Topics B49-55: Intestinal vasculature, malabsorption, enterocolitis, diverticulosis, IBD, tumors, appendix, peritoneum

Question 1

5 congenital/developmental problems affecting the small intestines

Answer 1

1. Stenosis (narrowing)
2. Atresia (complete blockage, no hollowing out)
3. Omphalocele: incomplete closure of abdominal wall, so small bowel herniates out. Causes peritonitis
4. Meckel’s diverticulum: failure of vitelline duct to involute, risk of bacterial overgrowth
5. Cystic fibrosis: thick, sticky mucous production. In utero, meconium is too thick and plugs ileum (meconium ileus)

Question 2

What are the causes of congenital and acquired megacolon?

Answer 2

Congenital: Hirschsprung disease. Lack of ganglion cells, and so normal peristaltic movement is blocked

Acquired: Chagas disease destroying myenteric plexuses, obstruction, toxic megacolon (IBD or C. difficile infection)

Question 3

What is the major vascular disorders that can affect the small bowel?
What are the causes and risks?

Answer 3

Hemorrhagic infarction can occur: remember this occurs in places with dual blood supply (intestines, lung, testicle). Small intestine mucosa is sensitive to hypoxia and will quickly undergo necrosis, which is then flooded with blood.

Most frequent causes: atherosclerosis narrowing vessels, thrombus formation or embolization in mesenteric arteries.

Risks: vascular ileus, perforation, peritonitis

Question 4

What two vascular disorders affect the large intestine and anus?

Answer 4

1. Angiodysplasia: tortuous dilations of submucosa and mucosal blood vessels. Usually in cecum or ascending colon. Can cause lower GI bleeds.
2. Hemorrhoids: variceal dilations of anal/perianal submucosal plexuses. Develop from chronically high venous pressure, possibly from straining during defecation or stasis during pregnancy. The thin-walled vessels bleed.

Question 5

10 causes of malabsorption

it’s a lot but most of them are pretty obvious

Answer 5

1. Pancreatic insufficiency or obstruction
2. Bile insufficiency or obstruction
3. Diarrhea (which itself is caused by many forms of malabsorption)
4. Lactose intolerance
5. Celiac disease
6. Inflammatory bowel disease
7. Intestinal resection
8. Whipple disease: bacterial infection blocks digestion
9. Parasites
10. Deficiency of apo-lipoprotein B (can’t make chylomicrons)

Question 6

6 possible clinical signs of malabsorption

Answer 6

1. Steatorrhea: key sign, fat-filled feces that can be pale and clay-like
2. General caloric deficit causes weight loss, anorexia, muscle wasting, loss of sexual function
3. Vitamin K deficiency -> trouble clotting (purpura, petechiae)
4. Neuropathy from B12 and vitamin A deficiencies
5. Anemia from iron, folate, or B12 deficiencies
6. Electrolyte loss, e.g. calcium loss causing tetany or osteomalacia

Question 7

4 categories of diarrhea

ewwwww

Answer 7

1. Secretory diarrhea: isotonic stool, persists during fasting
2. Osmotic diarrhea: e.g. in lactose intolerance, unabsorbed solutes are osmotically active and cause fluid retention in colon
3. Malabsorptive diarrhea: inadequate nutrient absorption causing steatorrhea. Relieved by fasting
4. Exudative diarrhea: inflammatory disease -> purulent, bloody stools that continue during fasting

Question 8

What is Celiac disease? What are the gross and histological changes?

Answer 8

Sensitivity to gliadin (component of gluten), which is absorbed and then the epithelium is attacked in manner similar to autoimmune diseases. In adults, it starts as molecular mimicry with bacterial infection where components are similar to gliadin.

Gross changes: mucosa become flat, no villi.

Histological changes: excessive amount of intra-epithelial lymphocytes

Question 9

What are 3 major forms of enterocolitis?

Answer 9

1. IBD (Ulcerative colitis only in colon, while Crohns can potentially affect any part of GI tract)
2. Pseudomembranous colitis: C. dificile, Shigella, Entamoeba histolytica, toxins
3. Necrotizing entercolitis: common cause of death in premature infants, probably from immature intestines, bacteria, and ischemia

(note also terminology for inflammations of specific areas: appendicitis, typhlitis [cecum], sigmoiditis, proctitis)

Question 10

What are some infectious causes of enteritis (small intestine inflammation)? 6 are listed

Answer 10

1. Giardiasis
2. Salmonellosis
3. Typhoid fever
4. Actinomycosis
5. Whipple disease
6. Tuberculosis (primary or secondary)

Question 11

What is colonic diverticulosis?
Where in the colon does it normally occur?
Why does it develop?

Answer 11

Outpouching of large bowel. Not all layers of the wall are outpouched, as they are in esophageal diverticuli.

Usually occurs in sigmoid colon

Diverticulosis can occur from fiber-poor diet where there is continuous accumulation of feces in lower colon. This increases intraluminal pressure, causing outpouchings. Focal defects and exaggerated peristaltic contractions are also factors.

Question 12

What are 3 complications of colonic diverticuli?

Answer 12

If feces accumulates, it can cause diverticuli. These have risk for
-Hematochesia: bleeding, fresh blood in the stool (as opposed to melena)

• Diverticulitis can perforate, causing peritonitis
• Chronic repeated inflammations -> connective tissue proliferation -> risk of tumor cell formation

Question 13

8 possible causes of bowel obstruction:

I don’t think you need to know all of them, wasn’t really taught and it’s not detailed in Robbins

Answer 13

1. Adhesions: most common cause. Can be metastases, endometriosis, etc.
2. Crohn’s disease: lumen is narrowed because of full-thickness inflammation of intestinal wall
3. Gallstone ileus: stone lodges in ileocecal valve, causing obstruction
4. Hernias: especially inguinal hernia (SI trapped in inguinal canal)
5. Meconium ileus (cystic fibrosis)
6. Volvulus: bowel twists around mesentery, causing obstruction.
7. Hirschprung disease and other disorders of nervous supply of GI tract (Chagas)
8. Intussusception: part of GI tract folds/telescopes into the distal tract

Question 14

6 gross and histological differences between Crohn’s disease and Ulcerative Colitis

Answer 14

1. Crohn involves the full thickness of the intestine (“transmural”), UC is limited to mucosa or submucosa
2. Crohn has multiple individual ulcers that are deep, knife-like. UC has shallow ulcers that are continuous.
3. UC has characteristic “crypt abscesses” - granulocytes in crypts
4. Crohn has non-caseating granulomas, lymphoid infiltration
5. Crohn has connective tissue proliferation that compresses vessels
6. Crohn can be anywhere in the intestine, but classicaly starts in terminal ileum. UC is only in colon and rectum

(despite this, nearly half of cases can’t be distinguished)

Question 15

What genetic mutations is important to know for Crohn’s disease?

What genetic mutation is relevant for both Crohn’s and Ulcerative Colitis? (probably not as important to remember as the first one)

Answer 15

Just Crohn: NOD2 mutation is present in many cases of Crohn’s disease. Codes for intracellular receptor that becomes ineffective at recognizing bacterial components, possibly allowing microbes to enter and trigger inflammation.

Crohn and UC: IL-23 receptor. IL-23 promotes production of IL-17, unclear mechanism of relation to inflammation.

In both UC and Crohn’s, the primary damaging agents are CD4+ T cells that are overreacting

Question 16

5 complications of Crohn’s disease

Answer 16

1. Normal peristaltic movement is inhibited -> obstruction, ilietis
2. Extensive adhesions between loops of small bowel
3. Fistulas are formed, may cause purulent abscess formation and malabsorption (especially note B12 if terminal ileum affected)
4. Ulcers, hemorrhage, maybe anemia
5. Increased risk for carcinoma

Question 17

5 complications of Ulcerative Colitis

Answer 17

1. Toxic megacolon: hypotonic, distended bowel
2. Adenocarcinoma: more of a risk in UC than Crohn’s.
3. Bleeding from ulcers, maybe anemia. More blood loss in UC than Crohn’s.
4. Sclerosing cholangitis (fibrotic obliteration of bile ducts): people with SC commonly also have UC.
5. Pseudopolyps from mucosal change

Question 18

What are the 3 morphologies of polyps?

Answer 18

1. Tubular: stalked. Low chance of malignant transformation
2. Tubulo-villous: usually stalked. Moderate chance of malignant transformation
3. Villous: No stalk (sessile polyp). Highest chance of malignant transformation

Question 19

What 2 kinds of benign tumors are seen in small intestine?

Answer 19

1. Mesenchymal-origin: e.g. lipoma, schwannoma
2. Peutz-Jegher polyps: hamartomas. May be several hundred polyps in the small bowel, hyperpigmented. AD inheritance but rare. Risk for many malignancies, including colon, pancreas, breast, lung, ovaries, etc.

Note that all types of tumors are extremely rare in the small intestine

Question 20

What are 3 kinds of malignant tumors are seen in small intestine?

Answer 20

1. Adenocarcinoma
2. Neuroendocrine / carcinoid tumors from enterochromaffin cells
3. Malignant lymphomas

Again, all are very rare

Question 21

What are the genetic mutations in colon carcinoma, in 2 familial vs 2 non-familial forms?

Answer 21

Familial: (both are AD inheritance)

• Familial Adenomatous Polyposis: APC mutation, tumor suppressor
• Familial non-polyposis cancer (Lynch syndrome): various mismatch repair genes

Non-familial:

• If already have UC, first hit is p53, then several other mutations where final step is APC mutation
• If completely sporadic, first hit is APC and the last is p53

Other mutations like KRAS and BAX also involved

Question 22

Common and uncommon causes of acute appendicitis

Answer 22

1. Fecalith obstruction, similar to diverticulitis
2. Less commonly: seeds, pinworm infection, gallstones

In any case, the appendix becomes infected with bacteria (usually E. coli, maybe Bacteroides fragilis)

Question 23

4 clinical signs of appendicitis, in sequence

maybe not too important for patho, but otherwise not much to say about appendix

Answer 23

1. Initial colicky (intermittent) periumbilical pain. Pain refers to midline.
2. Fever
3. Fever, nausea, vomiting
4. Pain shifts to lower right lower quadrant in 12-18 hours due to irritation of peritoneum. Rebound tenderness at McBurney point

Note that Meckel’s diverticulitis, gastroenteritis, ectopic pregnancy etc etc can have similar symptoms

Question 24

2 complications of appendicitis

Answer 24

1. Abscess of appendix that may or may not perforate into peritoneum, causing peritonitis
2. Pyelophlebitis: infection of portal vein that is risk for portal vein thrombosis.

[Note: A fecalith may also cause a mucocele in the appendix without causing appendicitis]

Question 25

2 types of tumors of the appendix

Answer 25

1. Carcinoid: most common. Arises from enterochromaffin cells. Rarely metastasizes
2. Mucinous or non-mucous adenomas and adenocarcinomas. Mucinous tumors may cause mucoceles, which can be severe enough to invade through the appendix wall and spread in the peritoneum. Abdomen may fill with mucin - “pseudomyxoma peritonei”

Question 26

complications of the peritoneum

Answer 26

1. Acute peritonitis (bacterial infection or “sterile” chemical irritation, e.g. bile. Usually the result of perforated organs)
2. Pneumoperitoneum: also from perforations or penetrating trauma
3. Ascites: from portal hypertension and low protein edema (transudate). May become infected
4. Hemascos: peritoneum filled with blood
5. Chylascos: peritoneum filled with bile
6. Neoplasia: primary (mesothelioma) or metastases (ovary, stomach, pancreas, colon, GIST)

Question 27

Should make more cards, especially on colon carcinoma (Wasn’t a whole lot in lecture though)

Answer 27

some things I missed:
some basics about Duke staging

CEA positivity in polyps, UC, and colon cancer

Colon cancer is second-most common lethal cancer