Topic: GI part 3
Lecturer: Dr. Mappala
Shifting /Date: 3rd /October 31, 2008
Trans group: Eis, Candy, Isay, Jassie
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
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
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:
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
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
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
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
Biologic Therapy
Anti-TNFα Therapy
• Infliximab
• Adalimunab
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?