Systemic Pathology - Intestines and Pancreas - Klein

  1. Bowel Function:
    • S.I.: primarily absorption of nutrients and secretion of some hormones (e.g. secretin)
    • L. I. and Rectum: absorption of water, and preparation for defection (i.e. production of the fecal mass).
    • Produce mucus (or mucin) - facilitate the contents moving forward during peristalsis.
    • A portion of the lymphoid cells, particularly plasma cells, important in innate and acquired immunity, are found here (SI predominantly).
  2. Bowel Structure:
    • Mucosal surface lined by tubular, mucous secreting glands (crypts of Lieberkuhn), muscularis mucosa, submucosa, and two layers (circular and Longitudinal) of muscularis propria
    • S.I. in addition has villi (finger-like projections), markedly increasing the surface area, further increased by cell-surface microvilli on the enterocytes which are absorptive cells.
  3. Obstructive bowel diseases most commonly involves
    the SI but may involve the colon as well
  4. Hernias
    • Get into the inguinal canal, femoral canal, umbilicus, previous incision site
    • - sliding
    • - incarcerated
    • - strangulated.
    • - Latter two are obstructive, the last is also infarcted.
    • Clinical manifestations:
    • - abdominal bloating, constipation, pain and vomiting
  5. Adhesions
    • Scar tissue forms between loops of bowel or between the bowel and other structures, e.g. bladder, abdominal wall. Frequently multiple.
    • 1. Abdominal surgery, bleeding, endometriosis or any inflammatory process involving the peritoneum.
    • 2. twisting of the bowel around the pivot point of the adhesion
    • 3. infarction
  6. Volvulus
    • Twisting of the bowel on its mesentery compromise of the mesenteric blood vessels, particularly the veins, can lead to hemorrhagic infarction of the twisted segment.
    • Mainly S.I. but may involve the colon (cecum).
  7. Intussusception
    • Telescoping of one part of the bowel into the next segment
    • Ileocecal valve - Most common place.
    • Spontaneously (in children) or secondary to polypoid tumors
    • 1. telescoping
    • 2. obstruction
    • 3. compromise of the mesenteric blood vessels
    • 4. infarction
  8. Diverticulosis
    • Outpouching of the wall of the intestine, most commonly the sigmoid colon.
    • Predominately in older individuals (50% >60 years) with constipation
    • Low fiber diets are a contributing factor.
    • 1. constipation
    • 2. increased intraluminal pressure
    • 3. herniation of the mucosa and submucosa through the weak points in the wall
    • 4. diverticula or pouch-like sacs. (mucosal edema)
    • 5. impaired movement of fecal material
    • 6. constipation, etc.
    • Complications
    • - diverticulitis: secondary bleeding from adjacent Intramural blood vessels or fecal material clogs up the openings
    • - Diverticulitis can go further, mesenteric abscess, peritonitis, death.
  9. Ileus
    • Functional obstruction.
    • Peristalsis stops (e.g. due to shock, trauma) and causes functional blockage.
    • Nothing moves through the aperistaltic area.
    • Occurs for several days after all abdominal surgery which is why no food is given post-operatively.
  10. Irritable Bowel Syndrome (IBS)
    • Functional disease.
    • Abdominal distention and pain, flatulence, disordered bowel function (diarrhea, IBS-D, or constipation, IBS-C)
    • ~15% of population.
  11. Malabsorption
    • Impaired ability of the bowel (mainly SI) to absorb.
    • Decreased absorption of fats and the fat-soluble vitamins, proteins and other substances.
    • Due to pathology of the intestinal mucosa or decreased other substances needed for digestion, e.g. pancreatic enzymes (due to chronic pancreatic disease) or bile (due to obstruction of the biliary system)
    • Diarrhea, either steatorrhea or protein-losing
    • systemic manifestations e.g. anemia, vitamin deficiencies (particularly Vitamins D and K)
  12. Celiac disease
    • Sprue, non-tropical sprue, gluten-sensitive enteropathy
    • Rising prevalence during recent 20 years - expansion of inclusion criteria (Gluten-sensitivity)
    • Carriers of HLA markers HLA-DQ2/DQ8, European descent, Rare in Asians and Africans.
    • Pathogenesis:
    • 1. Hypersensitivity to gliaden (component of wheat protein, gluten)
    • 2. Influx of CD8 T-cell into the intestinal mucosa, chronic inflammation of the mucosa
    • 3. atrophy of the villi
    • 4. malabsorption, anemia, vague abdominal pain, steatorrhea.
    • Complications:
    • - enteropathy-associated T-cell lymphoma, osteomalacia
    • - associated with dermatitis herpetiformis.
    • Diagnose - serum antibodies, biopsy of the jejunum
    • Cure - eliminate gluten in the diet!!
  13. Tropical sprue
    • similar pathological and clinical manifestations of celiac disease.
    • Travelers to endemic areas, particularly the Caribbean.
    • Acute disease caused by a bacteria
    • - responsive to antibiotic therapy
    • No hypersensitivity involved.
    • Diarrhea predominates.
    • No vitamin deficiency.
  14. Whipple’s disease
    • Infectious disease (Trophyrema whippelii)
    • Malabsorption and possible systemic manifestations (eg. cardiac and brain problems, axillary lymphadenopathy).
    • 1. Abnormal accumulation of foamy macrophages containing the bacilli in the mucosa (lamina propria) of the SI
    • 2. flattening of the villi
    • 3. malabsorption
  15. Crohn’s disease
    • Inflammatory disease of the small intestine and/or colon.
    • Can involve any area of GI tract (mouth to anus, sparing the rectum), most frequently the ileum, discontinuous involvement, starts in ileum and/or cecum and progresses distally.
    • 1. Transmural inflammatory disease
    • 2. ulceration and malabsorption
    • 3. bleeding and iron deficiency anemia, and Vitamin B12 deficiency and Pernicious anemia, respectively.
  16. Other malabsorptive
    • Extraintestinal - eg. Pancreatic or biliary secretion inadequacy (obstruction, chronic pancreatitis)
    • Intestinal
    • - Biochemical - eg. disaccharidase deficiency, lactase deficiency
    • - Morphological e.g. Primary lymphomas of the small intestine, Short bowel syndrome, Amyloidosis
  17. Causes of Inflammatory Diseases
    • Infectious (Enterocolitis)
    • Non-Infectious (IBD)
  18. Viral Gastroenteritis
    • Most common.
    • May occur in mini-outbreaks, particularly on cruise ships. e.g. Rotavirus (children), Norovirus, Norwalk virus, etc.
    • Acute - severe diarrhea, cramps, rarely fatal.
  19. Bacterial Gastroenteritis
    • Pathogen - E. coli, V. cholerae, Salmonella typhosa, Mycobacterium bovis, Shigellosis, Yersinia enterocolitica, Campylobacter jejuni, Clostridium difficile, Staphylococcus aureus.
    • Pathogenesis
    • - Toxins produced may be responsible. e.g.
    • - - V. cholera - massive watery diarrhea, dehydration, death.
    • - - E. coli (O157:H7) - significant diarrhea and cramps, may cause hemolysis and kidney failure in children.
    • - - C. difficile - Pseudomembranous colitis; MOST COMMON infection in hospitalized patients in the U.S.
  20. Appendicitis
    • 1. Blockage of the lumen of the appendix
    • 2. bacterial buildup
    • 3. acute inflammation of the wall
    • 4. perforation and peritonitis.
    • Right lower quadrant pain radiating to the periumbilical region, fever, leukocytosis.
  21. Parasitic Gastroenteritis
    • Protozoan:
    • - Giardia lamblia (owl eye), Cryptosporidia: mainly s.i.; diarrhea; no cell response; mechanical block of absorption.
    • - Entameba histolytica: colon (mainly Cecum); flask-shaped ulcers which may cause amebic liver abscesses.
    • Metazoan:
    • = Round worms (eg. Ascaris, Strongyloides, hookworms) - mainly s.i.
    • - Flatworms - Taenia species (pork and beef tapeworms)
    • - Flukes - Schistosomiasis, predominantly S. mansoni
    • - - adults live in the Inferior Mesenteric vein, ova migrate to liver via the portal vein (leads to portal hypertension, death) or down to the rectosigmoid area, causing ulcers.
  22. Idiopathic Gastroenteritis include
    • Ulcerative colitis.
    • Crohn’s disease.
  23. Ulcerative colitis
    • Chronic inflammatory disease, purely of the colon.
    • Unknown etiology; autoimmune.
    • Children and young adults predominantly, mainly Caucasians (7/100,000).
    • Typically begins in the rectum and progresses back up the colon in a continuous manner, sparing anus and terminal ileum.
    • universal or pan-colitis - When the entire colon is involved.
  24. Morphology of Ulcerative colitis
    • “horizontal” disease - characterized by inflammation of the mucosa and, to a lesser extent, the submucosa with ulcers that typically are broad-based but superficial. Unlike Crohn's.
    • “crypt abscesses” - chronic inflammation with eosinophils, associated with clusters of neutrophils, which penetrate the crypts.
    • pseudopolyps - intervening islands of inflamed but intact mucosa between ulcers.
  25. Symptoms of Ulcerative colitis
    • intermittent chronic crampy abdominal pain associated with bloody diarrhea, fever, weight loss.
    • exacerbations and remissions.
    • lasts years.
    • Patients may have diseases elsewhere: e.g. biliary tract (primary sclerosing cholangitis), eye (uveitis), joints (polyarthritis), necrotizing skin lesions, mouth (polystomatitis vegetans).
  26. Complications of Ulcerative colitis
    • Adenocarcinoma - May progress to involve the entire colon and predisposes the patient to develop adenocarcinoma of the colon or rectum.
    • Megacolon - Acute, life-threatening, toxic, mainly in the transverse colon, massively dilated, may rupture and cause peritonitis.
  27. Treatment of ulcerative colitis
    • Anti-inflammatory drugs.
    • Occasionally surgery to remove the colon and rectum if dysplastic lesions are found on biopsy.
  28. Crohn’s disease
    • Chronic inflammatory disease
    • Entire GI tract, from mouth to anus (sparing the rectum), mainly the terminal ileum and/or proximal colon (2/3 of patients).
    • Idiopathic.
    • Tends to occur in similar patient population as ulcerative colitis (3-5/100,000) although with a slightly greater frequency in Ashkenazic Jews.
  29. Symptoms of Crohn’s disease
    • Recurring bloody diarrhea and constipation,
    • crampy abdominal pain,
    • fever.
  30. Pathogenesis of Crohn’s disease
    Begins in the ileum or right colon and progresses distally toward the anus but in a discontinuous manner, i.e. there are “skip” areas.
  31. Morphology of Crohn’s disease
    • “vertical” disease - chronic inflammation of the mucosa AND submucosa with slit-like (aphthous) ulcers that penetrate the intestinal wall with inflammation extending to the serosal surface (transmural disease, as compare to UC), causing strictures.
    • Adhesions - between the affected segment(s) of bowel and other abdominal structures, e.g. other bowel segments, urinary bladder, vagina, abdominal wall.
    • Fistula tracts - abnormal communications between the bowel and bladder, bowel and skin, etc. developed from adhesions.
    • Granuloma - ~50% of patients have non-necrotizing, i.e. sarcoid-like, granulomas (delayed type IV hypersensitivity) in the inflamed areas. Significance unknown. No effect on prognosis.
    • Chronic draining sinus tracts - develop if mouth, vulva or anus are involved.
  32. Complications of Crohn’s disease
    Increased risk for adenocarcinoma of both the colon (but somewhat less than UC) and small bowel (D/Dx with UC).
  33. Treatment of Crohn’s disease
    • Anti-inflammatory drugs
    • Rarely surgery to remove strictures due to its "skipping" pattern.
  34. Polyp
    • A foot-like process bulging up from a skin or mucosal surface.
    • Anywhere in the GI tract (including the mouth), colon/rectum and stomach are most common.
    • Single, isolated lesions; multiple but sporadic; part of an inherited polyposis syndrome as multiple polyps +/- tumors elsewhere in the body.
    • Histology - hyperplastic / neoplastic mucosal tissue or neoplastic submucosal tissue.
    • Morphologic - classified as pedunculated (with a stalk) or sessile (broad-based).
    • Detected by bleeding or incidentally during screening colonoscopy or upper GI endoscopy for gastritis.
    • No gender predilection, typically arise in the 30s-40s.
  35. Hyperplastic polyps
    • most common GI polyps (~90%).
    • Typically in colon/rectum or stomach, never in the small bowel.
    • Sessile.
    • The neck portion of the glands is elongated and tortuous and, in the colon, on cross-section has a serrated (saw-toothed) appearance.
    • Hyperplasia of the superficial “normal” mucosa.
    • Non-neoplastic with no malignant potential.
    • Almost never part of any of the polyposis syndromes.
  36. Adenomas
    • ~10%.
    • True neoplasms, benign, malignant transformation potential.
    • ~90% of colon cancer arises from a pre-existing adenoma, the rationale for screening colonoscopy.
    • WHO classification - tubular (usually pedunculated), villous (papillary, usually sessile), or mixed.
    • Malignant potential increases with size (although villous type can undergo malignant change much earlier than tubular type and harder to remove) and presence of dysplasia.
    • Single or multiple sporadic lesions, or part of a polyposis syndrome.
  37. Hamartomas
    • Congenital overgrowths of indigenous tissue.
    • Frequently a mixture of mucosal and submucosal elements, all histologically normal.
    • Small bowel, colon/rectum and stomach.
    • May be single, but more commonly associated with a polyposis syndrome.
  38. Famliial adenomatous polyposis coli syndrome (FAP)
    • Autosomal dominant disease - deletion of chromosome 5 long-arm (the APC gene), >100 adenomas, all tubular, colon, rarely in upper small bowel and stomach.
    • Initiators in their 50s or 60s, occurs earlier and earlier with each successive generation.
    • Risk factor of becoming malignant - duration of presence of polyps. Prophylactic colectomies are performed on any individual diagnosed!
    • Gardner syndrome - a variant of FAP, less common, colonic polyps plus extra-intestinal benign and malignant soft tissue and visceral tumors.
  39. Peutz-Jeghers syndrome
    • Autosomal dominant.
    • Multiple hamartomatous polyps anywhere in the GI tract, mainly in the small intestine.
    • Tumors in many organ systems.
    • Perioral freckle-like pigmentation .
  40. Adenocarcinoma of the Colon/Rectum:
    • 3rd most common malignancy in men and women in U.S.; 2nd most common malignancy collectively in U.S.
    • Major cause of death in U.S., less in Asia (gastric carcinoma instead).
    • Mainly individuals >50, can occur in younger individuals sporadically or who have FAP, long-standing ulcerative colitis, or Lynch syndrome (associated with genetic defects in mismatch repair (MMR) of DNA damage).
    • Predisposing factor - low fiber, high fat diet.
    • 90% arise from adenoma (adenoma-carcinoma sequence) with APC gene mutation (5) and microsatellite instability (MSI) (70% of cases). - hence population-based screening colonoscopy.
    • Any part of colon and rectum, mainly the left side and potentially picked up by sigmoidoscopy.
    • Metastasize - regional lymph nodes, then liver, then lungs, brain, bone.
  41. Neuroendocrine tumors (NET)
    • Arise from neuroendocrine cells of GI tract (and lungs), frequently associated with hormonal production.
    • Most common site - appendix, followed by ileum, rectum, colon and stomach.
    • Low malignant potential.
    • - ileal NET tend to metastasize earlier;
    • - when metastasize to liver, may cause carcinoid syndrome (due to excess serotonin production).
  42. Malignant lymphomas
    • Both primary (stomach > small intestine > large intestine) and secondary (as a metastasis from a primary nodal lymphoma).
    • Predominantly B-cell types except for the ones associated with celiac disease.
    • When small bowel involved, may -> malabsorption syndrome.
  43. G.I Stromal Tumor (GIST)
    • Most common stromal malignancy.
    • Arise from Cajal (neuroregulatory) cells in the GI tract.
  44. Acute (Hemorrhagic) Pancreatitis
    • Most common causes - gallstones (F>M), alcohol (M>F); other causes include drugs (thiazide diuretics) and Mumps.
    • Patients go into shock and can die due to systemic collapse. Major medical emergency!
    • 1. Blockage of the main pancreatic duct or change in the viscosity of the pancreatic secretions;
    • 2. Backup of the pancreatic secretions (mainly enzymes, e.g. trypsin, chymotrypsin, lipase, amylase);
    • 3. Autodigest pancreatic parenchyma, necrosis (mainly the acini; forming pseudocyst, can be clinically mistaken for tumor). Or get into the blood stream and activate the clotting factors, disseminated intravascular coagulation.
  45. Chronic pancreatitis:
    • Complication of chronic alcoholism, mostly.
    • 1. Repeated bouts of acute pancreatitis;
    • 2. Fibrosis and chronic inflammation of the pancreatic parenchyma;
    • 3. Pancreatic insufficiency
    • 4. Malabsorption syndrome.
    • - Islets are relatively spared until very late, at which point Diabetes mellitus becomes a complicating factor.
  46. Pancreatic Adenocarcinoma
    • 3rd or 4th most common GI tract malignancy; incidence increasing recently.
    • Arises mainly from ducts, less commonly from acini;
    • Grows slowly, insidiously, invades local structures (particularly nerves causing intractable pain).
    • Solid or cystic tumor.
    • Highly fatal, sometimes very quick (< a year).
    • May be detected early if arises from the head (vs body or tail) of pancreas - blocks the common bile duct, show jaundice.
  47. Islet cell (Neuroendocrine) tumors
    • ~1-2% of all pancreatic tumors;
    • Much less common than adenocarcinoma.
    • Symptoms associated with the specific hormones the affected cells produce.
    • - Insulinoma (beta cells) - bouts of hypoglycemia;
    • - Glucagonoma (alpha cells) - hyperglycemia;
    • - Zollinger-Ellison syndrome / gastrinoma (G cells) - multiple peptic ulcers in the stomach and small intestine. Tumors may arise in the pancreas or in ectopic pancreatic rests in upper GI tract.
Card Set
Systemic Pathology - Intestines and Pancreas - Klein
Systemic Pathology - Intestines and Pancreas - Klein