Tuesday, December 5 (ellen)

Small and Large Intestine Pathology – December 5, 2006 Developmental Anomalies Small Intestine: ~ 1) atresia (Stenosis) – either complete failure of development of the intestinal lumen or narrowing. Only involved one segment of the bowel ~ 2) duplication – well formed structures, may or may not communicate with lumen of SI ~ 3) Meckel diverticulum – failed involution of omphalomesenteric duct, get blindended tubular protrusion ~ 4) Omphalocele – intestines herniated into this congenital defect membranous sac Large Intestine ~ 1) malrotation of developing bowel – predisposed to volvulus ~ 2) Hirschsprung disease – congenital megacolon Hirschsprung Disease: Congenital Megacolon ~ distention of colon ~ happens when caudal neural crest cells stops before it reaches the anus in embryo development ~ functional obstruction and progressive distention of parts of colon Acquired Megacolon ~ can result from: ~ 1) chagas diseases – from protozoans ~ 2) organic bowel obstruction ~ 3) toxic megacolon ~ 4) functional psychosomatic disorder Vascular Disorders Ischemic Bowel Disease ~ ischemic from obstruction of 1 of 3 major trunks of descending aorta after T12 ~ leads to hypoxia  infarction  necrosis  fibrosis Ischemic Bowel Disease ~ transmural  major mesenteric ~ mucosal/mural  usually local anatomical problem or hypoperfusion ~ predisposing conditions for all 3 ischemic forms ~ 1) arterial thrombosis ~ 2) arterial embolism ~ 3) venous thrombosis ~ 4) nonocclusive ischemia ~ 5) miscellaneous Hemorrhoids ~ variceal dilation in anal/perianal submucosal venous plexus

~ internal hemorrhoid – covered by rectal mucosa above anorectal line in superior and middle hemorrhoidal veins ~ external hemorrhoid – below anorectal line, cover by anal mucosa dilation of inferior hemorrhoidal plexus ~ internal and external bleed easily ~ internal can prolapse and get strangled by anal sphincter Diarrheal Diseases ~ biggest problem = dehydration Diarrhea and Dysentery ~ diarrhea: increase stool mass, stool frequency, and fluidity ~ see pain, urgency, perianal discomfort, and incontinence ~ dysentery: low-volume, bloody diarrhea ~ diarrheal disorders are categorized as follows: ~ 1) secretory diarrhea: same osmolarity as plasma, lasts even though fasting ~ 2) osmotic diarrhea: xs fluid that your body doesn’t really like ~ 3) exudative diseases: infection ~ 4) malabsorption: xs fat (steatorrhea) and not absorbing nutrients ~ 5) deranged motility: not pushing bolus properly, some move/some don’t Infectious Enterocolitis ~ microbial origin ~ rotavirus, calciviruses, and enterotoxigenic E. coli ~ major cause of chronic or recurrent infectious enterocolitis Viral Gastroenteritis ~ virus destroys microvilli and decreases absorption ~ osmotic diarrhea ~ villi repopulated with immature enterocytes and preservation of crypt secretory cells ~ have net water and electrolyte secretion Bacterial Enterocolitis ~ mechanisms underlying bacterial diarrheal illnesses ~ 1) take preformed toxin ~ 2) take toxigenic organism ~ 3) enteroinvasive  destroy mucosal cells ~ all 3 need: adherence, elaborate enterotoxin, need to invade Protozoal Infection ~ Entamoeba histolytica ~ causes dysentery ~ invade crypts of colonic glands  go into submucosa and therefore can move elsewhere ~ fecal oral spread ~ Giardia lamblia

~ in SI mucosa, no invasion ~ mucousy diarrhea ~ get through feces-contaminated water ~ Cryptosporidiosis ~ emergent cause ~ fatal complication of AIDS ~ waterborne contamination Malabsorption Syndromes ~ suboptimal absorption – fat, vitamine, protein, electrolytes, carbs, mineral, water ~ results in at disturbing at least one of: ~ 1) intraluminal digestion of proteins, cars, fats ~ 2) terminal digestion: hydrolysis of carbs, peptides at SI brush border ~ 3) transepithelial transport: nutrients, fluid, electrolytes across intestinal ~ M/C: pancreatic insufficiency, celiac disease, Crohn’s disease ~ osmotic diarrhea and steatorrhea ~ lactose intolerance – class example of defective mucosal cell absorption ~ abetalipoproteinemia – unable to export lipid b/c of autosomal recessive disorder ~ Gluten-sensitive enteropathy – reduction in SI absorptive surface area ~ celiac disease: gluten sensitivity ~ strong genetic susceptibility ~ early exposure of immature immune system to high gliadin levels ~ total flattening of mucosal villi ~ Tropical sprue: resemble celiac disease but occurs exclusively in tropics ~ Whipple disease: rare, systemic infection ~ mainly affects intestine, CNS, joints ~ cause: gram +ve Tropheryma whippelii ~ consequences: ~ 1) hematopoietic system ~ 2) MSK system ~ 3) endocrine system ~ 4) skin ~ 5) nervous system IBD ~ Crohn ds (CD) and ulcerative colitis (UC) ~ called idiopathic IBD b/c they share many symptoms ~ CD – affects any part of GI tract but mainly SI and colon ~ show noncaseating granulomatous inflammation ~ UC – nongranulomatous disease only in colon ~ pathogenesis: ~ 1) genetic predisposition? ~ 2) immunologic factors – T cells ~ 3) microbial factors – may provide antigenic trigger ~ IBD – heterogeneous group of diseases with exaggerated and destructive mucosal immune response

~ inflammation is final common pathway ~ see neutophils initially and mononuclear cells later ~ inflammation causes: ~ 1) impaired integrity of mucosal epithelial barrier ~ 2) loss of surface epithelial cell absorptive function ~ 3) activation of crypt epithelial cell secretion ~ bloody diarrhea Crohn Disease ~ any level of alimentary tract ~ extraintestinal complications of immune origin ~ systemic inflammatory disease with predominant GI involvement ~ worldwide distribution Ulcerative Colitis ~ ulceroinflammatory disease affecting colon ~ limited to mucosa and submucosa except in most severe cases ~ begin in rectum and goes proximally ~ systemic disorder Colonic Diverticulosis ~ diverticulum is a blind pouch leading off alimentary tract ~ it is lined by mucosa and communicates with lumen of gut ~ prototype: Meckel diverticulum ~ acquired diverticula – anywhere in alimentary tract (but m/c colon)  diverticular disease (Aka diverticulosis) ~ potential sites for herniations – where nerves and arterial vasa recta enter the inner circular muscle coat of the colon ~ 2 factors in genesis: ~ 1) exaggerated peristaltic contractions with increased intraluminal pressure ~ 2) focal defects to normal muscual colonic wall Bowel Obstruction ~ 1) Hernias ~ weakness or defect in peritoneal cavity wall ~ protrusion causes hernial sac ~ inguinal, femoral canals, umbilicus, surgical scars ~ if viscera that protrude and get trapped it can lead to permanent trapping (incarceration) and strangulation (infarction of trapped) ~ 2) Adhesions ~ surgery, infection, and endometriosis localized/general peritoneal inflammation (peritonitis) ~ adhesions might develop b/w bowel segments during healing process ~ fibrous bridges can create closed loops where intestines may slide and become trapped (internal herniation) ~ 3) Intussusception

~ telescoping proximal segment of bowel into distal segment ~ can be a tumour that becomes trapped by peristaltic wave and pulls its attachment into distal segment ~ 4) Volvulus ~ twisting of a loop of bowel or other structure ~ constricts venous outflow ~ affects small bowel