DERS 06 - GIT Pathology 3 - Small Intestine 1

Question 1

Facts to know about Meckel’s Diverticulum

Answer 1

• Caused by incomplete involution of vitelline duct
• Rule of 2 - 2% of population, 2 inches in length, within 2 feet of ileocecal valve
• On anti-mesenteric border
• True diverticulum (includes all layers of GIT)
• Gastric mucosa or pancreatic tissue may be present
• Usually asymptomatic but can result in hemorrhage, peptic ulcer, intestinal obstruction, diverticulitis, perforation, or fistula

Question 2

What are the malabsorption syndromes we need to know? What clinical features do they all have in common?

Answer 2

• Celiac Sprue, Tropical Sprue, Whipple disease
• Features in common
  
  • Chronic diarrhea
  • Steatorrhea
  • Impaired digestion or absorption

Question 3

Which populations experience celiac sprue more often?

Answer 3

• Whites
• 1-10yo

Question 4

Describe the pathogenesis of celiac sprue.

Answer 4

1. Gliadin, a gluten derived peptide, does two things
   
   1. Causes the enterocytes to release IL-15, activating the intraepithelial CD8+ T cells, triggering enterocyte proliferation, and causing inflammation
   2. Once past the enterocytes, tissue transglutaminase (tTG) deaminates gliadin which APCs with DQ2 or DQ8 human leukocyte antigen (HLA) can bind and present to CD4 T cells
2. Activated CD4 T cells release IFNγ and somehow stimulate B cells to release anti-gliadin, anti-endomysium, and anti-tTG antibodies.
3. Inflammation leads to disruption of the structure and function of the villi, causing malabsorption and the related symptoms

Question 5

Describe the histological changes seen in celiac disease.

Answer 5

Changes are more marked or only occur in proximal intestine

• Flattening and widening of the villi
• Increase of chronic inflammatory cells (macrophages and lymphocytes) in the lamina propria
• Crypt elongation, thickening, and deepening
• Increase in number of intraepithelial lymphocytes. >30 lymphocytes per 100 enterocytes

See image

Question 6

How is celiac sprue diagnosed?

Answer 6

• Documentation of malabsorption (iron deficiency in adults)
• Small intestine biopsy
• Serologic tests for
  
  • anti-gliadin
  • anti-endomysial
  • anti-tissue transglutaminase
• Genetic test for HLA DQ2 or DQ8
• Reversal of changes after starting gluten free diet

Question 7

What does celiac disease put you at risk of?

Answer 7

Development of intestinal T-cell lymphomas

and malabsorption

Question 8

Facts to know about Tropical Sprue

Answer 8

• AKA - Post infectious sprue, because pathogenesis is related to bacterial infection on a pre-existing small intestine injury
• Most commonly found in tropics
• Symptoms can appear months or years after visit to tropics
• Difficult differentiate from celiac disease. This is best done by:
  
  • Recent travel to tropics
  • Involvement of entire SI (not just proximal parts)
  • SI may appear normal with tropical sprue
• Responds to antibiotics

Question 9

What is a histiocyte?

Answer 9

A tissue macrophage or dendritic cell

Question 10

What is the cause of Whipple’s disease? What are the symptoms?

Answer 10

• Tropheryma whippelii invading histiocytes and causing inflammation
• Usual symptoms are diarrhea, abdominal pain, weight loss, and joint pain. Some patients develop confusion/dementia

Question 11

Answer the following about Tropheryma whippelii:

• Gram positive or negative?
• Shape?
• How are they detected?
• What populations do they usually infect?

Answer 11

• Gram positive
• Sickle shaped bacilli
• Stain pinkish/red with PAS
• More common in males

Question 12

Describe the histology of Whipple disease

Answer 12

• Macrophages (histiocytes) in the lamina propria of the intestine will have enlarged foamy-appearing cytoplasms
  
  • This also happens with mycobacterium tuberculosis infections so a PAS and Zieh-Neelsen stain must be done because the macrophages will stain pink with PAS if its tropheryma whippelii and will stain pink with Ziehl-Neelsen if its mycobacterium tuberculosis

Question 13

Facts to know about Giardia

Answer 13

• Protozoan gut pathogen with flagellum
• Trophozoites and cysts are shed in feces of infected people
• Usually acquired from drinking contaminated water
• Immunosupression increases risk
• On histology, they’re always in the lumen and appear as flattened disks with small nuclei

Question 14

Facts to know about cryptosporidium

Answer 14

• Self limited infection in normal host
• Chronic diarrhea in AIDS
• On histology they appear as dark purple balls on the surface of the cell. They’re actually intracellular.

Question 15

Where do intestinal obstructions most often occur?

Answer 15

Small intestines

Question 16

What is a luminal intestinal obstruction and what are their most common causes.

Answer 16

Obstruction caused by something in the lumen of the intestine

• Food bolus - usually due to improper mastication/digestion
• Therapeutic agents like barium sulphate or antacid gels
• Bezoars (ingested hair)
• Round worms (ascaris lumbricoides)
• Tumors
• Swallowed foreign bodies (most common in children)
• Meconium ileus in infants with CF
  
  • thick mucus at mid-terminal ileum

Question 17

What is intramural intestinal obstruction and what are the most common causes?

Answer 17

Intestinal obstructions caused by issues within in the walls

• congenital atresias
• Inflammatory conditions

Question 18

What is an extramural intestinal obstruction and its most common causes?

• Peritoneal diseases/adhesions/hernias
• Intestinal adhesions
• Intussusception - telescoping of proximal bowel into distal
• Volvulus - twisting of bowel loop

Question 19

What are the primary causes of ischemic small bowel? How does ischemic bowel appear grossly and histologically?

Answer 19

• Typically caused by volvulus or a strangulated hernia
• Grossly it appears as a darkened segment of the mucosa from the inside and out
• Histologically there will be a los of mucin and goblet cells in the villi

Question 20

Describe the typical pathogenesis of acute appendicitis

Answer 20

1. Something obstructs the lumen
2. The appendix continues to secrete mucinous fluid
3. Increased luminal pressure leads to collapse of draining veins
4. Ischemic injury
5. Bacterial proliferation
6. Inflammation and edema

Question 21

What are the clinical features of an acute apendicitis?

Answer 21

• Usually seen in adolescents and young adults
• Periumbilical pain that then becomes RLQ pain
• Nausea and Vomiting
• Tenderness at McBurney’s point
• Mild fever
• Leukocytosis

Question 22

What are the complications of acute appendicitis?

Answer 22

• Perforation
• Peritonitis
• Periappendiceal abscess
• Liver abscess
• Bacteremia

Question 23

What is pseudomyxoma peritonei and its usual cause?

Answer 23

A clinical condition caused by mucinous adenocarcinoma cells producing abundant mucin in the peritoneum

Typically casued by a mucinous lesion in the appendix that develops into an adenoma and then an adenocarcinoma that spreads to the peritoneum

Question 24

How is Hirschsprung Disease diagnosed? What are the complications of it?

Answer 24

• Rectal biopsy for absence of ganglion cells
• Complications
  
  • megacolon
  • enterocolitis (inflammation of colon)
  • perforation and peritonitis

Question 25

What is diverticulosis and diverticulitis? What causes it?

Answer 25

Diverticulosis is mucosal/submucosal (not the muscularis mucosae) outpouchings of the sigmoid colon (sometimes descending colon) resulting in the collection and impaction of feces. If these outpouchings become inflammed or infected, it is called diverticulitis.

Typically caused by a lack of dietary fiber leading to sustained bowel contractions and increased intraluminal pressure.