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Subject: Medicine 2

Topic: GI part 3
Lecturer: Dr. Mappala
Shifting /Date: 3rd /October 31, 2008
Trans group: Eis, Candy, Isay, Jassie

“Diarrhea is the too rapid evacuation of too fluid stools”

The Amazing Intestines


• 10 liters of ingested fluid and secretions enter
the intestine daily
• 90% absorbed in small intestine
• 90% of remaining fluid (~800-1000 mL)
absorbed in colon
• 80-100 mL fluid in stool daily
• Normal stool output: 200 grams/24hours
• Loose stool: increase of 50-60 mL

Diarrhea
• Acute diarrhea: diarrhea lasts less than 4 weeks
• Chronic diarrhea: diarrhea lasts longer than 4
weeks
• Excess water, electrolytes, fat, other substances
Pathophysiology of Diarrhea
in intestinal lumen
• Osmotic
• More than 200 grams stool in 24 hours
• Malabsorption/Maldigestion/Fatty
Is it Diarrhea? • Inflammatory
• Pseudodiarrhea – more frequent bowel • Secretory
movements but < 200 g/24 hours • Altered motility
• Incontinence – involuntary loss of stool
o Anal sphincter dysfunction Certain causes of diarrhea have several
o Neurologic impairment pathophysiologic mechanisms

Osmotic Diarrhea
• Excess amounts of poorly absorbed substances
that remain in intestinal lumen
• Substances that exert osmotic effect
• Obligate water retention in intestinal lumen
• Lactose, lactulose, magnesium, polyethylene
glycol (PEG)

MARY YVETTE ALLAIN TINA RALPH SHERYL BART HEINRICH PIPOY KC JAM CECILLE DENESSE VINCE HOOPS CES XTIAN LAINEY RIZ KIX EZRA GOLDIE BUFF MONA AM MAAN ADI KC
F is for Friends who do stuff together.
PENG KARLA ALPHE AARON KYTH ANNE EISA KRING CANDY ISAY MARCO JOSHUA FARS RAIN JASSIE MIKA SHAR ERIKA MACKY VIKI JOAN PREI KATE BAM AMS HANNAH MEMAY PAU
RACHE ESTHER JOEL GLENN TONI
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 2 of 18

• Abnormal connections between proximal and


Lactose Intolerance distal bowel
o Resection of ileocecal valve
o Fistulas

Pathophysiology of Malabsorption in Bacterial


Overgrowth
• Reduced nutrient availability
o Bacteria consumes nutrients
• Bile salt inactivation
o Excess bacteria deconjugate bile salts
o Unconjugated bile salts unable to
solubilize micelles → fat malabsorption

Diagnosis of Small Intestinal Bacterial Overgrowth


Syndrome
Fecal Osmotic Gap
• Direct aspiration of jejunal contents
290 mosm/kg H2O – 2 ([Na+] + [K+])
Osmotic diarrhea: >125 • Breath tests
o 14C glycocholate
Malabsorption  Conjugated bile acid –
• Luminal phase deconjugated by bacteria – 14C
o Intraluminal maldigestion metabolized to 14CO2
• Mucosal phase  Low sensitivity and specificity
o Mucosal loss (i.e. surgical resection)  Not widely used in US
o Mucosal disease o 14
C xylose – not widely available
• Transport phase o Glucose or Lactulose

Fat Malabsorption
 Measure expired H2 (breakdown
product of bacterial
• Steatorrhea – “oily” stool
fermentation)
• Possible deficiencies of fat soluble vitamins: A, D,
E, K Treatment of Small Intestinal Bacterial
• Causes: Overgrowth Syndrome
o Bacterial overgrowth • Correct predisposing condition
o Pancreatic insufficiency • Correct nutritional deficiencies
o Mucosal diseases • Antibiotics
• Diagnosis: Sudan stain stool; 72 hour stool
collection and measurement of fecal fat Increased Bile Salt Losses
• Mucosal disease in terminal ileum: Crohn’s
Bile Salt Inactivation: Small Intestinal Bacterial disease
Overgrowth Syndrome
• Surgical resection or bypass of ileum
• Normal concentration of bacteria in proximal
• Mechanism of diarrhea: (chlorrheic diarrhea, bile
small intestine: <104 organisms
acid diarrhea)
• Conditions that predispose to bacterial
o Bile acids that reach colon cause colonic
overgrowth cause:
secretion of electrolytes and water
o Intestinal stasis
o Fat malabsorption
o Abnormal connection between proximal
and distal bowel Defective Nutrient Hydrolysis
• Lipase inactivation by excess HCl (Zollinger-
Conditions Predisposing to Bacterial Overgrowth
Ellison syndrome)
• Intestinal Stasis
• Pancreatic enzyme deficiency
o Anatomic
o Chronic pancreatitis
 Intestinal Strictures
o Pancreatic cancer – obstruction of
 Small intestinal diverticulosis pancreatic duct
 Surgical procedures • Improper mixing or rapid transit of nutrients
o Motility disorders
 Scleroderma Test for Pancreatic Insufficiency
 Diabetes mellitus • Invasive
o Secretin stimulation test
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 3 of 18
 Inject secretin IV o 2+
Osteoporosis (vitamin D, Ca )
 Aspirated pancreatic juice from o Easy bruising (vitamin K0
duodenum o Peripheral neuropathy (Vitamin B12)
 Bicarbonate and amylase levels
• Associated Diseases
 Low levels consistent with o Dermatitis herpetiformis
pancreatic exocrine insufficiency
 IgA deposits in skin
 Pruritic, blistering
• Non-invasive
o Small intestinal lymphoma
o Fecal Chymotrypsin level
 Risk may be less adherence to
 Low with pancreatic exocrine
gluten free diet
insufficiency
o Fecal Elastase level
 Low in pancreatic exocrine
insufficiency
 Most sensitive/specific fecal test
o Serum trypsinogen level

Malabsorption: Mucosal Loss


• Extensive surgical resection
o Short bowel syndrome
• Extensive infarction

Malabsorption: Mucosal Disease


• Complication of radiation treatments
• Diagnosis
• Infections
o Biopsy of small intestine during
• Vascular insufficiency (ischemia)
endoscopy
• Inflammatory conditions o Blood tests
o Crohn’s disease
 Anti-gliadin antibodies (IgA and
o Celiac sprue
IgG)
 Anti-endomysial antibodies (IgA)
Celiac Sprue
 Tissue transglutaminase
• Gluten sensitive enteropathy
antibodies
• Reaction against gluten in diet
• Epidemiology: whites (highest in Northern
European descent)
• Pathogenesis
o Mostly Genetic & Environmental,
sometimes Autoimmune
o Ingestion of gliadins, hordeins, and
secalins: proteins found in wheat, barley,
and rye → infiltration of intestinal
mucosa with intraepithelial CD8+
lymphocytes and CD4+ lymphocytes in
lamina propria → villous atrophy
o CD4+ T cells mediate disease process • Treatment
o Genetic: very close association with HLA- o Gluten free diet
DQ2 (presents peptides to and binds
o Nutritional supplementation
CD4)
 Iron
 Lesser association with HLA-DQS  Vitamin D, calcium
• Pathology
o Villous atrophy: flattening of mucosa,  Vitamin B12 (intramuscularly)
o The future: ingesting substances that will
loss of villi
o Increased lamina propria lymphocytes breakdown gluten
• Clinical Presentation
Drugs Causing Malabsorption
o Varied – depends on extent of mucosal
• Luminal effect
disease
o Neomycin
o Typical: crampy abdominal pain, chronic
o Cholestyramine
diarrhea, bloating, weight loss,
o alcohol
steatorrhea
o Iron deficiency • Mucosal effect
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 4 of 18
o Villous flattening • Chronic or recurrent
 Colchicine • Lower abdominal pain
 Methotrexate • Disturbed defecation
• Stricture • Bloating
o NSAIDs • Not explained by structural or unknown
• Enterocyte damage biochemical abnormalities
o Direct toxicity
 alcohol IBS: Symptoms
• Brush border enzyme effect • Abdominal pain eith constipation or diarrhea
o Neomycin • Bloating, gas
o Alcohol • Abdominal distention
• Intracellular effect
o Laxatives
o Colchicine
o Biguanides
IBS: Epidemiology
D-Xylose Test: General Test for Malabsorption • Prevalence in North America is 10%-20%
• Xylose o Equally divided between IBS with
o Sugar absorbed in duodenum and diarrhea, IBS with constipation, and IBS
jejunum alternating between diarrhea and
o Not completely metabolized constipation
o Excreted in urine intact form o Prevalence of each subtype is ~ 5%
• Xylose administered orally and urine collected • 2:1 female predominance in North American
• Abnormal: <4 g xylose in urine after 25 g dose population-based studies
• Caveats
o Renal function
Extent and Impact of IBS
o Bacterial overgrowth
o Vary rapid intestinal transit IBS in 10%-20% of US Population
(approximately 35% of these patients seek medical care)
Secretory Diarrhea
• Abnormal ion transport in intestinal epithelial
Annual Cost of
cells
Reduce Extent and Disease is High
• Decreased abdorsption of electrolytes Quality of Life Impact of IBS (~$21 billion
• Electrolytes: major solutes in intestinal lumen
per annum)
• Electrolytes account for most of luminal
osmolality
• Congenital defects in ion absorption
Increases Absenteeism and
• Intestinal resection Decrease Work Productivity
• Diffuse mucosal disease
• Abnormal mediators
o Fatty acids: stimulate colon secretion IBS: Pathophysiology
o Bile acids: stimulate fluid and electrolyte • IBS is a condition associated with altered brain-
secretion in colon gut communication resulting in:
o Circulating agents released by o Distributed gut function and sensation
neuroendocrine tumors o Disturbed CNS function
• IBS patients display
Fecal Osmotic Gap o Altered CNS responsiveness to visceral
290 mosm/kg H2O – ([Na+} + [K+] stimuli
Osmotoc diarrhea: >125 o Visceral hyper responsiveness to
Secretory diarrhea: <50 environmental and luminal events (gut)
Altered Intestinal Motility Role of Enteric Nervous System
• Autonomic diabetic neuropathy – “diabetic • ENS contains many neurotransmitters, including
diarrhea” 5-HT, substance P, VIP and CGRP
• Hyperthyroidism • ENS controls motility and secretory functions of
• After vagotomy (peptic ulcer surgery) the intestine
• Irritable bowel syndrome (IBS) • ENS functions autonomously, but may be
modified by the parasympathetic and
Irritable Bowel Syndrome sympathetic nervous systems

F is for Friends who do stuff together. F.U.N. Here with my best buddy.
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 5 of 18
⇒ WBC↑
Selected Mediators of Motility and Visceral ⇒ ESR ↑
Hypersensitivity ⇒ Abnormal chemistry
Motility Visceral Hypersensitivity
o Serotonin o Serotonin Therapeutic Options for Patients with IBS
o Ach o Bradykinin • Antispasmodics: hyoscyamine and dicyclomine
o ATP o Tachykinins • Bulking agents
o Motilin o Calcionin gene- • Antidiarrheals
o Nitric Oxide related peptide
• Antidepressants
o Somatostatin (CGRP)
o Neurotropins • Alosetron
o Substance P
• Tegaserod
o Vasoactive
intestinal • Behavioural therapy
polypeptide (VIP)
Explanations for Diarrhea
• Bile salt malabsorption
- Cholerrheic diarrhea
• Bacterial Overgrowth Syndrome
• Secretagogue
• Pancreatic insufficiency – chronic pancreatitis
• Alcohol
• Possible nutrient deficienies:
- Vitamin A, D, E, K
- Vitamin B12

CASE PRESENTATION:

1) 62 year old woman complains of floating stool


with oil droplets around stool. She has lost
Rome Criteria 10lbs. She also notices that she bruises very
easily. She often feels bloated and distended.
• Atleast 12 weeks of continuous or recurrent
She had surgery 10 years ago to remove several
symptoms:
areas of small intestine after an episode of
o Abdominal pain and discomfort
ischemic bowel.
 Relieved with defecation or a. What is the most likely cause of her
 Associated with a change in symptoms?
frequency of stool or b. What tests would you order to help
 Associated with a change in confirm the diagnosis?
consistency of stool c. How would you treat her?
• 2 or more of the following, a least on ¼ of
accasions or days: 2) A 44 year-old man is admitted to the hospital
o Altered stool frequency with an acute upper GI bleed due to several
o Altered stool form gastric and duodenal ulcers seen on an urgent
o Altered stool passage upper endoscopy of the duodenum. The patient
o Passage of mucus also complains of a 1 year history of frequent
o Bloating or feeling of abdominal non-bloody diarrhea. A fecal osmotic gap is very
distention low.
a. What type of chronic diarrhea does this
IBS: Diagnosis (RED FLAGS) patient have?
 Physical: b. What is the most likely cause?
⇒ Abnormal exam c. What is the mechanism to explain the
diarrhea?
⇒ Fever
d. What blood test can you check to make
⇒ Positive occult stool the diagnosis?
 Historical: 3) 55 year old male alcoholic referred to GI with
⇒ Weight loss persistent (>4weeks) loose non-bloody stool.
⇒ Onset in elder patients Diarrhea often wakes him from sleep. 6 months
⇒ Nocturnal awakening earlier: surgical resection of 50cm of ileum due
⇒ Family History of CA or IBD to carcinod tumor of ileum. Reports no fever or
 Initial Labs: abdominal pain. He has lost approximately 10
lbs.
⇒ Hgb ↓
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 6 of 18

4) 28 year old man complains of abdominal - Puborectalis plus external anal-sphincter


bloating and foul smelling gas. He has contracting
intermittent diarrhea after eating ice cream. He • Skeletal muscle responses
has always been able to eat ice cream before. - Puborectalis plus external anal-sphincter
a. What is the most likely explanation for relax
the patient’s symptoms? - Levator ani, rectus muscles and
b. How would you treat his symptoms? diaphragm contract
• Smooth muscle responses
ANSWERS: - Internal anal sphincter relaxes
1) Short Bowel Syndrome (Malabsorption) - Rectal contraction
confirmed by sudan test. Bleeding due to ↓ in
vitamin K dependent factors. Causes of Constipation
2) Zollinger-Ellison  hypergastrenemia • mode of life
3) Short Bowel Syndrome; if NO surgical resection • drugs
• Metabolic
+ normal laboratory findings  IBS
4) Lactose intolerance (Osmotic diarrhea) or • Neurologic
Contaminated ice cream • GIT abnormalities
- Mechnical obstruction
NON-MALIGNANT COLONIC DISEASES • Anorectal abnormalities
• Constipation • Idiopathic
• Diverticula
• Appendicitis Drugs Associated With Constipation
• Hemorrhoids Class Examples
Prescription Drugs
• Anorectal Disease
Opiates Morphine
- fissures, fistulae, abscess
Anticholinergic drugs Librax, belladonna
Tricyclic antidepressants Amitryptiline>nortiptyline
CONSTIPATION
Calcium channel blockers Verapamil hydrochloride
• reported by 5-30% of the population Antiparkinsonian drugs Amandatadine
• women>men Sympathomimetics hydrochloride
• non-whites > whites Antipsychotics Ephedrine, terbutaline
• Older age – but any age group possible Diuretics Chlorpromazine
• 6.8% of >65 y.o. use laxatives weekly Antihistamines Furosemide
• 2.5 million office visits yearly Diphenhydramine
Nonprescription drugs
Symptoms Antacids, especially
• infrequent stools calcium containing
• stools difficult to pass Calcium supplements
Iron supplements
• digitate
Antidiarrheal agents Loperamide, attapulgite
• sense of incomplete evacuation NSAIDS Ibuprofen
• soiling clothes
• bloating
Metabolic Causes of Constipation
• Hypothyroidism
Definition
Two or more symptoms for at least 3 months: • Diabetes mellitus
• Training >25% of time • Hypercalcemia
• Hard stools >25% of time - Depressive effect on autonomic nervous
system
• Incomplete evacuation > 25% of time
- Smooth muscle hypotonicity
• Less than 3 bowel movements per week
- Dehydration
• Hypokalemia
Functions of Colon • Uremia
• absorb water and electrolytes • Heavy metal poisoning
• slow feel of passage in right colon
• propulsion of feces to rectosigmoid by left colon Neurologic Causes of Constipation
• storage of feces in rectum • Spinal cord injury
• defecation • Multiple sclerosis
• Parkinson’s Diseae
Mechanism of Defecation
• Autonomic neuropathy
• Holding

Hahahahaha… hahahahaha.. hahahahahaha…


Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 7 of 18
- Muscular hypertonicity
GIT Abnormalities  Faliure to relax
• Colon cancer  Incomplete relaxation
• External compression on colon from malignant  Paradoxical contraction of pelvic
lesion floor and external anal sphincter
- Ovarian cancer during attempted defecation
• Stricture
- Diverticular - Muscular hypotonicity
- Ischemia  Excessive perineal descent
• Post-surgical (anastamotic stricture) • mechanism unclear; heterogenous disorders

GIT Abnormalities: Hirschsprung Disease Irritable Bowel Syndrome


• Ruysch 1691  HIrschprung 1886  Swenson • altered motility
1948 • visceral hypersensitivity
• Heterogenous genetic disorder • alterations in enteric nervous system and
- Autosomal dominant and recessive forms interaction with central nervous system
• Congenital absence of ganglion cells in distal • impact of neurotransmitters  serotonin
colon
Serotonin (5-HT) in the Human Gut
- Begins at anus and extend proximally
5- 5- 5-
(variable distance)
HT1 HT2 HT4
• Myenteric (Auerbach’s) and submucosal
Gastric ↑ ↑
(Meissner’s) plexus are absent accommodation
- Problem with migration and development
Transit ↓ ↑ ↑
of neural crest cells
Colonic tone ↓ ↑
- Loss of neural inhibition – colon remains
Sensation ↑ ?
contracted
Secretion ↑
 Proximal colon is dilated
(“megarectum”)
• Diagnosis: newborns/infants Tests to Evaluate Cause of Constipation
• Treatment: surgery • Barium x-ray, colonoscopy – exclude structural
disease
Anorectal Abnormalities • Measurement of colonic transit time
• Rectocoele (if very large) - Colonic markers studies
- Protrusion of anterior rectal wall into • Defecography
vagina • Anorectal manometry
- Defect of recto-vaginal septum
• Anal fissure Treatment of Constipation
• Trauma • diet
- Recent vaginal delivery • life changes
• laxatives – avoid dependence
Idiopathic/Functional Constipation • enemas, suppositories
• Irritable bowel syndrome • Prokinetic drugs
• Slow colonic transit (colonic inertia)
• Evacuatory failure DIVERTICULA
- Pelvic floor dysfunction • may be located throughout intestinal tract
Idopathic Constipation: Slow Transit Constipation (esophagus colon)
• Slow Transit Constipation: slower than normal • most common in colon
movement of feces from right to left colon • rare in esophagus and stomach
- Colonic inertia • in SI may predispose to bacterial overgrowth
 Decreased numbers of high syndrome
amplitude propagated
contractions 1. Meckel’s Diverticulum
- increased, coordinated motor activity in • remnant of primitive yolk sac
distal colon • may be connected to umbilicus fibrous band:
 functional barrier/resistance to remnant of vitello-intestinal tract
normal transit • mostly located in distal ileum on anti-mesenteric
disorder
Idiopathic Constipation: Pelvic Floor Dysfunction • walls have all layers of intestine
• “Evacuatory failure”: inability to adequately
evacuate content from rectum 2. Colonic Diverticulosis
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 8 of 18
• associated with low fiber intake 4. Diverticulitis
• incidence increases with age • inflammation and perforation of diverticulum
• higher incidence in western countries • in 10-25% of patients with diverticulosis
• located most commonly on left side of colon • microperforation of diverticulum from
• 96% sigmoid impissiated stool using abrasions of mucosal
• 35% ascending, transverse, descending lining
• Herniations of mucosa and submucosal of colon • Symptoms: fever, left lower quadrant pain
through muscularis • High WBC
• Develop in rows between mesenteric and lateral
taniae Diverticulitis: Complications
• Penetrating vasa rectae – points of greatest • Abscess
weakness • Luminal obstruction
• Hypersegmentation of colon - increased luminal • Peritonitis
pressure • Fistula
• Clinical Manifestations: - Colo-enteric
- Most aysmptomatic - Colo-cutaneous
- Intermittent abdominal pain or bloating - Colo-vesical
- Altered stool caliber if colon is narrowed - Colo-vaginal
• Diagnosis: Colonoscopy
Diverticulitis Evaluation
• Physical exam
• No endoscopic procedures
• No barium enemas
• Blood work: CBC
• CT scan

Diverticulitis: Treatment
• Uncomplicated
- Conservative measures
- Antibiotics
• Diagnosis: Barium enema - Surgery in younger patients (<40 yo)
• Complicated
- Antibiotics
- Surgery – usually two stage

APPENDICITIS
Most common surgical emergency
• 5-10% of population
• Obstruction of appendiceal lumen by fecaliths
• In 1/3 of patients appendix has no obstruction –
pathogenesis unclear/ controversial

Variable locations of Appendix


• retrocecal
• Treatment: • subcecal
- High fiber diet • postileal
- Fiber supplements • preileal
- Rarely: surgical resection • pelvic

3. Diverticular Bleeding Appendicitis: Clinical Presentation


• Painless rectal bleeding • History most important
• 15-40% of patients with diverticulosis Classic:
• Caused by chronic injury to vasa recta - pain at some site in abdomen (peri-
• Diagnosis: Colonoscopy, nuclear medicine umbilical)
studies - anorexia, nausea, vomiting
• Treatmetn: - pain over appendix (RLQ) – McBurney’s
- Conservative point
- Angiography - Fever
- Surgery (rarely) • History may vary in retro-cecal appendix,
elderly, pregnancy, immunosuppressed
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 9 of 18

• not painful unless external and thrombosed


Appendicitis: Evaluation and treatment
• Physical exam Hemorrhoids: Diagnosis
• Blood tests: CBC • rectal exam
• Radiologic test not always necessary: • anoscopy
- CT Scan
• flexible sigmoidoscopy
- Ultrasound
• Treatment: Surgery Hemorrohids: Treatment
- Open Rationale Treatment
- Laparoscopic Reduce Downward Diet, bulk agents(fiber)
Pressure Avoid prolonged sitting at
HEMORRHOIDS defecation
• Prevalence in USA: ≈ 50% adult population
• Symtpomatic in 10-25% Fix cushions to underlying Sclerosants
• Collection of vascular tissue, “cushion”, in anal sphincter Rubber band ligation
canal Cryotherapy
• Normal – maintains continence Photocoagulation
Electrocoagulation
• Internal hemorrhoids
Reduce sphincter pressure Manual dilatation
- Dilatation of superior (internal )
Internal sphincterectomy
hemorrhoids veins
Excise hemorrhoids hemorrhoidectomy
- Covered by mucosa
• External hemorrhoids
ANAL FISSURES
- Dilatation of inferior (external )
hemorrhoids veins • longitudinal or elliptical defect in anal canal
- Covered by perianal skin • young – middle-aged
• May have both as these veins may form • 90-98% occur posteriorly in midline
anastomoses • Due to trauma from stool or associated with
Crohn’s disease; carcinoma
Anorectal Anatomy • Chornic anal fissure:
- Fissure
- Hypertrophic anal papilla at proximal end
- Sentinel at lower end
• symptoms: extreme pain with defecation,
bleeding
• treatment: fiber, bath, nitro, botox, surgery

Hemorrhoids Pathogenesis
• normal vascular cushions
• downward pressure during defecation
• muscle fiber anchor hemorrhoids loosen 1. Anorectal Abscess
• hemorrhoidal tissue slides, congested, bleeds • infections of tissue spaces adjacent to rectum
• prolapse and anal canal
• predisposing conditions: Crohn’s, hematological
Hemorrhoids: Symptoms disorders, immunodeficiency states
• bright red bleeding • pain, fever, mass
• prolapse ( may sense a protruding mass) • surgical drainage
• mucoid discharge with prolapse • antibiotics
• itching if poor hygiene
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 10 of 18
Mucosal Ulceration Transmural
Inflammation
in Colon

Ileocolitis
Ileitis Colitis

The Spectrum of IBD

Anorectal Abscess
1. submucosal
2. pelvirectal
3. ischiorectal
4. perianal
5. marginal
6. intersphincter

2. Anorectal Fistula
• hollow fibrous tract lined by granulomatous
tissue
Epidemiology of IBD
• opening inside anal canal or rectum and another
• 1-2 million IBD patients in the U.S.
orifice to perianal skin
• Equal incidence of ulcerative colitis and Crohn’s
• drainage of pus, blood, mucus stool
disease
• associated disorders: Crohn’s, cancer, prior
• Approximately 10,000 new cases diagnosed
radiation treatments
annually.
• Treatment: antibiotic, surgery
• Peak onset: 15 to 25 years of age
Anorectal Fistulas • Second peak incidence: 50 to 65 years of age
• Intersphincteric • Approximately equal between males and females
• Suprasphincteric • Incidence increased in industrialized nations
from 1970 to 1990
• Trans-sphincteric
• Extrasphincteric
IBD – Interaction of Genetic Susceptibility,
Immune Dysregulation, and Environmental
Case Presentation Triggers
52 year old woman with 25 year history of constipation.
She often goes 1-2 weeks without a bowel movement.
No trouble passing stool. She has bloating, cramping.
• What disorders should be excluded as a cause of
this patient’s constipation?
o Metabolic, mechanical obstruction,
mediations, neurologic
• What is the pathophysiology of idiopathic
constipation?
o Slow transit
o Pelvic floor dysfunction
• How would you treat her?
o Fiber
o Osmotic laxatives Environmental Triggers
o Tegaserod

INFLAMMATORY BOWEL DISEASE

Inflammatory Bowel Disease

Ulcerative Colitis Crohn’s Disease


Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 11 of 18
Familial Patterns of IBD
• 10-15% occurrence of IBD in relatives
• Strong concordance by disease category
• Genetic vs. environmental influences still
unresolved

Genetics of IBD
• Specific genes better understood
• NOD2/CARD15 gene on chromosome 16 –
identified by linkage studies
• NOD2/CARD 15 gene: encodes intracellular 30% - proctitis
protein NOD2 30% - Extensive/Pancolitis
o Innate immunity through NF-kB 40% - Distal/Left-Sided Colitis
mechanism
o Involved in apoptosis Diagnosis
o Involved in recognition of microbes • Clinical history
• Association of IBD with various MHC loci • Exclude infection
• Endoscopic appearance
Inflammatory Bowel Disease Process • Pathology
1. Antigen processing and presentation, activation • Serologic testing
of macrophages
• Antibiotics
• Probiotics
2. Antigen recognition, activation of CD4+ T cells
• CyA
• Tacrolinase
• ?MTX
3. Generation of Tk1/Tk2 response
• IL-10
4. Production of proinflammatory cytokinase
• Anti TNF antibodies
• Thalidomide
• Corticosteroids Complications
• IL-11 Toxic Megacolon
5. Recruitment, migration, and adhesion
• Antisense oligonucleotide to ICAM-1
• Anti-α4 integrin antibody
• ?Heparin
6. Inflammation and injury
• Aminosalicylates
• Corticosteroids
• ?Local anesthetics
7. Repair and restoration
• ?Heparin
2. CROHN’S DISEASE
• ?IL-11
• ?Nicotine Clinical Types
Inflammatory
1. ULCERATIVE COLITIS
• Pain
• Tenderness
Symptoms
• Bloody diarrhea • Diarrhea
• Urgency
Obstructive
• Abdominal pain (left-sided)
• Cramps
• Fever
• Distention
• Nocturnal diarrhea • Vomiting
• Frequent small volume bowel movement
Fistualizing
Location and Extent • Diarrhea
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 12 of 18
• Damage to skin o Family history
• Air/feces in urine • Physical exam
• Types • Radiologic evaluation
o Enteroenteric • Colonoscopy with intubation of ileum
o Enterovesicular • Serologic testing
o Enterocutaneous
Antibody Testing in IBD
• pANCA – perinuclear antineutrophil cytoplasmic
antibodies
o Targets histone 1, cross-reactive to
bacteria
o 65% sensitive, 85% specific for UC
• ASCA – anti-Saccharomyces cerevisiae
antibodies
o 61% sensitive, 88% specific for CD
o More common in small bowel CD

Extra-intestinal Complication of IBD


Eyes
• Episcleritis
• Uveitis
Gastroduodenal – 5%
Mouth
Small intestine alone – 5%
• Stomatitis
Right Colon – 35%
Distal Ileum – 35% • Aphthous ulcers
Colon alone – 20% Kidneys
• Stones (nephrolithiasis)
Endoscopy • Hydronephrosis
• Fistulae
• Urinary tract infection
Liver
• Steatosis
Biliary Tract
• Gallstonses
• Sclerosing cholangitis
Joints
Distinguishing Features • Spondylitis
• Granuloma • Sacroiliitis
• Focal lesions • Peripheral arthritis
• Perineal disease Skin
• Eythema nodosum
• Asymmetric involvement
• Pyoderma
• Small bowel involvement
o Gangrenosum
• Skip lesions
Circulation
• Fistulizaton
• Phlebitis
• Strictures
• Rectal sparing
• 20-30% without bleeding Extra-intestinal Complications of IBD: Relationship
to Disease Activity
Natural Courses of CD – The Facts • Related to activity of bowel disease
• Nearly 80% of patients require surgery within 2 • Peripheral arthritis
years of onset o Erythema nodosum
• Recurrence within 6 years of surgery: 90% o Episcleritis
endoscopic/radiologic, 58% symptomatic o Apthous oral ulceration
• 20% of patients treated with steroids fail to • Usually related
respond after 1 year o Pyoderma gangrenosum
• 36% of patients are unable to discontinue due o Uveitis
steroid to rapid recrudescence • Unrelated
o Sacroileitis
Diagnosis
o Spondylitis
• Clinical history
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 13 of 18
o Primary sclerosing cholangitis o Induction of Remission in CD and UC
• Toxicity
Systemic Complications of Ulcerative Colitis: o Metabolic
Peripheral Arthritis o Musculoskeletal
• Monoarticular  Avascular necrosis
• Asymmetrical  Arthralgias
• Large>small joint  Osteoporosis
• No synovial destruction o Gastrointestinal
• No subcutaneous nodules o Cutaneous
• Seronegative o Neuropsychiatric
o Ocular
Osteoporosis in IBD o Immunologic
• Incidence 20% to 30% o Growth failure
o Corticosteroid use, dose, and duration
important Remission Rates in Acute CD
o May occur in absence of corticosteroid Studies with Budesonide CIR
use
o Pathophysiologic considerations
(smoking, amenorrhea, exercise status,
etc)
• Corticosteroid-associated bone loss occurs early
• All IBD patients should have bone density
scanning
• Prophylactic use of calcium, vitamin D,
bisphosphonates, nasal calcitonin

Pediatric Complications of IBD


• Growth Failure
Role of Immunosuppresive Agents
6-Mercaptopurine, azathioprine, methotrexate,
IBD: Treatment
cyclosporine
• Steroid-sparing
• Induction of remission
• Speed of onset variable
• Maintains remission
• Requires periodic monitoring
• Generally acceptable side-effect profile

Biologic Therapy
Anti-TNFα Therapy
• Infliximab
• Adalimunab

Infliximab Side Effects


• Infusion reaction
Dose Response to Mesalamine in Active Ulcerative • Delayed type hypersensitivity reaction (human
Colitis
anti-chimeric antibodies)
o Less likely if on AZA/6-MP
• 15% had fistula-related abscess
• Headache
• Infections
o TB – all patients need pre-treatment PPD
• Malignancy
• Intestinal stenosis

Investigational Drugs
*Significantly different from placebo • Anti-sense oligonucleotides
o ICAM-1
Corticosteroids in IBD o NF-KB
• Role • Fish Oils
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 14 of 18
• Interleukin-10 o What would you most likely see on
• Interleukin-11 colonoscopy?
• Anti-integrin antibodies (natalizumab) – alpha-4  Erythema, punctuate ulcerations,
integrins involved in leukocyte migration loss of vascular markings,
• Thalidomide – anti-TNF friability
• Growth Hormone o What is he at risk for in the long term?
• Anti-TB therapy  Colon cancer
o If he had a fever, severe abdominal pain,
• G-CSF - ?Mucosal neutrophil deficiency in
and distention, what would be your
Crohn’s
immediate concern?
• Parasitic therapy – induces Th2 response (IL-4)
 Toxic megacolon
IBD: Indications for Surgery
Case Presentation
Ulcerative Colitis:
• 36 yo white woman with right lower quadrant
Panproctocolectomy
abdominal pain, diarrhea and weight loss
• Failure of medical therapy
• Has pain in perianal area with drainage
• Dysplasia or carcinoma
• No other past medical history
• Debility, poor QOL
• PE: no fever, stable BP, HR
• Intolerant of medications
o One oral aphthous ulcer
• Massive hemorrhage, perforation
o Mild fullness and tenderness in RLQ
• Intractable pyoderma, hemolysis o Fistula opening on labia and perineum
• What is the most likely diagnosis?
Crohn’s Disease:
o Crohn’s disease
Directed to specific complication
• What is the most likely result of the anti-
• Symptomatic obstruction
saccharomyces cerevisiae antibody test?
• Symptomatic fistulae
o Positive
• Perforation
• What is the most likely finding on small bowel
• Hemorrhage barium x-ray?
• Dysplasia or carcinoma o Narrowing, irregularity of ileum
• Perianal disease • What is an important pro-inflammatory cytokine?

Nutritional Therapy in IBD


o TNF α, IFNy
Food: best nutrition source • What is the effect of smoking on this disease?
Parenteral: o Worsens and reduces response to
• Ulcerative Colitis medical therapy
o No role in primary therapy
o Adjunct to surgery NOTES (Lecture from 3b)
Part of the intestine where most absorption occurs:
• Crohn’s Disease
o “Bowel rest” as primary therapy • Duodenum
o Fistula healing • Jejunum
o Adjunct to surgery Absorption of bile salts and Vit. B12 occurs in the ileum
o Short bowel syndrome If you lack bile saltsfat malabsorption
o Growth failure
Enteral: SMALL INTESTINE
• Ulcerative Colitis:
DIARRHEA
o No role in primary therapy
• predominant clinical manifestation of small
• Crohn’s Disease
intestine disorder
o Role in primary therapy
• may be acute or chronic
o Fistula healing
o Adjunct to surgery • acute: < 4 weeks
o Short bowel syndrome • chronic: > 4 weeks
o Growth failure • Acute Diarrhea may be:
1. infectious
Case Presentation: Ulcerative Colitis 2. non-infectious or parenteral diarrhea
• 22 year old man complains of 5 weeks of small • Chronic diarrhea may be caused by:
volume loose, bloody stool. He has urgency to 1. Luminal/mucosal disorder
move his bowels. He occasionally has crampy 2. Pancreatic insufficiency
left lower abdominal pain that diminishes after a 3. Motility disorder
bowel movement. He has occasional low grade 4. Large resection of the bowel
fevers. 5. Short Bowel Syndrome
6. Infectious: amoebiasis & TB
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 15 of 18
+ +
• Psuedodiarrhea: fecal stool <200g = 290 – 2 (Na + K )
True diarrhea: fecal stool of ≥200 g if >125, osmotic diarrhea
*these two are not clinically distinguishable if <50, secretory diarrhea
• Diarrhea is described as having: • most common cause of secretory diarrhea is
1. liquid consistency cholera (infectious diarrhea din)
2. increased frequency
• Normal stools – liquid but once a day (balance SECRETORY DIARRHEA
between liquid and fiber; high fiber, increase • Secretory tumors (gastrinomas,
liquid stool) somatostatinomas, Zollinger-Ellison syndrome,
neuroendocrine tumors such as VIPoma)
• Defecation controlled by:
• Laxative abuse: Bisacodyl (Dulcolax)
o Skeletal: pudendal/puborectalis, external
• Drugs (antibiotics especially Macrolides,
& internal anal sphincter
o Autonomic: sensation to defecate; if not Erythromycin)
regulated, rectum will be filled with feces • Erythromycin is a prokinetic used for dysmotility
disorder; it is not corrosive in stomach but
• Effort:
increase activity/motility that’s why people vomit
o Abdominal muscles: involved in Valsalva
because of relaxation of sphincters, increasing
maneuver
peristalsis
o Pelvic muscles
MALABSORPTION OF FAT
Types of Diarrhea
• it can mean pancreatic insufficiency (enzyme
1. Osmotic
deficiency involved in metabolism of fat,
2. Malabsorption/Maldigestion of Fat (Fatty carbohydrate and protein)
Diarrhea/ Steatorrhea) • Fat malabsorption develops steatorrhea
3. Inflammatory Diarrhea
4. Secretory
o Oly way to test is through Sudan’s test
5. Altered Motility or fecal fat (usually 10 grams, in books
*these types overlap 7 grams)
• Carbohydrate malabosorption overlaps with
• Altered motility lactose intolerance which causes to 2 types of
o Causes diarrhea:
- seen usually in cerebrovascular 1. osmotic diarrhea sec. to disaccharide
accidents 2. malabsorption
- neurological disorder (DM) o Dx:
- those who underwent • D-Xylose test - a general test used
surgery/resection to detect pancreatic insufficiency
- can be due to an infectious cause which works by stimulating
- those with mucosal abnormalities: pancreatic enzymes
celiac sprue
• Direct measurement of enzyme
 gluten (present in barley or
– such as chylose, trypsinogen,
wheat products) sensitivity
elastase, chymotrypsin
 usually in Western countries
• Can be categorized into defects of: luminal,
 Due to sensitivity to barley
mucosal and motility
or wheat products
1. Mucosal
 Dx: o involves SI mucosa
1. through biopsySee: o due to nutrient deficiency, bowel
atrophic villi resection, infectious causes of bowel
2. serologic markers: anti- involving mucosa
gliadin and anti-
endomysial
2. Altered motility delayed movement sec.
to stasis or short bowel syndrome which is
o transit is very slow --- strain bacterial due to resection
proliferate  infectious
INFECTIOUS
OSMOTIC DIARRHEA • common infectious disorder that affects terminal
• prototype: lactose intolerance ileum are S. Typhi and TB
• Disaccharide induces osmotic pressure that will
retain fluid in stools *if you have bile acid insufficiency and resection of ileum
• Magnesium is part of antacids which induces  fat malabsorption
diarrhea *Test for carbohydrate malabsorption is D-Xylose test
• Aluminum: constipation *General test together with pancreatic test: Secretin test
• Dx: take fecal osmolality gap
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 16 of 18
*Evaluate deficiency in terminal ileum: lactose and B 1. Straining >25% of the time
complex test for instrisic factor (Schilling’s test) 2. Hard stools
3. Incomplete evacuation
MOTILITY 4. Need to manipulate
• 3 Common Causes: DX: 3 out of 4  Chronic constipation
1. Post-surgical resections – also ____ bacterial • 3 Classification of Constipation
luminal/mucosal diarrhea 1. Normal transit
2. Endocrine disorder – DM paresis & o peristalsis is normal but the end
Neurological conditions result is constipation
3. IBS predominantly diarrhea o due to imbalance between fluid and
• Treatment:: Remove offending agent fiber (↓fiber  ↓fluid)
a. Infectious (bacterial): antibiotics o Most common cause of constipation
b. Lactose intolerance: avoid dairy products o Tx: Increase fiber in the diet or give
c. Tumors and IBD: surgery fiber supplements
2. Slow Transit
Cases o 2nd most common cause 
CASE 1: 44 y.o. male ate ice cream develops diarrhea. neurological or endocrine disorder
Hx shows he usually eats ice cream a lot. especially DM
Dx: Secretory Diarrhea (based on the history) 3. Outlet form or Obstructive
CASE 2: 62 y.o. has chronic abdominal pain, intermittent
o 3rd most common is seen in
diarrhea more than 4 weeks duration. He had conditions when there is obstruction
resection 10 years ago. Exams are normal. in outlet
o Most common cause
DDx: can be bacterial  ruled out because he
- Tumors in the rectum/anus
has no fever; Ask, why did he have a resection?
- Tumors in pelvic organs
Maybe she has a tumor.
o Non-tumor cause:
Dx: IBS  if everything is normal, think about
- Hemorrhoids
IBS
- Proctitis,
- Bolus of ascaris, polyps (occurs
CASE 3: 45 y.o. male chronic alcoholic starts to have oily
all over the colon but more on
stool
the rectosigmoid and anus)
Dx: Alcohol-induced pancreatitis
- Anismus (constriction is present
Mx: confirm steatorrhea by Sudan’s test or fecal
at all times)
count
• Dx of constipation:
*In acute diarrhea, think whether it is infectious or non- o Hx, personal/social, PMH, PE
infectious. o Most impt. PE is DRE
*In chronic diarrhea, the possible causes can be due to o DRE:
osmosis, malabsorption, secretory, altered motility, or 1. Ask patient to be in left lateral decubitus
inflammatory 2. Visually examine rectum first: if there is
tumor, you will see prolapse
COLON 3. Lubricate gloved forefinger
• For water absorption and fecal formation 4. If there is no tumor, start touching the
• Major manifestation: constipation anus
Major manifestation in SI is diarrhea. 5. Observe for:
a. anus starts to grin meaning it is
CONSTIPATION contracting
• Bowel movement should occur 3x/week b. insert finger, feel for constriction at
• It is also defined in terms of consistency and first
c. after which, sphincter starts to relax
frequency.
d. palpate for internal wall (look for
• Clinically, the most common symptoms of
prostate or hemorrhoids)
constipation are:
a. Infrequent bowel movement e. ask patient to strain  normally feels
b. Difficulty in defecation (straining) proximal colon getting in your finger
c. Incomplete evacuation = means there is normal transit time
d. Prolonged stay in the rest room If none, there is slow transit time.
e. Can manifest with bledding • Tx:
f. Digital manipulation o modify diet/give fiber supplements
g. Common among children: pellet like stools, o For slow transit:
M&M’s stools or goat like stools - Osmotic laxatives
• Major Criteria: - Polyethylene glycol
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 17 of 18
- Bulk-forming laxatives • 1/3 of acute appendicitis, negative for fecalith 
- Stimulating laxative: Bisacodyl
just inflammation bec. Appendix is a lymphoid
- Lubricating laxative: Mineral oil
tissue  autoimmune/immune responses
• Worst scenario in constipation: when tumors
cause obstruction • Classical manifestation of acute appendicits:
classic ap gait  “You are malicious!”
DIVERTICULAR DISEASE • Classic sequence: Abdominal pain usually.
• outpouching produced in the weakest part of Periumbilical (does not have to be epigastric
colonic wall: between vasa recta pain usually vague abdominal pain)  followed
• Types by nausea and vomiting or loss of appetite 
1. Pseudodiverticular localization to McBurney’s Point (RLQ pain)
o Most common manifest as AP walk and rebound tenderness 
o Does not involve the whole wall: fever
outpouching reaches the submucosa, • Most common differentials in females is: ectopic
mucosa, and muscularis only
pregnancy
o Due to weakening of the mucosa
2. True diverticular disease • Complications:
o Common in children is Meckel’s a. Same picture as diverticular disease because
o Involves all layers of the wall appendicitis is an outpouching and most
• 3 things that can happen in diverticulum: common cause is fecalith
b. Like diverticular disease, if with
a. Fecalith  stasis  bacterial overgrowth =
rupture/perforation leads to peritonitis,
diverticulitis
adhesions (comes later)
b. If eroded a vessel, it can lead to bleeding
which is bright red in color but c. If rupture/perforation is confined to the
spontaneously stop in most cases mesentery  appendiceal abscess
c. If diverticulitis becomes complicated, it can • Tx: surgery and antibiotics
rupture and get contained in the mesentery
with an end result: Abscess • Dx: mostly clinical (HX, P.E.)
• If appendiceal abscess is considered: UTZ
• Most are located in the sigmoid (where
• Rule out ectopic pregnanc by:
defecation process starts)
1. Pregnancy test
• Best way to dx diverticulitis: Barium enema 2. Obtained by UTZ: either pelvic/transvaginal
• Colonoscopy (more accurate than pelvic but drawback is
o not diagnostic, can miss divertiular disease discomfort especially in very young patients)
o can be done first if patients present with • Atypical manifestations may come because of
bleeding variable location of appendix (retrocaecal, post
o if too much bleeding, visualization can be caecal, inf. caecal, pelvic area)
difficult: Radionuclide imaging or RBC
tagging becomes the next best imaging
modality, used to identify the source of HEMORRHOIDS
bleeding • Can be internal or external
o only limitation of RBC tagging: needs to time
it because the requirement is for bleeding to • Internal: covered by mucosa thus not sensitive
persist 5 ml/min to pain; most common manifestation is
o other alternative: angiography bleeding
• Diverticulitis/Abscess Formation is diagnosed by: • External: covered by anoderm and rectum (pain
CT Scan which locate/visualize abscess sensitive areas, thus painful)
formation
• Only instance when internal hemorrhoids
o Clinically you can consider this if patient has become painful is when there is prolapse to
abdominal tenderness, fever & leukocytosis
anoderm  irritate anoderm
 manifestation of bowel stasis or bacterial
• Grading of Internal Hemorrhoids
overgowrth
o Best initial management: supportive thru
antibiotics; surgery can be done if vital signs
are normalize
o If bleeding does not stop  surgery
APPENDICITIS
• Most common theory: obstruction due to
fecalith (which happens in 2/3 of cases)
Subject: Medicine 2
Topic: GI part 3 (SI and LI)
Page 18 of 18
Grade 1 Non-prolapsing y uniform length, (normal intervening
Grade 2 Prolapsing but can be spontaneously perineal; signs of mucosa between
reduced congestion all lesions)
Grade 3 Prolapsing but needs to be digitally throughout
reduced mucosa
Grade 4 Prolapsing but non-reducible (like Both (+) ulcers
prunes, grapes) Deeper ulcer that’s
• When to do surgery? why TB ulcer is a
1. If hemorrhoids get thrombosed ddx bec. TB ileitis is
2. If there is repeated bleeding also seen in Crohn’s
3. Has a grade of III or IV disease
Biopsy Crypt of abscess Granuloma
TRAUMATIC ANAL DISORDER Ba enema Demonstrate Visualize deep
• Anal tears/Anal fissures/Anal lacerations leads to morbid ulcers and fistulas
compication UC;
infection  anal abscess
toxic megacolon,
• Most common cause of anal tear:
whole colon is
1. Constipation (most common cause is hard
dilated
stool)
Tx: Same
2. Self-induced/traumatic – usually seen in
1. 5-ASA
children
2. steroids
• Management 3. biologic agents addressing
1. Drain inflammatory cells (TNF)
2. Initiate antibiotics 4. Surgery
• Complications if infection is not addressed: Surgery Very good Very high recurrence
development of fistulous tract  anal fistula recovery rates
• In females, most common type is anal fistula Predispositi Yes Yes
because inadvertent suturing of colonic wall on to (but has more
during perineal episiotomy Malignancy chance)
• Same fistulas are also colo-vaginal but most get
out to perianal
• Management of fistulas: 2 or 3 stages of surgery
is done
- Depends on the length of the fistula
- Drawback: risk of recurrence if thorough
cleansing of fistula is not done properly
• Colorectal fistula: seen when patient starts to
urinate feces

INFLAMMATORY BOWEL DISEASE


• Types
1. Ulcerative colitis
2. Crohn’s Disease – manifests with
Tuberculous colitis
• Causes of IBD: genetic predisposition,
environmental toxins and autoimmune
• Commonality between the two is both have
diarrhea and bleeding

Ulcerative Crohn’s Disease


Colitis
Location Left Right
Proctitis or left Ileocolitiis; right of
side colitis colon and terminal
ileum are affected;
has rectal sparing
bec. of its
localization on the
right side
Manifestati Diarrhea, Diarrhea, bleeding
on bleeding
Colonoscop Diffuse lumps, Skip lesions