Injury………………………………………………………………………..56
13- POS Fluid & Electrolyte Management of Surgical patient……………………………………73
14- POS Hemostasis, Surgical Bleeding & Transfusion……………………….74
15- POS Shock…………………………………………………………………………………………………………...92
16- POS Surgical Infections……………………………………………………………………………………….99
17- POS Burns………………………………………………………………………………………………………….108
18- POS Wound Care & Wound Healing…………………………………………………………………125
19- POS Transplantation…………………………………………………………………………………………134
20- POS Surgical complications………………………………………………………………………………163
21- Physiologic Monitoring of Surgical Patient………………………………………………………183
22- POS Notes & Points from Previous Exams……………………………………………………….190
23- Radiotherapy……………………………………………………………………………………………………208

II Rhinology & Allergy:


24- Antimicrobial Guidelines for Acute bacterial Rhinosinusitis………………………….209
25- Olfactory Function & Dysfunction………………………………………………………………….211
26- Nasal Function & Evaluation……………………………………………………………………….….214
27- Sinus Anatomy & Function…………………………………………………………………………….218
28- Nose & Paranasal Sinuses………………………………………………………………………………225
29- Secrets- Nasal Septal Abnormalities………………………………………………………………232
30- Nonallergic Rhinitis………………………………………………………………………………………..233
31- Allergic Rhinosinusitis……………………………………………………………………………………239
32- Nasal Obstruction………………………………………………………………………………………….243
33- Sinus Surgery – External Approach………………………………………………………………..248
34- Midline Nasal Masses……………………………………………………………………………………251
35- Sinus Imaging………………………………………………………………………………………………….258
36- Rhinosinusitis- Current Concept & Management………………………………………….262
37- Endoscopic Sinus Surgery……………………………………………………………………………..272
38- Approaches to Sphenoid Sinuses…………………………………………………………………276
39- Sphenoid Sinus Diseases……………………………………………….…………………………….281
40- Complications of Sinus Surgery……………………………………………………………………284
41- Epistaxis………………………………………………………………………………………………………..289
42- Cumming's- Manifestation of Systemic Diseases of Nose…………………………..295
43- Cumming's- CSF Leaks…………………………………………………………………………………300
44- Pediatric Rhinosinusitis……………………………………………………………………………….306
45- Congenital Malformation of the Nose…………………………………………………………310
46- Juvenile Nasopharyngeal Angiofibroama…………………………………………………….314
47- Limmiere Syndrome……………………………………………………………………………………317
48- Medical Management of Acute Bacterial Sinusits……………………………………..318
49- Mucoceles of the Paransal Sinuses……………………………………………………………..321
50- Radiation induced Sarcoma…………………………………………………………………………336
51- Secrets-Anatomy & Physiology of the Nose………………………………………………..338
52- Secrets- Rhinitis …………………………………………………………………………………………..339

III General Otolaryngology:


53- Cervical Fascia & Spaces……………………………………………………………………………….340
54- Anatomy & Physiology of Salivary Glands…………………………………………………….346
55- Salivary Glands Imaging………………………………………………………………………………….350
56- Nonneoplastic Diseases of the Salivary Glands……………………………………………..355
57- Controversies of Salivary Gland Diseases ……………………………………………………..359
58- Taste……………………………………………………………………………………………………………….361
59- Stomatitis……………………………………………………………………………………………………….364
60- Pharyngitsis…………………………………………………………………………………………….........373
61- Odontogenic Infections…………………………………………………………………………………377
62- TMJ Disorders……………………………………………………………………………………………….382
63- Snoring & OSA………………………………………………………………………………………………..386
64- Deep Neck Infection……………………………………………………………………………………..393
65- Neck………………………………………………………………………………………………………………400
66- Salivary Glands……………………………………………………………………………………………...406
67- Secrets- ENT Manifestation of AIDS……………………………………………………………..408

IV Airway & Swallowing:


68- Bronchosopy & Esophagoscopy…………………………………………………………………..409
69- Upper Digestive Tract Anatomy & Physiology…………………………………………….410
70- Upper Airway Anatomy & Function…………………………………………………………….413
71- Upper Digestive Tract Evaluation & Imaging……………………………………………….417
72- Airway Evaluation & Imaging………………………………………………………………………..419
73- Esophageal Disorders…………………………………………………………………………………421
74- Tracheotomy & Intubation…………………………………………………………………………429
75- Controversies in Upper Airway Obstruction ………………………………………………433
76- Management of Intractable Aspiration………………………………………………………435
77- Evaluation of Dysphonic Patient………………………………………………………………….439
78- Oral Cavity & Pharynx…………………………………………………………………………………..441

V Voice:
79- Alaryngeal Speech…………………………………………………………………………………………….443
80- Laryngitis……………………………………………………………………………………………………………446
81- Hoarseness & VC Paralysis………………………………………………………………………………..451
82- Benign Lesion of the Larynx……………………………………………………………………………...458
83- Controversies in Laryngology……………………………………………………………………………462
84- Cumming's- Larynx Anatomy……………………………………………………………………………..465
85- Cumming's- Electromyogaraphy of Latyngeal & Pharyngeal Muscles……………….470
86- Cumming's- Laryngeal & Pharyngeal Function…………………………………………………..472
87- Cumming's- Neurological Evaluation of Larynx & Pharynx………………………………..478
88- Cumming's- Phonosurgical Procedures……………………………………………………………..483
89- Cumming's- Benign Vocal Fold Disorders…………………………………………………………..488
90- Cumming's- Laser Surgery in Larynx……………………………………………………………………496
91- Voice Rehabilitation after Laryngectomy………………………………………………………….…499
92- Glottic & Subglottic Stenosis……………………………………………………………………………….502
93- Laryngeal Development………………………………………………………………………………………504
94- Larynx…………………………………………………………………………………………………………………..509

VI Trauma:
95- Auricular Trauma Salvage……………………………………………………………………………………512
96- Facial Trauma………………………………………………………………………………………………………514
97- Auricular Trauma…………………………………………………………………………………………………519
98- Laryngeal Trauma…………………………………………………………………………………………………521
99- Management of Soft Tissue Trauma……………………………………………………………………525
100- Mandibular Fractures……………………………………………………………………………..528
101- Maxillary & Periorbital Fractures……………………………………………………………534
102- Fractures of Nasal & Frontal Sinuses………………………………………………………541
103- Penetrating Face & Neck Trauma…………………………………………………………….548
104- Complex Facial Trauma with Plating…………………………………………………………552
105- POS- Trauma……………………………………………………………………………………………..554

VII Pediatric Otolaryngology:


106- Airway Imaging in Children……………………………………………………………………….569
107- Pediatric Sleep Disordered Breathing………………………………………………………571
108- Laryngeal Stenosis……………………………………………………………………………………573
109- Stridor, Aspiration & Cough……………………………………………………………………..578
110- Causatic Ingestion & FB in the Aerodigestive Tract…………………………………584
111- Congenital Neck Masses & Cysts……………………………………………………………..588
112- Congenital Anomalies of the Nose……………………………………………………………593
113- Cleft Lip & Palate………………………………………………………………………………………597
114- Tonsillitis, Tonsillectomy & Adenoidectomy…………………………………………….601
115- Contarvorsies in Tonsillectomy, Adenoidectom & T-tubes………………………606
116- RCTsin Tonsillectomy, Ad, & T-tubes………………………………………………………..608
117- Congenital Anomalies of Aerodigestive Tract………………………………………….609
118- Neonatal Respiratory Disorders……………………………………………………………….613
119- Recurrent Respiratory Papillomatosis………………………………………………………614
120- The Syndromal Child…………………………………………………………………………………618
121- Pediatric Malignancies……………………………………………………………………………..621
122- Otitis Media with Effusion ……………………………………………………………………….627
123- Genetic Hearing Loss…………………………………………………………………………………631
124- Pediatric Audiology…………………………………………………………………………………...636
125- Pediatric Facial Fractures………………………………………………………………………….639
126- Congenital Vascular Lesion………………………………………………………………………643
127- Embryology of Face Lip & Palate………………………………………………………………646
128- ENT Problems in Syndromic Child…………………………………………………………….650
129- Eustachian Tube………………………………………………………………………………………..663
130- Cleft Palate Repaire…………………………………………………………………………………..669
131- Non Genetic HL………………………………………………………………………………………….672
132- Pediatric Taracheotomy Decanulation………………………………………………………675
133- SNHL Evaluation…………………………………………………………………………………………676
134- Tonsils & Adenoid……………………………………………………………………………………..678

VIII Head & Neck Surgery:


135- Carotid Body Tumors………………………………………………………………………………. 737
136- Cumming's- Hemangioma & Vascular Anomalies of H & N ……………….......743
137- Cumming's- Malignant Lesion of Oral Cavity……………………………………………749
138- Principle of Chemotherapy………………………………………………………………………753
139- Principle of Radiation Oncology……………………………………………………………….758
140- Cutaneous Malignancies………………………………………………………………………….764
141- Malignant Melanoma……………………………………………………………………………….772
142- Neoplasm of Nose & PNS………………………………………………………………………….778
143- Orbital Tumors……………………………………………………………………………………………788
144- Salivary Glands Neoplasm………………………………………………………………………….795
145- Lip Cancers………………………………………………………………………………………………….805
146- Neoplasm of Oral Cavity…………………………………………………………………………..…811
147- Odontogenic Cysts, Tumors, & Related Jaw Lesions…………………………………..818
148- Head & Neck Dissection…………………………………………………………………………...…825
149- Controversies in Management of N0 Neck………………………………………………….834
150- Cumming's- Malignant Tumors of Larynx & Hypopharynx…………………………..838
151- Lymphoma of the Head & Neck…………………………………………………………………..842
152- Thyroid Diseases & Surgery………………………………………………………………………….847
153- Parathyroid Diseases & Surgery……………………………………………………………………859
154- Nasophryngeal Carcinoma……………………………………………………………………………864
155- Oropharyngeal Cancers…………………………………………………………………………………870
156- Hypopharyngeal Cancers………………………………………………………………………………875
157- Cervical Esophageal Cancers………………………………………………………………………880
158- Early Glottic Carcinoma………………………………………………………………………….……884
159- Early Supraglottic Carcinoma………………………………………………………………………888
160- Early Glottic & Supraglottic Carcinoma……………………………………………………….891
161- Advance Cancer of Larynx………………………………………………………………………….893
162- Tracheal Tumors…………………………………………………………………………………………900
163- Vascular Tumors………………………………………………………………………………………….903
164- Cranial Base Surgery…………………………………………………………………………………...911
165- Surgical Techniqu to Enhance Prosthetic Rehabilitation…………………………….926
166- Cut. Malig. Merk Cell Carcinoma………………………………………………………………...929
167- Neck Cancers – Unknown Primary………………………………………………………………931
168- Osteoradionecrosis & Hyperbaric Oxygen Therapy…………………………………….933
169- TNM Staging of Head & Neck Tumors…………………………………………………………935
170- Tracheal Resection……………………………………………………………………………………..948
171- Treatments Outcomes………………………………………………………………………………..949
172- Velopharyngeal Insufficiency………………………………………………………………………954

IX Otology:
173- Audiological Tests………………………………………………………………………………………958
174- Cumming's – Tympanostomy Tubes…………………………………………………………..962
175- Development of Ear …………………………………………………………………………………..965
176- Anatomy & Physiology of Hearing………………………………………………………………971
177- Vestibular Function & Anatomy…………………………………………………………………977
178- Balance Function Tests……………………………………………………………………………….981
179- Audiotary Assesment………………………………………………………………………………….986
180- Cumming's – Temporal Bone Anatomy………………………………………………………994
181- Neurophysiologic Intraoperative Monitoring……………………………………………1006
182- Imaging Studies of Temporal Bone1…………………………………………………………1009
183- Imaging Studies of Temporal Bone2…………………………………………………………1015
184- Imaging Studies of Temporal Bone.…………………………………………………………..1020
185- Infections of the External Ear…………………………………………………………………….1031
186- Neoplasm of the Ear & Lateral Skull Base………………………………………………….1037
187- Congenital Aural Atresia…………………………………………………………………………….1045
188- Intracranial & Intratemporal Complications of OM……………………………………1050
189- Middle Ear & Temporal Bone Trauma………………………………………………………..1056
190- Cholesteatoma……………………………………………………………………………………………1061
191- Surgery of Mastoid & Petrosa…………………………………………………………………….1066
192- Reconstruction of TM & Ossicular Chain…………………………………………………….1074
193- Otosclerosis………..………………………………………………………………………………………1078
194- Acute Paralysis of Facial nerve…………………………………………………………………...1083
195- Otologic Manifestation of Systemic Diseases……………………………………………..1095
196- Infections of the Labyrinth…………………………………………………………………………..1101
197- Noise Induced HL……………………………………………………………………………………….1107
198- Ototoxicity……….…………………………………………………………………………………………1110
199- CPA Tumors………………………………………………………………………………………………..1112
200- Sudden Sensory Hearing Loss…………………………………………………………………….1120
201- Tinnitus………………………………………………………………………………………………………1123
202- Autoimmune Inner Ear Diseases……………………………………………………………....1127
203- Aging in the Auditory & Vestibular System……………………………………………....1129
204- Cochlear Implant & Other Implantable Prosthesis………….…………………………1132
205- Hearing Aid & Assistive Listening Devices………………………………………………….1138
206- PERIPHERAL VESTIBULAR DISORDERS……………………………….……………………….1143
207- CENTRAL VESTIBULOPATHY………………………………..........................................1147
208- MED. MANAGEMENT OF VEST. DISORDERS AND VEST. REHABILITATION….1151
209- SURGICAL MANAGEMENT OF VESTIBULAR DISORDERS…………………………….1153
210- Cumming's- TEMPORAL BONE NEOPLASMS AND LATERAL CRANIAL BASE
SURGERY…………………………………………………………………………………………………………………1156
211- Cumming's- AGING AND AUDITORY SYSTEMS – PRESBYCUSIS….……………….1160
212- CONGENITAL AURAL ATRESIA…………………………………………………..………………..1162
213- Ear & Temporal Bone………………………………………………………………….……………….1165
214- ELECTRONYSTAGMOGRAPHY……………………………………………………………………..1171
215- MENIERE’S DISEASE………………………………………………………………….……………..…1175
216- ELECTRONYSTAGMOGRAPH.,……………………………………………………………………..1177
217- FACIAL NERVE ANATOMY…………………………………………………………………………..1189
218- The Halmagyi (Head Impulse)Test ……………………………………………………………..1192
219- Head-Shaking Nystagmus (HSN) ……………………………………………………………....1193
220- Malignant Otitis Externa ………………………………………………………………………..….1194
221- NEOPLASMS OF THE EAR AND LATERAL SKULL BASE PATHOLOGY…………….1195
222- Otoplasty………………………………………………………………………………………………….…1197
223- PERIPHERAL VESTIBULAR DISORDERS……………………………………………….……...1198
224- TBD – Lateral Approach…………………………………………………………………….…..…..1208
225- TBD – Middle Fossa Approach……………………………………………………………………1213
226- Temporal Bone Anatomy……………………………………………………………………………1215
227- Vestibulo-Ocular Reflex (VOR)…………………………………………………………………..1230

X Facial Plastic & Reconstructive Surgery:


228- Local Skin Flaps……………………………………………………………………………………………1231
229- MICROVASCULAR FREE FLAPS…………………………………………………………………..1238
230- MANDIBULAR RECONSTRUCTION………………………………………………………..……1247
231- SURGICAL RECONSTRUCTION AFTER MOHS SURGERY……………………………..1253
232- SCAR CAMOUFLAGE……………………………………………………………………………….…1256
233- NASAL RESTORATION WITH FLAPS AND GRAFTS- Large defect ……………….1259
234- NASAL RESTORATION WITH FLAPS AND GRAFTS- Small defect…………………1263
235- SURGERY FOR EXOPHTHALMOS………………………………………………………………..1265
236- FACIAL REANIMATION……………………………………………………………………………….1268
237- FACIAL ANALYSIS………………………………………………………………………………………..1273
238- PREOPERATIVE EVALUATION OF THE AESTHETIC SURGERY PATIENT……….1278
239- SURGICAL ANATOMY OF THE NOSE………………………………………………………….1280
240- INTRODUCTION TO RHINOPLASTY…………………………………………………………….1284
241- EXTERNAL RHINOPLASTY APPROACH……………………………………………………..…1288
242- REFINEMENT OF THE NASAL TIP………………………………………………………………..1290
243- SPECIAL CONSIDERATIONS IN RHINOPLASTY…………………………………………..…1294
244- REVISION RHINOPLASTY………………………………………………………………………….…1298
245- BLEPHAROPLASTY………..…………………………………………………………………………….1302
246- THE AGING FACE (RHYTIDECTOMY)………………………………………………………..…1306
247- THE AGING NECK………………………………………………………………………………………..1311
248- THE AGING FOREHEAD………………………………………………………………………………1312
249- CONGENITAL AURICULAR MALFORMATION………………………………………………1318
250- CHIN AND MALAR AUGMENTATION……………………......................................1322
251- CHEMICAL PEELING…………………………………………………………………………………….1325
252- CERVICOFACIAL LIPOSURGERY……………………………………………………………………1328
253- MANAGEMENT OF BENIGN FACIAL LESIONS……………………………………………..1331
254- MANAGEMENT OF ALOPECIA………………………………......................................1336
255- LASER SKIN RESURFACING…………………………………………………………………………1338
256- TISSUE EXPANDERS…………………………………………………………………………………...1343

IX OTOLARYNGOLOGY FACTS AND POINTS……………………………………….………………1345

IIX Review Questions:


- IN FACIAL PLASTICS AND RECONSTRUCTIVE SURGERY…………………………………………..1355
- IN GENERAL OTOLARYNGOLOGY…………………………………………………………………………...1361
- IN HEAD AND NECK ONCOLOGY………………………………………………………………………………1367
- IN LARYNGOLOGY…………………………………………………………………………………………………..1378
- IN OTOLOGY AND NEUROTOLOGY……………………………………………………………………….…1381
- IN PEDIATRIC OTOLARYNGOLOGY…………………………………………………………………………..1394
- IN RHINOLOGY…………………………………………………………………………………………………………1402
- IN TRAUMA………………………………………………………………………………………………………………1407
MICROBIOLOGY AND DRUG SELECTIONS
FOR TREATMENT OF INFECTIONS
IN THE EAR, NOSE, THROAT, HEAD AND NECK

ACUTE OTITIS MEDIA

Microbiology Primary Alternatives

-Streptococcus pneumoniae (25%) -amoxicillin or clavulin -cefpodoxime, cefdinir


-Hemophilus influenzae (20-25%) -high-dose amoxicillin or -cefuroxime, cefditoren
-Moraxella catarrhalis (10-20%) clavulin if pneumococcal -cetriaxone IM (one injection
-Streptococcus pyogenes (group A - resistance every other day x 3)
2%) -levo-gati-moxifloxacin (adults)
-Staphylococcus aureus (1%) -azithromycin
-others (20%)
-mixed infections (5%)

-children < 2ya, pts with frequent OM, previous Abx within 3 months, seriously ill high dose
amoxcillin/clavulanate or ceftriaxone IM
-for high-penicillin-resistant pneumococcal strains:
-ceftriaxone IM or IV
-levo-gati-moxifloxacin (adults)
-vancomycin IV
-treatment course: 5 days usually

ACUTE BULLOUS MYRINGITIS and ACUTE SUPPURATIVE OTITIS MEDIA


-in absence of prior tympanic membrane perforation or cholesteatoma are variants of acute otitis media
-caused by the same organisms and treated with the same agents

PERSISTENT OTITIS MEDIA WITH EFFUSION


-if asymptomatic, antibiotics not required

ACUTE MASTOIDITIS

Microbiology Primary Alternatives

-Streptococcus pneumoniae -vancomycin IV plus ceftriaxone -levofloxacin IV


-Streptococcus pyogenes (group A) IV -gatifloxacin IV
-coag-negative Staphylococcus -moxifloxacin IV
-others: -clindamycin IV plus ceftriaxone
-S. aureus IV
-hemophilus -ampicillin/sulbactam IV
-proteus
-bacteroides

F.Ling - Antimicrobial Therapy (1)

1
CHRONIC SUPPURATIVE OTITIS MEDIA
-with TM perforation, with or without cholesteatoma

Microbiology Primary Alternatives

-Pseudomonas aeruginosa -ototopicals: -adjunctive therapy


-Staph. aureus and epidermidis -ofloxacin -oral ciprofloxacin +/-
-Proteus sp. -ciprofloxacin clindamycin
-Klebsiella sp. -IV pip/tazo
-E. coli
-anaerobes with cholesteatoma -IV ceftazidime +/- clindamycin

ACUTE (DIFFUSE) OTITIS EXTERNA

Microbiology Primary Alternatives

-Pseudomonas aeruginosa -alcohol/acid mixtures -neomycin/polymyxin/


-S. aureus -ciprofloxacin hydrocortisone

ACUTE LOCALIZED OTITIS EXTERNA (FURNUCULOSIS)

Microbiology Primary Alternatives

-S. aureus -cephalexin -clindamycin


-cloxacillin

OTOMYCOSIS

Microbiology Primary Alternatives

-Aspergillus niger -clotrimazole solution -acetic/citric acids in alcohol


-Aspergillus flavus -non prescription: (VoSol)
-Aspergillus fumigatus -3% boric or 2% acetic acid in -aqueous merthiolate
-Candida albicans 70% isopropyl alcohol -betadine
-Gentian violet
-M-cresol acetate (Cresylate)
-boric acid/iodine powder

F.Ling - Antimicrobial Therapy (2)

2
NECROTIZING (“MALIGNANT”) OTITIS EXTERNA

Microbiology Primary Alternatives

-Pseudomonas aeruginosa -topical ciprofloxacin

PLUS
-oral antipseudomonas quinolone
(Cipro)

PLUS added intravenous


antipseudomonals:
-ceftazidime or cefepime
-ciprofloxacin or levofloxacin
-piperacillin/tazobactam plus:
-gentamicin or tobramycin
or amikacin
-imipenem or meropenem

ACUTE RHINOSINUSITIS

Microbiology Primary Alternatives

-Hemophilus influenzae (38%) -for mild, no prior treatment -for moderate-severe or prior treated
-Streptococcus pneumoniae -amoxicillin +/- clavulanate -clavulin
(37%) -erythromycin plus TMP/SMX or -double dose amoxicillin (90
-other hemophilus sp (8%) doxycycline mg/kg/day children, 3-4 g/day
-Streptococcus pyogenes (group adults, in divided doses)
A - 6%) -respiratory quinolones
-Moraxella catarrhalis (5%) -levofloxacin
-alpha streptococci (3%) -gatifloxacin
-gram negative bacilli/mixed -moxifloxacin
anaerobes (3%) -cefpodoxim, cefdinir, cefuroxime,
cefditoren

-length of treatment: courses of 3, 4, 5 and 8 days yield similar cure rates as do 10 day courses
-nonresponders (in 5 days) will need to be switched to one or the alternative agents to treat virulent or resistant
bacteria for 10-14 days or more with even a third agent

F.Ling - Antimicrobial Therapy (3)

3
MICROBIOLOGY, INFECTIONS AND ANTIBIOTIC THERAPY

ANTIMICROBIAL AGENTS

Penicillins
-pen G and V:
-highly active against:
-Strep pyogenes (B-hemolytic group A)
-Strep pneumoniae
-actinomycosis
-inactivated by penicillinase (B-lactamase):
-S. aureus
-H. influenzae
-M. catarrhalis
-S. pneumoniae: becoming increasingly resistant to penicillins and cephalosporins due to protein
binding
-antistaphylococcal penicillins
-methicillin, oxacillin, cloxacillin, dicloxacillin, nafcillin
-resist penicillinase
-aminopenicillins:
-ampicillin, amoxicillin
-extend activity spectrum to gram-negative organisms:
-Proteus, E. coli, H. influenzae
-resistance in B-lactamase producing organism
-augmented penicillins:
-clavulanate (amoxil) and sulbactam (ampicillin)
-for management of staphylococci, H. influenzae, M. catarrhalis, anaerobic organisms

Cephalosporins
-commonly and safely used by pts with history of penicillin rashes
-first generation:
-Keflex and Ancef:
highly effective against gram-positive organisms such as streptococci, pneumococci
except for penicillin-resistant strains, and staphylococci except MRSA
-mostly used for S. aureus
-second-generation:
-cefuroxime:
-highly active against gram-positive cocci
-H. influenzae and M. catarrhalis including pen-resistant strains
-penetrates blood-brain barrier fairly well
-third-generation:
-cefixime:
-oral agent highly effective against H. influenzae and M. catarrhalis
-ceftriaxone:
-parenteral agent effective against H. influenzae, M. catarrhalis, S. pneumoniae, N.
meningitidis, N. gonorrheae
-first choice for treating patients with intracranial and orbital complications of acute
sinusitis and otitis media
-usually less active against gram-positive bacteria
-anaerobic bacteria are also relatively resistant

F.Ling - Antibiotics (1)

4
Other B-Lactam Antibiotics
-imipenem and meropenem
-active against S. pyogenes, most S. pneumoniae organisms, S. aureus, H. influenzae, B. fragilis
and most anaerobic organisms and the coliforms including P. aeruginosa
-used as single agent against infection by unidentified organisms but CSF penetration is not assured

Macrolides
-has anti-inflammatory effect
-elevate theophylline levels
-erythromycin
-effective for respiratory infections d/t streptococci, most pneumococci, mycoplasmata and
chlamydiae, legionellosis, diptheria, and pertussis
-azithromycin and clarithromycin
-extend antimicrobial activity to include H. influenzae and M. catarrhalis

Clindamycin
-highly active against gram-positive cocci, including many but not all strains of penicillin-resistant
pneumococci
-effective against S. aureus and anaerobic infections of the aerodigestive tract (B. fragilis)
-risk of pseudomembranous colitis

Tetracyclines
-effective against Mycoplasma, Chlamydia, and Legionella
-stain enamel in forming teeth: avoided in children younger than 10 and pregnant women

Quinolones, Fluoroquinolones
-broad spectrum
-elevate theophylline levels
-potential for cartilage damage and arthropathy in children
-ciprofloxacin and ofloxacin:
-antipseudomonas quinolones
-levofloxacin, gatifloxacin, gemifloxacin:
-respiratory quinolones
-for respiratory and pharyngeal infections
-effective against B-hemolytic S. pyogenes, S. pneumoniae, S. aureus, H. influenzae, M.
catarrhalis , Mycoplasma, Chlamydia, Legionella, Bordetella pertussis

Vancomycin
-highly active against gram-positive cocci including MRSA, penicillin-resistant strains of pneumococci,
enterococci, and gonococci
-high concentrations in patients with renal impairment can cause ototoxicity

Metronidazole
-highly active against anaerobic bacteria
-B. fragilis
-all aerobic bacteria are resistant to this agent
-penetrates BBB well

Aminoglycosides
-used against P. aeruginosa and other hospital-acquired infections
-ineffective in anaerobic infections
-risk of ototoxicity (~10%)

F.Ling - Antibiotics (2)

5
Sulfonamides
-older agents effective in the management of H. influenzae but not of pneumococcal, streptococcal, and
staphylococcal infections

TREATMENT STRATEGIES

Otitis Media
-S. pneumoniae, H. influenzae, M. catarrhalis
-first line:
-amoxil:
-most strains of S. pneumoniae
-H. influenzae (20% resistant) and M. catarrhalis (80% resistant)
-second line:
-clavulin, 2nd generation cephalosporin
-macrolides
-high dose penicillin for penicillin resistant organisms
-for high-level resistance:
-vancomycin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin

Sinusitis
-acute:
-same bacteria as in OM
-same drug choices
-intracranial or orbital complications:
-pneumococcal infection suspected Rx ceftriaxone, cefuroxime or trovafloxacin
-chronic:
-anaerobes and S. aureus
-clindamycin or clavulin

Pharyngitis
-caused by S. pyogenes in 30%
-also N. gonorrhoeae, Mycoplasma, Chlamydia and H. influenzae

Tonsillitis
-frequently caused by S. pyogenes
-clindamycin, cephalexin effective

Mastoiditis
-same treatment as AOM
-pneumococci and H. influenzae tend to intracranial extension Rx ceftriaxone
-chronic suppurative otomastoiditis including cholesteatoma: S. aureus, Proteus, B. fragilis and other
anaerobic organisms
-Pseudomonas

Suppurative Otitis
-necessitates combination drug therapy:
-polymyxin for pseudomonal infection and neomycin for S. aureus, Proteus organisms and others

F.Ling - Antibiotics (3)

6
DEGENERATIVE AND IDIOPATHIC DISEASES

BONY LESIONS OF THE SKULL

Fibrous Dysplasia
-medullary bone replaced by fibroosseous tissue
-three clinical forms:
-monostotic FD (75-80%)
-polyostotic FD (20-25%)
-Albright syndrome:
-polyosotic fibrous dysplasia associated with abnormal skin pigmentation, precocious
puberty and other non-skeletal diseases
-20-25% of polyostotic pts
-onset usually <30 ya
-90% asymptomatic
-symptoms: local swelling, pain, displaced teeth or nerve-compression symptoms
-most commonly affected bones: ribs, femur for MFD; femur, tibia for PFD
-head and neck (25%): maxilla and mandible
-radiographic sign: expanded “ground glass” lesion
-histology: marrow replaced by whorled spindle cells with lack of “osteoblastic rimming”
-1/200 cases undergoes malignant degeneration osteosarcoma
-treatment: complete excision

Ossyfying Fibroma
-similar to fibrous dysplasia, but onset is 10 years later
-usually more discrete
-osteoblastic rimming present
-treatment: excision

Paget Disease
-most often occurs between 55-70 ya
-90% have polyostotic disease
-classic symptoms: enlarging skull, dorsal kyphosis, bowing of legs
-other symptoms:
-bone pain (most common)
-spinal root compression
-normal pressure hydrocephalus
-repeated fracture with nonunion
-disease process:
-lytic phase: increased osteoclastic activity with replacement with vascular stroma
-mixed phase: increased osteoblastic activity with osteoclastic activity “cotton wool” appearance
on X-rays
-osteoblastic phase sclerosis on X-rays
-elevated ALP levels and increased urine hydroxyproline levels; hypercalcemia
-occurs more commonly in skull than in face
-can undergo malignant transformation to osteosarcoma ~1-5%
-treatment: calcitonins, disodium etidronate or mithramycin

F.Ling - Degenerative and Idiopathic Diseases (1)

7
Fibrous Dysplasia Compared with Paget’s Disease
Characteristic Fibrous Dysplasia Paget’s Disease

age <30 yr >40 yr

presentation monostotic polyostotic

most commonly affected bones ribs, femur lumbar sacrum

most commonly affected head and neck region maxilla skull

treatment curettage calcitonin

RECURRENT PAROTID SWELLING DIFFERENTIAL


DIAGNOSES FOR
-Mikulicz disease: RECURRENT PAROTID
-autoimmune “pseudosialectasis” localized to parotid gland SWELLING
-primary Sjogren: Autoimmune diseases
-sicca syndrome: autoimmune parotitis associated with -Mikulicz’s disease
xerophthalmia or xerostomia -Primary Sjogren’s
-secondary Sjogren: -Secondary Sjogren’s
Mikulicz’s syndrome
-primary Sjogren associated with connective tissue disorder -recurrent sialadenitis
-Mikulicz syndrome: all cases of recurrent parotid swelling that are not -sialosis
autoimmune conditions -multinodular gland

-sialographic appearance of recurrent parotid swelling:


-autoimmune diseases -normal main ductal system, diffuse spherical collection of contrast
material
-chronic sialadenitis -dilation and stricture of main ductal system, rare sialectasis
-sialosis -enlarged gland, sparse peripheral ducts
-multinodular gland -displacement of ductal system around multiple masses

Autoimmune Parotid Swelling


-on x-ray, globular collections are d/t weakened acini allowing extravasation of contrast material
-usually presents as unilateral recurrent swelling that is painless, of unpredictable duration and rarely
associated with edema
-Sjogren syndrome
-second most common connective tissue disorder
-ages 40-60
-F:M = 9:1
-xerostomia, xerophthalmia, parotid swelling
-other symptoms: dry skin, vaginal pruritus, arthralgia, myalgia
-autoantibodies:
-SS-A and SS-B (primary Sjogren)
-HLA-B8 and HLA-DW3 (primary Sjogren)
-HLA-DW4 (secondary Sjogren)
-other: RF, ANA may be present; ESR elevated; polyclonal hypergammaglobulinemia
-5% develop lymphoproliferative neoplasm
-lip biopsy:
-focus is 50 or more lymphocytes, histiocytes or plasma cells
-score determined by counting # foci in 4 mm2
-focus score > 1 characteristic of Sjogren syndrome
-treatment: supportive; XRT and parotidectomy an option

F.Ling - Degenerative and Idiopathic Diseases (2)

8
Mikulicz Syndrome
-recurrent sialadenitis:
-unilateral, swollen, red, tender gland with purulent discharge
-sialography: dilation and focal narrowing of Stensen duct
-treatment:
-demonstration and removal of any stones
-antibiotics, warm compresses and sialogogues
-excision of gland in severe cases
-sialosis:
-recurrent bilateral nontender parotid swelling
-secondary to various conditions:
-cirrhosis, diabetes, alcoholism, malnutrition, ovarian insufficiency, thyroid
insufficiency, pancreatic insufficiency
-drugs: sulfisoxazole, phenalbutazone, catecholamines, iodide-containing compounds
-multinodular gland:
-autoimmune diseases
-granulomatous diseases: tuberculosis, sarcoidosis
-lymphoproliferative neoplasms
-Warthin’s tumour
-other tumours

MIDLINE DESTRUCTIVE DISEASES

“Lethal midline granuloma”


-Wegener’s granulomatosis
-polymorphic reticulosis
-idiopathic midline destructive disease
-non-Hodgkin lymphoma

Wegener Granulomatosis
-vasculitis, multinucleated giant cells and palisading histiocytes
-granuloma and typical polymorphonuclear cells
-tx: azathioprine, cyclophosphamide and steroids

Lymphomatoid Granulomatosis (T-Cell Lymphoma)


-aka: angiocentric T-cell lymphoma, polymorphic reticulosis, midline lethal granuloma
-composed of a polymorphic rather than a monomorphic infiltrate
-occurs in all age groups; peak 40-50 ya
-M:F = 1.7:1
-usually present with pulmonary symptoms: cough, SOB, hemoptysis
-H+N symptoms:
-ulcerating lesions of upper respiratory tract usually confined to nose and paranasal sinuses
-similar to Wegener granulomatosis
-histology:
-sheets of atypical polymorphonuclear cells
-no granuloma or palisading histiocytes
-treatment: XRT for localized disease; cyclophosphamide and prednisone for multiregional disease
-mortality rate: 50-70%

Malignant Lymphoma

F.Ling - Degenerative and Idiopathic Diseases (3)

9
Idiopathic Midline Destructive Disease
-differentiated histologically from Wegener granulomatosis and lymphomatoid granulomatosis
-composed of sheets of typical polymorphs; no granuloma and no vasculitis

Polyarteritis Nodosa
-affects only small to medium-sized arteries
-rarely affects lungs

Allergic Granulomatosis and Vasculitis


-Churg-Straus syndrome:
-asthma, systemic vasculitis and tissue and peripheral eosinophilia
-polyps, rhinorrhea, obstruction, crusting and septal perforation
-palisading histiocytes, granuloma, vasculitis, typical polymorphs

Foreign-Body Granulomas
-cocaine use; intranasal steroid injections for allergies
-multinucleated giant cells and presence of foreign material
-absence of vasculitis

NONNEOPLASTIC NONTRAUMATIC SUBGLOTTIC STENOSIS

-Wegener’s, amyloidosis, sarcoidosis, relapsing polychondritis

Amyloidosis
-deposition of extracellular fibrillar proteins in various tissues
-rare in pediatric age group
-types:
-primary systemic form (56%):
-heart, tongue, GI tract
-secondary systemic form (8%):
-associated with chronic destructive diseases: tuberculosis, rheumatoid arthritis and
osteomyelitis
-kidney, adrenals, liver, spleen
-localized form (9%):
-any of above
-myeloma associated (26%):
-heart, tongue, GI tract
-histochemical studies: amyloid composed of light-chain immunoglobulins
-extracellular proteins that are green and birefringent under polarized light after staining with Congo red
-orbit most common site of deposition for localized amyloid in H+N

Sarcoidosis
-idiopathic disease characterized by noncaseating granuloma
-usually occurs in 3rd and 4th decade
-may be associated with impaired T-cell function, delayed hypersensitivity and energy
-H+N symptoms:
-cervical adenopathy (most common)
-deposits in supraglottic larynx dysphonia, dyspnea, dysphagia
-nasopharyngeal lesions
-parotid gland enlargement
-neurologic impairment

F.Ling - Degenerative and Idiopathic Diseases (4)

10
-orbital mass or lacrimal gland enlargement
-uveitis
-diagnosis:
-CXR - mediastinal lymphadenopathy
-hypercalcemia
-ACE (angiotensin converting enzyme) levels used to follow course of disease
-Kveim reaction: granulomatous reaction appearing 4 weeks after intradermal injection of sarcoid
spleen or lymph node extracts (experimental)
-treatment: oral steroids

Relapsing Polychondritis
-inflammation of cartilage and other tissues with a high concentration of glycosaminoglycans
-manifestations:
-auricular chondritis (50%)
-nonerosive polyarthritis (50%)
-nasal chondritis (15%)
-inflammation of ocular structures (15%)
-chondritis of respiratory tract (15%)
-cochlear and vestibular damage
-chondritis rapidly develops and resolves in 5-10 days
-involved cartilage becomes deformed: saddle-nose deformity; cauliflower ear
-mortality related to respiratory involvement (ie laryngeal collapse) or cardiovascular disease (eg. aneurysm
or valvular insufficiency)
-treatment: symptomatic; steroids for life threatening conditions

THYROIDITIS

Hashimoto Thyroiditis
-most common form of thyroiditis
-goitrous thyroiditis associated with elevated levels of antithyroid antibodies
-slowly progressive painless enlargement
-histology: lymphocytic infiltration with fibrosis and Hurthle cell change of follicular cells
-disease progresses to hypothyroidism
-most specific test: antimicrosomal antibody; positive in 90% of pts
-treatment: thyroid hormone replacement; FNA for solid lesions to r/o associated lymphoma or neoplasms

Subacute Thyroiditis
-two types:
-granulomatous
-thought to be caused by viral infection
-painful
-infiltration of giant cells
-transient hyperthyroidism transient hypothyroidism
-complete recovery in most cases; 10% have persistent goiter
-lymphocytic
-painless
-lymphocytic infiltrate
-permanent goiter and hypothyroidism more commonly seen than in granulomatous
thyroiditis

F.Ling - Degenerative and Idiopathic Diseases (5)

11
Acute Suppurative Thyroiditis
-mostly seen in immunocompromised
-typical pathogen: S. aureus
-treatment: antibiotics and surgical drainage

Reidel Thyroiditis
-rare fibrosing thyroiditis
-seen predominantly in women
-treatment: thyroid hormone replacement or surgical release of obstruction if required

F.Ling - Degenerative and Idiopathic Diseases (6)

12
CONNECTIVE TISSUE DISEASES

Autoantibody Relationships

-SLE -anti-native DNA, Anti-Sm


-RA -RF, Anti-RA33
-Sjogren -Anti-Ro (SS-A), Anti-La (SS-B)
-Systemic sclerosis -Anti-Scl-70, Anti-centromere
-Polymyositis/dermatomyositis -Anti-Jo-1
-Mixed connective tissue disease -Anti-U1-RNP
-WG -c-ANCA

-prevailing histopathologic feature is varying amount of connective tissue and blood vessel inflammation
with abundant fibrinoid deposits

SYSTEMIC LUPUS ERYTHEMATOSUS

Head and Neck Manifestations


-skin and mucosal lesions
-malar rash in 50% of pts
-oral ulcerations; secondary moniliasis and xerostomia
-orthokeratosis and parakeratosis
-keratotic plugging, acanthosis and pseudoepitheliomatous hyperplasia
-ulceration or perforation of nasal septum: 3-5%
-laryngeal and tracheal manifestations
-true vocal fold thickening or paralysis
-cricoarytenoid arthritis
-subglottic stenosis
-acute enlargement of parotid glands: up to 10%
-neuropathy: cranial nerve dysfunction

Treatment
-rheumatologic assessment
-NSAIDS, topical and low-dose systemic steroids, antimalarial
-low-dose methotrexate
-high-dose steroids and azathioprine and cyclophosphamide reserved for visceral involvement
-oral ulcers:
-Klack’s solution: tetracycline, cortisone, diphenydramine, nystatin

RHEUMATOID ARTHRITIS

-inflammation of synovial tissue with symmetric involvement of peripheral joints

Head and Neck Manifestations


-TMJ dysfunction
-cricoarytenoid joint involvement
-~30% pts with RA are hoarse
-may present with dyspnea on exertion, anterior neck or ear pain, fullness in throat, dysphagia and
aspiration
-ossicular joint involvement rare conductive hearing loss during RA flare

F.Ling - Connective Tissue Diseases (1)

13
Treatment
-salicylates, NSAIDs, gold salts, penicillamine, hydroxychloroquine, immunosuppressive agents

SJOGREN SYNDROME
-see Ch 13 - Degenerative and Idiopathic Diseases
-increased (33-44 times) risk of lymphoma
-salivary gland biopsy best single criterion (spec 83%, sens 81%)

SYSTEMIC SCLEROSIS

Head and Neck Manifestations


-typical facies: tight skin, thin lips, vertical perioral furrows
-dysphagia most common initial complaint
-decreased or absent peristalsis with mild to moderate dilatation
-decreased ability to open mouth secondary to skin changes
-skin manifestations: telangiectasia, calcinosis, linear scleroderma
-laryngeal involvement: voice change

Treatment
-symptomatic
-PPIs for reflux esophagitis

POLYMYOSITIS AND DERMATOMYOSITIS

-characterized by proximal muscle weakness and nonsuppurative inflammation of skeletal muscle

Head and Neck Manifestations


-weakness of neck muscles
-difficulties in phonation and deglutition d/t weak tongue muscles
-nasal regurgitation
-dysphagia

Treatment
-steroids for symptomatic patients
-methotrexate and other immunosuppressives

RELAPSING POLYCHONDRITIS
-see Ch 13 - Degenerative and Idiopathic Diseases

VASCULITIDES

Polyarteritis Nodosa
-rare: 1/100000 per year
-M=F; 5th or 6th decade
-involves small and medium-sized arteries
-ENT manifestations few:
-thromboembolic occlusion of end arteries of inner ear

F.Ling - Connective Tissue Diseases (2)

14
-sudden bilateral SNHL
-vestibular disturbance
-cranial nerve palsies

Churg-Straus Syndrome
-allergic angiitis granulomatosis
-systemic small-vessel vasculitis, extravascular granulomas, hypereosinophilia

Hypersensitivity Vasculitides
-include hypersensitivity angiitis, Henoch-Schonlein purpura, cryoglobulinemia vasculitis

Wegener Granulomatosis
-1/100000 per year
-triad: respiratory tract granuloma, vasculitis, glomerulonephritis
-white; 5th decade
-typical clinical features: bilateral pneumonitis (95%), chronic sinusitis (90%), mucosal ulceration of
nasopharynx (75%) and evidence of renal disease (80%)
-most common oral cavity findings: hyperplasia of gingiva and gingivitis
-subglottic stenosis in 8.5%: poor prognostic sign
-otologic problems in 20-25%: serous otitis media, suppurative otitis media, SNHL, pinna changes

Giant Cell Arteritis


-headache (47%)
-tender temporal artery (50%)
-jaw claudication (50%)
-ESR > 50 mm/h
-dx: temporal artery biopsy
-tx: corticosteroids

Behçet Disease
-vasculitis affecting Japanese and Mediterranean population
-3rd decade
-oral and genital ulcers and uveitis or iritis
-aphthous-like ulcers; punched out and covered with a pale pseudomembrane
-heal in a few days with scarring
-morbidity secondary to CNS involvement, arthritis, and large-vessel arthritis
-tx of ulcers: corticosteroid creams

Cogan Syndrome
-Meniere-like audiovestibular dysfunction, interstitial keratitis, and nonreactive tests for syphilis
-bilateral deafness results in 65% of cases
-accompanied by large- or medium-vessel systemic vasculitis

Kawasaki Disease
-mucocutaneous lymph node syndrome
-pediatric age group
-most common cause of acquired heart disease in children
-symptoms:
-fever (spiking despite Abx treatment)
-conjunctivitis
-red and dry lips
-erythema of oral mucosa

F.Ling - Connective Tissue Diseases (3)

15
-polymorphous truncal rash
-desquamation of fingers and toes
-cervical lymphadenopathy
-“strawberry tongue”
-20-25% untreated children develop coronary artery dilatation or aneurysm
-death from rupture or thrombosis of coronary aneurysm from 2-12 weeks after onset of disease
-treatment with IV gammaglobulin and aspirin in first 10 days reduce incidence of coronary abnormalities
10-fold

F.Ling - Connective Tissue Diseases (4)

16
GRANULOMATOUS DISEASES
OF THE HEAD AND NECK

NEOPLASTIC DISORDERS

Histiocytosis X
-sheets of polygonal histiocytes (Langerhans’ cells) with variable eosinophil, plasma cells, and
lymphocytes
-Langerhans’ cells = histiocytes containing cytoplasmic inclusions known as X bodies
-otitis media most frequent otologic finding

Eosinophilic Granuloma
-localized form of histiocytosis X
-affects children and young adults
-osteolytic lesions with predilection for frontal and temporal bones
-other symptoms:
-proptosis (sphenoid involvement)
-acute mastoiditis
-middle ear granulation tissue
-tympanic membrane perforations
-facial paralysis
-tx: surgical excision; XRT for inaccessible lesions
-excellent prognosis

Hand-Schuller-Christian Disease
-chronic disseminated form of histiocytosis X
-presents in children and young adults (rare in elderly)
-classic triad in 10%:
-skull lesions (polyostotic), exophthalmos and diabetes insipidus
-other symptoms:
-facial paralysis
-external auditory canal polypoid lesions
-tx: XRT, surgery, chemotx or combination
-mortality 30%

Letterer-Siwe Disease
-acute disseminated form of histiocytosis X
-children < 3ya
-uniformly fatal
-clinical:
-fever, proptosis, splenomegaly, hepatomegaly, exfoliative dermatitis, thrombocytopenia
-tx: radiation therapy and chemotherapy

Fibrous Histiocytoma
-painless mass lesion occurring in sun-exposed skin and orbital tissues
-histology:
-biphasic cell population of fibroblasts and histiocytes with spindle-shaped cells with elongated
nuclei arranged in cartwheel pattern
-tx: local excision with clear margins

F.Ling - Granulomatous Diseases (1)

17
Lobular Capillary Hemangioma
-risks: young males, postpubescent females, pregnancy
-circumscribed aggregates of capillaries arranged in lobules
-clinical:
-painless, friable, ulcerated or polypoid lesion on lips (40%), nasal cavity (30%, epistaxis), tongue
(20%), or oral mucosa (15%)
-mainly arise on septum
-female predominance in pts 18-39; based on hormonal factors
-in pregnant women, regresses after delivery
-tx: surgical excision

Necrotizing Sialometaplasia
-pathophysiology:
-infarct of mucosal salivary gland tissue resulting in a self-healing inflammatory process
-histology:
-metaplastic epithelial cells lining small salivary gland ducts with preservation of lobular
architecture
-lobular necrosis
-pseudoepitheliomatous hyperplasia
-most often occurs at junction of hard and soft palate
-lesion is sharply demarcated ulcer may be mistaken for SCCa
-spontaneous resolution over course of weeks to months

INFLAMMATORY DISEASES OF UNKNOWN ETIOLOGY

Sarcoidosis
-multisystem granulomatosis
-cause unknown
-clinical course variable
-most often in 3rd-5th decade
-histology:
-non-caseating epithelioid granuloma
-accumulation of T-cells
-mononuclear phagocytes
-derangement of normal tissue architecture
-symptoms:
-40% asymptomatic
-pulmonary involvement (88%, cough, hilar adenopathy, dyspnea)
-cervical adenopathy (25-50%, most common H+N presentation)
-salivary glands parotid mass, uveoparotid fever (Heerfordt’s disease)
-larynx supraglottic region most commonly affected in larynx (epiglottis most common);
submucosal infiltration
-other:
-uveitis, nasal mass, orbital mass, nasal perforations
-cutaneous lesions (erythema nodosum, rashes)
-“Darrier Rousey” nodule (subcutaneous lesion)
-hepatic and renal involvement
-splenomegaly
-cardiac (arrhythmia)
-bone lesions
-neuropathies

F.Ling - Granulomatous Diseases (2)

18
AUTOIMMUNE OR VASCULITIC DISEASE

Wegener Granulomatosis
-systemic disorder: ELK (ENT, Lungs,
HEAD AND NECK MANIFESTATIONS OF WG
Kidney)
-4th to 5th decade; M:F ~2:1 Nasal (60-80%) -chronic sinusitis, nasal crusting, bloody
-necrotizing granuloma with vasculitis in one rhinorrhea, PND, septal perforation
Otologic (20-25%) -SOM +/- SNHL 2o cochlear vasculitis
or more major organ systems
Ocular (40%) -granulomatous keratitis, uveitic, retinal
-granuloma, necrotizing vasculitis, artery involvement
and arthritis involving small arteries Tracheal -stridor from subglottic narrowing
must be demonstrated
-C-ANCA:
-cytoplasmic staining anti-neutrophil cytoplasmic antibodies
-used for diagnosis; high specificity (> 90%)
-used to monitor disease activity as levels parallel this

Goodpasture Syndrome
-antiglomerular basement membrane nephritis
-lacks sinus involvement

Relapsing Polychondritis
-intermittent inflammation of cartilage
-pinna, nose, trachea and larynx most commonly involved
-tx: NSAIDs, steroids or dapsone

Systemic Lupus Erythematosus


-laryngeal involvement:
-thickening of true vocal cords
-limited excursion of arytenoids
-perichondritis and chondritis of laryngeal and tracheal cartilages
-cricoarytenoid and cricothyroid arthritis
-nasal:
-septal perforation

Sjogren Syndrome
-autoimmune disorder of exocrine glands
-xerostomia, keratoconjunctivitis sicca and connective tissue disease

Periarteritis Nodosa
-fibrinoid necrosis of medium sized arteries with frequent involvement of kidneys
-non-specific nasal mucosal lesions

Churg-Strauss Syndrome
-triad: hyper-eosinophilia, allergic rhinitis, asthma and systemic vasculitis of medium and small muscular
arteries
-three phases:
-prodromal phase: atopy and allergic rhinitis
-hypereosinophilia
-systemic necrotizing vasculitis
-tx: high dose systemic steroids

F.Ling - Granulomatous Diseases (3)

19
Behcet Disease
-recurrent aphthous ulceration of upper aerodigestive tract and genitalia
-ocular inflammation
-cutaneous vasculitis
-no treatment known

FOREIGN BODY REACTIONS

Cocaine-induced Midline Granuloma


-secondary to infection with S. aureus

Cholesterol Granuloma
-arise as consequence of inadequate ventilation with impaired drainage and haemorrhage of middle ear or
paranasal sinuses
-cholesterol precipitates from erythrocyte breakdown causes FB reaction with neovascularization and
formation of granulation tissue

Gout
-rare
-involvement of cricoarytenoid joint: pain, dysphagia, hoarseness, aspiration, stridor and possible airway
compromise

INFECTIOUS DISEASES

Bacterial Infections

Cat-Scratch Disease
-Rochalimae (Bartonella) henselae
-intracellular, pleomorphic, gram-negative, non-AFB
-seen with Warthin-Starry silver stain
-hx of cat exposure, primary inoculation site, regional adenopathy
-histology:
-suppurative and necrotizing granulomatous lymphadenitis with stellate abscesses
-tx: supportive with I+D for abscesses

Bacillary Angiomatosis
-young adults
-cutaneous papules and subcutaneous nodules

Brucellosis
-aerobic, gram-negative bacilli
-exposure from infected cattle (butter)
-tx: tetracycline

Rhinoscleroma
-Klebsiella rhinoscleromatis
-tx: tetracyline or streptomycin

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20
Leprosy
-Mycobacterium leprae
-laryngeal ulcerations, lymphadenopathy, hyposmia, nasal collapse, fish-mouth deformity, facial nerve
paralysis, eyebrow and eyelash loss
-tx: dapsone

Nontuberculous Mycobacteria
HEAD AND NECK MANIFESTATIONS OF
-children aged 1-6 years more frequently TUBERCULOSIS
affected
-more commonly causes (1) corneal ulceration Lymph nodes -lymphadenopathy
and/or (2) cervical lymphadenopathy Larynx -granulomas or ulcerations, edema, polyploid
changes; most common site of involvement is
-transmission from soil to mouth or eye the arytenoids
-Dx: biopsy for C+S; AFB staining Eyes -conjunctivitis, keratitis, uveitic
Salivary glands -diffuse glandular involvement, usually of the
Tuberculosis parotid
Oral cavity -painful or painless ulcers, most frequently
-scrofula involving tongue
-rare in head and neck Ear -granulomas, tympanic membrane
-Dx: positive PPD, CXR, biopsy perforations, watery otorrhea, mastoiditis
-tx: isoniazid and rifampin daily for 9-12
months

Actinomycosis
-anaerobic or micro-aerophilic Actinomyces species
-from dental manipulation or trauma
-visible sinus tracts and lymphadenopathy
-purplish discolouration of overlying skin
-histology: sulfur granules
-tx: surgical debridement and Pen G IV x2-6 weeks

Syphilis
-Treponema pallidum
-dx:
-VDRL for screening
-dark-field examination
-fluorescent treponemal antibody-absorption test (ft-Abs)
-Warthin-Starry tissue staining
-histopathology:
-mononuclear infiltrate
-obliterative arteritis
-hydrops
-gummas and osteolytic lesions in otic capsule
-stages:
-primary:
-chancre at inoculation site, lymphadenopathy
-secondary: “Great Imitator”
-highly contagious, general malaise and fever, arthralgia, hepatosplenomagaly, genital
condyloma lata, nephrotic syndrome, “mucous patches”
-latent: asymptomatic phase
-tertiary:
-noninfectious stage
-may occur years after initial infection
-slow progressive

F.Ling - Granulomatous Diseases (5)

21
-neurosyphilis
-aortic involvement
-gummas

-H+N symptoms:
-lymphadenopathy
-laryngeal: laryngitis with mild edema of the larynx, vocal fold paralysis, dysphagia
-oral cavity: chancre, granulomatous infiltration of tongue, palate
-otologic: abrupt profound SNHL, Meniere’s symptoms, interstitial keratitis, TM perforation,
gummas of temporal bone
-nasal: saddle nose deformity, rhinitis, osseous and cartilaginous destruction, septal perforation

-tx: penicillin, ampicillin, tetracycline, erythromycin, steroids for otologic involvement

Anthrax
-Bacillus anthracis
-painless necrotic ulcer with surrounding edema +/- regional lymphadenopathy

Tularemia
-ticks, rabbits, deer
-photophobia, decreased visual acuity and cervical and preauricular lymphadenopathy
-exudative pharyngitis
-tx: streptomycin

Granuloma Inguinale
-Calymmatobacterium granulomatis
-tx: tetracycline, ampicillin or SMX-TMP

Fungal Infections

Histoplasmosis
-Histoplasma capsulatum
-airborne transmission
-endemic to Missouri and Ohio River Valley causes chronic pulmonary infection
-most infections are subclinical
-immunocompromised: granulomatous lesions of lips, gingiva, tongue, pharynx and larynx
-may mimic carcinoma
-dx: culture on Sabouraud’s medium, skin test, complement fixation test, latex agglutination
-tx: amphotericin B

Blastomycosis
-Blastomyces dermatitidis
-airborne transmission
-endemic to Central America and the Midwest USA)
-cutaneous disease, pulmonary involvement and constitutional symptoms
-oropharyngeal and verrucous laryngeal lesions
-histopathology:
-pseudoepitheliomatous hyperplasia
-intraepithelial microabscess
-single bifringent broad based bud (yeast form)
-tx: amphotericin B; itraconazole

F.Ling - Granulomatous Diseases (6)

22
Coccidioidomycosis
-Coccidioides immitis
-rare: skin, mucous membranes, thyroid, eyes, trachea, salivary glands, epiglottis

Candidiasis
-Candida albicans
-tx: nystatin or ketoconazaole

Rhinosporidiosis
-Rhinosporidium seeberi
-indolent, painless, warty excrescences on nasal, palatal and conjunctival mucous membranes
-tx: excision

Phycomycosis
-Mucor, Rhizopus or Absidia
-facial pain, fever, bloody rhinorrhea, facial swelling and sinus tenderness
-proptosis, visual loss, cranial nerve palsies and obtundation
-tx: amphotericin B and aggressive surgical debridement

Cryptococcosis
-Cryptococcus neoformans
-d/t immunosuppression
-rare: membranous nasopharyngitis, meningitis, hearing loss

Aspergillosis
-Aspergillus fumigatus
-allergic, noninvasive or invasive

Parasitic Infections

Leishmaniasis
-Leishmania from sandfly bites
-cutaneous or mucocutaneous lesions
-bloodborne spread to oral cavity and oropharynx
-progressive inflammation and destruction of soft tissues of mouth and nose may occur

Myiasis
-infestation of body by maggots and transmitted by screwworm fly

Toxoplasmosis
-Toxoplasma gondii
-from cat feces or infected poorly cooked lamb or pork

TRAUMA-INDUCED DISORDERS

Intubation Granuloma
-involve vocal process of arytenoids
-contact ulcer granuloma pedunculate polyp

F.Ling - Granulomatous Diseases (7)

23
Teflon Granuloma
-from vocal cord injections

Reparative Granuloma
-secondary to local trauma in oral cavity

Pyogenic Granuloma
-granulation tissue formed in response to minor trauma with secondary infection

F.Ling - Granulomatous Diseases (8)

24
GERIATRIC OTOLARYNGOLOGY

HEARING, PRESBYCUSIS, HEARING AIDS, AND ASSISTIVE DEVICES

TYPES OF PRESBYCUSIS
Audiometric Profile

Location in Cochlea Pure Tones Discrimination

Sensory Basal end High-tone abrupt slope Related to frequency range

Neural All turns All frequencies Severe loss

Metabolic Apical region All frequencies Minimal loss

Cochlear Conductive All turns: basal > apical High-tone gradual slope Related to steepness of slope

-increasing number and decreasing cost of assistive listening devices are factors in improving quality of life
for pts with mild presbycusis

TINNITUS

-incidence increases with age


-present in 20% of people over age 50
-severe tinnitus in 4% of people over 50
-may be factor contributing to depression
-nortriptyline seems to effectively reduce the severity of tinnitus in depressed pts

DISEQUILIBRIUM AND ATAXIA OF THE ELDERLY

-presbyastasis:
-disequilibrium
-degenerative changes such as vacuolization of sensory epithelium of SCC ampullae plus
fragmentation of otoconia
-morphologic changes in vestibular nerves, Scarpa ganglion, and cerebellum
-decreased sensory input, decreased integrating ability and weakened muscular function balance
problems

VOICE DISORDERS IN THE ELDERLY VOICE EFFECTS OF AGING

-atrophic changes
-voice quality deteriorates with aging -mostly in males
-anatomic and functional causes known: -increased pitch
-ossification of laryngeal cartilages -thin reedy voice
-limitation of arytenoid cartilage excursion -edema and polyploid change
-females
-incomplete glottic closure -lower pitched voice
-decreased number of collagen and elastin fibers -pharyngeal formants also lower
-atrophy of laryngeal muscles -smoking relationship
-fundamental vocal frequency increases but may decrease if -voice stability
-wobbling and tremolo (standard
there is edema or polyploid degeneration of vocal folds deviation from fundamental
-some changes in vocal quality may result from unsuccessful frequency and jitter)
efforts to compensate for effects of aging

F.Ling - Geriatric Otolaryngology (1)

25
-males:
-attempts to drop pitch
-gravelly, breathy, glottal fry
-easy fatigue
-apparently bowed vocal cords
-females:
-attempts to raise pitch
-squeezed, strained
-effortful voice
-variable ventricular band adduction

OLFACTION AND GUSTATION IN THE ELDERLY

-aging is associated with specific morphologic changes:


-loss of zonal distribution of receptor sustentacular, and basal cells
-dilatation of Bowman glands and invagination of respiratory epithelium into lamina propria
-area of olfactory neuroepithelium may be reduced with replacement by respiratory epithelium
-degenerative diseases, drugs that decrease cell turnover, radiation therapy, viral infections, endocrine
disorders, neoplasms, and trauma may account for decrements in taste smell in the elderly

GERIATRIC SINUSITIS AND NASAL SYMPTOMS

-older pts more likely to consult physicians for nasal drainage, postnasal drip, gustatory rhinitis, and
decreased olfactory ability
-diminished capacity of immune system is believed to be a factor in increased frequency and severity of
sinusitis in geriatric age group

PRESBYPHAGIA

-predisposing factors: stroke, epilepsy, drugs, tumours, and infection


-progressive decrease in pharyngeal sensation with increased age may lead to increased aspiration
-cricopharyngeal achalasia:
-dysphagia secondary to cricopharyngeal muscle dysfunction
-may be helped by cricopharyngeal myotomy

PERIPHERAL NERVES

-general tendency to lose myelinated nerve fibers with increasing age, pathologic changes in Schwann
cells, an increase in cross-sectional area of nerves, and vascular changes (such as endothelial proliferation
and media fibrosis)

GERIATRIC IMMUNOLOGY

-with increasing age, immune system becomes less effective in protecting against infections and neoplastic
disease
-lymphocytes are not as effective in older people for the following reasons:
-function of helper and cytotoxic T-cell activity declines

F.Ling - Geriatric Otolaryngology (2)

26
-general response to antigens and immunogen decreases
-thymus gland involutes
-older T and B cells seem to produce a weaker response intrinsically
-quality of overall response is decreased (less IgG and fewer antibodies are produced)

BENIGN AND NONSQUAMOUS NEOPLASMS

-anaplastic or undifferentiated thyroid cancer is much more common in pts over 65


-medullary carcinoma and thyroid lymphomas seen more often
-well-differentiated thyroid carcinoma behaves much more aggressively
-recurrence rate for papillary carcinoma higher
-salivary gland malignancies seen more frequently

SKIN CHANGES OF AGING

-level of mitotic activity decreases, leading to evidence of atrophy


-age related skin changes:
-decreased moisture content and cellular cohesion in stratum corneum
-effacement of rete ridges of epidermis
-heterogeneity of keratinocyte nuclei
-decreased population of melanocytes and Langerhans’ cells
-thinning of dermis
-decreased elastic tissue
-loss of oxytalan fibers
-haphazard collagen deposition
-fewer small vessels, fibroblasts, macrophages, mast cells, Pacini’s corpuscles, Meissner’s
corpuscles, and sweat glands
-smaller sebaceous glands

F.Ling - Geriatric Otolaryngology (3)

27
HEADACHE AND FACIAL PAIN

PATTERNS OF REFERRAL FOR JAWS AND TEETH

-TMJ and muscles of mastication


-source of pain that radiates to head and ear
-TMJ innervated by auriculotemporal nerve
-muscle pain more intense and more common
-tooth pain
-poorly localized
-pulpal death results in localization of pain to offending tooth

CLINICAL SYNDROMES

Tension-type Headache
-bilateral
-stress related
-continuous nonpulsatile headache
-usually responsive to NSAIDs
-persists days or weeks, not disabling

Migraine
-premonitory symptom
-aura
-disabling unilateral headache
-often reported as a sick headache or sinus headache
-nausea and vomiting common
-photo- and phonophobia common
-precipitated by red wine and some foods
-preventive therapy initiated in pts suffering two or more attacks per month
-treatment strategies:
-aborting further development of pain by starting drugs shortly after first warning symptoms or at
earliest onset of pain
-treating pain if abortive therapy fails
-preventing headache by limiting predisposing events; promote healthy lifestyle

Cluster
-provoked by EtOH
-seasonal
-may be associated with allergy
-stereotypic attacks
-autonomic symptoms can cause confusion with sinusitis

OTHER CAUSES OF FACIAL PAIN

Trigeminal Neuralgia
-lancinating pain along distribution of CN V
-brief but may result in significant functional impairment
-occurs in 5th, 6th and 7th decades
-triggers are small areas on face that precipitate an attack when touched

F.Ling - Headache and Facial Pain (1)

28
-not associated with any neurological impairment
-must rule out other neurological causes
-treatment:
-trials of carbamazepine, gabapentin, baclofen, phenytoin, sodium valproate, chlorphenesin
-2 week trial for a drug
-adjunctive therapy: TCA and NSAIDs

Glossopharyngeal Neuralgia
-unilateral lancinating pain located in posterior pharynx, soft palate, base of tongue, ear, mastoid or side of
head
-workup and treatment same as for trigeminal neuralgia

Post-traumatic Neuralgia
-most often include lateral parietal and occipital regions
-treatment includes same medications used for trigeminal neuralgia
-local infiltration of trigger points with bupivicaine can be effective

Postherpetic Neuralgia
-VSV infection of trigeminal nerve in childhood as chickenpox
-reactivation later in life by trauma or stress
-immunocompromised pts treated with acyclovir, NSAIDs or opioids for pain during acute phase
-other patients treated with 10d course of oral prednisone 40 mg/day, tapering after 5 days
-pain persisting > 2 months = postherpetic neuralgia
-opioid and NSAIDs often are of little use at this stage
-anticonvulsants most useful; combined with TCA or baclofen

Atypical Facial Pain


-diagnosis of exclusion
-bilateral and changes locations frequently over weeks to months
-daily, constant, psychological factors common (60-70%): depression, somatization, and adjustment
disorders most common

Brain Tumour
-30% of pts with brain tumour have headache at time of diagnosis
-characteristic feature is crescendo quality of headache with greater intensity and frequency of pain along
with less response to analgesics over time

Pseudotumour Cerebri (Benign Intracranial Hypertension)


-papilledema, normal neurologic examination, normal CT, CSF pressure above 200 mmH2O, normal CSF
chemistries
-treatment: weight reduction, low-salt diet, medications directed at reducing CSF production (eg.
acetazolamide), lumbar drain

Subdural Hematoma

Subarachnoid Hemorrhage

Temporal Arteritis
-95% pts are > 60 ya
-daily moderate to severe headache, scalp sensitivity, generalized fatigue
-carotid artery pain, jaw claudication
-enlarged, thickened or tender scalp arteries

F.Ling - Headache and Facial Pain (2)

29
-treatment: prednisone (60 mg od)

Hypertension
-poor correlation between headache and chronic elevations in blood pressure
-acute headache associated with rapid rises in BP may be indication of pheochromocytoma, renal artery
stenosis, or hyperadrenalism

Post-traumatic Headache
-typically frontal and occipital, often present at some level day and night, poorly responsive to medications
-treatment: reassurance and a course of antidepressants (eg. TCA, SSRI)

Low Intracranial Pressure Headache


-most often as complication of lumbar puncture
-worse in sitting position
-nausea is common, and episodes of transient CN IV or III paresis are reported
-spontaneous recovery within days

Infection of the Nervous System


-meningitis, encephalitis etc..

Chronic Daily Headache


-use of pain relievers >3x/wk often associated with refractory headache

F.Ling - Headache and Facial Pain (3)

30
MANIFESTATIONS OF AIDS

Head and Neck Manifestations of HIV by Anatomical Location

Oral and Pharynx Neck Otologic


-oral candidiasis -deep-space neck abscess -acute and chronic otitis media
-oral hairy leukoplakia -infectious lymphadenopathy -otitis externa
-herpes stomatitis (mycobacterium, pneumocystis, CMV, -mastoiditis (invasive aspergillosis,
-thrombocytopenic purpura EBV, totxoplasmosis, cat-scratch pneumocystis, mycobacterium)
-recurrent apththous ulcers disease, bacterial) -malignant otitis
-bone loss (bacillary angiomatosis) -neoplastic lymphadenopathy -SNHL
-gingivitis (acute necrotizing ulcerative (Hodgkin’s and NHL, metastatic disease, (cryptococcal or mycobacterial
gingivitis, necrotizing stomatitis) thyroid tumours) meningitis, otosyphilis, toxoplasmosis,
-Kaposi’s sarcoma, NHL, SCCa -persistent generalized adenopathy autoimmune demyelisation of the
cochlear nerve, CPA tumours)
Larynx Salivary Glands -TM perforations
-epiglottitis -lymphoepithelial cysts of parotid gland -aural polypa
-Kaposi’s Sarcoma -parotitis -facial nerve paralysis
-NHL -salivary gland neoplasms (Herpes Zoster, CMV, EBV, HIV,
-laryngitis (mycobacterium, fungal, autoimmune demyelisation, malignant
CMV, EBV, bacterial) Paranasal Sinus otitis externa, meningitis and
-rhinosinusitis encephalitis)
(mucor, aspergillosis, pseudomonas) -temporal bone neoplasms
-nasal tumours (Hodgkin’s and NHL, Kaposi’s
(Kaposi’s sarcoma, nasal lymphomas) sarcoma)

-HIV is a retrovirus that attaches to CD4+ cells marker of T-helper cells, macrophages, and other
immunological cells
-results in a decrease in T-helper lymphocytes and impaired function of macrophages, neutrophils, B-
lymphocytes and complement activation
-AIDS defining illness:
-candidiasis, CMV disease, Kaposi’s sarcoma, Pneumocystis carinii, etc..
-CD4+ count < 200 cells/ul

DERMATOLOGIC

-molluscum contagiosum
-pearly umbilicate papules; usually 2-5 mm, occasionally giant; predilection for eyelids
-tx: surgical excision, curettage or cryotherapy
-complics: frequent recurrence following treatment; can cause functional problems if extensively
involving and treated in eyelid areas

-bacillary angiomatosis
-subcutaneous nodules or friable papules; multiple organ involvement; negative cultures; classic
histopathologic appearance
-tx: erythromycin, 500 mg qid or rifampin 600 mg qd
-if unrecognized and untreated, can have multisystem involvement and possibly death

-cutaneous Cryptococcus
-most common dermatologic condition associated with HIV
-pustular or granulomatous lesions; histopathologic or culture identification
-tx: search for systemic infection, and treat systematically with amphotericin B and/or flucytosine
-complics: cryptococcal meningitis associated with 30% mortality rate even when treated

F.Ling - Manifestations of AIDS (1)

31
-seborrheic dermatitis
-white scaly plaques or patches with or without erythema and inflammation
-tx: hydrocortisone cream; ketoconazole cream
-complics: can become secondarily infected with S. aureus

-herpes zoster/Ramsay Hunt


-typical dermatomal distribution
-tx: oral acyclovir, 800 mg 5 times/day; analgesic
-complics: often produces permanent cranial nerve palsy; systemic disease associated with high
morbidity

-Kaposi sarcoma
-violaceous papular or ulcerated skin lesions, often multiple; can be associated with regional
adenopathy and mucosal lesions
-tx: low-dose XRT, systemic (vincristine or vinblastine), or intralesional (vinblastine)
chemotherapy
-complics: secondary infection produces severe symptoms; occasionally causes airway obstruction
or other functional problems

OTOLOGIC
-primary dermatologic conditions affecting EAC: KS and seborrheic dermatitis
-serous and acute otitis media most common otologic conditions
-ETD 2o to nasopharyngeal lymphoid hypertrophy
-Staphylococcus and Pseudomonas in acute or chronic OM is more common
-P. carinii and Candida have been cultured in middle ear aspirates of AIDS patients
-mild to moderate SNHL often reported: viral infection suspected

NOSE AND PARANASAL SINUSES

-can be sites of herpetic lesions, KS and NHL


-recurrent and chronic sinusitis
-persistent low-grade viral or bacterial infection of OMC
-usual pathogens: Staphylococcus species, S. pneumoniae, H. influenzae and anaerobic bacteria
-Pseudomonas aeruginosa implicated in 20% tx /w clindamycin and ciprofloxacin
-invasive fungal sinusitis must be suspected in individuals with pain out of proportion to findings on
examination despite being on empiric antibiotics

ORAL CAVITY AND PHARYNX

-Oral candidiasis:
-most common oral lesion in AIDS
-pseudomembranous plaques with underlying red inflamed mucosal surface
-tx: topical antifungal: nystatin tid or clotrimazole;
systemic antifungal: ketoconazole 200 mg qd or fluconazole
-can produce severe local symptoms; candida esophagitis must be considered

-Herpetic stomatitis:
-ulcerative, punched-out lesions occurring on any mucosal surface
-tx: oral acyclovir, 200 mg 5 times/day; topical analgesics

F.Ling - Manifestations of AIDS (2)

32
-frequent recurrence; may develop drug resistance

-Aphthous ulcers:
-usually single, but may be multiple; usually on mobile mucosal surface; may become extremely
large “giant apththous ulcers”
-tx: topical analgesics; topical steroids in Orabase; occasionally intralesional or systemic steroids
-can produce severe debilitating symptoms resulting in nutritional imbalance

-Hairy leukoplakia:
-whitish thickening of mucosa on lateral tongue; often has corrugated appearance
-usually asymptomatic
-EBV present in epithelium
-tx: none necessary; treat candidal superinfection when present; acyclovir may be beneficial

-Kaposi’s sarcoma:
-violaceus lesions; predilection for hard palate
-may be flat or nodular; may become ulcerated and secondarily infected
-tx: intralesional or systemic chemotherapy; palliative surgical or laser excision, radiation therapy
-can produce local symptoms when ulcerated or infected; occasionally causes airway obstruction
or severe dysphagia

-Non-Hodgkin’s lymphoma:
-second most common neoplasm associated with AIDS
-nodular, ulcerative; Waldeyer’s ring area often involved; biopsy diagnostic
-tx: chemo or XRT
-often causes local symptoms of obstruction or pain; frequent dissemination including
lymphomatous meningitis

-Gingival and periodontal disease:


-ulcerative and necrotizing gingivitis; poorly responsive to aggressive therapy
-tx: aggressive local hygiene, debridement of severely involved tissue followed by Betadine and
Peridex mouth rinses; oral metronidazole is often an effective adjunct

LARYNX

-must consider fungal, viral and mycobacterial infections


-KS and NHL can also occur in the larynx

NECK

-salivary gland disease:


-xerostomia common complaint
-generalized parotid enlargement caused by lymphocytic infiltration
-parotid masses: usual parotid neoplasms, KS, NHL or lymphoepithelial cysts
-indications for cervical lymph node biopsy:
-marked constitutional symptoms
-localized lymphadenopathy
-single disproportionately large node in a patient with persistent generalized lymphadenopathy
-cytopenia or elevated ESR or both and a patient with otherwise negative evaluation
-patient reassurance of an ambiguous tissue diagnosis

F.Ling - Manifestations of AIDS (3)

33
-ddx lymphadenopathy:
-malignancy
-tuberculous, atypical mycobacterial infections
-histoplasmosis
-toxoplasmosis
-cat-scratch disease

F.Ling - Manifestations of AIDS (4)

34
F.Ling - POS notes and points (1)

Principles of Surgery
“69" other notes and points from previous exams ;)

Last minute facts to cram into your already saturated brain.


The following sources have been used:
-Harrison’s 14th ed.
-Schwartz 7th ed
-Ganong - Review of Physiology
-Merck Manual 17th ed
-Katzung - Review of Pharmacology
-Robbin - Pathology of Disease
-Rush Review
-Sanford Antimicrobial Manual (1997)
-Way - Current Management in Surgical Disease

1. Internal maxillary does pass through the deep lobe of the parotid
2. Aldosterone mechanism of action: resorption of sodium at cortical collecting duct (Ganong 345)
3. Non-caseating granulomas
-TB (can be caseating also) and sarcoid (Robbin 81)
4. Actinomycosis:
-draining sinuses
-involves skin sinus tracts with pus
-sulfur granules on histo
-tx: surgical drainage, penicillin for at least 8 weeks can be up to 1yr until drainage stops
-(Merck 1181)
5. Horner’s Syndrome: miosis, ptosis, anhydrosis, enophthalmos (Merck 652)
6. Early endoscopy is OK for caustic ingestion (Harrison 1585, Schwartz 1159)
7. Nasal fractures most common facial fracture in trauma; mandibular fracture second
8. Azathioprine causes cholestasis (Schwartz 430)
9. Renin (Ganong 421):
-factors that increase secretion: sympathetic activity, circulating catecholamines, prostaglandins
-factors that decrease secretion: hyperaldosteronism, angiotensin II, vasopressin, reabsorption across
macula densa, afferent arteriolar pressure
10. Melanoma treatment (Schwartz 525):
-Clark level I - < 0.75mm: 2cm margin, no lymph node dissection if not affected
-Clark levels II, III, IV - 0.76-4mm: excise with 2-3cm margin, lymph node dissection controversial
-Clark level V - > 4.0 mm: metastasis likely, no lymph node dissection
11. Most common type of melanoma: superficial spreading (70-80%)
12. Bites (Sanford 1997, Harrison 836)
-dogs:
- responsible for 80% domestic animal bites
-only 15-20% get infected
-bugs: strep viridans, staph, pasturella, anaerobes etc...
-cats:
-80% of bites get infected
-P. multocida most responsible
-humans:
-more frequently infected than other animal bites
-bugs: strep viridans (100%), staph epi (53%), staph aureus (29%), eikenella (15%), anaerobes
etc..
13. Presentation of CMV post transplantation:
-leukopenia with fever, pneumonia, gastroenteritis, hepatitis, retinitis, sepsis

35
F.Ling - POS notes and points (2)

14. Highest risk for surgery: CHF (Goldman index 11) > MI less than 6 months (Goldman index 10)
15. Indications for thrombolytics in PE (Way 800)
-shock, RV failure, severe pulmonary hypertension and may die with additional emboli
16. Pancreatic alpha cells rich in beta-adrenergic receptors (stimulation) glucagon
Pancreatic beta cells rich in alpha-adrenergic receptors insulin
17. Growth Hormone secretion:
-stimulated by: ACTH, thyroxine, alpha-adrenergic stimulation, glucagon
-inhibited by: hyperglycemia, FFA, cortisol, somatostatin
18. Effects of PTH:
- sCa: renal and intestinal resorption
- sPO4 via renal excretion
-1 hydroxylation of 25-OH vitamin D
-stimulates osteoclasts
19. ATN: hemegranular casts; SG < 1.015
Prerenal: hyaline casts; SG > 1.018
20. Amikacin for treatment of pseudomonas that is resistant to tobramycin or gentamicin (Merck 1174)
21. Oral Abx for pseudomonas: cipro (or other quinolones), oral indanyl carbenicillin
22. Persantine = dipyrimadole: decreases platelet aggregation, dilates coronary arteries
23. OCP and DVT (Merck 1998, Schwartz Ch 11):
-related to increases in blood clotting factors
-possibly increased platelet adhesion
-increased levels of globulins, particularly factors VII and X hypercoagulable state
-decreased antithrombin III
24. TTP (Merck 945)
-syndrome of: platelets, fragmented RBC, renal failure, fever, manifestations of ischemic damage (eg.
confusion, seizure, jaundice etc.)
-tx: plasmapheresis, steroids; if refractory, splenectomy, vincristine or cyclophosphamide have been used
25. Cytochrome P450 inducers: barbiturates, phenytoin, rifampin, carbamazepine
26. Cytochrome P450 inhibitors: cimetidine, INH, ketoconazole, allopurinol, erythromycin, MAOI, disulfiram,
verapamil
27. Thromboxanes synthesized in platelets; prostacyclines synthesized in endothelial cells
28. Serotonin found in enterochromaffin cells of the gut, CNS, and platelets
29. Arginine (Schwartz 246, Rush 48):
-helps to decreases protein catabolism
-reduces urinary nitrogen excretion
-improve immune function (T-cell proliferation)
-improve wound healing (?accelerates it)
-secretagogue activity on pituitary and pancreatic hormones: GH, PRL, glucagon, insulin, IGF,
catecholamines
30. Cryptococcus (Merck 1218)
-cannot be contracted via blood transfusion
-acquired by inhalation of soil contaminated with encapsulated yeast
-tx: Ampho B (with flucytosine)
31. Ionized calcium required for neuromuscular stability (Rush 15)
32. Preoperative TPN (Schwartz 444)
-increases wound healing
-increases risk of nosocomial and catheter related sepsis in non-severely malnourished individuals
-increases immune function pre-op and lowers mortality and decreases septic complications
33. Arthus reaction (Merck 1010)
-aka. Type III hypersensitivity
-due to presence of Ab that binds to injected Ag immune complex formation, complement activation and
neutrophil chemotaxis

36
F.Ling - POS notes and points (3)

34. Ramsay-Hunt Syndrome:


-facial palsy, vesicular eruption over distribution of cranial nerve or cervical plexus, severe ear pain
-associated SNHL and vestibular dysfunction
-tx: acyclovir
35. 75-80% of IgG is intravascular
36. Three classic landmarks to identify main trunk of facial nerve for parotidectomy:
-mastoid tip
-posterior belly of digastric
-“cartilagenous pointer” of the tragus
37. Renal Tubular Acidosis (Merck 1900)
I: unable secrete H+ at distal nephron
-metabolic acidosis, volume contraction, hypokalemia
-hypercalciuria, increased mobilization of bone Ca
II: unable to reabsorb bicarbonate in proximal tubule
-metabolic acidosis, volume contraction, hypokalemia
III: rare, combination of I and II
IV: unresponsiveness of distal tubule/CCD to aldosterone hyperkalemia
38. Daily fluid requirements in children (Rush 436):
-premature infants: 150 ml/kg/d
-newborn: 80-90 ml/kg/d
-infants > 30d to adulthood: use 100:50:20 rule
39. Cord injury syndromes (Way 824):
-anterior cord syndrome: damage to spinothalamic (P+T) tracts and corticospinal (motor) tracts
-central cord syndrome: preservation for distal leg and sacral motor and sensory fibers
-Brown-Sequard syndrome: ipsilateral loss of motor, proprioception, LT; contralateral P+T loss
40. Renal graft rejection:
-oliguria, weight gain, hypertension, increased BUN/Cr, increased graft size, graft tenderness, fever and
leukocytosis
41. Jaundice of Pregnancy (Harrison 1675):
-2nd-3rd trimester
- ALP, bilirubin
-AST/ALT normal
-benign, self-limited
42. Glucose requiring tissues: neurons, RBC, renal medulla, bone marrow (Rush 42)
43. Paget’s Disease of Bone (Merck 473):
- bone turnover
-Pelvis > femur > skull > tibia > vertebrae > clavicle
-X-ray: bone density, cortical thickening, bowing, overgrowth
-Labs: ALP, hydroxyproline in urine, Ca normal or , phosphate normal
-osteosarcoma
44. High Output renal failure (Rush 103):
-may occur with no antecedent oliguric phase
-clinical and lab findings may be similar to oliguric RF
-damage to distal nephron with patchy necrosis
-usually spontaneously resolves
45. Autosomal dominant conditions:
-vWD, MEN, familial adenomatous polyposis, Marfan’s syndrome
46. Esophageal perforations:
-most common cause: instrumentation
-most common non-iatrogenic cause: Boerhaeve’s syndrome
47. Maximum dose of lidocaine: 300-(?500) mg; bupivicaine 2mg/kg, 175mg/dose or 400mg/24h (Epocrates)
48. Hepatitis B: 10-15% will have chronic hepatitis

37
F.Ling - POS notes and points (4)

49. Hepatitis C: 75-80% will develop chronic hepatitis


50. Drugs that do not need adjusting in renal failure (Schwartz 150)
-chloramphenicol
-ampicillin (minor)
-erythromycin
-clindamycin
-ceftriaxone
51. NO released from endothelium and causes vasodilation and capillary permeability
52. Renal failure blood values: H, K, PO4, Mg; Ca, Na
53. Magnesium: clinical effects similar to calcium; blood levels parallel potassium levels
54. Paraneoplastic syndromes:
-ACTH/Cushing: small cell lung ca
-SIADH: small cell lung ca
-Horner’s syndrome (not really paraneoplastic): SCC/Pancoast tumour
-Hypercalcemia/PTH-like hormone: SCC lung, breast ca, RCC
-Erythrocytosis/erythropoietin: RCC
-Acanthosis nigricans: gastric/uterine/lung ca
55. Gompertzian curve: sigmoid curve describing growth of tumours early exponential growth that slows as
tumour size increases
56. Radiation to thyroid: 40% risk of developing thyroid carcinoma
57. Contraindications for thrombolytics:
-absolute:
-prior hemorrhagic stroke, any stroke w/n past 6-12 months, brain neoplasm, suspected aortic
dissection
-relative:
-major surgery or trauma prior 2-3weeks, bleeding diathesis, coumadin, prolonged CPR > 10 min,
pregnancy, uncontroled HTN > 180/110
-streptokinase contraindicated if given in prior year
58. Tissue ischemia times (Schwartz 2037):
-skin 12h
-nerve 8h
-muscle 6h
-(brain 4min)
59. Most common non-bacterial infection in late burns: candida
60. Nerve most likely injued in 4 compartement fasciotomy following tibial fracture: peroneal (superficial)
61. Contraindications to flex/ex views of C-spine:
-altered sensorium, subluxation on lateral C-spine film, any neurological deficit (eg. Brown Sequard)
62. Prostate cancer:
-does not metastasize to brain
-can metastasize to colon
-can cause DIC
63. Sensory innervation of ear:
-middle ear: CN XI
-tympanic membrane and EAC: CN V3 (auriculotemporal branch), VII, X
-pinna:
-CN V3
-cervical plexus:
-lesser occipital nerve (C2): skin posterior to auricle
-great auricular nerve (C2,3): lower ½ of auricle
64. Methyldopa hemolytic anemia Coomb’s test
65. HIV most often presents as generalized lymphadenopathy
66. CEA elevated in: heavy cigarette smokers, cirrhosis, ulcerative colitis, maligancies

38
F.Ling - POS notes and points (5)

67. Radiological signs of hyperparathyroidism aka osteitis fibrosa cystica (Harrison 2229):
-reabsorption of phalangeal tufts and subperiosteal absorption
-thinning of dura lamina of teeth
-salt and pepper appearance of skull
68. Tissue expansion (Schwarz 2105):
-epidermal thikening in first week goes back to normal
-decreased dermal thickness
-increases vascularity of skin
69. Hydrogen secretion in kidneys (Ganong 660-661):
-three major reactions to remove tubular fluid hydrogen:
a. HCO3 CO2+H2O
b. HPO4 H2PO4
c. NH3 NH4

39
Staging criteria: primary tumor (T)
Tx Minimum requirements to assess primary tumor cannot be
met
T0 No evidence of primary tumor
TIS Carcinoma in situ
T1 Tumor confined to antral mucosa of infrastructure with no
bone erosion or
destruction
T2 Tumor confined to suprastructure mucosa without bone
destruction, or to infrastructure with destruction of medial or
inferior bony walls only
Osama Marglani
T3 More extensive tumor invading skin of cheek, orbit, anterior
ethmoid sinus, or pterygoid muscle
T4 Massive tumor with invasion of cribriform plate, posterior
ethmoid sinus,
sphenoid sinus, nasopharynx, pterygoid plate, or base of skull

Inflammatory polyp.
Inverted papillomas and The medium-power microscopic
exophytic squamous papillomas appearance of this lesion is
are both characterized by characteristic of a nasal
proliferations of the same type inflammatory polyp. Note the
of epithelium. In inverted edematous connective tissue
papillomas, this epithelium filled with numerous eosinophils
characteristically grows down (bright pink granules) and
into preexisting mucosal plasma cells (blue cells with
glands, displacing and eccentric round nuclei and
replacing the normal epithelium perinuclear pink zone in the
as it proliferates. As the cytoplasm). The overlying
abnormal epithelium continues respiratory-type epithelium
to expand below the surface, it shows some reactive expansion
causes a broad-based mucosal (hyperplasia) of the basal cell
elevation. layer but the overlying ciliated
epithelial cells are still present.

Rhinosporidium
seeberi .
Rhinosporidiosis
occurs in the
Americas, Europe,
Africa, and Asia but is
most common in the
tropics, with the
highest prevalence in
southern India and Sri
Lanka.
R. seeberi is
visualized with fungal
stains such as
methenamine silver
and Periodic acid-

40
1
clival chordoma, "Large cells with
multiple vacuoles
depicting tumor and are called
cranial nerve 'physaliferous
relationships prior to cells' because of
a resemblance to
resection of the jellyfish.
petrous apex and These
removal of the tumor. neoplasms
arise from
remnants of
primitive
notochord .

Carcinomas may arise within a Squamous papilloma


preexisting papilloma or directly
from non-papillomatous epithelium. These are finger-like
All of the epithelial cells here have structures that project into
malignant cytologic features
(nuclear enlargement, variability in the air passages above the
size and shape) and they are surrounding mucosa. They
arranged in a disorganized growth
pattern. are surfaced by abnormally
A most important feature is that thick, non-keratinizing
these abnormal cells have invaded stratified squamous
the connective tissue where they
infiltrate as small irregular nests epithelium. The epithelial
and even as individual cells. cells are arranged in an
Contrast this growth pattern with orderly pattern and they do
the smooth, expansile epithelial
proliferations in the inverted not have the cytologic
papilloma. features of malignancy.

Contrast the normal surface


3 types. squamous epithelium with that
of the adjacent invasive
WHO. carcinoma. This tumor is
classified as a squamous cell
I keratinizing, carcinoma because some of the
tumor cells exhibit recognizable
II nonkeratinizing, squamous differentiation (note
the glassy pink nests of
keratinized malignant cells
III undifferentiated within the tumor). Keratinizing
and non-keratinizing squamous
subtypes cell carcinomas may arise
anywhere from the nasal
vestibule to the lung as well as
inside the oral cavity.

41
2
! !
Cystic lesions The ameloblasts are
the palisaded cells
with the nuclei pulled
away from the
basement membrane
around a stellate
reticulum like tissue
and in a fibrous stroma
.
REVERSED
POLARIZATION.

Normal thyroid tissue with


follicles filled with colloid .
Thyroid cells form follicles,
spheres of epithelial cells
(always single-layered in
health, usually more-or-less
cuboidal, variably tall or
short).
The C-cells (parafollicular
cells) of the thyroid are
visible between the follicles

" "
Psammoma body within a
papillary cancer . calcified sphere, or
large clear areas within the psammoma body
nuclei which look like "Little
Orphan Annie" eyes are
circled in blue .
Although these nuclear
features are
characteristic of
papillary carcinoma, Papillary thyroid
they are not carcinoma accounts
pathognomonic for about 80% of all
Papillary cancer (low thyroid carcinomas
resolution). Notice the
frond-like projections.

42
3
$ % & ' #
Medullary (C-cell) Follicular
carcinoma of the adenoma H/E
thyroid with amyloid preparation
stroma . x 100
Immunohistochemica
l anti-calcitonin Follicular
antibody stain of a carcinoma
medullary carcinoma accounts
showing strong red for less than
positivity 10%

Lymphocytic Anaplastic
infiltrate in the carcinoma
thyroid, with histology H/E
lymphoid follicle preparation
formation and x 200
fibrosis.

) " (
Schwannoma
(neurilemoma) is a
benign neoplasm of
the Schwann cells of
the neural sheath .

43
4
% ' )
(HE x100). Antoni type A tissue shows
fascicles of spindle-shaped
Typical cellular Schwann cells streaming
around numerous acellular,
groups ("Zellballen") eosinophilic areas
surrounded by a surrounded by paralleled or
palisaded spindled cells
capillary network. with blunt, elongated nuclei
Round, fairly regular The cells of these Verocay
bodies all orient their long
nuclei. Variable, axes toward the acellular
often granular area, and the areas
themselves are oval, linear
cytoplasm. or serpiginous in shape.

Tx Primary tumor cannot be assessed


T0 No evidence of primary tumor
T1 Tumor < 2cm in greatest dimension
T2 Tumor 2-4 cm in greatest dimension
T3 Tumor 4-6 cm in greatest dimension
T4 Tumor > 6 cm in greatest dimension

All categories are subdivided: (a) no local extension; (b) local


extension.
Local extension is clinical or macroscopic invasion of skin, soft
tissue, bone, or nerve.
Microscopic evidence alone is not a local extension for
classification purposes.

pleomorphic adenomas
originate from the
intercalated duct cells
and myoepithelial cells
oncocytic tumors
originate from the
striated duct cells
acinous cell tumors
originate from the acinar
cells,
Mucoepidermoid
tumors and squamous
cell carcinomas develop
in the excretory duct
cells.

44
5
The diverse microscopic pattern
of this lesion is one of its most pleomorphic
characteristic features.
Islands of cuboidal cells
adenoma showing
arranged in ductlike structures the epithelial (E) and
is a common finding.
the stromal (S)
Loose chondromyxoid stroma,
hyalinized connective tissue, components.
cartilage(,arrows) and even
osseous tissue are observed.
This neoplasm is typically
encapsulated, although tumor
islands may be found within the
fibrous capsule.

Nerve (N) invaded by Adenoid cystic


carcinoma with Swiss
adenoid cystic cheese pattern.
carcinoma It is the second-most
(the blue area common malignant
surrounding the tumor of the salivary
glands.
nerve). ACC is the most
Spread may occur common malignant
by emboli along the tumor found in the
submandibular,
nerve lymphatics sublingual, and minor
salivary glands.

, + ( +
Warthin's tumor (benign Hodgkin's disease
papillary cystadenoma
lymphomatosum) is the involving the
second most common parotid
benign tumor of the parotid
gland. gland. Note the
It accounts for 2-10% of all Reed-Sternberg
parotid gland tumors. cell. (Fine needle
Bilateral in 10% of the aspiration, Pap,
cases.
630x)
may contain mucoid brown
fluid inFNA

45
6
High Power Mid Power
Lymphocytc
infilterates.

The acinic cell adenocarcinoma


occurs mainly in the parotid Electron microscopy shows
gland, a tremendous number of
This lesion is characterized by a mitochondria in the epithelial
benign histomorphologic picture cells, which are responsible
but by occasional malignant for its granular eosinophilic
behavior.
appearance.
These lesions are treated by
surgical excision with a Mitochondria-rich oncocytes
generous margin of normal are found in Warthin’s
tissue on the periphery. tumors .
They do not tend to metastasize
to lymph nodes but favor bone Oncocytes selectively
and lung as metastatic sites. incorporate technetium Tc
Bilateral involvement occurs 99m and appear as hot
in 3% of patients, making spots on a radionucleotide
acinic cell carcinoma the scan.
second-most common
neoplasm, after Warthin’s
tumor, to exhibit bilateral
presentation.

$
$
Mucoepidermoid carcinoma (MEC) is the MECs contain two
most common malignant tumor of the parotid major elements:
gland and the mucin-producing cells
and epithelial cells of
second-most common malignancy the epidermoid variety.
(adenoidcystic carcinoma is more common) MEC is divided into
of the submandibular and minor salivary low-grade (well
glands. differentiated), high-
MECs constitute approximately 35% of grade (poorly
salivary gland malignancy, and 80% to 90% differentiated)
of MECs occur in the parotid gland.

46
7
-

It is composed of uniform
basaloid epithelial cells with
a monomorphous pattern.

The arrangement of tumor


cells may be trabecular ,
tubular or solid.

Histologically, these tumors


are distinguished from
pleomorphic adenomas
by their absence of
chondromyxoid stroma and
the presence of a uniform
epithelial pattern.

Tx Primary tumor cannot be assessed


T0 No evidence of primary tumor
T1 Tumor < 2cm in greatest dimension
T2 Tumor 2-4 cm in greatest dimension
T3 Tumor 4-6 cm in greatest dimension
T4 Tumor > 6 cm in greatest dimension

All categories are subdivided: (a) no local extension; (b) local


extension.
Local extension is clinical or macroscopic invasion of skin, soft
tissue, bone, or nerve.
Microscopic evidence alone is not a local extension for
classification purposes.

& &
A very high power Spider web.
view of the The buccal
dermoepidermal
mucosa
junction
involved most
Civatte bodies often
(arrows),
reticular form
keratinocyte
enlargement, and
most common
coarse collagen
bundles are illustrated.

47
8
ominous
characteristic of
squamous
carcinoma is its
ability to surround
nerves and to
infiltrate for long
distances in a
perineural fashion

Many nuclei show marked


clumping of hyperchromatism
chromatin. There is and extremely
an abnormal mitotic atypical mitoses
figure in the center of
the photomicrograph.

Most cells are easily


identifiable as
squamous cells. At
one end there is a
mass of parakeratin
("keratin pearl").

48
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Otolaryngology - Head and Neck Surgery Page 1 of 7

Dr. F. Ling's

Otolaryngology - Head and Neck


Surgery Notes

Selected Pharmacopoeia
ANALGESI CS

Nonsteroidal Anti-Inflammatories - COX-2 Inhibitors

 celecoxib (Celebrex): 200 mg PO qd or 100 mg PO bid


 rofecoxib (Vioxx): 50 mg PO qd < 5 days
 valdecoxib (Bextra): 10 mg PO qd

Nonsteroidal Anti-Inflammatories - Other

 ibuprofen (Motrin, Advil, Nuprin, Rufen): 200-800 mg PO tid-qid.


Peds > 6 mo: 5-10 mg/kg PO q6-8h
 ketorolac (Toradol): 15-30 mg IV/IM q6h or 10 mg PO q4-6h prn
 naproxen (Naprosyn): 250-500 mg PO bid

Opioids

Approximate Recommended Starting Dose


Opioid equianalgesic Adults > 50 kg Children/Adults 8-50 kg
Agonists
IV/SC/IM PO IV/SC/IM PO IV/SC/IM PO

10 mg 30-60 mg 10 mg 30 mg 0.1 mg/kg 0.3 mg/kg


morphine
q3-4h q3-4h q3-4h q3-4h q3-4h q3-4h
75 mg 130 mg 60 mg 60 mg 1 mg/k q3-
codeine n/r
q3-4h q3-4h q2h q3-4h 4h

0.1 mg 0.1 mg
fentanyl n/a n/a n/a n/a
q1h q1h
0.015 0.06
1.5 mg 7.5 mg 1.5 mg 6 mg q3-
hydromorphone mg/kg q3- mg/kg q3-
q3-4h q3-4h q3-4h 4h
4h 4h

0.75
100 mg 300 mg 100 mg
meperidine n/r mg/kg q2- n/r
q3h q2-3h q3h
3h

30 mg 10 mg 0.2 mg/kg
oxycodone n/a n/a n/a
q3-4h q3-4h q3-4h

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Equianalgesic Table

Drug SC PO

Morphine 10 mg 20 mg

Hydromorphone 2 mg 4 mg
Oxycodone N/A 7.5-10 mg

Codeine 60 mg 120 mg

Fentanyl 100-150 ug TD

Meperidine 75 mg 300 mg
Methadone N/A 2 mg

Breakthrough Doses with TD Fentanyl


Hydromorphone
Fentanyl TD Morphine PO
PO

25 mcg/h 10 mg q2h prn 2 mg q2h prn

50 mcg/h 20 mg q2h prn 4mg q2h prn


75 mcg/hr 30 mg q2h 6 mg q2h prn

100 mcg/h 40 mg q2h prn 8 mg q2h prn

 codeine: 0.5-1 mg/kg up to 15-69 mg PO/IM/IV/SC q4-6h

 fentanyl: 1 patch q72h [25, 50, 75, 100 mcg/h]

 hydromorphone (Dilaudid): Adults: 2-4 mg PO q4-6h. 0.5-2 mg


IM/SC or slow IV q4-6h. 3 mg PR q6-8h

Opioid Antagonists

 naloxone (Narcan): Opioid overdose: 0.4-2.0 mg q2-3 min prn

ANAESTHESI A

 midazolam (Versed): adult sedation/anxiolysis: 5 mg or 0.07 mg/kg


IM; or 1 mg IV slowly q2-3 min up to 5 mg

 propofol: 20-40 mg IV q10sec until induction (2-2.5 mg/kg)

Local Anaesthetics

 Maximum recommended doses:

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 Lidocaine 5 mg/kg. Max 300 mg

 Lidocaine with epinephrine 7 mg/kg. Max 500 mg

 Cocaine 3 mg/kg. Max 200 mg

ANTI M I CROBI ALS

Antifungal Agents

 fluconazole (Diflucan): 200 mg first day, then 100 mg IV/PO qd. Peds:
6 mg/kg first day, then 3 mg/kg qd

 itraconazole: 100-200 mg PPO qd

 ketoconazole (Nizoral): 200-400 mg PO qd . Contraindicated iwth


midazolam, pimozide, triazolam

 nystatin: Thrush: 4-6 ml PO swish and swallow qid. [Susp 100,000


units/ml]

Antiviral Agents

 acyclovir: Zoster: 800 mg PO qid x 7-10 days

Cephalosporins

 cefazolin (Ancef): 0.5-1.5 g IM/IV q6-8h. Peds: 25-50 mg/kg/day


divided q6-8h

 cephalexin (Keflex): 250-500 mg PO qid. Peds: 25-50 mg/kg/day

 cefprozil (Cefzil): 250-500 mg PO bid. Peds otitis media: 15


mg/kg/dose PO bid

 cefuroxime (Cefin, Kefurox): 750-1500 mg IM/IV q8h. Peds: 50-100


mg/kg/day IV divided q6-8h. 250-500 mg PO bid. Peds: 20-30
mg/kg/day susp PO divided bid

 cefotaxime: 1-2 g/day IM/IV q12h. Peds: 50-180 mg/kg/day IM/IV


divided q4-6h

 ceftazidime: 1 g IM/IV or 2 g IV q8-12h. Peds: 30-50 mg/kg IV q8h

 ceftriaxone: 1-2 g IM/IV q24h. Peds: 50-75 mg/kg/day up to 2 g


divided q12-24h

Macrolides

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 azithromycin (Zithromax): 500 mg IV qd. PO: 10 mg/kg upt to 500


mg on day 1, then 5 mg/kg up to 250 mg qd to complete 5 days. GAS
pharyngitis: 12 mg/kg up to 500 mg qd x 5d. Short regimens for peds
OM: 30 mg/kg PO single dose or 10 mg/kg PO qd x 3 days

 clarithromycin (Biaxin): 250-500 mg PO bid. Peds: 7.5 mg/kg PO bid

 erythromycin base: 250-500 mg PO qid, 333 mg PO tid, or 500 mg PO


bid

Penicillins

 penicillin G: Pneumococcal pneumonia and severe infections: 250,000-


400,000 units/kg/day (8-12 MU in adult) IV divided q4-6h

 penicillin V: Adults: 250-500 mg PO gid. Peds 25-50 mg/kg/day


divided bid-qid

 amoxicillin: 250-500 mg PO tid, or 500-875 mg PO bid. Acute sinusitis


with antibiotic use in past month and/or drug-resistant S penumoniae rate
> 30%: 3-3.5 g/day PO. Peds: 40 mg/kg/day PO divided tid or 45
mg/kg/day divided bid. OM/sinusitis in children at high risk for
penicillin-restant S pneumoniae (age <2 yo, antibiotics within <3 mo,
day care): 90 mg/kg/day PO divided bid-tid x 10 days for < 2yo, x5-7
dyas for > 2yo [Caps 250, 500 mg, tabs 500, 875 mg, susp 125, 250
mg/5ml, 200& 400 mg/5ml]

 amoxicillin-clavulanate (Clavulin): 500-875 mg PO bid or 250-500 mg


tid. Peds: 45 mg/kg/day PO divided bid or 40 mg/kg/day divided tid for
otitis, sinusitis, pneumonia

Prophylaxis for Bacterial Endocarditis (for dental, oral, respiratory tract,


or esophageal procedures)

 amoxicillin 2 g PO 1h before procedure

 ampicillin 2 g IM/IV within 30 minutes before procedure

 clindamycin 600 mg PO/IV; cephalexin 2 g PO or cefazolin 1 g IM/IV


within 30 minutes before procedure

Quinolones

 ciprofloxacin: 200-400 mg IV q8-12h. 250-750 mg PO bid

 levofloxacin (Levaquin): 250-500 mg PO/IV qd

 gatifloxacin (Tequin): 400 mg IV/PO qd

Sulfonamides

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 trimethoprim-sulfamethoxazole (Bactrim, Septra): One tab PO bid,


double strength (DS, 160 mg/800 mg) or single strenth (SS, 80 mg/400
mg). Peds: 5 ml susp/10 kg (up to 20 ml)/dose PO bid

Other

 clindamycin: 600-900 mg IV q8h. 150-450 mg PO qid. Peds: 20-40


mg/kg/day IV divided q6-8h or 8-25 mg/kg/day susp PO divided tid-qid

 metronidazole (Flagyl): 500 mg PO bid. Anaerobic infections: 1 g or


15 mg/kg IV, then 500 mg or 7.5 mg/kg IV/PO q6h. Peds: 7.5 mg/kg
IV q6h. C difficile diarrhea: 500 mg (10-15 mg/kg/dose for peds) PO
tid

 vancomycin: 1 g IV q12h. Peds: 10-15 mg/kg IV q6h. C difficile: 40-


50 mg/kg/day up to 500 mg/day PO divided qid x7-10 days

CARDI OVASCULAR

ACE Inhibitors

 captopril (Capoten): 25 mg PO bid-tid. Max 450 mg/day

 enalapril (Vasotec): 5 mg PO qd. Max 40 mg/day

 fosinapril (Monopril): 10 mg PO qd. Max 80 mg/day

 ramipril (Altace): 2.5 mg PO qd. Max 20 mg/day

Beta-blockers

 metoprolol: 100 mg PO qd or 50 mg PO bid. Max 450 mg/day

Diuretics

 furosemide (Lasix): 20-80 mg IV/IM/PO, increase dose by 20-40 mg


q6-8h until desired response, max 600 mg/day

 hydrochlorothiazide: 12.5-25 mg PO qd. Max 50 mg/day

 triamterene + HCTZ (Dyazide): 37.5/25 mg and 50/25 mg

DERM ATOLOGY

 fucidic acid (Fucidin): apply tid-qid [cream 2% fusidic acid 5,15,30 g,


ointment 2% sodium fusidate 5,15,30 g]

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 mupirocin (Bactroban): apply tid [cream/ointment 2% 15,30 g]

ENDOCRI NE

 calcium supplementation
 normal range: 2.2-2.6 mmol/L
 mild depletion: 1.9-2.2 mmol/L
 moderate depletion: 1.5-1.9 mmol/L
 severe depletion: < 1.5 mmol/L

I V replacement
 Hypocalcemia (severe or symptomatic)
 100 to 200 mg of elemental calcium (approx. 4.5 to 9 mEq
or 10 to 20 mL of a 10% solution) injected slowly IV over
10 minutes
 will usually raise serum total calcium by 0.25 mmol/L
(1 mg/dL) with levels returning to baseline in about
30 minutes
 To maintain levels above baseline, intermittent boluses a
continuous infusion of 1-2 mg/kg/hour of elemental calcium
may be necessary
 eg. 10 g calcium gluconate to 1L NS or D5W and run
at 50-100 cc/h (500-1000 mg/h ~ 45-90 mg elemental
Ca/h)
 serum calcium will usually normalize with this
infusion regimen in 6-12 hours
 infusion rate may need to be decreased to 0.3 to 0.5
mg/kg/hour of elemental calcium as the serum
calcium begins to approach normal levels

Name Type Strengthper tab (mg) Elemental Calcium(mg)


Alka-Mints calciumcarbonate 850mg 340mg
Caltrate calciumcarbonate 1500mg 600mg
OsCal calciumcarbonate 625or 1250mg 250or 500mg
Rolaids calciumcarbonate 550mg 220mg
TitralacTablets calciumcarbonate 420mg 168mg
TitralacLiquid calciumcarbonate 1000mg 400mg
TumsandTumsE-X calciumcarbonate 500or 750mg 200or 300mg
TumsUltraandTums
calciumcarbonate 1000or 1250mg 400or 500mg
500

Calcium Strength of each Amount of elemental Number of tablets to


supplement tablet (mg) calcium per tablet (mg) provide 1000 mg calcium
Calcium carbonate 625 250 4
650 260 4
750 300 4
835 334 3

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1250 500 2
1500 600 2
Calcium citrate 950 200 5
Calcium gluconate 500 45 22
650 58 17
1000 90 11
Calcium lactate 325 42 24
650 84 12
Calcium 500 115 9
phosphate, dibasic
Calcium 800 304 4
phosphate, tribasic 1600 608 2

PULM ONARY

 racemic epinephrine: Severe croup: 0.05 ml/kg/dose diluted to 3 ml


with NS. Max dose 0.5 ml [2.25% racepinephrine in 15 & 30 ml]

 dexamethasone (Decadron): Croup: 0.15-0.6 mg/kg PO or IM x1.


Acute asthma: >2 yo: 0.6 mg/kg to max 16 mg PO qd x 2 days

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!

" #

$ !$ % & ! ' () (
-hormone response pathways activated by:
-mediators released by injured tissue
-neural and nociceptive input originating from site of injury
-baroreceptor stimulation form intravascular volume depletion

Hormones Regulated by the Hypothalamus, Pituitary, and Autonomic System


Hypothalamus Pituitary Autonomic System

Corticotropin-releasing hormone Anterior pituitary: Norepinephrine


(CRH) ACTH: Cortisol IGF Epinephrine
Thyrotropin-releasing hormone TSH: Thyroxine, Aldosterone
(TRH) Triiodothyronine Renin-angiotensin
Growth hormone-releasing hormone Growth hormone Insulin
(GRH) FSH, LH: sex hormones Glucagon
Luteinizing hormone-releasing Somatostatin Enkephalins
hormone (LHRH) Prolactin
(endorphin)
Posterior pituitary:
Vasopressin
Oxytocin

Hormone-Mediated Receptor Activity:


-three major types of signal transduction mechanisms:
-receptor kinases (eg. insulin and IGF)
-G protein-coupled receptors (activated by peptide hormones, neurotransmitters, prostaglandins)
-ligand-gated ion channels

Hormone-Mediated Intracellular Pathways:


-cAMP:
-one of most common intracellular second messengers
-activation of adenylate cyclase converts ATP to cAMP activation of intracellular protein kinases
- cAMP associated with functional lymphocyte responses that generally are immunosuppressive:
- T-cell proliferation, lymphokine production, and cytotoxic function
- plasma cell production of Ab
- PMN chemotaxis and production of superoxides, H2O2 and lysosomal enzymes
- histamine release by basophil and mast cells
-intracellular receptors:
-eg. cytosolic glucocorticoid receptor

! ( ! ! ! )! * +)

Corticotropin-Releasing Hormone:
-synthesis:
-stress (pain, fear, anxiety) paraventricular nucleus of hypothalamus CRH synthesis
-proinflammatory cytokines and ADH
-negative feedback: circulating glucocorticoid decrease CRH mRNA transcription

56
-secretion:
-stimulated by angiotensin II, neuropeptide Y, serotonin, ACh, IL-1, IL-6
-inhibited by GABA, substance P, ANP, endogenous opioids, l-arginine
-stimulates ACTH production and release
-mechanism:
-via cAMP production in ACTH producing corticotrophs

Adrenocorticotropic Hormone (ACTH):


-synthesized, stored and released by anterior pituitary upon CRH stimulation
-precursor: proopiomelanocortin (POMC)
-cleaved to: alpha-melanocyte stimulating hormone, beta-lipotropic, beta-endorphin, and ACTH
-diurnal variation:
-highest late at night and lasts until just before sunrise
-most injury is characterized by elevations in CRH and ACTH; proportional to severity of injury
-pain and anxiety are prominent mediators
-other mediators include ADH, AT II, cholecystokinin, VIP, catecholamines, oxytocin, proinflammatory
cytokines
-ACTH acts in zona fasciculata of adrenal increased glucocorticoid production
-desmolase-catalysed side-chain cleavage of cholesterol pregnenolone

Cortisol/Glucocorticoids:
-cortisol essential for survival after significant physiological stress
-functions:
-potentiates actions of glucagon and epinephrine hyperglycemia
-promotes gluconeogenesis in liver (eg. inducing PEP-carboxykinase and transaminase)
-decreases insulin-binding to insulin receptors in muscles and adipose tissue
-induces proteolysis and augments release of lactate in skeletal muscle shifts substrate for hepatic
gluconeogenesis
-stimulates lipolysis and inhibits glucose uptake by adipose tissues
-adrenal insufficiency (Addison’s Crisis):
-from adrenal suppression secondary to exogenous glucocorticoid
-weakness, nausea, vomiting, fever, hypotension
-hypoglycemia (from gluconeogenesis), hyponatremia ( renal Na absorption), hyperkalemia

Macrophage Inhibitory Factor:


-glucocorticoid antagonist produced by anterior pituitary
-can potentially reverse immunosuppressive effects of glucocorticoid systemically via anterior pituitary secretion
and at local sites of inflammation where MIF is produced by T-lymphocytes

Thyrotropin-Releasing Hormone and Thyroid Stimulating Hormone:


-TRH synthesis, storage, and release of TSH
-TSH thyroxine (T4) production
- TSH release by TRH and estrogen
- TSH release by T3, T4, corticosteroids, growth hormones, somatostatin, and fasting
-T4 converted to T3 by peripheral tissues
-T4 and T3 involved in negative feedback to inhibit TRH and TSH release
-function of thyronines:
-enhance membrane transport of glucose and increase glucose oxidation
-increase formation and storage of fat when CHO intake is excessive
-increase in cellular metabolism
-after major injury:
-reduced available T3 and circulating TSH:
-d/t inhibitory effects of cortisol and conversion of T4 to rT3 (inactive)
-“euthyroid sick syndrome or non-thyroidal illness”

57
-thyroid hormone alteration in systemic inflammation not mediated by endogenous IL-1
-in severely injured or critically ill patients, a reduced free T4 concentration predictive of high mortality
-experiments have shown that thyroid hormone depletion significantly decreases cellular and humoral immunity
-repletion is associated with enhancement of both types of immunity

Growth Hormones:
-GHRH stimulates pituitary release of GH in pulsatile fashion during sleeping hours
-GH release also affected by:
-autonomic stimulation, thyroxine, ADH, ACTH, alpha-melanocyte stimulating hormone, glucagon, and
sex hormones
-physical exercise, sleep, stress, hypovolemia, fasting hypoglycemia, decreased circulating fatty acids, and
increased amino acid levels
-inhibited by:
-hyperglycemia, hypertriglyceridemia, somatostatin, beta-adrenergic stimulation, cortisol
-function:
-promote protein synthesis while enhancing mobilization of fat stores
-hepatic ketogenesis
-inhibits insulin release and decreases glucose oxidation elevated glucose levels
-role of GH during stress:
-promote protein synthesis while enhancing mobilization of fat stores
-direct stimulation
-potentiation of adrenergic lipolytic effects on adipose stores
-promote hepatic ketogenesis
-inhibit insulin release and decrease glucose oxidation
-protein synthesis:
-mediated by secondary release of insulinlike growth factor-1 (IGF-1)
-promotes amino acid incorporation and cellular proliferation
-attenuates proteolysis in skeletal muscle and liver
-IGFs:
-mediators of hepatic protein synthesis and glycogenesis
-adipose tissue: increases glucose uptake and lipid synthesis
-skeletal muscles: increases glucose uptake and protein synthesis
-promote incorporation of sulfate and proteoglycans into cartilage skeletal growth

-associated decrease in protein synthesis and observed negative nitrogen balance attributed to reduction in
IGF-1 levels
-IGF produced predominantly in liver; dysfunction may contribute to negative nitrogen balance after injury

-GH and IGF-1 are immunostimulatory and promote tissue proliferation

Somatostatin:
-potent inhibitor of GH, TSH, renin, insulin, and glucagon release
-may regulate excessive nutrient absorption and activities of GH and IFG during convalescence form injury

Gonadotrophins and Sex Hormones:


-GnRH (hypothalamus) stimulates FSH and LH release from anterior pituitary
-release can be blocked by CRH, prolactin, estrogen, progestins, and androgens
-FSH and LH release suppressed after injury, stress, or severe illness (d/t inhibitory activity of CRH)
-estrogens:
-inhibit cell-mediated immunity, NK cells activity and neutrophil function
-stimulatory for antibody-mediated immunity
-androgens:
-predominantly immunosuppressive

58
Prolactin:
-GnRH and dopamine suppresses PRL secretion from anterior pituitary
-stimulants: CRH, TRH, GHRH, serotonin, VIP
-elevated levels seen after injury
-may account for amenorrhea frequently seen in women after injury or major operations
-has immunostimulatory properties

Endogenous Opioids:
-beta-endorphins attenuate pain perception; capable of inducing hypotension through a serotonin-mediated pathway
-enkephalins produce hypertension
-in GI tract: reduces peristaltic activity and suppresses fluid secretion
-in glucose metabolism:
-B-endorphins and morphine induce hyperglycemia, but also increase insulin and glucagon release by
pancreas
-endorphins influence immune system by increasing NK cell cytotoxicity and T-cell blastogenesis
-IL-1 activates release of POMC
-opioids compromise natural and specific immune system:
-inhibit proliferation and differentiation of lymphocytes and monocytes/macrophages

! ( ! ! ! )! * +)

Arginine Vaspressin (or ADH):


-synthesized in anterior hypothalamus and transported by axoplasmic flow to posterior pituitary for storage
-release stimulated by:
-elevated plasma osmolality (via sodium-sensitive hypothalamic osmoreceptors)
-changes in effective circulating volume (~10%)
-release enhanced by beta-adrenergic agonists, angiotensin II stimulation, opioids, anesthetic agents, pain,
and elevated glucose concentrations
-release inhibited by:
-alpha-adrenergic agonists and atrial natriuretic peptide (ANP)
-function:
-promotes reabsorption of water from distal tubules and collecting ducts
-mediates vasoconstriction peripherally:
-may cause trauma-induced ischemia/reperfusion phenomenon that precedes gut barrier
impairment
-stimulates hepatic glycogenolysis and gluconeogenesis hyperglycemia that increases osmotic effect
-elevated secretion is another characteristic of trauma, hemorrhage, open-heart surgery, and other major operations
-SIADH:
-low u/o, highly concentrated urine, and dilutional hyponatremia
-plasma osmolality < 275 mOsm/kg H2O and urine osmolality > 100 mOsm/kg H2O
-commonly seen in pts with head trauma and burns
-Diabetes Insipidus:
-voluminous output of dilute urine
-seen in comatose patients

Oxytocin:
-role in injury response unknown
-stimulates contraction of lactating mammary glands and induces uterine contractions in parturition

59
! &

Catecholamines:
-hypermetabolic state observed after severe injury has been attributed to activation of adrenergic system
-norepinephrine: from synaptic leakage during sympathetic nervous system activity
-epinephrine: from secretions of chromaffin cells of adrenal medulla
-functions:
-promotes stress-induced hyperglycemia
-liver: promotes glycogenolysis, gluconeogenesis, lipolysis and ketogenesis
-pancreas: decreased insulin secretion and increased glucagon secretion
-adipose: increases lipolysis
-skeletal muscle: inhibits insulin-facilitated glucose uptake
-other:
-thyroid: increase secretion of PTH, T4, T3
-secretion of renin
-inhibits release of aldosterone
-immune function:
-enhances leukocyte demargination with resultant neutrophilia and lymphocytosis
-lowers ratio of CD4 to CD8 T-cells

Aldosterone:
-mineralocorticoid
-synthesized, stored, and released in adrenal zona glomerulosa
-release induced by: AT II, hyperkalemia, and aldosterone stimulating factor (ASF) from pituitary
-ACTH is most potent stimulus for aldosterone release in injured patient
-function:
-maintain intravascular volume by conserving sodium and eliminating potassium and hydrogen ions
-early distal convoluted tubule: increases Na, Cl reabsorption and excretion of H+
-late distal convoluted tubule: Na reabsorption with excretion of K
-major effect on kidneys, but also acts on intestines, salivary glands, sweat glands, vascular endothelium,
and brain

Renin-Angiotensin:
-renin synthesized and stored in renal juxtaglomerular apparatus
-activation and release by:
-ACTH, AVP, glucagon, prostaglandins, potassium, magnesium and calcium
-barorecepors in JGA sense decrease in BP increase secretion
-angiotensin:
-angiotensinogen synthesized by liver
-renin converts angiotensinogen to angiotensin I
-angiotensin-converting enzyme on pulmonary endothelial surfaces converts AT I to AT II
-AT II:
-potent vasoconstrictor that stimulates aldosterone and vaspressin synthesis
-stimulates heart rate and myocardial contractility
-potentiates release of epinephrine by adrenal medulla, increases CRH release, and activates
sympathetic nervous system
-can induce glycogenolysis and gluconeogenesis

Insulin:
-derived from pancreatic beta islet cells
-released by certain substrates, autonomic neural input, and other hormones
-glucose major stimulant of insulin secretion
-others: amino aids, free fatty acids, and ketone bodies
-inhibition of release:

60
-epinephrine and sympathetic stimulation
-glucagon, somatostatin, GI hormones, beta-endorphins, IL-1
-function:
-global anabolic effect: promotes hepatic glycogenesis and glycolysis, glucose transport into cells, adipose
tissue lipogenesis, and protein synthesis
-in injured patient, biphasic pattern of insulin release observed:
-first phase: few hours after injury
-relative suppression of insulin, reflecting influence of catecholamines and sympathetic
stimulation
-later phase:
-return to normal or excessive insulin production with persistent hyperglycemia d/t
peripheral resistance to insulin
-ratio of insulin to glucose is used as a predictor of mortality and survival
-enhances T-cell proliferation and cytotoxicity

Glucagon:
-product of pancreatic alpha islet cells
-stimulants of secretion: plasma glucose concentrations and exercise
-function:
-stimulates hepatic glycogenolysis and gluconeogenesis
-promotes hepatic ketogenesis and lipolysis in adipose
-release after injury is initially decreased, but returns to normal 12 h later

'' #

, ' () (
-cytokines are produced by diverse cell types at site of injury and by systemic immune cells
-activity exerted locally via cell-to-cell interaction (paracrine)
-small polypeptide or glycoprotein; modulate gene transcription
-may be pro- or anti-inflammatory
-direct inflammatory response to infection and injury; actively promotes wound healing
-responsible for:
-fever, leukocytosis, hyperventilation, tachycardia (systemic inflammatory response syndrome SIRS)
-hemodynamic instability characteristic of septic shock
-metabolic derangements of injured patients (eg. muscle wasting and cachexia)
-contribute to end-organ injury multiple organ failure; death

Tumor Necrosis Factor-alpha:


-earliest and one of most potent mediators of injury/infectious response
-source: monocytes/macrophages, T-cells
-release is rapid and short-lived
-presence of effective endogenous modulators, which serve to prevent any propagation of unregulated
TNF-a activity
-major cytokine related to muscle catabolism and cachexia during stress
-amino acids mobilized from skeletal muscles and shunted toward hepatic circulation as fuel substrates
-other functions:
-coagulation activation
-promoting release of PGE2, PAF, glucocorticoid, eicosanoids

Interleukin-1:
-TNF-a induced synthesis of IL-1 by macrophages and endothelial cells
-types:
-IL-1a: cell membrane-associated; exerts influence via cellular contact

61
-IL-1b: in circulation in greater quantities; induces characteristic systemic derangements after injury
-synergistic and similar effects to TNF-a
-half-life (~6 min) less than TNF-a
-effects:
-induces classic inflammatory febrile response to injury: stimulates local prostaglandin activity in anterior
hypothalamus
-anorexia effect on satiety center
-augments T cell proliferation by enhancing IL-2 production
-may influence skeletal muscle proteolysis: cachexia
-decrease pain perception: promote release of endorphin, increasing number of central opioid-like
receptors
-potent stimulant for ACTH and GC release via hypothalamus and pituitary gland
-regulated by IL-1 receptor antagonists (IL-1ra): competes for IL-1 receptor binding

Interleukin-2:
-promotes T-cell proliferation, immunoglobulin production, and gut barrier integrity
-not readily detectable in circulation during acute injury
-secretion impaired in: cancer and AIDS
-attenuated IL-2 expression contributes to transient immunocompromised state of the surgical patient

Interleukin-4:
-glycoprotein molecule
-produced by activated TH2 cells
-functions include:
-induction of B-lymphocyte proliferation
-enhances macrophage MHC class II (HLA-DR and LHA-DP) expression and adhesion molecules
-induces class switching in differentiating B-lymphocytes IgG4 and IgE
-also a potent anti-inflammatory cytokine:
-down-regulates effects of IL-1b, TNF-a, IL-6, IL-8, and superoxides production
-induce apoptosis in inflammatory macrophages (abrogated by IFN-gamma)

Interleukin-6:
-used frequently as an indicator of SIRS and predictor of preoperative morbidity
-levels proportional to extent of tissue injury during an operation
-induced by TNF-a and IL-1
-long half-life
-functions:
-with IL-1, important mediator of hepatic acute-phase protein response
-enhances C-reactive protein, fibrinogen, haptoglobin, amyloid A, a-1-antitrypsin, and
complement production
-induces PMN activation; may delay the phagocytic disposal of senescent or dysfunctional PMNs
-anti-inflammatory effects:
-attenuates TNF and IL-1 activity while promoting release of sTNFRs and IL-1ra
-prolonged and persistent expression of IL-6 associated with immunosuppression and postop
infectious morbidity
-can reduce plasma glutamine

Interleukin-8:
-has been proposed as an additional biomarker for the risk of multiple organ failure
-serves a PMN activator and potent chemoattractant
-does not produce hemodynamic instability characteristic of TNF-a and IL-1

Interleukin-10:
-important endogenous regulatory mediator during inflammatory response

62
-modulates TNF-a activity: reduces TNF-a levels and associated deleterious effects
-may promote sTNFR and IL-1ra production

Interleukin-12:
-promotes differentiation of TH1 cells and production of IFN-gamma
-prevents apoptosis in certain T-lymphocyte populations after their activation

Interleukin-13:
-pleiotropic cytokine sharing may properties of IL-4
-produced during TH2 responses
-with IL-4, modulates macrophage function, but no effects on T-cells
-can upregulate macrophage MHC class I and II antigens and other surface antigens, such as CD23
-can inhibit NO production and expression of proinflammatory cytokines; can enhance production of IL-1ra
-net effect of IL-13, along with IL-4 and IL-10 is anti-inflammatory

Interferon-gamma:
-TH cells activated by the bacterial antigens IL-2 or IL-12 readily produce IFN-gamma
-conversely, IFN-gamma can induce production of IL-2 and IL-12 by TH cells
-important role in activating circulating and tissue macrophages

Granulocyte/Macrophage-Colony Stimulating Factor:


-GM-CSF production induced by IL-2 and endotoxins
-prominent role in delaying apoptosis of macrophages and PMNs
-promotes maturation and recruitment of functional leukocytes necessary for normal inflammatory cytokine
response, and potentially in wound healing

* +) & &+) ) ! ++" )

Programmed Cell Death:


-apoptosis is the principal mechanism by which senescent or dysfunctional cells, including macrophages and PMNs,
are systematically disposed of without activating other immunocytes or the release of proinflammatory contents
-several proinflammatory cytokines delay the normal temporal sequence of macrophage and PMN apoptosis in vitro:
-TNF, IL-1, IL-3, IL-6, GM-CSF, G-CSF, and IFN-gamma
-IL-4 and IL-10 accelerate apoptosis in activated monocytes
-failure of apoptosis of inflammatory immunocytes may perpetuate and augment the inflammatory response,
precipitating multiple organ failure in severely injured and critically ill patients

TNF Receptor-Mediated Programmed Cell Death:


-TNFR activation induce specific cell responses that may include initiation of apoptosis
-two specific transmambrane TNFRs (type I, p55; and type II, p75)
-p55:
-induces apoptosis, cytotoxicity, expression of adhesion molecules on endothelial cells, and
activation of sphingomyelin pathway and nuclear factor-kappa B
-p75:
-induces proliferation of T cells, fibroblasts, NK cells, and proinflammatory cytokine release
-during sepsis, down-regulation of TNFR activity may delay apoptosis of inflammatory macrophages and PMNs,
prolonging the inflammatory response

Fas/CD95 Receptor-Mediated Programmed Cell Death:


-along with p55 TNFR, Fas receptors exhibit similar cytoplasmic sequence motifs, known as “death domains”
-FasR predominantly expressed in liver, lung, heart, intestine, skin, and lymphocytes
-when triggered by FasL (specific ligand) apoptosis
-only known role of the Fas receptor

63
-while induction of apoptosis via Fas/FasL cross-linking in activated immunocytes may be advantageous during
systemic inflammation, this activity at the tissue level may be detrimental to the host

! ) ( , !)

Cortisol/Glucocorticoids:
-glucocorticoid administration before or concomitantly with endotoxins infusion in healthy human beings is able to
attenuate the symptoms, catecholamine response, and acute phase response, but it increases IL-10 release
-increased IL-10 release may contribute to acute anti-inflammatory effect of glucocorticoid
-the proinflammatory cytokine IL-1 and TNF and IL-6 can activate the HPA axis and induce the release of CRH and
ACTH increased circulatory GC levels inhibit endotoxins-induced production of TNF at the level of mRNA
translation
-dexamethasone inhibits neutrophil apoptosis and prolongs their functional responsiveness

Catecholamines:
-inhibit endotoxins-induced macrophage production of TNF-alpha
-endogenous epinephrine or exogenous administration as a component of sepsis treatment may serve to limit
excessive proinflammatory effects of the cytokine network during the early phase of systemic infection

' " #

( +)+ ++' ( ) !

Endothelial Cell Function:


-in a paracrine fashion, local mediators (eg. TNF-a, IL-1, endotoxins, thrombin, histamine, and IFN-g) are capable
of stimulating or activating the endothelial cell during local tissue injury
-endothelial cell can release several mediators:
-IL-1, PAF, PGI2 and PGE2, GM-CSF, growth factors, endothelin, NO, and TxA2
-modulate CV and renal function and influence the HPA axis
-collagenase secretion to permit neovascularization and vascular remodelling
-ACE convert AT I to AT II potent regulator of vascular tone
-if activated, up-regulates expression of leukocyte adhesion receptor molecules:
-E-selectin (requires stimulation of TNF-a and IL-1), P-selecting, ICAM-1, ICAM-2
-local injuries and inflammatory mediator stimulation promote the marination of circulating PMNs to endothelial
surfaces
-rolling, diapedesis
-activated PMNs and the subsequent release of inflammatory mediators and reactive oxygen metabolites
are implicated in capillary leakage, acute lung injury, and postischemic injury

Endothelium-Derived Nitric Oxide:


-EDNO can be released in response to ACh stimulation, hypoxia, endotoxins, cellular injury, or mechanical shear
stress from circulating blood
-induction of SMC relaxation by EDNO via activation of soluble guanylate cyclase and cGMP within the myocytes
-EDNO induces vasodilation and platelet deactivation
-formed from oxidation of L-arginine

Prostacyclin:
-PGI2 an important endothelium-derived vasodilator synthesized in response to vascular shear stress and hypoxia
-derived from arachidonic acid
-causes vasorelaxation and platelet deactivation by increasing cAMP

64
Endothelins:
-produced by endothelial cell in response to:
-injury, thrombin, TGF-beta, IL-1, AT II, ADH, catecholamines, and anoxia
-potent vasoconstrictor properties
-ET-1 most biologically active and potent vasoconstrictors known
-increased serum levels of ET are correlated with the severity of injury after major trauma, major surgical
procedures, and in cardiogenic or septic shock

Platelet-Activating Factor:
-phopsholipid constituent of cell membranes that can be induced by TNF, IL-1, ADH, and AT II
-stimulates production of TxA2 promotes platelet aggregation and vasoconstriction
-increases glucagon and catecholamine activity experimentally
-can induce hypotension, increase vascular permeability, hemoconcentration, pulmonary hypertension,
bronchoconstriction, primed PMN activity, eosinophil chemotaxis/degranulation, and thrombocytopenia
-alters shape of endothelial cells, causing them to contract and increase permeability
-chemotactant for leukocyte adherence to vascular wall and facilitates migration out of vascular compartment

Atrial Natriuretic Peptides:


-released by CNS and by specialized endothelium found in atrial tissues in response to wall tension
-potent inhibitors of aldosterone secretion and prevent reabsorption of sodium

!) ++ +)! ' ( ) !

Heat-Shock Proteins:
-production induced by heat, hypoxia, trauma, heavy metals, local trauma, and haemorrhage
-presumed to protect cells from traumatic stress
-function intracellularly in the assembly, disassembly, stability, and transport of proteins

Reactive Oxygen Metabolites:


-cause tissue injury by peroxidation of cell membrane unsaturated fatty acids
-cells are not immune to damage by their own ROMs but are generally protected by oxygen scavengers that include
glutathione and catalases
-activated WBCs are potent generators of reactive oxygen metabolites
-ROMs can induce apoptosis

! &+) ) ! ' () !

Eicosanoids:
-oxidation derivatives of arachidonic acid
-secreted by virtually all nucleated cells except lymphocytes
-phospholipids –(PLP-A2) arachidonic acid
-two major pathways:
-cyclooxygenase: production of all prostaglandin and thromboxanes
-lipoxygenase: production of leukotrienes and HETE
-synthesis stimulated by:
-hypoxic and ischemic injury, direct tissue injury, endotoxins, norepinephrine, ADH, AT II, bradykinin,
serotonin, ACh, and histamine
-function:
-diverse effects systemically on endocrine and immune function, neurotransmission, and vasomotor
regulation
-major components of the inflammatory response in injured tissue, characterized by vascular permeability,
leukocyte migration, and vasodilation

65
Kallikrein-Kinin System:
-bradykinins are potent vasodilators produced through kininogen degradation by the serine protease kallikrein
-release stimulated by hypoxic and ischemic injury
-kallikrein activated (from prekallikrein) by:
-Hageman factor, trypsin, plasmin, factor XI, glass surfaces, kaolin, and collagen
-function:
-increase capillary permeability and tissue edema, evoke pain, and increase bronchoconstriction
-increase renal vasodilation and reduce renal blood flow
-increase glucose clearance by inhibiting gluconeogenesis
-may also increase nitrogen retention

Serotonin:
-tryptophan derivative found in enterochromaffin cells of intestine and platelets
-stimulates vasoconstriction, bronchoconstriction, and platelet aggregation
-also capable of acting as a myocardial chrono- and inotrope

Histamine:
-derived from histidine and stored in neurons, skin, gastric mucosa, mast cells, basophil, and platelets
-release activated by increased calcium levels
-H1 receptor binding:
-increased histamine precursor uptake (l-histidine)
-bronchoconstriction, intestinal motility, and myocardial contractility
-H2 receptor binding:
-inhibits histamine release
-both: induces vasodilation and increased vascular permeability
-hypotension, peripheral pooling of blood, increased capillary permeability, decreased venous
return, and myocardial failure

' - #

' ). + ) *

Substrate Metabolism:
-healthy 70 kg adult expends 1700-1800 kcal/day of energy
-sources: lipid, carbohydrate, protein
-obligate glycolytic cells (eg. neurons, leukocytes, erythrocytes)
-require 180 g glucose per 24 h for basal energy needs
-hepatic glycogen ~75 g glucose
-skeletal muscle:
-cannot directly release free glucose d/t lack of glucose-6-phosphatase
-fasting decreased serum glucose net effect of body to increase glucose production
-decrease insulin release
-increased glucagon and more transient elevations of GH, catecholamines, ADH, and AT II
-glucagon and epinephrine enhance cAMP promotes glycogenolysis
-cortisol and glucagon promote gluconeogenesis
-norepinephrine, ADH, ATII –(PIP3+Ca++) promote glycogenolysis
-reduction in anabolic growth factors (eg. IGF-1)
-gluconeogenesis:
-mainly by liver, but also by kidneys (up to 45% in late starvation)
-precursors: lactate, glycerol, amino acids (eg. alanine and glutamine)
-lactate sources:
-skeletal muscles via glycogenolysis and glycolysis
-erythrocytes and WBCs after aerobic glycolysis

66
-lactate converted to glucose in liver via Cori cycle
-protein metabolism:
-75 g protein must be degraded (mostly from skeletal muscle) daily during fasting and starvation to provide
gluconeogenic amino acids to liver
-proteolysis (results from insulin and cortisol) BUN excretion
-after 5d, rate diminishes to 15-20 g/day
-occurs as CNS and other tissues adapt to ketone oxidation as predominant energy source
-amount of protein required for GNG significantly reduced
-lipid metabolism:
-160 g TG provides energy requirements for GNG and basal enzymatic and muscular function
- insulin, glucagon and catecholamines promotes lipolysis
- free fatty acids and glycerol
-FFA and ketone bodies (from liver) source of energy for heart, kidney, muscle, and liver
-lipid stores provide up to 40% of caloric expenditure during starvation
-lipid oxidation reduces glucose requirements:
-decreased amount of mandatory glycolysis, which requirements for GNG and protein
degradation
-once initial obligatory neuroendocrine stress hormone response recedes, whole-body energy expenditure also
decreases during prolonged fasting

' ). + & ! !

Energy Balance:
-associated increase in energy expenditure and increased oxygen consumption
-d/t increased sympathetic activity
-may be related to influences on cell membrane sodium permeability the energy required for ion pump
action to maintain normal transmembrane concentrations

Lipid Metabolism:
-FFA principle sources of energy after injury
-lipolysis enhanced:
-d/t ACTH, cortisol, catecholamines, glucagon and GH; insulin; sympathetics
-hormone-sensitive lipase stimulated by catecholamines
-FFA can be oxidized by cardiac and skeletal muscle to produce energy
-lipoprotein lipase (clears plasma TG):
-suppressed in adipose tissue after trauma, but not in muscle
-suppressed in both in sepsis
-ketogenesis:
-decreased after major injury, severe shock, and sepsis
-suppressed by insulin and other energy substrates, uptake and oxidation of FFA
-increased after minor injury or mild infection

Carbohydrate Metabolism:
-systemic glucose intolerance after injury state of relative insulin resistance
-increases in plasma glucose levels proportional of severity of injury; correlated to survival
-d/t increased hepatic production and peripheral insulin resistance
-deprivation of glucose to non-essential organs (eg. skeletal muscles and adipose) mediated via catecholamines
-mediator-induced reduction of skeletal muscle pyruvate dehydrogenase AcetylCoA for TCA cycle
results in shunting of pyruvate to liver for GNG
-glucose provided for inflammatory and healing cells in the wound environment

Protein and Amino Acid Metabolism:


-daily protein intake ~ 80-120g or 13-20 g of nitrogen

67
-loss of lean tissues after significant injury:
-skeletal muscle is depleted while visceral tissues (eg. liver and kidney) are relatively preserved
-severe trauma, burns, and sepsis are associated with increased whole-body protein turnover and increased
net protein catabolism
-accelerated proteolysis and GNG persist after major injury and during sepsis
-after trauma, substrate cycling of amino acid occurs b/n skeletal muscle, liver, and the wound:
-major source is skeletal muscle
-proteolysis enhanced by:
-oxidative species and diminished antioxidant activities
-increased ubiquitin-dependent proteolytic pathways
-glutamine and alanine released:
-glutamine: major energy source for lymphocytes, fibroblasts, and GI tract

!* ! / !) )/

Catabolic Phase:
-adrenergic-corticoid phase:
- glucagon, GC and catecholamines with insulin
-rates of GNG, acute phase protein production, and immune cell activity are all still altered during the
catabolic phase
-administration of glucose produces little or no change in rate of protein catabolism
-glucose turnover increased
-Cori cycle activity stimulated: 3C intermediates glucose by pyruvate carboxylase and PEP carboxylase
-lipolysis and FFA oxidation

Early Anabolic Phase:


-corticoid-withdrawal phase:
-within 3-8 days after uncomplicated elective surgery or after weeks in patients with extensive cross-
sectional tissue injury, sepsis, or ungrafted thermal injury
-characterized by sharp decline in nitrogen excretion and restoration of appropriate potassium-nitrogen
balance
-early acute phase reactants are supplanted by tissue repair and anabolic factors (eg. IGF-1)
-clinically: initial diuresis of retained water and renewed interest in oral nutrition
-synthesis of proteins (positive nitrogen balance):
-rapid progressive gain in weight and muscular strength
-gain of over 100 g of lean body mass/day
-rate of gain much slower than rate of initial loss

Late Anabolic Phase:


-may last from several weeks to several months after severe injury
-gradual restoration of adipose stores and positive nitrogen balance declines to normal
-weight gain is much slower because of high caloric content of fat

) ( 0 !

-history: -presence of weight loss and chronic illnesses or dietary habits influencing the quantity an quality
of food intake
-physical: -assess loss of muscle and adipose, organ dysfunction, and subtle change in skin, hair, or
neuromuscular function

68
-biochemical: -creatinine excretion, albumin, transferring

-fundamental goals of nutritional support:


-meet energy requirements of metabolic processes, core temperature maintenance, and tissue repair

-Basal Energy Expenditure (BEE):


-estimated with Harris-Benedict equations:
BEE (men) = 66.47 + 13.75(W) + 5.0(H) - 6.76(A) kcal/day
(women) = 65.51 + 9.56(W) + 1.85(H) - 4.68(A) kcal/day
W = weight (kg); H = height (cm); A = age (years)

-meet substrate requirements for protein synthesis


-dependent on degree of insult, source and amount of exogenous protein, previous nutritional
status
-maintain calorie-nitrogen ratio of 150-200:1
-precluding renal or hepatic dysfunction, ~ 0.25-0.35 g of nitrogen/kg daily should be provided

-vitamins usually not given in absence of preoperative deficiencies


-pts maintained on elemental diets or parenteral hyperalimentation require complete vitamin and mineral
supplementation
-intravenous feeds require all micronutrients to prevent development of deficiencies:
-eg. vit K, B12, folic acid, trace minerals, essential fatty acids

( ) ) (' ( &! ! )+ !

-reasonably well-nourished and otherwise healthy individual who undergoes an uncomplicated major operative
procedure has sufficient body fuel reserves to withstand the catabolic insult and partial starvation for at least 1 week
-requires: IV fluids /w min of 100 g glucose daily to minimize protein catabolism
-defined formula diets and TPN are unnecessary
-during early anabolic phase, pt needs adequate caloric intake of proper composition to meet energy needs
of the body and to allow protein synthesis
-chronically debilitated preoperatively from diseases or from malnutrition and patients who have suffered trauma,
sepsis, or surgical complications cannot maintain adequate caloric intake
-should receive consideration of nutritional support early
-in general, the indications for preoperative nutritional support appear largely confined to patients with
evidence of more severe erosion of lean body mass and adipose tissue stores

-enteral route should always be used when possible because it is considered to be more economical and well
tolerated in many patients
-NG, gastrostomy, and jejunostomy tube feedings for those with normal GI tract but cannot or will not eat
-ability to tolerate enteral feeds depends on:
-rate of infusion
-osmolality of feeds
-chemical nature of the product
-usually start with 30-50 cc/h then increased by 10-25 cc/h/d until optimal volume is delivered
-after full volume is attained, concentration is increased slowly to desired strength
-measure gastric residuals to monitor risk of aspiration
-decrease rate if abdo cramps or diarrhea occurs
-parenteral route used for supplementation in pt with limited oral intake or for complete nutritional management in
the absence of oral intake
-potentially enhances the magnitude of macroendocrine and microendocrine mediator responses to an
antigenic challenge
-loss of intestinal barrier function occurs

69
-experimental approaches for preserving GI mucosa integrity and gut mass:
-luminal stimulation by digestible or nondigestible substrates, and infusion of critical
intestinal fuel sources (eg. glutamine or short-chain fatty acids)

!)+ ( *

Nasoenteric Tube Feeding:


-contraindications for nasoesophageal or gastric tube feeding:
-unconsciousness or lack of protective laryngeal reflexes
-nasojejunal tubes to bypass dysfunctional gastric stomas and high GI fistulas
-infusion pumps:
-decrease incidence of GI side effects induced by overly rapid delivery of hyperosmolar solutions
-allows safer administration of larger daily volumes of nutrients; minimizes gastric distention

Gastrostomy Tube Feeding:


-for pts with chronic GI lesions arising at or above the cardioesophageal junction
-contraindicated for mentally obtunded pts with inadequate laryngeal reflexes
-used only in alert patients or in patients with total obstruction of distal esophagus
-feeding mixture may be pureed foods
-hyperosmolarity of the feeding formula is not generally a problem as long as pylorus is intact

Jejunostomy Tube Feeding:


-for pts in which nasoesophageal or gastrostomy tube feedings are contraindicated:
-comatose pts
-pts with high GI fistulas or obstructions
-pts in whom a nasojejunal feeding tube cannot be placed
-types:
-Roux-en-Y (permanent)
-Witzel (temporary):
-insertion of 18 Fr. rubber catheter into proximal jejunum ~30 cm distal to ligament of Treitz
-if tube is accidentally removed, pt should be observed for peritonitis for 12-18h after feedings restarted
-feedings are safely begun 12-18h after jejunostomy construction
-if the pt /w jejunostomy has proximal bowel or biliary fistula draining > 300 cc/d for prolonged period, fistular
drainage may be collected by sump suction, cooled, and promptly re-fed in small increments throughout the day

" & ( ! +) "


-useful for patients with depleted protein reserves secondary to GI tract disease (eg. UC, malabsorption syndrome)
and for pts with only partial function of the GI tract (eg. short bowel syndrome or gastric or small-bowel fistulas)
-contents include:
-baseline electrolytes, water, fat-soluble vitamins, and trace minerals
-no bulk minimal residuals
-no lactose
-partially hydrolysed or completely hydrolysed proteins
-complications:
-nausea, vomiting, and diarrhea d/t high osmolarity
-hypertonic nonketotic coma may occur in presence of excessive water losses or if diets are administered at
concentrations above those recommended
-hyperglycemia and glycosuria

70
)! !)+ + )

-continuous infusion of hyperosmolar solution containing carbohydrates, proteins, fat, and other necessary nutrients
through indwelling catheter into SVC
-ratio of calories to nitrogen must be at least 100-150 kcal/g nitrogen and the two materials must be infused
simultaneously in order to maximize nitrogen use

Indications for the Use of Intravenous Hyperalimentation:


-exclusively for intravenous nutrition:
-newborns with catastrophic GI anomalies (eg. tracheoesophageal fistula, gastroschisis, omphalocele, massive intestinal atresia)
-infants who fail to thrive nonspecifically or secondarily to GI insufficiency associated with short bowel syndrome, malabsorption,
enzyme deficiency, meconium ileus, or idiopathic diarrhea
-might be appropriate for enteral or parenteral nutrition:
-adults with short bowel syndrome secondary to massive resection or fistulas
-high alimentary tract obstructions without vascular compromise (achalasia, stricture, esophageal/gastric ca, pyloric obstruction)
-prolonged paralytic ileus after major operations, multiple injuries, blunt or open abdominal trauma
-malabsorption secondary to celiac disease, hypoproteinemia, enzyme or pancreatic insufficiency, regional enteritis or UC
-functional GI disorders such as esophageal dyskinesia after CVA, idiopathic diarrhea, psychogenic vomiting
-etc. etc.. see Schwartz pg. 43

-contraindications to hyperalimentation:
-lack of specific goal for pt management, or when instead of extending a meaningful life, inevitable dying
is prolonged
-period of cardiovascular instability or severe metabolic derangement requiring control or correction before
attempting hypertonic intravenous feeding
-feasible GI tract feeding
-patients in good nutritional status, in whom only short-term parenteral nutrition support is required or
anticipated
-infants with less than 8 cm of small bowel, since virtually all have been unable to adapt sufficiently
despite prolonged periods of parenteral nutrition
-patients who are irreversibly decerebrate or otherwise dehumanized

Preparation and Administration of Solutions:


-basic solution:
-20-25% dextrose
-3-5% crystalline amino acids
-vitamin supplementation:
-vitamin K (10 mg) and folic acid (5 mg) IM once weekly and B12 once a month b/c these are unstable in
hyperalimentation solution
-essential fatty acid deficiency: dry, scaly dermatitis and loss of hair
-prevented by periodic infusion of fat emulsion at rate equivalent to 10-15% of total calories
-trace mineral deficiencies (seldom seen, usually in pts with extended TPN use):
-zinc: eczematoid rash diffusely and at intertriginous areas
-copper: microcytic anema
-chromium: glucose intolerance
-insulin may be required for glucose intolerance
-administration of adequate amounts of K is essential to achieve positive nitrogen balance and to replace depleted
intracellular stores
-hypokalemia may cause glycosuria, which would be treated with potassium, not insulin

Fat Emulsions:
-derived from soybean or safflower oils are widely used as an adjunctive nutrient to prevent development of
essential fatty acid deficiency
-major energy source in TPN, but no evidence of enhanced metabolic efficacy if greater than 10-15% of calories is
provided as lipid emulsions
-pts with abnormal fa transport or metabolism, lipid nephrosis, coagulopathy, or serious pulmonary disease should

71
not receive fat emulsions
-limit administration to between 2.0-2.5 g/kg TBW/d

Special Formulations:
-renal failure patients (oliguric):
-final dextrose concentration of 40-45% and only essential L-amino acids
-hepatic failure:
-solutions contain increased levels of branched-chain amino acids and decreased concentrations of
aromatic amino acids to decrease encephalopathy
-cardiac cachexia:
-highly concentrated dextrose and amino acid formula that are low in sodium

Complications:
-sepsis secondary to contamination of CV catheter
-earliest signs: sudden development of glucose intolerance in a patient previously been maintained on
parenteral alimentation w/o difficulty
-if suspected, remove and culture catheter; replace at a different site
-problems with catheter placement:
-pneumothorax, hemothorax, or hydrothorax
-subclavian artery injury
-cardiac arrhythmia
-air embolism
-cardiac perforation and tamponade
-hyperosmolar nonketotic hyperglycemia:
-may occur with normal rates of infusion in patients with impaired glucose tolerance or in any pt if the
hypertonic solutions are administered too rapidly
-must monitor urine and blood glucose levels and electrolytes
-tx: volume replacement with correction of electrolyte abnormalities and administration of insulin
-excess calorie infusion may result in:
-carbon dioxide retention and respiratory insufficiency
-hepatic steatosis or marked glycogen deposition

72
! " #$ !

% & &

% '
-50-70% TBWt; ~ 60% (M), 50% (F)
-greater proportion of water in lean individuals
-newborns: 75-80% TBWt

-30-40% TBWt; largest proportion in skeletal muscle


-principal cations: potassium and magnesium
-principle anions: phosphates and proteins

(
-20% TBWt plasma (5% TBWt) + interstitial (15% TBWt)
-transcellular fluid (CSF, synovium) ~ 10% ECF = 1-2% TBWt
-principle cation: sodium
-principle anion: chloride and bicarbonate

)" ))
-proteins in plasma primarily responsible for effective osmotic pressure b/n plasma and interstitial fluid colloid
oncotic pressure

* & &

' ($ !
-normal individual consumes ~2000-2500 ml H2O/day; ~1500 ml by mouth
-daily water loss: 250ml stool, 800-1500 ml urine, ~600ml insensible loss
-insensible loss: skin (75%) and lungs (25%); by hypermetabolism, hyperventilation and fever
-can exceed 250ml/day per degree of fever
-unhumidified tracheotomy up to 1500ml/day
-gain in water: excessive cellular catabolism (up to 500ml/day)

)) )
-50-90 mEq (3-5g) as sodium chloride
-kidneys excrete excess salt
-gastrointestinal losses usually isotonic or slightly hypotonic

% & &

+ " $ ! )
-diagnosed by clinical examination
-indirect measurements:
-BUN rises with ECF deficit of sufficient magnitude to reduce GFR
-hematocrit: with ECF deficit; with excess
-[Na] NOT related to volume status of ECF

73
(1) Volume Deficit:
-most common causes of ECF deficit are GI losses from vomiting, NG suction, diarrhea, fistular drainage
-also sequestration of fluid in soft tissues injuries and infections, intraabdominal and retroperitoneal
inflammatory processes, peritonitis, intestinal obstruction, burns

(2) Volume Excess:


-iatrogenic
-secondary to renal insufficiency, cirrhosis, or CHF

$ ! )
-sodium primarily responsible for osmolarity of ECF
-clinical signs of hypo- or hypernatrema are not present until changes are severe

(1) Hyponatremia:
-acute symptomatic hyponatremia (<130) CNS signs of ICP; tissue signs of intracellular water
-risk of oliguric renal failure which may not be reversible if treatment delayed

(2) Hypernatremia:
-CNS and tissue signs characterize acute symptomatic hypernatrema

( + " , " )

-ECF deficit and hyponatremia:


-continuing to drink while losing large volumes of GI fluids
-post-op replacement of GI losses with hypotonic fluids
-ECF deficit and hypernatremia:
-loss of large amount of hypotonic salt solution (eg. sweat) in absence of fluid intake
-ECF excess and hypernatremia:
-prolonged administration of excessive sodium salts with restricted water intake
-ECF excess and hyponatremia:
-excessive administration of water or hypotonic salt solution in pt with oliguric renal failure

"- ) $ ! )

./0 % ) %

-buffers: (1) proteins; (2) phosphates; (3) bicarbonate-carbonic acid system


-carbonic acid excreted by lungs as CO2; inorganic acid anions excreted by kidneys with hydrogen or as ammonium
salts
pH = pK + log [BHCO3/H2CO3] = 6.1 + log [20/1] = 7.4

Respiratory Acidosis:
-associated with retention of CO2 secondary to decreased alveolar ventilation
-inadequate ventilation:
-airway obstruction, atelectasis, pneumonia, pleural effusion, pain from upper abdominal incision,
abdominal distention
-narcotic use

Respiratory Alkalosis:
-hyperventilation secondary to apprehension, pain, hypoxia, CNS injury, assisted ventilation

74
-PaCO2 should not be allowed to fall below 30 mmHg
-dangers related to potassium depletion ventricular arrhythmias and fibrillation, particularly in
patients who are digitalized or have preexisting hypokalemia
-d/t entry of K+ into cells in exchange for H+; excessive urinary K loss in exchange for
Na
-shifting oxyhaemoglobin dissociation curve to left limits unloading of oxygen
-tetany and convulsions if ionized calcium significantly depressed

Metabolic Acidosis:
-retention or gain of fixed acids (DKA, lactic acidosis, azotemia)
-loss of base bicarbonate (diarrhea, small bowel fistula, renal insufficiency)
-develops when capacity of kidneys for handling a large chloride load is exceeded (biliary, pancreatic,
small-bowel secretions) and are maintained on parenteral fluids for an extended period
-use of Ringer’s solution indicated
-non-anion gap: loss of bicarbonate or gain of chloride acid (eg. administration of ammonium chloride)
-most common cause of elevated anion gap: shock or inadequate tissue perfusion
-common causes of severe metabolic acidosis in surgical patients: acute circulatory failure with
accumulation of lactic acid
-used of Ringer’s solution does not accentuate lactic acidosis
-indiscriminate use of bicarbonate during resuscitation of patients in hypovolemic shock is
discouraged:
-citrate in transfused blood and lactate in Ringer’s solution are metabolized to
bicarbonate by liver severe metabolic alkalosis can result if excessive bicarbonate
administered
-treatment: correct underlying disorder when possible
-indication for bicarbonate administration: severe metabolic acidosis after cardiac arrest

Metabolic Alkalosis:
-loss of fixed acids or gain of bicarbonate
-aggravated by any preexisting potassium depletion
-majority of pts have some degree of hypokalemia: influx of K+ into cells, efflux of H+ into serum
-hypochloremic, hypokalemic metabolic alkalosis:
-persistent vomiting or gastric suction in pt with pyloric obstruction
-results in urinary bicarbonate excretion net H+ resorption by renal tubular cells, with
K+ excretion
-volume deficit aldosterone mediated Na+ resorption with K+ excretion
-hypokalemia excretion of H+ paradoxic aciduria
-treatment: replace ECF volume with NS + KCl

.0 )) " , " )

-normal dietary intake: 50-100 mEq/d


-majority excreted in urine
-90% of potassium within ICF (~150 mEq/L); major intracellular cation
-critical to cardiac and neuromuscular function

Hyperkalemia:
-signs:
GI: nausea, vomiting, intermittent intestinal colic, diarrhea
Cardiac: ECG high peaked T waves, widened QRS, depressed ST segments
-disappearance of T waves, heart block, diastolic cardiac arrest
-treatment:
-1g of 10% calcium gluconate temporary suppression of myocardial effects

75
-bicarbonate/glucose/insulin (45 mEq NaHCO3 in 1000 ml D10W with 20 u regular insulin)
promotes cellular uptake of potassium
-cation exchange resins: Kayexalate
-dialysis

Hypokalemia:
-more common problem in than hyperkalemia:
1. excessive renal excretion
-occurs with respiratory and metabolic alkalosis
-K+ in competition with H+ for renal tubular excretion in exchange for Na+
-increased K+ excretion in alkalosis in exchange for Na+ permits H+ conservation
-hypokalemia may produce metabolic alkalosis: increased excretion of H+ when [K+] in
tubular cells is low
-renal tubular excretion of K increased when large quantities of sodium are available
2. movement of potassium into cells
3. prolonged administration of potassium-free IV fluids
4. TPN with inadequate potassium replacement
5. loss in gastrointestinal secretions
-signs:
-related to failure of normal contractility of skeletal, smooth and cardiac muscle
-flaccid paralysis, DTR, paralytic ileus
-sensitivity to digoxin, with cardiac arrhythmias and ECG signs of low voltage, flattening of T
waves, depression of ST segments
-treatment:
-prevention
-no more than 40 mEq/L; rate should not exceed 40 mEq/h
-potassium should not be given to the oliguric patient or to patients during first 24h after severe
surgical stress or trauma

.10 " , " )

-total body calcium = 1000-1200 g


-majority found in bone as calcium phosphate or carbonate
-normal daily intake: 1-3g
-most excreted via GI tract; 200 mg excreted in urine daily
-~45% of serum calcium is ionized; ~50% bound to plasma proteins
-related to pH: acidosis Ca++; alkalosis Ca++

Hypocalcemia:
-symptoms: numbness/tingling of circumoral region and tips of fingers and toes
-signs: DTR, +Chvostek’s sign, muscle and abdominal cramps, tetany with carpopedal spasm,
convulsions, prolongation of QT interval on ECG
-common causes:
-acute pancreatitis
-massive soft tissue infections (necrotizing fasciitis)
-acute and chronic renal failure
-pancreatic and small-bowel fistulas
-hypoparathyroidism
-other causes: severe magnesium depletion
-treatment:
-correction of underlying cause and repletion of deficit
-IV calcium gluconate or chloride
-majority of patients receiving blood transfusion do not require calcium supplementation; binding

76
of ionized calcium by citrate generally compensated by mobilization of calcium from body stores
-for rapid transfusion: 500 ml q5-10min 2ml 10% calcium chloride for every 500 ml

Hypercalcemia:
-symptoms: vague GI, renal, MSK, CNS origin
-easy fatigue, lassitude, weakness, anorexia, nausea, vomiting, weight loss coma
-severe headaches, pains in back and extremities, thirst, polydipsia, polyuria
-major causes:
-hyperparathyroidism
-cancer with bony metastasis: most frequently seen in patient with metastatic breast cancer
receiving estrogen therapy
-other causes: sarcoidosis, myelomas, lymphomas, leukemias
-treatment:
-IV fluids +/- furosemide administration

.20 ! ) " , " )

-total body content: ~2000 mEq; ~ half incorporated into bone


-serum [Mg] = 1.5-2.5 mEq/L
-normal dietary intake: ~20 mEq (240 mg) daily

Magnesium deficiency:
-causes:
-starvation, malabsorption syndromes
-protracted losses of GI fluid
-prolonged IV therapy with Mg free fluids
-TPN with inadequate Mg
-other causes:
-acute pancreatitis
-treatment of DKA
-primary aldosteronism
-chronic alcoholism
-amphotericin B therapy
-protracted course after thermal injury
-functions: requirement for most enzyme systems
-signs and symptoms similar to calcium deficiency
-treatment:
-IV magnesium sulfate or magnesium chloride
-calcium chloride or calcium gluconate available to counteract any adverse effects of rapidly rising
serum magnesium level

Magnesium excess:
-commonly seen with severe renal insufficiency
-retention and accumulation of magnesium with impaired glomerular or renal tubular function
-other causes:
-magnesium-containing antacids and laxatives
-early thermal injury
-massive trauma or surgical stress
-severe ECF volume deficit
-severe acidosis
-signs and symptoms:
-lethargy and weakness with progressive loss of DTR
-ECG: PR interval, widened QRS, elevated T waves

77
-coma and muscular paralysis
death by respiratory or cardiac arrest
-treatment:
-correct co-existing acidosis
-ECF volume replenishment
-withholding exogenous magnesium
-acute symptoms temporarily controlled with IV 5-10 mEq of calcium gluconate
-peritoneal dialysis or hemodialysis if elevated levels persist

& &

Ringer’s Lactate:
-for replacement of GI losses and ECF deficits
-physiologic
-Na: 130 mEq; Cl: 109 mEq; lactate: 28 mEq
-minimal effects on body fluid composition and pH

Normal Saline:
-Na: 154 mEq; Cl: 154 mEq
-may induce dilutional acidosis by decreasing bicarbonate relative to carbonic acid
-ideal in correcting ECF deficit in presence of hyponatremia, hypochloremia, and metabolic alkalosis

0.45% NaCl: D5W:


-reasonable solution to use for maintenance requirements postoperatively in patients with no complications
who requires only a short period of parenteral fluids

- 3 $ -

(1) Correction of Volume Changes


-depletion of ECF without changes in concentration or composition is a common problem
-volume deficits:
-external loss of fluids
-internal redistribution (“third spacing”)
-massive ascites, burns, crush injuries, massive infection of subcutaneous tissues
-a slight increase in thickness from sequestration of fluid in the peritoneum may result in
a functional loss of several litres of fluid
-mild loss ~ 4% TBWt; moderate loss ~ 6-8% TBWt; severe loss ~ 10% TBWt
-prompt fluid replacement with balanced salt solution should be started
-reversal of signs of volume deficit, combined with stabilization of BP and pulse and an hourly
urine output of 30-50 cc are used as general guidelines
-rate of fluid administration:
-most severe volume deficits may be safely replaced initially with isotonic solutions at rates up to
2000 cc/h, with the rate reduced as the fluid status improves

(2) Correction of Concentration Changes


-Hyponatremia:
-Na deficit (mEq) = 0.6 Wt (140 - [Na])
-initially up to ½ of calculated amount of sodium administered slowly
-only to relieve acute symptoms; further correction is facilitated when renal function is

78
restored by correction of volume deficit
-if hypervolemic, then water restrict patient
-Hypernatremia:
-if symptomatic, D5W infused slowly until symptoms relieved
-if ECF osmolarity reduced too rapidly convulsions and coma
-ideally correct with ½ NS

- 3 ! "
-blood should be replaced to maintain an acceptable RBC mass irrespective of any additional fluid and electrolyte
therapy
-replacement of ECF should begin during the operative procedure
-balanced salt solution needed during operation is approximately 0.5 to 1 L/h, but only to a maximum of 2-3 L
during a 4h major abdominal procedure, unless there are other measurable losses

) - 3 ! "

(1) Immediate Postoperative Period


-initial fluid orders are written to correct any existing deficit, followed by maintenance fluids
-it is unnecessary and probably unwise to administer potassium during the first 24 h after operation unless
a definite potassium deficit exists
-if renal failure develops, the administration of small quantities of potassium may be detrimental

(2) Later Postoperative Period


-replacement of sensible and insensible losses
-insensible losses ~ 600 cc/day; increased by fever, hyperventilation, hypermetabolism 1500 cc/day
-replaced with D5W
-daily maintenance fluid given at steady rate while losses are incurred
-if given over shorter period, renal excretion of excess salt and water may occur while normal
losses continue over the full 24 h period
-potassium replacement: 40 mEq daily for renal excretion; ~20 mEq/L for replacement of GI
losses

(3) Special Considerations in the Postoperative Patient

Volume Excesses:
-earliest sign of volume overload is weight gain during the catabolic period, when the patient should be
losing 1/4 to ½ lb/day
-circulatory and pulmonary signs appear late and represent a massive overload

Hyponatremia:
-hyponatremia associated with surgical procedures and traumatic injury is prevented by the replacement of
extracellular fluid deficits
-hyperglycemia may cause a dilutional hyponatremia
-endogenous water release: without adequate caloric intake, cellular catabolism causes pt to gain up to 500
cc/day of water between the fifth and tenth days
-intracellular shifts: bacterial sepsis precipitous drop in serum sodium concentration

Hypernatremia:
-high serum sodium level may indicate a significant deficit of total body water
-often the result of excessive or unexpected water losses

79
a. Excessive Extrarenal Water Losses:
-sweat; tracheotomy; burns etc..
b. Increased Renal Water Losses:
-hypoxic damage to distal tubules and collecting ducts or loss of ADH stimulation from damage to
CNS large volumes of solute-poor urine
c. Solute Loading:
-high protein intake increased osmotic load of urea excretion of large volumes of water
-prevent by an intake of 7 ml of water per gram of dietary protein
-excessive glucose administration, osmotic diuretics

(4) Acute Renal Failure


-prerenal, renal or postrenal
-most common cause is sequestered or third-space loss in area of surgical procedure
-common intrarenal causes: endotoxemia, trauma, drugs (aminoglycosides), myoglobinuria, destabilized
haemoglobin
-postrenal causes: obstruction of ureter, bladder or urethra

Biochemical Abnormalities:
1. Metabolic acidosis results from failure of renal excretion of fixed acids and the inability to maintain respiratory compensation
2. Hyperkalemia d/t large amounts of intracellular potassium released in acute renal failure
3. Hyponatremia d/t production of metabolic water from metabolism of nutrients and liberation of water from intracellular
breakdown
4. Hyperphosphatemia and hypocalcemia d/t inadequate excretion and excessive release from injured tissue
5. Hypermagnesemia: kidney is the major organ for regulating magnesium balance

Predisposing Factors:
-Trauma:
-hypovolemic shock, myoglobinuria from rhabdomyolysis, intravascular haemolysis and
hemoglobinuria from transfusions
-Sepsis:
-endotoxins releases TNF produce renal failure
-Cardiopulmonary Bypass: hypoperfusion of kidneys
-Renal Transplantation:
-problems with renal artery, obstruction of urinary flow
-Urologic Surgery:
-obstruction in kidney, ureter, bladder, or urethra
-Vascular Disease:
-blood flow to kidney interrupted during clamp times of vascular surgeries
-Preexisting Renal Disease:
-nephrosclerosis, diabetes, chronic glomerulonephritis, chronic tubular interstitial nephritis
-Radiographic contrast agents
-Drugs:
-aminoglycosides, cyclosporine, amphotericin B, NSAIDs

Laboratory Studies:
-Urinalysis
-Urine osmolarity
-Urine urea and creatinine ratio:
-most useful in diagnosing acute renal failure postoperatively:
< 20 acute renal failure
> 40 prerenal azotemia
-Urine sodium:
-the underperfused kidney is sodium retaining, and a low urine sodium concentration is
characteristic of prerenal azotemia

80
Management of the Patient with Established Acute Renal Failure:
-correct reversible causes
-fluid and electrolyte management:
-treat hyperkalemia
-fluid intake should be restricted to replacing measured fluid losses plus 500-600 cc/d of
insensible losses
-hyponatremia: if below 120, dialysis is the only therapeutic endeavour that corrects
-metabolic acidosis
-use of dialysis:
-best initiated before the occurrence of life-threatening complications of acute renal failure such
as hyperkalemia, severe acidosis, uremic encephalopathy, or uremic pericarditis
-four forms:
-hemodialysis, peritoneal dialysis, continuous arterial-venous dialysis, continuous
venovenous ultrafiltration

81
! "# #" # $ #

! %

-endothelial cells prevent clotting by:


-inactivating adenosine diphosphate (ADP) interfering with platelet recruitment
-provide environment for antithrombin III inactivates thrombin
-release thrombomodulin decreases coagulation process

-Physiologic events in hemostasis: (1) vascular constriction; (2) platelet plug formation; (3) fibrin formation; (4)
fibrinolysis

& # #
-initial vascular response to injury
-vasoconstrictors:
-thromboxane A2 (TXA2) - powerful
-serotonin (5-hydroxytryptamine, 5-HT)
-bradykinin and fibrinopeptides
-contribution of pressure provided by surrounding tissues
-low perivascular pressures increased persistent bleeding:
-muscle atrophy accompanying aging, pts on steroids, Ehlers-Danlos syndrome

# #
-life span is 7-9 days
-Primary Hemostasis
-platelet plug formation on damaged intima within 15s of traumatic event
-requires vWF
-not affected by heparin
-principle mediators: ADP and serotonin
-plug process inhibited by cAMP
-Platelet release reaction stimulated by:
-ADP
-platelet factor 4
-trace thrombin on platelet surface
-Ca++, Mg++
-Release factors promote recruitment and aggregation and result in formation of amorphous plug:
-ADP, K+
-PDGF
-serotonin
-platelet factor 3:
-contributes phospholipid to several stages of coagulation cascade
-activates X (with IXa, VIII, and Ca++)
-activates II (with Xa, V, and Ca++)
-platelet factor 4 and B-thromboglobulin:
-inhibit heparin and modify fibrin formation
-Platelets provide lipoprotein surface:
-for conversion of prothrombin to thrombin
-initial activation of XI and XII
-Release inhibitor of plasminogen activation

82
#
-prothrombin thrombin: proteolytic enzyme which cleaves fibrinogen fibrin stabilizes platelet plug

-Intrinsic Pathway:
-starts with XII
-IXa + VIII + Ca++ (platelet surface): X Xa
-Xa + V + Ca++ (platelet surface): II (prothrombin) IIa (thrombin)

-Extrinsic Pathway:
-initiated by tissue lipoprotein
-thromboplastin + VII + Ca++: X Xa
-thromboplastin + Xa + V + Ca++: II (prothrombin) IIa (thrombin)

-Thrombin:
-activates XIII (fibrin stabilizing factor)
-cleaves fibrinopeptides A and B from fibrinogen fibrin
-makes VIII more potent
-XIIIa: cross-links fibrin monomers stable clot
-Actions of thrombin prevented by:
-antithrombin: binds thrombin to thrombomodulin on endothelium, preventing cleavage of fibrinogen
-activation of protein C: inactivates V and VIII
-circulating protease inhibitors
-Factors not synthesized by liver:
-thromboplastin, Ca++, most of factor VIII
-Vitamin K dependent: II, VII, IX, X

' # (
-dependent on plasmin
-lyses fibrin
-lyses others: fibrinogen, V, VIII
-split products interfere with normal platelet aggregation
-larger fragments incorporate into clot and form unstable clot

% )

#* #
(1) Autosomal dominant: von Willebrand’s disease, hereditary haemorrhagic telangiectasia, XI deficiency
(2) Autosomal recessive: deficiencies in factors X, V, VII, I
(3) Sex-linked recessive: hemophilia A (VIII) and B (IX, Christmas disease)

) $ #
-production: hereditary thrombocytopenia
-destruction: Wiskott-Aldrich syndrome
-von Willebrand disease: missing vWF
-Bernard-Soulier syndrome: normal vWF - missing glycoprotein I complex on platelet membrane receptor for vWF
-Glanzmann’s thrombasthenia: failed aggregation in presence of ADP; impaired mediation of factors in clot
retention
-Congenital afibrinogenemia: fibrinogen required for platelet aggregation
-Hermansky-Pudlak syndrome: storage pool disease platelets cannot store ADP
-oculocutaneous albinism, ceroidlike deposits in macrophages, bleeding diathesis

83
# # ) $ $ #

+, & ) $ # (- .* /
-male; sex-linked recessive; spontaneous mutations in 20%
-incidence 1:10000 to 1:15000

Clinical Manifestations:
-severity based on degree of deficiency: >5% of normal levels VIII: mild; 1-5%: moderately severe
-bleeding into joints (hemarthrosis), epistaxis, hematuria
-intracranial bleeding (trauma in 50% of cases): 25% of deaths
-vascular and neural compromise from pressure secondary to bleeding into soft-tissue closed space:
-Talipes equines contracture deformity: bleeding into calf
-Volkmann’s, flexion contractures of knees and elbos
-retroperitoneal bleeding: Psoas sign, hypovolemic shock
-intramural intestinal haematoma:
-n/v, crampy abdo pain, fever, WBC, “picket fence/stack of coins” appearance on UGI series

Treatment:
Replacement Therapy:
-half-life of VIII is 8-12h
-1 unit = amount present in 1 ml of normal plasma; FFP contains 0.6 u/ml; cryoprecipitates contain 9.6 u/ml
-minimum hemostatic level of VIII:
-mild haemorrhages: 30%
-joint and muscle bleeding and major haemorrhages: 50%
-major surgery and life-threatening bleeding: 80-100% pre-op and maintained > 30% x 2weeks
-amount given:
R = pt’s weight x [desired rise of VIII (% average normal)]/[total units of VIII in dose]
-half of R is subsequently administered q4-6h to maintain a safe level

-DDAVP in mild hemophila A and mild vWD:


-effects a dose-dependent increase of all VIII activits and release of plaminogen activator
-reduces blood loss associated with major surgical procedures by 40%
-continue replacement of VIII for at least 10 days after surgery
-for complications: avoid fasciotomy, aspiration of hemarthrosis, operations in general; mainstay of treatment is to
give coagulation factors

0, 1 ) $ # (- * ) /
-X-linked recessive; accounts for 20% of hemophiliacs
-severe (50% of cases), moderate, mild forms according to level of IX
-prolonged PTT

Treatment:
-FFP or rarely, IX concentrates
-levels of 20-50% for severe haemorrhage for 3-5days then maintain at 10-20% for 10 days
-daily dose: 30-50 u/kg followed by 20 u/kg/d
-levels of 50-70% if operation required
-development of antibodies is a serious complication of treatment (10% of pts)

, 2 #3 ' #"4 ) 5
-autosomal dominant
-diminution of VIII:C (procoagulant) activity; variation in level may be noted
-prolonged bleeding time, prolonged aPTT

84
Clinical Manifestations:
-mild bleeding, epistaxis, menorrhagia
-serious bleeding after dental extractions, tonsillectomy

Treatment:
-cryoprecipitate (VIII R:vWF): 10-40 u/kg/12h
-replacement therapy should be begun 1 day pre-operatively
-aspirin must be avoided 10 days before operative procedure

) $ # $ #

-Factor XI (Rosenthal’s syndrome): no significant bleeding


-Factor V deficiency (parahemophilia): rare; significant bleeding in homozygotes; tx with FFP
-Factor VII deficiency: significant bleeding in homozygotes
-Factor X (Stuart-Prower) deficiency: associated with amyloidosis and familial carotid body tumours
-Factor II (prothrombin) deficiency: rare

+, #* " ' # # '# 5


-rare; fewer than 200 cases reported; autosomal recessive

0, # # 1 ) $ # (5
-rare autosomal recessive
-manifested by umbilical bleeding in the newborn and slow wound healing after an operation
-tx is FFP, cryoprecipitate, or XIII concentrates

6 ) % )

'#
-thrombocytopenia: most common abnormality of hemostasis that results in bleeding in surgical patient
-causes:
-disease processes: ITP, TTP, SLE
-hypersplenism/splenomegaly: sarcoid, Gaucher’s dz, lymphoma, portal hypertension
-reduced production in marrow: leukemia, uraemia, pts on cytotoxic therapy
-massive blood transfusion
-heparin induced: 0.6% of patients; after 4-15 days in pts given heparin for the first time
-impaired function: uraemia, thrombocythemia, PCV, myelofibrosis
-drugs: ASA, indomethacin, ibuprofen, dipyridamole, phenothiazine, penicillins, chelating agents,
lidocaine, dextran, beta-blockers, nitroglycerin, furosemide, antihistamines
-acute alcoholism
-viral infection
-vitamin B12 or folate deficiency
-no therapy for counts greater than 50000/mm3
-steroid therapy or plasmapheresis for idiopathic thrombocytopenia or SLE
-platelet transfusion:
-one unit = 5.5x1010 platelets: increases count by about 10x109/L
-4 to 8 units should be sufficient for adequate hemostasis

85
7 " (. $' # #

+, ) $' # # (#" 5
-Disseminated intravascular coagulation (DIC)
-caused by the introduction of thromboplastic materials into the circulation
-patchy necrosis of skin, hematuria and oliguria, confusion 2o cerebral ischemic, GIB, haemorrhage into adrenal
cortex acute hypotension
-causes: -retained dead fetus, premature separation of placenta, amniotic fluid embolus
-complication of dialysis, head trauma, mucin-producing and disseminated carcinoma, lymphomas,
thrombotic thrombocytopenia, rickettsial infection, snakebite, burns, aortic surgery, and shock from any
cause
-gram negative sepsis
-no lab test to confirm or exclude diagnosis; highly suggestive with combination of:
-low platelet count
-positive plasma protamines test presence of fibrin monomer-fibrinogen complexes
-reduced fibrinogen (<100mg/dL)
-context of patient’s underlying disease

Treatment:
-treat cause; supportive measures
-IV fluids + vasodilators
-plasma expanders if increased viscosity of blood
-active bleeding treated with FFP, cryoprecipitate (for fibrinogen), and platelet concentrates

0, ' # ( 5
-may occur in patients with metastatic prostatic carcinoma, shock, sepsis, hypoxia, neoplasia, cirrhosis, portal
hypertension, cardiopulmonary bypass

%( . $ 2 )
-major surgical risk for patients with marked thrombocytosis
-spontaneous thrombosis a complication of PCV: increased blood viscosity, platelet count and stasis
-myeloid metaplasia frequently represents part of the natural history of PCV

Treatment:
-thrombocyosis reduced with alkylating agents (eg. busulfan, chlorambucil)
-delay elective surgical procedures weeks to months after treatment
-emergency procedures: reduce RBC/plts by phlebotomy and replacement with RL

* )
-advanced cirrhosis:
-deficiencies in factors II, V, VII, X and XIII
-failure for liver to clear plasminogen activators increased fibrinolysis
-macroglobulinemia: abnormal production of proteins coat platelets
-multiple myeloma: cryoglobulins bind certain blood-clotting factors

# # #" ! "#
-spontaneous bleeding as a complication of anticoagulant therapy
-ecchymoses, petechia, or haematoma

86
+, " . # ( !(. *
-complications:
-overheparinization, heparin rebound, inadequate protamines neutralization, protamines excess,
thrombocytopenia
-two factors most important in triggering excessive bleeding: excessive fibrinolysis and platelet function
defects
-management:
-6 to 8 units of platelets
-if overheparinized: protamines
-excess fibrinolysis: EACA

% ) ! )

Platelet Count
-spontaneous bleeding only rarely for counts greater than 40000/mm3
-counts of 60000-70000/mm3 sufficient for hemostasis in surgery and trauma

Bleeding Time
-assessment of interaction b/n platelets and damaged blood vessel and formation of platelet plug
-abnormal in:
-thrombocytopenia
-qualitative platelet disorders
-vWD
-some patients with Vdeficiency or hypofibrinogenemia
-ASA ingestion

Prothrombin Time
-measures speed of the Extrinsic Pathway
-will detect deficiencies of factors II, V, VII, X and fibrinogen

Partial Thromboplastin Time


-screening test for Intrinsic Pathway
-sensitive to VIII, IX, XI, and XII as well as II, V, VII, X

Thrombin Time
-detects qualitative abnormalities in fibrinogen
-detects circulating anticoagulants and inhibitors of fibrin polymerization
-clotting time of pt’s plasma measured after thrombin added

Tests of Fibrinolysis
-fibrin degradation products (FDPs) measured immunologically
-euglobulin clot lysis time, dilute whole-blood or plasma-clot-lysis time: more sensitive, rapid evaluation of
fibrinolysis

& % 8

. 2 2 # $

-History:
-prolonged bleeding or swelling after biting lip or tongue
-bruises without apparent injury

87
-prolonged bleeding after dental extraction
-excessive menstrual bleeding
-bleeding problems associated with major and minor operations
-medical problems within past 5 years
-medications including aspirin within past 10 days
-relative with a bleeding problem

-Preoperative assessment:
Level 1: -negative history, minor procedure
-no screening test needed
Level 2: -negative history, major procedure
-platelet count, PTT
Level 3: -history suggestive, procedure where hemostasis is impaired (eg. cell savers)
-procedures where minimal bleeding could be injurious (eg. intracranial bleed)
-platelet count, bleeding time, PT/PTT
Level 4: -highly suggestive history
-hematologist consult, platelet count, bleeding time, PT/PTT

2 # $ 9 2 # . 2 $ . 2 ! "#

-May be due to:


-ineffective local hemostasis
-complications of blood transfusion
-previously undetected hemostatic defect
-consumptive coagulopathy
-fibrinolysis
-Operations on prostate, pancreas and liver: operative trauma ma stimulate local plasminogen activation and lead to
increased fibrinolysis on the raw surface
-Transfusion purpura:
-uncommon cause of thrombocytopenia; considered if bleeding follows transfusion by 5-6 days
-donor platelets are of uncommon PlA1 group sensitize recipient to make antibody to foreign platelet
-antibody then destroys recipient’s own platelets
-usually self-limited
-Be aware of DIC, gram-negative sepsis (endotoxins-induced thrombocytopenia)
-Complications of biliary tract surgery in cirrhotic patients:
-related to portal hypertension and coagulopathy associated with chronic liver disase
-tx: vasopressin IV to reduce portal HTN; EACA to correct increased fibrinolysis

% * # "
-digital pressure
-haemostat and subsequent ligation with sutures or clips
-non-absorbable sutures evoke less tissue reaction and absorbable materials
-non-absorbable material in an infected wound can lead to extrusion or sinus tract formation
-cold packs promote hemostasis by inducing vascular spasm and increasing endothelial adhesiveness

* #
-heat denatures protein which results in coagulation of large areas of tissue
-advantage: time; disadvantage: more tissue is necrose

88
* #
-epinephrine: induces vasoconstriction; used on oozing sites in mucosa areas
-gelatin foam (Gelfoam), oxidized cellulose (Oxycel), oxidized regenerated cellulose (Surgicel), and micronized
collage (Avitene)
-fibrin glue (Tisseal)

* $ . # * .(

Banked Whole Blood


-rarely indicated and rarely available
-shelf life 40 +/- 5 days
-changes in red cell: reduction of intracellular ATP and 2,3-DPG decreases oxygen transport function
-poor source of platelets
-within 21 days: pH to 6.68, lactic acid, K, NH3

Typing and Crossmatching


-crossmatching between donor’s red cells and recipient’s serum
-Rh negative ~ 15% of donor population
-Rh-positive blood should not be transfused to Rh-negative females who are capable of child-bearing
-emergency blood transfusion with type O blood
-cryoglobulins in patients with malignant lymphoma and leukemia: blood administered through blood warmer

Packed Red Cells and Frozen Red Cells


-provides oxygen carrying capacity
-reduced amount of sodium, potassium, lactic acid
-frozen red cells not available for use in emergencies: often used in pts previously sensitized; cells have been
selected for lack of certain antigens

Leukocyte-Poor Washed Cells


-aspiration of buffy coat and passing them through white-cell filter
-red cells washed with sterile isotonic solution
-for patients with demonstrated hypersensitivity to leukocytes or platelets

Platelet Concentrates
-indications:
-thrombocytopenia due to massive blood loss and replacement with platelet-poor products
-thrombocytopenia due to inadequate production
-qualitative platelet disorders
-may transmit infectious diseases and account for allergic reactions
-transfuse to elevate platelet levels to range of 50,000 to 10,000/mm3 for surgeries
-isoimmunity most important factor limiting usefulness

Frozen Plasma and Volume Expanders


-FFP: provide factors V and VIII
-RL, dextran, albumin: rapid plasma expansion
-prolongation of bleeding time and haemorrhage can occur with amounts of dextran exceeding 1L/day

Concentrates
-antihemophilic concentrates
-albumin: 25 g osmotic equivalent of 500 ml of plasma; hepatitis free product

89
#" # $ . # $! " #

Improvement in Oxygen-Carrying Capacity


-no correlation however between anemia and dehiscence or severity of post-operative infection

Volume Replacement
-restore circulating blood volume
-measurement of haemoglobin and hematocrit can be misleading and do not reflect severity of blood loss
-in OR: blood loss up to 20% replaced with crystalloids; above 50%, replaced with crystalloids, RBC, and albumin
or plasma +/- FFP if continued bleeding

Replacement of Clotting Factors


-treatment of certain haemorrhagic conditions

. $ #" #

Massive Transfusion
-single transfusion greater than 2500 ml or 5000 ml transfused over a period of 24h
-complications:
-circulatory overload or DIC may occur
-dilutional thrombocytopenia, impaired platelet function, deficiencies of V, VIII, XI
-citrate toxicity: excessive binding of ionized calcium; rarely have a significant effect
-reduced 2,3-DPG increased affinity of RBC for O2 and less efficient delivery
-hypothermia decreases CO and rate
-hemolytic transfusion reaction
-infectious diseases

% * " $ " # # ! "

Routine Administration
-usually 5 ml/min for 1 min then 10-20 ml/min
-with marked oligemia: 500 ml over 10 min, second 500 ml over 10 min
-no practical advantage in intraarterial transfusion

Other Methods
-intraperitoneally: 90% enter circulation but uptake not complete for at least 1 week
-via medullary cavity of sternum and long bones: painful; limited rate
-cell saver: 250 ml in 5-6 min
-hemodilution: remove blood and maintain intravascular volume with crystalloids or colloid; removed blood may be
then retransfused

. #

(1) Hemolytic Reactions


-incidence of non-fatal reactions: 1 per 6000 units
-incidence of fatal reactions: 1per 100,000 units
-clerical or laboratory errors account for reactions d/t incompatibility of A,B,O and Rh groups
-haptoglobin binds haemoglobin complex is cleared by reticuloendothelial system
-free haemoglobin combines with albumin to form methemalbumin
-red cell stromal lipid; antibody-antigen complexes activating XII end complement may initiate DIC

90
Clinical Manifestation:
-pain, sensation of heat along vein; facial flushing, lumbar pain, constricting chest pain
-chills, fever, respiratory distress, hypotension, tachycardia
-if anaesthetized: abnormal bleeding and continued hypotension
-fall in platelet count, increased fibrinolysis, consumption of coagulation factors (esp V, VIII)
-Rudowski: oliguiria 56%; hemoglobinuria 56%; hypotension 50%; jaundice 40%; n/v 30%; flank pain 25%;
cyanosis and hypothermia 22%....

Treatment
-immediately stop transfusion
-send sample of patient’s blood to blood bank for comparison with pretransfusion samples
-determine bilirubin levels
-foley hourly urine measured
-initiate diuresis and alkalinize urine (mannitol or furosemide, 45 mEq bicarbonate)
-maintain hydration

(2) Febrile and Allergic Reactions


-occur in 1% of transfusions
-urticaria, fever within 60-90 min
-caused by transfusion of antibodies from hypersensitive donors or transfusion of antigen
-tx: antihistamines, epinephrine, steroids

(3) Bacterial Sepsis


-gram-negative, esp Pseudomonas are most common cause
-shock: administration of adrenergic blocking agents, oxygen, antibiotics

(4) Embolism
-normal adult generally can tolerate embolism of 200 ml of air
-venous air embolism:
- venous pressure, cyanosis, “mill wheel” murmur over precordium, hypotension, tachycardia and
syncope
-tx: left lateral decubitus position in Trendelenburg
-arterial air embolism: dizziness and fainting, LOC, convulsions; air may be visible in the retinal arteries

(5) Thrombophlebitis
-discontinue transfusion and compress locally

(6) Overtransfusion and Pulmonary Edema


-rise in venous pressure, dyspnea, cough

(7) Transmission of Disease


-malaria, Chaga’s disese, brucellosis, syphilis
-viral hepatitis: most common fatal complication; risk 0.035% per unit blood
-AIDS: one case per 225,000 patients transfused

91
-pathophysiologic condition: state of inadequate tissue perfusion

!"
-return of venous blood to heart produces ventricular end-diastolic wall tension, a major determinant of cardiac
output
-veins in skeletal muscles respond to external factors: gravitational forces and muscle pump
-exercise and increased sympathetic reflexively decrease the splanchnic capacitance
-salt and water balance from the kidneys via hormonal effects of renin, angiotensin and antidiuretic hormone

# $! !
-Frank-Starling curve: force of contraction dependent on initial muscle length
-affected by variety of disease states: MI, valve dysfunction, cardiac hypertrophy

!"
-force acting to resist myocardial work during contraction
-arterial pressure is the major component that influences the ejection fraction
-determined by precapillary smooth muscle sphincter
-in normal heart, stroke volume maintained in lieu of increased afterload by increased reload

# %

-decreased circulating or effective intravascular volume


-increased peripheral vascular resistence to protect blood pressure in compensation for falling CO
-differential increases in skin, gut, and kidney to protect other vital organs

&' (! ) (' ((

1. -increased vascular tone elevates PVR redistribution of blood flow among organ systems
-“autoregulated” organs (heart, brain) preferred

2. -increased sympathetic activity


-diminished vagal inhibition of rate and force of cardiac contraction greater contractility and enhanced venous return CO,
myocardial O2 consumption

3. -decreased capillary hydrostatic pressure transcapillary influx of extravascular ECF


-this intravascular volume and blood viscosity by dilution

4. -increased tissue extraction of oxygen by presence of acidosis and 2,3-DPG


-rightward shift of oxyhaemoglobin dissociation curve
-hypoxia hyperventilation resp. alkalosis increased rate of erythrocyte synthesis of 2,3-DPG

5. -diminished renal flow afferent and efferent arterioles stimulated


-u/o decreases as H2O and sodium are retained

6. -increased release of catecholamines by adrenals


-produce vasoconstriction and tachycardia
-glycogenolysis, lipolysis, skeletal muscle breakdown stimulated, insulin release inhibited promote glucose mobilization, protein
catabolism, and negative nitrogen balance
-retention of sodium and water in proximal tubule of nephron

92
7. -ACTH released (stimulated by various stresses)
-cortisol potentiates actions of epinephrine and glucagon, further stimulates mobilization of amino acids from skeletal muscle, and
results in renal sodium and water retention

8. -insulin secretion diminished

9. -ADH secreted in response to increased serum osmolarity and hypovolemia


-potent splanchnic vasoconstrictors
-increases water permeability and passive sodium transport in the distal nephron tubule
-Renin-angiotensin system activated
-response to sympathetic stimulation of juxtaglomerular cells (B-adrenergic action), renal perfusion pressure, and
compositional changes in tubular fluid
-Angiotensin II:
-powerful arterial and arteriolar vasoconstrictors
-stimulates renal prostaglandin production
-stimulates release of aldosterone and ACTH
-Aldosterone: increases sodium resorption in exchange for potassium and hydrogen ions in distal nephron
-Prostaglandins (esp PGE2), kallidreins produced in kidney dilate renal vessels and increase renal blood flow

$& !) ! * & (

-Acute Respiratory Distress Syndrome (ARDS)


-hypoxia (despite oxygen therapy), decreased pulmonary compliance, diffuse infiltrates on CXR, non-
pulmonary edema

Etiology
-ARDS is the final common pathway to various pulmonary insults
-initiation of inflammatory mediators increases microvascular permeability proteinaceous fluid deposition in
alveolar epithelial and pulmonary capillary endothelial interface V/Q mismatch
-fluid overwhelms pulmonary lymphatic clearance
-pulmonary edema refractory to diuretics and fluid restriction; colloid administration not useful

Diagnosis
-clinical suspicion

Therapy for ARDS


-maintain tissue oxygenation: PaO2 > 65 mmHg
-volume ventilator with tidal volume and rate set to allow adequate CO2 exchange
-PEEP initiated at 5 cmH2O; used to maintain oxygenation at nontoxic (50% or less) levels
-set ventilator at 100% O2; increase PEEP by increments of 2.5 allowing at least 30 min for equilibration
-measure arterial and mixed venous blood gases, PCWP, and CO
-increase PEEP to as much as 20 without compromise of CO
-decrease O2 incrementally but keep PaO2 of 65 mmHg
-PEEP can then be decreased if oxygenation maintained by increments of 2.5 q12h
-potential risks of PEEP are exacerbated by hypovolemia: intrathoracic pressure and venous return CO

)' + &

$" ($( !

Composition of Resuscitation Fluids

1. Ringer’s Lactate:

93
-lactate content will not aggravate lactic acidosis
-safe inexpensive, equilibrates rapidly throughout ECF

2. Colloid solutions:
-raise intravascular colloidal pressure intravascular influx of interstitial fluid
-more expensive, may bind and decrease ionized serum calcium, decrease circulating immunoglobulins,
decrease immune reaction to tetanus toxoid, decrease endogenous production of albumin
-may not necessarily be better for fluid resuscitation over crystalloids
-no clinical evidence that appropriate resuscitation with balanced slat solution is associated with
any harmful effects on pulmonary function

3. Hypertonic Saline:
-can be effective initial resuscitative solution but requires close monitoring of electrolytes to prevent
hypernatrema and hyperosmolar coma
-long-term benefits not established

4. Hetastarch:
-slow equilibration can lead to rapid fluctuations in CVP
-mild and transient coagulopathies noted

5. Dextran:
-greater risk of anaphylaxis; has produced coagulation defects and immunoglobulin depression

6. Blood substitutes:
-stroma-free haemoglobin (SFH) eliminates side effects secondary to erythrocyte stromal elements
-high affinity for oxygen, short plasma half-life, available only from human sources
-not a practical substitute
-perfluorodecalin:
-require emulsification to be water soluble
-use requires higher inspire oxygen concentrations
-effective substitute for haemoglobin

",$+! !')

(1) Vasopressors
-may elevate BP at expense of further PVR and tissue perfusion
-do not substitute for adequate fluid resuscitation

(2) ATP
-in experimental models, found to improve survival rates in potentially lethal shock (in combination with fluids)
-limited usefulness in clinical treatment since may result in marked homodynamic instability in hypovolemic pt

(3) Positioning
-Trendelenberg may interfere with respiratory exchange
-preferred position is elevation of both legs while maintaining head, trunk and arms supine autotransfusion of
pooled blood in venous circulation

(4) MAST Garment


-resultant increase in total PVR may elevate sBP while CO and peripheral perfusion
-may compress IVC and impair venous return and increase venous resistance
-risk of reperfusion injury
-of value only as temporizing device or as specific treatment of bleeding pelvic fractures

94
(5) Pulmonary Support
-beneficial in patients with abnormal oxygen saturations: eg. PTX, pulmonary contusion, aspiration, a/w
obstruction, COPD etc..

(6) Antibiotics
-no support for protective mechanism against ravages of hypovolemia
-use in patients with open or potentially contaminated wounds

(7) Analgesics
-if causative injury produces severe pain, control of pain becomes mandatory
-small doses of narcotics should be given intravenously to prevent profound sedation

(8) Steroids
-specific instances, steroid depletion with hypovolemic shock may occur:
-elderly patient
-Addison’s disease, post-adrenalectomy, adrenal suppression with exogenous steroids
-IV hydrocortisone desirable in these cases
-steroids not indicated in trauma patient with hypovolemia

(9) Monitoring
-CVP:
-normal to depressed despite administration of fluids continuing hypovolemia
-elevated or rapid rise impairment of pumping mechanism
-if shock is refractory to treatment, must look for:
-continuing blood loss into chest or abdomen
-inadequate volume replacement
-inadequate clotting
-multisystem trauma with occult thoracic injuries (cardiac tamponade, hemopneumothorax)
-myocardial insufficiency (contusion or hypoperfusion)

!" *

-heart unable to generate sufficient cardiac output to maintain adequate tissue perfusion
-hypotension in the face of adequate intravascular volume

Pathophysiology
-secondary to valvular heart disease, cardiomyopathy, myocardial contusion
-AMI most frequent cause; fatal if >40% loss of left ventricular mass
-complications:
-papillary muscle dysfunction, ischemic ventricular septal defects, massive LV infarction,
arrhythmia
-vicious cycle created: increased myocardial oxygen demand, hypotension, shortened diastole, increased PVR and
afterload

Treatment
-initial therapy: optimizing ventricular reload by manipulating filling pressure, decreasing afterload in patient with
adequate sBP, correcting arrhythmia, improving contractility to sustain vital organ perfusion

1. Monitoring and Volume Management:


-supplemental oxygen, pain relief and sedation, continuous ECG
-Foley catheter for urine output, art line, oximetry, Swan-Ganz
-small increase in LV filling pressure by volume infusion may maximize CO via Frank-Starling mechanism
-must r/o mechanical obstruction such as tamponade or embolism

95
-watch for pulmonary edema intubation and ventilation will myocardial oxygen demand from increased
work of breathing

2. Inotropic Agents:
-beta1-adrenergic receptors increased contractility and CO
-increases myocardial oxygen demand
-Dopamine:
- may reverse life-threatening hypotension and restore MAP to about 80 mmHg
-low doses:
2-5 ug/kg/min splanchnic, coronary, renal vasodilation
5-8 ug/kg/min adrenergic-mediated in contractility and heart rate
-high doses:
alpha-adrenergic effects: CVP and coronary vasoconstriction
-variable increase in heart rate
-can precipitate other arrhythmia
-Dobutamine:
-synthetic catecholamine with predominantly inotropic effect
-Digitalis:
-controversial; useful in supraventricular arrhythmia
-increased MO2: adds very little homodynamic benefit relative to therapy the sympathomimetic
agents

3. Vasodilator Agents:
-some patients with low CO and high filling pressures have near-normal arterial blood pressures
-systolic ventricular wall stress is high, and reducing afterload should increase cardiac output and decrease
myocardial work therefore can use nitroprusside, but with extreme caution in hypotensive patients

4. Mechanical Support
-intraaortic balloon pump: unloading LV and reduce myocardial work
-elevates diastolic BP: increases pulmonary perfusion, decreases myocardial work, increases
cardiac output distal to ventricle
-unclear if improves long-term survival
-good bridge until surgically correctable problems are addressed
-left ventricular assist devices: currently limited to cardiac surgery patients

5. Arrhythmias
-decreased ventricular EDP from decreased filling time
-digoxin drug of choice for atrial fibrillation or flutter - cardioversion if hypotension or hypoperfusion
-verapamil for tachyarrhythmias of atrial origin
-propranolol for sinus tachycardia
-defibrillation for ventricular fibrillation
-lidocaine for premature ventricular complexes which may lead to ventricular tachyarrhythmias
-bradyarrhythmias: electrical pacing

$ *

-occurs after serious interference with the balance of vasodilator and vasoconstrictors influences to the arterioles
and venules
-clinical syncope
-paralysis of vasomotor influences; eg. high spinal anaesthesia, spinal cord injury
-reflex interruption of nerve impulses: acute gastric dilatation
-low BP, low pulse rate, dry, warm, flushed skin
-decreased CO, decreased PVR

96
-can result in kidney failure and brain damage

Treatment
-gastric dilation NG tube insertion
-high spinal anaesthesia fluids, vasopressor (Neo-synephrine)
-spinal trauma maintain normal CVP that rises slightly with rapid fluid administration and using a vasopressor
judiciously to support arterial pressure

'

-most frequent causative organism: gram-negative bacteria, occasionally gram-positive bacteria


-most common source is GU system; second is respiratory, then GI

Clinical Manifestations
-normovolemic but has hypotension despite increased CO and good filling pressure
-paradoxical “warm shock”
-high CO associated with decrease in oxygen utilization and narrowed arteriovenous oxygen difference
-thrombocytopenia may be early indicator of gram-negative sepsis
-systemic illness may result form inappropriate systemic effects of mediators used to contain local infection
-myocardial depression despite hyperdynamic CO

Pathophysiology
-TNF is a central and proximal mediator of the host response to endotoxemia and bacteremia
-produced predominantly by cells of macrophage lineage
-reduction in membrane potential preceded onset of hypotension
-TNF-alpha:
-capable of inducing membrane depolarization in vitro
-important mediator of septic shock
-induces synthesis and secretion of secondary mediators: cytokines, PG, leukotrienes,
PAF, complement, coagulation cascade
-may synergise with lipopolysaccharide to induce many toxic effects mediated by TNF-alpha
-naturally occurring inhibitors of TNF-alpha activity: extracellular type I and II TNF receptors
shed from cell surface in response to inflammatory stimuli
-Interleukin-1
-key mediators of host response to infection, inflammation and injury
-IL-1 receptor antagonist (IL-1ra) blocks many functions of IL-1:
-lymphocyte proliferation, increased adhesion of endothelial cells for neutrophils and
eosinophil; synthesis of IL-1, TNF-alpha, IL-6, and IL-8 by monocytes; nitric oxide
production in SMC
-anti-endotoxins antibodies fail to confirm beneficial effects
-other potential mediators of septic shock: linins, endogenous opiates, other recently purified cytokines

Therapy
-antibiotics and early surgical debridement or drainage of abscess
-fluid therapy, vasoactive drugs as adjuncts
-broad spectrum should include anaerobic coverage
-steroids offer no advantage; use only in hypoadrenalism and stress coverage in those already taking steroids

1. Pharmacologic support
-dopamine: improves hypotension
-dobutamine: may not be tolerated by hypotensive patients
-use of pressors is primarily for transient support while primary definitive therapy with antibiotics and
drainage of surgical infection are being instituted

97
2. Manipulations of Humoral Responses
-difficult because of the complex and ill-defined interactions among a large number of mediators
-only a few showed statistical benefits in studies: HA-1A (human monoclonal IgM against lipid A of
endotoxins), E5 (murine monoclonal IgM against lipid A)

98
!

-infections requiring operative treatment:


1. necrotizing soft tissue infections
2. body cavity infections (eg. peritonitis, suppurative pericarditis, empyema)
3. confined tissue,organ, joint infection
4. prosthetic device-associated infections

" # "$
-operative treatment generally required when host defences cannot function properly or when continuing
contamination with microorganisms

! %

(1) Microbial Pathogenicity:


-thick capsules in bacteria and fungi resistant to phagocytosis
-resist intracellular killing (phagocytosis by lysosome):
eg. Mycobacterium tuberculosis, Aspergillus flavus, Toxoplama gondii
-exotoxins: eg. Clostridium sp., Staph. aureus, Strep. pyogenes
-neurotoxins: Clostridium tetani, Clostridium botulinum
-endotoxins: lipopolysaccharide-protein complexes (gram negative bacteria)

(2) Host Defenses:


-Local Host Defenses:
-epithelium
-lack of moisture (skin), flushing action of tears and urine, cilia (trachea, bronchi), peristalsis,
mucous, pH, local immunity (IgA)
-Systemic Host Defenses:
-phagocytic cells, immune system, molecular cascades (complement, coagulation, kinin)
-Macrophages: liver (Kupffer cells), spleen, lymphoid tissue, lung, grain (glial cells), connective
tissue (histiocytes), pleura and peritoneum

(3) Local Environmental Factors:


-phagocytic cells do not function effectively in the presence of devitalized tissue or foreign bodies
-fluid collections and edema inhibit phagocytosis
-peripheral vascular disease and shock prevent blood (and hence cells and mediators) to reach sites of
microbial contamination
-lowered tissue oxygen tension inhibits function of phagocytic cells; promotes growth of anaerobes

(4) Surgical Technique:


-important determinant of postoperative wound infection

99
&' ( $% "#
-cellulitis:
-spreading infection of skin and subcutaneous tissues
-local pain/tenderness, edema, erythema
-usually indistinct borders
-+/- systemic symptoms
-caused by: Strep. pyogenes, Staph. aureus, Strep. pneumoniae, Haemophilus influenzae, other
streptococci, aerobic and anaerobic gram-negative bacteria
-erysipelas:
-caused by strep. pyogenes
-intense erythema with sharp line of demarcation
-lymphangitis:
-inflammation of lymphatic channels
-presents as visible red streaks

)' *
-carbuncle:
-subcutaneous abscess from confluent infection of multiple contiguous hair follicles
-most commonly Staph. aureus
-felon:
-purulent collection in distal phalanx
-intense pain and pressure in compartment; treat with lateral incision
-breast abscess:
-usually Staph. aureus
-treat with incision and drainage and antibiotics
-perirectal abscess:
-infection of crypt glands that extends into perirectal space
-aerobic and anaerobic gram-negative bacteria

+' ,
-most caused by mixed aerobic and anaerobic gram-negative and gram-positive bacteria
-Clostridium sp. (C. perfringens, C. novyi, C. septicum) - gram positive rods
-most common, most dramatic infections, rapid progression, high mortality
-“gas gangrene”
-subcutaneous emphysema: anaerobic bacterial metabolism hydrogen, nitrogen, methane
-Strep. pyogenes
-Vibrio
-fungi necrotizing infections progress more slowly than bacterial infections
-surgical treatment requires debridement of all necrotic tissue
-hyperbaric oxygen: inhibits production of alpha toxin in Clostridia
-no improvement in patients with nonclostridial infection
-complications: middle ear injury, trauma to sinus, PTX, air embolism

-'
-caused by Clostridium tetani
-majority of cases appear after punctures, lacerations, and abrasions
-two toxins:
-tetanospasmin
-actons on anterior horn cells of spinal cord and brainstem

100
-blocks inhibitor synapses muscle spasms and hyperreflexia
-testanolysin
-cardiotoxic and causes haemolysis; not thought to be of major clinical importance

Clinical Manifestations:
-generalized muscle spasms generalized convulsions
-orthotonos, opisthotonos, emprosthotonos
-spasm of laryngeal and respiratory muscles fatal acute asphyxia
-mortality rate can exceed 50%
-diagnosis on clinical grounds; laboratory investigations not helpful in diagnosis

Treatment:
-tetanus immune globulin (TIG) 500-10,000 units ASAP
-ICU admission intubation, ventilation, paralytic drugs
-mild cases: sedation, muscle relaxants, analgesics
-(hyperbaric oxygen is ineffective)
-treat wound to remove C.tetani and nonviable tissue +/- antibiotics

Prevention:

Summary of Recommendations for Tetanus Prophylaxis in Routine


Wound Management
History of Clean Minor Wounds All Other Wounds*
Adsorbed
Tetanus
Td TIG Td TIG
Toxoid (Doses)

Unknown or < Yes No Yes Yes


3 doses

> 3 doses No No No No
(Yes if > 10y (Yes if > 5y
since last dose) since last dose)
*such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds;
avulsions; and wounds resulting from missiles, crushing, burns, or frostbite

. ($ / $

&' ( *( % *
-Primary peritonitis: caused by single organism; commonly seen in pts with ascites or renal failure on PD
-Secondary peritonitis:
-defect in GI tract
-requires operative intervention; antibiotics against aerobic and anaerobic enteric bacteria
-Tertiary peritonitis:
-peritonitis-like syndrome as a result of a disturbance in host’s immune response
-peritonitis without evidence of pathogens
-may also be caused by fungi or low-grade pathogenic bacteria
-Intraabdominal abscess: percutaneous or operative drainage along with Abx therapy needed

)' % "$ %
-causes:
-pneumonia (most common), pulmonary infact, septic embolic to lung, tracheal or bronchial
fistula, leaking esophageal anastomosis, hepatic abscess, subphrenic abscess, trauma, leaking
bronchial closure, infected hemothorax, paravertebral absces

101
-chronic empyema: dyspnea, fatigue, anemia, debility, clubbing of fingers
-treated with chest tube; may be converted to open drainage after 2 to 3 weeks
-open drainage if multiple pus pockets, thick pus, or inadequate drainage via CT

# ( " (
-septic arthritis
-suppurative pericarditis

# ! / (
-cardiac valves, pacemakers, vascular grafts, artificial joints
-total removal to eradicate infection

" 0 (1 % 2

-urinary tract infections (most common), wound infection, lower respiratory tract infection, bacteremia, cutaneous
infection

&' 3 (

Classification:

Classification of Operative Wounds in Relation to Contamination and Increasing Risk of


Infection

Clean (1.5-3.9% infection rate)


-elective, primarily closed, undrained
-non-traumatic, uninfected
-no inflammation encountered
-no break in asepsis
-respiratory, alimentary, genitourinary, or oropharyngeal tracts not entered

Clean-contaminated (3-4% infection rate)


-alimentary, respiratory, or genitourinary tracts entered under controlled conditions
and without unusual contamination
-appendectomy
-oropharynx entered; vagina entered
-GU entered in absence of culture-positive urine
-biliary tract entered in absence of infected bile
-minor break in technique
-mechanical drainage

Contaminated (8.5% infection rate)


-open, fresh traumatic wounds
-gross spillage from gastrointestinal tract
-GU or biliary tracts entered in presence of infected urine or bile
-major break in technique
-incisions where acute non-purulent inflammation present

Dirty (28-40%)
-traumatic wound with retained devitalized tissue, FB, feces, delayed treatment
-perforated viscus
-acute bacterial inflammation with pus encountered during operation

102
Definition of Surgical Wound Infection:

Superficial:
-infection occurs at incision within 30 days after operation
-involves skin or subcutaneous tissue above fascial layer with any of the following:
-purulent drainage
-organism isolated from culture
-wound opened deliberately by the surgeon

Deep:
-infection occurs at incision within 30 days after operation (no prosthesis); within 1 year of an implant
-infection beneath fascial layer and any of the following:
-wound spontaneously dehisces or deliberately opened when T>38 and/or pain
-abscess seen on direct examination, operation, or histopathologic examination
-surgeon diagnoses infection

)' "#$ 4

Operating Room Environment:


-air filtration to reduce number of microbes
-positive pressure relative to air
Instruments and Drapes:
-proper sterilization; drapes should be kept as dry as possible
Hand Washing:
-washing for 5 minutes sufficient
-hexachlorophene, povidone-iodine, chlorhexidine commonly used
Gloves:
Other Barriers:
-caps to prevent hair and skin scales falling into wounds
-masks prevent droplets entering wounds
-no data that demonstrate unequivocally reduction of infection rate
Preoperative Stay
-longer preoperative hospitalization more likely to have post-operative wound infections
-may acquire more virulent or antibiotic-resistant bacteria
-compromised host defences
Remote Infections:
-can triple rate of infection; due to moisture
-elective operations should be delayed until infection eliminated
Hair removal:
-nicks and cuts from shaving: sites where bacteria can proliferate
-clipping preferred; shaving done in operating room to prevent bacterial proliferation
Skin Preparation:
Reduction of Colonic Bacteria:
-enemas before colonic surgery
-oral antibiotics: neomycin and erythromycin
Improving host Defenses:
-correct malnutrition, obesity, abnormal physiologic states
-smoking cessation
Surgical Technique:
-minimize injury to tissue and prevent accumulation of agents that facilitate bacterial growth or
inhibit host defences
-latex rubber drains leads to a higher wound infection rate than not using a drain

103
Prophylactic Antibiotics:
-Principles:
1. Choose Abx effective against most likely pathogen
2. Abx with low toxicity
3. Give single, fully therapeutic dose IV 30-60 minutes preoperatively
4. Give second dose if surgery > 4h or twice half-life of Abx
5. Give 2-3 doses post-op; no need to extend beyond 24h
6. Use of Abx appropriate when infection frequent or when consequences of infection
unusually severe
-cephalosporins most commonly used because of broad spectrum

)' # " 0 (

Urinary Tract Infection:


-40% of hospital-acquired infections
-from operations of lower urinary tract, instrumentation of the bladder, or catheterization
-higher risk in pregnant women, elderly or debilitated pts, urologic abnormalities
-indwelling catheter: 5-10% risk/d

Lower Respiratory Tract Infection:


-third most common nosocomial infection
-risks factors:
-aspiration
-pain from thoracic or upper abdo surgery and trauma atelectasis predispose to infection
-pulmonary edema: fluid in alveoli inhibits phagocytic capacity of pulmonary macrophages
-tracheotomies and respiratory care devices
-causative organisms:
-Staph. aureus, Pseudomonas aeruginosa, Klebsiella sp., E.coli, Enterobacter sp.

Vascular Catheter-Related Infection:


-central lines > peripheral lines; polyethylene > silastic
-mostly from skin organisms at skin exit site: Staph. aures and S. epidermidis
-hematogenous: yeast, gram-negative enteric bacteria

5 .

&' % /

Staphylococcus
-facultative anerobes
-found on moist areas of body, anterior nares, mucous membranes

(1) Staph. aureus:


- most common pathogen in wound infections
-pathogenic factors:
-coagulase: major factor in its pathogenicity
-cell wall and capsules inhibit opsonization and thus phagocytosis
-enterotoxin food poisoning
-epidermolytic toxin exfoliative bullae (Scalded Skin Syndrome)

104
-TSS toxin-1 toxic shock syndrome
-catalase: resists H2O2-mediated intracellular killing

(2) Staph. epidermidis:


-thought to be commensal
-causes infection in presence of FB (eg. plastic catheters, ventricular shunts, prosthetic joints,
valves)

Streptococcus
-S. pyogenes, S. pneumoniae
-viridans group: S. mutans, S. mitior, S. salivarius, S. sanguis, S. milleri
-grouped according to:
a. Lancefield classification: cell surface antigens
b. Hemolytic ability on blood agar:
-alpha haemolysis: zone of green discolouration around colonies; intact RBC
-beta haemolysis: complete clearing of area around colonies; destroyed RBC
-gamma haemolysis: no haemolysis

(1) Group A Streptococci:


-Strep. pyogenes: GABHS
-pathogenic factors:
-cell surface M protein and capsule resistant to phagocytosis
-hyaluronidase and streptokinase promote spread of infection
-streptolysin O and streptolysin S: hemolysins
-proteinases tissue invasion
-pyogenic exotoxins

Manifestations:
-pharyngitis scarlet or rheumatic fever
-erysipelas
-cellulitis, wound infection, endocarditis, UTI, bacteremia
-primary necrotizing soft tissue infections (although S. pyogenes an uncommon cause) and abscesses

)' * ( / $ * % / .

-Escherichia, Klebsiella, Proteus, Enterobacter, Serratia, Providencia


-Vibrio: in marine and water bacteremia and necrotizing soft tissue infections
-Pseudomonas: obligate aerobes; frequently found in immunologically compromised patients
-cause necrotizing infections, esp pneumonia and vasculitis
-Ecthyma gangrenosum: cutaneous manifestations of necrotizing vasculitis d/t Pseudomonas
-due to resistance, frequently treated with two antibiotics

+' * .

-found in mouth, vagina, and GI tract; infections usually endogenous


-low redox potential common to all anaerobic infections
-factors for predisposition:
-vascular disease, cold, shock, edema, trauma, devitalized tissue, operation, foreign bodies, malignant
disease, growth of aerobic microorganisms
-examples:
-Bacteroides fragilis, Fusobacterium, Peptostreptococcus
-Clostridium:
-produce exotoxins: C. perfringen, C. septicum, C. novyi

105
-enterotoxins: C. difficile, C. perfringins
-neurotoxins: C. tetani, C. botulinum

-primary pathogens: cause disease in immunocompetent pts


-Histoplasma, Coccidioides, Blastomyces
-opportunists: cause disease in immunocompromised pts
-Candida, Cryptococcus, Aspergillus, phycomycetes (Mucor, Absidia, Rhizopus)
-treatment consists of:
-stopping antibiotics, correcting host defences, therapy with amphotericin B or one of the azole antifungal
agents

6
-Herpesvirus family: CMV, HSV, VZV, EBV
-CMV: -causes most viral infections in organ transplant recipients
-ulcerative lesions of the GI tract bleeding or perforation
-EBV: -polyclonal B-cell lymphoma in transplant recipients

% %% ( $6
-retrovirus of lentivirus family
-RNA virus with cylindrical core containing RNA, RNA-dependent DNA polymerase (reverse transcriptase), and
core proteins
-GP-120: affinity for CD4+ receptor on TH cells
-infected CD4+ cells cannot carry immune functions opportunist infections, Kaposi’s sarcoma
and primary CNS lymphomas
-CD4 count < 200/mm3 = AIDS

Surgery in HIV-Infected Patients:


-HIV related problems:
-peritonitis secondary to bowel perforation due to CMV infection
-GI obstruction from Kaposi’s or lymphoma of GI tract
-intestinal haemorrhage d/t CMV, lymphoma, Kaposi’s
-intraabdominal or retroperitoneal infection by mycobacterial and other opportunistic organisms

5 .

! * % *

-need adequate concentration delivered to site of infection


-should exceed minimum inhibitory concentration (MIC)
-pharmacokinetics dependent on protein binding of drug and lipid solubility

(1) Blood:
-concentration determined by rapidity of excretion and protein binding
-highly protein-bound antibiotics not excreted as rapidly do not have to be given as frequently

(2) Urine:
-sulfonamides, penicillins, cephalosporins, aminoglycosides, tetracyclines, quinolones, azoles
-excreted principally in urine and achieve high concentrations

(3) Bile: -besides urine, only bile regularly has antibiotic concentrations higher than serum levels

106
(4) Interstitial Fluid and Tissue:
-high, prolonged serum concentration and low protein binding favourdiffusion from serum into
extravascular tissue

(5) Abscesses:
-reduced antimicrobial efficacy d/t:
-acidic pH
-low redox potential
-large numbers of microbial and tissue products that can bind antibiotics
-drainage is key

* $

Prophylactic Antibiotics:
-discussed earlier
-administer to all patients with previously placed prosthetic devices such as cardiac valves or artificial
joints who are having any operation or dental procedure

Therapeutic Use of Antibiotics:


a. Empiric Therapy:
-intraabdominal surgical infections and necrotizing soft tissue infections: mixed gram-negative
and gram-positive aerobic and anaerobic bacteria
b. Definitive Therapy

! (%

Route: intravenous

Duration: most surgical infections can be treated effectively in 5-7 days of antibiotic therapy

Treatment Failure:
-wrong antibiotic, intraabdominal abscess, resistant bacteria, other causes (other sites of infection)
-inadequate dose, inappropriate route

Drug Toxicity:
-in renal failure, give a first dose of 80-100% then estimate timing and amount of second dose according to
various schedules based on the normal half-life of the antibiotic

107
-depth of injury proportionate to temperature applied, duration of contact and thickness of skin

(1) Scald Burns:


-hot water most common cause of burns
-60oC deep dermal or full-thickness burn in 3s
-69oC 1 s
-exposed areas tend to be burned less deeply than areas covered with thin clothing
-immersion scalds are always deep, severe burns
-deliberate scalds commonest form of reported child abuse (~5% of admission to burn centers)
-most common in children < 8 y

(2) Flame Burns:


-second most common burn

(3) Flash Burns:


-third most common burn
-explosions of natural gas, propane, gasoline
-mostly dermal; generally heal without requiring extensive skin grafting

(4) Contact Burns:


-usually limited in extent but invariably very deep

!"!

-critical legislative actions have decreased burns and burn mortality


-smoke detectors, maximum temperature for home and public hot water heaters

Burn Severity and Classification:


-severity of injury proportionate to:
-size of total burn
-depth of burn
-age of patient
-associated medical problems or injuries
-ABA and ACSCT classification:
a) Minor:
-superficial burns < 15% TBSA
b) Moderate:
-superficial burns 15-25% TBSA in adults; 10-20% TBSA in children
-full thickness burns < 10% TBSA
-burns not involving eyes, ears, face, hands, feet or perineum
c) Severe

108
Burn Center Referral Criteria:
1. Second- and third-degree burns > 10% TBSA in pts under 10 or over 50 yoa
2. Second- and third-degree burns > 20% TBSA in other age groups
3. Second- and third-degree burns involving face, hands, feet, genitalia, perineum, and major joints
4. Third-degree burns > 5% TBSA in any age group
5. Electrical burns, including lightning injury
6. Chemical burns
7. Inhalation injury
8. Burn injury in patients with preexisting medical disorders that could complicate management, prolong
recovery, or affect mortality
9. Any burn patients with concomitant trauma where burn injury poses greatest risk of morbidity or
mortality
10. Burn injury in children admitted to a hospital without qualified personnel or equipment for pediatric
care
11. Burn injury in patients requiring special social, emotional, and/or long-term rehabilitative support,
including cases involving suspected child abuse, substance abuse, etc.

# ! # $! %! !

(1) Airway:
-secure airway
-if suspicion of smoke inhalation 100% oxygen by mask
-endotracheal tube for unconscious patients

(2) Cold Application:


-smaller burns application of cold water
-does not prevent further tissue damage, but delays edema formation probably by reducing initial
thromboxane production
-ice water should never be used associated cutaneous vasoconstriction can extend thermal damage

(3) Emergency Room Care:


-careful search for other life-threatening injuries is first priority
-burn is attended to after ABC’s

(4) Emergency Assessment of Inhalational Injury:


-suspect if flame burn or anyone burned in enclosed space
-hoarseness and expiratory wheezes signs of potentially serious airway edema or smoke poisoning
-elevated carboxyhemoglobin is presumptive evidence of associated smoke poisoning
-decreased P/F ratio (arterial PO2/FIO2)
-400-500 is normal
-< 300 in patients with impending pulmonary problems
-< 250 indication for aggressive pulmonary support
-bronchoscopy to assess edema of upper airway

(5) Fluid Resuscitation in the Emergency Room


-systemic inflammatory response
-capillary leak: loss of fluid and protein into extravascular compartment
- CO d/t peripheral resistance
- flow to skin may convert zone of stasis to one of coagulation increases depth of burn
-inadequate fluid resuscitation end organ damage
-begin with 1000 cc/h Ringer’s solution in adults; 20 cc/kg in children

109
-CVP monitoring in pts with burns 50% TBSA, associated medical problems, very young or very old,
smoke inhalation
-Swan-Ganz catheters in pts with > 65% TBSA b/c of homodynamic instability

(6) Tetanus
-burns are tetanus-prone wounds

(7) Gastric Decompression


-tube feeding to protect stomach from stress ulceration

(8) Pain Control


-morphine 2-5 mg IV until pain control adequate

(9) Psychosocial Care


-social worker

%$# & # ' #% &

Chest Escharotomy:
-early respiratory distress may be due to compromise of the ventilatory function caused by a cuirass effect
related to a deep circumferential burn wound of the chest
-escharotomy: anterior axillary line bilaterally

Escharotomy of Extremities:
-circumferential burn wounds of extremities may lead to permeant, serious neurologic and vascular deficits
-intramuscular compartment pressure: treat if > 30 mmHg
-local anaesthesia unnecessary because 3rd degree eschar is insensate
-incisions along mid-medial or mid-lateral aspect of extremity; should extend to subcutaneous fat
-burn patients are at risk for developing compartment syndrome up to 72 h postinjury frequent
assessment of involved extremity needed

-burn extent, patient age, and depth of burn are primary determinants of mortality

Burn Size:
-Rules of Nines:
-upper extremity: 9% TBSA x 2 = 18%
-lower extremity: 18% TBSA x 2 = 36%
-anterior and posterior trunk: 18% TBSA each = 36%
-head and neck: 9% TBSA = 9%
-perineum 1% TBSA = 1%
TOTAL = 100%

-Hand ~ 2.5% TBSA: dorsal surface 1% TBSA, palmar surface 1%, vertical surface 0.5%
-infants: head almost 20% TBSA

Burn Depth:
-primary determinant of long-term appearance and function
-healing from remaining epithelium lined skin appendages: sweat glands, hair follicles with attached
sebaceous glands

110
-deeper the burn fewer appendages longer burn takes to heal
-burns taking > 3 weeks to heal often produce hypertrophic scars, functional impairment, and thin fragile
epithelial cover
-these burns should be treated surgically
-depth dependent on:
-heat of burn source
-thickness of skin
-duration of contact
-heat-dissipating capability of skin (blood flow)

(1) Superficial (Shallow) Burns:

First Degree Burns:


-involve only epidermis
-erythema d/t dermal vasodilation
-painful
-desquamation at ~ day 4

Superficial Dermal Burns (Second Degree):


-include upper layers of dermis
-blisters with fluid collection at interface of epidermis and dermis
-usually heal spontaneously in 3 weeks if no infection
-usually no scar formation

(2) Deep Burns:

Deep Dermal Burns (Second Degree):


-extend into reticular layers of dermis
-blisters, wound surface mottled pink and white colour; blanche with pressure
-discomfort rather than pain
-will heal in 3-9 weeks if no infection
-will invariably have scar formation; joint function at risk if no physiotherapy

Full-Thickness Burns (Third Degree):


-involve all layers of dermis
-heal only by wound contracture, epithelialization from wound margin, or by skin graft
-white, cherry red, or black +/- deep blisters; do not blanche with pressure
-leathery and firm; insensate

Fourth Degree Burns:


-involve subcutaneous fat and deeper structures

-Systemic Inflammatory Response Syndrome (SIRS) commonly seen in burn patients

$ %*
-hypovolemic shock and tissue trauma formation and release of local and systemic mediators vascular
permeability or in microvascular hydrostatic pressure
-Histamine:
-involved only in the very early increase in permeability
-released by mast cells immediately early after injury increased capillary permeability

111
-increased intravascular junction space in venules
-Serotonin:
-released immediately upon postburn platelet aggregation
-increases pulmonary vascular resistance
-indirectly amplifies vasoconstrictive effects of norepinephrine, histamine, angiotensin II, PG
-Prostaglandins:
-contribute to formation of burn edema
-PGE2 and PGI2 (prostacyclin) arterial dilatation in burn tissue blood flow and hydrostatic
pressure accentuate edema process
-Proteolytic cascades:
-coagulation, fibrinolysis, kinins, complement system
-Bradykinins: increase vascular permeability in the venule

-reduction of CO after burn injury is a result of hypovolemic and cellular shock, increased systemic vascular
resistance due to sympathetic stimulation and hypovolemia
-after successful resuscitation, CO normalizes after 18-24h and increases to supernormal levels during wound-
healing phase

! #+ % !, ! -

Hypermetabolism:
-glucose:
-metabolism elevated
-gluconeogenesis from alanine and glycogenolysis are increased
-plasma insulin levels elevated; hepatic insulin resistance basal rate of glucose production
elevated despite normal or elevated insulin level
-protein:
-excreted primarily as urea progressive depletion of protein stores
-proteolysis increased increased efflux of amino acids (particularly alanine)
-increased gluconeogenesis from amino acids makes them unavailable for reincorporation
of body protein
-wound repair requires amino acid protein synthesis and increased immunologic activity and may
require accelerated protein synthesis
-recommended protein intake: 1-2 g/kg/d
-fatty acids:
-released at rates in excess of requirement of fatty acids and energy substrates
-not oxidized but re-esterified into TG fat accumulation in liver

Neuroendocrine-Mediator Response:
-catecholamines are the major endocrine mediators of hypermetabolic response in thermally injured
patients
-thyroid hormonal serum concentrations not elevated in patients with large burns

Immune Response to Burn Injury

Cytokine Cascade:
-after injury, a number of cytokines are induced rapidly, including TNF, IL-1 and IL-6
-TNF-alpha detectable early in burn shock; maximum level is of prognostic significance
-IL-1 and IL-6 are up regulated in inflammatory sites inducing PMN chemoattraction
-IL-2, a key cytokine in cellular immune response, is significantly suppressed in pts with large burns
-IL-6 induces hepatic synthesis of acute phase response proteins (eg. alpha-glycoprotein, C3, fibronectin)

112
Arachidonic Cascade:
-PGE2: major product after thermal injury
-produced by macrophages
-immunosuppressive effect by:
-inhibition of lymphocyte IL-2 production and T-cell activation
-down-regulation of IL-6
-massive increases in thromboxane B2
-leukotriene B4 is a potent neutrophil chemotactin produced after thermal injury

Cell-Mediated Immunity:
-impaired after burn injury
-functional capacity of T cels to perform their normal physiological response is impaired

Macrophages:
-function impaired after thermal injury
-products suppress mitogenic responsiveness in normal lymphocytes

Neutrophils:
-decreased Fc receptor expression, depressed intracellular killing capacity, and leukocyte chemotaxis
-CD16 (FcR, Fc, IgG receptors) and CD11 (adhesion molecules) on neutrophils is impaired
-baseline granulocyte oxidative activity is increased

Humoral Immunity:
-marked diminution of total serum IgG concentration
-levels return to normal between 10-14 days postburn
-low levels of IgG predictive of poor prognosis
-classical and alternative complement pathways are depleted
-production of GCSF and GM-CSF also impaired

Pathophysiology of Burn Shock:


-resuscitation complicated by obligatory burn edema and voluminous transvascular fluid shifts
-increase in total body capillary permeability
-maximal edema formation b/n 8-12 h postinjury in smaller burns; 12-24 h in major burns
-burns greater than 30% TBSA systemic decrease in cell transmembrane potential, involving non-
thermally injured cells
-d/t increase in intracellular [Na] secondary to decreased Na-ATPase activity
-fluid resuscitation only partially restores membrane potential and intracellular [Na]

Resuscitation from Burn Shock:


-primary goal is to replace fluid sequestered as a result of thermal injury
-massive fluid shifts can occur even though total body water remains unchanged

(1) Crystalloid Resuscitation:


-RL most popular resuscitation fluid
-Parkland Formula:
-4 ml/kg/%burn in first 24 h
-one-half over 8 hours; other half over then next 16 h
-Modified Brooke formula:
-2 ml/kg/%burn in first 24 h

113
(2) Hypertonic Saline:
-results in less edema because of smaller total fluid requirements
-advantages over RL controversial

(3) Colloid Resuscitation:


-Evans Formula:
-1 ml/kg/%burn for colloid and RL over the first 24 h
-Brooke Formula:
-0.5 ml/kg/%burn for colloid; 1.5 ml/kg/%burn for RL
-Slater Formula:
-RL 2L/24 h; FFP 75 ml/kg/24 h
-restoration and maintenance of plasma protein content are not effective until 8 h postburn, when
adequate levels can be maintained with infusion

(4) Dextran

Special Considerations in Burn Shock Resuscitation:

Fluid Resuscitation in the Thermally Injured Pediatric Patient:


-children have limited physiologic reserve require proportionately more fluid for burn shock resuscitation
than adults
-~5.8 ml/kg/%burn
-Cincinnati Shriners Burns Institute:
-4 ml/kg/%burn + 1500 ml/m2 BSA for the first 24 h
-Galveston Shriners Burns Institute:
-5000 ml/m2 %burn + 2000 ml/m2 BSA for the first 24 h

Inhalational Injury:
-increases fluid requirements
-require 5.7 ml/kg/%burn

Rate of Administration:
-volume infused should maintain urine output of 30-50 cc/h in adults and 1 cc/kg/h in children

Fluid Replacement Following Burn Shock Resuscitation:


-burn edema at 24 h postburn is near maximal, and the interstitial space may well by saturated with sodium
-additional fluid requirements depend on type of fluid used during initial resuscitation:
-if hypertonic solutions initially free water will be needed to restore iso-osmolar state
-if colloid was not used protein repletion frequently needed:
Brooke Formula: 0.3-0.5 ml/kg/%burn of 5% albumin during second 24h
Parkland Formula: replace (circulating plasma volume x 20%) with colloid
-maintenance fluids:
Total maintenance fluid = (1500 ml/m2 TBSA) +
evaporative water loss[(25+%burn) x m2 TBSA x 24]

-use 50% normal saline with potassium supplements


-after initial 24-48 h, adult patients with major thermal injuries require a urine output of 1500-2000 ml/24h;
children require 3-4 ml/kg/h

114
)

./0 # + 1 '!
-60-70% of deaths from house fires attributed to CO poisoning
-affinity for haemoglobin 200 times greater than oxygen and interferes with oxygen delivery:
1. prevents reversible displacement of oxygen on haemoglobin
2. shifts oxygen haemoglobin dissociation curve to the left decreasing oxygen unloading from at tissue
level
3. CO inhibits cytochrome oxidase a3 complex less effective cellular respiration
4. CO may bind to cardiac and skeletal muscle, causing direct toxicity
-COHb levels:
-< 10%: no symptoms
-20%: headache, nausea, vomiting, loss of manual dexterity
-30%: weak, confused, lethargic
-40-60%: coma
->60%: death
-half-life of COHb: room air 4-5 h; 100% O2 45-60 mins; HBO at 2 atm 30 min; HBO at 3 atm 15-20 min
-use of hyperbaric oxygen still controversial

.20 $! & # 3# -
-usually limited to upper airway:
-nasopharynx and oropharynx: very effective mechanism for heat exchange d/t relatively large surface area
and associated air turbulence, as well as their mucosa water lining that acts as a reservoir
-sudden exposure to hot air reflex closure of vocal cords reduces potential for lower airway injury
-greatest risk in those injured in an explosion and those who have been unconscious in a fire
-presence of significant intraoral and pharyngeal burns early intubation ETT for 3-5 days

.40 & *! $# #
-hydrogen cyanide: more effective inhibitor of cellular respiration than CO
-inhalation of aldehydes and caustic acids and bases mucosa coagulation and liquefaction necrosis
-direct epithelial damage: loss of bronchial epithelial cilia and decreased alveolar surfactant
-increase in bronchial blood flow with stimulation of alveolar macrophages
-airway edema, sloughing of necrotic epithelial mucosa, impairment of mucociliary clearance of secretions airway
obstruction V/Q mismatch hypoxia
-in the presence of burns, smoke poisoning approximately doubles the mortality from burns of any size

Diagnosis:
-anyone with flame burn and anyone burned in an enclosed space should be assumed to have smoke
poisoning until proved otherwise
-physical examination
-edema, strider, soot impaction smoke inhalation
-wheezing or rhonchi on chest auscultation injury to lower airways
-LOC decreased with hypoxemia, CO poisoning, or cyanide poisoning
-neurological deficits CO poisoning
-carboxyhemoglobin levels, ABG (to get P/F ratio)

Treatment:
(1) Upper Airway:
-in the presence of increasing laryngeal edema, nasotracheal or orotracheal intubation is indicated
-tracheotomy should never be used as an emergency procedure
-treatment of postextubation strider includes administration of racemic epinephrine and Heliox
(2) Lower Airway and Alveolar Damage:
-tracheobronchitis wheezing, coughing, retained secretions

115
-supplemental oxygen immediately
-efficacy of bronchodilators is questionable
-presenting sign of lower airway damage is hypoxemia
-treatment for smoke poisoning is supportive maintain ventilation with PEEP and oxygenation
until lung heals itself
-tracheotomy for those requiring long term ventilation (performed b/n 3 and 30 days after
intubation)
-anterior neck burns require excision and grafting 5-7 days prior to creation of
tracheotomy

./0 # 1% # ' #6
-for deeper burns, the eschar is surgically removed and the wound closed, with grafting techniques and
procedures for immediate placement of flaps tailored to meet patients’ individual needs
-early wound closure shortens hospital stay and duration of illness

.20 ! # 65 ' #!
Evidence Based Conclusions:
1. Small (<20%) full-thickness burns, and burns of indeterminate depth, if treated by an experienced surgeon, can be safely
excised and grafted with a decrease in hospital stay, cost to the patient, and time away from work or school
2. Early excision and grafting dramatically decreases the number of painful debridement required by all patients
3. Patients with burns between 20-40% TBSA will have fewer infectious wound complications if treated with early excision and
grafting
4. In animals with experimental burns, the depressed immune response and hypermetabolism associated with burns can be
ameliorated by early burn wound removal

Clinical Impressions:
1. Scarring is less severe in wounds closed early, leading to better appearance and fewer reconstructive procedures
2. Mortality from wound infection is lower in patients with major burns after early excision
3. Mortality from other complications of major burns may be lower with early excision and grafting

.40 !%$ %# '! #


-Tangential (Sequential) Excision:
-shaving very thin layers of burn eschar sequentially until viable tissue is reached
-if bed does not bleed briskly, another slice of the same depth is taken until a viable bed of dermis
or subcutaneous fat is reached
-Fascial Excision:
-reserved for patients with very deep burns or for patients with very large, life-threatening, full-
thickness burns
-advantages:
-results in reliable bed of known viability
-tourniquets can be routinely used for extremities
-operative blood loss less than sequential excision
-less experience is required to ensure an optimal bed
-disadvantages:
-operative time longer
-may be severe cosmetic deformity
-higher incidence of distal edema
-damage to superficial tendons and nerves
-cutaneous denervation
-skin graft loss from relatively vascular fascia over joints can lead to an ungraftable bed
and require eventual flap coverage

116
-Early Reconstruction:
-skin graft junctures should be avoided over joints, and grafts should be placed transversely when
possible
-thick skin grafts yield a better appearance than thin skin grafts:
-used for face, neck and other cosmetically important areas
-adjacent pieces of skin graft should be approximated carefully
-Donor Sites:
-with early excision the patient was spared the painful daily debridement, and with burn pain
diminished, patients concentrated on donor site pain
-all dressing seem to work, and difference in healing time are only 1 or 2 days
-complications: hypertrophic scarring, changed pigmentation, blistering, infections
-infections treated with systemic antibiotics and continuously moist dressings or silver
sulfadiazine

Cultured Epidermal Autograft


-in vitro culturing of epidermal cells (keratinocytes)
-bacterial contamination and colonization of the grafted bed results in rapid CEA disappearance from the
site
-persistent fragility of CEAs is related to the delayed formation of rete ridges

1. Cultured keratinocytes can be grown within 3 weeks and can be grafted successfully on a viable, non-infected excised burn
wound bed. For a massive burn with few or no available donor sites, this may be life-saving, especially in children
2. Take varies from poor to fair, with an optimistic range of 30-40%
3. Because epidermal cells lack a dermis, in early stages of wound healing, CEAs can provide only a barrier function to prevent
fluid exudation and bacterial invasion
4. The cover is fragile and must be protected from mechanical disruption for months, limiting daily activities and vigorous
physical and occupational therapy
5. CEAs are a temporary measure, permitting survival in the patients with massive burns.

Dermal Substitutes
-bovine collagen matrix with fiber size and distance similar to that of dermis, with a ground substance,
chondroitin 6-sulfate, filling the pores
-provides template on which native fibroblasts, endothelial cells, and macrophages can replace the collagen
with a dermal matrix resembling dermis

./0 # % !8 !& !
-hypermetabolism and hypercatabolism are universal consequences of injury
-magnitude of increase in metabolic rate is directly proportional to the size of burn injury
-requirements estimated from the Harris-Benedict equation
-routine determination of resting energy expenditure (REE) conducted at least twice weekly on burn patients for
proper adjustments of caloric needs
-caloric goal should be calculated at 120-130% of the measure REE

Carbohydrates:
-glucose is the best source of non-protein calories in the burn patient
-peripheral amino acids (alanine, glutamine and other glycogenic amino acids gluconeogenesis) and
wound lactate (glucose production by the Cori cycle) account for approximately one-half to two-thirds of
new glucose produced by the liver
-depletion of body protein during period of starvation leads to energy deficits and malfunctioning of
glucose-dependent energetic processes at the cellular level

117
Protein:
-energy and protein cooperatively contribute to improvement in protein conservation
-amino acid administration promotes synthesis of visceral and muscle protein without affecting the rate of
protein breakdown
-glucose retards whole-body protein breakdown and decreases the total amino acid pool, but exerts little
effect on protein synthesis
-both mechanisms improve nitrogen balance
-glutamine an important energy source for GI tract; broken down to alanine used in gluconeogenesis
-arginine may diminish protein catabolism and has secretagogue activity on pituitary and pancreatic
hormones improves immune function

Fat:
-appears to be a poor calorie source for the maintenance of nitrogen equilibrium and lean body mass in
hypermetabolic patients with large burns
-enthral tube feeding products are largely devoid of omega-3 fatty acids; alpha-linolenic deficiency has
been demonstrated in patients on long-term tube feedings.

.20 ( #& # ' !#


-All vitamins should be supplemented
-ascorbic acid has an essential role in wound repair, and plasma levels are frequently depressed in burn patients
-supplement 250-500 mg of vitamin C daily
-frequent determinations of Na, K, Cl, Ca, Mg, and PO4 are best guides to electrolyte replacement
-Zinc: important cofactor in enzymatic function and wound repair; deficiency documented in burn patients

.40 ! 6 '& #
-seems to influence outcome
-TPN used only when patient’s needs cannot be wholly met by enteral route
-functionally intact alimentary tract always should be used
-safest route for infusion of nutrients is distal to the ligament of Treitz
-advantages of enteral route over TPN:
-maintains integrity of GI tract
-increased hepatic protein synthesis may reduce incidence of bacterial translocation from the gut
-preserves gut mucosa mass and maintains digestive enzyme content
-stimulates trophic hormones, particularly gastrin
-initiate greater insulin release and promotes anabolism
-blunts intensity of hypercatabolic response and more effectively maintains preinjury weight
-prolonged postresuscitation ileus, overuse of narcotics, and constipation are frequently causes of failure of
successful enteral alimentation
-sepsis is associated with ileus and severe glucose intolerance

Composition of Enteral Nutrition:


-specialized feeding regimens improve disease-related metabolic derangements while enhancing nutritional
status
-in burn patients, significant amounts of omega-3 fatty acids should be used

.90 % # # ,, !# !
-burn patients require higher ambient temperatures for comfort because of the apparent change in the hypothalamic
set point of thermal neutrality
-warming burn patients to 38.2oC decreases the metabolic rate and corresponding energy requirements
-warming blankets, and heat lamps may be required
-administration of narcotics reduces metabolic rate associated with pain
-systemic infection requires additional calories to maintain nitrogen balance
-vigorous physical therapy promotes preservation of muscle bulk and must be provided on a daily basis to all
patients requiring prolonged hospitalization

118
-burns cause severe immunosuppression that is directly related to the size of the burn wound

!' % 6 6!%
-extent of burn injury is one of the major demographic predictors of outcome
-presence of inhalation injury correlates highly with infection and mortality
-burns involving less than 10-20% TBSA in otherwise healthy burn patients are almost never associated with life-
threatening infection

%# # 6! #
-diagnosis remains one of infection because many of the cardinal signs of sepsis are also present in uninfected burn
patients
-thrombocytopenia is one of the major manifestations of infection
-a precipitant onset of hyperglycemia, fall in blood pressure, and decrease in urinary output should suggest the
possibility that the patient is becoming unstable
-if associated with hypothermia, leukopenia, and falling platelet count, the patient is probably developing
sepsis

5 ' 6!%
-gram-negative bacteria (Pseudomonas species) is the dominant organism causing fatal wound infections
-pathological feature of burn wound sepsis is invasion of the organisms into viable tissue
spread to perivascular structures capillaritis and vascular occlusion haemorrhagic necrosis
-likelihood of septicaemia increases in proportion to the size of the burn wound

! & #
-respiratory tract most common locus of infection
-diagnosis confirmed by presence of characteristic CXR patterns, and presence of offending organisms and
inflammatory cells in sputum
-damaged lung tissue from inhalational injury can become infected
-antibiotic prophylaxis only selects resistant organisms and does not reduce the incidence of pneumonia

,, # "! $ & + ,$ !+
-major cause of sepsis in burn patients in up to 5% of major burns
-associated with use of IVcatheters

#% ! # ' %# '
-should be suspected in patients with positive blood cultures and no other identifiable source of bacteremia
-systemic antibiotic therapy should be instituted and continued for at least 4 weeks

# #% 6!%
-the majority of patients with positive urine cultures do not require antimicrobial treatment
-candiduria in the absence of signs of systemic infection can be treated with bladder irrigations with amphotericin B

$ ' 6 $! #
-rare complications
-a conservative approach with drainage of the helix centrally, in an attempt to preserve the out cartilages, is usually
successful

!# & ! 6 6!%
-definitive treatment of the septic burn wound is the expeditious excision of the wound

119
Topical Antimicrobial Therapy:
-proved wide-spectrum antimicrobial activity:
-silver nitrate:
-associated with electrolyte imbalances and methemoglobinemia (unusual)
-mafenide acetate:
-able to penetrate eschar; only agent capable of suppressing dense bacterial proliferation
beneath eschar surface
-disadvantage is strong carbonic anhydrase inhibition interferes with renal buffering
mechanisms
-silver sulfadiazine: most common agent used

Silver Nitrate Mafenide Acetate Silver Sulfadiazine


Active Component 0.5% in aqueous solution 11.1% in water miscible base 1.0% in water miscible base

Spectrum of Antimicrobial Gram (-) - good Gram (-) - good Gram (-) - variable
Activity Gram (+) - good Gram (+) - good Gram (+) - good
Yeast - good Yeast - poor Yeast - good

Method of Wound Care Occlusive dressings Exposure Exposure or single-layer


dressings

Advantages -Painless -Penetrates eschar -Painless


-No hypersensitivity reaction -Wound Appearance readily -Wound appearance readily
-No gram-negative resistance monitored monitored when exposure
-Dressings reduce evaporative -Joint motion unrestricted method used
heat loss -No gram-negative resistance -Easily applied
-Greater effectiveness against -Joint motion unrestricted when
yeasts exposure method used
-Greater effectiveness against
yeasts

Disadvantages -Deficits of sodium, potassium, -Painful on partial-thickness -Neutropenia and


calcium, and chloride burns thrombocytopenia
-No eschar penetration -Susceptibility to acidosis as a -Hypersensitivity - infrequent
-Limitation of joint motion by result of carbonic anhydrase -Limited eschar penetration
dressings inhibition
-Methemoglobinemia - rare -Hypersensitivity reactions in
-Argyria - rare 7% of patients
-Staining of environment and
equipment

Subeschar Clysis and Surgical Treatment:


-when burn wound sepsis has developed, the probability of survival is less than 10%
-injection of semi-synthetic penicillins beneath the infected eschar is associated with markedly improved
survival
-generalized wound sepsis in stable patients should be treated by surgical excision

Antibiotics:
-indiscriminate use of multiple agents promotes overgrowth of Candida species, enterococci, and multiple-
antibiotic-resistant organisms in the patient and in the burn center
-infection caused by an identified organism is treated by a single antibiotic
-altered pharmacokinetics of antibiotics in burn patients result in lowered serum drug levels when the usual
recommended dose is used inappropriate peak levels should prompt alterations in the dosage

120
!% %#

Care at the Scene:


-rescuer must avoid touching patient until current can be turned off
-ventricular fibrillation is common
-once ABCs completed, a careful search must be made for associated life-threatening injuries
-intense tetanic muscle contractions associated with electrocution can fracture vertebra or cause major joint
dislocations

Acute and Definitive Care:


-electric current is converted to heat in direct proportion to the amperage of the current and the electrical resistance
of the body parts through which it passes
-smaller the size, the more intense the heat and the less the heat is dissipated: fingers, hands, forearms,
feet, and lower legs are frequently totally destroyed
-massive underlying tissue destruction may be present
-myoglobinuria frequently accompanies severe electrical burns
-cardiac damage may be present; normal cardiac function on admission generally means that subsequent cardiac
dysrhythmia is unlikely
-nervous system is particularly sensitive to electricity
-severe brain damage or spinal cord injury is possible
-delayed transverse myelitis can occur days or weeks after injury
-damage to peripheral nerves common permanent dysfunction
-posttraumatic stress disorders are much more frequent after electrical burns than after thermal burns
-cataracts are a well-recognized complication of electrical contact burns
-frequently bilateral; often occur within a year or two of injury

Wound Management:
-early surgical treatment indicated:
-massive deep tissue necrosis which will not clear up with standard resuscitation techniques, major
debridement and/or amputation may be necessary
-compartment syndrome
-otherwise definitive surgical procedures can be done between days 3 and 5, before bacterial contamination occurs
and after the tissue necrosis is delineated

$!& %#

Emergency Care:
-involved clothing should immediately be removed and the burns thoroughly flushed with copious amounts of water
-will limit severity of the burn
-neutralizing agents may cause burns themselves; they frequently generate heat while neutralizing the offending
agent
-chemical burns cause progressive damage until the chemicals are inactivated by reaction with the tissue, or diluted
by flushing with water
-chemical burns considered deep dermal or full-thickness, until proven otherwise
-phenol: can have severe systemic effects
-hydrofluoric acid: may cause death from hypocalcemia

121
)

# # !& ! 6

Treatment at the Scene of the Accident:


-place in tepid water rather than ice water
-wrap in clean cloth and victim taken to an emergency facility
-chemical burns irrigated with copious amounts of water

Initial Medical Management:


-determine if there is any possibility of smoke inhalation injury
-tetanus prophylaxis given
-cleanse wound with bland soap and water
-shave hair in areas of and adjacent to burns
-removal of tar and asphalt Medisol (citrus and petroleum distillate)
-chemical burns irrigated with water for 20 mins; neutralizing agent should not be applied
-blisters (options):
-left intact and underlying wound allowed to heal
-fluid evacuated and overlying skin allowed to cover underlying wound
-debridement

Follow-up Wound Care:


-problems of immunosuppression, hypermetabolism, and increased susceptibility to infection are not associated with
minor burns
-keep wound clean and in a moist environment
-systemic antibiotics rarely indicated; may predispose wound to later opportunistic infection
-follow-up care (do twice daily):
1. washing wound with bland soap and water
2. patting wound dry with a clean towel
3. applying a bland ointment
-vigorous program of ROM exercise: prolonged edema retards wound healing and is minimized with physical
therapy
-usually wound will totally epithelialize in 2-3 weeks
-wounds not healing within 14 days, then primary excision and grafting should be performed
-examine superficial partial-thickness wounds at 6 weeks for hypertrophic scarring
-use compression dressings if hypertrophic; worn ~12-18 months
-avoid sun exposure until wound is completely healed hyperpigmentation may occur; sun block recommended

Alternative Methods of Wound Management:


-Biobrane and OpSite: prosthetic skin substitutes in the treatment of partial-thickness outpatient burns

Management of Critical Areas:

Face: -should be left exposed; washed regularly

Ears: -treated with bland ointment

Eyes: -confirm corneal burns with fluorescein


-treat similarly to corneal abrasions

Hands: -elevate hand for 24-48h to minimize swelling


-circumferential burns may require hospitalization for observation
-ROM as soon as possible

122
Feet: -ROM important
-elevate feet when not walking

Perineum:
-require hospitalization for 24-48h for observation of urinary obstruction secondary to edema

Complications:
-most complications in small burn injuries result from overtreatment:
-too-vigorous dressing changes that pull off newly formed epithelium, or the use of a variety of topical and
systemic antibiotics that can cause secondary infection or formation of a pseudomembrane

# # !& ! 6 '! # ! #-

Medical Criteria for Outpatient Management:


1. No existing complications of thermal injury, such as inhalation injury
2. Fluid resuscitation completed
3. Stabilized hospital course
4. Adequate nutritional intake
5. Adequate pain tolerance
6. No anticipated septic complications

Outpatient Treatment Program:


-two phases of treatment:
-home-treatment:
-wash wound twice daily etc..
-exercise every hour
-physical therapy:
-hydrotherapy, debridement of burn wounds, and a supervised exercise regimen
-treatment reviewed and modified if necessary

-pharmacological modalities:
-hypnotics and analgesics: morphine, methadone, codeine, acetaminophen, NSAIDs
-anesthetic agents: ketamine, fentanyl
-antianxiety drugs, major tranquillizers and antidepressants
-non-pharmacological modalities:
-verbal and/or physical comfort
-relaxation therapy

!$#+ #

Inpatient Therapy:
-maintaining function and preventing the complications of prolonged immobility are the specific goals of the
rehabilitative treatment of burn patients
-position of maximal comfort promotes the formation of scar contractures
-edema is reduced by compression and elevation
-active and passive exercises implemented
-scar hypertrophy can be retarded by the use of custom-fitted pressure garments over healed scars

123
Outpatient Therapy:
-continuous follow-up of persisting functional deficits
-evaluation for corrective surgical procedures
-modification and evaluation of rehabilitation therapy

Psychological Support:
-anxiety, depression, denial, withdrawal, regression
-post-traumatic stress disorder:
-in nearly half of older children and adults suffering burn injury
-recurrent intrusive recollections, avoidance of circumstances that invoke memories of event, loss of
interest in daily activities, feelings of isolation, hyperalertness/vigilance, memory impairment, sleep
disturbances
-psychosocial support is critical for the burn patients for the duration of the course of treatment and follow-up

$ % + !&

Hypertrophic Scar and Keloid Formation:


-hypertrophy typically develops in deeper partial-thickness injuries and third-degree burns allowed to heal by
primary intention
-keloids overgrows the original dimensions of the initial injury and hypertrophic scar develops in the bed of the
injured tissue and is confined to its original anatomic boundaries
-hypertrophic scars flatten with time; keloids do not
-other forms of therapy for hypertrophic scarring: radiotherapy, cryotherapy, and reexcision and wound closure
-most successful approach is initial pressure therapy until wound matures, followed by subsequent excision
and application of skin grafts
-for keloids, excision alone has a recurrence rat > 50%
-intralesional injection of corticosteroids may reduce the bulk of keloid and hypertrophic scar mass
-acts by decreasing collagen synthesis and increasing collagen degradation through the collagen
inhibitors a2-macroglobulin and a1-antitrypsin
-major side effects are hypopigmentaion and atrophy of the skin surrounding the keloid

Marjolin’s Ulcer:
-chronic ulceration leading to malignant degeneration
-squamous cell carcinoma is most common
-rare tumours: malignant fibrous histiocytoma, sarcoma, neurotropic malignant melanoma
-chronic breakdown of a healed burn wound scar should lead to suspicion of malignant degeneration
-~30% of burn scar carcinomas occur in the head and neck
-adjuvant radiotherapy improves survival

Heterotopic Ossification:
-occurs in up to 13% of burn patients; ossification of soft tissue
-most commonly involves patients with full-thickness burns greater than 20% TBSA, and is found adjacent to the
involved joint 1-3 months after injury
-elbow most commonly affected joint
-limited physical activity precedes radiographic evidence of calcification

Fractures:
-up to 10% of burn patients have associated fractures
-treated with splints and traction until resuscitation complete

124
!" # !
-acute: “normally proceed through an orderly and timely reparative process that results in sustained restoration of
anatomic and functional integrity”
-chronic: “wounds that have failed the above”

$% !
Primary Closure:
-approximates the acutely disrupted tissue with sutures, staples, or tape
Delayed Primary Closure:
-approximation of wound margins is delayed for several days after the wound has been created
-prevents infection in wounds in which there is significant bacterial contamination, foreign bodies,
or extensive tissue trauma
-during the time the wound is open, events occur that will significantly decrease the chances of
wound infection after closure
Secondary Wound Closure:
-margins of the open wound move together by the biologic process of contraction

& "' ( ) )
Epithelialization:
-keratinocytes migrate and then divide to resurface partial-thickness loss of skin or mucosa
Contraction:
-spontaneous closure of full-thickness skin wounds or constriction of tubular organs after injury
Connective tissue matrix deposition:
-fibroblasts are recruited and produce a new connective tissue matrix

' !

*+, #
-damaged vessels and lymphatic trigger a cascade of events:
-vasoconstriction; mast cell release of vasoactive compounds: bradykinin, serotonin, histamine;
diapedesis of cells into wound; hemostatic clot of platelets
-platelets release clotting factors to produce fibrin; also produce several essential cytokines which modulate
the subsequent wound healing events

*-, ! (( #
-migration of leukocytes into the wound
-24h: predominantly PMNs, then by macrophages

*., / %
-fibrous protein collagen is synthesized
-cross-linking of collagen provides strength and integrity
-increased synthesis within 10h of injury
-synthesis peaks after 5-7 days and then declines gradually

(4) Remodelling
-acute and chronic inflammatory cells diminish gradually, angiogenesis ceases, and fibroplasias ends
-equilibrium between collagen synthesis and collagen degradation is gradually restored

125
$# 0
Cytokine Source Functions
Platelet Derived Growth Platelets, macrophages, -chemotactic for PMNs, macrophages, fibroblasts, and SMCs
Factor (PDGF) including endothelial cells, keratinocytes, -activates PMNs, macrophages, and fibroblasts
isoforms AA, AB, and BB smooth muscle cells -mitogenic for fibroblasts, endothelial cells, and SMCs
-stimulates production of MMPs, fibronectin, and HA
-stmulates angiogenesis and wound contration
-remodelling
-inhibits platelet aggregation
-regulates integrin expression

Transforming Growth Platelets, T lymphocytes, -chemotactic for PMNs, macrophages, lymphocytes, fibroblasts, and SMC
Factor Beta (TGF-B) macrophages, endothelial cells, -stimulates TIMP synthesis, keratinocyte migration, angiogenesis, and
including isoforms b1, b2, keratinocytes, SMCs, fibroblasts fibroplasias
b3 -inhibits production of MMPs and keratinocyte proliferation
-regulates integrin expression and other cytokines
-induces TGF-B production

Epidermal Growth Factor Platelets, macrophages, saliva, -mitogenic for keratinocytes and fibroblasts
(EGF) urine, milk, plasma -stimulates keratinocyte migration and granulation tissue formation

Transforming Growth Macrophages, T lymphocytes, -similar to EGF


Factor Alpha (TGF-A) keratinocytes, and many tissues

Fibroblast growth factor-1 Macrophages, mast cells, T -chemotactic for fibroblasts


and -2 family (FGF) lymphocytes, endothelial cells, -mitogenic for fibroblasts and keratinocytes
fibroblasts, and many tissues -stimulates keratinocyte migration, angiogenesis, wound contraction and
matrix deposition

Keratinocyte growth factor Fibroblasts -stimulates keratinocyte migration, proliferation, and differentiation
(KGF; aka FGF-7)

Insulin-like Growth Liver, macrophages, -stimulates synthesis of sulfated proteoglycans, collagen, keratinocyte
Factor-1 (IGF-1) fibroblasts,a nd others migration, and fibroblast proliferation
-endocrine effects similar to growth hormone

Connective tissue growth Endothelial cells, fibroblasts -chemotactic and mitogenic for various connective tissue cells
factor (CTGF)

Vascular endothelial cell Keratinocytes -increases vasopermeability


growth factor (VEGF) -mitogenic for endothelial cells

Tumour Necrosis Factor Macrophages, mast cells, T -activates macrophages


(TNF) lymphocytes -mitogenic for fibroblasts
-stimulates angiogenesis
-regulates other cytokines

Interleukins (IL-1 etc..) Macrophages, mast cells, -chemotactic for PMNs (IL-1) and fibroblasts (IL-4)
keratinocytes, lymphocytes, and -stimulates MMP-1 synthesis (IL-1)
many tissues -angiogenesis (IL-8)
-TIMP synthesis (IL-6)
-regulates other cytokines

Interferons (IFN-a etc) Lymphocytes and fibroblasts -activates macrophages


-inhibits fibroblast proliferation and synthesis of MMPs
-regulates other cytokines

-“wound hormones” that can be endocrine, paracrine, autocrine, intracrine


-functions of cytokines:
-regulate cell proliferation:
-competence factors: get cell into G1 phase (eg. PDGF)
-progression factors: promote the cell through the proliferation cycle (eg. IGF-1)
-chemotaxis
-direct production of specific components needed for matrix repair

126
PDGF: platelet derived growth factor
-initiates many wound healing events and stimulates production of several other cytokines
-chemotaxis for fibroblasts, neutrophils, macrophages, SMC
-stimulates production of fibronectin and hyaluronic acid
-may stimulate wound contraction

TGF-beta: transforming growth factor


-increases collagen synthesis by specifically enhancing matrix gene expression and by inhibiting
collagenase production and activity
-isoforms:
TGF-B1: most abundant
TGF-B2: found in amniotic fluid, saliva, breast mild, aqueous and vitreous humour of eye
TGF-B3: least studied

FGF: basic fibroblast growth factor (bFGF):


-potent angiogenic factor
-causes increased epithelial cell migration
-hastens wound contraction

EGF: epithelial growth factor


-stimulates epithelial migration and mitosis

1# " & # 1& # / (

-collagen is the major component of the extracellular matrix of all soft tissues, tendons, ligaments, and bone
-matrix also contains glycosaminoglycancs, proteoglycans, fibronectin, laminin, elastin

Synthesis:
-transcription mRNA translation on RER proline hydroxylation glycosylation (galactose/glucose)
procollagen (soluble) secretion into extracellular matrix cross-linking (lysyl oxidase) and cleavage of
amino and carboxyl terminals (procollagen peptidase) collagen (insoluble)
-three polypeptide chains: glycine-proline-X
-hydroxyproline important for collagen stability; ascorbic acid and oxygen required for
hydroxylation process

Degradation:
-breakdown mediated by matrix metalloproteinases (MMPs)
-MMPs synthesized by variety of cells: inflammatory cells, fibroblasts, epithelial cells
-MMP-1, 8, and 13: initiate degradation of collagen by splitting molecule into specific 3/4 and 1/4
fragments (TCA and TCB fragments)
-after this initial split, other nonspecific proteases further degrade collagen
-MMPs are zymogens which are activated by other proteases such as plasmin
-MMPs inhibited by alpha-2-macroglobulins and tissue inhibitors of metalloproteinases (TIMPs)
Ground Substance:
-proteoglycans and glycosaminoglycans
-molecular “shock absorbers”, provide for moisture storage, and also sequester cytokines

# "#

Mechanism:
-myofibroblasts: peak during and after the process of wound contraction
-extracellular matrix also important in contraction process

127
-precise mechanism of contraction not fully understood

Clinical Approaches:
-for scar revision, must assess maturity of scar:
-mature scar: soft and pliable
-skin graft may be used to correct contracture
-FTSG contracts much less than STSG
-splinting of wound required
-immature scar: stiff, indurated, hypertrophic, tender
-still contains inflammatory cell components and myofibroblasts that contribute to
contracture
-use musculocutaneous flap to fix defect or wait until scar matures

% #' 2#

-epidermis provides barrier protection from external environment


-collagen rich dermis provides all the strength attributed to skin
-basement membrane provides structural support for the epidermis and attaches it to dermis

Mechanism:
-healing by migration and mitosis
-epithelial destruction scab for dermal protection
-migration of cells from margins of wound and from hair follicles and sebaceous glands
-cells flatten out and send cytoplasmic projections into surrounding tissue
-epithelial cells, secrete proteases and migrate as a sheet of cells
-fibronectin and vitronectin support migration
-move by actin-myosin contractile system
-mitosis begins when there are not enough cells for further migration
-factors involved:
-bFGF, PDFG, TGF-a and EGF stimulate keratinocyte migration and mitosis
-TGF-B inhibits epidermal cell proliferation but stimulates motility

##

-nutrition important for collagen synthesis and immune response


-Ascorbic acid:
-essential; lack is most common cause of wound healing deficiency
-deficiency = scurvy
-co-factor in hydroxylation of proline; essential for addition of molecular oxygen
-60 mg/day RDI; up to 1 g/day recommended in trauma patients
-iron: required for prolyl hydroxylation
-calcium and magnesium: required for collagenase activity and protein synthesis in general
-oxygen: required for hydroxylation and energy needed for bacterial killing and cell viability

(( %%

-only a small number of immunosuppressed patients actually manifest clinical wound healing problems
-chemotherapeutic anticancer drugs inhibit healing
-malignancies deplete nutrients and also inhibit wound healing directly

128
#" ! "#) & #/ (

(1) Osteogenesis Imperfecta


-mutation in genes for Type I collagen
-four types: mild to lethal
-brittle bones, dermal thinning, increased bruisability
-normal scarring and skin extensibility

(2) Ehlers-Danlos Syndrome


-joint laxity, skin hyperextensibility and fragility, poor wound healing, vascular rupture
-ten types each with different enzyme or biochemical defects
-patients at risk for surgical vascular complications

(3) Marfan’s Syndrome


-tall stature, arachnodactyly, lax ligaments, myopia, scoliosis, pectus excavatum
-dissecting aneurysm of the root and ascending portions of the aorta
-defects in collagen structure; abnormal fibrillin in elastin

(4) Epidermolysis Bulla


-blistering and ulcerations
-excessive production of MMPs by fibroblasts; abnormal matrix adhesion to epidermis and associated
basement membranes
-complications: stenosis and strictures in GI tract surgery
-phenytoin decreases collagenase activity in fibroblasts; has been used to treat patients with recessive
dystrophic epidermolysis bulla

"# #' # !! "#

Factors that Affect Healing in Surgical Practice Factors that Contribute to Wound Infection
Local Factors General Factors Surgeon
Surgical technique
Blood supply Age Devitalized tissue
Denervation Anemia Impaired local circulation
Hematoma Anti-inflammatory drugs Hematoma
Infection (local) Cytotoxic drugs Foreign body
Mechanical stress Hormones Organism
Protection (eg. Dressings) Infection (systemic) Infective nature
Surgical technique Jaundice Source: (a) Endogenous, eg. skin, biliary, colorectal
Suture material and technique Malignant disease (b) Exogenous (cross-infection)
Type of tissue Malnutrition Patient
Obesity Disease: eg. DM, neoplasia, malnutrition, anemia,
Temperature chronic granulomatous disease
Trauma, hypovolemia, hypoxia Medications: eg. steroids, cytotoxics, intensive antibiotic
Uremia therapy, radiotherapy
Vitamin deficiency Immune response of individual
Trace metal deficiency Remote active infection

3 &

# # # "#

Anatomy:
-inner mucosa layer for absorption

129
-outer muscularis mucosa layer for motility
-both wrapped by serosa layer

Layers:
-Epithelium: one-cell thick; regenerates q8days
-Laminia propria: collagen types I, III, and V and elastin
-Muscularis mucosa
-Submucosa
-Muscularis propria: densely packed SMC with types I and III collagen
-Serosa

Injury and Repair:


-quality of healing determined by depth of injury and chronicity of injury
-inflammation and erosion healing w/o scar
-no mesenchymal cell response if injury confined to mucosa
-penetration of submucosa mesenchymal cell repair response: SMC migration and collagen production
-if acute ulcer normal architecture of intestine eventually restored
-if chronic ulcer stricture and obstruction can ensue as scar accumulates
-Crohn’s Disease:
-inflammation of submucosa to serosa
-increased collagen Type I and Type V
-therefore causes symptoms of intestinal obstruction
-Ulcerative Colitis:
-inflammation limited to mucosa
-thinning of matrix perforation rather than stricture
-Radiation Injury:
-extensive and progressive submucosa, muscularis, and serosa fibrosis
-Lye ingestion:
-mucosa penetrated fibrosis and stricture occur

Keloids and Hypertrophic Scars:


-Hypertrophic Scars:
-remain within boundaries of original wound
-almost always regress over a period of time
-Keloids:
-extend beyond the boundaries of the original wound
-usually do not regress
-usually recur after excision unless additional therapy provided
-overabundant collagen deposition and decreased degradation:
-increased mRNA for Type I collagen; keloids may contain increased TGF-B
-keloid tissue contains more soluble collagen and greater water content
-collagenase inhibitor a2-macroglobulin abundant in keloids and hypertrophic scars
-current treatments not consistently effective
-surgical excision
-intralesional injection of triamcinolone 40 mg/ml, no more than 2 ml q6-8weeks to avoid
systemic side effects
-adverse effects: local atrophy, depigmentation, telangiectasia
-keloids have increased histamine containing mast cells itching: oral antihistamine for relief

Factitious Wounds:
-self-mutilation

130
Marjolin’s Ulcer:
-nonhealing wound in an area of previous trauma may represent squamous cell carcinoma
-normal immunologic surveillance decreased because of dense scar unable to destroy malignant
transformation within scar

-type I collagen with significant amount of proteoglycan


-meticulous technique and early mobilization required for repair of flexor tendons in fibrous flexor sheaths
-preservation of vincula (which supplies blood to the tendon) needed to prevent ischemic and scarring
-early motion provides stress forces to lengthen and remodel scar; enhances lubrication from synovial fluid

3
-injury haematoma formation, edema, and pain
-migration of cells into and neovascularization into fracture site
-formation of soft callus: fibrocartilaginous splint of granulation tissue and cartilage
-endochondral ossification over 6-8 weeks by osteoblasts from periosteum and medullary canal
-remodelling over years
-rigid internal fixation: no soft callus formation direct bone to bone healing across injury without endochondral
ossification
-delayed union of nonunion (factors):
-site of fracture, presence and degree of soft-tissue injury, bone loss, inadequate reduction, inadequate
immobilization, infection, previous radiation, malignant growth at the fracture site, poor blood supply to
the fracture
-bone grafts:
-Osteogenesis: formation of new bone by cells that survive in the graft
-Osteoconduction: blood vessels and cells from the surrounding tissue grow into the bone graft scaffold
-osteoinduction: transformation of local, undifferentiated cells into bone-forming cells

#
-has little propensity to heal
-deep injury to articular cartilage that goes into subchondral bone produces exuberant inflammatory and healing
response fibrocartilage intermediate hyaline cartilage formed over time

' "

Pathophysiology:
-arise form physical and biochemical insults of extended duration
-prolonged inflammatory stage of wound repair extensive tissue damage and impaired healing by PMNs
-products released by PMNs continue to degrade extracellular matrix and prevent or impair the migration
of other reparative cells in to the wound

Venous Stasis Ulcers:


-result of deep venous obstruction or valvular incompetence
-typically occur superior to or near the medial malleolus
-tend to be large and irregularly shaped
-perivascular “fibrin cuffs”

Pressure Ulcers:
-pressure and hear forces over bony prominences cell death in least vascularized tissues
-can be complicated with osteomyelitis
-Marjolin’s ulcers rarely occur in these chronic ulcers

131
-spinal cord injury patients at risk: do not have normal leukocyte response to injury below level of
enervation
-fecal and urinary incontinence maceration and skin breakdown
-antibiotics should not be used to treat these wounds unless they are causing systemic toxicity

Classification:
Stage I: Non blanchable erythema of intact skin, the heralding lesion of skin ulceration
Stage II: Partial-thickness skin loss involving epidermis and/or dermis
Stage III: Full-thickness skin loss involving damage or necrosis of subcutaneous tissue that may extend
down to, but not through, underlying fascia
Stage IV: Full-thickness skin loss with extensive destruction, tissue necrosis, or damage to muscle,
bone, or supporting strictions (eg. tendon, joint capsules, etc..)

Diabetic Ulcers:
-typically present as foot ulcers
-neuropathy is most important causative element
-tissue trauma and pressure are promoting factors
-lack of sensation results in increased mechanical stress, prevents timely detection of skin
punctures, or improper shoes, or the detection of foreign bodies in shoes
-angiopathy: capillaries are thicker and more permeable

Mechanisms Involved in the Healing of Chronic Ulcers:


-pressure and diabetic ulcers heal mainly by contraction
-venous ulcers heal mainly by epithelialization

Chronic Wound Care:


-most wounds regardless of cause will heal by secondary intention only if the underlying cause is corrected
-tissue perfusion and cellular oxygenation are important factors for chronic wound repair
-no evidence however that hyperbaric oxygen can improve the healing (with the exception of
osteoradionecrosis)
-debridement to remove damaged and necrotic tissue often helps to accelerate healing
-disinfectants should be avoided since they may injure normal tissue

Factors that Influence Healing of Chronic Wounds


Pressure Smoking
Ischemia Cancer
Age Radiation
Nutrition Distant malignancy
Perfusion Chemotherapy
Metabolism (diabetes) Hereditary healing disorders
Infection Glucocorticoid steroid treatment

-partial-thickness wounds require semiocclusive dressings to provide moist environment for epithelialization
-combining an absorbent dressing material with the polyurethane film or hydrocolloid alleviates the
problem of excess wound fluid
-occlusive/semiocclusive dressings may exacerbate infection when covering areas in which the bacterial count is
higher than 100,000/g of tissue.
-dressings are used to deride:
-exposed tendon: slower more gentle process needed use hydrogens to keep wound moist
-eschar use hydrocolloid; debridement through autolysis

132
&
-tissue reactivity to particular sutures and its significance in the healing process has never been validated
-woven suture material should not be used in the closure of contaminated wounds
-more likely to facilitate infection than a smooth suture
-staples must be removed within a few days if permanent skin marks are to be avoided
-tape strips may be used to substitute dermal sutures as long as wound edges are well approximated

-fetal wound repair is characterized by a significantly reduced inflammatory response


-fetal platelets have different aggregative characteristics and reduced cytosine release
-instead of collagen, the major component of the wound matrix is hyaluronic acid
-amniotic fluid may inhibit fetal wound contraction, but the mechanisms and component(s) remain unclear

133
-orthotopic transplantation: graft placed into its normal anatomic location (eg. heart transplant)
-heterotopic transplantation: graft placed in a different site (eg. kidney transplant)
-syngeneic: transplantation b/n individuals of identical genetic strain
-allogeneic: transplantation b/n genetically different members of same species
-xenogeneic: transplantation b/n different species
-autotransplant: one site to different site within same individual

! "#
-epitope: molecular unit of specific immune recognition (carbohydrate/peptide moiety)
-antigen: epitope containing molecules that can be bound by T-cell receptors or antibodies of B-cells
-may contain several epitopes
-major histocompatibility complex (MHC):
-cluster of genes on chromosome 6
-known as human leukocyte antigen (HLA)
-polymorphic gene: differ in detail while conforming to the same basic structure

$ $ % &!!' #

-innate vs. acquired immunity:


-innate: non-specific
-acquired: specific recognition; based on antigen receptors
-immunological memory
-mediated by lymphocytes, T cells (cellular immunity) , and B cells (humoral immunity)

Cellular Immunity:
-TCR recognizes processed peptide antigens bound to MHC molecules
-parenchymal cells express class I MHC molecules
-display peptides from within (eg. viral replication)
-bind to T-cells /w CD8 molecule
-hematopoeitic cells express class II MHC molecules
-display peptides that have been phagocytized from surrounding extracellular spaces
-bind to T-cells /w CD4 molecules
-CD4+ T-cells are first alerted of an invasion of the body by antigen presenting cells (APCs) and activate CD8+ T-
cells to search the body for cells that have been infected by this invader

Humoral Immunity:
-B cells bind soluble antigens and secrete soluble forms (Abs) to bind these foreign molecules
-material bound by Ab is opsonized for destruction by cells of the innate system of immunity
-ie. macrophages, monocytes, PMNs
-activate complement system membrane destroyer

-Cytokines amplify response of one cell to one antigen


-prototypical cytokine of T-cell activation is IL-2

134
( ) '( ' * ( ( & "
-antigens responsible for human allografts rejection are encoded by HLA region of chromosome 6
-class I molecules (HLA-A, B, and C)
-class II molecules (HLA-DR, DP, and DQ)
-other genes encoded by HLA:
-TNF-alpha and beta
-components of complement cascade (class III molecules)
-heat-shock protein (HSP-70)
-peptide transporter proteins TAP 1 and TAP 2; proteosome proteases LMP 2 and LMP 7
-other polymorphic transplant antigens: ABO blood group

-Class I molecule:
-single polymorphic gene + nonpolymorphic protein B2-migcroglobulin (from chr 15)
-30-50 alleles per locus
-structure:
-expressed as single MHC-encoded, transmembrane alpha chain (/w 3 domains alpha 1, 2 and 3),
in combination /w B2M
-binding via groove made by alpha 1 and alpha 2 domains
-binds peptides synthesized in the endoplasmic reticulum
-found on all nucleated cells except neurons
-Class II molecule:
-two chains: alpha and beta
-differ by alleles represented at each locus and in number of loci present in HLA class II region
-structure:
-formed by two MHC-encoded chains (alpha and beta) each /w two domains
-binding site via alpha 1 and beta 1 domains
-binds peptides derived from endocytosed proteins
-found primarily on cells of the innate immune system (phagocytes, macrophages, monocytes)
-can be upregulated to appear on other parenchyma cells by cytokines

-inheritance of HLA genes follows simple Mendelian genetics:


-25% offspring HLA identical
-50% haploidentical
-25% nonidentical

+ "# & "

-physiologic role of MHC molecules:


-provide mechanism for T-cell inspection of parenchyma cells (class I)
-provide interface between innate immune cells and T-cells (class II)
-in transplant, T-cell responses to either class can generate a rejection episode
-T-cells can recognize foreign MHC molecules and activate
-CD8+ T-cells:
-if self-peptides are presented to T-cells, then no activation occurs
-alterations in peptide content (eg. viral replication), causes activation immune response
-enhanced cytotoxic capabilities for infected cell destruction
-CD4+ T-cells:
-can activate CD8+ T-cells and Ab-producing B-cells
-release of cytokines to recruit CD8+ T-cells
-B cells are stimulated to release Ab
-release of INF-gamma induces expression of class II molecules on local cells and increase expression of
class I molecules locally

135
-matching donors and recipients /w regard to HLA type has been shown to improve outcome after kidney, heart, and
pancreas transplantation
-no such correlation for liver transplantation
-matching may reduce overall survival:
-HLA compatibility potentiates the inflammation during viral reinfection after
transplantation for viral hepatitis and increases the chances for clinical recurrence of the
original disease

( & & "


-historically MHC polymorphism defined by:
-lymphocytotoxicity assay and MLC
-both assays only define MHC epitopes but not the entire molecule
-lymphocytotoxicity assay:
-donor serum /w anti-MHC Ab of known specificity; mix /w recipients lymphocytes
-if Ab binds to MHC activates complement (rabbit) recipients lymphocytes stained /w blue dye
-MLC assay:
-incubate recipient T-cells /w irradiated donor T-cells in presence of 3H-thymidine
-recipient cells proliferate if they differ from donor cells increased radionuclide uptake
-prospective typing assay limited to living-related donors
-other methods:
-restriction fragment length polymorphism (RFLP)
-oligonucleiotide hybridization
-polymorphism-specific amplification (PCR-SSP): most commonly used for class II typing
-sequence polymorphism that do not alter the TCR:MHC interface are unlikely to affect allografts survival;
enhanced precision of molecular typing may provide more information than is clinically relevant

( ) '( ' * ( ( & " (

T-Cell Receptor:
-T-cells formed in fetal liver and bone marrow
-migrate to thymus during 1st trimester
-at thymus, a series of DNA rearrangement and recombination occurs (V, J, D and C regions)
-individual cells recombine to express a single TCR /w a single specificity
-results in population of T-cells capable of binding 109 different specificities: essentially all
combinations of MHC and peptide
-now also able to express CD4 and CD8
-after recombination, thymic selection occurs to avoid “self-destruction”
-cells initially interact /w MHC-expressing cortical thymic epithelium
-first positive selection occurs: if no binding cells are useless (unable to function in
periphery) apoptosis occurs
-then negative selection: surviving cells move to thymic medulla
-lose either CD4 or CD8
-if binding to self-MHC occurs apoptosis results
-only cells released into periphery are those that can bind self MHC /wout activation

Antibody:
-maturation occurs in the bone marrow
-two light-chain loci (kappa and lambda) each /w V, D, J, and C regions
-types: IgM, IgG, IgA, IgE, or IgD; defined by heavy chain usage
-Fc portion: binds cells of the innate system

136
-in IgM and certain classes of IgG can activate complement
-isotype switching: alteration of heavy-chain gene usage from IgM to either:
-IgG: significant soluble mediator of opsonization
-IgA: mucosa immune responses
-IgE: mast-cell mediated immunity
-IgD: primary cell-bound Ab
-affinity maturation:
-D and J regions undergo random additions resulting in clones that have altered antigen affinity
-those /w increased affinity are retained for future encounters; will have a more vigorous response

+ "# & " ( " ) '(

T-Cell Activation:
-initial binding to APC or endothelial cell is non-specific and mediated by adhesion molecules (eg. ICAM-
1, VCAM-1, LFA-1)
-MHC recognition:
-single interaction of TCR /w an MHC is not sufficient for activation
-~8000 TCR ligand interactions /w same antigen must be reached
-initiation of a series of intracytoplasmic protein tyrosine kinases (PTK)
activation of phosphokinase C-gamma hydrolysis of PIP2 IP3 + DAG
-IP3 binds to ER release of Ca++ induces calmodulin to bind to and activate
calcineurin initiate transcription of IL2
-IL2 autocrine activation of T-cell potentiates DAG activation of protein
kinase C (PKC) gene regulatory steps in cell cycle
-also requires second confirmatory signal by binding CD28 (on T-cell) /w B7 molecules (on
APC) potentiates the TCR-initiated tyrosine phosphorylation
-reduces the number of binding events of TCR-MHC from 8000 to 1500

T-Cell Amplification:
-cytokines (particularly IL-2 and IFN-gamma) recruit other T-cells
-T-cells develop one of two phenotypes:
-Th1 cells:
-mediate cytotoxic responses (eg. delayed-type hypersensitivity)
-express IL-2, -12, -15, and IFN-gamma
-Th2 cells:
-support the development of humoral or eosinophilic responses
-express IL-4, -5, -10, and -13
-immunosuppression produces artificial patterns of gene expression, resulting in nonphysiologic patterns of
cytokine secretion

-in the late phases of rejection, the inflammatory response recruits cells /w nonspecific cytotoxic activity to
the organ
-IL-8, released by activated macrophages and T cells, also recruits PMNs to the scene to remove necrotic
tissue

T-Cell-Mediated Cytotoxicity:
-amplification generally performed by CD4+ T-cells: best suited to interact /w class II expressing APCs
-cytotoxicity best mediated by CD8+ T-cells
-in the artificial situation of transplantation, both CD4+ and CD8+ mediate cytotoxicity
-Ca++ mediated exocytosis of cytolytic granules: contain perforin and serine proteases called
granzymes
-T-cells can also induce apoptosis
-after activation, non-MHC-restricted, T-cell-mediated cytotoxicity occurs other T-cells /wout the
specific TCR can participate in cytotoxicity

137
-T-cells expressing the gamma-delta TCR are prominent effector of non-MHC-restricted cytotoxicity
-this is induced by high levels of IL-2

B-Cell Activation and Clonal Expansion:


-surface Ab cross-linking by antigen leads to B-cell proliferation and differentiation into a plasma cell
-B-cells can also internalize antigens bound to surface Ab and process them for presentation to T-cells
-can bind antigen in circulation and initiate a T-cell response
-Plasma cells hypertrophied Golgi apparatus
-secrete large amounts of monoclonal Abs
-antigen exposure generally leads to B-cell affinity maturation and isotope switching, and produces high-
affinity IgG Ab

Antibody-Mediated Cytotoxicity:
-Ab serves as anchoring site for complement C1q:
-Classical Complement Activation Cascade:
-two Fc bind C1q and activate it C3 activation formation of membrane attack
complex (MAC) of polymerized C5, 6, 7, 8, and 9
-results in disruption of cell membrane and cell lysis
-several byproducts of C3 cleavage serve as chemoattractant to phagocytic cells and as
opsonins potentiating antigen phagocytosis
-Ab can act as opsonin
-phagocytic cells have receptors for Fc portion of IgG Ab-dependent cellular cytotoxicity
-Ab binding to endothelium complement activation on endothelial cell cellular retraction and exposure
of underlying matrix potentiates platelet activation and aggregation
microvascular thrombosis, a hallmark of the tow Ab-mediated graft rejections: hyperacute
rejection and acute vascular rejection

( ,( # ) !

Hyperacute Rejection (HAR):


-caused by presensitization of recipient to antigen expressed by donor
-develops minutes to hours following graft reperfusion
-initiates complement-mediated lysis and induces immediate graft thrombosis
-exposure usually d/t prior transplant, transfusion, or pregnancy
-no treatment, but can be prevented by preoperative screening (prevents HAR in 99.5% of transplants):
-lymphocytotoxic crossmatch
-mix donor (nonactivated T-cells) /w serum from recipient in the presence of complement
-lysis indicates presence of Abs directed against donor
-detection of IgG Abs directed against class I MHC molecules represents a positive test
and a contraindication to transplantation
-ABO typing
-vascular rejection; a delayed variant
-mediated by humoral factors
-occurs when offending alloantibodies exist in circulation at levels undetectable by crossmatch
assay
-re-exposure leads to restimulation of memory B-cells responsible for donor-specific Abs
-initial graft function followed by deterioration ~ POD#3
-can occur through de novo Ab synthesis spurred by T-cell-dependent B-cell activation

Acute Rejection:
-caused primarily by T-cells
-evolves over days to weeks; most common in the first 6 months
-T-cells bind antigen via TCR (either directly or after phagocytosis of donor tissue and re-

138
presentation of MHC peptides by self APC) cell activation
-results in massive infiltration of graft of T-cells, /w destruction of the organ
-incidence of acute rejection declines /w decreasing MHC disparity, but any mismatch can cause T-cell
mediated destruction. Therefore T-cell specific immunosuppression required
-treatment leads to graft restoration in 90-95% of cases
-monitoring for acute rejection mus be intense, particularly during the first year after transplantation
-unexplained graft dysfunction should prompt biopsy and evaluation for lymphocytic infiltration
and graft parenchyma necrosis characteristic of acute rejection

Chronic Rejection:
-poorly understood
-insidious onset: months to years
-pathophysiology undefined, untreatable
-heightened immunosuppression not effective in reversing or retarding progression
-characterized by parenchymal replacement by fibrous tissue /w a relatively sparse lymphocytic infiltrate
-direct cell-mediated tissue destruction is not a primary mechanism
-requires re-transplantation

!!' '

-the event occurring at the time of transplantation are the most critical in establishing the state of immune
unresponsiveness necessary for long-term graft survival
-immunosuppression is extremely intense in the early post-op period and subsequently tapers
-induction immunosuppression: usually involves deletion of T-cell response completely and
cannot be maintained indefinitely /wout lethal consequences
-maintenance immunosuppression: well tolerated if dosed appropriately
-rescue agents: immunosuppressant used to reverse an acute rejection episode (same as agents
used for induction)

Corticosteroids:
-used in conjunction /w other agents, improves graft survival
-can contribute significantly to the morbidity of transplantation
-anti-inflammatory agent
-bind to an intracellular receptor after nonspecific uptake into the cytoplasm
-prevents the function of NF-KB, a key activator of proinflammatory cytokines
-prevents the primary mechanism by which lymphocytes amplify their responsiveness
-block transcription of IL-1 and TNF-alpha and IFN-gamma production, PMN migration, and
lysosomal enzyme release by PMNs
-inhibits PLA2 and arachidonic acid cascade
-mutes upregulation of MHC
-do not have a significant influence on Ab production
-most commonly used is prednisone or methylprednisolone
-effects of steroids:
-suppressed HPA axis
-need coverage /w steroid preparation in the amount equal to their endogenous adrenal
capacity; should not exceed 50 mg hydrocortisone q8h
-impaired glucose tolerance
-delayed wound healing
-salt and fluid retention
-hypertension
-CNS effects (insomnia, depression, nervousness, euphoria)
-chronic effects:
-Cushing’s syndrome, cataracts, muscle wasting, and growth retardation n prepubertal

139
children
-peptic ulcers
-osteoporosis (inhibition of bone matrix formation and intestinal absorption of calcium)
-HLA-identical donors: no need for steroids
-pts who have survived a year /wout a rejection episode can be considered for /wdrawal from steroids

Antiproliferative Agents:

Azathioprine:
-hepatic conversion azathioprine 6-mercaptopurine (6-MP) 6-thio-inosine monophosphate (6tIMP)
-inhibits DNA synthesis by alkylating DNA precursors and inducing chromosomal breaks through
interference /w DNA repair mechanisms
-inhibit conversion of IMP to AMP and GMP
-effects are nonspecific
-effectively inhibits rejection as a maintenance agent but, has no value as a rescue or induction agent
-1-3 mg/kg/day
-toxicity: bone marrow, gut mucosa, liver
-decrease dose as total WBC or leukopenia (< 0.3)
-hold in the presence of infection
-hepatotoxin: rarely used in liver transplantation

Mycophenolate Mofetil (MMF):


-noncompetitive, reversible inhibitor of IMP dehydrogenase
-prevents a critical step in RNA and DNA synthesis by limiting GTP and dGTP production
-there is a “salvage pathway” for GMP production in most cells except lymphocytes
-therefore has selective immunosuppressive effects
-blocks proliferative response of both T and B lymphocytes
-inhibits Ab formation
-prevents generation of cytotoxic T-cells
-advantages over azathioprine:
-does not cause nephrotoxicity or hepatotoxicity
-less bone marrow suppression
-reduces the rate of rejection/treatment failure from 48% to 31%
-effective as rescue agent
-may interact /w tacrolimus, potentiating the effect and possibly the side effects of this drug

Calcineurin Inhibitors:

Cyclosporine:
-mainstay immunosuppressant in most maintenance regimens
-mechanism of action:
-binds to cytoplasmic cyclophilin (cis-trans peptidyl-prolyl isomerases critical for protein folding)
-does not effect immunosuppression but is related to toxic side effects
-cyclosporin-cyclophilin complex binds to calcineurin-calmodulin complex
-prevents Ca++-dependent phosphorylation and activation of transcription-regulating
factor NF-AT
-prevents transcription of IL-2 and other genes critical for T-cell activation
-reversible inhibition of T-cell-mediated immune responses, but does not prevent antigen recognition by T
cells. Effects can be overcome /w exogenous IL-2
-ineffective as rescue agent b/c effects are abolished in the presence of IL-2
-metabolised by cytochrome P-450 of liver:
-concentrations increased by inhibitors (eg. ketoconazole, erythromycin, CCBs)
-concentrations decreased by inducers (eg. rifampin, phenobarbital, phenytoin)
-side effects:

140
-renal:
-causes dose-related nephrotoxiciy d/t vasoconstrictors effect on proximal renal arterioles
-idiosyncratic reaction producing hemolytic uremic syndrome
-hyperkalemia
-hypertension
-neurologic:
-tremors, paresthesia, headache, depression, confusion, somnolence, seizures
-hypertrichosis
-gingival hyperplasia
-hepatotoxicity: increased LFTs

Tacrolimus (FK506):
-macrolide produced by Streptomyces tsukubaenis
-blocks NF-AT arrests T-cell activation
-intracellular target is an immunophilin distinct from cyclophilin
-100x more potent in blocking IL-2 and IFN-gamma production than cyclosporine
-mainly maintenance agent; has shown promise as rescue agent
-side effects:
-similar to cyclosporine wrt renal and hepatic toxicity
-tremors and mental status changes
-diabetogenic effect
-effective in liver transplants (drug of choice)

Antilymphocyte Preparations:

Antilymphocyte Globulin (ALG):


-targets central mediator of acute rejection, the T-cell, by coating multiple epitopes on this cell type and
promoting their clearance through complement-mediated lysis, opsonin-induced phagocytosis, and
internalization of key surface receptors
-thrombocytopenia may be a problem (cross-reactivity to platelets)
-dose 10-20 mg/kg/day IV for 10-14 days
-commonly used as part of multidrug induction immunosuppression protocol in renal transplantation /w
cyclosporine, azathioprine or MMF and prednisone
-side effects:
-fever, chills
-skin rash
-thrombocytopenia and leukopenia (require an alteration in treatment)
-daily CBC required
-reactivation of CMV, HSV, EBV and VSV

OKT3:
-murine monoclonal Ab to the signal transduction subunit on human T cells (CD3)
-mechanism of action:
-binds to CD3 and prevents signal transduction of T-cell receptor antigen binding event and
arrests amplification of a rejection episode
-downregulates TCR complex “blind” T-cell
-blocks cytotoxic activity of already activated T cells through inappropriate activation and
degranulation
-dose 5 mg/day for 10-14 days
-pre-treat /w methylprednisolone to prevent adverse reactions
-monitor /w flow cytometry to measure percentage of CD3+ cells
-good rescue agent (better than steroids) but limited to steroid-resistant rejection b/c of side effects

New Immunosuppressive Agents:

141
Rapamycin:
-macrolide antibiotic derived from Streptomyces hygroscopicus
-similar to tacrolimus; have been shown to antagonize each other
-interacts /w FK-BP but does not affect calcineurin activity
-does not inhibit expression of NF-AT or IL-2, but impairs signal transduction by the IL-2
receptor
-prevents T-cells from entering the S phase of cell replication
-advantage: interrupts T-cell activation even if IL-2 is present from an exogenous source or ongoing
rejection
-hypertriglyceridemia may be a significant side effect

Deoxyspergualin:
-isolated form Bacillus laterosporus
-has the strongest antiproliferative properties via anti-monocyte-anti-macrophage effect
-prevents the nuclear translocation of NF-KB
-inhibit antigen presentation or the costimulatory function of APCs
-effective in prolonging allografts survival in animal models of renal, pancreas, liver, and heart transplant
-side effects:
-GI disturbances
-headache, fatigue, perioral numbness, decreased white blood cell and platelet counts and
hematocrit
-synergistic /w cyclosporine

Brequinar:
-selectively inhibits T- and B-cell proliferation
-inhibits enzyme dihydro-rotate dehydrogenase interferes /w pyrimidine synthesis
-inhibits lymphocyte DNA synthesis and interrupts rejection process at level of clonal expansion
-synergistic /w cyclosporine
-side effects: leukopenia

Anti-IL-2 Strategies:
-high-affinity IL-2 receptor is dependent on up-regulation of 55-kD subunit Tac
-induction /w anti-Tac Abs has prevented and reduced frequency of early rejection when used in
combination /w cyclosporine
-synergistic /w cyclosporine, may reduce the dose of cyclosporine
-other Abs: 33B3.1, BT563

Costimulation Blockade:
-interruption of the CD28 pathway of costimulation may selectively energize only those cells undergoing
binding to the allografts, leaving non-reactive cells unaffected
-agents under investigation include Abs directed against B7-1 and B7-2, CD28, CD40, gp39, and fusion
protein, CTLA4-Ig

Concordant Xenografts:
-derived form closely related species, such as Old world monkeys and apes
-most of the critical molecular elements responsible for antigen presentation and T-cell-mediated rejection
are revolutionarily conserved in mammals
-feasible /w available immunosuppressive pharmaceutical agents
-widespread application of concordant xenografts would quickly deplete the supply of nonhuman primates
-concern that zoonotic transfer of disease would put the pt and the public at undue risk

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Discordant Xenografts:
-rapid HAR, generally from IgM Abs directed against atypical carbohydrate residues
-intervention at all levels of innate and acquired immunity will be required for successful engraftment
-transgenic alteration of pigs to express human proteins is the key for future clinical applications of
discordant xenografts

. .

-Vascular grafts
-used as autografts
-replacement of damaged or atherosclerotic arteries
-vein grafts (eg. saphenous) are optimal conduits for CABG
-autografting of arteries used occasionally for arterial replacement of diseased renal artery (hypogastric
artery)
-allogenic arterial conduits are the ideal replacement material for transplant renal artery stenosis
-Nerve grafts
-serves as a route along which the pt’s own nerve can regenerate

-prevention or amelioration of systemic complications may be possible by achieving more precise glucose control
-most successful approach to restoring normal long-term glucose homeostasis in Type I diabetes is whole-organ
pancreas transplantation

Historical Background:
-using a whole pancreaticoduodenal allografts /w anastomosis of the duodenal segment to the bladder is the safest
and most popular method of handling exocrine secretions

Indications:
-Type I insulin-dependent diabetics younger than 45 years
-no significant CAD
-no major amputations or severe visual impairment
-contraindications: untreated malignancy, active infection, HIV seropositivity

-three circumstances:
-pancreas transplantation alone (PTA) - in the non-uremic pt /w normal kidney
-pancreas transplantation after successful kidney allografting (PAK)
-offered to young diabetics /w tow ore more end-organ complications, who have undergone prior
living-related or cadaveric renal transplantation
-simultaneous pancreas-kidney transplant (SPK) - in uremic pt
-~90% are SPK

Operative Procedure:
-most widely used duct management technique of pancreas transplantation is bladder drainage, in which a
duodenal segment is anastomosed side-to-side to the dome of the bladder
-advantages of bladder drainage:
-urinary amylase determinations as screening test for rejection
-avoidance of enteric anastomosis and spillage of bowel contents
-reduced potential for peripancreatic infections
-advantages of enteric drainage:
-avoidance of post-operative urologic complications
-avoidance of chronic dehydration and need for bicarbonate replacement

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-early removal of foley
-technique:
-vascular reconstruction of pancreatic blood supply is performed /w donor iliac artery “Y” graft to
donor splenic artery and superior mesenteric artery
-duodenum segment is shortened to approximately 10-12 cm
-spleen removed by ligating splenic artery and vein
-intraabdominal placement of graft
-pancreas usually is placed into the right iliac fossa, and the kidney, if transplanted
simultaneously, is implanted on the left side
-venous anastomosis performed: portal vein of graft to distal inferior vena cava or iliac
vein
-arterial anastomosis: iliac “Y” graft /w recipient iliac artery
-bladder drainage side-to-side anastomosis of duodenal segment to dome of bladder
-enteric drainage side-to-side anastomosis to ileum
-generous IV doses of mannitol and albumin administered to limit reperfusion injury and tissue
edema
-irrigation /w antibiotic solution, including amphotericin B, miconazole, and cephalothin, to
minimize risk of peripancreatic infection, abscesses, and mycotic aneurysm

Postoperative Management:
-quadruple drug regimen: ATGAM or OKT3, MMF, cyclosporine or tacrolimus, and steroids
-antibiotic therapy for 10-14 days post-op
-acute rejection in 70-80% of pts, usually in the first year
-rescue: high-dose steroids x 2 days; if no response, OKT3 or ATGAM
-/w early treatment, 90% reversible
-lymphocytic infiltrates initially involve exocrine portion of gland; islet cells removed later
-monitor exocrine secretions of amylase in urine; a consistent drop > 25% strongly suggests possibility of
rejection, but it is not a reliable indicator of rejection
-obtain biopsies (gold standard) b/c only 55% of hypoamylasuria have biopsy evidence of rejection
-diagnosis of rejection after SPK transplantation relies almost entirely on serum creatinine and renal biopsy since
rejection of pancreas graft alone is unusual

Complications:
-urologic complications most common
-hematuria:
-early: usually mild and self-limiting
-late: d/t suture granulosa, urinary tract infection, or ulceration of duodenal segment
-if persists despite appropriate therapy, conversion to enteric drainage indicated
-postoperative urinary leak:
-three sites: urethral implantation site, duodenocystostomy anastomosis, duodenal segment
-early: usually located in bladder-duodenum suture line
-late (> 4 weeks): lateral duodenal staple lines or as the result of an ulcer /win duodenal segment
-significantly elevated serum amylase and development of pancreatic ascites discernible on CT
scan are highly suggestive
-diagnosis /w voiding cystourethrogram (VCUG)
-tx: Foley catheter bladder decompression for 2-3 weeks
-may require re-exploration and conversion to enteric drainage
-urinary tract infections:
-d/t alkalinization of urine secondary to bicarbonate and exocrine secretions, presence of a
diabetic neurogenic bladder /w incomplete emptying, mucosa injury at the bladder anastomosis,
and prolonged catheter drainage
-persistent urethritis:
-digestive action of pancreatic enzymes on urothelium
-treat /w Foley drainage for several weeks; may require conversion to enteric drainage

144
-early postoperative hyperamylasemia:
-may cause ARDS from preservation-induced pancreatitis
-late graft pancreatitis:
-sudden-onset lower abdo pain; elevation of serum amylase; absence of leak; evidence on
CT scan of gland edema and retroperitoneal inflammation and peripancreatic
inflammation, /wout evidence of abscess or fluid collections; resolution of symptoms
/win 24h of Foley catheter drainage
-metabolic acidosis:
-result of excessive urinary loss of bicarbonate-containing exocrine fluids
-tx /w oral replacements and fluids
-peripancreatic fluid collections:
-drained if suspicion of infection

-exocrine secretions of the pancreas transplant must be converted from bladder drainage to enteric drainage in 10-
25% of pancreas transplant recipients
-common indications are persistent hematuria and urinary leaks from the duodenal segment

Results:
-two most significant factors affecting graft survival are the circumstances in which the pancreas transplant occurs
and the duct management technique used
-good pancreatic graft survival: > 75% 1-year graft survival

Effect of Pancreas Transplantation on Secondary Complications of Diabetes


-enhanced quality of life, reversal of neuropathies, prevention of diabetic nephropathy, amelioration or stabilization
of diabetic retinopathy
-a functioning pancreas graft prevents the recurrence of diabetic nephropathy in the renal transplant
-subjective improvement of neuropathic symptoms: requires tight control of glycemic index

-transplant of small intestine resulted in unacceptable morbidity and mortality rates


-TPN has been shown to be an excellent treatment modality that has allowed many pts /w intestinal failure to
survive /w reasonable quality of life

Potential Candidates:
-pts /w short-bowel syndrome
-Crohn’s disease, mesenteric thrombosis, trauma (adults)
-Necrotizing enterocolitis, intestinal pseudoobstruction, gastroschisis, volvulus, intestinal atresia (children)

Operative Procedures:
-three methods:
-pts w/o liver failure isolated intestinal grafting
-/w liver failure combined liver intestine transplant
-multivisceral procedure

Donor Issues:
-most clinicians consider an identical ABO blood type mandatory b/c of previously reported hemolytic reactions
-a limiting factor is the required size match between donor and recipient (for children)

Management and Pretreatment:


-mechanical cleansing as well as antibiotic decontamination /w erythromycin and neomycin
-ALG/ATG or OKT3 has been used to pretreat donor in order to prevent graft-versus-host disease; however donor
pretreatment is not used routinely

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Preservation:
-University of Wisconsin solution used for preservation
-intestines more sensitive to ischemia and reperfusion injury
-good results for up to 16h cold ischemic time
-it is recommended that the intestine be transplanted /win 12h of retrieval

Immunology:
-problems /w graft-versus-host disease (GVHD) and host-versus-graft disease (rejection)
-reducing the number of lymphocytes by using shorter segments, irradiation, or poly/monoclonal Abs affects the
severity of GVHD and possibly reduces its incidence
-cyclosporine or tacrolimus has been used
-prednisone and azathioprine insufficient; tacrolimus significantly improved the out come after intestinal
transplantation

Diagnosis of rejection:
-symptoms: fever, abdo pain, elevated WBC, ileus, increased stomal output, gastrointestinal bleeding, positive
blood cultures
-intestinal biopsies: cryptitis, shortening of villi, mononuclear infiltrate, mucosal sloughing
-immunopathology: increased class II or IL-2 receptor expression
-Loss of mucosal integrity: measures of intestine permeability: 99mTc-DTPA po and urinary excretion measured
value greater than 5% indicates increased permability and possibly an acute rejection

Results:
-1-year graft survival: 65%
-3-year graft survival: 29%

Indications:
-indicated for treatment of irreversible liver failure from acute or fulminant disease or chronic liver disease
-fulminant disease: cause usually unknown, but may be secondary to viral hepatitis, Wilson’s disease, hepatotoxins,
or alcoholic hepatitis
-posthepatitic cirrhosis resulting from hepatitis B or C is associated /w the risk of recurrence of viral hepatitis and
cirrhosis in the transplanted liver.
-strategies to prevent recurrence of hep B: hep B hyperimmune globulin, interferon, lamivudine
-tranplant for PBC associated /w high success rate; primary dz may recur and is difficult to distinguish from chronic
rejection
-PSC should be treated before cholangiocarincoma develops
-alcoholic liver disease account for 75% of liver failure; a period of abstinence and evidence of family and social
support are required before the candidate can be eligible for transplantation
-tranplantation for cancer is controversial; immunosuppression usually favors the reemergence of underlying
malignancies

Preoperative Evaluation:
-signs and symptoms of liver failure
-pts /w stage IV coma must be managed aggressively to prevent cerebral edema or hemorrhage
-increased INR and thrombocytopenia: bleeding should be treated /w FFP and platelets
-GIB related to underlying portal hypertension constitutes an indication for liver transplantation
-ascites: diuretics and paracentesis
-hepatorenal failure, is reversible after liver transplantation; search for any underlying cause of renal dysfunction
-pts /w liver failure are immunocompromised; SBP can be treated /w antibiotics
-patient /w advanced cirrhosis often have a substantial loss of their non-parenchymal liver mass and
reticuloendothelial system, rendering them highly susceptible to sepsis, particularly by translocation across

146
the gut
-hyperdynamic state: elevated CO and low systemic vascular resistance; pulmonary hypertension may develop
risk for cardiac-related intraoperative death

Contraindications:
-multisystem organ failure
-sepsis outside the liver, although pts /w a septic focus /win the liver may appropriately be treated /w liver
transplantation
-noncompliance /w medical therapy (eg. Active alcohol or drug abuse)
-severe cardiac or pulmonary disease
-disseminated cancer

Immunologic Considerations:
-graft failure more frequently due to primary nonfunction, recurrence of original disease, or biliary and vascular
complications; usually not d/t immunologic rejection
-rejection episodes common during first 3 months posttransplant
-ABO blood groups compatibility is required, but this is not absolute; ABO-incompatible liver transplants have been
performed successfully
-ABO compatible but non-identical liver (eg. blood type O donor to type A recipient) may be associated /w a self-
limited graft-versus-host reaction, leading to haemolysis of recipient RBCs
-HLA matching is not a consideration in liver transplantation b/c the shorter preservation times required make it a
practical impossibility

Donor Procedure, Procurement, and Preservation:


-all hepatic arteries must be preserved and reconstructed as necessary in order to avoid infarction of the transplanted
liver
-preferred technique is aortic and portal vein flushing /w University of Wisconsin (UW) solution prior to
hepatectomy, followed by ex vivo portal vein, celiac axis, and superior mesenteric artery flushing and cold storage
on ice
-liver then biopsied:
-presence of more than 40% macrovesicular fat replacing hepatic parenchyma, severe microvesicular fat, or
severe hydropic change predictive of primary non-function
-increased incidence of biliary strictures and primary nonfunction can occur /w long preservation times

Recipient Operative Procedure:


-begins /w native hepatectomy followed by implantation of donor liver
-requires occlusion of IVC and portal vein simultaneously during anhepatic phase may lead to hemodynamic
instability
-venovenous bypass was developed to limit this instability
-“piggyback” technique: venovenous bypass rarely needed
-a donor liver procured from an adult may be reduced in size as necessary for transplantation to a pediatric recipient
-split-liver techniques can be used to supply one liver to two pts
-heterotopic and auxiliary liver transplantation have been used; advantage is that, should the native liver recover, the
pt can be weaned from immunosuppressive drugs, allowing the transplanted liver to atrophy or be removed
surgically

Postoperative Management:
-avoidance of vasoconstrictive inotropic agents, such as epinephrine, norepinephrine, phenylephrine, or high-dose
dopamine will reduce blood flow to the liver
-prostaglandin E1 infusions may be useful for increasing renal and hepatic perfusion in the immediate postoperative
period
-diuretics in the first 24-48 h to help mobilize fluids sequestered as a result of cirrhosis
-maintenance immunosuppression: cyclosporine or tacrolimus

147
-tapering steroids also used
-induction /w ALG or OKT3 is optional; may be useful in pts recovering form hepatorenal failure allows a delay
in starting nephrotoxic agents such as cyclosporine or tacrolimus
-elevations in LFTs prompt percutaneous liver biopsy
-rejection typically responds to bolus steroid therapy; steroid-resistant rejection treated /w ALG or OKT3

Complications:
-primary nonfunction: high INR, low fibrinogen level, high ammonia level in first several days posttransplant
-pts develop hepatic encephalopathy progressing to coma
-urgent transplant required
-portal vein thrombosis:
-rare complication
-marked rise in serum ammonia level or variceal bleeding
-diagnosed by Doppler ultrasonography
-required thrombectomy, restoration of portal flow, and evaluation of the cause of thrombosis
-hepatic artery thrombosis:
-5% in adults; higher incidence in pediatric liver transplantation
-early: d/t technical problems; late: immunologic injury of hepatic arterial tree
-results in ischemic changes of bile ducts leading to plugging and obstruction biloba formation liver
abscess and sepsis
-mx: retransplant or observation
-bilomas can be drained percutaneously, and strictures of the common bile duct can be treated /w
resection and Roux-en-Y drainage
-bile leaks:
-must be treated immediately may lead to peritonitis, sepsis and graft loss
-tx /w operative intervention or by ERCP /w papillotomy and temporary stenting of the CBD
-recurrence of original disease: PBC, Hep B and C
-hepatoma or cholangiocarcinoma recurring in a transplanted liver contraindicates retransplantation
-posttransplant lymphoproliferative disorder (PTLD)

Results:
-certain indications, such as PBC in adults and biliary atresia in children, are associated /w higher-than-average
success rates

Preoperative Considerations for Cardiac Transplantation:

Recipient Selection:
-long waiting lists; ~15-20% mortality rate among pt on the waiting list

Indications:

148
General Indications Warranting Consideration for Adult Cardiac
Transplantation
Severe cardiac disability despite maximal medical therapy
-History of recurrent hospitalization for CHF
-New York Heart Association functional class III or IV
-Peak metabolic oxygen consumption <15 mL/kg/min
Symptomatic cardiac ischemic refractory to conventional treatment
-Unstable angina not amenable to coronary artery bypass grafting or PTCA /w left
ventricular ejection fraction < 30%
-Recurrent symptomatic ventricular arrhythmias
Exclusion of all surgical alternatives to cardiac transplantation
-Revascularization for significant reversible ischemic
-Valve replacement for critical aortic valve disease
-Valve replacement or repair for severe mitral regurgitation

-most cardiac transplant recipients suffer from end-stage, inoperable coronary artery disease (38%) or
idiopathic cardiomyopathy (40%)
-other diagnoses: defined cardiomyopathy (eg. viral, postpartum, familial), congenital anomalies, and
valvular disease
-peak oxygen consumption, a function of peak cardiac output and peripheral oxygen extraction, correlates
well /w functional class and is an independent predictor of outcome in heart failure pts
-if < 15 mL/kg/min (< 50% normal), then 1 -year mortality rate exceeds 50%; these pts would
benefit from transplantation

Contraindications:
-advanced age, irreversible hepatic, renal, or pulmonary dysfunction, active or extrapulmonary infection,
severe peripheral or cerebral vascular disease, unresolved malignancy, severe, pulmonary hypertension,
psychiatric illness or history of medial noncompliance, drug or alcohol abuse, current tobacco use, and
cachexia or morbid obesity
-studies demonstrated that older pts (>60years):
- more likely to die of late infectious complications or malignant disease after transplantation
-higher risk for developing steroid-induced diabetes and clinically significant osteoporosis
-severe COPD: FEV1 < 1L or 50% or predicted
-chronic infective agents (eg. hep Ba nd C, HIV) preclude transplant
-previous malignancies < 5 years of cure (except SCC of skin)
-severe fixed pulmonary hypertension: increased incidence of posttransplant RV failure
-higher mortality rates /w transpulmonary pressure gradient > 15 mmHg
-these pts should be considered for combined heart-lung transplantation

Evaluation and Management of Pts Awaiting Cardiac Transplantation:

Candidate Evaluation and Listing:


-Status I:
-require an ICU setting receiving parenteral inotropic drugs or mechanical device support
-less than 6 months old
-Status II: all other waiting pts
-selected tests are performed, particularly peak oxygen consumption and hemodynamic measurements
(repeated every 6 months)

Medical Management:
-goal: relieve debilitating symptoms; preserve organ function and optimize pt’s condition for
transplantation
-usually treated /w digoxin, diuretics, vasodilators, and ACEi +/- anticoagulants
-amiodarone has improved survival in pts /w end-stage heart failure /wout increasing perioperative risk

149
Mechanical Support:
-intraaortic balloon pump (IABP)
-improves coronary perfusion and reduces afterload and mitral regurgitation
-cannot be used for extended periods of time
-ventricular assist system (VAS)
-intermediate ro long-term circulatory support for pts in severe ventricular failure
-considered when:
- CI < 2.0 L/min/m2 BSA
-ventricular filling pressure > 20 mmHg
-u/o < 20 cc/h
-systemic vascular resistance is > 2100 dynes sec/cm-5
-reduced mortality rates in those awaiting cardiac transplantation

Donor Selection and Management:

Criteria:
-irreversible brain death
-tests: ECG, ABG, echo, serologic screening (eg. HIV, hepatitis, HBsAg, hep C Ab, HSV, CMV,
toxoplasma), pancultures
-normal cardiac function and absence of significant cardiac history and significant coronary atherosclerosis
-absolute contraindications:
-severe coronary or structural disease, prolonged cardiac arrest, prior MI, CO-Hb > 20%, SaO2 <
80%, metastatic malignancy, HIV+

Management:
-maintenance of hemodynamic stability
-IV fluids to maintain CVP b/n 5-12 mmHg
-DI is common and requires IV vasopressin (0.8-1.0 U/h)
-dopamine, alpha agonists may be used judiciously
-blood tranfusion sparingly to maintain Hb ~ 10g/dl
-avoid hypothermia

Donor-Recipient Matching:
-parameters include ABO compatibility and body size
-ABO mismatch hyperacute rejection
-size matching and graft ischemic time particularly important for recipients /w elevated pulmonary vascular
resistance
-grafts from donors whose weight is < 80% of that of recipient or /w ischemic times longer than 2 h are avoided
-no upper donor size limit in adults
-recipient is screened for preformed Abs against a standardized panel of random donors

Operative Procedures:

Procurement:
-median sternotomy pericardial well created
-heart inspected and palpated for contusions, perforations, thrills, and CAD
-intravenous heparin administered at a dose of 300 u/kg and allowed to circulate for 3-5 min
-ligation and division of vessels
-hyperkalemic cardioplegic solution at 2-4oC rapidly infused into aortic root @ 150 mmHg arrest in
diastole
-cold saline at 4oC poured onto heart and into pericardial well
-remainder of pulmonary vessels divided
-heart removed and placed in cold saline medium

150
Orthotopic Transplantation:
-pt prep: CV access via (L) IJ vein; sparing right for future endomyocardial biopsies
-median sternotomy; routine cannulation of aorta and vena cavae
-see Fig 10-23

Heterotopic Transplantation:
-operative technique bypasses the left heart and involves anastomoses between the left atria, aorta,
pulmonary arteries, and donor superior vena cava to recipient right atrium
-indications:
-irreversible severe pulmonary hypertension
-diminished donor heart function anticipated b/c of size mismatch or prolonged ischemic time

Postoperative Management:

Early Postoperative Period:


-monitor cardiac rhythm and arterial and central venous pressures
-primary objective is to maintain adequate perfusion while minimizing cardiac work
-10-20% have some degree of transient sinus node dysfunction (usually sinus bradycardia)
-usually resolves /win a week
-persistent dysfunction in <5% permanent pacemaker
-heart rate maintained b/n 90-110 bpm (temporary pacing or isoproterenol)
-sBP maintained b/n 90-110 mmHg (using nitroglycerin or nitroprusside if necessary)
-renal dose dopamine (3-5 ug/kg/min) used to augment renal blood flow and u/o
-cardiac function normalizes /win 3-4 days wean parenteral inotropes and vasodilators
-optimize pulmonary function:
-FIO2 100%, tidal volume of 10-15 ml/kg, rate of 10-14 bpm, PEEP of 3-5 cmH2O
-adjust settings q30min to achieve PaO2 > 75% mmHg /w FIO2 40%, PaCO2 30-40 mmHg, pH
7.35-7.45
-weaning when pt deemed stable, awake and alert
-expedient removal of vascular lines to reduce incidence of line-related infections
-pacing wires removed after 7-10d if pacing not required
-in cardiac surgery ward: immunosuppressant dosage adjustment, initial endomyocardial biopsy, and early
rehabilitation
-second endomyocardial biopsy and baseline coronary arteriogram ~ 2weeks post-op

Graft Physiology:
-de-nervated heart (from sympathetic and parasympathetic plexus) is isolated from normal autonomic
regulatory mechanisms
-resting HR higher b/c of absence of vagal tone, sinus arrhythmia and carotid reflex bradycardia
-increased sensitivity to catecholamines increased B-adrenergic receptor density and loss of
norepinephrine uptake in postganglionic sympathetic neurons
-cardiac output at low end of normal range
-delayed increase in heart rate

Immunosuppression:
-“triple drug” combination: cyclosporine, azathioprine, glucocorticoid
-high dose, then taper
-cyclosporine:
-inhibits T lymphocyte activation (blocking release of IL-2 from helper T cells)
-trough serum concentration of 150-250 ng/ml x first few weeks 50-150 ng/ml
-side effects: nephrotoxicity, hypertension, hepatotoxicity, hirsutism, increased incidence of
lymphoma
-azathioprine:
-cytotoxic agent and bone marrow suppressant

151
-dosed to maintain WBC < 5000 mm3
-side effects: generalized bone marrow depression (leukopenia, anemia, thrombocytopenia)
-glucocorticoid:
-potent immunosuppressive effects by inhibiting leukocyte elaboration of inflammatory mediators
-methylprednisone bolus 500 mg IV then 125 mg IV q8h x 24h
-then 1.0 mg/kg/day during first week 0.2 mg/kg/day if no acute rejection
-side effects: cushingoid features, hypertension, diabetes, osteoporosis, peptic ulcer disease
-addition of OKT3 to triple-drug regimen over first 10 post-op days has delayed time to first rejection and
has reduced early rejection rates, but has not resulted in significant differences in overall recipient survival
-side effects: hypotension, bronchospasm, fever
-premeditate /w acetaminophen, antihistamines, corticosteroids
-most side effects are manageable or reversible /w dose reduction

Postoperative Complications:

Acute Rejection:
-major cause of death after cardiac transplantation
-highest incidence during first 3 months
-using OKT3 /w triple therapy reduces rejection from 84% to 75%
-after 3 months: incidence ~ 1 episode per pt a year
-endomyocardial biopsy is gold standard for diagnosis
-acute rejection characterized by:
-lymphocytic infiltration and myocytic necrosis
-treatment:
-severe or moderate in early posttransplant period: pulsed steroid dosing
-methylprednisone IV @ 1000 mg/d x 3d
-subsequent severe or moderate rejection episodes on routine surveillance:
-steroid pulsing or by po prednisone to 100-200 mg/day x 3d taper over 2 weeks
-mild rejection not treated unless persistent
-refractory rejection to steroids:
-ATG or OKT3
-MTX and total lymphoid irradiation
-repeat biopsy q 10-14 days after antirejection therapy

Chronic Rejection:
-accelerated atherosclerosis major limiting factor
-may lead to arrhythmias, MI, sudden death, or impaired LV function and CHF
-angina not experienced b/c graft is de-enervated
-risk factors for developing CAD:
-older donor age
-older recipient age
-incompatibility at HLA-A1, A2 and DR loci
-hypertriglyceridemia
-frequent acute rejection episodes
-recipient CMV infection
-elevated levels of antiendothelial Abs correlate /w graft CAD
diffuse vascular narrowing; concentric intimal proliferation /w SMC hyperplasia
-coronary angiograms on a yearly basis; intracoronary ultrasonography is a sensitive test for graft
atherosclerosis
-tx: PTCA or CABG for proximal lesions; retransplantation for diffuse disease

Infection:
-leading cause of morbidity and mortality
-risk peaks during first few months after transplantation

152
-early infections (first month after transplantation)
-bacterial (gram negative bacilli)
-pneumonia, mediastinitis, catheter sepsis, urinary tract and skin infections
-late infections:
-opportunistic viral, fungal, and protozoan pathogens
-CMV infection most common viral infection (73-100% transplant pts)
-reactivation ~ 1-4 months after transplant
-donor organ though to be most common vector of primary CMV infections
-leukopenia /w fever, pneumonia, gastroenteritis, hepatitis, and retinitis
-CMV pneumonitis most lethal (13% mortality)
-retinitis most refractory to treatment
-trigger for accelerated graft CAD and inhibitor of cell-mediated immunity
-tx: ganciclovir (DHPG) and hyperimmune globulin
-fungal infection:
-tx: amphotericin B, fluconazole and flucytosine
-infection prophylaxis:
-vaccinations: pneumococcal, hepatitis B and DPT boosters; annual influenza vaccine
-in children, MMR before transplantation
-perioperative antibiotics: cefazolin
-long-term prophylaxis: nystatin for thrush, SMX-TMP for opportunistic bacterial and
Pneumocystis carinii infections, and antiviral agents such as acyclovir or ganciclovir

Neoplasm:
-recipients predisposed to skin cancer, B-cell lmphoproliferative disorders, carcinoma in situ or cervix,
carcinoma of vulva and anus, and Kaposi’s sarcoma
-appear ~ 5 years after transplantation
-lymphomas frequently seen in recipients < 20 ya
-thought to be d/t EBV infection in setting of T-cell suppression
-tx /w reduction in immunosuppression and antiviral agent (acyclovir or ganciclovir)

Retransplantation:
-indications are graft failure from accelerated graft CAD or recurrent acute rejection

) ( ) (

-indications:
-acquired dilated cardiomyopathy
-congenital heart disease
-blood type and donor size are most important considerations in donor-recipient matching
-moderate oversized heart grafts are preferred for recipients /w and elevated pulmonary vascular resistance
-immunosuppression therapy similar to adults; steroids are tapered more quickly to minimize growth retardation
and infectious complications
-acute rejection treated /w pulsed steroids; antilymphocyte preparations, total lymphoid irradiation, and methotrexate
reserved for refractory cases

153
' " ) ' "

Preoperative Considerations:

Recipient Selection Criteria:


-Single-Lung Transplantation:
-pulmonary fibrosis
-emphysema
-bronchopulmonary dysplasia
-primary pulmonary hypertension w/o significant right heart dysfunction
-post-transplant obliterative bronchiolitis
-Bilateral Single-Lung Transplantation: (avoids risk for infection from retained native lung)
-cystic fibrosis/bronchiectasis w/o cardiac decompensation
-emphysema/COPD w/o cardiac decompensation
-Heart-Lung Transplantation:
-severe primary pulmonary hypertension /w RV decompensation and/or cardiomyopathy
-severe Eisenmenger’s syndrome /w RV decompensation or uncorrectable congenital heart disease
(eg. truncus arteriosus, large septal defect)
-intercurrent cardiac and pulmonary disease

-contraindications similar to those in cardiac transplantation


-upper age limit 50-60 years
-systemic disease /w significant renal or hepatic dysfunction, acute illness, unresolved malignancy, or
psychiatric illness

Evaluation and Management of Pts Awaiting Lung or Heart-Lung Transplantation:


-cardiac function:
-ECHO, doppler and saline-contrast flow studies, radionuclide angiography, Holter monitoring,
cardiac catheterization
-treatment of heart failure: dietary restrictions, diuretics, vasodilators
-treatment of pulmonary hypertension: supplemental oxygen therapy to eliminate stimuli for hypoxic
pulmonary vasoconstriction and secondary erythropoiesis
-if severely ill, prostacyclin may reduce PA pressures, but this is only temporary
-interstitial lung disease:
-corticosteroids are used to treat, but interfere /w tracheal healing significant dose reductions
needed in anticipation of heart-lung transplantation (prednisone to less than 0.1 mg/kg/day)

Donor Selection and Management:


-same criteria as for heart transplantation
-donor PaO2 should exceed 100 mmHg on FiO2 30% and 400 mmHg on FiO2 100%
-peak inspiratory pressures should be < 30 cmH2O
-donors should receive broad-spectrum antibiotics for infection prophylaxis before explanation
-absolute contraindications:
-severe coronary or structural heart disease
-prolonged cardiac arrest
-prior MI
-CO-Hb > 20%
-SaO2 < 100%
-active malignancy
-significant smoking history (> 5 pack years or 1 ppd over past year)
-HIV
-primary objective is maintenance of hemodynamic stability and pulmonary function
-to maintain adequate perfusion pressures, dopamine is the standard inotropic agent used
-avoid FiO2 levels in excess of 40% may be toxic to enervated lung

154
Donor-Recipient Matching:
-parameters include ABO compatibility and body size
-matching donor and recipient height seems to be the most reproducible method of selecting
appropriate donor lung size
-donor lungs should not be > 4 cm over similar measurements
-panel-reactive Abs (PRA) level greater than 50% prompts prospective specific crossmatch between the
donor and recipient

Operative Techniques:
-see Schwartz pg. 413-415

Management of Recipients:

Early Postoperative Period:


-ischemic and reperfusion injury result in increased vascular permeability and impaired mucociliary
clearance mechanisms
-lower tidal volumes and flow rates may be necessary to limit peak airway pressures to less than 40 cmH2O
-most pts are extubated /win 3 days and weaned from supplemental oxygen by 10 days after
transplantation
-“reimplantation response”: graft edema due to inadequate preservation, reperfusion injury, or early
rejection
-judicious administration of fluids and loop diuretics is required

Immunosuppression:
-protocols similar to those used in cardiac transplantation
-induction therapy /w anti-lymphocytic Ab preparations can be used

Postoperative Complications:
-early morbidity and mortality most commonly caused by infection, graft failure, and heart failure
-mortality after 1 year caused most commonly by obliterative bronchiolitis, infection, and malignancy
-majority of acute rejection occurs in first 3 months
-fever, dyspnea, impaired gas exchange: PaO2, FEV1, interstitial infiltrate on CXR
-dx /w bronchoscopy /w transbronchial parenchyma lung biopsy and BAL
-lymphocytic perivascular infiltrates
-tx /w IV steroid boluses; persistent rejection treated /w ATG or OKT3
-pulmonary and cardiac rejection present asynchronously in most cases
-transbronchial biopsy: 89% sensitivity in predicting cardiac rejection
-endomyocardial biopsy: 34% sensitivity in predicting lung rejection
-chronic lung rejection:
-obliterative bronchiolitis (OB): dense eosinophilic submucosa scar tissue that partially or totally
obliterates lumina of small airways
-decreases in PaO2 and FEV1
-no effective treatment; augmentation of immunosuppression
-dx in 20-50% of long-term lung transplant survivors

Infection:
-bacterial, viral, fungal infections leading causes of M+M
-bacteria:
-gram-negative: predominate during early post-op period
-lack of cough reflex in denervated lung, abnormal mucociliary clearance mechanisms, and
deficiencies in lymphatic drainage predispose grafted lungs to infection
-invasive infections caused by organisms cultured form donor
-viruses:
-CMV most common and clinically significant

155
-b/n 2 weeks and 100 days after transplant
-primary infection in previously seronegative recipients more serious than reactivation in
seropositive pts
-dx /w BAL or transbronchial biopsy
-tx /w ganciclovir
-prophylaxis: ganciclovir, acyclovir, and polyvalent immune globulin
-Herpes Simplex pneumonia: tx /w acyclovir
-risk of developing lymphoproliferative disease; in association /w EBV infection
-treat by lowering immunosuppression and administering acyclovir
-fungal infections:
-peak in frequency b/n 10 days and 2 months posttransplant
-Candida albicans and Aspergillus
-tx /w fluconazole, itraconazole or amphotericin B
-prophylaxis: inhaled amphotericin B
-Pneumocystis carinii: prophylaxis /w oral TMP/SMX or inhalational pentamidine

-most common airway complications are partial anastomotic dehiscence and stricture
-dx during bronchoscopic examination
-tx: dehiscence: reoperation or close observation and supportive care
stricture: laser ablation or dilation /w rigid bronchoscopy or balloon and bougie dilators

) ( ' " ) ' "

-indicated for children /w end-stage pulmonary vascular or parenchyma disease:


-pulmonary hypertension and cystic fibrosis
-potential recipients generally have a life expectancy of less than 1 year, have normal hepatic and renal function, are
free of active systemic infection, and are in a stable psychosocial environment
-blood group and lung size are primary criteria for donor-recipient matching

Preoperative Management:

Transplant Recipient Evaluation:


-history, physical
-labs: CBC, lytes, BUN, creatinine, urinalysis, serologic studies for hepatitis B and C, CMV, HIV
-CXR, ECG
-metastatic workup for pt /w remote history of malignancy

Indications and Contraindications:


-Absolute:
-recently treated cancer (other than BCC or SCC of skin)
-HIV
-hepatitis /w evidence of cirrhosis or chronic hepatitis on biopsy
-severe IHD not amenable to CABG or PTCA
-Relative:
-obesity, noncompliance /w medical therapy, hx of tuberculosis, several renal diseases (eg.
oxalosis and sickle cell disease)

Histocompatibility Testing:
-blood group typing and HLA typing

156
-for living donor transplants, exception is ABO subtype A2 less antigenic
-/w plasmapheresis and preoperative preparation, an A2 donor kidney can be transplanted into a
non-A2 recipient
-HLA-typing:
-lymphocytotoxic serologic test
-potential recipient’s cells are tested against a battery of sera (from multiparous women or as
monoclonal Ab preparations)
-all cadaveric and potential living donors are HLA typed as well
-class I antigens HLA-A,B and C and class II antigens HLA-DR, DP, and DQ
-not necessary to type every antigen in a living-related donor situation b/c all HLA
antigens are found together on chromosome 6
-HLA-A,B and DR is sufficient
-siblings: zero-, one- or two-haplotype match
-parents and children: always one haplotype match
-two-haplotype matched living donor kidneys have near 100% graft survival /w extremely low rate
of acute rejection
-if a healthy donor is available that is blood-group-compatible, the pt should be considered even
/w a poor HLA match
-one year survival advantage for six-antigen matches over completely mismatched cadaveric
transplants is ~5%
-serum screening for anti-HLA Abs
-multiparous women who have lost a transplant are at highest risk for sensitization
-test pt’s serum against a panel of lymphocytes selected to represent the known HLA antigens
-an important factor in predicting the likelihood of finding a suitable donor for a given recipient:
-if panel reactive Abs (PRA) > 90% will likely have reactivity against 90% of potential
donors
-final crossmatch
-cells from potential donor and serum from recipient incubated together
-Ab binding detected using a cytotoxic technique or flow cytometry or antihemophilic globulin
(AHG) est
-performed before proceeding /w transplantation
-a positive T-cell crossmatch is considered an absolute contraindication to transplantation
-along /w blood typing, the final crossmatch constitutes the most important histocompatibility test
and is mandatory before all renal transplants

Renal Donor:

Evaluation of the Living Donor:


-advantages of live donation:
-excellent immediate graft function and avoidance of posttransplant dialysis
-better short-term and long-term results
-preemptive transplantation
-avoidance of waiting time for a cadaveric kidney
-reduction of immunosuppressive therapy (in HLA-identical transplants)
-risks to donor:
-1/10,000 risk of death and 10% or less risk of morbidity
-contraindications (inappropriate donors)
-presence of DM, HTN, Ca, significant cardiopulmonary disease, hx of renal dz, > 65 years
-proteinuria > 250 mg/24h, creatinine clearance < 80 ml/min, significant urologic abnormalities
-further donor evaluation:
-CT of collecting systems, ureter and bladder
-if minor urologic abnormalities detected in one kidney chosen for donation
-kidney /w the fewest number of renal arteries usually is chosen; left kidney is preferable b/c of longer
renal vein

157
Evaluation of the Cadaver Donor:
-account for ~ 75% of all kidney transplants
-marginal donors may be used:
-older and may have other dz not affecting kidneys, including low-grade brain tumours
-mild renal dysfunction or acute tubular necrosis

Donor Nephrectomy:
-most common complications after live donation: UTIs, wound infections, and PTX

Organ Preservation:
-hypothermia is the cornerstone of organ preservation
-however, hypothermia induced cell swelling may occur b/c Na-K pump is slowed
-mechanisms of preservation injury:
-loss of energy-generating capabilities resulting from mitochondrial damage b/c of loss of precursors for
ATP regeneration
-oxygen free radicals in reperfusion injury
-activation of catabolic enzymes
-activation of arachidonic acid cascade and production of cytotoxic products such as thromboxane and
leukotrienes
-two basic methods of preservation: cold storage and machine perfusion
-majority of kidney transplant centers still cold-store kidneys

Surgical Procedures:

Preoperative Preparation:
-cardiac stress testing or cardiac catheterization:
-for long-standing diabetes, hx of cardiac dz, age > 50
-bilateral native nephrectomy before transplantation:
-poorly controlled hypertension, chronic pyelonephritis and hydronephrosis
-polycystic kidney disease: if pain, hematuria, and UTI accompany disease
-cystoscopy, cystometrogram or VCUG may be required for those /w urologic history
-pts /w hx of pancreatitis: pancreatic U/S or CT scan and w/u for hyperparathyroidism
-cholecystectomy before transplant in pts /w symptomatic cholelithiasis
-pretransplant sigmoid colectomy: hx of diverticulitis, esp. pts /w PKD (higher incidence of diverticulosis)
-active hepatitis or chronic liver diseases and cirrhosis are not candidates
-but, those /w hepatitis B who are HbeAg negative and /w chronic persistent hepatitis C may be considered

Anesthesia:
-Swan-Ganz catheter and art line for older pts and those /w significant hypertension, diabetes, or previous CABG
-avoid succinylcholine in hyperkalemic pts: may exacerbate hyperkalemia and result in cardiac arrest
-renal-dose dopamine may be used to enhance renal transplant perfusion
-pts usually are given methylprednisolone, mannitol, and furosemide before removal of vascular clamps and
reperfusion of the kidney

Postoperative Care:

Immediate Care:
-u/o (from obligatory diuresis) usually is replaced /w half-normal saline solution /w 5% dextrose /wout potassium
-replace u/o plus 30 ml/h (insensible losses) not exceeding 200 ml/h
-early delayed graft function occurs in approximately 25% of cadaveric transplants
-fluid replacement linked to u/o will help to prevent fluid overload and the need for urgent hemodialysis
-anuria/oliguria in live donor kidney should alert to serious problem b/c these are expected to function immediately
-assess for any blood clots in Foley – irrigate or replace FC

158
-assess volume status; if CVP < 12 mmHg – give fluid bolus (500 cc) until CVP rises
-trial of furosemide (up to 200 mg) if no response from fluid boluses
-if no change in u/o despite above, then doppler U/S of kidney to assess blood flow
-if blood flow ok, then obstruction or urine leak (usually at UV junction) assessed /w U/S or
nuclear scintigraphy
-delayed graft function if above evaluation unremarkable: managed /w hemodialysis

Technical Complications:
-early: graft thrombosis, urine leaks, bleeding, wound infections
-late: lymphoceles, ureteral strictures, renal artery stenosis

-graft thrombosis:
-arterial or venous thrombosis
-technical in origin
-abrupt cessation of u/o
-dx on U/S
-early post-op bleeding:
-dysfunctional platelets in uremic pts
-DDAVP at time of operation to help /w platelet function if operative field not dry
-urine leaks:
-at UV junction most commonly
-usually technical failure, but also occur b/c of distal ureteral slough from inadequate blood supply
-dx: decreasing u/o, lower abdo pain, scrotal or labial edema, and rising serum creatinine
-U/S: fluid collection; renal scan: extravasation of radioisotope beyond collecting system
-tx: early exploration and repair
-UV leaks: reimplantation
-bladder leaks: primary closure
-lymphoceles:
-perinephric collections of fluid in ~5% transplants
-result of excessive iliac dissection and failure to ligate lymphatics overlying iliac artery
-may present as swelling over transplant, unilateral leg edema from iliac vein compression, increased
creatinine level from ureteral compression
-dx: aspiration: high protein content and creatinine concentration equal to serum
-drainage if symptomatic (ie. Causing compression)
-options: sclerosis /w tetracycline or peritoneal window for intraabdominal drainage
-renal artery stenosis:
-in 10%; usually in first 6 months
-primarily presents /w HTN
-may also have fluid retention, bruit over transplanted kidney
-worsening renal function when ACEi are used to treat HTN
-dx: angiogram; U/S and MRI angio may be used as screening tools
-may occur distal to anastomosis from rejection, atherosclerosis, and clamp or perfusion cannula injury
-more common if end-to-end anastomosis used vs end-to-side
-tx: >80% can be corrected /w balloon angioplasty at time of angiography; else repaired surgically
-ureteral obstruction:
-rising Cr /w hydronephrosis
-d/t lymphocele or stricture in distal ureter
-strictures d/t ischemia and sometimes rejection;
-dx: antegrade pyelogram

Immunosuppression:
-antithymocyte globulin (ATG), OKT3, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, prednisone
-numerous protocols for cadaveric transplants
-triple therapy:

159
-azathioprine (or MMF), cyclosporine and prednisone
-cyclosprine 5-8 mg/kg po bid
-MMF 1000 or 1500 mg po bid (watch for GI sxs and leukopenia)
-prednisone 500-1000 mg IV then rapid taper to 5-10 mg od after 3-6 months
-steroids usually for life
-quadruple therapy:
-addition of ATG or OKT3
-to avoid nephrotoxic effects of cyclosporine and tacrolimus
-cyclosporine or tacrolimus not given until Cr level < 3.0 mg/dL; overlapped /w ATG or OKT3 until target
cyclosporine levels achieved
-two-haplotype living-related protocols:
-cyclosporine-based protocol /w azathioprine or MMF; steroid /wdrawal
-one-haplotype and living-unrelated protocols similar to cadaveric protocols

Treatment of Rejection:
-rejection occurs in 40-50%
-first line: high-dose steroids (usually methylprednisolone 500-1000 mg for 3-5 days)
-second line: OKT3 effective in reversing 90%
-polyclonal preparations such as ATG used in those /w Abs to OKT3 or serious side effects from OKT3-
induced cytokine release
-OKT3 as first line if biopsy-proven vascular rejection
-if rejection, then switch pt to MMF
-if refractory to steroids and OKT3, then treat /w tacrolimus (reversal in 75% of pts on tacrolimus)

Long-term Complications:
-most common causes of death: cardiovascular disease, infectious disease, malignancy
-noncompliance responsible for 10-15% of late graft losses
-recurrence of disease
-cardiovascular dz more common in pts /w DM, HTN, elevated serum cholesterol and triglyceride levels, and
smokers
-risk of IHD 3-4x greater in posttransplant pts than general population
-prevention is key:
-reduce hyperlipidemia /w diet and weight loss +/- statins
-minimized use of steroids, treatment of HTN, exercise
-hepatic dysfunction:
-common after transplantation; may be secondary to hep B, C, or drug toxicity (azathioprine, cyclosporine)
-hep B: progression to cirrhosis accelerated /w immunosuppression: may enhance viral replication
-hep C: more common than hep B; causes chronic liver disease in majority of pts
-hepatotoxicity from azathioprine/cyclosporine uncommon
-azathioprine: cholestatic pattern (d/c drug)
-cyclosporine: increased bilirubin and transaminase levels (usually responds to decreasing dose)
-may also be caused by pancreatitis, cholelithiasis and choledocholithiasis
-bone and mineral metabolism:
-hypophosphatemia and hypercalcemia (may be from persistent hyperparathyroidism)
-subtotal parathyroidectomy if: severe mental status changes, renal stones, fractures, pancreatitis, serum
calcium > 12.5 mg/dl after 1 year
-severe osteopenia or osteonecrosis
-minimize steroid dosage and correct hyperparathyroidism
-estrogen and calcium supplements in post-menopausal women
-may require etidronate and nasal calcitonin
-hyperglycemia:
-secondary to steroids: increase glucose production, impair peripheral use, and increase glucagon levels
-cyclosporine and tacrolimus decrease beta cell excretion and cause peripheral insulin resistance
-malignancies:

160
-lymphomas (1-2%)
-carcinoma of colon, rectum, prostate, breast and lung NOT increased
-skin cancer (esp. SCC) up to 20x higher
-higher incidence of Kaposi’s sarcoma and genital neoplasm (eg. Vulvar, vaginal, and cervical carcinomas)
-Posttransplant lymphoproliferative disease (PTLD):
-driven by EBV
-polymorphic B-cell hyperplasia nuclear atypia malignant monoclonal B-cell lymphoma
-occurs more frequently in those who have received antilymphocyte preparations (eg. ALG, ATG, and
OKT3)
-tx by lowering or stopping immunosuppression
-may respond to antiviral treatment /w acyclovir or ganciclovir

Special Problems:

Diabetes:
-diabetics at higher risk for HD and PVD
-all should have noninvasive cardiac evaluation for ischemia
-transplantation contraindicated if diffuse coronary disease (not amenable to surgery) /w LV dysfunction
-diabetic candidates for renal transplantation should be evaluated for combined kidney-pancreas transplantation
-juvenile diabetics /w transplants have 5 year survival rates ~80% (vs ~30% in non-transplanted pts on dialysis)

Pediatric Pts:
-pediatric pts /w functioning kidneys grow more normally, have significant catch-up growth, and potentially can
have more normal lifestyles
-work-up similar to adults, but less need for evaluation for comorbid conditions
-look for urologic as well as neurologic (eg. spina bifida) abnormalities
-recommended that pts < 1 year be allowed to grow before consideration for transplant
-pediatric pts have poorer overall graft survival than adult pts, particularly in cadaveric tx
-outcome better /w living-donor transplants
-high risk of non-compliance

Retransplant Pts:
-retransplant recipients have poor overall graft survival compared to first transplant recipients
-factors which increase graft loss in retransplant:
-extremely short survival of first transplant d/t acute rejection in < 6 months
-high PRA levels: generalized sensitization from a previous failed graft
-best outcomes have been demonstrated /w induction therapy, and the use of OKT3 or ATGAM can be
recommended for these pts

-acceptable preservation times vary with organ


-heart: within 5h
-kidney: 40-50h
-pancreas: 10-20h
-liver: within 6-12h
-injury to organ could occur because of cardiovascular instability and hypotension
-goal is to reduce warm ischemic time, cool organ rapidly via flushout of vascular system
-hypothermia (4oC) and composition of preservation solution are key factors in successful preservation
-flushout should remove blood as completely as possible at an acceptable pressure (60-100 cmH2O)
-warm ischemic depletes ATP and redistributes electrolytes across cell membrane
-degradative reactions continue (accumulation of lactic acid, pH, proteolysis, and lipolysis) causes
structural alterations in membranes that may be irreversible

161
-ideal preservation solution:
-presence of impermeant molecules that suppress hypothermically induced cell swelling
-ion pumps slow down, loss of electrical potential across membranes, and entry of Cl down its
chemical gradient leads to accumulation of water in cell swelling organ damage
-appropriate biochemical environment
-University of Wisconsin (UW) solution:
-lactobionic acid as primary impermeant:
-large MM (358 kD)
-negatively charged
-also contains raffinose, hydroxyethyl starch, adenosine (stimulates ATP synthesis during reperfusion of
the organ)
-machine perfusion for kidneys decreases delayed graft function (<10% vs 25-30% seen in simple cold storage)
-gluconate is used in place of lactobionic acid

162
! "

-sum total of abnormalities of all organ systems and their interactions that determine the outcome of an operation

#$ % &
-estimation using Goldman’s cardiac risk index
-risk of surgical cardiac death:
-no previous MI: 1.0-1.2%
-MI > 6 months: 6.0%
-MI (transmural) < 3 months: 16-37%

-predisposing factors for perioperative cardiac death:


1. infarction within 6 months
2. congestive heart failure
3. arrhythmias
4. aortic stenosis
5. emergency or major surgery
6. age greater than 70 years
7. poor medical condition

-ECG and hematocrit level are significant


-stress test indicated to identify patients at risk
-positive if any or all of the following:
-ST depression > 0.2 mV, inadequate heart rate response to stress, or hypotension

-delay surgery (if possible) to > 6 months after MI


-angioplasty or CABG may be necessary before any major surgical procedure
-treat CHF and a-fib

#'$ ( &
-risk factors:
1. smoking
2. obesity
3. advanced age
4. industrial exposure
5. PCO2 > 45 mmHg diffusion defect
6. abnormal PFTs:
-FVC < 70% predicted
-FEV1 < 2.0L or < 70% predicted
-PEFR < 200 L/min
-FEV1/FVC < 65%
7. PAP > 30 mmHg

-exercise oxygen consumption (prior to thoracotomy) (VO2) > 20 ml/kg/min less likely to have post-op pulmonary
complications
-8 weeks smoking cessation prior to surgery beneficial

#)$ * &
-serum abnormalities of BUN and Cr are not manifest until > 75-90% of renal reserve lost
-creatinine clearance (ml/min) = [1.23 x weight (140-age)]/creatinine in umol/L

163
-correct reversible causes: infection, uncontrolled hypertension, obstruction, and dehydration
-peritoneal, hemodialysis, or continuous ultrafiltration occasionally required

#+$ * &
-patients with cirrhosis
-Child-Pugh criteria: based on presence of ascites, bilirubin, encephalopathy, nutritional status, albumin
-class A < 5%; B 5-10%; C 20-50% mortality following non-cardiac surgery
-generally die of high-output CV failure and low peripheral resistance
-see Table 11-4
-measures that can be taken:
-abstinence from alcohol important prior to elective procedures
-improve protein tolerance by use of branched-chain amino acid
-control ascites:
-spironolactone and lasix combined with fluid restriction to 1500 ml/day
-limit sodium to 2g/day

#,$ * & see Chap. 3

#-$ . */*
-difficult to assess
-severely malnourished patient:
-weight loss > 15% over previous 3-4 months
-serum albumin < 3.0 g/dL
-energy to injected skin-test antigens
-serum transferring level < 200 mg/dL
-if severely malnourished, then enteral or parenteral (only if severe) nutrition for 4-5 days preop
-normalize retinol binding protein, thyroxin-binding prealbumin, and transferring

#0$ ! &# 1 2 * 2 $
-no definite guidelines
-see appendix

. 3 4

Pathophysiology:
-lack of metabolically effective circulating insulin
-deficient utilization of glucose by peripheral tissues
-increased output of glucose by liver
-increased fatty acids ketones urine
-glycosuria osmotic diuresis loss of sodium and potassium

-anaesthetic agents can cause an exaggerated hyperglycemic epinephrine response and an increased
resistance to exogenously administered insulin
-stress of operation aggravates hyperglycemia
-epinephrine: glycogenolysis
-glucocorticoid: mobilized protein, anti-insulin effect
-growth hormone

Management:
-DM pts should have preference on operative schedule to minimize effects of fasting and ketosis
-mild DM frequently do not require insulin; dietary control sufficient
-pts using OHA should continue their use until day before operation

164
Insulin Therapy:
-see appendix for protocols

Ketoacidosis:
-IV hydration, insulin therapy, and electrolyte replacement (potassium)
-need for potassium usually does not exceed 80 mEq

Nonketotic Hyperglycemic Hyperosmolar Coma:


-relatively uncommon
-usually occurs in elderly diabetic or nondiabetic obese patients and those receiving TPN
-treat with large amounts of hypotonic solutions and intravenous insulin (est dose of 10 U)

Pathophysiology:
-disorder of normal body thermoregulation
-controlled by anterior hypothalamus
-?protective mechanism to combat infection
-all pyrogens evoke common mediator IL-1 (endogenous pyrogen)
-alters activity of temperature-sensitive neurons raises set-point increased body temperature
-vasoconstriction chills, shivering

Perioperative Fever:
-fever in the immediate postoperative period usually is not serious, is not very high, and is self-limited
-usually ascribed to atelectasis

Malignant Hyperthermia:
-incidence ~ 1/100000 general anaesthetic procedures
-succinylcholine, halothanes metabolic acidosis and electrolyte imbalances
-hypercalcemia, hypotonicity, hyperthermia (~40OC), oxygen denaturation, hypercapnia, cardiac
dysrhythmia
-treat with dantrolene IV 1 mg/kg, repeat to total dose of 10 mg/kg prn
-supportive measures; ventilation/oxygenation, treatment of possible myoglobinuria

Fever within 24 Hours:


-usually due to atelectasis or failure to clear pulmonary secretions
-unnecessary to do extensive tests at this point
-if high fevers with rigours, hypotension, and changes in mentation: consider severe wound complications
such as necrotizing fasciitis or intestinal leak

Fever at 24-48 Hours:


-usually respiratory complications
-catheter related problems - UTI
-inspect wound for cellulitis, necrotizing fasciitis, or clostridia myositis

Fever after 48-72 Hours:


-thrombophlebitis
-most common cause of fever after 72h is wound infection
-also suspect UTI
-less common infections: pneumonitis, acute cholecystitis, idiopathic postoperative pancreatitis
-drug allergy
-candidiasis may complicate IV TPN tx with amphotericin B
-fever after 1 week leaking anastomosis, abscess, deep wound infection

165
5 . 4

5 % /*

Predisposing Factors:
-staphylococcus aureus most frequently involved offending organism
-enteric organisms in bowel surgery; other less common pathogens: enterococci, Psedomonas, Proteus,
Klebsiella
-hemolytic strep responsible for 3% of wound infections

Classification of Operative Wounds


Class Wound Description Examples Incidence of
Infection

I Clean Nontraumatic, uninfected operative wounds 1.5-3.9%


in which the respiratory, alimentary, or
genitourinary tract is not entered. Usually
closed without drains

II Clean-contaminated Respiratory, alimentary, or genitourinary 3-4%


tract is entered with only minimal
contamination

III Contaminated Fresh traumatic wounds; wounds with a 7.4-8.5%


major break in sterile technique; wounds
encountering non-purulent inflammation;
wounds made in or near contaminated skin

IV Dirty Purulent infection is encountered 28-40%

Factors: -type of operative wound


-age: 15-24 years (4.7%); > 65 years (10%)
-diabetes: not an independent risk factor when adjusted to age
-steroids: increase rates from 7 to 16%
-obesity: doubles rate
-remote infection
-duration of operation: < 30 min (3.6%); > 6 hours (18%)
-malnutrition
-others (see Table 11-9)

Prevention:
-skin preparation: -clipping (2% infection rate) preferred over shaving (5%) of hair
-bowel preparation: -clear liquids, cathartics, antibiotic regimens
-prophylactic antibiotics
-maintenance of temperature: -warming blankets, warm fluids
-meticulous technique: -gentle handling of tissue, hemostasis
-appropriate drainage

Clinical Manifestations:
-infections usually evident between 5th and 8th POD; may manifest after weeks if pt on antibiotics
-necrotizing fasciitis or clostridia myositis can occur within 24 hours

Management:
-open incision and pack wound with gauze
-cellulitis and edema add antibiotics; Gram stain may help guide treatment
-if hemolytic strep penicillin for 1 week
-clostridia myositis/necrotizing fasciitis surgical debridement

166
-Fournier’s gangrene: necrotizing fasciitis of perineum or groin in diabetic patients
-30-70% mortality rate

5 % *
-inadequate hemostasis
-provide good culture medium for bacteria
-early haematomas return to OR ligate responsible vessel primary closure of wound
-late haematomas manage patient expectantly with hope that haematoma has not become contaminated

5 % *
-lymph collections
-aspiration and pressure dressings
-continuous closed-suction drainage

5 % . *1 * *
-< 45ya: 1.3%; > 45ya: 5.4%
-generally caused by a technical factor
-contributory factors:
-malnutrition, hypoproteinemia, morbid obesity, malignancy with immunologic deficiency, uraemia,
diabetes, coughing with increased abdominal pressure, remote infection
-local factors: hemorrhage, infection, excessive suture material, poor technique
-monofilament sutures have lower incidence of disruption than braided sutures
-vitamin C deficiency: 8x increase in wound dehiscence
-zinc deficiency associated with poor healing
-steroids interfere with wound healing; use vitamin A to counteract these effects
-chemotherapeutic agents inhibit wound healing
-usually wait 1-2 weeks post-op before chemotherapy started
-radiation causes obliteration of small vasculature and fibrosis

Clinical Manifestations:
-salmon-coloured fluid draining from wound at 4th or 5th POD (85% of the time)

Treatment:
-depends on pt’s condition
-if no evisceration non-operative treatment with sterile occlusive wound dressing and binder
-evisceration moist sterile towels applied and pt returned to OR
-perioperative broad-spectrum antibiotics should be given

4 4

( **
-requires release of alpha-adrenergic receptors in SMC of bladder neck and urethra and parasympathetic stimulation
to contract bladder
-stress, pain, spinal anaesthesia, and various anorectal reflexes conspire to increase alpha-adrenergic stimulation
-if retention urinary catheter used

* * *

Etiology:
-inadequate resuscitation: -sympathetics decreases renal blood flow; RAA system will shunt blood away
from afferent arterioles

167
-drug toxicity: aminoglycosides, vancomycin, amphotericin B, high doses of penicillin G or sulfonamides
-see Table 11-12 for other nephrotoxic drugs

Pathophysiology of Renal Dysfunction:

Prerenal:
-BUN/Cr 20:1
-commonly observed with dehydration
-hepatorenal syndrome:
-two mechanisms: hypovolemia (type I) and maldistribution of blood flow (type II)
-Type I: deficiency in intravascular volume secondary to blockage of liver outflow ascites
-Type II: failing liver, elevated bilirubin, other stigmata of cirrhosis; CO and low PVR
-kidneys are normal; recovery is rare and depends on recovery of intrinsic liver disease

Intrinsic Damage:
-acute tubular necrosis:
-most common cause in surgical setting is renal perfusion d/t prolonged and sustained
hypotension (from sepsis, blood los, hypovolemia, dehydration, or myocardial infarction)
-mechanism:
-kidney tries to maintain glomerular blood flow afferent dilatation and efferent
constriction of arterioles
-perceived hypoperfusion angiotensin by RAA system afferent constriction
- sympathetics norepinephrine afferent constriction
-this results in tubular ischemic and hypoperfusion of renal cortex ATN
-myoglobinuria and transfusion reaction (free Hb) may complicate renal injury
-other causes:
-radiocontrast dyes with dehydration
-atheromatous embolic during aortic vascular surgery
-clamping of renal artery

Postrenal Failure:
-ureteral clots or stones; BPH

Prevention of Acute Renal Failure:


-chronic UTI treat with Abx
-BPH TURP or balloon dilation
-chronic renal impairment ensure adequate hydration
-in low flow states, mannitol, bicarbonate, and diuresis induced by furosemide should be used
-mannitol increases renal corticla blood flow and produces an osmotic diuresis

Manifestations:
-oliguria with u/o of 0.4-0.5 cc/kg/h in adult
-anuria: uncommon; usually from ATN as a result of renal artery thrombosis or obstructive uropathy
-fractional excretion of sodium (FENa) = [UNa / PNa] / [UCr/PCr]
-if > 1% intrinsic renal damage
-UNa < 10 mEq/L prerenal cause or intrinsic liver disease
-intrinsic UNa > 40 mEq/L, FENa > 3%

Management:
-if diagnosis is uncertain:
-volume challenge if suspect hypovolemia
-once adequate volume status established furosemide (20-40 mg) to improve u/o
-stop nephrotoxic drugs
-established renal failure:

168
-treat hyperkalemia: infusion of calcium, hypertonic dextrose solution, and insulin then resins
-maintenance of nutrition in patients with ATN: enterally or parenterally
-IV “Giordano-Giovannetti diet” of essential AA and hypertonic dextrose, with minimum
of fat, decreases mortality in patients with ATN
-dialysis for critical ionic excesses, volume overload, or BUN concentration > 80-100 mg/dl

Pathophysiology:
-VC and FRC may be reduced after upper abdominal surgery (50-60% and 30% respectively)
-postoperative pain alters mechanics of respiration
-closing volume (lung volume at which airway closure is first detectable) decreases in the postoperative
period
-other physiologic causes of insufficiency: diffusion defects, abnormalities in V/Q, reduction in CO with
persistent shunt, alterations in Hb level and persistent shun, and shunting that is anatomic or related to
atelectasis

Predisposing Factors:

Smoking: -must abstain at least 8 weeks to achieve any demonstrable benefit


Age: -must look at physiologic age rather than chronological age
Obesity: -related to underlying pulmonary dysfunction characteristic of this patient population
-decreased FRC d/t chest wall compliance
COPD: -ensure adequate pain control
-use gastrostomy tube rather than NG found to statistically decrease incidence of
respiratory complications
Cardiac dz: -beware of pulmonary edema in CHF patiens

**
-collapse of alveoli resulting from anaesthesia, diaphragmatic dysfunction, postoperative incisional pain, and patient
positioning
-prevention is key:
-coughing and deep breathing, chest physiotherapy, incentive spirometry,
-intermittent positive pressure breathing, and CPAP
-medication for prophylaxis:
-expectorants: provide more liquid secretions
-detergents and mucolytic solutions: alter surface tension of secretions and render their elimination more
likely
-bronchodilators: eliminate bronchospasm

*
-third most common nosocomial infection (after wound and UTI)
-pathogens include Psueudomonas, Serratia, Klebsiella, Proteus, Enterobacter, Streptococcus
-use of H2-blockers may breakdown acid barrier, allowing overgrowth and colonization of the stomach by intestinal
flora (gram negatives)

Clinical Manifestations:
-fever, productive cough, dyspnea, pleuritic chest pain, and purulent sputum
-if hypotensive, consider gram negative pneumonia

169
Management:
-cultures obtained via routine ETT suctioning have little predictive benefit in correctly identifying the
pathogen responsible for noscomial pneumonia
-empiric therapy with aminoglycoside and antipseudomonal penicillin initiated until definitive culture
results obtained (via BAL ideally)

-most likely setting is during emergency induction of anaesthesia, particularly in pts with GERD or hiatal hernia

Clinical Manifestations:
-presence of gastric contents in mouth followed by wheezing, hypoxia, bronchorrhea, and cyanosis
-CXR: progression of local damage and infiltration accute respiratory failure results
-causes chemical pneumonitis that results in bacterial colonization with subsequent development of
pneumonia

Management:
-prevention: empty stomach and neutralization of gastric contents
-suction then ETT to complete clearance of tracheobronchial tree

( %*
-pulmonary-capillary hydrostatic pressure exceeds plasma oncotic pressure
-most common causes: fluid overload or myocardial insufficiency secondary to MI
-others: sepsis, valvular dysfunction, neurogenic stimulation, and hepatic failure
-increased capillary permeability:
-sepsis, ARDS, acute pancreatitis

Clinical Manifestations:
-two peak phases:
-during resuscitation if too aggressive with fluid replacement
-post-operative when fluid mobilization occurs
-rales, distended neck veins, cyanosis, peripheral pitting edema
-CXR: vascular redistribution, septal lines (Kerley’s B lines), peribronchial and perivascular cuffing

Management:
-depends on inciting cause
-for overload:
-pulmonary catheter may aid diagnosis and management
-PAWP 18-25 mmHg; CI decreased with increased PVR
-if PAWP normal or low, look for other causes
-?ARDS
-ECG look for evidence of pump failure
-treat with diuretics, IV nitroglycerin ( venous capacitance and preload)
-dobutamine or amrinone may improve cardiac output
-consider afterload reduction with nitroprusside if above maneuvers fail to produce a sufficient CI

2 ( % *
-fat embolism extremely common pathologic finding after trauma
-26% in patients with single fracture to 44% in patients with multiple fractures
-fat embolism syndrome with pulmonary dysfunction, coagulopathy, and neurologic disturbances associated with
increased circulating fat globules is ncommon

170
Pathophysiology:
-long bone fractures with release of marrow fat into circulation

Clinical Manifestations:
-respiratory insufficiency
-CXR shows characteristic bilateral alveolar infiltrates
-may evolve into ARDS
-CNS involvement in 86% confusion and disorientation with eventual progression to coma
-characteristic petechial rash occurs in axillae, neck , and skin folds
-fat globules in urine not specific for fat embolism syndrome
-associated findings:
-unexplained drop in hct, thrombocytopenia, hypocalcemia, and hypoalbuminemia

Management:
-immobilize any long bone fracture
-early surgical fixation decreases incidence of pulmonary complications of fat embolism
-oxygenation and supportive measures

* * (. * ( % *# . $
-pt incapable of maintaining adequate oxygenation, adequate ventilation, adequate tissue delivery, or some
combination of these defects
-syndrome that includes:
-lung injury, acute in nature
-bilateral infiltrates on frontal chest radiograph
-PaO2/FIO2 < 200
-PCWP < 19 mmHg with no evidence of CHF
-may be due to specific single cause or may represent endpoint of a poorly understood pathway with a common final
denominator of lung damage and subsequent decompensation of oxygenation and ventilation

Etiology and Pathophysiology:


-abnormal cytokine response to injury:
-activation of complement cascade, activtionof thromboxane-leukotrienes pathway, disorders in
NO production, degranulation of neutrophils, production of increased permeability factors by
macrophages
transudation of fluid and reactive materials into alveoli
-causes V/Q mismatch
-CXR shows “whiteout”; CT scan demonstrate regional changes in lung function
-volutrauma: maldistribution of inspired tidal volume secondary to PPV and the heterogeneous nature of
lung injury in ARDS
-overdistention of alveolus beyond its normal maximum

Management:
-reduce volutrauma:
-early use of PEEP adjusted to the inflection point (as seen on pressure-volume curve)
-pressure-limited ventilation with plateau pressures less than 35 cmH2O
-permissive hypercapnia
-use of inhalational NO
-PEEP has remained the mainstay of treatment of ARDS
-recruits collapsed alveolar units
-attenuates lung injury associated with PPV
-may prevent loss of FRC and prevent alveolar collapse at end-expiration
-permissive hypercapnia limits potentially detrimental effects of increased peak airway pressures, the
number of breaths necessary per minute, which reduces the risk of barotrauma and volutrauma

171
-inhalation of NO at mall doses has reduced pulmonary hypertension and improved oxygenation in a
variety of patients
-newer modalities using partial liquid ventilation (PLV) and perfluorocarbon-assisted gas exchange
(PAGE)

. 4

4( % /
-mortality from perioperative MI ranges from 54% to 89%
-presence of coronary artery disease: risk of perioperative MI increased from 0.1-0.7% to 1.1%
-patients over 40: infarction rate is 1.8%
-previous MI: infarction rate 27% (within 3 months); 11% (b/n 3 and 6 months); 5% (> 6 months)

Identification of the Patient at Risk:


-Goldman index
-look for cardiac signs, symptoms and risk factors

Clinical Manifestations:
-most cases occur on operative day or during first 3 PODs
-most important precipitating factor is shock risk of coronary thrombosis and myocardial ischemic
-chest pain only in 27% of patients b/c may be masked by narcotics
-may manifest as a sudden appearance of shock, dyspnea, cyanosis, tachycardia, arrhythmia, or CHF
-evaluate with ECG, serial cardiac enzymes, ABG (rule out respiratory causes)

Management:
-pre-operative:
-optimize CHF (digitalization for pts with enlarged hearts)
-treat anemia
-optimize fluid and electrolyte balance
-continue beta-blockers until morning of operation
-operation after 6 months of an MI
-intra-operative:
-regulation of BP important
-avoid hypoxia, hypotension, haemorrhage, dehydration, electrolyte disturbance and arrhythmias
-treatment:
-+/- monitoring in ICU
-pain relief: morphine and sedation
-+/- heparin, ASA; nitro and beta-blockers
-hypoxia relief: oxygen
-shock treated by vasopressor agents
-early emergency cardiac catheterization, angioplasty, or stenting may reverse an evolving MI

1( 1
-sinus tachycardia (not an arrhythmia) is the most common disturbance of rhythm, followed by PVC and sinoatrial
arrhythmia

Etiology:
-intrinsic cardiac disease
-perioperative release of catecholamines d/t stress or pain
-organ manipulation that stimulates reflex response
-electrolyte abnormalities and metabolic disturbances:

172
-hypokalemia PACs and PVCs
-hyperkalemia conduction abnormalities
-hypocalcemia QT interval ventricular arhythmias
-hypercalcemia bardycardia and heart block
-cardiac medications:
-digitalis toxicity supraventricular-atrial flutter with varying block, PVCs, VT or VF
-antihypertensive meds sinus bardycardia or induction block
-anaesthetic agents:
-halothanes ventricular dysrhythmias
-parasympathetic stimulation (neostigmine, physostigmine, succinylcholine) bardycardia
-other factors:
-hypercapnia may suppress sinoatrial node function ectopic pacemaker or aberrant reentry
mechanisms
-thyrotoxicosis atrial fibrillation
-pheochromocytoma

Management of Preexisting Arrhythmias:


-digoxin for patients with supraventricular tachycardia
-reversible causes, such as electrolyte disturbances, drug toxicity, hypoxia, etc. should be controlled
-cardiac pacing for significant conduction defects:
-third degree AV block
-Mobitz II block
-sick sinus syndrome

Management of New-onset Arrhythmias:


-ECG:
-P waves present supraventricular origin
-variable morphology ectopic focus, MAT or SVT
-P waves absent A-fib
-QRS narrow supraventricular origin
-QRS wide ventricular origin or supraventricular with aberrant conduction, conduction block
-Acute tachyarrhythmias with hypotension cardioversion (100 360J)
-Symptomatic bradycardia 0.5mg atropine IV q5min to max of 0.04 mg/kg
-consider transcutaneous pacing

Sinus Tachycardia:
-find and treat cause: pain, hypovolemia, hypoxia, acidosis, sepsis, CHF, hypoperfusion, hypercapnia

Paraoxysmal Supraventricular Tachycardia:


-re-entry tachycardia
-rates between 150 and 250 bpm
-primary treatment with
-adenosine 6 mg IV; repeat with 12 mg after 1-2 min
-then verapamil 2-5 mg IV with second dose after 15-30 min
-may consider cardioversion

Atrial Fibrillation:
-lack of “atrial kick” may result in 10-15% decrease in cardiac output
-causes:
-thyrotoxicosis, valvular heart disease, hypertension, CAD, PE, MI
-common after pneumonectomy
-cardioversion if hemodynamically unstable
-anticoagulate if long standing A-fib
-control rate (eg. with CCB, BB) and rhythm

173
Sustained Supraventricular Tachycardias:
-may be a result of digitalis toxicity
-obtain serum potassium and digitalis levels

Atrial Flutter:
-if unstable cardioversion
-digitalis used to maintain heart rate once controlled

Ventricular Tachycardia and Fibrillation:


-if pulseless precordial thump and immediate defibrillation at 200 J
-(review ACLS protocols)

( * *

Preoperative Hypertension:
-preoperative hypertension that is untreated or poorly controlled does increase the risk of perioperative
blood pressure lability, which may result in increased incidence of stroke, TIA, arrhythmias, post-op MI,
and possibly post-op renal failure

-postpone operation until hypertension controlled if:


-previous hypertension with diastolic pressure > 110
-new-onset hypertension
-sudden increases in hypertension
-recent deterioration in critical end-organ status

-delay operation in patients with mild or moderate hypertension with:


-ECG changes of MI or ischemic
-new-onset dysrhythmias
-emergence of LVH on ECG
-new onset or unstable angina
-CHF, whether established or new
-recent neurological deficit
-new onset of high-grade hypertensive retinopathy

-continue antihypertensive medications until day of operation

Postoperative Hypertension:
-systolic pressures > 200 mmHg result in bleeding from suture line, haemorrhagic cerebral infarction,
myocardial ischemic or infarction, and acute renal failure
-~ 80% of post-op HTN episodes occur within first 3 h of emergence form anaesthesia
-d/t ETT, inadequate analgesia, acute bladder distention, fluid overload
-tracheal stimulation, hypothermia, hypercapnia, hypoxemia
-if uncontrollable sodium nitroprusside or labetalol is given
-late post-op:
-d/t hypervolemia 2o fluid mobilization into intravascular space, inadequate analgesia, or failure to
resume previous antihypertensive medications

174
3

6 *% ( * 2* *

Lupus Anticoagulant Factor (Anticardiolipin Syndrome):


-antibodies that interfere with in vitro PTT by prolonging phospholipid-dependent clotting factors
-increased risk of arterial and venous thrombosis
-patients normally do not require anticoagulation therapy
-those undergoing major procedures should receive prophylactic anticoagulation therapy and mechanical
prophylaxis

Heparin-Induced Thrombocytopenia:
-form of consumptive platelet activation
-not dose dependent
-mechanism: autoantibody formation directed toward heparin and platelet surface antigens
-mild: occurs 2-4 days after heparin exposure
-severe: 6-12 days after exposure and associated with thrombosis
-arterial thrombosis common
-significant mortality rate
-phlegmasia cerulea dolens amputation rate up to 30%
-treatment: stop heparin; +/- surgical thrombectomy; Greenfield filter, anticoagulation with warfarin

1* *% 1 2 . %*

Antithrombin-III Deficiency:
-AT-III the most important inhibitor of coagulation
-inactivates thrombin, Xa, IXa, XIa, plasmin, kallikrein, XIIa
-deficiency is autosomal dominant
-recurrent thrombosis in 60%; pulmonary embolus in 40%
-treatment: heparin; if OR FFP to raise level of AT-III

Protein C Deficiency:
-Protein C: vit K-dependent inhibitor of procoagulant system
-inactivates V and VIII
-seen in 4-5% of patients < 45y with unexplained venous thrombosis
-deficiency is autosomal dominant: (CRM-: lack of protein; CRM+: dysfunctional protein)
-significant when serum activity < 70%
-treatment: warfarin

Protein S Deficiency:
-Protein S: vit K-dependent; produced by hepatocytes and megakaryocyte
-cofactor for Protein C
-significant when serum activity < 60%

!
-associated with high mortality related mainly of primary disease
-75% of pts are > 70y
-causes: poor oral hygiene, dehydration, use of anticholinergic agents, lack of oral intake
-staphylococci infection via probable transductal inoculation of parotid gland
-routes of spread for suppurative parotitis:
-downward into deep fascial planes of the neck
-backward into external auditory canal

175
-outward into skin of face

Clinical Manifestations:
-swollen tender parotid
-may progress rapidly to severe cellulitis on affected side of face and neck
-may require tracheotomy if airway compromised

Management:
-prophylaxis: adequate hydration, good oral hygiene
-start with broad spectrum Abx against staph; take C+S of pus
-surgical drainage; should not be delayed beyond 5th day

Prognosis:
-mortality approximated 20%, but his was frequently related to the patient’s basic disease

* % 3 7* 2
-small bowel normally does not manifest ileus post-op, because it continues to function throughout and after
operation
-tube feedings may start almost immediately after operation
-if inflammation or several anastomoses in small bowel 24h ileus might be experienced
-gastric ileus: 24-48h
-colonic ileus: 3-5 days
-caused by:
-surgical manipulation, inflammation, peritonitis, blood in peritonem
-blood in retroperitoneum
-hypokalemia, hypocalcemia, hyponatremia, hypomagnesaemia
-opiates and phenothiazine
-treatment:
-correct underlying disorder, if any; mostly supportive treatment
-long tube decompression
-measure serum albumin prolonged ileus in hypoalbuminemic patients
-12.5g q8-12h to raise albumin > 3.0 mg/dL often results in return of bowel function

* & %

General Considerations:
-factors that increase likelihood of anastomotic leakage:
-emergency procedures, poorly prepared patients, inadequately resuscitated patients, prolonged
intraoperative hypotension, hypothermia
-etiological factors: poor surgical technique, distal obstruction, inadequate proximal decompression

Duodenal Stump Blowout:


-disastrous complication with a high mortality
-complications: peritonitis, subhepatic abscess, pancreatitis, sepsis, establishment of an external fistula wit
fluid, and electrolyte abnormalities
-most likely to occur between 2nd and 7th POD
-adequate drainage required: incision below (R)CM and insertion of large sump catheter
-fluid and electrolyte therapy, TPN instituted

176
Intestinal Leaks and Fistulas:
Leaks: -fever, leukocytosis, unexplained ileus in absence of intestinal obstruction, complicated post-op course
-if patient is in jeopardy, sepsis uncontrolled, no effective drainage abdomen re-explored
-anastomosis must be resected and redone
-if hemodynamically unstable separation of both ends and diversion should be done
Fistula: -increased wound pain and redness/drainage on POD #4-5
-usually result from operations involving inflammatory bowel disease, cancer, or lysis of adhesions
-allow fistula to close spontaneously

Therapy of an Established Fistula:


-five phases: stabilization, identification and diagnosis, decision, operation, healing

1. Stabilization:
-resuscitation using crystalloids, RBC, and albumin
-Abx only if septic
-sump-type drain placed around skin; skin protected with Stomadheisve and ion exchange paste to keep
pH acidic and prevent activation of pancreatic enzymes that require basic pH
-TPN: 5-6% AA, 15-25% dextrose, 20% fat
-nutrition can be monitored with RBP, TBP, transferring
-enteral feeds may be attempted but they must be supplemented with TPN

2. Identification and Diagnosis:


-obtain fistulogram/sinogram
-degree of bowel continuity, size and depth of defect, presence of distal obstruction, nature of bowel
adjacent to fistula, presence of large abscess
-fistulas unlikely to close spontaneously:
-ileal, gastric, fistulas at ligament of Treitz
-total anastomotic disruption; partial disruption with adjacent abscess; lateral fistula with distal
obstruction; fistula in strictured intestine; end fistula with no distal communication
-local sepsis or systematic sepsis
-spontaneous closure usually within 5 weeks of adequate nutrition support in a patient w/o sepsis

3. Decision:
-somatostatin used to promote closure
-if short-turnover protein levels are increasing, the serum albumin concentration is approaching 3.0 g/dl,
and the patient is maintaining the albumin level without infusions of exogenous albumin, operation can
take place
-failure to maintain or increase in levels of transferring, retinol-binding protein, and thyroxin-binding
prealbumin indicative of mortality

4. Operation:
-mortality ~10-11% if operated during first 10 days or after 4 months; ~20% between 10 days and 4months
-resection and end-to-end anastomosis; protection with omentum onlay
-for duodenal fistula: vagotomy and gastrojejunostomy, feeding jejunostomy and gastrostomy, area of
fistula drained
-chronic pancreatic fistula:
-excise fistula down to pancreas, identify leak, distal pancreatectoy and splenectomy
-Roux-en-Y anastomosis can be used to provide internal drainage for the pancreatic fistula

5. Healing:
-feeding delayed 7-10 days
-difficulties eating:
-lack taste sensation: use zinc sulfate or lactate
-may be necessary to allow alcohol to induce eating

177
Colocutaneous Fistulas:
-fluid and electrolyte abnormalities and skin digestion are rare, but infectious complications are significant
-percuaneous drainage of intraabdominal abscesses and local care of wound infections
-antibiotics as indicated
-spontaneous closure likely
-persistence if sepsis, distal obstruction, anastomotic dehiscence, Crohn’s disease, or carcinoma present
-lack of spontaneous close by 5 weeks surgical repair
-resection of fistula and affected colonic segment with primary anastomosis and temporary
diversion of the fecal stream by colostomy

* ( ( % *

Dumping:
-loss of pyloric valve that normally prevents hyperosmolar material from entering duodenum and small
bowel
-d/t pyloroplasty, pyloromyotomy, gastrojejunostomy, gastric resection, Billroth I or II anastomosis
-results in release of vasoactive substances:
-serotonin, bradykinin, substance P, peptides (VIP, pancreatic polypeptide, insulin, glucagon,
neurotensin, enteroglucagon)
-results in decreased plasma volume hypotension; hypokalemia
-symptoms:
-early postprandial bloating, borborygmus, cramps, sensation of light-headedness, palpitations,
sweating, hypotension
-eating solids at meal and drinking liquids afterwards diminishes symptoms
-avoid carbohydrates which are more likely to provoke dumping
-in severe cases, long-acting octreotide may oppose some of the action of released peptides and ameliorate
the symptoms
-surgical treatments: conversion of BII to BI; 6 cm reverse loop of jejunum to slow transit of hypertonic
solution

Postvagotomy Diarrhea:
-5-20% of patients have troublesome diarrhea post-truncal vagotomy
-factors:
-dysmotility or dysfunction of small bowel motility stasis and overgrowth of bacteria,
malabsorption of fat, increased and incoordinate bile flow into small bowel
-treatment difficult:
-antibiotics have little success
-10-cm reversed jejunal loop 100 cm distal to ligament of Treitz has been advocated

Afferent Loop Syndrome:


-syndrome almost always occurs when the afferent loop is anastomosed to the greater curve after a BI
gastrectomy
-obstruction of afferent loop from adhesions, kinking, intussusception, volvulus of afferent loop, stomal
ulcer, or obstruction of the efferent limb
-duodenal secretions increases in afferent loop regurgitated into stomach
-haemorrhagic pancreatitis or perforation can occur
-symptoms:
-eating is regularly followed by RUQ epigastric distention and pain, borborygmus, and cramps
relieved by projectile vomitus of clear bile that is never mixed with food
-operation require for relief of these symptoms:
-afferent loop is anastomosed into Roux-en-Y efferent loop ~60 cm downstream to prevent reflux
of bile into stomach
-vagotomy to prevent marginal ulcer

178
Alkaline Reflux Gastritis:
-stomach sensitive to bile; eating associated with burning epigastric pain
-large amounts of bile emanating form afferent loop
-acute and chronic inflammation, evidence of decreased parietal cells, and increase in mucous-secreting
cells, and intestinalization of the gastric glands
-most effective treatment: cholestyramin and sucralfate
-if medically unmanageable: Tanner-19 procedure with vagotomy and long bile-containing loop
anastomosed 60 cm down stream

Nutritional Complications:
-fat malabsorption chronic nutritional deficiency, failure of absorption of fat-soluble vitamins, chronic
bile salt diarrhea
-iron and calcium absorbed primarily in duodenum
-after BII many pts hypocalcemic and iron-deficiency anemic
-loss of intrinsic factor monthly B12 injections required
-may require conversion of BII to BI

Recurrence of Disease:
-complications for ileostomies: ulcerative colitis 4%; Crohn’s disease 30%
-Crohn’s: granulomatous, ulcerations; peristomal fistulas
-ciprofloxacin and metronidazole should be initiated
-no point in resiting stoma recurrence will likely happen again

Stomal Necrosis and Retraction:


-necrosis or retraction superficial to fascia no immediate action required
-necrosis extends below fascia immediate laparotomy and reconstruction of stoma
-retraction below level of fascia immediate laparotomy to prevent further fecal contamination of
peritoneal cavity

Skin Complications:
-usually result of siting and inability to obtain appropriate seal around stoma
-Caraya powder, ion exchange paste, +/- nystatin powder and systemic fluconazole (if yeast) are helpful
-cellulitis requires antibiotics

Stomal Stricture:
-development of serositis in immediate postoperative period
-most common cause of stricture is necrosis or retraction, resulting in mucocutaneous separation, exposure
of the serosa, and subsequent serositis
-tx: stoma separated from skin, skin opening enlarged, new maturation performed
-if stricture at fascial level, fascial opening enlarged

Peristomal Hernias and Prolapse:


-prolapse occurs when there is vigorous peristalsis and insufficient fixation of bowel to underside of
anterior abdominal wall

4 3 4

( % * / * * * / % * *# . $
-most common metabolic complication after surgery

179
-may result in CNS damage, seizures and death
-secretion of ADH is more prolonged or more intense than after normal operative procedures
-management:
-if slight edema and [Na] ~125-130 fluid restriction is all that is required
-if CNS disturbance:
-symptoms not severe mannitol given slowly provokes diuresis of excess water secreted with
minimum of sodium; furosemide can be added
-if severe 3% saline; small increments 50-100 ml over 3-4 hours
-permanent CNS damage can occur if rapid correction of hyponatremia
-prevention: avoid overresuscitation of patients; limit free water

. %* / 1( %4* 2

Thyroid Storm:
-mortality of 10-20%
-occurs in patients with existing thyrotoxicosis that is unrecognized or uncontrolled
-any traumatic event, such as surgery, infection, or embolism, may complicate thyrotoxicosis and provoke
thyroid storm
-once hypotension supervenes, it is a preterminal event
-irreversible cardiac failure usually is the mode of death
-tx: -control of catecholamine-induced cardiac symptoms: propranolol IV 1mg/min to max of 10 mg
to control HR
-dobutamine may be necessary
-PTU 200 mg and KI 5-10 gtts given to decrease T3 and T4 release
-hydrocortisone 200 mg IV followed by 100 mg q8h diminishes thyroid hormone release

Myxedema Coma:
-pts with chronic hypothyroidism that is unrecognized or inadequately controlled; provoked by stress of
operation
-inciting factors: trauma, infection, GIB, surgery, narcotics and phenothiazine
-tx: -warming, hydration, assisted ventilation
-L-thyroxine 300-500 mg IV then 50-100 mg/d

%* // * (
-d/t suppression of pituitary-adrenal axis by previous administration of steroids or destruction or exhaustion of
adrenal glands
-in patients with carcinoma, bilateral adrenal metastasis may occur
-symptoms:
-unexplained hypotension, fever, abdominal pain, light-headedness, weakness, palpitations, mental status
changes, nausea, and vomiting
-lab findings:
-hypoglycemia, hyponatremia, occasionally hyperkalemia
-tx: -measure serum cortisol and initiate treatment
-hydrocortisone 200 mg IV
-hypotension should resolve in 1-2h if dx is correct
-400 mg hydrocortisone in divided doses over 24h should b given if hypotension not resolved

8* *
-most common cause is pre-existing liver disease
-cirrhosis, alcoholic hepatitis, fatty infiltration
-general anaesthesia should be avoided in patients with established liver dz:
-portal vein’s contribution is diminished and hepatic artery supplies at least 50% of hepatic flow

180
-splanchnic vasoconstriction of hepatic artery markedly decreases hepatic flow
-therefore, regional or epidural anaesthetic is preferred
-liver failure usually on 3rd or 5th POD
-somnolence, jaundice, u/o, ascites
-treatable reversible causes:
-hypovolemia, hypokalemia, hypomagnesaemia, GIB, constipation, remote infection
-must r/o SBP
-tx: -correct lytes, administration of neomycin, cathartic, or lactulose, and provision of nutritional support
-enteral feeds preferred:
-modified low aromatic, high branched-chain amino acid formulation
-hepatorenal syndrome type II can complicate hepatic failure; if liver does not recover post-op death

-delirium (20%), depression (9%), dementia (3%), functional psychosis (2%) of elderly post-op patients

Clinical Manifestations:
-manifestations are extremely variable
-delirium: occurs most commonly in elderly patients and those who are immobilized for long periods
-depressive reactions: pt characteristically uncooperative or recovery may be impeded by listlessness,
anorexia, and disinterest
-suicide a major risk in pts with depressive reaction
-paranoid psychotic disorder

Management:
-efforts should be directed at removing toxic causes of the acute brain syndrome, removing unnecessary
stimuli without isolating the patient, and providing psychologic or pharmacologic tranquillization
-consultation with psychiatry is indicated in the case of any acute and severe emotional disturbance

.* * * % 1* /. *
-delirium usually follows operation within 48h but may be delayed
-hyperactivity with irritability, delusions, hallucinations, restlessness, and agitation
-cause is multifactorial
-Haldol 2-15 mg PO bid or 1-5 mg IV followed by 5-10 mg/h may help agitation
-prophylactic medication with lorazepam should be administered in the perioperative period to patients with severe
alcoholic histories who are candidates for DTs

.* *
-characteristically occurs late in the post-op period
-use of SSRIs are useful

*
-very yound gan old patients are particularly vulnerable to the development of psychiatric complications after
surgical treatment

Pediatric Surgery:
-severe anxiety states may be precipitated by the shock of operation
-emotional needs must be attended to
-maturity is important and decreases post-op anxiety reactions

181
Surgery in the Aged:
-more prone to become emotionally disturbed when confronted with new situations, esp. if inadequate
comprehension and generalized feeling of insecurity

Gynecologic and Breast Surgery:


-high incidence of depression, anxiety and sexual difficulties
-contact with other mastectomy patients expedites psychologic rehabilitation
-the more the procedure antedates menopause, the greater the likelihood of associated psychologic
disturbance (ie. hysterectomy)

Cancer Surgery:
-two major threats: disease and extensive surgical treatment
-depression is related to an anticipated interference with valued activities
-tendency toward seclusion, withdrawal, and nonparticipation
-depression frequent

Cardiac Surgery:
-serious psychiatric disturbances observed with considerable frequency afte mitral valvulotomy and open-
heart surgery
-manifestations usually after initial lucid interval of 3-5 days; resolve shortly after transfer from CICU to
ward
-postoperative incapacitation and increased time on heart-lung machine are factors increasing the
likelihood of delirium ?organic brain damage from operation

Dialysis and Transplantation:


-suicide rate is 300 times greater in dialysis and transplantation patients
-uraemia, debilitating disease, and the undergoing of repeated procedures are contributing factors

182
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Indications:
1. Continuous monitoring of blood pressure
-shock, acute hypertensive crisis, use of potent vasoactive or inotropic drugs, high levels of
respiratory support, high-risk patients undergoing extensive operations, controlled hypotensive
anaesthesia, rapidly changing cardiac function
2. Frequent sampling of arterial blood
-any acute illness involving cardiovascular or respiratory dysfunction

-contraindications of specific sites of catheterization:


-severe occlusive arterial disease with distal ischemic, presence of a vascular prosthesis, and local
infection

Clinical Utility:
-observation of arterial pressure waveform may permit a qualitative assessment of cardiovascular status

Sites of Catheterization:
-radial artery:
-mean and end-diastolic radial pressures usually accurate estimates of aortic pressure
-systolic pressure often much higher than that of aorta d/t overshoot caused by resonant behaviour
of radial artery
-test collateral supply with Allen’s test (6s return of blood or less)
-axillary artery:
-long-term direct arterial pressure monitoring
-better representation of aortic pressure waveform and minimal systolic pressure overshoot
-because of extensive collateral circulation, thrombosis will not lead to compromise in distal arm
-femoral artery:
-easier localization and cannulation
-dorsalis pedis artery:
-relatively small size and overestimation of systolic pressure at this level
-superficial temporal artery:
-surgical exposure required for cannulation
-risk of cerebral embolization has been reported in infants
-brachial artery is not used often because of high complication rate:
-may lead to loss of forearm and hand if collateral flow is not sufficient

Complications:
-failure to cannulate, haematoma formation, disconnection from monitoring system with bleeding
-increased of radial artery occlusion:
-female gender, low CO states, vasoconstrictors drugs, severe PVD, small wrist circumference,
insertion by surgical cut-down, multiple puncture attempts, haematoma formation, and increased
duration of cannulation
-increased risk of infection:
-placement > 4 days, insertion by surgical cut-down, local inflammation

183
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Indications:
-secure access for fluid therapy
-drug infusions
-parenteral nutrition
-CVP monitoring
-other: aspirate air embolism, placement of cardiac pacemakers or IVC filters, hemodialysis access

-contraindications for specific sites of catheterization:


-vessel thrombosis, local infection or inflammation, distortion by trauma or previous surgery

Clinical Utility:
-CVP:
-can differentiate pericardial tamponade from hypovolemia
-tracing:
-absent a-wave: A-fib
-prominent v-wave: tricuspid insufficiency
-used to measure RAP; indirectly measures RVEDP, and estimates RVEDV
-cannot be used to assess LV function

Sites of Catheterization:
-subclavian vein:
-easiest to cannulate, but risk of PTX and inability to compress vessel if bleeding occurs
-internal jugular vein:
-lower risk of PTX; good compressibility
-risk of arterial puncture
-external jugular vein:
-high incidence of failure
-femoral vein:
-risk of infection and thrombosis continue to limit general acceptance of long-term cannulation

Complications:
-long-term: infection or thrombosis
-three types of thrombi:
-mural thrombus
-catheter thrombus
-sleeve thrombus

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Indications:
-in general, a PA catheter indicated whenever the data obtained will improve therapeutic decision making
without unnecessary risk
-see Table 12-1

Clinical Utility:
-measures directly:
- CVP, PADP, PASP, MPAP, CO, PAWP, mixed venous blood gases, continuous mixed venous
oximetry
-others:
-LAP:
-PAWP is a reliable index of LAP even in the presence of elevated pulmonary vascular

184
resistance
-if measuring in West’s Zone I or II, then PAWP may reflect alveolar pressure and not
LAP (esp. if low pulm. vasc. pressures or high PEEP)
-must be in West’s Zone III (catheter should be below LA in supine position) to
accurately measure LAP
-LVEDP:
-in absence of MV dz or premature MV closure d/t AR, LAP reflects LVEDP
-LVEDV:
-if no alterations in LV compliance, LVEDP will reflect LVEDV

-intrathoracic pressures introduces artifact that affects all intrathoracic vascular pressures:
-if respiratory insufficiency:
-“stiff” lungs do not transmit alveolar pressure as readily to pulmonary circulation
-PEEP artifact should not exceed 1 mmHg for every 5 cmH2O PEEP applied
-hypovolemic patients:
-may cause greater discrepancy higher measured PAWP than actual
-intravascular measurements should be performed at end-expiration and obtained from a calibrated
oscilloscope rather than digital display which may average artifact

-cardiac output: via thermodilution method


-CO is inversely proportional to area under thermodilution curve
-measures in reality RV CO - in the absence of intracardiac shunting, (R) and (L) CO are
equivalent

Catheter Insertion:
-mean PAWP should be lower than the MPAP and lower than or equal to the PADP

Complications:
-development of dysrhythmias (up to 50% of patients, but <1% are serious)
-RBBB seen in 3-6%, therefore need for transvenous pacemaker on standby
-coiling, looping or knotting in RV
-infections
-thromboembolism
-pulmonary artery rupture:
-more likely in elderly patients and those with hypertension
-other: thrombocytopenia, cardiac valve injuries, catheter fracture, balloon rupture

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-Cardiac output (CO)


-preload: changes in PAWP frequently are used as an estimate of changes in LV preload (preload ~
LVEDV ~ LVEDP ~ PAWP)
-afterload: SVR most commonly used measure of ventricular afterload
-methods to increase stroke volume (SV):
-increase preload by augmentation of intravascular volume
-a major increase in PAWP during infusion suggests poor ventricular compliance, exhausted
preload reserve, and increased risk of pulmonary edema with further volume loading
-if PAWP rises modestly, if CI improve, and if PAWP returns to within several mmHg of the
original value within 10 min of stopping infusion, additional fluid can be given w/o high risk of
exacerbating pulmonary venous congestion
-if inadequate tissue perfusion after volume infusion:
-increase myocardial contractility with inotropic drugs and/or ?decreasing ventricular afterload
with vasodilators

185
'" $

Lung Volumes:
-Tidal volume (VT): volume of air moved in or out of lungs in any single breath
-Vital capacity (VC): maximal expiration following a maximal inspiration
-reduced in diseases involving respiratory muscles or their neural pathways, obstructive and
restrictive ventilatory impairment, and in pts who fail to cooperate fully
-Minute volume (VE): total volume of air leaving lung each minute
-increase in VE required to maintain normal PaCO2 suggests increased dead space relative to VT or
an abnormally high CO2 production
-Dead space (VD): portion of tidal volume that does not participate in gas exchange
-the VD/VT ratio ~ 0.33-0.45 in healthy subjects
-increased in ARDS, emphysema, PE, shock with low CO, PPV with excessive PEEP
-if > 0.6, usually wearable from ventilator

Pulmonary Mechanics:
-Maximal inspiratory force: maximal pressure below atm exerted against an occluded airway
-more negative than -20-25 cmH2O used as one clinical parameter to confirm recovery from NM
block after general anaesthesia
-more negative than -30 cmH2O predict successful weaning from mechanical ventilation
-limited power in predicting weaning outcome; assess only strength without taking into account
the demands placed on respiratory muscle pump
-Compliance:
-change in volume divided by a change in pressure
-decreased values are observed with disorders of the thoracic cage or a reduction in the number of
functioning lung units (resection, bronchial intubation, PTX, atelectasis, pulmonary edema)
-Work of breathing:
-measure of the process of overcoming the elastic and frictional forces of the lung and chest wall

Blood-Gas Analysis:
-pulmonary and cardiac function must be assessed to evaluate any given set of ABGs accurately
-a decreasing PaO2 without a change in PaCO2 suggests that blood oxygenation is deteriorating
despite constant alveolar ventilation
-usually attributable to V/Q imbalance or intrapulmonary shunting
-oxyhaemoglobin dissociation curve:
-right shift: increased DPG, temperature, PCO2; decreased pH
-left shift: carboxyhemoglobinemia; decreased temperature and PCO2; increased pH
-little evidence that shifts of oxyhaemoglobin dissociation curve are clinically significant in the
majority of patients
-hypercapnia ( PaCO2):
-d/t hypoventilation (ie. CNS depression), increased CO2 production (eg. hyperthermia,
hyperthyroidism), increased physiologic dead space
-mixed venous blood:
-mixture of all blood that has traversed the capillary beds capable of extracting oxygen
-reflects total body balance between oxygen delivery and oxygen consumption of perfused tissues

Parameters Derived from Blood-Gas Analysis:


-see Table 12-3

186
Capnography:
-patients with COPD and other derangements associated with increased dead space have increased arterial
to end-tidal CO2 gradient [P(a-ET)CO2]
-PETCO2 (end-tidal CO2 gradient):
-determine proper ETT placement
-in CPR an increase from zero (circulatory arrest) provides an immediate bedside validation of the
efficacy of CPR; provides earliest evidence of successful resuscitation
-detection of increased CO2 production in malignant hyperthermia
-detection of disconnection or malfunction of anaesthesia breathing circuit

Pulse Oximetry:
-in the presence of elevated carboxyhemoglobin or methemoglobin levels, SPO2 overestimates fractional
saturation at all saturation values
-methemoglobinemia maybe induced by a large number of drugs, including local anesthetics (prilocaine,
benzocaine), NTG, phenacetin, phyenytoin, Pyridium, and sulfonamides

Continuous Mixed Venous Oximetry:


-helpful in assessment of oxygen supply-demand relationship in critically ill pts
-SVO2 (mixed venous saturation) will decrease if:
-increase in oxygen consumption; decrease in cardiac output or haemoglobin
-normal range: 0.6-0.8
-below normal range:
-increased oxygen consumption:
-fever, shivering, seizures, exercise, agitation
-decreased oxygen delivery:
-low cardiac output, anemia, arterial Hb denaturation
-above normal range:
-increase in oxygen delivery relative to consumption:
-hyperdynamic phase of sepsis, cirrhosis, peripheral left-to-right shunting,
general anaesthesia, cellular poisoning, marked arterial hyperopia
-uses:
-indicator of adequacy of oxygen supply-demand balance of perfused tissues
-may function as early warning signal of untoward events
-may improve the efficiency of the delivery of critical care by providing immediate feedback as to
the effectiveness of interventions

-Gastric tonometry has been propsed as a relatively noninvasive monitor of the adequacy of aerobic metabolism in
organs whose superficial mucosa lining is extremely vulnerable to low flow and hypoxemia and in which blood
flow is sacrificed first in both shock and the systemic inflammatory response syndrome
-intramucosal pH (pHi) is measured

Clinical Utility:
-in critically ill patients, used as predictor of organ dysfunction and mortality
-better predictor of mortality than base deficit, lactate, oxygen delivery, and oxygen consumption
-can provide metabolic end point of resuscitation

RENAL MONITORING

-kidneys are excellent monitors of the adequacy of perfusion

187
Glomerular Function Tests:
-BUN:
-affected by GFR and urea production
-may be increased in UGIB, catabolic states induced by trauma, sepsis, or steroids
-may be lowered during starvation and in advanced liver disease
-not a reliable monitor of renal function in critically ill patients
-Creatinine:
-inversely related to GFR
-not influenced by protein metabolism or the rate of fluid flow through the renal tubules
-plasma creatinine level will double with a 50% reduction in GFR (constant production of Cr)
-acute reductions are not immediately reflected, 24-72h required for equilibration to
occur
-CCr = (140-age) x weight in kg / 72 x PCr multiply by 0.85 for females

Tubular Function Tests:


-with prerenal azotemia, the tubules can appropriately reabsorb sodium and water
-in intrinsic renal failure, tubular function is markedly compromised, and the ability to reabsorb sodium and
water is impaired
-FENa appears to be the most reliable for distinguishing prerenal azotemia from acute tubular necrosis
-in an oliguric patient, a value <1% is usually d/t a prerenal cause
->2-3% tubular cause
-correct interpretation is not possible if the patient had received diuretics in the 6-12h preceding the test

Intracranial Pressure Monitoring:


-CPP = MAP - ICP
-CPP may be insufficient if ICP > 20 mmHg
-aim to keep CPP level of at least 70 mmHg
-common indication for monitoring: severe head injury
-others: subarachnoid haemorrhage, hydrocephalus, postcraniotomy, Reye’s syndrome
-methods: ventricular catheter, subarachnoid bolt, epidural bolt, fiberoptic catheter
-complications: infection, haemorrhage, malfunction, obstruction, malposition

Electrophysiologic Monitoring:
-EEG used in:
-CEA, cerebrovascular surgery, open heart surgery, epilepsy surgery, induced hypotension for a
variety of surgical procedures
-somatosensory evoked potentials:
-reflect integrity of dorsal spinal columns and sensory cortex
-useful for monitoring during resection of spinal cord tumours, spine instrumentation, CEA, and
aortic surgery
-brainstem auditory-evoked potentials:
-reflect integrity of CN VIII and auditory pathways
-monitoring for surgery in posterior fossa
-visual evoked potentials:
-monitor optic nerve and upper brainstem
-pituitary surgery

Transcranial Doppler Ultrasonography:


-used to monitor cerebral blood flow
-may detect vasospasm following spontaneous or traumatic subarachnoid haemorrhage and can help
identify hyperemic or low-flow states

188
Jugular Venous Oximetry:
-invasive method of continuously monitoring jugular venous bulb oxyhaemoglobin saturation
-provides a measure of the relationship b/n total cerebral blood flow and total cerebral oxygen consumption

Assessment of Caloric Expenditure:


-Basal energy expenditure (BEE) can be estimated with the Harris-Benedict equation
-Resting energy expenditure (REE) can be approximated form the BEE by increasing it by 10%
-must find balance:
-certain conditions (eg. trauma, burns, sepsis etc.) increases caloric requirements
-however excessive caloric administration is potentially detrimental
excess calories converted to fat CO2 production
-liver may develop fatty infiltration resulting in hepatic dysfunction

Measurements:
-the ratio of CO2 production to oxygen consumption is the respiratory quotient (RQ)
-average ~ 0.8
-monitoring oxygen consumption and CO2 production and calculating the RQ provide inferences into the
adequacy of total calories as well as the mixture of substrates:
-prolonged starvation fat metabolism: RQ ~0.6-0.7
-excessive carbohydrate administration RQ > 1.0
-no great method of measuring this all prone to errors

189
F.Ling - POS notes and points (1)

Notes and points from previous exams

Anatomy and Physiology

1. Testes does not drain into inguinal lymph nodes.


2. Intercostobrachial nerve innervates skin on inner side of upper arm.
3. Left recurrent laryngeal nerve loops around arch of aorta next to ligamentum arteriosum prior to heading
cephalad.
4. Superior laryngeal nerve provides sensation to supraglottic larynx (internal branch) and innervation to
cricothyroid muscle (external branch).
5. Recurrent laryngeal nerves provide sensation to subglottic larynx
6. Carotid sheath contains: common carotid artery, internal jugular vein, vagus nerve
7. Sympathetic chain: T1-L2
8. Anterior shoulder dislocation: axillary nerve injury (deltoid muscle)
9. Colles’ fracture numb thumb and index finger: median nerve injury
10. Injury to common peroneal nerve foot drop, deficit in tibialis anterior
11. Herniation of disc at L4-5 (L5 nerve root) loss of extensor hallucis longus and loss of sensation to dorsum
of foot
12. Contents of carpal tunnel: median nerve plus long flexor tendons
13. Horner’s Syndrome associated with injury at T1
14. Structures that traverse the parotid gland: CN VII, retromandibular vein
15. Sympathetic fibers exit the spinal cord through anterior roots
16. Decreased sensation to pain in left lower extremity right spinothalamic tract severed
17. Origin of vertebral artery: subclavian artery
18. Common association with Meckel’s diverticulum: ectopic gastric mucosa
19. Penis/clitoris supplied by pudendal artery
20. Small muscles of the hand are supplied by median and ulnar nerve
21. Cremaster muscle derived from internal oblique
22. Muscle contraction without joint movement isometric
23. Superior epigastric artery lies anterior to posterior rectus sheath and posterior to posterior rectus muscle
24. Circulation of lymph in vessels is by action of valves, muscles, gravity, intraabdominal pressure
25. Sensory supply to anterior 2/3 of tongue: V3
26. Taste to anterior 2/3 of tongue: VII
27. Sensory and taste to posterior 1/3: XI
28. Spinal cord ends at L2
29. Sigmoid colon is not a retroperitoneal structure

Anaesthesia

1. Succinylcholine contraindicated in major trauma in up to 60 days because of hyperkalemia secondary to


increased sensitivity of muscle cells to depolarising agents. Causes increased efflux of potassium out of
cells.
2. Local anaesthesia:
-all are alkaline
-toxicity decreased with epinephrine
-metabolized by liver
-CNS symptoms before cardiac (circumoral numbness, tinnitus, dysarthria, seizures)
3. Amides: lidocaine, prilocaine, etidrocaine, bupivicaine (two “i”s)
4. Esters: procaine, cocaine, tetracaine (one “i”)

190
F.Ling - POS notes and points (2)

-procaine allergy possible due to its preservatives


5. Lidocaine toxicity: 3-5mg/kg; 7mg/kg with epinephrine
-to determine amount contained, multiply % with amount in ml and add a zero
-eg. 5ml of 2% contains 100mg
6. Longest acting local anaesthetic: Tetracaine
7. Main risk of chronic exposure to inhalational agents: spontaneous abortion
8. Preferred anaesthetic agent with short duration for outpatient procedures: Propafol
9. Malignant hyperthermia:
-caused by succinylcholine and all inhalational agents (except N2O)
-earliest and most consistent sign: tachycardia and increased end-tidal CO2
-masseter muscle spasm in children
-dantrolene for treatment
10. Dantrolene: Ca release from sarcoplasmic reticulum inhibits contraction
11. Best post-op analgesia for obese patient with thoracotomy/abdominal surgery: epidural
12. ASA Classification:
I: normal
II: mild to moderate disease, not limiting activity (eg. HTN, DM)
III: severe disease limiting activity but not incapacitating (eg. heart disease that limits activity)
IV: severe disease that is life-threatening
V: moribund, little chance of survival
E: emergency surgery
13. Helium improves laminar flow
14. Ketamine: smooth muscle relaxer and bronchodilator
15. Appropriate size ETT in children = age/4 + 4
16. Safe agent to use in malignant hyperthermia: Thiopental
17. Patient given 15 mg morphine and gravol post-op, becomes somnolent and decreased RR. Best first action:
administer naloxone
18. General anaesthesia preferred for long cases
19. Patient hypotensive under anaesthesia (with spinal/epidural) after putting patient in reverse Trendelenburg:
loss of sympathetic tone
20. Long term steroid use about to have major surgery: hydrocortisone 100 mg 8h pre-op then q8h for several
days post-op
21. Elderly patient on chronic thiazide treatment for HTN going for surgery. Most important complication is
hypotension
22. Mortality from general anaesthesia in otherwise healthy patient: 1 in 100,000
23. Change in radius will result in the most significant change in flow

Pharmacology
1. Bethanacol contraindicated in CAD and bladder outlet obstruction
-negative inotrope and chronotrope
-smooth muscle constriction in bronhioles, bladder and uterus
2. Ciprofloxacin:
- theophylline levels
-s/e: n/v, diarrhea, headache, dizziness, insomnia
3. Ampicillin and amoxicillin ineffective in the presence of penicillinase
4. Penicillinase resistant: methicillin, nafcillin, oxacillin, cloxacillin
-others: clavulin, sulbactam, tazobactam, vancomycin
5. Vancomycin least likely to become resistant to bacteria producing penicillinase
6. Advantage of 3rd generation cephalosporins: better gram negative coverage and CSF penetration
7. Cephalothin (1st generation cephalosporin) most likely side effect: hypersensitivity

191
F.Ling - POS notes and points (3)

-others: phlebitis, painful IM, nephrotoxic with aminoglycoside


8. No dose adjustment needed in renal insufficiency for: erythromycin
9. Pharmacokinetic alterations in elderly patients are due to decreased renal clearance
10. Pharmacokinetic alterations in infants are due to immature hepatic function
11. Corticosteroids do not cause renal failure
12. ASA inhibits cyclooxygenase; decreases arachidonic acid to prostaglandins
13. Four year old male, 15kg post-op appendectomy; analgesia:
-morphine 0.05-0.10mg/kg: 1.5 mg IV q3-4h prn
14. Clofibrate can increase the effect of coumadin
15. Bacteriostatic antibiotics:
-erythromycin (50S)
-clindamycin (50S)
-chloramphenicol (50S)
-tetracyclin (30S)
-sulfonamides
16. Cocaine is a potent vasoconstrictor
17. Digoxin works in A-fib by slowing AV conduction
18. Barbiturate will reduce action of coumadin (by inducing cytochrome P450)
19. Acetazolamide: carbonic anhydrase inhibitor
-s/e: metabolic acidosis from HCO3 diuresis, increased excretion of Ca, K, Mg and Na; hyperglycemia,
hyperuricemia
20. Epinephrine: beta-effects at low doses, alpha-effects at high doses
21. Epinephrine from adrenal medulla; norepinephrine from sympathetic nervous system
22. Amikacin: synthetic aminoglycoside that does not develop antimicrobial resistance
23. 70 yo on methyldopa (s/e is hemolytic anemia) develops anemia with Hb 80 MCV 70. First priority is to
order Coomb’s test
24. Lasix can induce increased urine output with GFR. May be used in patients with GFR as low as 10cc/min
25. Antibiotic not associated with nephrotoxicity: erythromycin
26. Gentamicin does not cover for bacteroides
27. Gentamicin, ciprofloxacin are antipseudomonas antibiotic
28. Dilantin side effects: lymphadenopathy, rash, gingival hyperplasia
29. Anti-cholinergic effects: confusion, dilated pupils, dry mouth, anhydrosis, constipation
30. Penicillin resistance not seen in treponema pallidum
31. Least nephrotoxic aminglycoside: tobramycin
32. Antibiotics avoid in pregnancy: tetracyclin, ciprofloxacin, streptomycin
33. Antibiotics that interfere with bacterial cell wall synthesis: penicillins, cephalosporins, vancomycin
34. Cimetidine, erythomycin will increase serum dilantin by inhibiting P450

The Systemic Response to Injury

1. Mast cells are not phagocytes


2. Vasopressin can coronary vasospasm
3. Energy used for actin-myosin complex: ATP
4. NO:
-release from endothelial cells
-causes vasodilation and increased capillary permeability
-inhibition of platelet aggregation and monocyte adhesion to endothelial cells
-inhibition of smooth muscle proliferation
5. Bradykinin:
-vasodilation, increased vascular permeability, bronchospasm, pain, edema, inhibits gluconeogenesis
6. Growth hormone decreases insulin release, promotes protein synthesis, promotes mobilization of fat stores

192
F.Ling - POS notes and points (4)

7. Growth hormone during trauma: hyperglycemia


8. End product of anaerobic glycolysis: lactate
9. TXA2: vasoconstriction and platelet aggregation
10. PGI2: vasodilation and decreased platelet aggregation
11. Osteoclastic activity is responsible for bone remodelling after fracture
12. Anti-inflammatory cytokines: IL-4, 10, 13
13. Most important mediator in septic shock: TNF
14. Growth factors: promote growth of endothelium and are important mediators of inflammatory response

Fluid and Electrolyte Management of the Surgical Patient

1. Sodium deficit:
-Na = %body water x TBW(140-[Na])
-%body water = 50% female, 60% male (note previous exam may give volume of distribution of Na as
20%)
2. Plasma volume in 70kg male = 3.5L (5% body weight)
3. Blood volume is ~7% body weight (hct 40%, plasma 60% blood volume)
4. SIADH:
-hyponatremia, urine Na concentration, urine K, urine osmolality
5. Hypokalemia caused by all: lasix, hydrochlorothiazide, mannitol, ventolin
- except: metoprolol
6. Hypermagnesemia:
-hyporeflexia
-CNS: lethargy, coma, paralysis
-CVS: ECG changes and cardiac alterations similar to Ca
7. Hypomagnesemia:
-increased DTR, cardiac dysrhythmias, weakness, mental status changes, seizure
8. Patient with post-op, receiving only IV fluids: Na 112, Cl 105, K 3, BUN 12. Cause is dilutional
hyponatremia
9. Use calcium IV for cardiac effects of hyperkalemia
10. 70% of CO2 is transported in the blood as HCO3-
11. Most common cause of hypercalcemia:
-outpatient: parathyroid adenoma
-inpatient: metastatic disease (esp. breast cancer)
12. pH from 7.0 to 7.4, [H] less than half; from 7.4-7.0, [H] more than double
13. Pyloric stenosis: hypokalemic, hypochloremic, metabolic alkalosis
-signs and symptoms: projectile vomitting, non-bilous, olive mass, stomach peristalsis
14. Four year old boy with pyloric stenosis and 25% dehydration. Fluid for resuscitation: D5 0.45NS with 30
mEq Kcl at 25cc/h
15. Neonatal nutritional needs:
-90-120 kcal/kg/day
-Free H2O
-Na 3-5 mmol/kg/day
-K 2-3 mmol/kg/day
-protein 2-3.5 g/kg/day
16. When giving contrast dye, to avoid renal insufficiency: ensure patient is well hydrated
17. Ringer’s lactate: Na 130, Cl 109, Ca 3, K 4, HCO3- 28
18. Emphysema does not cause respiratory alkalosis
19. Urinary Na > 40 suggests renal cause to acute renal failure
20. Hypoaldosteronism (Addisonian crisis): everything decreased except K (will be )
21. Hyperaldosteronism: hypokalemia, hypertension, Na and H2O retention

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22. Hyperadrenalism: hypokalemia, hypervolemia, hyperglycemia, hypernatremia, hypertension but NO delayed


closure of growth plates
23. Site of action of aldosterone: distal tubule
24. Diabetes causes polyuria with increased specific gravity
25. Mannitol: increased osmotic diuresis, hyponatremia, increased serum osmolality
-does not cause cellular overhydration
26. Renal clearance: removal of a substance for blood per unit time (Cx = UcV/Px)
27. Anion gap = Na - (Cl + HCO3); non-anion gap seen in diarrhea
28. Hyperkalemia does NOT cause paralytic ileus
29. Symptomatic hyponatremia < 120 treated with hypertonic saline
30. Most likely cause of hyperosmolar diuresis is DM
31. In DI, urine is most dilute in collecting ducts
32. Renin levels decrease in primary hyperaldosteronism
33. Albumin contributes to 70% of oncotic pressure; t ½ = 18-21 days
34. Albumin contributes to anion gap
35. Excretion of acids: 1/3 titratable acids and 2/3 ammonium
36. Main action of Ca is to muscle contractility
37. Patient with advanced cancer presenting with hypercalcemia. Initial treatment: normal saline with lasix
38. Bone fractures do not cause hypercalcemia
39. Patient with hyperkalemia. Treatments: insulin and dextrose, kayexalate, Ca gluconate, Lasix
40. Propranolol does NOT lower serum potassium
41. Suggestion of ATN:
-urine Na > 40
-FeNa > 2-3%
-urine osmolality < 350
42. PTH: net effect serum Ca and serum PO4
- Ca and phosphate absorption in intestine
- Ca and PO4 excretion in kidney
- Ca and PO4 resorption in bone
43. DI:
-central: failure to secrete ADH from hypothalamus
-nephrogenic: kidney unresponsive to ADH
44. Osteomalacia bone matrix and mineralization
45. Osteopenia bone matrix and normal mineralization
46. Characteristic radiologic finding in primary hyperparathyroidism: subperiosteal resorption of bone of the
radial aspect of middle ....?
47. Increased renin does not increase ADH

Nutrition

1. Salivary amylase inactivated by low pH in the stomach (optimal pH = 7)


2. Elevated LFTs with TPN
-not associated with any other abnormalities
-usually not clinically significant
-may occur regardless of patients’ nutritional status
-possibly due to excess lipids to glucose ratio
3. TPN solution of 20% dextrose and 5% amino acids infusing at 42 cc/h (1L/d):
-Daily non-protein calories: 720 kcal (dextrose = 3.4 kcal/g)
-Daily nitrogen load: 8g (6.25g AA = 1g nitrogen)
4. Carbohydrates in TPN at rate no greater than 5mg/kg/min
5. Fat administered in TPN at no more than 2.5g/kg/min

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6. Complications of enteral feeding, except: hypoglycemia


7. Primary source of nutrition for enterocytes: glutamine
8. Arginine:
-improves wound healing
-improves macrophage function and enhances cellular immunity (antitumour)
9. Starvation:
-carbohydrates supply energy for >24h
-fat is anhydrous compared to proteins and carbohydrate stores and is more calorie dense (9.4 kcal/g)
-protein catabolism increased (10g of nitrogen per day)
10. Best/safest site for long-term TPN: subclavian vein
11. Patient on TPN with renal insufficiency. Best means to determine amount of proteins to be given: creatinine
levels
12. Best indication for TPN: severe pancreatitis
13. Free ammonia is formed from metabolism of cells in the gut; ?most derived from deamination of amino acids
in the liver
14. Patient with central line and TPN - 4 days later becomes febrile. Best initial management: draw blood culture
from line and from periphery
15. Best way to assess successful enteral feeding by ?BM <600cc/24h
16. Best time to start pre-op TPN: 2 weeks pre-op (Schwartz: 7-10days)
17. Serum creatinine is a reflection of skeletal muscle breakdown
18. Starvation does not increase metabolic rate
19. Action of lipoproteins: to carry cholesterol
20. Patient on TPN presents with Na 119, K3.5 Cl 140, BS 13. Likely situation: excessive H2O has been given
21. Best method to confirm dx of iron deficiency anemia: lack of stainable iron
22. Zinc deficiency: dermatitis, wound healing problems
23. Copper deficiency: microcytic anemia
24. Selenium deficiency: muscle pain, fatal cardiomyopathy

Hemostasis, Surgical Bleeding, and Transfusion

1. Best pre-operative screening for bleeding risk: history and physical (ie. prior bleeding problems)
2. Heparin actions:
-inhibition of antithrombin III
-increases PTT
3. Coumadin:
-vitamin K antagonist
-prevents carboxylation of factors II, VII, IX, and X (“1972")
4. Major crossmatch: mixing donor RBC with recipient serum
5. Minor crossmatch: mixing donor serum with recipient RBC
6. Patient with obstructive jaundice and hypoprothrombinemia: due to poor fat absorption (unable to absorb
vitamin K)
7. Acute DVT management: Heparin 5000u IV bolus followed by 800-1000u/h infusion
8. Most common cause of transfusion related death: Hepatitis C
9. Management of hemolytic transfusion reaction:
-most important: stop transfusion
-least important: Lasix
-others: IV hydration, alkalinization of urine, Lasix or Mannitol, Foley
10. Patient with VonWillebrand’s disease going for surgery:
-DDAVP prior to surgery
-if active bleeding, use cryoprecipitate
11. Woman with hypernephroma, on coumadin for MVP, presents with gross hematuria. 4 units PRBC given

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and she is now stable with INR 2.2, Hb 98. Next step is: give FFP
12. VonWillebrand’s disease: autosomal dominant, most common bleeding disorder (1% population), variable
expression
13. Risk of infection from donor increases with number of units transfused
14. Defect in CRF hemostasis: Quality of platelets bleeding time prolonged
15. Papaverine does not affect platelet function
16. Sickle cell disease: presence of fetal hemoglobin does not promote sickling
17. Side effects of protamine:
-hypotension (most common)
-pulmonary hypertension
-anaphylaxis, n/v
18. Most common complication of massive transfusion: dilutional thrombocytopenia/hypothermia
19. Most common coagulation defect: dilutional thrombocytopenia
20. Most common cause of asystole from massive transfusion: hypothermia
21. Most common cause of febrile transfusion reaction: WBCs in donor blood
22. Patient with hemophilia going for surgery. Need 30-60% factor VIII activity before, during and after surgery
for at least 2 weeks. Ideally for surgery, levels should be 80-100%.
23. Classical hemophilia: mild (>5% factor VIII activity); moderate (2-5%); severe (<2%)
24. Most characteristic in classical hemophilia: prolonged PTT (normal PT and bleeding time)
25. Platelet transfusion can transmit syphilis if stored at room temperature (should be stored at 4oC)
26. Albumin and plasma proteins do not transmit hepatitis and syphilis
27. Patient receiving transfusion intra-op begins bleeding from operative field and decreased urine output
-hemolytic transfusion reaction
-stop transfusion, infuse saline and mannintol/lasix etc.. (“all except: steroid”)
-check recent hemolytic reaction: urine free hemoglobin
28. Father with hemophilia: all his sons will be normal, his daughter will be carriers
29. Oral contraceptives predispose to DVTs by:
- antithrombin III levels
- protein S
- fibrinolytic activity
- coagulation factors (fibrinogen, VII, VIII, IX,X)
30. Platelets secrete:
-alpha granules: PDGF, TGF-B, IGF-1, fibronectin, fibrinogen, thrombospondin, vWF
-dense bodies: serotonin
-lysosomes: hydrolases and proteases
31. Heparin-induced thrombocytopenia:
-due to antibody formation directed towards heparin and platelet surface
-treatment: stop heparin (can use danaparoid, hirudin, or LMW heparin)
32. Post massive transfusion (48h): pCO2 40, CVP 15, pO2 50 on 100% most likely cause is pulmonary edema
33. Primary fibrinolysis: euglobin lysis time, fibrinogen, FDP
34. EACA inhibits plasminogen activation - for treatment of primary fibrinolysis
35. Factor VIII:C produced by endothelial cells (also in liver); other coagulation factors made by liver
hepatocytes
36. TTP improves with steroids and splenectomy; high success rate with plasmapheresis
37. Elevated PT in: coumadin use, extrinsic pathway defects, VII deficiency
38. DIC: diffuse bleeding, PT and PTT, fibrinogen, FDP; must treat primary cause
39. Blood volume increases with all except: hepatic venous congestion
40. Hypofibrinogenemia is associated with DIC, cancer of prostate, advance liver disease

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Surgical Infections
1. Clean contaminated operations:
-entering respiratory tract, GI, GU, gyne procedures
2. Antibiotics given 30 mins prior to incision
3. Endocarditis prophylaxis prior to GU procedure: Penicillin (Vancomycin if allergic) and Gentamicin
4. Best method to diagnose C.difficile colitis: C.difficile toxin
-tx: oral or IV metronidazole: oral vancomycin
5. Subcutaneous air NOT pathognomic for clostridial myonecrosis
6. Skin preparations:
-best for persistent effect: Chlorhexidine
-immediate reduction of bacterial counts: Alcohol
7. Shave 24 hours before surgery increases chance of wound infection
8. Tetanus:
-booster every 10 years
-2yo never vaccinated, with laceration: tetanus toxoid and TIG at different site (plus future doses)
9. Endocarditis prophylaxis required for esophagoscopy with sclerotherapy injection
10. Abscess secondary to Bacteroides fragilis, best Abx: Clindamycin
11. Parotitis: most common organinsm is Staph. aureus; best Abx is cloxacillin
12. Strep gives diffuse erythematous rash use penicillin
13. Central line infection, most likely organism: Staph. epidermidis
14. Pre-op antibiotics for inguinal hernia repair: 1st generation cephalosporin (Ancef)
15. Patient with chills and fever 6 hours after insertion of Foley catheter, first thing done: blood cultures
16. Most suitable agent to sterilize surgical instruments: glutaraldehyde
17. Rabies:
-single stranded RNA virus
-Boy bitten by neighbourhood dog, best management: quarantine dog for 10 days do not treat for rabies
-Treatment if not vaccinated: local wound management, HRIG 20IU/kg (½ in wound, ½ IM gluteal), and
vaccine (HDCV or RVA) 1.0 ml deltoid for 5 doses (days 0,3,7,14 and 28)
18. Most common etiology of CJD: corneal transplant
19. Post-splenectomy organisms: S. pneumonia, H. flu, Neisseria sp. (encapsulated organisms)
20. Punctured right index finger swollen finger: tenosynovitis
21. Most common etiology for isolated aortic regurgitation: Endocarditis
22. C-section: prophylactic antibiotics given after cord is clamped
23. Patient does not need prophylaxis for cardiac catheterization
24. Strep causes erythema with serous exudate, even with bacterial count of 103/gm tissue
25. Most likely cause of wound infection from domestic animal bite: Pasteurella multocida
26. Most likely cause of wound infection from human bite: Staph and strep; Eikenella corrodens (15%)
27. Least likely to require prophylactic antibiotics: history of rheumatic fever as child
28. Most common cause of empyema is pneumonia
29. Central line infection:
-staph epi: can use sterilized line again
-staph aureus: remove line, 48 hours w/o line, Abx for 6 weeks
30. Toxic shock syndrome staph aureus toxin
31. Most common nosocomial infection: UTI
32. Most common organism causing nosocomial pneumonia: gram negatives (pseudomonas)
33. Systemic candidiasis frequently seen in immune suppressed patients
34. Treatment of chlamydia: doxycyline
35. Pseudomembranous colitis associated with any antibiotics (esp. clindamycin, ampicillin, cephalosporins)
36. Patient with tissue expander, presents with redness and discharge from area. Management: remove expander
37. Patient had C-section, on 1st generation cephalosporin and develops temperature post-op. Additional
coverage for: ?gram-negatives vs. enterococcus

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38. Surgicele has bacteriocidal property


39. Maculopapular rash over V3 distribution treated with acyclovir
40. Bladder cancer does not increase the chance of UTI
41. Patient on TPN with episode of bacteremia. Most common source of infection: infection along outside of
catheter
42. Endotoxin released from cell wall
43. Mechanism of bacterial resistance to antibiotics is production of penicillinase, mutation..
44. Most common cause of adult bronchiectasis: childhood pulmonary infections
45. Gram positive cocci: staph aureus, staph epi, strep pyogenes, strep viridans, strep pneumonia, anaerobic strep
46. Gram negative cocci: moraxella cataralis, niesserria sp
47. Most common presenting symptom in otitis media: pain
48. Immune compromised patient with severe sepsis, best regimen: aminoglycoside and piperacillin
49. Least likely bacteria found in human bite: pseudomonas
50. Major constituent of stool bacteria: E.coli vs ?bacteroides
51. Cellulitis and lymphangitis: usual organism is streptococcus
52. Penicillin is the drug of choice for Corynebacterium and diptheria
53. Most common organism found in mouth: strep viridans
54. Health care worker with herpetic whitlow should be relieved of OR duties until lesion is healed

Infectious Disease in Surgery

1. Patient with mononucleosis like presentation in whom you suspect HIV:


-ELISA best screening test; Western blot best confirmatory test
2. Hepatitis B:
-65% of new infection will be subclinical
-10-15% will be chronic
3. Kaposi’s sarcoma:
-10% AIDS patients of those 10% will die 1% incidence of death by Kaposi’s sarcoma in AIDS
4. Best method for diagnosis pneumocystis carinii: BAL; second: lung biopsy
5. Most common infection transmitted to operating room personnel: HBV
6. Needlestick injury (risks of contracting diseases):
-HIV: 0.3% (~1/200)
-HCV: 3.3%
-HBV: 33.3%
7. HAV transmitted via fecal-oral route
8. HCV detected within 6 months of exposure
9. Best protection from contracting AIDS: universal precautions
10. HIV is least transmissible in saliva
11. CNS infections in AIDS: toxoplasmosis, CMV, herpes, cryptococcus, TB, progressive multifocal
leukoencephalopathy

Trauma
1. Basically intubate everyone with airway problems
2. Most common cause of hypotension post trauma: hypovolemia
3. Child with head injury, decision to sending patient home based on length of time he was unconscious
4. Child with poor IV access:
-percutaneous peripheral vein, saphenous vein, venous cut down
-intraosseus up to 6 years (emergency)
5. Aortic tear most commonly in decelerating injuries at the level of ligamentum arteriosum distal to left

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F.Ling - POS notes and points (10)

subclavian artery
6. 40yo male, MVA, HR 140 RR 40 deviation of trachea: 14 gauge needle to 2nd ICS followed by chest tube in
5th ICS AAL
7. Revised trauma score, Triage score and Abbreviated injury scale take all into account except: urine output
8. Hemotympanum: mostly associated with base of skull fracture
9. MVA, widened mediastinum and loss of left CVA aortogram
10. Complete tracheo-bronchial disruption presents as: Massive air leak in chest tube with no lung expansion
11. Signs of ruptured diaphragm: air fluid level in lower lung field with NG tube in lung on CXR
12. Woman 36 wks gestation involved in MVA. Abdominal pain, uterus hard tender, bleeding PV: abruption
13. Treatment of neurogenic shock does not include MAST pants
14. Management of patient with spinal cord injury. First thing to do is manage airway
15. Best time to get critical x-rays in trauma is: after primary survey
16. Pathophysiology of neurogenic shock: increased venous capacitance due to decreased peripheral resistance
17. Most common complication of CSF leak: meningitis
18. Patient with knee dislocation and absent distal pulses. After reduction, pulse returns but remains weak do
femoral angiogram
19. DPL positive except: amylase level 20IU (should be over 80IU)
-poor for assessing retroperitoneal hematoma
20. Goal of CPR: maintain cerebral perfusion
21. Carotid sheath exposed due to injury. Best managed by: primary closure
22. Know GCS scoring
23. Cephalic vein should be catheterized for hypotensive MVA patient
24. Pelvic fracture, still showing signs of hemorrhage despite volume resuscitation. Next step: apply external
fixator.
25. Chest tube drains 1200cc blood originally followed by 600cc in next 3 hours. Next step: thoracotomy
-most common source of bleeding: intercostal artery
-indications:
->1500 cc initially
->200cc/h for 4 hours
->100cc/h for 8 hours
26. Relief of symptoms immediate with aspiration of pericardial effusion
27. Spinal cord injury having intact sensation, flaccid paralysis in upper limbs and able to hold lower limbs
against gravity. Patient has: central cord injury
28. Patient with extensive facial fractures:
-fixation can be delayed until patient is more stable
-CT is best method for evaluation
29. Revised Trauma Score: GCS, RR, BP
30. Cranial nerve injury most commonly seen with intracranial injury: olfactory (I)
31. Cranial nerve injury most commonly seen with increased ICP: abducens (VI)
32. Compartment syndrome:
-most reliable sign: pain out of proportion to injury and on passive movement
-least reliable sign: absent pulses
33. Child with supracondylar fracture of humerus. Suspect Volkmann’s ischemic contracture. Confirm with:
pain on passive extension of fingers
34. Treatment for frostbite: rapid rewarming of extremities
35. Child presents with frost bite hands and feet, you should: elevate the core temperature if significantly reduced
36. Post MVA, bleeding at urethral meatus with comminuted fracture of pelvis: retrograde urethrogram
37. Common finding in IVP for trauma patient: decreased perfusino with renal contusion
38. Most sensitive indicator of pericardial tamponade is: ?pulsus paradoxus
39. The following ICP in trauma: hyperventilation, elevating HOB, loosen tight clothing around neck, mannitol
-except: steroids
40. Most common solid abdominal organ injured in blunt injury: spleen

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41. Most common viscus abdominal organ injured in blunt injury: duodenum
42. Most common organ abdominal injured in penetrating injury: liver
43. Coverage for distal 1/3 of tibia: musculocutaneous free flap

Burns
1. A man with 1st degree burns to face, 2nd degree burns to anterior thorax and abdomen, circumferential burns
to right thigh and lower leg. Body surface affected: 36%
2. STSG will have better take on contaminated surface than FTSG
3. Less contraction with FTSG, better cosmetic results (skin colour matching)
4. Respiratory complications most common cause of death in burn patients
5. Most common cause of pneumonia is via bronchoalveolar route (vs. hematogenous route)
6. Parkland formula for burns: 4cc/%burn/kg. 50% in first 8 hours and 50% in next 16 hours.
7. Patient with inhalational injury, first step in management: secure airway
8. Patient with inhalational injury, all execpt: tracheostomy
9. Unconscious patient with head injury in a house fire is most likely to have inhalational injury
10. Inhalational injury will require more fluids than calculated by Parkland formula
11. Most sensitive sign of inhalational injury: carbonaceous sputum
12. Severity of inhalational injury proportional to time of exposure, closed room
13. Most important s/e of silver sulfadiazine: leukopenia (neutropenia)
14. Alkali causes liquefaction necrosis; acids causes coagulation necrosis
15. 14 yo with 25% partial thickness burns to left side of face, chest and upper arm. Most appropriate initial
management: assessment and treatment of respiratory system
16. Patient with 3% full thickness burns secondary to molten metal in the middle of the back. Treatment of
choice: early excision and skin grafting

Wound Care and Wound Healing

1. Site of enzymes to destroy tissues during inflammation is: polymophonuclear neutrophils


2. Collagen:
-via fibroblasts
-begins depostion: 10 hours
-peak rate of synthesis: 6-7 days
-maximum content: 6 weeks (42 days); cross-linking: 6 weeks
-tensile strength:
-30% at 3 weeks
-most rapid increase in first 6 weeks
-maximum at 1-2 years - reaching only 80% of original skin strength
-rate limiting step in synthesis: hydroxylation of proline
3. Strength of incisional wound does not increase until collagen is deposited
4. Polypropyline suture:
-least reactive (amongst those listed in question)
-maintains tensile strength at 2 months (~90% one year)
5. Best property of dressing a wound: decreases disruptive physical forces
6. In musculocutaneous free-flap, skin is least sensitive to ischemia
7. Sutures provide the maximum strength of a wound at 3 days
8. Predominant cell type at 7 days: fibroblasts
9. Elastin:
-decreases with age, has elastic recoil, no effect on tensile strength, present in skin and blood vessels
-any defect of elastin in aorta dissecting aneurysm

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10. Keloids extend beyond the margins of the surgical wound; best treated by steroid injections; difficult to
distinguish microscopically from hypertrophic scars
11. Best moisture barrier: keratinocytes in epithelium
12. Effect of delayed wound healing due to radiation caused by: Damaged endothelium
13. Steroid effects:
-inhibit inflammatory response
-inhibit fibroblast proliferation
-inhibit protein synthesis in wound
-delays wound contracture
-alters t-cell function
-decreases tensile strength of closed wound
-retards epithelialization and angiogenesis
14. Chronic steroid use causes thinner dermis than normal with less collagen
15. Steroid effects can be reversed by: Vitamin A
16. Hypertrophic:
-increased water content, beta-growth factor
17. In urine, best indication of collagen breakdown: hydroxyproline
18. Donor site on thigh for STSG heals by epithelialization
19. Severity of contracture which could affect the patients function is influenced by: site and depth of the wound
20. Pyoderma gangrenosum:
-hypersensitivity vasculitis seen in Crohn’s, UC, RA, lymphoma, leukemia
-50% idiopathic
-tx: dapsone, steroid therapy and local wound care
21. Best indicator of muscle viability is bleeding after incision
22. Staples, suture and tape provide same strength to healing wound
23. Staples better than sutures when it comes to wound infection
24. Bone remodelling continues even after 6 months. Osteoclastic activity is the dominant force.
25. Regeneration can occur from cell of the following except: ?dermal papilla
26. Macrophages digests tissue within an abscess
27. Wound infection most likely to occur from normal flora of skin
28. Most important factor to prevent wound dehiscence is: surgical technique
29. Dermal papillae: basal cell layer; does not contribute to epithelialization
30. Repair of peripheral nerve, the least and last function to be retained: two point discrimination
31. Vitamin C required in hydroxylation of proline and lysine in collagen synthesis

Oncology

1. Transcription of mRNA from DNA occurs in the nucleus catalysed by RNA polymerase
2. Translation occurs on ribosomes; synthesis of protein from mRNA sequence
3. Most specific finding for malignancy histologically: mitotic figures and prominent nucleoli
4. Tumour arising from sympathetic nervous system in pediatric population: Neuroblastoma
-most common abdominal tumour in children between 2-4 years
5. Tumour associated with SIADH: small cell (oat cell) ca
6. Symptomatic malignant pericarditis: treat with intraoperative pericardial window
7. Alkylating agents: non-cell cycle specific
-cyclophosphamide, busulphan, cisplatin, dacarbazine, chlorambucil, mustard gas
8. Most serious side effect of 5FU (cell-cycle specific): myelosuppression
9. Most important side effect of bleomycin: pulmonary fibrosis
10. Most important effect of doxorubicin: cardiac toxicity
11. Vincristine (cell-cycle specific, m-phase):
-prolonged ileus, peripheral neuropathy, alopecia, mild myelosuppression, ADH effect, vesicant

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12. Cyclophosphamide:
-alkylating agent, non-cell cycle specific
-s/e: hemorrhagic cystitis, neutropenia, n/v, alopecia, infertility
13. Most likely tumour to cause hemorrhage after metastasis to brain: melanoma
14. Colon carcinoma least likely to metastasize to bone (PTBLK)
15. Aneuploidy:
-absence of normal complement of DNA
-most common genetic aberration seen in malignant cells
16. Brachytherapy gives least radiation to the skin
17. Multiple ports used in radiation therapy because it protects radiosensitive tissue
18. Molecular oxygen enhances the effects of radiation
19. Radiotherapy most dependant upon:
-adequate oxygen tension
-mitosis
-vascularity
-temperature
20. Most common neoplasm associated with Paget’s disease: Osteosarcoma
21. 35yo with previous history of radiation, has solitary asymptomatic thyroid nodule, cold on thyroid scan and
FNA consistent with thyroiditis. Next step: thyroidectomy
22. Sero-sanguinous discharge from single breast duct. Concerned about cancer.
23. Mortality from cancer in females: lung breast colorectal
24. Mortality from cancer in males: lung prostate colorectal
25. Incidence of cancer in males: prostate lung colorectal
26. Patient with lump in breast 2 cm in size, last month 3 cm in size. Next step: FNA
27. Patient with 2cm neck mass in upper cervical nodes of 2 months duration. Plan should be: examination of
aerodigestive tract first, then FNA
28. Pain control in cancer patients: use of ASA may potentiate the effect of narcotics
29. Fractionation of radiation allows normal tissue to heal between doses
30. Oncogenes: genes that, when expressed, contribute to the development of malignancy
31. Proto-oncogenes: genes found in normal tissues that, when activated may lead to transformation of the cell to
a malignant phenotype
32. Best method to perform anterior scalene lymph node biopsy: borders of dissection should include internal
jugular vein lateral, omohyoid muscle superior
33. Most common cause of SVC obstruction: small cell ca
34. Antidote to methotrexate: folinic acid (leucovorin)
35. Barrett’s esophagus: most predictive of malignancy in severe dysphagia
36. Pathological changes in radiation pneumonitis:
-1h-1day: immediate release of surfactant
-1-3 months: compensatory swelling of type II cell
->3 months: disappearance of type II cell and alveolar collapse
37. Malignant melanoma: ratio of white:black = 20:1
38. 2cm lesion on bone scan can been because of: osteoblastic activity
39. Nasopharyngeal carcinoma most commonly presents as: neck mass (60%)Changes in skin secondary to
radiation:
-end arteritis obliterans, atrophic skin changes, erythema, hyperpigmentation
40. Radiomimetic chemotherapy: alkylating agents
41. Anti-tumour agent produces its effect on tumour cells by decreasing the number of tumour cells by a constant
fraction
42. Neoadjuvant chemotherapy: chemo used prior to definitive tx (eg. surgery or radiation)
-benefits: size of tumour, determines response to chemo to predict the efficacy in an adjuvant setting
43. Lesions associated with malignant melanoma: Lentigo maligna, congenital nevus, dysplastic nevus
44. 40 year old asymptomatic, CT scan shows 2 cm adrenal mass. Most likely adenoma

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45. Pancreatic Ca:


-anatomic distribution: 70% head, 20% body, 10% tail
-LFTs: bili, ALP, sl. transaminases
-glucose intolerance
-occasional elevation of amylase, lipase
46. Prostate Ca does not metastasize to lung and brain
47. Tumours associated with increased alpha-fetoprotein: hepatocellular ca, choriocarcinoma, testicular teratoma,
endodermal yolk sac tumour of ovary
48. Alpha-fetoprotein: higher in cigarette smokers, useful in detecting recurrence of colon cancer
49. Clarke stage I melanoma with no inguinal metastasis. Management: 2 cm margins with no inguinal dissection
50. Metastatic spread to lymph nodes first to sub-capsular area
51. Rectal and anal tumour treatment: combination surgery and radiation therapy

Transplantation and Immunology

1. Apoptosis: programmed cell death (with reaction of T-cells)


2. Allograft: tissue from different individuals of same species
3. Hyperacute rejection:
-due to preformed antibodies
-characterized by PMN infiltration and complement-mediated injury to vascular endothelium
4. Acute rejection mediated by T-cells
5. Chronic rejection may be due to antibody response, cell-mediated response or combination of the two
6. T-cells: suppressor, helper and cytotoxic
7. Screening of donors for organ transplantation does NOT include Legionella
8. Variable portion of light and heavy chain confers specificity of antibody to antigen binding
9. OKT3 most antigenically specific agent in prevention of graft rejection
10. Highest immunogenicity: skin
11. HLA on chromosome 6
12. Class I antigen:
-encoded on chromosome 6
-expressed in all nucleated cells except neurons
-targets of CD8+ cells (cytotoxic cells)
13. Antigen present cells of skin: Langerhan’s cells
14. BCG: active, non-specific immunization
15. Cyclosporin:
-specific immunosuppressant
-s/e: hepatotoxic, nephrotoxic, neurotoxic, gingival hyperplasia, hypertrichosis, hypertension
-increased incidence of lymphoma, may be diabetogenic
16. CMV:
-DNA virus
-most common infection in transplant patients (esp. cardiac > renal)
17. Specific immunosuppressive effects: cyclosporin, OKT3, ALG
18. Tumours in immunosuppressed patients:
-epithelial tumours: SCC
-mesenchymal tumours: lymphoma (10-100x than general population)
19. Signs of renal transplant rejection:
-pain, fever, leucocytosis, proteinuria, hypertension, oliguria anuria, increase in graft size
20. Delayed hypersensitivity reaction:
-requires more than 5days to appear
-requires previous exposure at least once
21. Primary immunoglobuin response: IgM; secondary immunoglobulin response: IgG

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22. IgA released in aerodigestive tract and GI tract


23. Function of spleen is to produce gammaglobulins
24. Optimal immune response: B-cell, T-cell, macrophages
25. Most common cause of death in post-transplantation: infection

Surgical Complications

1. Contraindications to elective surgery: subendocardial MI one month ago (<6months)


-Goldman Index: S3 gallop, PVC > 5/min, non-sinus or PAC on last preoperative ECG, age > 70,
emergency operation, intrathoracic, intraperitoneal or aortic site, significant AS, poor general medical
condition
-highest risk for non-cardiac surgery: MI, unstable angina, CHF, arrhythmia, valvular heart disease
2. FEV1: objective means of assessing lung function pre-op
-increased risk if FEV1 <50% for thoracic procedures; <30% for other surgeries
3. Increased pulmonary complications of PaCO2 > 45 mmHg
4. Most common complication of popliteal aneurysm: Thrombosis (40%)
5. High output renal failure resolves spontaneously
6. Management of post-obstructive diuresis: replace 50% of urine output with D5W
7. A fistula in GI tract will not heal if there is 200cc/day output
8. Tracheostomy:
-1st ring: subglottic stenosis
-5th ring: tracheo-innominate fistula
9. Post-esophageal dilation esophageal rupture (pneumomediastinum, chest pain, subQ emphysema).
Management: OR for primary repair within 6 hours
10. Most common complication using cautery: cutaneous burns
11. Monopolar: more tissue injury vs bipolar
12. Venogram is gold standard in detecting DVT in lower limb
13. Insertion of IVC filter NOT indicated in streptokinase allergy
14. 6 hours post-splenectomy, patient develops fever of 39oC, most likely cause: atelectasis
15. Vertical incisions do not contribute to wound dehiscence in laparotomy
16. Post-thyroidectomy patient has acute airway compromise and swollen neck. Initial management: open the
incision and evacuate hematoma
17. Best test to assess tracheal function after repair of tracheal stenosis: Maximum expiratory flow
18. Testicular torsion presents with decreased epididymal flow on ultrasound
19. Acute onset of left testicular pain: emergent surgical exploration
20. Patient POD#4 abdominal surgery with left leg pain. Femoral pulse barely palpable, pedal pulse cannot be
felt, with leg cyanosed and pitting edema to mid-thigh: ?iliofemoral thrombosis vs femoral artery embolism
21. Patient with asthma on prednisone (20mg/day) for 10 days, if stopping drug: there would be no adverse effect
(has to be used at > 20mg/d for > 3 weeks for adrenal suppression)
22. Fat embolism:
-lipiduria, thrombocytopenia, respiratory failure, PCO2 due to hyperventilation
-symptoms usually 48-72h after insult
-radiographic finding most typically evidenced 24-48h
-most common cause of death: respiratory failure
23. Reflex sympathetic dystrophy:
-pain with emotion and temperature changes
-chronic pale and cool
-hyperhydrosis, smooth skin, ?osteoporosis
-relieved by regional sympathetic block
-mx: local heat, analgesia, physio, alpha-adrenergic blockade, sympathectomy
24. Following TAHBSO, patient found to have asymptomatic pelvic hematoma observe

204
F.Ling - POS notes and points (16)

25. Most likely finding in patient with early ARDS: refractory hypoxia
26. Most common source of bleeding from tracheostomy: inferior thyroid artery
27. Most common source of massive bleeding from tracheostomy: innominate artery
28. Damage to thoracic duct NOT seen in catheterization of right IJ
29. PE causes less than 10% infarction
30. Cause of hypoxia in PE is due to no perfusion of ventilated alveoli
31. Least sensitive method of diagnosing DVT in legs: history and physical
32. Persanten is NOT and acceptable method for DVT prophylaxis
33. Platelet inhibitors are not effective in DVT prophylaxis
34. Pathophysiology of high output renal failure: retention of BUN
35. Best method to follow glucose levels in a diabetic patient post-op: blood sugar
36. Most likely cause of hypoxia post-op in patient with known IHD: pulmonary edema (2o CHF)
37. Patient with urinary retention, foley inserted giving 1300cc urine. Patient continues to have u/o, most likely
cause: post-obstructive polyuria
38. Patient administered penicillin and develops urticaria and faints. Initial management: epinephrine

39. Most common site for DVT: calf vein (soleus and posterior tibial and peroneal veins)
40. Steroid therapy produces muscle wasting seen first in: pelvic and shoulder region (proximal muscle
weakness)
41. Contrast reaction: urticaria, hypotension, chest pain, dyspnea
42. 30 year old with bilateral hilar adenopathy and non-caseating granulomas on mediastinosopic biopsy:
sarcoidosis
43. Most likely cause of acute scrotum in 30 year old: acute epididymal orchitis
44. ATN: secondary to ischemia, septicemia, tubular toxins (myoglobin, contrast, drugs), acute pancreatitis,
prolonged hypotension
45. All can cause paralytic ileus: peritonitis, retroperitoneal hematoma, opioids, myxedema
46. Gynecomastia caused by: renal failure, liver failure, Kleinfelter’s, adrenal cortical tumours, spironolactone
47. Superficial femoral embolism, definitive treatment is embolectomy
48. Least effective drug in preparing patient with thyrotoxicosis for surgery: phenylephrine
49. Air embolism:
-100-300cc produce typical features
-IV line can be used to release air; place patient in LLD position
-hypocapnic secondary to hyperventilation
50. Pathology seen in ARDS:
-small stiff wet lungs
-atelectatic changes
-patchy diffuse hemorrhages
-alveolar infiltrates

Critical Illness and Physiologic Monitoring of the Surgical Patient

1. PCWP reflects (L) atrial pressure


2. In a patient with PE all the following are present except: PCWP
3. Post-op patient with stable SVT unresponsive to carotid massage. Best drug: adenosine adenosine
verapamil
4. Cardiogenic shock management: start dopamine infusion (old)
5. CVP most accurately taken in a ventilated patient at: End-expiration
6. Arterial embolus most likely to have originated from left atrium
7. VC = TLC - RV
8. All increase shunt fraction except: decreased flow in the bronchiolar arteries
9. Multiorgan failure: each organ involved increases mortality rate by 30%

205
F.Ling - POS notes and points (17)

10. 57yo male has infected appendectomy. Several days later he is hypotensive with SVR 600 and CVP 8, most
likely diagnosis: Septic Shock
11. Patient with massive PE and in shock. What would suggest he is a candidate for thrombolytic therapy: he
requires inotropic support
12. Brain death: absence of cerebral blood flow on cerebral angiogram
13. Coronary blood flow is determined by myocardial oxygen demand
14. Diastolic blood pressure is dependent on peripheral vascular resistance
15. Phenylephrine acts on alpha-receptors to cause vasoconstriction
16. Intra-aortic balloon pump:
- MAP, coronary blood flow, peak diastolic pressure, afterload
-contraindicated in severe aortic regurgitation, aortic stenosis, ventricular aneursym, dissection of aorta,
ventricular septal defect, recent prosthetic graft in aorta within 12 months
17. Effects of PEEP:
-prevent alveolar collapse by maintaining FRC above critical closing volume; improves lung compliance
- V/Q mismatch
- venous return CO
- afterload
- EDV
- ICP, CVP
18. Young male with disappearance of distal pulses following exercise can best be explained by: redistribution of
peripheral vascular resistance
19. GFR affected by:
-arterial oncotic pressure, interstitial oncotic pressure, AV pressure difference, renal blood flow
-except: reflux
20. Oxygen dissociation curve:
-SaO2 vs oxygen tension
-right shift: T, [H], CO2, DPG
-left shift: T, [H], CO2, DPG, carboxyhemoglobin
21. ARDS: 4 stages:
-I: hypoxia and hypocapnia
-II: hypoxia and hypercapnia
-III: x-ray changes
-IV: massive x-ray changes
22. ARDS earliest and best indicator: refractory hypoxemia
-PaO2:FiO2 < 200
23. Best method to assess capillary perfusion in a patient with shock: urine output
24. Patient developed A-fib with rapid ventricular response, most effective treatment initially:
-unstable: cardioversion
-stable: digoxin (old)
25. Interstitial pulmonary disease: FEV1, pO2, pCO2, residual volume
26. Best indicator of alveolar ventilation: pCO2
27. Starling’s law: SV relationship to EDV
28. Best treatment for mild digitalis toxicity: stop the drug
29. Cerebral auto-regulation: regulation of brain blood flow according to variation in arteriovenous pressure
30. Best non-invasive test to differentiate primary pulmonary hypertension from thromboembolic pulmonary
hypertension: radioisotope perfusion/ventilation scan
31. At sea-level, mixed venous oxygen of 40 mmHg considered normal
32. One gram of 100% saturated Hb contains 1.39 ml of O2
33. Indications for artificial ventilation:
-PO2 < 70 on oxygen mask
-PCO2 > 50
-alveolar-arterial difference 60 after 100% O2

206
F.Ling - POS notes and points (18)

-RR > 25/min


34. Absence of DTR not required for declaration of brain death
Medico-legal/Ethics
1. Surgeon NOT liable when recurrence of breast malignancy occurs when patient enters a clinical trial of
adjuvant therapy
2. Informed consent: if patient decides not to undergo an operation you have to explain the risks of his decision

Statistics

1. Power is determined by Type II error


2. Case control: best retrospective study design to determine if a given result was due to specific intervention
3. Double blind: both investigator and patient do not know who is receiving placebo or drug
4. Standard deviation:
-1 SD = 66%
-2 SD = 95%
-3 SD =99%

207
Methods of Fractionation

Conventional Fractionation:
-1.8-2.2 Gy per day for 5 days/week for 5 weeks (45-55 cGy total)

Method Fractions Dose per Total Total Acute side Late side
per day fraction treatment treatment effects effects
dose time

Hyperfractionation increased decreased increased same increased decreased

Accelerated fractionation increased same decreased decreased increased decreased

Accelerated hyperfractionation increased increased increased decreased increased increased

Hypofractionation same increased same decreased increased increased

Other fractionation schemes include hyperfractionation, hypofractionation, and accelerated fractionation. In


hyperfractionated regimens, the goal is to deliver higher tumor doses while maintaining a level of long-term tissue
damage that is clinically acceptable. The daily dose is unchanged or slightly increased while the dose per fraction is
decreased, and the overall treatment time remains constant. The œ/ß for the tumor must be greater than that of the
dose-limiting tissue.

An additional rationale for hyperfractionation is to allow radiosensitization through redistribution. The greater the
number of fractions, the greater the likelihood that the tumor will be in a sensitive phase of the cell cycle at some
time during the treatment. This strategy invariably results in more intense acute reactions when compared to
conventional treatment.

In the accelerated fractionation schemes, the dose per fraction is unchanged while the daily dose is increased, and
the total time for the treatment is reduced. Three basic variations are possible.

Continuous hyperfractionated accelerated radiation therapy (CHART) is an intense schedule of treatment, where
multiple daily fractions are administered within an abbreviated period of time. An intense acute reaction develops in
most patients. This reaction usually limits the total dose.

In a concomitant boost technique, the first fraction of the day is administered in a larger volume, while the second
fraction is targeted to a reduced-boost field of treatment. The boost may be administered early in the course of
therapy or toward the end of treatment. This regimen is based upon the recognition that the treatment can induce an
accelerated repopulation of the tumor cells so that reduction of the overall treatment time results in improved
control.

Clinical trials are in progress with the goal of evaluating these various altered fractionation patterns and comparing
them to conventional treatment. Preliminary results from the recently completed randomized trial, RTOG-9003,
supports the benefit of altered fractionation over conventional treatment for head and neck cancer.

208
ANTIMICROBIAL TREATMENT GUIDELINES
FOR ACUTE BACTERIAL RHINOSINUSITIS 2004
Sinus and Allergy Health Partnership

ADULTS

Initial Therapy Clinical Bacterio- Switch therapy options (no


efficacy logic improvement or worsening
(%) efficacy after 72 hours)
(%)

Mild disease with no recent antimicrobial use (past 4-6 weeks)


Amoxicillin/clavulanate (1.75-4 g/250mg/d) 90-91 97-99

Amoxicillin (1.5-4 g/d) 87-88 91-92 Gatifloxacin, levofloxacin, moxifloxacin

Cefpodoxime proxetil 87 91 Amoxicillin/clavulanate 4g/250 mg

Cefuoxime axetil 85 87 Cetriaxone

Cefdinir 83 85 Combination Therapy

Beta-lactam allergic

TMP/SMX 83 84

Doxycycline 81 80 Gatifloxacin, levofloxacin, moxifloxacin

Azithromycin, claritromycin, erythromycin 77 73 Rifampin plus clindamycin

Telithromycin 77 73

Mild disease with recent antimicrobial use (past 4-6 weeks) or moderate disease
Gatifloxacin/levofloxacin/moxifloxacin 92 100

Amoxicillin/clavulanate (4 g/250 mg/d) 91 99 Reevaluate patient

Ceftrizxone 91 99

Combination therapy (high-dose amoixillin or clindamycin + cefixime or rifampin)

Beta-lactam allergic

Gatifloxacin/levofloxacin/moxifloxacin 92 100 Reevaluate patient

Clindamycin and rifampin

F.Ling - Antibiotic Guideline for ABRS (1)

209
CHILDREN

Initial Therapy Clinical Bacterio- Switch therapy options (no


efficacy logic improvement or worsening
(%) efficacy after 72 hours)
(%)

Mild disease with no recent antimicrobial use (past 4-6 weeks)


Amoxicillin/clavulanate (90 mg/6.4 mg/kg/d) 91-92 97-99

Amoxicillin (45-90 mg/kg/d) 86-87 90-92 Cetriaxone

Cefpodoxime proxetil 87 92 Combination Therapy

Cefuoxime axetil 85 87

Cefdinir 84 86

Beta-lactam allergic

TMP/SMX 83 84 Reevaluate patient

Azithromycin, claritromycin, erythromycin 77 73 Combination therapy

Mild disease with recent antimicrobial use (past 4-6 weeks) or moderate disease

Amoxicillin/clavulanate (90 mg/6.4 mg/kg/d) 91-92 97-99 Reevaluate patient

Ceftriaxone 91 99 Combination therapy

Beta-lactam allergic

TMP/SMX 83 84 Reevaluate patient

Azithromycin, claritromycin, erythromycin 78 76 Combination therapy (clindamycin or


TMP/SMX plus rifampin)

Clindamycin 79 78

F.Ling - Antibiotic Guideline for ABRS (2)

210
OLFACTORY FUNCTION AND DYSFUNCTION

INTRANASAL CHEMOSENSATION

-adult humans possess at least three intranasal systems:


-CN 0 - nervus terminalis
-high gonadotropin-releasing hormone content (animals)
-CN I: main olfactory system
-CN V: trigeminal somatosensory system
-also: rudimentary vomeronasal organ

ANATOMY OF THE MAIN OLFACTORY SYSTEM

-First olfactory bulb layer:


-neuroepithelium: pseudostratified columnar epithelium situated on cribriform plate and segments
of superior septum and both superior and middle turbinates
-six different cell types:
-bipolar receptor cell
-ciliated cell projects from nasal cavity to brain
-sustentacular (supporting cell)
-microvilli rather than cilia
-insulate bipolar cells and regulate composition of mucous
-deactivate odorants and assist in protecting epithelium from foreign agents
-contain xenobiotic-metabolizing enzymes
-microvillar cell
-located at epithelial surface
-function not well understood
-cells lining Bowman glands
-responsible for most of mucus adjacent to olfactory neuroepithelium
-horizontal basal cells
-globose basal cells
-have potential for giving rise to neurons and nonneural cells
-1000 different receptor genes

-Second olfactory bulb layer (glomerular layer):


-each olfactory bipolar receptor neurons makes synapse with dendrites second order neurons
(mitral and tufted cells) within a glomerulus located within the olfactory bulb
-cells within this layer decrease with age

-Third olfactory bulb layer (external plexiform layer)


-contains the cell bodies of tufted cells
-sends axons through olfactory tract

-Fourth olfactory bulb layer (mitral cell layer)


-contains cell bodes of large mitral cells
-also sends axons through olfactory tract

-granule cells: maintain synaptic contact between tufted cells and mitral cells

F.Ling - Olfactory Function and Dysfunction (1)

211
OLFACTORY DISORDERS

Terminology
-anosmia: loss of ability to smell
-hyposmia or microsmia: decreased ability to smell
-total anosmia: inability to smell all odorants on both sides of nose
-dysosmia: distorted smell perception

Causes of Olfactory Loss (Anosmia and Hyposmia)


-types:
-sensorineural loss: eg. trauma
-conductive loss: eg. nasal obstruction from polyps

-obstructive nasal and paranasal sinus disease: most common


-upper respiratory infection: second most common
-head trauma: third most common

-2/3 of causes due to prior URI, head trauma, nasal and paranasal sinus disease; usually permanent

-other causes:
-congenital:
-familial dysautonomia
-Kallmann’s syndrome
-autosomal dominant
-hypogonadotrophic
-anosmia secondary to incomplete olfactory bulb and stalk, hypothalamus, or
olfactory epithelium -
-iatrogenic: septoplasty, rhinoplasty, turbinectomy, XRT
-intranasal neoplasms
-intracranial tumours
-olfactory groove meningiomas, frontal lobe glioma, pituitary adenoma, meningioma)
-epilepsy
-psychiatric disorders
-exposure to environmental chemicals, medications
-smoke, sulfur dioxide, putrid gases, cocaine, cadmium, heavy metals, radiation,
chemotherapy

Causes of Olfactory Distortions (Dysosmia)


-usually reflect dynamic elements associated with degeneration of the olfactory epithelium
-aura-like hallucinations
-psychiatric disorder

Causes of Heightened Smell Function (Hyperosmia)


-rare
-epilepsy

Influences of Aging on Ability to Smell


-decreases with age; between ages 65-80 ~50% have decreased ability to smell
-olfactory dysfunction maybe the first sign of AD and idiopathic PD

F.Ling - Olfactory Function and Dysfunction (2)

212
CLINICAL ASSESSMENT AND PATIENT MANAGEMENT

Olfactory Testing
-reliability of a number of olfactory tests is low
-UPSIT (University of Pennsylvania Smell Identification Test)
-4 booklets containing 10 odorants a piece
-multiple choice (forced choice) with 4 response alternatives
-chance performance = 25%
-very low scores reflect avoidance, and hence recognition of the correct answer
-high reliability
-Electrophysiologic Tests:
-still experimental
-OERPs: odor event-related potentials; not reliable, non-localizing

DETECTION OF MALINGERING

-suspected if pt reports smell loss yet a clear OERP is documented

PATIENT MANAGEMENT

Conductive Olfactory Loss


-allergy management, topical and systemic corticosteroid therapy, antibiotics, surgical intervention (ie.
FESS)

Sensorineural Olfactory Loss


-metabolic and regenerative activity in olfactory epithelium induced by environmental agents
-smoking cessation will improve smoking-induced anosmia
-no treatment for presbyosmia

F.Ling - Olfactory Function and Dysfunction (3)

213
NASAL FUNCTION AND EVALUATION

THE NASAL AIRWAY

Nasal Blood Vessels


-resistance vessels
-control blood flow: arterioles and precapillary sphincter
-exchange vessels (subepithelial capillaries)
-filtration and absorption of fluid: capillaries
-allow for transport of solutes and fluids
-capacitance vessels
-blood volume: venous sinusoids, veins
-arteriovenous anastomoses
-regulate nasal blood flow by allowing blood to flow directly from the resistance vessels to the
venous sinusoids

Vasomotor Control

Sympathetic
-norepinephrine (primary neurotransmitter)
-avian pancreatic polypeptide
-neuropeptide Y

Parasympathetic
-acetylcholine (primary neurotransmitter)
-vasoactive intestinal polypeptide
-peptide histamine isoleucine

Other
-substance P
-stimulation of smooth muscle, vasodilation and stimulation of nasal secretion
-H1 and H2 histamine receptor agonist vasodilator
-leukotriene D2 vasodilator

RESPIRATION

Nasal Airway Resistance


-accounts for more than 50% of total airway resistance
-three areas of resistance

-nasal vestibule
-aka: external nasal valve
-skin-lined region beginning anteriorly at nares and extending to level of caudal end of
upper lateral cartilage
-dilator nares muscles prevents collapse from negative inspiratory pressure
-potential cause of obstruction during inspiration
-nasal valve
-aka: internal nasal valve, limen nasi
-borders: nasal septum, caudal end of upper lateral cartilage, anterior end of inferior
turbinate, nasal sill
-narrowest segment of nasal airway (50% of total nasal resistance)

F.Ling - Nasal Function and Evaluation (1)

214
-nasal cavum
-region posterior to piriform aperture
-engorgement of inferior turbinates contributes to resistance

-resistance can change with posture, disease, physiologic state and psychologic factors
-major sites for regulation of airway resistance:
-dilator nares muscles
-venous sinusoids of nasal turbinates
Nasal Cycle
-intrinsic variability of nasal airway resistance that occurs in cyclic pattern in as may as 40% of persons
-duration 2-6 hours
-positional effect:
-congestion of nasal chamber in lower position
-d/t neural response to stimulation of pressure receptors on surface of body

EVALUATION OF THE NASAL AIRWAY

History
-character of nasal obstruction:
-onset and duration
-constant vs intermittent
-unilateral (tumours, normal nasal cycle) vs bilateral
-associated mouth breathing, snoring, anosmia/hyposmia/taste disturbances, tearing (nasolacrimal
duct obstruction or allergy)
-contributing factors:
-potential toxin and allergen exposure Common Classifications of Drugs that Cause
-known drug allergies Rhinorrhea and Nasal Congestion
-medications -antihypertensives
–history of immunodeficiency, asthma, sinusitis, -psychotropic medications
otitis media, allergy, sleep disturbances, facial -oral contraceptives
trauma or surgery -chronic nasal decongestants: rhinitis
medicamentosa
-associated symptoms: -cocaine: local vasoconstriction
-allergic component (sneezing, itchy and watery -tobacco: irritates mucosa and impairs ciliary
eyes, clear rhinorrhea) clearance
-antithyroid medication
-sinus involvement (facial pain, headaches)
-aspirin: activates peripheral chemoreceptors
-acute infection (fevers, malaise, purulent or -marijuana
odorous rhinorrhea, pain)
-other head and neck symptoms:
-sore throat, postnasal drip, cough, ear complaints, halitosis, ocular pain, hoarseness

Physical Exam
-external nasal exam:
-external deformities, nasal flaring, nasal airflow
-anterior rhinoscopy:
-examine with and without topical decongestion
-quality of turbinates, nasal mucosa
-nasal septum
-osteomeatal complex obstruction
-foreign bodies, nasal masses, choanal opening
-quality of nasal secretions:
-purulent or thick (infectious)

F.Ling - Nasal Function and Evaluation (2)

215
-watery and clear (vasomotor rhinitis, allergy)
-salty and clear (CSF leak)
-H&N exam:
-facial tenderness, tonsil and adenoid hypertrophy, cobblestoned posterior pharynx, cervical
adenopathy, otologic exam

Ancillary Test
-allergy evaluation
-paranasal plain films
-CT/MRI
-biopsy of nasal mass
-ciliary biopsy and mucociliary clearance tests
-nasal secretion protein and glucose (evaluate CSF leak if suspected)
-culture and sensitivity
-pulmonary function tests
-olfactometry
-rhinomanometry: provides an objective measurement of airway resistance, largely not utilized in clinical
practice since highly time consuming, not cost effective, and inaccurate

Rhinomanometry
-used to measure pressure needed to produce airflow through nasal airway ie. resistance
-does not measure location of nasal obstruction
-anterior rhinomanometry:
-measurement of transnasal pressure at anterior end of nose
-differential pressure transducer inserted into occluded nostril, difference between atmospheric
pressure and nasal pressure = pressure difference b/n nasopharynx and air = driving pressure for
airflow through unobstructed nostril
-limitations:
-cannot be used in cases of complete occlusion of one nasal passage
-septal perforation or marked flaccidity of septum
-posterior rhinomanometry:
-air pressure in nasopharynx measured with catheter placed in mouth
-interpretation:
-two major types of nasal obstruction: mucosal hypertrophy/congestion and structural deformity
-resistance measured before and after decongestion to determine relative importance of the above
two factors
-nasal resistance greater than 0.3 Pa/cm3/s usually symptomatic
-threshold for subjective obstruction varies

Unilateral Nasal Resistance:


-high variability between individuals
-no strict limits set

Total Nasal Resistance:


-less variable - not affected by nasal cycle
-better predictor of presence of obstructive symptoms
-pts treated for nasal obstruction with septal surgery are more likely to have subjective improvement if
initial nasal resistance is greater than 0.3 Pa/cm3/s

Effect of Decongestion:
-if decongestion causes less than 35% decrease in resistance, a structural cause can be inferred
-eg. septal deformity, conchal hypertrophy, stenosis, concha bullosa

F.Ling - Nasal Function and Evaluation (3)

216
Airway Collapse:
-typical rhinomanometric finding of collapse is an asymmetric nasal pressure-flow curve
-collapse only occurs during inspiration, therefore higher inspiratory resistance c/f expiratory resistance

Acoustic Rhinometry
-noninvasive measurement of cross-sectional area of regions of nasal airway
-can help identify location of flow-limiting segments in nasal airway
-results reproducible and accurate
-graph produced of nasal cross-sectional area as function of distance
-able to find narrow segments of airway
-acoustic pulse is introduced and reflected pulse measured
-does not measure effect of narrow regions on airflow dynamics or airway resistance
-area distal to severe constriction may not be accurately estimated

-Characteristics of Rhinograms:
-initial flat tracing = nosepiece
-first depression (I notch) = nasal valve
-second trough (C notch) after a small peak = head of inferior turbinate
-upward slope (climbing W) with small peaks and troughs = posterior nasal cavity and its
increasing cross-sectional area

-region of maximum narrowing ~1.73 cm = region of nasal valve


-vasoconstriction of nasal mucosa does not markedly change this region of narrowing
-subjects with subjective feeling of near total obstruction and objective severe septal deformity
had a mean MCA of 0.3 cm3

F.Ling - Nasal Function and Evaluation (4)

217
SINUS ANATOMY AND FUNCTION

EMBRYOLOGY AND DEVELOPMENT

-4th week gestation:


-frontonasal process identified, arises over developing forebrain
-ectodermal
-contributes to nasal capsule
-9th and 10th week gestation:
-nasoturbinals:
-become Agger nasi cells
-ethmoturbinals or basal lamellae
-six ridges on lateral wall numbered anterior to posterior direction; separated by furrows
-first becomes uncinate process
-furrow between first and second becomes ethmoid infundibulum
-second becomes anterior wall of bulla ethmoidalis
-third forms attachment of middle turbinate to lateral nasal wall
-fourth forms attachment of superior turbinate
-fifth to sixth coalesce and disappear by birth
-maxilloturbinal
-becomes inferior turbinate
-inferior turbinate not related to ethmoturbinals

-chronologic sequence of development:


-maxillary (65th day) ethmoid (3rd - 4th month) frontal (4th month) sphenoid (4th month)

-maxillary and ethmoid sinuses are the only sinuses at birth which are large enough to be of
clinical significance

Maxillary sinus:
-first sinus to begin development (65th day GA)
-not evident on x-ray until 4-5 months of age fluid filled
-biphasic growth:
-first 3 years of life
-second growth acceleration between 7-12 ya pneumatization laterally
-slow expansion until 18 years
-adult dimensions: 34x33x23 mm; 15 ml

Ethmoid air cells:


-begin development in 3rd fetal month
-anterior cells as evaginations in middle meatus, then posterior cells in superior meatus
-3-4 cells at birth (most developed paranasal sinus at birth)
-not evident on x-ray until 1 ya
-reach adult dimension by 12 ya
-dimensions: 20x20x10 mm; 15 ml

Frontal sinus:
-begins development during 4th month
-visible usually after 2nd year on radiographs
-sinus invades frontal bone by 5 ya, reaching adult size in late adolescence
-dimensions: 17x28x27; 6-7ml
-4-15% of population: developmental failure of one frontal sinuses present

F.Ling - Sinus Anatomy and Function (1)

218
Sphenoid sinus:
-pneumatization begins at 3 ya
-growth to sella turcica by 7 ya
-adult size by 18 ya
-dimensions: 23x20x17 mm; 7.5 ml

ANATOMY

Ethmoidal Sinus
-lateral wall: lamina papyracea
-medial wall: functions as lateral wall of nose
-midline vertical plate of ethmoid bone:
-superior portion termed crista galli
-inferior portion termed perpendicular plate of ethmoid bone
-roof of ethmoid bone = horizontal plate: separates anterior cranial fossa from nasal cavity
-thin medial portion: cribriform plate
-thick lateral portion: fovea ethmoidalis
-lateral lamella: extremely thin lateral part of cribriform plate

-Keros classification:
-Type I: cribriform plate 1-3 mm below fovea ethmoidalis
-Type II: 4-7 mm below
-Type III: 8-16 mm below

-anterior vertical attachment of middle turbinate to horizontal plate separates cribriform plate from lateral
lamella and fovea ethmoidalis
-dissecting lateral to turbinate prevents entrance into horizontal part of cribriform plate
-presence of Keros type II or III ethmoid roof risk of entering anterior cranial fossa through
lateral lamella

-dome of ethmoid bone in horizontal plate:


-area where anterior ethmoidal artery traverses ethmoid roof
-may cause orbital hematoma if injured

-anterior cells:
-drain into ethmoid infundibulum of middle meatus
-frontal recess cells:
-most anterior cells
-0-4 cells
-form frontal sinus, supraorbital air cells
-infundibular cells:
-next most anterior
-1-7 cells
-agger nasi cells extend outside ethmoid capsule
-represent superior remnant of the first ethmoturbinal
-in close proximity to frontal recess
-often opened during FESS to get better view of nasofrontal duct
-can obstruct outflow of frontal sinus
-bullar cells
-1-6 cells
-consistent location in middle meatus

F.Ling - Sinus Anatomy and Function (2)

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-form bulla ethmoidalis
-may form suprabullar recess if anterosuperior wall of bulla does not reach ethmoid
roof
-uncinate process:
-thin semilunar piece of bone; part of ethmoid bone
-remnant of first ethmoturbinal

-middle turbinate:
-concha bullosa:
-pneumatization of middle turbinate; in 12% of population
-may result in nasal obstruction
-anterior end attaches to horizontal plate
-posterior end inserts laterally on lamina papyracea
-divides anterior from posterior ethmoid cells
-sinus lateralis or retrobullar recess: occurs if posterior wall of bulla ethmoidalis does not
contact third basal lamella

-posterior cells:
-drain into superior meatus
-Onodi cell:
-posterior ethmoid cell that can pneumatize an area of sphenoid bone superior and lateral
to sphenoidal sinus in 9-12% of population
-optic nerve and carotid artery can be exposed and injured during dissection in this area
-vasculature:
-anterior and posterior ethmoid arteries
-maxillary and ethmoid veins (cavernous sinus)
-innervation:
-anterior and posterior ethmoidal nerves (from nasociliary nerve, V1)

Maxillary Sinus
-supraorbital nerve dehiscent in 14% of population
-Haller cell:
-pneumatization of ethmoid complex into the roof to the maxillary sinus
-may occlude ostia
-1st and 2nd molars: two most dehiscent teeth in maxillary sinus (2.2% and 2.0% of persons, respectively)
-removal of teeth may result in oral-antral fistula
-accessory ostia present in 15-40% of cases
-Vasculature:
-maxillary and facial artery
-facial vein
-Innervation:
-infraorbital nerve (V2)

Frontal Sinus
-develops from anterosuperior ethmoidal cells
-frontal recess:
-medial wall: middle turbinate, uncinate process
-lateral wall: lamina papyracea
-posterior wall: anterior face of bulla ethmoidalis
-anterior wall: agger nasi cells

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-drainage pattern:
-A: UP LP (80%); drainage medial to uncinate process to middle meatus
-B: UP base of skull; drainage lateral to uncinate process to infundibulum
-C: UP middle turbinate; drainage lateral to uncinate process to infundibulum

-vasculature:
-supraorbital and supratrochlear arteries
-ophthalmic (cavernous sinus) and supraorbital (anterior facial) veins
-innervation:
-supraorbital and supratrochlear nerves (V1)
-structure of sinus variable
-anterior wall is strongest, twice as thick as posterior wall
-drainage ostium in posteromedial portion of sinus floor
-Foramina of Breschet: small venules that drain the sinus mucosa into the dural veins

Sphenoidal Sinus
-anatomical relationships of sphenoid ostium:
-face of sphenoid sinus lies 7 cm from nasal sill at 30o angle with floor of nasal cavity
-empties into sphenoethmoidal recess via small ostium
-adjacent to posterior border of nasal septum
-adjacent to posterior border of nasal septum
-0.5-4 mm in diameter
-located 10-15 mm above sinus floor or 30 degree above floor of nasal cavity
-1/3 up from choana to base of skull

-Congdon classification of pneumatization:


-Conchal (5%): posterior extent of sinus well anterior to sella turcica
-Presellar (24%): posterior wall of sphenoidal sinus reaches anterior face of sella turcica
-Postsellar (67%): sinus extends past level of sella turcica to approach pons posteriorly and allows
sell to make superior indentation in the sinus

-cavernous sinus external and lateral to sinus


-bony tubercle surrounding optic nerve dehiscent in 4% of population
-dehiscent internal carotid artery in 7%
-maxillary branch of trigeminal nerve and vidian nerve produce bulges in sphenoidal sinus in 30%
population
-vasculature:
-sphenopalatine artery

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-maxillary vein (pterygoid plexus)
-innervation:
-sphenopalatine nerve (parasympathetic fibers and V2)

Lymphatic Drainage of the nose and sinuses


-anterior 1/3 of nose submandibular nodes
-posterior 2/3 of nose and sinuses retropharyngeal nodes (Rouviere) and superior deep cervical nodes

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PHYSIOLOGY

Functions of Sinuses (theories)


-humidification of inspired air
-lightening of skull
-aids in resonance of speech
-increased surface area for olfaction
-absorption of shock to the face or skull
-regulation of intranasal pressure
-secretion of mucous to keep nasal chambers moist

Sinus Epithelium
-pseudostratified ciliated columnar epithelium
-four basic cell types:
-ciliated columnar epithelial cell:
-50-200 cilia per cell; 9+2 microtubule doublets; 10-20 beats/s
-nonciliated columnar cells:
-contain microvilli that expand surface area to improve humidification and warming of
air
-basal cell:
-may be primitive stem cell that can differentiate into other epithelial cells
-goblet cell:
-produce thick mucous after stimulation by irritating substance
-higher amount in maxillary sinus than other sinuses

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-submucosal glands: serous and mucinous glands penetrate lamina propria
-parasympathetics thick mucous
-sympathetics thin mucous
-density highest at ostia of maxillary, sphenoid, and anterior ethmoidal sinuses

Mucous Blanket
-two layers:
-sol layer:
-thin, periciliary fluid allowing cilia to be mobile
-produced by microvilli
-gel layer:
-upper layer of thick mucous (mucoglycoproteins) that supplies insertion point for tips of
the cilia
-produced by goblet cells and submucosal glands
-provides protection against low humidity and cold
-traps foreign particles and bacteria
-IgA inhibits adherence of bacteria to epithelial surface
-causes agglutination then clearance by phagocytosis
-IgG and interferon to provide antiviral role
-lactoferrin
-transports iron into bacteria antioxidant activity
-lysozyme
-secreted by serous cells

-mucociliary clearance:
-3-25 mm/min towards natural ostium
-maxillary sinus: star-shaped drainage pattern from sinus floor superiorly to ostium
-frontal sinus: medial wall of frontal recess roof lateral downward and medially toward
sinus ostium

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Review of Anatomy: Nose and Paranasal Sinuses Page 1 of 8

Nose and Paranasal Sinuses

A. External Nose

 anterior, caudal portion of nose is cartilaginous, while posteriorly and


superiorly it is bony

 Framework
 Cartilages: greater alar (lower lateral), septal, lateral nasal (upper
lateral), lesser alar, sesamoid.
 b. Bones: Nasal, maxillary, frontal

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 Musculature: Nasalis, depressor septi, procerus, dilator naris.

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 Blood supply
 External carotid
 external maxillary: lateral nasal, angular, alar, septal, external
nasal.
 Internal carotid
 ophthalmic, which gives rise to anterior ethmoid, posterior
ethmoid, and dorsal nasal vessels

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 Lymphatics: facial artery, submandibular, parotid nodal drainage.


 Nerve supply
 Sensory trigeminal
 Ophthalmic division: nasociliary, external nasal, infratrochlear.
 Maxillary division: infraorbital
 Motor facial: buccal, zygomatic branches

B. Internal Nose:

 Floor
 floor of nose is formed by hard palate
 nasal cavity extends as far back as soft palate, where posterior
choanae opens into nasopharynx.
 Roof
 roof of nose is adjacent to anterior cranial fossa
 cribriform plate contains numerous tiny perforations which transmit
sensory fibers to olfactory bulbs
 posteriorly, roof slants downward as anterior wall of sphenoid sinus.
 Lateral Walls

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 turbinates, three or sometimes four bony shelves covered by erectile


mucosa, project from lateral wall of nose
 serve to increase interior surface area of nose to facilitate heat and
water exchange.
 Inferior Meatus
 inferior to inferior turbinate. Contains orifice of nasolacrimal
duct.
 Middle Meatus
 inferior to middle turbinate. Contains semilunar hiatus, with
openings of maxillary, frontal, and anterior ethmoidal sinuses
 Superior Meatus
 drains posterior ethmoid cells
 Spheno- ethmoid recess
 orifice of sphenoid sinus

 Blood Supply
 Anterior ethmoid - to roof and anterior superior portion of septum
and lateral wall.
 Sphenopalatine - to lateral wall of nose
 Nasopalatine - supplies roof, septum, and floor
 Lateral nasal - supplies lateral nasal wall anteriorly.
 Descending palatine - supplies lateral nasal wall posteriorly.
 Pharyngeal - supplies roof posteriorly
 Posterior ethmoid - supplies septum and lateral nasal wall superiorly
 Septal - supplies septum inferiorly and floor
 Nerve supply
 Medial internal nasal - to septum, anterosuperiorly
 Lateral internal nasal - to lateral wall, anterosuperiorly
 External nasal - to skin of back of nose
 Posterior superior nasal - supplies septum and lateral wall
posteroinferiorly, to middle turbinate
 Posterior inferior nasal - to floor and inferior turbinate

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 Pharyngeal - to choana
 Anterior superior alveolar - to inferior meatus
 Infraorbital - to vestibule
 Lymphatics: drained by
 Facial venous drainage
 Retropharyngeal
 Superior deep cervical
 Submandibular

PARANASAL SINUSES

These are air- filled, mucosal- lined cavities which develop in facial and cranial
bones. spaces communicate with nasal airway. Their function is unknown but has
been subject to a great deal of speculation. They could serve to decrease weight
of skull or to function as resonators for voice. In lower animals with a more acute
sense of smell, sinuses are largely lined by olfactory epithelium. Sinuses may
have originally developed to increase available surface area for sense of smell.
Therefore, in humans, with olfaction limited to a much smaller area, sinuses may
be vestigial anachronisms.

Though their function is obscure, their medical significance is not. Sinuses


frequently become infected due to obstruction of normal drainage, and negative
pressure in a sinus can cause headache. Neoplasms which arise in sinuses can
be occult for quite a long time, so that they are usually very advanced at time of
diagnosis. There are four groups of sinuses:

A. Frontal - Paired, in frontal bone. Posterior wall is adjacent to anterior cranial


fossa. Usually asymmetrical, occasionally absent.

B. Maxillary - Paired, in maxilla. Superior wall - floor of orbit. Medial wall -


lateral wall of nose. Inferiorly related to tooth- bearing area of maxilla.

C. Ethmoid - Numerous cells in superior and lateral walls of nose, and in medial
walls of orbits.

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D. Sphenoid - Paired, in sphenoid bone. Sella turcica projects into this space.

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NASAL SEPTAL ABNORMALITIES

Most common deformity of nasal septum resulting form trauma:


-caudal deformity involving anterior cartilaginous septum
-septum displaced off maxillary crest

Complications from trauma of nasal septum:


-epistaxis
-hematoma
-dislocations of quadrangular septal cartilage

Causes of septal perforation:


-trauma
-digital trauma
-surgery (submucous resection)
-chrome inhalation septal perichondritis
-granulomatous/vasculitic disease
-cocaine

Nasal biopsy in Wegener’s Granulomatosis:


-granulomatous inflammation
-focal necrosis
-fibrinoid degeneration
-multinucleated giant cells

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NONALLERGIC RHINITIS

-nasal congestion, rhinnorhea, sneezing, itching and/or


Causes of Nonallergic Rhinitis
postnasal drainage
-nonallergic = not caused by IgE-mediated Infectious
immunopathologic events -viral
-bacterial
-rhinoscleroma
-rhinosporidiosis
CLASSIFICATION -rhinocerebral mucormycosis
Hormonal
Vasomotor
Infectious Rhinitis Nonallergic rhinitis with eosinophilia syndrome
-aka: coryza, common cold Occupational
-viral infection; spread via infected droplets Drug-induced (rhinitis medicamentosa)
-pathogens: rhinoviruses (most common, >100 types), Gustatory
Atrophic
respiratory syncytial virus, parainfluenza virus, influenza Anhidrotic Ectodermal dysplasia
virus, adenovirus
-SSx and stages:
-dry prodromal stage:
-nasal drying and irritation, low-grade fever, chills, general malaise, anorexia
-catarrhal stage:
-watery clear rhinorrhea, anosmia, congestion, lacrimation, worsening or constitutional
symptoms
-mucous stage:
-thickened rhinorrhea, improved constitutional symptoms
-may result in bacterial rhinosinusitis
-tx:
-usually self-limiting
-antibiotics for suspected bacterial infections only
-symptomatic therapy includes decongestants (topical and systemic), antihistamines, ipratropium
bromide sprays, hydration, humidification, nasal saline irrigations, analgesics, mucolytic agents

Bacterial Rhinitis
-common pathogens: pertussis, diphtheria, group A strep, chlamydia
-tx: antibiotic regimen, symptomatic therapy similar to viral rhinitis

Rhinoscleroma
-pathogen: Klebsiella rhinoscleromatis (Frisch’s bacillus)
-endemic to East Europe, North Africa, South Asia, Central and South America
-SSx and stages:
-catarrhal: persistent purulent rhinorrhea, nasal honey comb-colour crusting
-granulomatous: small, painless granulomatous nodules in upper respiratory tract (including glottis
and subglottis)
-sclerotic: lesion heals with extensive scarring (dense fibrotic narrowing of nasal passage)
-dx: biopsy and culture
-histopathology:
-Mikulicz’s cell: foamy histocytes continuing the bacteria, “moth eaten” cytoplasm
-Russell bodies: bloated plasma cells with bifringent inclusions
-pseudoepitheliomatous hyperplasia
-tx: long-term antibiotics, debridement, consider laser excision or cryotherapy

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Rhinosporidiosis
-pathogen: Rhinosporidium seebri
-endemic to Africa, Pakistan, India, Sri Lanka, spread from contaminated water
-SSx:
-friable, “strawberry” red polypoid nasal lesion
-epistaxis, obstruction
-dx: culture and biopsy
-histopathology:
-pseudoepitheliomatous hyperplasia, submucosal cyst, fungal sporangia with chitinous shells
-tx: surgical excision with cauterization of the base and oral antifungal angents, corticosteroid injections,
may consider dapsone

Hormonal Rhinitis
-causes:
-hypothyroidism (myxedema)
-elevated estrogen 2o pregnancy
-OCP
-menstrual cycle
- estrogen inhibits acetylcholinesterase ACh in parasympathetic ganglia edema, hypersecretion and
vascular engorgement of nasal mucosa
-manifests near end of first trimester and resolves after delivery
-tx: refractory to most regimens, conservative management (nasal saline irrigations, avoidance of allergens,
may consider nasal steroids), avoid decongestants (may place fetus at risk)

Vasomotor Rhinitis
-low nasal eosinophil counts and negative skin test results for allergy
-theory: abnormal functioning of parasympathetic input to turbinate and septal mucosa
-SSx:
-similar symptomatology to allergic rhinitis except with negative allergy evaluation, morning
rhinorrhea, alternating sides, pale nasal mucosa
-triggers:
-environmental conditions: cold air, high humidity, irritants
-medications: antihypertensives, antipsychotics, cocaine
-psychotropic: anxiety, stress, exercise
-diagnosis of exclusion
-tx:
-attempt to eliminate irritants and address causal factors if possible
-medical management:
-anticholinergic sprays
-corticosteroid sprays
-hypertonic saline sprays
-may consider short course of oral and topical decongestants or antihistamines
-surgical procedures:
-surface turbinate cautery
-septoplasty: removes mechanical points of irritation
-vidian neuronectomy (efficacy controversial)
-partial turbinectomy or turbinate ablation
-total turbinactomy risks atrophic rhinitis

Nonallergic Rhinitis with Eosinophilia Syndrome (NARES)


-lacks IgE-mediated immunopathologic events
-nasal smears contain eosinophil

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-symptoms of perennial rhinitis
-dx: allergic symptoms with negative allergic tests
-tx: symptomatic relief similar to allergic rhinitis (nasal corticosteroids, antihistamines, decongestants)

Occupational Rhinitis
-nasal discharge or congestion due to exposure to airborne substance at work
-allergic or non-allergic
-treatment: identification and avoidance of offending irritant

Drug-induced Rhinitis
-caused by systemic drugs
-antihypertensives most often implicated
-reserpine, guanethidine, phentolamine, methyldopa, prazosin, chlorpromazine, beta-blockers,
ACEi
-Rhinitis medicamentosa:
-from prolonged used of topical vasoconstricting agents (> 7 days)
-pathophysiology:
-causes down-regulation of alpha-adrenergic receptors “rebound effect”
-refractory vasodilation of mucosal blood vessels
-increased parasympathetic activity
-increased vascular permeability
-mucosal injury can result: loss of cilia, metaplasia, fibrosis
-may be irreversible if vagale tone becomes atonic
-treatment:
-cessation of topical vasoconstrictors
-replacement with nasal saline
-acute nasal obstruction: some administer high burst of prednisone with rapid taper to
reduce mucosal edema
-may add oral antihistamines and/or steroid sprays

Gustatory Rhinitis
-food allergy possible but rare
-alcohol has direct vasodilating effect
-spicy foods watery rhinorrhea via vagally mediated mechanism

Atrophic Rhinitis (Ozena)


-SSx:
-atrophic mucosa on septum, turbinates or lateral nasal walls wide nasal cavity
-may be associated with ozena (thick, foul smelling, dry crust)
-subjective nasal congestion and constant foul-smelling odour despite lack of objective evident of
obstruction
-sensation of nasal obstruction from decreased sensation of nasal airflow or decreased
airflow from increased nasal air turbulence
-histology:
-transformation of pseudostratified columnar epithelium into islands of keratinized squamous
epithelium
-minimal or absent glandular cells; inflammatory cells and mast cells
-smears: neutrophils, bacteria and metaplastic squamous cells with few columnar and goblet cells
-causes:
-primary form:
-may be caused by infection with Klebsiella ozaenae
-seen more in developing countries; may be due to iron or vitamin A deficiency

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-secondary causes:
-over-aggressive nasal surgery
-chronic rhinosinusitis
-granulomatous disease of the nasal cavity
-radiation
-tx:
-saline irrigations, oil based ointment impregnated nasal tampons, vitamin A and D and iron
supplements, systemic or topical antibiotics (for secondary infections), consider nasal
vestibuloplasty or periodic nostril closure for failed medical therpy

Rhinitis among Children


-common
-viral rhinitis ~6x/year in 2-6 yo
-10% of children and 20% of adolescents have allergic rhinitis
-unilateral rhinorrhea: foreign body
-caused by GERD in infants

Anhidrotic Ectodermal Dysplasia


-X-linked genetic disorder resulting in scant mucous production and atrophic rhinitis
-triad: anhidrosis, hypotrichosis, anodontia
-tx: pressure equalization tubes, saline irrigations, nasal hygiene, denture appliances

DIFFERENTIAL DIAGNOSIS
-allergic rhinitis
-rhinosinusitis
-anatomic nasal obstruction
-choanal atresia
-adenoid hypertrophy
-septal deviation, turbinate enlargement, neoplasia
-polyps (Samter syndrome: asthma, nasal polyposis, asthma)
-systemic disease:
-Wegener granulomatosis
-sarcoidosis
-relapsing polychondritis
-granulomatous obstruction: tuberculosis, leprosy, sporotrichosis, blastomycosis, histoplasmosis,
coccidiomycosis, rhinoscleroma

CLINICAL EVALUATION

History
-PMHx, medications, FHx (immunodeficiency, ciliary dyskinesia, CF)
-onset: allergic rhinitis usually before age of 20 y
-unilateral fixed obstruction: structural cause
-daytime congestion: occupational rhinitis
-cyclical: nasal cycle
-onset of symptoms with relocation: environmental factors
-hyposmia or anosmia: polyposis
-mucopurulent discharge: primary or secondary rhinosinusitis
-epistaxis: neoplasm

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Physical Examination
-otology: SOM, TM retractions from allergy-induced ETD
-nasal exam:
-“allergic salute”: transverse crease across bridge to nose
-boggy pale mucosa typical of allergic rhinitis
-hyperaemia: infection or abuse of topical decongestants
-submucosal bumpiness and crusting suggestive of granulomatous disease
-watery secretions indicative of rhinitis
-nasal endoscopy

Other Tests:
-serum IgE and serum eosinophil levels: controversial clinical use because of unexceptional sensitivity or
specificity
-nasal cytology
-eosinophil allergic etiology
-neutrophils infectious etiology

MANAGEMENT

-avoidance: cigarette smoke


-medications:

Antihistamines
-first line therapy in children with allergic rhinitis
-reduce symptoms of allergic rhinitis
-second generation H1 antagonists:
-non-sedating
-cetirizine, fexofenadine (Allegra), loratadine (Claritin), desloratadine (Aerius)
-no efficacy in management of nonallergic rhinitis
-intranasal antihistamines to relieve nasal congestion

Decongestants
-topical:
-phenylephrine, oxymetazoline, xylometazoline
-for short term use only: infectious rhinitis, ETD and acute exacerbations of allergic
rhinitis
-oral:
-pseudoephedrine, phenylephrine, phenylpropanolamine
-used alone for vasomotor rhinitis and infectious rhinitis
-used in combination with antihistamines in allergic rhinitis
-avoid in pts with hypertension, CAD, glaucoma, diabetes, urinary retention or
hyperthyroidism
-contraindicated with MAO inhibitors or TCAs

Corticosteroids
-topical:
-control congestion, rhinorrhea, itching and sneezing
-systemic absorption is ~2% but becomes rapidly metabolized
-no suppression of HPA axis
-inhibition of inflammation through inhibition of PLP A2 and subsequent release of
arachidonic acid

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-oral:
-high burst with rapid tapering no more than 2 weeks
-used mostly for polyposis

Intranasal Cromolyn Sodium


-inhibits degranulation of mast cells
-useful in management of seasonal allergic rhinitis
-not useful in management of nonallergic rhinitis

Intranasal Anticholinergics
-for parasympathetically mediated rhinitis: gustatory or vasomotor rhinitis
-also can be used in allergic rhinitis
-contraindicated in pts with narrow-angle glaucoma or those taking another anticholinergic agent

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ALLERGIC RHINOSINUSITIS

THE ALLERGIC RESPONSE

-pathophysiology:
-allergens contact nasal mucosa
-early-phase response (IgE mediated)
-occurs within 5 minutes of allergen exposure with maximum effect at 15 minutes
-cross-linking of IgE receptors on mast cells causes degranulation:
-histamine
-leukotrienes (LTC4, LTD4, LTE4)
-PGD2
-PAF
-HETE5
-cytokines
-increases local vascular permeability and proteolysis
-late phase response
-starts 5-7 h and peaks at 6-8 hours after allergen challenge
-cytokines recruit eosinophil, neutrophils and basophil

DIAGNOSIS OF ALLERGY

History and Physical Exam


-nasal: sneezing, congestion, rhinorrhea
-ocular: redness, itchiness, watery, conjunctivitis, burning
-otologic: ETD, MEE
-laryngeal: scratchiness, dry, irritated, cough
-other:
-seasonal pattern
-food hypersensitivity
-fatigue
-OE:
clear rhinorrhea, congested turbinates, periorbital puffiness, “allergic salute”, open-mouthed
breathing (“adenoid facies”), prominent pharyngeal lymphoid tissue, conjunctivitis

Adjunctive Tests
-nasal smear:
-obtained from inferior turbinate mucosa
-eosinophil (>25%) allergy
-neutrophils infection

Definitive Testing for Atopy

Skin Testing:
-scratch test: not widely used
-prick test:
-series of allergens inserted by needle into skin
-positive “wheal-and-flare” reactions compared to controls
-grading is subjective
-risk of anaphylaxis

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-intradermal testing:
-similar to prick test except allergen is placed intradermally
-more sensitive than prick test
-grading is subjective and risk of anaphylaxis
-serial dilution endpoint titration:
-quantitative
-multiple solutions with differing concentrations given intradermally to titrate to a
positive response
-time consuming process
-test results obscured by histamines

In Vitro Testing:
-radioallergosorbent test (RAST)
-antigen bound to surface of paper disc
-pts serum obtained binds to antigen
-radiolabelled anti-IgE identifies specific antigen-IgE complexes
-enzyme-linked immunosorbent assay (ELISA)
-similar to RAST except fluorescing agents are used for markers of antigen-IgE
complexes
-indications:
-equivocal skin tests results
-high risk of anaphylaxis
-skin disorders
-failed immunotherapy
-uncooperative patient
-advantages:
-highly specific, no risk of anaphylaxis, no effect from skin condition or medications
-disadvantages:
-less sensitive, requires up to 1-2 weeks for results, more expensive

MANAGEMENT OF ALLERGIC RHINITIS

Anaphylaxis
-ABCs: airway, oxygenation, IV access
-inject up to 0.3 ml of epinephrine intramuscularly
-consider dopamine for hypotension
-add diphenhydramine (Benadryl) 50 mg, dexamethasone 4 mg, and cimetidine 300 mg through IV

Level I: Avoidance, Symptomatic Relief

Prevention of Symptoms by Avoidance

Environmental Control
-pets out of primary living and sleeping areas
-clean for dust
-avoidance of smoke
-nasal saline to cleanse mucous membranes

First-line Pharmacotherapy
-OTC medications: antihistamines, decongestants, cromolyn

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Second-generation and Third-generation Antihistamines
-lipid insoluble: do not cross BBB
-loratadine
-cetirizine
-fexofenadine

Topical Glucocorticoids
-reduce local inflammation

Cromolyn:
-stabilizes mast cells preventing release of mediators in acute and late phase reactions
-effective only for prophylaxis

Level II: Management of Complicating factors


-evaluate and treat potential concurrent disorders which may mimic allergy including vasomotor rhinitis,
sinusitis, and rhinitis medicamentosa

Level III: Chronic Symptoms (Corticosteroids)


-mechanism of action:
-decreasing capillary permeability
-stabilizing lysosomal membranes
-blocking migratory inhibitory factor
-inhibits arachidonic acid metabolism
-adverse local effects:
-candidiasis
-nasal irritation
-dryness
-bleeding and crusting
-septal perforation (rare)
-adverse systemic effects:
-increased gastric acid production
-hypertension
-masks signs of infection
-sodium retention
-hypokalemia
-posterior subcapsular cataracts
-psychosis, seizures, insomnia
-menstrual irregularities
-aseptic necrosis of femoral head
-intraturbinal glucocorticoid injection:
-has been associated with blindness: reflexive vasospasms or retrograde embolization into retinal
arteries

Level IV: Immunotherapy


-last resort treatment
-criteria:
-pts with symptoms not easily controlled with pharmacotherapy
-sensitive to allergens that cannot be avoided
-symptoms that span two or more allergy seasons or are severe
-are willing to cooperate in program of immunotherapy
-disadvantages:
-patient must be reliable for multiple injections

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-requires a chronic regimen (3 years)
-risk of worsening symptoms and anaphylactic shock
-contraindications:
-pregnancy
-autoimmune disorders
-immunological compromised patients
-B-blockers (increases sensitivity to allergens)
-easily avoidable allergens
-noncompliant patients
-involves parenteral administration of antigens to stimulate formation of allergen-specific IgG-blocking
antibodies, which eventually compete with IgE antibodies for target sites on mast cells of basophil

DISORDERS ASSOCIATED WITH ALLERGIC RHINOSINUSITIS

-polyps
-sinusitis
-asthma
-otitis media
-allergic fungal sinusitis
-fungal immunotherapy has been shown to prevent recurrence and minimize dependence on
systemic glucocorticoids

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NASAL OBSTRUCTION

ANATOMY AND PHYSIOLOGY

-functions of the nose:


-airway: -conduction of environmental air into and out of respiratory system
-filtration: -mucus, vibrissa and cilia trap and remove airborne viral, bacterial and
particulate matter (usually >30 um)
-heating: -provides radiant heating of inspired air to 31-37oC
-humidification: -increases relative humidity to 95% before reaching nasopharynx
-chemosensation: -detects irritants, chemicals and temperature abnormalities
-nasal reflex: -nasal sensation may be linked to lower respiratory and vascular reflexes
-olfaction, endocrine, pheromone detection

-respiratory epithelium:
-goblet cells: -produce protective mucous layer containing salts, glycoprotein,
polysaccharides, and lysozymes
-ciliated cells: -removes wastes for digestion and excretion
-others: -stromal cells, inflammatory cells, nerves, blood vessels, arteriovenous
anastomoses, venous sinusoids

Innervation of Nasal Mucosa


-sensory:
-olfactory nerve/neuroepithelium
-at roof of nasal vault at cribriform plate, superolateral aspects of septum and medial
surfaces of superior turbinates
-trigeminal nerve
-pain, temperature and touch
-internal nasal branch of anterior ethmoid (CN V1): anterosuperior nasal cavity
-posterior ethmoid nerve (CN V1): posterior nasal cavity
-sphenopalatine nerve (CN V2): posterior and inferior nasal cavity
-superior alveolar nerves (CN V2)
-autonomic:
-regulates vascular tone, turbinate congestion and nasal secretion
-parasympathetic:
-superior salivatory nucleus nervus intermedius presynaptic fibers travel along facial
nerve GSPN deep petrosal nerve join vidian nerve sphenopalatine ganglion
-postsynaptic fibers in sphenopalatine ganglion innervate nasal mucosa
-increased vasodilator or secretomotor activity obstruction
-sympathetic:
-vasoconstrictive decongestion

Mathematical Aspects of Nasal Obstruction


-nasal airflow directly proportional to r4
-feeling of obstruction can be due to decreased air flow secondary to increased intranasal turbulence

Nasal Valve Obstruction


-medial boundary: septum
-lateral boundary: junction of distal section of upper lateral cartilage and proximal section of lateral crura
of greater alar cartilage
-inferolateral boundary: anterior head of inferior turbinate and inferior rim of piriform aperture
-valve maintains median airflow through flow resistance

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EVALUATION AND ASSESSMENT

History
-onset, duration, unilateral vs bilateral, duration, contributing factors
-rhinorrhea/epistaxis
-nasal or orbital pain
-history of middle ear disease, respiratory illness
-drug/smoke
-nasal surgery/trauma

Physical Examination
-Cottle manoeuver: widening alae with index finger and thumb restoration of nasal patency
-obstruction that resolves with decongestion caused by mucosal abnormality

Differential Diagnosis
Congenital Tumour
-neurogenic tumours -papilloma
-glioma -polyps
-encephalocele -hemangiomas
-meningocele -pyogenic granulomas
-dermoid -JNA
-choanal atresia -malignancy
-congenital cysts
-Tornwaldt cyst Endocrine
-nasolacrimal duct cyst -hypothyroidism
-teratoma -pregnancy
-diabetes
Infectious/Idiopathic
-infectious rhinitis Neurologic
-chronic sinusitis -vasomotor rhinitis
-adenoid hypertrophy
-rhinoscleroma Systemic
-tuberculosis -Wegener’s
-syphilis
Toxin/Trauma -sarcoidosis
-septal hematoma -tuberculosis
-septal deviation -fungal infection
-septal perforation -allergy
-medication side effects -cystic fibrosis
-rhinitis medicamentosa -relapsing polychondritis
-synechia
-environmental irritants
-foreign bodies
-valvular collapse

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SPECIFIC ETIOLOGIES OF NASAL OBSTRUCTION

Anatomic Abnormalities

Deviated Nasal Septum


-most common cause of nasal obstruction
-pts with unilateral septal deviation most often have nasal obstruction of contralateral side
-compensatory turbinate hypertrophy
-+/- sinusitis secondary to hypertrophic mucosa
-impingement reduces nasal airflow through turbulent resistance and can induce thickening, atrophic
mucosal changes, or crusting of the nasal mucosa

Turbinate Hypertrophy
-bony and/or mucosal
-bony hypertrophy may be long term result of prolonged hypertrophy of mucosal tissue or result of
traumatic injury to septum with associated enlargement of nasal turbinates
-50% of inspired air flows along inferior extent of inferior turbinate or between middle and inferior
turbinates
-morbidity associated with radical inferior turbinate resection: haemorrhage, ozena, atrophic rhinitis
-inferior turbinoplasty:
-conservative submucous turbinate resection
-provides 3-5 years of relief without previously mentioned sequelae
-does not address mucosal hypertrophy
-performed when inferior turbinate projects medially and obstructs nasal cavity or when
hypertrophic turbinate mucosa remains unresponsive to vigorous medical management
-chronic hyperplastic mucosal disorders (eg. vasomotor rhinitis)
-available therapy: intraturbinal injection, cryotherapy, electrocautery, laser ablation

Septal Perforation
-causes:
-septoplasty (most common cause, > 50%)
-infections (tertiary syphilis)
-trauma (nose picking)
-neoplasms
-granulomatous disease, vasculitis
-cocaine abuse
-chrome inhalation septal perichondritis
-dx: consider biopsy of granulation tissue or abnormal mucosa to evaluate for malignancy, sarcoidosis,
tuberculosis and other granulomatous diseases
-tx:
-saline irrigation
-antibiotic ointment can be used to control crusting and bleeding around perforation
-polymeric silicone button used to stop whistling
-surgical repair:
-contraindications:
-cocaine abusers
-malignancy
-granulomatous or vascular diseases
-rotation flaps from septal cartilage or bone, nasal floor and lateral nasal wall
-transposition of inferior turbinate flap

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Valvular Collapse
-nasal valve is narrowest portion of nose
-insufficient cartilage support negative pressure will cause collapse
-surgical reconstruction via open approach, can include
-internal spreader cartilage grafts
-suture repair of drooping upper lateral cartilage
-autogenous cartilage grafts to support columella
-spanning grafts or simple lateral crus onlay grafts to support lateral crura (alar batten grafts)

Choanal Atresia
-see Congenital Anomalies of the Nose

Growths and Neoplasms

Adenoidal Hypertrophy
-“adenoid facies”
-associated with improper orofacial development: dry, thin upper lip, retrognathic mandible,
narrowed maxilla, broad nasal arch, upturned nose

Nasal Polyposis
-associated with:
-Samter triad: ASA sensitivity, asthma, nasal polyposis
-cystic fibrosis (strongly suggested if polyps seen in children)
-medialization of medial maxillary sinus wall by polyps
-fungal sinus infection
-pathogenesis:
-characterized by chronic eosinophilic inflammation
-inflammatory cytokines and mediators increase polyp water retention by increasing
sodium ion uptake
-ASA believed to block COX metabolism of arachidonic acid while stimulating 5-lipooxygenase
overproduction of leukotrienes increase vascular permeability, increase mucous secretion and
bronchoconstriction
-treatment:
-medical management:
-topical corticosteroids
-decrease capillary permeability
-decrease excretion in response to cholinergic stimulation
-suppress cytokine synthesis in eosinophil, basophil and lymphocytes
-inhibit influx of eosinophil and basophil into nasal epithelium and decrease
production of inflammatory mediators arachidonic acid production
-oral corticosteroids
-used for recurrent conditions
-short high burst with rapid taper
-surgical management:
-FESS with polypectomy

Mucosal Disease
-allergic and nonallergic rhinitis

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Miscellaneous Causes of Nasal Obstruction

Septal Hematoma
-risk of vascular septal cartilage necrosis saddle nose deformity
-treatment: I+D via Killian incision through perichondrium, nasal packing, prophylactic antibiotics

Septal Abscess
-from untreated haematoma
-complications:
-septal perforation
-cavernous sinus thrombosis
-intracranial infection
-saddle nose deformity
-most common pathogen: Staphylococcus aureus

Foreign Bodies

Relapsing Polychondritis
-nasal obstruction secondary to loss of cartilaginous support in the nasal septum

Granulomatous Disease
-polymorphic reticulosis, nonhealing lethal midline granuloma, Wegener granulomatosis, rhinoscleroma,
sarcoidosis, tuberculosis
-infections: blastomycosis, coccidioidomycosis, histoplasmosis, leprosy, sporotrichosis, syphilis

Rhinoslceroma
-granulomatous stage: antibiotics (eg. streptomycin, tetracycline)
-fibrotic stage: surgical treatment: resection of fibrotic tissue and intranasal stent placement

Sarcoidosis

Tuberculosis
-intranasal infection usually involves anterior portions of turbinate and septum
-histopathology:
-caseating necrosis in center of granuloma containing epithelioid cells and multi nucleated giant
cells

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SINUS SURGERY

CALDWELL-LUC OPERATION

Indications:
-mycotic maxillary sinusitis
-multiseptate maxillary sinus mucocele
-antrochoanal polyp
-oroantral fistula closure
-revision procedures
-preparation for transantral sphenoethmoidectomy, orbital decompression, exploration of pterygomaxillary
fossa

Technique:
-nasal mucosa decongested
-superior buccogingival sulcus and lateral wall of interior meatus infiltrated with 1% lidocaine with
1:100,000 epi
-incision made from canine to second molar
-canine fossa exposed, infraorbital nerve protected
-antrum entered through canine fossa
-nasoantral window can be made in central third of inferior meatus

Complications:
-edema and ecchymosis of cheek
-infraorbital nerve dysesthesia
-oroantral fistula
-epiphora
-antral contracture due to fibrosis and bony thickening of antral walls can make revision surgery difficult

INTRANASAL ETHMOIDECTOMY WITHOUT AN ENDOSCOPE

Indications:
-nasal polyposis with hyperplastic pansinusitis
-recurrent and chronic suppurative sinusitis
-uncomplicated frontoethmoid mucopyocele
-access for intranasal sphenoethmoidectomy

Technique:
-standard nasal decongestion; eyes and medial canthal regions observed throughout procedure
-uncinectomy followed by dissection proceeding posteriorly into ethmoidal bulla
-anterior ethmoidal artery against fovea ethmoidalis and lamina papyracea are key preserved landmarks
-anterior attachment of middle turbinate is not to be disrupted to preserve the frontal recess
-middle turbinate preserved: pain and crusting appear to be more common among patients with total
resection of middle turbinate

Complications:
-retrobulbar hemorrhage
-optic nerve injury
-CSF leak
-intracranial hemorrhage
-horizontal gaze diplopia: trauma to medial rectus with subsequent fibrosis

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EXTERNAL ETHMOIDECTOMY

Indications:
-frontoethmoid mucopyocele or sinusitis with orbital involvement
-revision surgery with absent or distorted landmarks - distortion can increase risk of intranasal procedure
-CSF leak repair
-anterior skull base lesion

Technique:
-Lynch incision:
-incision beginning at inferior margin of medial aspect of eyebrow, curves down toward medial
canthus, angles acutely back on to side of dorsum of nose
-incision carried to periostium
-angular vessels secured and supraorbital bundle preserved
-periosteal elevation medially and laterally - periosteal elevation ensures integrity of medial canthal
ligament and trochlea
-anterior ethmoidal artery encountered in frontoethmoidal suture line ~24 mm posterior to anterior lacrimal
crest clipped and divided
-posterior ethmoidal artery encountered ~10 mm posterior to anterior artery and ~ 5 mm anterior to optic
foramen
-exposes: lacrimal bone, frontal process of maxilla, lamina papyracea, orbital process of frontal bone
-ethmoid entered through lacrimal fossa
-frontoethmoid suture identifies level of anterior cranial fossa
-lamina papyracea taken down to allow complete exenteration of ethmoidal cells

Complications:
-same as for intranasal ethmoidectomy
-risk of orbital injury and intracranial penetration lower with external approach
-hypertrophic scar formation, medial canthal scarring, rounding of medial canthus
-injury to lacrimal apparatus uncommon

TRANSANTRAL ETHMOIDECTOMY

Indications:
-orbital decompression

Technique:
-exposure of floor of orbit via Caldwell-Luc operation
-delicate bone at junction of posterior orbital floor and medial antral wall gently perforated with
Wilhemlminski punch, and entrance into ethmoidal sinuses carefully enlarged with fine biting forceps
-exposure of ethmoid sinus is limited to anterior cells

FRONTAL SINUS SURGERY

Frontal Sinus Trephination


-useful to relieve pain and obtain cultures for acute frontal sinusitis
-may be used as an adjunctive procedure with endoscopic sinus surgery

Lynch Procedure (frontoethmoidectomy)


-consists of removal of the frontal sinus floor, middle turbinate, and anterior ethmoids

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-risk of recurrent mucocele formation from stenosis of nasofrontal duct

Riedel Method
-removal of frontal sinus floor and anterior wall (disfiguring)
-allows for complete obliteration

Killian Method
-modification of Riedel by preserving a bridge at the supraorbital rim to reduce deformity

Lothrop Method
-creates a large drainage opening into the nasal cavity be removing bilateral anterior ethmoids, middle
turbinates and frontal septum

Osteoplastic Flap with Frontal Sinus Obliteration


-indications:
-chronic or recurrent sinusitis
-mucoceles
-frontal bone osteomyelitis
-benign tumours
-frontal sinus fractures
-orbital or intracranial complications
-technique:
-bicoronal flap for exposure
-trapdoor access to frontal sinus via periosteal and bone flap
-obtain template from a 6' Caldwell view plain film
-remove mucosa
-obliterate cavity and occlude frontonasal recess
-fat, muscle or bone

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MIDLINE NASAL MASSES

NASAL ANATOMY

-two important embryologic defects can occur in nasopharynx:


-Rathke pouch:
-remnant of invagination of ectoderm that forms anterior pituitary gland
-cysts are located high in nasopharynx near sphenovomer junction
-tumours are called craniopharyngioma
-composed of well-differentiated epithelial elements
-tx: antibiotics with marsupialization or excision for infected lesions
-nasopharyngeal bursa of Tornwaldt:
-remnant of caudal notochord
-can become infected
-tx:
-no treatment required if asymptomatic
-if infected, consider marsupialization

CONGENITAL MIDLINE MASSES

Neurogenic Tumours

Congenital Masses of Neuroectodermal Origin


Lesion Dural Trans- Furstenberg Meningitis Histologic Findings
Connection illumination Test

Glioma None No Negative No Solid mass of glial tissue with a fibrous stalk

Encephalocele Always Yes Positive Yes Ependyma-lined space that communicates with
ventricles

Dermoid Rare Rarely Negative Rare Fluctuating cyst with sinus track leading to skin

-fonticulus frontalis: unfused space between frontal bones


-prenasal space exists between nasal bones anteriorly and cartilage posteriorly
-any defect in obliteration of dural canal leaves pathway for neural tissue to extend to prenasal space

-Nasal Glioma
-60% extranasal; 30% intranasal; 15% connect to dura by fibrous stalk
-pathophysiology:
-sequestered glial tissue or “pinched-off encephaloceles” results in unencapsulated
collection of heterotrophic glial cells
-SSx:
-intranasal or extranasal firm mass
-does not become larger with crying or straining (negative Furstenburg)
-CT/MRI scan mandatory for preoperative evaluation to r/o intracranial extension
-tx: surgical excision
-small tumours:
-transnasal endoscopic resection with immediate repair of skull-base defect with
free mucosal graft, pedicled mucosal flap or conchal cartilage with fibrin glue
and nasal packing for 3 weeks
-large tumours:

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-extranasal approach
-may require neurosurgical consultation for intracranial involvement

-Encephalocele
-contains ependyma-lined space with CSF
-communicates directly with ventricles
-meningocele contains meninges
-meningoencephalocele contains meninges and brain
-meningoencephalocytocele contains meninges, brain and part of ventricular system
-clinical features:
-positive Furstenberg test: compression of jugular veins increase size of mass
-transillumination of mass
-types by location:
-occipital:
-most common
-defect occurs over occiput
-sincipital:
-defect occurs between frontal and ethmoid bones at foramen cecum
-involves frontoethmoid area and is external
-defect is anterior to crista galli in region of foramen cecum
-subtypes:
-nasofrontal (glabellar lesion)
-nasoethmoid (lateral nose)
-nasoorbital (medial orbital wall)
-basal:
-lesions are internal
-defect in floor of anterior cranial fossa between cribriform plate and clinid
process or through superior orbital fissure
-subtypes:
-transethmoidal
-transsphenoidal
-sphenoethmoidal
-sphenomaxillary

Neurofibroma
-usually associated with generalized neurofibromatosis
-excision only when tumours large enough to produce facial asymmetry, visual disturbances or severe pain

Dermoid Cyst
-entrapment of epithelial elements as dural tract resorbs
-cysts can occur anywhere from nasal tip to foramen cecum
-simple cysts: involve only skin and nasal bones
-complex cysts: extend through cribriform plate to the dura
-SSx:
-presents at birth
-forms a fistulous tract, pit or cyst on midline or off-midline of nasal dorsum or septum
-tuft of hair may protrude from pit
-dx: CT/MRI to evaluate for intracranial extension
-tx:
-meticulous excision, must excise complete tract
-craniotomy for known dural connections

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Hemangioma
-sclerosing therapy has been a mainstay of treatment

NASOPHARYNGEAL MASSES

Nasopharyngeal Cysts
-three types described:
-intra-adenoidal
-extra-adenoidal - located deep in the pharyngobasilar fascia
-branchial cleft cysts from 1st and 2nd pharyngeal pouches
-treatment: excision if infected

Nasopharyngeal Teratoma
-50% of H+N teratomas occur in the nose
-F>M ~ 6x
-hair, skin, bone, cartilage and teeth can be found in teratomas

ACQUIRED MIDLINE NASAL MASSES

Infection

Furuncle
-most common infectious lesions of nasal vestibule
-Staph aureus
-complications: septal abscess, septal chondritis, saddle-nose deformity, cavernous sinus
thrombosis
-tx: I+D; antistaphylococcal antibiotics

Septal Abscess
-caused by furuncle or trauma with resultant septal haematoma
-tx: surgical drainage; Abx
-complication: saddle nose deformity, cavernous sinus thrombosis, meningitis, septal perforation

Rhinoscleroma
-Klebsiella rhinoscleromatis
-stages:
-catarrhal: purulent rhinorrhea lasting weeks to months
-granulomatous: formation of soft nodules in the nose, pharynx, larynx and
tracheobronchial tree
-may cause progressive airway obstruction
-histology:
-Mikulicz cells: foamy histiocytes containing intracellular Klebsiella
organisms
-sclerotic: dense fibrotic narrowing of nasal passages
-treatment:
-tetracycline for 4 weeks (effective in 70% of patients)

Rhinosporidiosis
-Rhinosporidium seeberi
-public bathing inoculates nasal epithelium with colonizing fungi

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-small tumour-like masses in nose, nasopharynx and eye
-tx: surgical extirpation with cautery at base

Other Infectious Granulomatous Diseases


-leprosy
-histoplasmosis
-coccidioidomycosis
-blastomycosis
-tuberculosis

Infectious Nasal Disorders Manifesting as Midline Nasal Masses


Lesion Cause Treatment Features

Furuncle S. aureus I+D, oral antibiotics may form abscess

Septal abscess S. aureus I+D, IV antibiotics saddle-nose deformity

Rhinoscleroma Klebsiella rhinoscleromatis tetracycline -three stages


-mistaken for ozena
-rubbery granulation tissue - Hebra nose

Rhinosporidiosis Rhinosporidium seeberi amphotericin polyploid tumours causing obstruction

Leprosy Mycobacterium leprae dapsone, rifampin congestion followed by atrophy of the mucosa,
confused with atrophic rhinitis

Coccidioidomycosis Coccidioides immitis amphotericin pulmonary involvement common

Blastomycosis Blastomyces dermatitidis ketoconazole confused with squamous cell carcinoma

Tuberculosis Mycobacterium rifampin, isoniazid, ethambutol nonspecific sinusitis, ulcers, and polyps
tuberculosis common

Inflammatory

Rhinophyma
-massive hypertrophy of sebaceous glands (form of acne roascea
-associated with Demodex folliculorum
-SSx:
-begins with coarsening of nasal skin over cartilaginous portion of nose
-develops into large protuberant lobular swelling of nasal tip
-nasal obstruction
-tx:
-surgical full thickness excision (laser, cold scalpel, or dermabrasion) until normal nasal
contour
-may require STSG

Benign Lesions

Benign Tumours of Ectodermal Origin

Papilloma
-verrucous lesions cause by HPV (types 6 and 11)
-managed by surgical excision or laser ablation
-for septal keratotic papilloma, a cuff of normal mucoperichondrium should be taken with lesion

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to avoid recurrence

Inverting Papilloma
-M>F ~ 3x
-arise from lateral nasal wall
-malignant growth occurs in as many as 15% of cases
-SSx:
-unilateral obstruction, sinusitis, epistaxis, rhinorrhea, diplopia, typically presents on
lateral nasal wall (rarely on nasal septum), may be associated with a benign nasal polyp
-histopathology:
-cristae-laden senescent mitochondria
-inflammatory cells throughout epithelium
-endophytic growth of epithelium
-complications:
-malignant degeneration
-extension into sinuses, orbit, or intracranial and skull base
-treatment:
-surgical removal by medial maxillectomy via lateral rhinotomy or endoscopically
-recurrence rate of 44%, therefore multiple procedures might be required
-radiation therapy ineffective

Benign Salivary Gland Tumours


-relatively rare
-most common is pleomorphic adenoma
-tx: surgery

Benign Tumours of Neuroectodermal Origin


-schwannoma, neurofibroma, traumatic neuroma, paraganglioma

Benign Connective Tissue Tumours

Lobular Capillary Hemangioma


-granuloma gravidarum: involutes spontaneously after parturition
-often located on anterior nasal septum in area of Kiesselbach plexus
-tx: surgical excision with good prognosis for cure

Angiofibroma
-occurs exclusively among boys and men
-non-metastasizing tumour that is locally aggressive
-high risk of uncontrollable haemorrhage with biopsy
-tx:
-preoperative embolization
-surgical removal: open or endoscopic

Benign Tumours of Mesenchymal Origin


-chondroma, osteoma, bone cyst
-fibrous dysplasia:
-three forms:
-monostotic
-polyostotic
-McCune-Albright syndrome: precocious puberty, hyperpigmentation, hyperthyroidism
-conservative treatment; surgery for deforming lesions

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Benign Neoplastic Lesions Manifesting as Midline Nasal Masses
Lesion Characteristics Treatment Complications

Papilloma probable viral origin, HPV excision recurrence, septal perforation

Inverting papilloma unilateral nasal mass, confused wide excision recurrence, SCC
with simple polyp

Salivary tumour relatively rare, pleomorphic type wide excision minor gland tumours have high rate of
most common malignancy

Hemangioma congenital or acquired steroids, excision, laser therapy scarring, haemorrhage

Angiofibroma juvenile males, obstruction plus embolization, wide excision recurrence, haemorrhage, especially with
epistaxis biopsy

Malignant Lesions

Malignant Tumours of Epithelial Origin

Squamous Cell Carcinoma


-most common malignant neoplasm of sinonasal tract
-more aggressive behaviour:
-less squamoid differentiation
-higher rate of metastasis
-nasal septum and turbinate most frequent intranasal tumour sites
-exposure risk factors: nickel, chromate, flour dust, isopropyl alcohol
-tx: surgery or radiation therapy

Basal Cell Carcinoma


-most common malignant tumour of external nose and vestibule
-ulcerated nodules with raised, smooth borders
-tx: surgical excision

Intranasal Verrucous carcinoma


-rare
-HPV proposed etiologic factor
-tx: wide local excision

Malignant Salivary Gland Tumours

Adenoid Cystic Carcinoma


-most common
-“cylindroma”
-painful: neural invasion
-10-year survival rate < 10%
-tx: surgery

Mucoepidermoid Carcinoma
-rare
-manage like SCCa

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Neuroectodermal Lesions

Olfactory Neuroblastoma
-arise for olfactory tissue, possibly bipolar neurons
-lobular pattern of uniform cells surrounded by vascular stroma
-aggressive local growth with occasional metastasis to regional lymph nodes
-tx: radical surgery with chemotherapy and radiation therapy

Malignant Melanoma
-second only to SCCa
-primary endonasal site of origin is nasal septum pigmented masses
-50% recurrence rate with poor prognosis
-median survival 2 years; 5-yr survival 25%
-tx: wide local excision; lymph node dissection not usually used for N0 disease b/c low incidence
of nodal metastasis

Malignant Mesenchymal Tumours

Hemangiopericytoma
-arises from pericytes of Zimmermann (small cells external to capillary endothelial cells)
-tx: preoperative embolization and en bloc resection of tumour

Kaposi Sarcoma
-dark-brown nodules appear on skin or mucosa
-histology: capsule surrounding spindle cells with prominent nuclei
-tx: excision

Lymphoreticular Tumour
-lymphoma
-Hodgkin disease
-extramedullary plasmacytoma

Malignant Lesions Manifesting as Nasal Masses


Tissue Origin Lesion Characteristic Management

Epithelial SCC ulcerating lesion aggressive treatment

BCC ulcerated nodule, raised borders wide excision

Salivary Adenoid cystic carcinoma pain common, hematogenous metastasis poor prognosis, aggressive treatment

Mucoepidermoid carcinoma rare lesion low grade has good prognosis; high
grade has poor prognosis

Neuroectodermal Olfactory neuroblastoma pink or brown friable lesion aggressive radical surgery

Malignant melanoma nasal septum pain and swelling 50% recurrence rate

Mesenchymal Hemangiopericytoma lobulated mass, Zimmermann cells, epistaxis embolization, en block resection

Kaposi sarcoma Dark brown nodule HIV-associated Laser excision or surgery

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SINUS IMAGING

INFLAMMATORY DISEASE AND POLYPOSIS

Acute Sinusitis
-thickening of sinus mucosa alone is specific for neither
acute nor chronic inflammatory change
-presence of an air-fluid level if there has been no
recent antral lavage suggests acute inflammation

Chronic Sinusitis
-long-standing chronic inflammatory disease can
produce osteitic changes of sinus walls that result in
bony thickening
-bone erosion can occur with chronic inflammatory
disease and often is associated with polyposis
-erosion into retromaxillary space is extremely unusual
and suggests presence of neoplasia or a mucocele

Clinical Significance of Mucosal Thickening


-presence of incidental abnormalities of the ethmoidal sinuses when there is no history of allergic or
inflammatory sinusitis is significant
-if pt does not have symptoms, such findings have no adverse consequences
-when sphenoidal sinusitis is identified on an imaging study, risk of optic complications should be
considered

CONSIDERATIONS FOR ENDOSCOPIC SINUS SURGERY

-osteomeatal complex, sphenoethmoidal recess, and frontal recess become prime areas of interest
-complete or partial obstruction of these outlets causes inflammatory changes in associated sinus
cavities
-anatomic variations that can contribute to disease:
-concha bullosa cell
-septal deviation and spur
-lateral convexity of middle turbinate (paradoxical turbinate)
-pneumatization and inversion of uncinate plate
-prominent agger nasi cell
-prominent ethmoidal bulla and Haller cell

GRANULOMATOUS SINUSITIS

-infectious: actinomycosis, nocardiosis, blastomycosis, tuberculosis, syphilis, rhinoscleroma, and


leprosy
-noninfectious: Wegener granulomatosis, sarcoidosis, foreign-body reactions from beryllium, chromate
salts and cocaine
-potentially destructive and can erode both cartilage and bone
-perforation of cartilaginous nasal septum is the hallmark of this group of disorders
-destruction of bony septum and sinus walls occurs later as disease progresses

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FUNGAL SINUSITIS

-entities:
-invasive fungal sinusitis in immunosuppressed pt
-associated with mucormycosis or aspergillosis
-acute, fulminant destructive disease marked by vascular invasion and necrosis
-chronic indolent sinusitis
-in pt with normal immune function
-tissue-invasive infection, typically unilateral and not responsive to antibiotics
-mycetoma
-noninvasive fungal ball that causes complete or near-complete opacification of a sinus
cavity
-organisms: Aspergillus fumigatus, Pseudallescheria boydii, Alternaria
-CT:
-can be associated with thickening of sinus walls
-usually hyperdense and contains calcifications in 25% of cases
-MRI:
-hypointense on MRI (T1and T2)
-allergic fungal sinusitis
-pt with heightened immune function or atopy
-hypersensitivity reaction to fungal antigens
-CT:
-involved sinus contains peripheral
rim of low density
-edematous mucosa and complete
opacification of central cavity by
homogeneous high-attenuation
material corresponding to thick
allergic mucin
-often scattered flecks of calcific
material
-sinus walls can be surprisingly
expanded and destroyed
-MRI T2:
-mucin is extremely hypointense,
mimicking an aerated sinus cavity

RETENTION CYSTS

-common and occur with chronic inflammatory sinus disease


-mucous cysts from as result of mucous gland obstruction
-incidental finding in 10% of instances

POLYPOSIS

-smoothly rounded or pedunculated soft-tissue masses


-multiple, packed polyps can exert pressure on adjacent bony structures and enlarge involved cavity
-intersinus septation fairly well preserved
-polyps: low density on CT scans, hypointense on T1 and hyperintense on T2
-secretions: hyperdense on CT, hyperintense on T1, hypointense on T2

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MUCOCELE

-occur as obstructive complications of chronic sinus inflammation, polyposis, trauma, surgery, or tumour
-CT: mucocele contents have low density and do not enhance
-MRI: intensity characteristics vary with protein content of mucocele and degree of hydration

NEOPLASTIC DISEASE

-malignant disease of nose and paranasal sinuses account for less than 1% of all malignant lesions in the
body and 3% of all H+N tumours
-MRI particularly useful, because nearly 95% of all sinonasal tumours are low to intermediate in signal
intensity during T2-weighted sequence

Benign tumours of soft-tissue origin


-inverted papilloma arises from lateral nasal wall near middle turbinate
-most common radiologic appearance is a nasal mass that erodes lateral nasal wall and extends
into maxillary antrum
-actual tumour invasion of bone occurs only with malignant transformation and occurs in about
13% of cases
-juvenile nasopharyngeal angiofibroma
-originates near sphenopalatine foramen
-exhibits marked enhancement on both CT and MRI
-flow voids seen on MRI
-neurogenic tumours (schwannoma, neurofibroma)
-well circumscribed, slowly growing lesions associated with bone expansion and remodelling

Malignant tumours of soft-tissue origin


-epithelial tumours:
-SCC (most common, 80%), glandular tumours, melanoma, and esthesioneuroblastoma
-nonepithelial tumours:
-lymphoma and various sarcomas

Benign tumours of bony origin


-fibroosseous or of giant cell origin
-fibroosseous lesions:
-osteoma
-seen particularly in frontal and ethmoidal sinuses
-multiple osteomas of face and skull seen in Gardner syndrome
-osteochondroma
-ossifying fibroma
-fibrous dysplasia
-hazy ground-glass appearance
-TI: signal intensity ranges from mildly hyperintense to hypointense
-T2: marked homogeneous hypointensity
-giant cell lesions:
-giant cell granuloma
-brown tumour of hyperparathyroidism
-most common giant cell lesion of facial bones
-unilocular or multilocular cystic, expansile masses with well-defined margins

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Malignant tumours of bony origin
-most common malignant bone tumours of paranasal sinuses are multiple myeloma, osteogenic sarcoma,
and chondrosarcoma

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RHINOSINUSITIS: CURRENT CONCEPTS AND MANAGEMENT

ANATOMY AND PHYSIOLOGY OF THE SINUSES

-function of sinuses:
-dampening of sudden increased intranasal pressure
-voice resonance
-possible participation in olfaction
-humidification of inspired air
-decreasing weight of skull
-frontal sinus:
-varies greatly in size and shape
-nasofrontal duct drains into frontoethmoidal recess of middle meatus
-10-12% of adults have rudimentary frontal sinus or lack pneumatization of frontal bone
-ethmoid sinus:
-most developed at birth
-anterior and middle ethmoidal cells drain to middle meatus
-posterior cells drain to superior meatus
-maxillary sinus:
-present at birth
-drains into middle meatus
-sphenoid sinus:
-begins developing in 2nd or 3rd year of life
-completely pneumatized by 17th or 18th year
-drains into sphenoethmoidal recess

-maxillary sinusitis is caused by disease in the ostiomeatal complex:


-frontal recess
-ethmoid bulla
-infundibulum
-maxillary sinus ostium
-middle turbinate
-middle meatus
-semilunar hiatus
-uncinate process

PATHOPHYSIOLOGY

Pathophysiologic Characteristics of Sinus Disease


Ostial patency Ciliary Function Mucous

-Edema -Decreased ciliary beat frequency -Changes in quantity


-allergens -ciliotoxins -allergens
-infection -cold air -airway irritants/pollutants
-Polyps -Loss of metachronous coordination -goblet cell metaplasia
-atopy -scarring, synechiae -Changes in quality
-CF -Loss of ciliated cells -abnormal water-electrolyte
-chronic infection -airway irritants/pollutants transport
-Structural factors -increased intranasal airflow -dehydration
-septal deviation -inflammatory mediators -CF
-Haller’s cells -viral/bacterial-mediated cell
-concha bullosa death
-instrumentation -surgical

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-osteal patency:
-hypo-oxygenation and osteal obstruction accumulation of secretions in sinus ideal culture
medium for bacteria
-mucociliary layer:
-double layer:
-superficial viscid gel layer
-underlying serous sol layer
-nasal mucous produced by:
-goblet cells
-submucosal mucous-producing glands

LOCAL, REGIONAL, AND SYSTEMIC CAUSES OF SINUSITIS

Local
-impairment of mucociliary transport function
-cold/dry air
-medications

Regional
-suppurative sinusitis: apical dental infection (main predisposing factor)
-nasal/midface trauma (alters anatomic configuration of OMU)
-septal pathology mechanical obstruction
-choanal atresia interferes with drainage of nose
-edema 2o to URTI
-barotrauma produces edema of sinus ostium
-swimming in contaminated water
-nasal polyps, FB, nasal packing, nasal tumours
-immotile cilia syndrome
-congenital: disorientation of cilia and abnormalities of dynein arms
-sinusitis and bronchitis

Systemic
-general debilitation:
-malnutrition, long-term steroid therapy, uncontrolled diabetes, blood dyscrasia, chemotherapy
-critically ill patients:
-regional obstruction from NG tubes
-colonization of UGI and URT by gram negative bacilli
-immune deficiencies (eg. IgG deficiency, AIDS)
-pseudomonas in HIV patients; microsporidium, CMV, Aspergillus (invasive), histoplasma,
Cryptococcus, atypical mycobacteria
-non-Hodgkin lymphoma in HIV patients

CLASSIFICATION OF SINUSITIS

Five axes:
a) clinical presentation (acute, subacute, chronic)
b) anatomic sites of involvement (ethmoid, maxillary, frontal, sphenoid)
c) responsible organism (viral, bacterial, fungal)
d) presence of extrasinus involvement (complicated, uncomplicated)
e) modifying or aggravating factors

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-Acute sinusitis: 1 day to 4 weeks
-management is medical, rarely surgical
-drainage if orbital or intracranial complications threaten
-Subacute sinusitis: 4 weeks to 3 months
-medical management indicated
-Chronic sinusitis: > 3 months
-sinusitis that is uncontrolled or inadequately managed
-process irreversible without surgical intervention
-osteal patency must be restored surgically to allow clearance of mucopus from sinus

CLINICAL EVALUATION

History
-Acute sinusitis:
-pain: nasal, facial, headache
-ethmoidal pain: medial portion of nose or retro-orbital area
-sphenoidal pain: vertex or bitemporal headaches
-nasal obstruction/discharge
-fever, malaise, lethargy
-diagnosis depends on presence of > 2 major factors or 1 major and 2 minor factors:

Major factors:
-facial pain or pressure
-facial congestion or fullness
-nasal obstruction
-nasal purulence or discoloured PND
-hyposmia or anosmia
-fever

Minor factors:
-headache
-halitosis
-fatigue
-dental pain
-cough
-ear pain, pressure, or fullness
-fever

-Chronic sinusitis:
-mucopurulent discharge and symptoms of mild nasal obstruction
-pain and systemic symptoms are conspicuously absent

Physical Examination
-mucosal edema and erythema
-+/- mucopurulent discharge
-facial pain/tenderness over affected sinuses
-look for periorbital edema, malodorous breath
-nasopharynx: adenoidal obstruction, tumours, choanal atresia, PND
-look for otitis media or serous otitis media
-transillumination not reliable
-nasal endoscopy: pus in middle meatus

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-periorbital edema; blindness can be a complications of sinusitis
-children much less likely to report classic sinus headaches
-“cold” lasting more than 7-10 days, daytime cough with nocturnal exacerbation, mucopurulent
nasal discharge, fetid breath, low grade fever

Investigations
-plain radiography:
-indications: screening study for acute sinusitis
-evaluates presence of air-fluid levels, opacification, and bone destruction
-high rate of false positives and false negatives to evaluate for chronic sinusitis
-CT of paranasal sinuses:
-indications:
-complications of severe acute sinusitis
-medical failure of chronic sinusitis
-diagnosis of epistaxis, nasal or sinus tumours, nasal polyps
-CSF leaks
-trauma
-preoperative films
-MRI of paranasal sinuses:
-improved soft tissue detail, poor bone resolution
-indications:
-complicated sinusitis (intracranial and intraorbital extension)
-evaluation of soft tissue masses
-fungal sinusitis (hypodensity in T2-weighted sequences form the presence of metallic
proteinaceous material, magnesium, iron, and calcium)

Ancillary studies
-sinus cultures:
-obtained through an anterior maxillary puncture or from an endoscope
-indications:
-failed medical management
-complicated sinusitis (sepsis, orbital infection, intracranial extension)
-immunocompromised patients
-immunological profile:
-qualitative immunoglobulins including IgG subclasses
-ciliary biopsy
-allergy testing

MICROBIOLOGY OF SINUSITIS

-little correlation between culture results with specimens from nose or nasopharynx and those from sinus
aspiration
-antibiotic management of acute sinusitis usually empiric

-Acute (community acquired):


-viral: rhinovirus (most common)
-bacterial:
-Streptococcus pneumoniae (most common - 30%), Haemophilus influenzae (20%),
Moraxella catarrhalis (20%)
-other streptococci (S. pyogenes)
-anaerobes: Peptostreptococcus, Fusobacterium, Bacteroides (6-10%)

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-Acute (nosocomial):
-Pseudomonas aeruginosa, enteric gram-negative bacilli (KEEPS), Staph. aureus, Candida,
streptococci
-anaerobes
-Chronic sinusitis:
-anaerobes (Bacteroides, anaerobic cocci), fungus (1-2%)
-alpha streptococci, H. influenze, S.aureus, S. pneumoniae, M. catarrhalis
-Immunosuppression:
-usual organisms plus: Pseudomonas, S. aureus, Listeria monocytogenes, Leigionella
-CMV
-Fungi (fulminant): Aspergillus, Candida, Mucor, Phaehyphomycosis, Rhizopus
-Atypical mycobacteria
-Microsporidia, Cryptococcus
-Cystic Fibrosis:
-P. aeruginosa, S. aureus

Viral sinusitis
-often follows viral rhinitis
-rarely requires treatment except in immunosuppressed (eg. with CMV infection)

Fungal sinusitis
-types:
-noninvasive: (1) mycetoma and (2) allergic fungal sinusitis
-invasive: (3) fulminant (immunosuppressed); (4) indolent (immunocompetent)

-modifying factors can predispose a patient to sinus infection or can prevent complete resolution of
infection:
-eg. atopy, immunosuppression, ciliary dyskinesia, mechanical obstruction

Mycetoma:
-pathogens: Aspergillus fumigatus (most common), Pseudallescheria boydii, Alternaria
-SSx: unilateral chronic or recurrent sinusitis, unilateral proptosis, facial hypesthesia
-dx: CT/MRI, biopsy with culture
-aspergillosis histology:
-septated 45 degree, Y-shaped (Sabouraud’s agar stain)
-tx: adequate surgical debridement, consider adjuvant less toxic antifungal medications

Allergic Fungal Sinusitis


-chronic sinusitis: nasal obstruction, sinus pain, rhinorrhea, frequent orbital symptoms (proptosis)
-characteristics:
-thick, viscid, brown-green mucus with peanut butter-like consistency
-histology:
-sheets of eosinophil
-Charcot-Leyden crystals
-breakdown products of eosinophils
-fungal hyphae (non-invasive: not in tissues)
-most commonly aspergillus sp
-demitaceous molds: Alternaria, Bipolaris, Curvularia, Exophilia
-caused by allergic reaction to a fungus colonizing sinus cavities (Gell and Coombs type I and
type III hypersensitivity)
-eosinophil secrete mediators that damage cilia

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-promotes polyp growth
-sinus imaging:
-often unilateral involvement of one or two sinuses
-CT: areas of hyperdensity in opacified sinus cavities
-MRI: hypointensity on T1 and signal void on T2
-erosion of bony sinus wall frequently encountered:
-osteolytic factors secreted by fungi
-cytokine-mediated osteoclast activation
-long-standing pressure on sinus walls

Diagnostic criteria (Bent and Kuhn - 1994)

Major Criteria:
1. testing or history positive for fungal atopy (RAST, skin testing)
2. nasal polyposis
3. CT showing hyperdense material in sinus cavity and possible sinus wall erosion
4. allergic mucus with eosinophilic preponderance
5. identification of fungus
6. no histologic evidence of tissue invasion

Minor Criteria:
1. chronic rhinosinusitis
2. CT scan demonstrating serpiginous areas of high attenuation especially in
ethmoidal and maxillary sinuses, with bone thinning and erosions with
dislocation of adjacent structures
3. MRI showing decreased signal intensity leading to hypointense T1-weighted
and markedly hypointense T2-weighted images with typical void signal

Treatment
-ethmoidectomy
-middle meatal antrostomy with extirpation of allergic mucous and polypectomy
-post-op steroid sprays and saline irrigations
-systemic anti-fungals are of no use because fungi are not invasive
-consider immunotherapy for refractory cases

Chronic Invasive (Indolent) Fungal Sinusitis:


-pathogen invades soft tissue
-pathogens:
-Aspergillosis
-saprophytic: Mucor, Rhizopus, Absidia
-SSx:
-chronic sinusitis with or without symptoms of local invasion
-tx:
-surgical debridement and long-term amphotericin B and itraconazole (1 year)

Fulminant Fungal Sinusitis and Mucormycosis


-pathogen invades soft tissue
-in mucormycosis, pathogen invades vessel walls causing local vascular occlusion,
thrombosis, infarction and tissue necrosis
-pathogens:
-Aspergillosis
-saprophytic: Mucor, Rhizopus, Absidia

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-risk factors: immunocompromised host (diabetic ketoacidosis, chemotherapy, HIV, bone marrow
transplant)
-SSx:
-necrotic black turbinates and soft palate, epistaxis, cranial nerve involvement, progresses
rapidly into obtundation and death
-mucormycosis histology:
-non-septated, 90 degree broad branching hyphae
-tx:
-correct metabolic abnormality if present
-urgent surgical debridement
-IV amphotericin B

MANAGEMENT

Acute rhinosinusitis:
-First-line empiric therapy:
-Amoxicillin:
-covers H. influenzae, M. catarrhalis, S. pneumoniae
-does not cover strains that have beta-lactamase enzyme
-Erythromycin and a sulfonamide
-cephalexin and a sulfonamide
-Amoxicillin-clavulanate
-for beta-latamase producing strains of H. influenzae and M. catarrhalis, but not
effective against penicillin-resistant pneumococci
-second-generation cephalosporins: cover beta-lactamase producing organisms
-Second-line therapy:
-amoxicillin-clavlanate
-clarithromycin and second-generation cephalosporin
-respiratory quinolones (levofloxacin, gatifloxacin, moxifloxacin), ciprofloxacin
-contraindicated in children and pregnant women - interference with cartilage
development
-Orbital or intracranial complications:
-IV Ceftriaxone: excellent penetration of BBB
-IV Flagyl: better CSF penetration than clindamycin

-Nosocomial sinusitis:
-cover gram-positive, gram-negative (eg. Pseudomonas), and anaerobic bacteria
-IV Flagyl + ampicillin + ceftazidime, cefotaxime, or ciprofloxacin
-imipenem
-piperacillin-tazobactam

-clinical improvement usually occurs within 48 to 72 hours of initiation of therapy


-most important management measure is antibiotic therapy for a minimum of 7 days after all
symptoms have disappeared (although trends are changing toward shorter treatment times ~5
days)
-treatment usually for 10 days to 3 weeks
-treatment for shorter periods can allow relapse, or the disease can progress to chronic sinusitis
-topical decongestants
-advocated and are beneficial, provided not used for more than 3 days
-antihistamines not recommended:
-can produce further inspissation of secretions and cause substantial side effects

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-analgesics for pain
-humidification, mucolytics and expectorants, saline nasal irrigation to help clear secretions

Chronic sinusitis
-Antibiotics for 3-6 weeks:
-clavulin
-clindamycin
-cephalexin and metronidazole
-ciprofloxacin
-itraconazole
-cefuroxime
-clarithromycin
-nasal corticosteroid sprays
-nasal hypertonic saline irrigations
-oral decongestants and mucolytic agents
-allergy management
-surgical management frequently required

Cystic Fibrosis and Sinusitis


-patients at higher risk for pseudomonal and MRSA infections
-tx:
-attempt initial conservative medical management with mucolytics, topical steroids, hypertonic
saline irrigations
-avoid antibiotics (may develop resistant pathogens)
-avoid surgical management (high recurrence rate, increases nasal scarring, patients do not tolerate
long-term general anaesthesia d/t retained pulmonary secretions)
-surgery may be considered for uncontrolled pain, nasal obstruction, mucocele, unresolved fevers,
and fungal infections

Kartagener’s disease
-aggressive antibiotic therapy
-avoid functional antrostomies (no mucociliary clearance)
-consider “gravity dependent” inferior antostomies for refractory disease

SURGICAL MANAGEMENT

-main indication for maxillary sinus irrigation is the presence of mucopurulent material in an
immunosuppressed patient or a patient with suspected subacute or chronic maxillary sinusitis or acute
sinusitis that has not responded to antibiotic therapy
-surgery for acute maxillary sinusitis is indicated if the pain persists for more than 24-48h despite
appropriate antibiotic therapy or if ophthalmic and neurologic complications occur

COMPLICATIONS

Ophthalmologic (most common)


-intraorbital pathways:
-direct extension (especially through thin walled lamina papyracea)
-thrombophlebitis (valveless veins)
-congenital dehiscence
-trauma

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-direct lymphatics
-orbital cellulitis, abscess, proptosis
-subperiosteal and orbital abscess
-blindness, loss of ROM, increased IOP
-osteomyelitis
-mucoceles

Stages of Orbital Complications (Chandler Classification)

1. Periorbital/Preseptal Cellulitis:
-eyelid edema, erythema, tenderness
-no vision changes, chemosis, proptosis, or restriction of ocular muscles
-tx: IV ABx and concurrent aggressive sinusitis regimen
2. Orbital Cellulitis:
-proptosis, chemosis
-may cause vision changes (anterior pupillary defect)
-may limit extraocular muscles
-tx: IV ABx and concurrent aggressive sinusitis regimen +/- FESS
3. Subperiosteal Abscess:
-collection of pus between bone and periosteum
-chemosis, proptosis
-restricted extraocular motion
-decreased vision
-tx: urgent surgical decompression
4. Orbital Abscess:
-collection of pus in orbital soft tissue
-proptosis, chemosis, restricted extraocular motion
-decreased vision
-tx: urgent surgical decompression
5. Cavernous Sinus Thrombosis:
-pathogens:
-S. aureus (most common), hemolytic Streptococcus and type III Pneumococcus
-SSx:
-spiking fevers, toxaemia
-proptosis, facial edema, ophthalmoplegia
-tx:
-IV ABx
-may require ligation of IJV if septic emboli
-anticoagulants (controversial)
-sinus surgery

Neurologic (rare)
-intracranial pathways
-congenital dehiscence
-trauma
-direct extension
-lymphatics
-olfactory nerve sheath
-venous system
-foramina of Breschet
-meningitis (most common intracranial complication)
-epidural or subdural abscesses

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-brain abscess, cavernous sinus thrombosis
-venous sinus thrombosis

Pott’s puffy tumour:


-osteomyelitis of anterior wall of frontal sinus
-infection via direct extension or by thrombophlebitis of diploic veins
-most often seen in adolescents and young adults d/t more extensive system of diploic veins
-most common offending organism: S. aureus
-tx: IV Abx, trephination, may require surgical debridement

Superior Orbital Fissure syndrome:


-fixed globe, dilated pupil, ptosis (CN III, IV, VI)
-hypesthesia of upper eyelid (CN V1)

Orbital Apex Syndrome:


-superior orbital fissure syndrome with added involvement of optic nerve

EMERGENCIES

Ophthalmologic:
-orbital cellulitis/abscess
-ethmoid sinus most common sinus contributing to orbital complications
-third nerve palsies may be result of sphenoid sinusitis
-IV Abx, surgical drainage, early consultation if any present:
-visual changes
-change in ocular mobility
-change in ocular pressure
-proptosis
-acute ethmoidal sinusitis with orbital complications probably best managed through external
ethmoidectomy approach; if no complications then endoscopically and intranasally is reasonable

Neurologic:
-abscess (epidural/subdural/intraparenchymal), meningitis, cavernous sinus thrombosis
-IV Abx, surgical drainage, early consultation if any present:
-CN involvement (II, III, IV, VI)
-papilledema
-altered mental status/LOC
-nuchal rigidity

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ENDOSCOPIC SINUS SURGERY

ANATOMY OF THE LATERAL NASAL WALL

-agger nasi:
-ascending (frontal) process of maxilla forming a thick bony ridge inside the nose
-agger nasi cells: cells anterior to opening of frontal sinus
-ostiomeatal unit:
-medial border: anterior middle turbinate
-lateral border: lateral nasal wall
-uncinate process bisects region
-anteriorly joined to posteromedial portion of lacrimal bone by membranous attachment
-may attach anterosuperiorly to LP or to skull base
-inferolaterally fused with medial wall of maxillary sinus
-ethmoidal infundibulum:
-lateral wall is medial wall of orbit and antrum
-posterior aspect empties into inferior hiatus semilunaris
-ethmoid bulla:
-constitutes posterior boundary of inferior hiatus semilunaris
-bony medial wall of maxillary sinus:
-natural ostium of maxillary sinus
-anterior (inferior to inferior limb of uncinate process) and posterior (superior to inferior limb of
uncinate) fontanelles
-usually covered by mucosa
-perforated in 10-28% of patients accessory ostium
-frontal recess:
-typically drains medially to uncinate process and laterally to middle turbinate
-occasionally drains into inferior hiatus semilunaris
-sinus lateralis = retrobullar recess
-most posterior aspect of anterior ethmoidal cells
-basal lamella:
-lateral, sigmoid, bony attachment of middle turbinate to medial orbital wall
-separates anterior and posterior ethmoidal air cells
-ethmoidal roof classification (Keros)
-type 1: cribriform plate is 1-3 mm
-type II: 4-7 mm deep
-type III: 8-16 mm deep
-Onodi cell = sphenoethmoidal cell
-pneumatization of sphenoid bone by an ethmoidal air cell
-clinical bony dehiscence of cavernous portion of carotid canal occurs among 22% of patients

PREOPERATIVE EVALUATION

Comprehensive Nasal Endoscopy


-first pass:
-along floor of nose
-visualize inferior turbinate, inferior meatus, nasopharynx, eustachian tube
-drainage under torus tubaris suggests disease with anterior ethmoidal, maxillary, or frontal
sinuses
-drainage over torus emanates from sphenoethmoidal recess and signifies posterior ethmoidal or
sphenoidal sinus disease

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-second pass:
-between middle turbinate and inferior turbinate
-visualize anterior and inferior portions of middle turbinate and meatus
-natural opening to sphenoidal sinus viewed
-third pass performed during withdrawal of scope
-visualize ethmoidal bulla, inferior hiatus semilunaris and uncinate process
-natural ostium of maxillary sinus usually hidden behind uncinate process

Radiographic Evaluation
-optimal time to perform CT is during
Preoperative Radiographic Checklist
quiescent phase of disease
-pts should undergo comprehensive medical 1. Shape of skull base and orbit
therapy before CT scan -medially down-sloping versus flat, particularly in region of
lateral lamella of cribriform plate
-fungal disease suspected if:
-metal-like or diffusely increased 2. Relative thickness of skull base and orbit in different areas
densities within soft tissues of along roof of ethmoid bone and presence of medial orbital or
involved sinuses bone dehiscence along skull base
-reduced signal intensity of a T2- 3. Position of anterior ethmoidal neurovascular bundles
weighted image -look just behind globe on true coronal CT scans

4. Vertical height of posterior ethmoid labyrinth relative to


posteromedial roof of maxillary sinus
SURGICAL INDICATIONS AND
CONTRAINDICATIONS 5. Presence and development of sphenoethmoid cells (Onodi
cells)
Advantages of Endoscopic Approach to Chronic
6. Relation of septa within sphenoid sinus to carotid artery and
Rhinosinusitis optic nerve and degree of protrusion of these structures into
-no surgical trauma to external skin and the sinus cavity
intervening bone and ability to minimize
intranasal and intrasinus trauma 7. Atelectasis of ethmoidal infundibulum with lateralization of
the uncinate process
-preservation of bony framework within
critical area of frontal recess 8. Maxillary sinus hypoplasia
-unparalleled visualization of nasal anatomy -associated with congenital underdevelopment of the uncinate
-preservation of mucous membranes for process
restoration of normal mucociliary clearance

Relative Indications for Endoscopic Surgery


-unresponsive, recurrent acute rhinosinusitis
-unresponsive, obstructive nasal polyposis
-extramucosal fungal rhinosinusitis
-closure of CSF rhinorrhea
-removal of foreign body
-antrochoanal polyp
-chronic rhinosinusitis
-mucocele
-periorbital cellulitis
-epiphora related to lacrimal duct obstruction
-excision of selected tumours
-epistaxis control
-nasal septal obstruction
-dysthyroid orbitopathy

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Relative Contraindications to Endoscopic Surgery
-absence of defined ostiomeatal abnormality
-osteomyelitis
-inaccessible lateral frontal sinus disease
-frontal sinus disease accompanied by stenosed internal ostium
-threatened intracranial or intraorbital disease

ANAESTHESIA

Local Anaesthesia with Sedation


-oxymetazoline used before application of cocaine to slow absorption and diminish cardiovascular effect
-anaesthetize branches of ethmoidal and sphenopalatine vessels and nerves
-sphenopalatine block:
-intraoral through greater palatine foramen
-do not advance needle tip more than 2.5 cm into foramen reduces risk of trauma to contents of
posterior orbit and blindness
-risks temporary diplopia and visual loss
-lateral wall injections:
-ascending process of maxilla (agger nasi)
-medial surface of middle turbinate
-portions of nasal septum

Rationale for Local Anaesthesia


-surgeon-patient communication possible
-improved visualization d/t decreased blood loss
-surgeon may be alerted when pain sensitive areas along base of skull and medial orbital wall are reached
-if orbital hematoma arises, can do vision checks to assess status and severity of injury

SURGICAL PROCEDURES

Complete Sphenoethmoidectomy
-indicated for extensive disease

Concurrent Septoplasty
-usually begun after endoscopic procedure is completed on side away from septal deflection
-hemitransfixion incision made on side contralateral to deflection

Functional Endoscopic Sinus Surgery


-philosophy: removal of disease from a target area such as OMU, normal mucociliary flow is restored and
disease in dependent sinuses resolves
-transition space surgery or small hole surgery (Messerklinger approach)
-theory: disease of secondarily involved sinuses resolves once obstructed area is adequately
ventilated
-CF pts are candidates for large middle meatal antrostomy that extends from natural ostium to floor of nose
-will never have normal mucociliary clearance
-four bony landmarks followed while medial orbital wall is skeletonized in an anteroposterior direction
-uncinate process
-ethmoid bulla
-basal lamella of middle turbinate, roof of maxillary sinus, superior turbinate
-anterior face of sphenoidal sinus

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-anterior ethmoidal artery typically just anterior to vertical portion of basal lamella, immediately below
base of skull and posterior to frontal recess
-tight nasal packing should be avoided when integrity of orbital wall is in question: blood can dissect into
orbit and cause delayed haematoma and vision loss
-base of skull usually thinnest where anterior ethmoidal artery crosses from medial orbital wall to
cribriform plate

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APPROACHES TO THE SPHENOIDAL SINUS

ANATOMY
-classification: three types of pneumatization; incidence
varies depending on series
-Harnberger:
-sellar (86%)
-presellar (11%)
-concha (3%)
-Congdon:
-postsellar (67%)
-presellar (24%)
-conchal (5%)
-conchal pneumatization not a contraindication to sphenoid
surgery
-dehiscent carotid artery in 4%
-dehiscent optic nerve in 4%

-Cavernous Sinus:
-contents:
-internal carotid artery
-indents posterior inferior surface of sphenoid sinus
-abducens nerve travels in close association with lateral wall of artery
-oculomotor nerve
-trochlear nerve
-abducens nerve
-ophthalmic division of trigeminal
-maxillary division of trigeminal

PREOPERATIVE EVALUATION
-active sinus infection if the main contraindication to a transnasal intracranial procedure

OVERVIEW OF APPROACHES

-transseptal:
-sublabial
-intranasal
-external rhinoplasty
-transantral
-transethmoidal
-external
-intranasal
-endoscopic:
-intranasal sphenoethmoidectomy
-transantral sphenoehtmoidectomy
-transpalatal

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TRANSSPHENOIDAL HYPOPHYSECTOMY

Transseptal Approaches
-indications:
-large pituitary neoplasms with extensive suprasellar involvement
-total removal impossible, but tissue diagnosis and decompression of optic chiasm can be
obtained
-pituitary microadenoma

-Sublabial Transseptal Approach


-Intranasal Transseptal Approach
-External Rhinoplasty Transseptal Approach
-columellar flap raised
-medial crura are separated to expose caudal edge of quadrilateral cartilage
-traditional transeptal approach is then continued

Columellar Flap Modification


-complete transfixion incision made caudad to quadrilateral cartilage through membranous septum
-incision extends from domes superiorly to nasal spine inferiorly
-transverse incision carried posteriorly around feet of mesial crura on both sides to join transfixion
incision

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Previous Septal Surgery
-strategies to avoid septal perforation:
-avoidance of problem area using traditional septoplasty techniques to go around scar tissue
-careful dissection through adherent mucosal areas; usually feasible when reoperation needed
soon after initial procedure
-lateral displacement of septum

Transantral Approach
-not commonly used at present
-allows widest exposure and is 1-2 cm closer to sphenoidal sinus than transeptal approach
-increased risk of damage to cavernous sinus, optic nerve and anterior cranial fossa

Transethmoidal Approach
-external and intranasal
-only external route appropriate for hypophysectomy (not popular)
-same disadvantages as transantroethmoidal route
-intranasal approach used for extensive nasal polyposis

SPHENOID INFLAMMATORY DISEASE

-acute and chronic sinusitis


-intranasal and transantral sphenoethmoidectomies are classic approaches

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Endoscopic Approaches to the Sphenoid Sinus
-sphenoidal sinus lies at medial inferior portion of posterior ethmoid cell
-anterior wall ~7 cm posterior to anterior nasal spine
-posterior wall ~9 cm
-approach transethmoidal or direct

Intranasal Sphenoethmoidectomy
-middle turbinate infractured
-Glasgow forceps used to enter middle ethmoid cells
-dissection continued medial to turbinate
-ostium is enlarged toward midline with Kerrison forceps

Transantral Sphenoethmoidectomy
-used by some to manage chronic hyperplastic disease, especially if extensive benign maxillary disease
encroaches on ethmoidal and sphenoidal sinuses
-antral cavity entered through sublabial canine fossa approach
-removal of nasoantral wall
-anterior sphenoid wall is opened to expose the sinus

SPHENOID TUMOURS

-transseptal, transethmoidal or endoscopic approach


can be used

Transpalatal Approach
-for neoplasms of nasopharynx, posterior
pharyngeal wall, and choanae
-tumours isolated to sphenoidal sinus and
sella are better resected with alternative
methods
-Dibble and King:
-midline palatal split; hard palate,
posterior vomer removed as
necessary
-palate closed in two layers, muscle
and nasal mucosa first, followed by
oral mucosa
-Mullan:
-U-shaped incision at junction of
soft and hard palate
-hard palate resected
-incision closed in two layers
-preserves palatal motor function
best, but exposure is limited
inferiorly
-Kennedy:
-S-shaped incision originating along
lingual alveolus and curing back
across palatal aponeurosis to dive
soft palate off midline

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Sphenoidal Mucocele
-transsphenoidal endoscopic approach successful in management of sphenoidal and ethmoidal mucoceles
with orbital and intracranial extension and with cholesterol granuloma of petrous apex

COMPLICATIONS

Nasal
-poor appearance (saddle and tip deformities)
-septal perforation
-infection
-epistaxis

Neurologic
-injury to optic nerve and cranial nerves III, IV, V1, V2
-trauma to optic chiasm
-late prolapse of chiasm into sella
-trauma to hypothalamus
-CSF leak

Vascular
-haemorrhage from internal carotid artery
-haemorrhage from cavernous sinus

EMERGENCIES

Preoperative:
-acute sinusitis with meningitis or other neurologic signs surgical drainage
-developing visual loss in sellar or parasellar tumour surgical decompression, radiation therapy

Intraoperative:
-retrobulbar haemorrhage with proptosis and visual compromise lateral canthotomy, ophthalmologic
consultation
-persistent haemorrhage from sphenoid or cavernous sinus region interventional arteriography

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SPHENOID SINUS DISEASE

DEVELOPMENT
-begins early in third month of fetal development and continues throughout first decade of life
-progressive pneumatization after age 3

ANATOMY
-neighbouring structures of the sphenoid sinus
-dura
-pituitary
-optic nerve and chiasm
-rests against superolateral wall
-bone overlying optic canals becomes increasingly dehiscent with increasing age
-cavernous sinus
-internal carotid artery
-located within medial aspect of cavernous sinus
-passes directly across lateral wall and produces a medial deflection of the lateral wall
into the lumen of the sinus (carotid sulcus)
-abducens nerve
-oculomotor nerve
-trochlear nerve
-ophthalmic nerve
-maxillary nerve
-sphenopalatine ganglion
-sphenopalatine artery
-pterygoid canal and vidian nerve
-sphenoid ostium:
-1.5 cm above sinus floor on anterior wall
-drainage dependent on mucociliary flow

INFLAMMATORY DISEASE

Acute Bacterial Sphenoiditis


-risk factors:
-diving in contaminated waters
-cocaine or steroid use
-diabetes
-nasal fractures
-treatment often by broad-spectrum antibiotics; mucolytics, decongestants, saline irrigations
-indications for surgery:
-failure of medical management
-complication resulting from spread of infection to neighboring structures
-complications:
-orbital cellulitis
-hypopituitarism
-sepsis
-subdural and epidural abscess
-cavernous sinus thrombosis
-meningitis
-intracranial abscess

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-cerebral infarction
-blindness

Invasive Fungal Sinusitis


-immunocompromised pts
-Mucor, Rhizopus, Absidia favour high glucose acidic environment
-Aspergillus in neutropenic pts
-tx geared toward reversing underlying immunologic insult, excision of all necrotic tissues and treatment
with appropriate antifungal medications

Allergic Fungal Sinusitis


-typically presents with polyposis and pansinusitis
-sinuses filled with allergic mucin:
-eosinophil-laden mucin mixed with Charcot-Leyden crystals and noninvasive fungal forms
-vascular compromise and frank necrosis not observed
-capable of significant bony erosion and sinus expansion
-organisms:
-Aspergillus, Bipolaris, Curvularia, Alternaria, Cladosporium
-pathophysiologic mechanism believed to be allergic rather than infectious
-treatment:
-exposure to fungal antigen reduced by surgical removal of allergic mucin
-perioperative use of systemic corticosteroids, nasal saline irrigations and debridement of nasal
crusts
-immunotherapy with fungal antigens initiated

Mycetomas
-fungal balls
-occur despite adequate host immunity and are noninvasive

Chronic Sphenoiditis
-from obstructive polyposis
-obstruction, mucin stasis, chronic bacterial infection
-tx: removal of obstructing polyps, regular saline irrigations, use of nasal steroids, extended course of
antibiotics

Mucoceles
-treatment requires creation of wide sphenoidotomy with decompression of the mucocele

NEOPLASTIC DISEASE

Fibrous Dysplasia
-bony encroachment on optic nerve and ocular muscles

Chordoma
-typically arise from clivus and extend by direct expansion
-derived from notochordal remnants
-treatment involves surgical removal and XRT

Malignant Tumours of the Sphenoid


-primary malignancies rare
-most common tumours: adenocarcinomas, chondrosarcomas, lymphoepitheliomas

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OPERATIVE TECHNIQUES

Open Approaches
-transseptal approach
-columellar incision or sublabial incision
-via ethmoid air cells:
-transmaxillary approach
-transorbital approach
-transpalatal approach

Endoscopic Approaches
-minimally invasive
-Bolger technique:
-relies on entering superior meatus through basal lamella, allowing identification of anteroinferior
aspect of superior turbinate
-dissection proceeds laterally to define posterior limit of lamina papyracea
-Bolger’s parallelogram:
-medial limit: lateral aspect of superior turbinate
-lateral limit: lamina papyracea
-superior limit: skull base
-inferior limit: horizontal portion of superior turbinate (attaching to lateral nasal wall)
-anterior face of sphenoid sinus is posterior wall of this box
-natural ostium located by gently removing inferior portion of superior turbinate
-safe area of entry: medial-inferior portion of parallelogram

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COMPLICATIONS OF SINUS SURGERY

RELEVANT ANATOMY

-lamina papyracea is superior to and just lateral to the natural ostia


-operate laterally to middle turbinate, never medially and superiorly
-antrostomy :
-placed just above inferior turbinate
-should not be more anterior than anterior end of middle turbinate
-is at the level of the inferior orbital rim
-in adults, distance from nasal spine:
-5 cm: -bulla ethmoidalis
-6cm: -frontal recess
-basal lamella of middle turbinate
-nasofrontal duct ostia (6-6.5 cm)
-7 cm: -anterior ethmoidal artery
-base of skull
-sphenoidal sinus anterior wall
-choanal bridge
-nasopharyngeal wall approximates posterior sphenoid wall to within 1 cm
-ostium of sphenoidal sinus:
-adjacent to septum ~1.5 cm above choanal bridge, or ~1/3 up from choana to base of skull
-approaches:
-medially: medial to middle turbinate
-laterally: plane between superior inferior turbinate and just above attachment of middle
turbinate to choanal bridge
-if middle turbinate must be removed, remove only inferior or anterior part of the turbinate and preserve the
superior part as an anatomic landmark

COMPLICATIONS OF SPECIFIC PROCEDURES

Inferior Meatal Antrostomy


-bleeding (greater palatine artery), synechiae, osteomyelitis, tooth numbness, pain, injury (children:
proximity of developing canines)

Middle Meatal Antrostomy


-bleeding, blindness, facial pain, numbness, nasolacrimal duct injury, synechiae
-relatively complication-free procedure with sporadic reports of numbness and pain

Frontal Sinus Surgery with Osteoplastic Flap


-postoperative headache, incomplete obliteration, recurrent disease
-hypesthesia in distribution of supraorbital nerve
-early complications: hematoma, seroma, abscess, dural injuries intraoperatively
-other: necrosis of skin dorsum of nose, anosmia, temporary ptosis, temporary dysfunction of frontalis
muscle
-CSF leak, meningitis, brain injury unusual

Intranasal Ethmoidectomy
-blindness, permanent diplopia, CSF fistula with meningitis, brain injury, major vessel injuries
-synechiae, orbital hematoma, subcutaneous emphysema, loss of smell, hemorrhage
-contributing factors: repeated procedures, extensive disease, loss of landmarks

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Transantral Ethmoidectomy (TE) and External Ethmoidectomy (EE)
-fewer major complications because of direct vision
-distance to ethmoidal and sphenoidal sinuses through transantral approach is half that of an intranasal
approach
-EE: orbital edema, supraorbital anesthesia, hemorrhage, wound infection
-TE: intracerebral hemorrhage, pneumocephalus, CSF fistula

Sphenoidotomy
-injuries to carotid artery, cavernous sinus, optic nerve, and brain can be catastrophic but they are rare
-CSF fistula, blindness, carotid artery injury, carotid cavernous fistula, meningitis

Caldwell-Luc Procedure
-most common immediate: facial swelling, cheek discomfort
-most common long-term: recurrent sinusitis, recurrent polyps, facial paresthesia, dacryocystitis,
-other: fever, hemorrhage, facial asymmetry, oroantral fistula, gingivolabial fistula, devitalized teeth,
recurrent polyps, blindness

ORBITAL COMPLICATIONS

Orbital Hematoma
-risk of hematoma with retention in retrobulbar space increases greatly with penetration of the periorbita
-most frequently caused by trauma to orbital veins lining lamina papyracea
-rarely by injury to anterior and posterior ethmoidal arteries (quick hematoma formation)
-orbital septum:
-fibrous membrane dividing eyelid into anterior and posterior chambers
-preseptal hematoma: darker and more diffuse and produces more lid edema
-postseptal hematoma: proptosis, conjunctival changes such as chemosis, pupillary changes,
mydriasis, and a dilated pupil
-most cases of orbital hematoma do not have associated proptosis and pupillary changes - these findings
signal increased orbital pressure and potential damage to the optic nerve
-ecchymosis usually resolves in ~ 7-10 days

Blindness
-direct (optic nerve injury) or indirect (orbital hematoma)
-temporary or permanent
-from increased orbital pressure compromised vascular supply to optic nerve
-retinal tolerance:
-venous hematoma: 60-90 minutes
-arterial hematoma: 15-30 minutes
-neural tissue vulnerable to ischemic injury
-intranasal procedures:
-right-handed surgeon more prone to cause injury on right side
-left ethmoidal sinuses are actually more medial than appreciated by a right-handed surgeon
-do not over pack nose if dehiscence present may press into periorbita and posterior chamber
-treatment: fast arterial hematoma:
-Medical treatment:
-eye consultation
-mannitol 1-2 g/kg in 20% infusion
-orbital massage: redistributes orbital blood
-remove nasal
-high dose steroids (controversial): dexamethasone 1-1.5 mg/kg/24h

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-Surgical treatment:
-lateral canthotomy
-medial external (lynch) decompression
-endoscopic decompression
-control bleeding artery (anterior ethmoidal artery)

Diplopia
-injury to ocular muscles: medial rectus and superior oblique
-direct muscle injury or injury to nervous or vascular supply to muscle
-persistent diplopia rare complication with poor prognosis

Nasolacrimal Duct Injury


-agger nasi cells adjacent to lacrimal sac
-ethmoidal sinus and natural antrostomy associated with lacrimal duct
-avoid operating anterior to attachement of uncinate:
-as a rule, ethmoidal sinuses or natural antrostomy should not be opened anterior to the anterior
end of the middle turbinate or into the hardened bone separating the antrostomy from the
nasolacrimal duct
-inferior antrostomy is 1 cm or more behind the anterior inferior turbinate in the inferior meatus
-most cases of epiphora resolve
-early epiphora is associated with permanent injury to the nasolacrimal system
-tx: dacryocystorhinostomy if necessary

Subcutaneous Emphysema
-from resultant fracture or perforation of lamina papyracea
-observe for orbital hematoma
-treatment in most cases is simple observation and reassurance
-emphysema resorbs within 7-10 days

Intraoperative Orbital Fat Penetration


-increases risk of retrobulbar hematoma
-tx: avoid further trauma; avoid tight nasal packing; observe for vision changes, proptosis or restricted
ocular gaze

INTRACRANIAL COMPLICATIONS

Cerebrospinal Fluid Fistula


-areas of potential injury:
-cribriform plate (most common)
-thinnest bone
-dura more adherent
-near frontal recess
-anterior ethmoid artery
-posterior ethmoid sinus
-almost any type of living tissue membrane can be used to patch a fistula:
-eg. fascia temporalis, septal or turbinate mucosa, fascia lata
-local flaps of septal mucosa or middle turbinate
-delayed fistula identification
-CT with contrast agents helps localize active leak
-diluted fluorescein injected intrathecally located with endoscope after 20-30 minutes
-endoscopic examination

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-treatment for persistent leaks: bedrest +/- lumbar drain
-use of antibiotics is controversial and should be used with caution so as not to select out resistant
organisms
-conservative management often allows CSF fistula to heal without surgery
-if persists for 2-3 weeks should be closed surgically

Intracranial Infections
-meningitis
-brain abscess

Brain injury and Major Vessel Injury


-anterior communicating artery can be injured through cribriform plate
-can go into spasm stroke
-frontal lobe syndrome from entrance through roof of nose into brain
-carotid artery and cavernous sinus injury from sphenoidal surgery
-slight injury to the brain can be managed quickly and with minimal deficit
-serious injury always life-threatening

NEURAL AND VASCULAR INJURY

Anosmia
-three types of causes:
-interference with access of odorant to olfactory nerve
-damage to olfactory nerve
-damage to central olfactory pathway

Paresthesia and Hypesthesia


-most common complications of Caldwell-Luc, external ethmoidectomy, and frontal sinus surgery
-usually temporary, resolved in 3-6 months

Hemorrhage
-one of the most common complications during or after sinus surgery
-preoperative sedation and vasoconstriction with a topical spray improves blood pressure control and
decongestion and diminish any systematic reaction to topical cocaine
-only diseased tissue should be removed
-areas of injury:
-sphenopalatine
-carotid
-ethmoid
-carotid-cavernous fistulas
-posterior septal artery:
-runs below sphenoid bone and feeding into posterior middle turbinate can cause marked
intraoperative and postoperative hemorrhage
-tx:
-if bleeding is too great then operation is terminated and nasal packing instituted
-electrocautery
-consider embolization for carotid injuries

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SYNECHIA

-most common complication of FESS


-amputation of anterior end of middle turbinate may avoid synechiae
-any reduction of middle turbinate can predispose it to weakness, giving it a natural tendency to lateralize,
blocking the anterior or posterior ethmoidal sinus, frontal recess, or antrostomy
-removal of agger nasi cells often opens the meatus, dramatically reducing the chances of middle turbinate
lateralization

ABNORMALITY OF FACIAL GROWTH AND SINUS DEVELOPMENT

-although growth disturbance and retarded sinus development have occurred in animals, no clinical study
has shown growth problems

OTHER COMPLICATIONS

-residual disease
-facial edema
-aspiration of packing material
-toxic shock syndrome
-osteomyelitis
-tooth numbness and pain (Caldwell-Luc)
-embossment (frontal sinus obliteration)

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EPISTAXIS

ANATOMY

a) Internal Carotid
-internal carotid a. opthalmic a.
-branches (within orbit):
posterior ethmoidal a. (absent in 31%)
anterior ethmoidal a. (absent in 7-14%)

-posterior ethmoid artery enters posterior ethmoidal foramen within 4-7 mm of the optic nerve > 80% of
the time
-anterior ethmoid artery enters anterior ethmoidal foramen 14-22 mm posterior to maxillo-lacrimal suture >
80% of the time
-ethmoidal arteries branch into medial and lateral branches in ethmoidal cells
-medial branches: supply superior septum and Little’s area
-lateral branches: supply superior and middle turbinates

b) External Carotid
- facial artery superior labial artery
nasal arterial branches
medially to septum
laterally to ala
- maxillary artery
sphenopalatine a.: supplies septal mucosa
posterior nasal a.: supplies lateral nasal wall and turbinates
anastomosis superiorly with ethmoid arteries
anastomosis inferiorly with pharyngeal branches of maxillary artery
(Woodruff naso-nasopharyngeal plexus)
pharyngeal artery
descending palatine a. (greater palatine canal and foramen) greater palatine a.
(supplies septum and floor of nose) incisive foramen
Little’s area

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-Kiesselbach’s plexus (Little’s area) anastomosis of:
-sphenopalatine artery
-greater palatine artery
-anterior ethmoid artery
-nasal branches of facial artery

PHYSIOLOGY AND PATHOPHYSIOLOGY

-turbinate arterioles pass within conchal bone and are


surrounded by a venous plexus
-dilatation of arterioles blocks venous outflow
mucosal congestion
-cavernous nasal plexus - venules > arterioles
-septal cartilage depended on overlying
mucoperichondrium for blood supply

ETIOLOGY

-anterior epistaxis 90-95% of the time


-severe or recurring epistaxis should prompt further
etiologies

Local Factors
-trauma
-digital manipulation
-septal perforation turbulence and impaired
laminar airflow drying, scab formation
epistaxis
-nasal fracture
-probably posttraumatic pseudoaneurysm of internal carotid artery triad of prior
monocular blindness, ipsilateral orbital fractures, delayed epistaxis
-local inflammation
-decongestants and nasal steroids
-foreign bodies
-tumours: eg. juvenile angiofibroma, nasopharyngeal carcinoma

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-chemical inhalants
-nasal prong O2, CPAP
-surgery: septoplasty and FESS

Systemic Factors
-vascular disorders:
-Osler-Weber-Rendu:
-autosomal dominant: mucocutaneous telangiectasias and epistaxis
-thin vessel walls without smooth muscle, increased angiogenesis resulting in vascular
proliferation, arteriovenous fistulae, mucosal fragility
-most common disease of vascular structures leading to recurrent epistaxis
-aging:
-fibrosis of muscular tunica media of arteries
-atherosclerosis NOT a risk factor
-hypertension NOT a significant risk factor for anterior epistaxis
-some possible association of increased risk for posterior epistaxis
-blood dyscrasias:
-VonWillebrand disease
-most common hereditary bleeding disorder associated with epistaxis
-AD
-epistaxis in 60%
-recommended presurgical prophylaxis: desmopressin
-Hemophilia A and B
-hematologic malignancies: leukemia, multiple myeloma, thrombocytopenia
-malnutrition
-alcohol
-drugs: ASA, NSAIDS, anticoagulants, chloramphenicol, carbenicillin, dipyrimdamole
-infectious/inflammatory:
-TB
-syphilis
-Wegener