Pathology Of The Lower Gastrointestinal Tract PDF

M. Vincent Mesa, DO PATHOLOGY OF THE LOWER GASTROINTESTINAL TRACT  Topics to Cover  Histology overview  Congenital Defects  Obstruction  Vascular Problems  Malabsorption/Diarrhea  Infectious enterocolitis  IBD/colitis  Appendicitis  Tumors of Intestines SI ENDOSCOPIC VIEW LI END...

M. Vincent Mesa, DO PATHOLOGY OF THE LOWER GASTROINTESTINAL TRACT  Topics to Cover  Histology overview  Congenital Defects  Obstruction  Vascular Problems  Malabsorption/Diarrhea  Infectious enterocolitis  IBD/colitis  Appendicitis  Tumors of Intestines SI ENDOSCOPIC VIEW LI ENDOSCOPICALLY  HISTOLOGY  FOUR BASIC LAYERS  Mucosa: epithelium, lamina propria, muscularis mucosa  Submucosa: loose connective tissue, Meissner’s plexus  Muscularis Propria: inner circ., outer long, myenteric plexus  Serosa: fibroelastic tissue, mesothelium SMALL INTESTINE SMALL INTESTINE MUCOSA DUODENAL MUCOSA SI MUCOSA BRUSH BORDER COLONIC MUCOSA CONGENITAL ABNORMALITIES  ATRESIA/STENOSIS  DUPLICATION  MALROTATION  OMPHALOCELE  GASTROSCHISIS  MECKEL’S DIVERTICULUM (rule of 2s)  HIRSCHSPRUNG DIESEASE (AGANGLIONIC MEGACOLON)  INTESTINAL OBSTRUCTION  HERNIAS  ADHESIONS  VOLVULUS  INTUSSUSCEPTION  IMPACTION , fecaliths, foreign bodies  STRICTURES/ATRESIAS  TUMORS/Infarction INTESTINAL OBSTRUCTION  VASCULAR DISEASES ISCHEMIA/INFARCTION  ANGIODYSPLASIA  HEMORRHOIDS  ISCHEMIA/INFARCTION  Hemorrhage* and abdominal pain  Mucosal ➔Mural ➔ Transmural  > 50yrs, but also infants (necrotizing enterocolitis)  “Watershed” areas, patchy or segmental  Causes: “non-occlusive” vs. occlusive  Often idiopathic  Hypoperfusion (HF, shock,  H20, drugs, marathon)  Bowel obstruction, neoplasm  Arterial/Venous thrombus or embolism, iatrogenic  Small vessel vasculitis, diabetes, BCPs  ANGIODYSPLASIA  Malformed blood vessels, mucosa, submucosa  Most often cecum and right colon  > sixth decade; < 1% pop,  20% of major episodes LI bleeding  Pathogenesis? Mech. vs. developmental ANGIODYSPLASIA ANGIODYSPLASIA  HEMORRHOIDS  Dilated/thrombosed veins in hemorrhoid venous plexus, external or internal  5% of general population  Painful if thrombosed  Most frequent predisposing factors  Strained defecation  Pregnancy  Other possible causes: portal HTN, neoplasms  DIARRHEA  DEFINITION: Increase in stool mass, frequency or stool fluidity (3 or more loose stools/day  Differs from DYSENTERY: low volume, painful, bloody diarrhea  Four categories:  Secretory  Osmotic  Exudative  Malabsorptive  SECRETORY DIARRHEA  > 500ml/day, isotonic, persist w/fasting  Viral damage to mucosa  Rotavirus, Norovirus, Adenovirus  Enterotoxins, bacterial  V. cholera, E. coli, B. cereus, C. perfringens  Neoplasms secreting GI hormones  Excessive laxatives  OSMOTIC DIARRHEA  Increased stool osmolality  Disaccaridase (lactase) deficiency  Bowel preps  Antacids, egs., MgS04  Abates with fasting  EXUDATIVE DIARRHEA  Purulent bloody stools, persist with fasting  Bacterial damage to GI mucosa  Shigella, Salmonella, C. jejuni, E. histolytica  Inflammatory Bowel Disease (IBD)  Typhilitis (Cecitis, immunosuppression colitis), chemo, AIDS, kidney transplant MALABSORPTIVE DIARRHEA  Defective intraluminal digestion  Abates with fasting  Mucosal cell dysfunction  Reduced bowel surface area  Lymphatic obstruction  STEATORRHEA (hallmark)  MALABSORPTION  Defective absorption of nutrients + H20  Most common causes in U.S.  Celiac sprue  Pancreatic insufficiency  Crohn’s disease  Less common: infectious vs. non-infectious  Disturbance in at least one of four phases  Intraluminal digestion (def. peptic enz., bile salts, etc.)  Terminal digestion (def. disaccharidases, peptidases at brush border)  Transepithelial transport  Lymphatic transport NON-INFECTIOUS MALABSORPTION  CELIAC DISEASE  CYSTIC FIBROSIS  TROPICAL SPRUE (Environ)  AUTOIMMUNOENTEROPATHY  DISACCARIDASE DEFICIENCY  CELIAC DISEASE  AKA: celiac sprue, non-tropical sprue, gluten- sensitive enteropathy  Major cause of malabsorption, symptoms  Western countries, prev. 0.5-1.0%  A sensitivity to GLUTEN, a wheat protein, gliadin, alleles HLA-DQ2 & DQ8  Immobilized T-cells, cytotoxic to enterocytes  Progressive mucosal atrophy, villous flattening  Dx: symptoms, serological (AGA, TGA, EMA), duod. Bx., gluten withdrawal CELIAC DISEASE  TROPICAL SPRUE  Malabsoption syndrome  People living in/visiting tropics  No causal organism identified yet  E. coli, cyclospora, Haemophilis?  RECOVERY with broad-spectrum antibiotics  Variable villous atrophy AUTOIMMUNE ENTEROPATHY  X-linked disorder, mutation FOXP3 gene  Antibodies to intestinal epithelial cells  Severe watery diarrhea infants/children  Requires TPN  Similar adult condition related to other immunoregulatory disorders such as Type I diabetes, rheumatoid arthritis, hemolytic anemia DISACCARIDASE DEFICIENCY  LACTASE by far most common  Congenital: rare, AR, mutation of gene encoding for lactase  Acquired: down-regulation of lactase gene expression  Lactose ➔ Glucose + Galactose  Lactose (fermented) ➔ XXXXXXX  Osmotic diarrhea  Tx: Dietary elimination of milk products  ABETALIPOPROTEINEMIA  Rare, Autosomal recessive (mutation in MTP gene)  Inability to make chylomicrons from FFAs and monoglycerides  Deficient in fat soluable vitamins (A, D, E, K)  Recognizeable lipid membrane defects on PBS, acanthocytes (burr cells)  Infant failure to thrive, diarrhea, steatorrhea  INFECTIOUS ENTEROCOLITIS  BACTERIAL  Vibrio, Campylobacter, Shigella, Salmonella, Yersinia, E. coli, Clostridium difficile, Tropheryma whippelii  VIRAL  Norovirus, Rotavirus, Adenovirus  PARASITIC  Cestodes, Nematodes, Protozoan  CLOSTRIDIUM DIFFICILE  Causes pseudomembranous colitis (aka: antibiotic-associated colitis/diarrhea  Nosocomial, up to 30% hospitalized adults colonized  Acute colitis with adherent inflammatory exudate at sites of mucosal injury  Clinical disease due to toxins (toxin A > B)  Dx: Detect C. diff. toxin in stool  WHIPPLE’S DISEASE  Rare infection, Tropheryma whippelii, gram + intracellular actinomycete  Proximal intestine, mesenteric LNs  Organism-laden macrophages in lamina propria and LNs cause lymphatic obstruction  Malabsorption, diarrhea, wt. loss, abd. pain, occas. polyarthritis, c/o CNS, enlarged LNs  Fatal without antibiotics WHIPPLE’S DISEASE H&E STAIN PAS STAIN GIARDIA LAMBLIA INFLAMMATORY BOWEL DZ. (IBD)  “Inflammatory bowel disease (IBD) is a chronic condition resulting from inappropriate mucosal immune activation.”  Proposed mechanisms:  Environmental  Microbial flora  Genetic susceptibility  Impaired immunity  INFLAMMATORY BOWEL DZ. (IBD)  Crohn’s Disease (CD), Ulcerative Colitis (UC)  Is not Irritable Bowel Syndrome (IBS)  Chronic change in bowel habits  Idiopathic (psychologic, diet, abn. GI motility)  Females >>> Males, 20-40 years of age  NOT characterized by intestinal inflammation  Diagnosis of exclusion  No cure INFLAMMATORY BOWEL DZ. (IBD)  COMMON FEATURES  IDIOPATHIC  DEVELOPED COUNTRIES  COLON INFLAMMATION  SYMPTOMS  EXTRAINTESTINAL MANIFESTATIONS  SIMILAR Rx  INCREASED CANCER RISK  IBD DIFFERENCES  CROHN’S (CD)  ULCERATIVE (UC)  Transmural, thick wall  Mucosal  Not limited to colon  Limited to colon  Granulomas  No granulomas  Fistulae common  Fistulae rare  Terminal ileum often  Terminal ileum never  Skip areas  No skip areas (diffuse)  “Crypt” abscesses  “Crypt abscesses infrequent common  No pseudopolyps  Pseudopolyps  Malabsorption  No malabsorption  Crohn’s Disease (CD)   Ulcerative Colitis (UC)  OTHER CHRONIC COLITIDES  DIVERSION  Complication of ileostomy or colostomy  MICROSCOPIC COLITIS  lymphocytic colitis  collagenous colitis  GVHD  Follows allogeneic BMT  Donor T-cells attack antigens on recipient GI epith.  DIVERTICULITIS  MICROSCOPIC COLITIS  Describes lymphocytic & collagenous  Chronic watery diarrhea, non-bloody  Cause unknown; Infect., meds, immune?  Middle-aged, older women  Strong assoc. with autoimmune dz.  RA, thyroiditis, celiac, myasthenia gravis, A. gastritis  MICROSCOPIC COLITIS LYMPHOCYTIC COLLAGENOUS  SIGMOID DIVERTICULITIS  Inflammation of diverticuli (diverticulosis)  Sigmoid colon, spares rectum  LLQ pain, fever, leukocytosis, sometimes rectal bleeding  Tx: high fiber diet, antibiotics, occas. surgery  Good prognosis  SIGMOID DIVERTICULITIS    ACUTE APPENDICITIS  Generally, dz. of younger people  Most commonly caused by fecalith  RLQ pain, leukocytosis, fever  Need to find neutrophils in the muscularis to confirm the DIAGNOSIS  25% normal rate, usually  Perforation ➔ peritonitis the rule, if no surgery  ACUTE APPENDICITIS   TUMORS of INTESTINES NON-NEOPLASTIC EPITHELIAL MESENCHYMAL (STROMAL)  VASCULAR LYMPHOID BENIGN MALIGNANT  INTESTINAL POLYPS  ANY mucosal bulging, blebbing, or bump HYPERPLASTIC (NON-NEOPLASTIC)  HAMARTOMATOUS (NON-NEOPLASTIC) ADENOMATOUS (TRUE NEOPLASM, and regarded by many as “potentially” PRE-MALIGNANT as well)  SESSILE vs. PEDUNCULATED  TUBULAR vs. VILLOUS POLYPS HYPERPLASTIC POLYP ADENOMATOUS POLYP (TUBULAR) ADENOMATOUS POLYP (VILLOUS) PEDUNCULATED vs SESSILE  BENIGN vs. MALIGNANT  Usual, atypia, pleo-, hyper-, mitoses, etc.  Stalk invasion!!!  “FAMILIAL” NEOPLASMS  1) POLYPOSIS (NON-NEOPLASTIC, hamartomatous), JP and PJS  2) Famililal Adenomatous Polyposis (NEOPLASTIC, i.e., cancer risk), inherited APC mutation  3) HNPCC: (Hereditary Non Polyposis Colorectal Cancer), inherited mutation in DNA mismatch repair enzymes Colon CANCER RISK FACTORS  Family history (sporadic, syndromic)  Age (rare