Pathology of the Small Intestine

Question 1

What parts of the small bowel are intraperitoneal vs retroperitoneal? What marks the beginning of the jejunum?

Answer 1

The duodenum is entirely intraperitoneal except for its proximal part, then is retroperitoneal.

After the ligament of Treitz, the small intestine becomes the jejunum, which is intraperitoneal like the ileum

Question 2

What is the blood supply of the small intestine?

Answer 2

Gastroduodenal artery supplies the first part of the duodenum (off of Celiac trunk), then SMA supplies the rest

Question 3

What are the circumferential submucosal folds in the small intestine? What is their function?

Answer 3

Plicae circularis

These serve to increase the surface area of the small intestine along with the mucosal folds (villi)

Question 4

What is serosa vs adventitia?

Answer 4

Serosa - discrete layer of mesothelial cells on outside of a peritoneal structure

Adventitia - made of loose connective tissue with no descrete mesothelial covering

Both would be the outer layers of a given structure depending on if it’s intra or retroperitoneal

Question 5

What are microvilli made of?

Answer 5

Actin which is cross-linked to the cell membrane by myosin and anchored down by the terminal web

Question 6

What explains the post-viral diarrhea that occurs after the infection has been cleared?

Answer 6

Younger stem cells in the crypts of Lieberkuhn are involved in secretion of Na/Cl/H20 -> when new cell populations are being repopulated, these cells predominate and increase excretion

Question 7

What are Paneth cells?

Answer 7

Cells unique to the small intestine which secrete antibacterial substances like lysozyme to regulate the normal flora

Question 8

What is the luminal phase of digestion?

Answer 8

Digestion by pancreatic enzymes and emulsification of fat by bile acids
-> occurs via substances exogenous to the native GI tract lumen

Question 9

What is the mucosal phase of digestion?

Answer 9

Digestion via brush border enzymes, i.e. disaccharidases, lipases, and peptidases which are tethered to the brush border. These facilitate the final step of digestion before absorption

Question 10

What is absorbed maximally in the duodenum vs jejunum vs ileum?

Answer 10

Duodenum - water soluble vitamins, iron, and calcium

Jejunum - most nutrient absorption of macromolecules (maximal here), vitamin B9

Ileum - bile salts, vitamin B12

Question 11

Who tends to get hypertrophic pyloric stenosis, and what are the common presenting signs and symptoms?

Answer 11

Firstborn Caucasian males

1. Olive-shaped mass in epigastric region
2. Visible peristaltic waves after eating (hypertrophy)
3. Nonbilious projecting vomiting starting after feedings about 3-4 weeks after birth (takes a while for food to build in stomach)

Question 12

What is the treatment for hypertrophic pyloric stenosis?

Answer 12

Pyloromyotomy - make an incision in pylorus (don’t penetrate mucosa), which is just enough to relieve the pressure and allow normal expansion of sphincter

Question 13

What is the most common place for intestinal atresia to occur and what is thought to cause it?

Answer 13

Duodenum - failure to recanalize due to loss of blood supply during development

Associated with Down’s syndrome

Question 14

What happens in normal rotation of the gut and what will happen if this is done incorrectly?

Answer 14

Normally, the gut rotates 270 degrees around the superior mesenteric artery via a counterclockwise rotation from the frontal view. This allows the colon which was pointing downwards to sit on your right side on your posterior abdomen, anterior to the duodenum

If this is done incorrectly -> malrotation occurs

Question 15

How does omphalocele occur and is its prognosis better or worse than gastroschisis?

Answer 15

Ompalocele - failure of physiologic hernation (which occurs during growth rotation of gut during development) to return from umbilical cord back into abdomen. Will be covered by peritoneum and amnion.

Prognosis is worse than gastroschisis even though it looks less ugly, because more genetic abnormalities are associated with it

Question 16

What is gastroschisis? Where does it typically happen?

Answer 16

Extrusion of abdominal contents through abdominal wall, not covered by peritoneum or amnion -> typically due to an abdominal wall defect on the right side

Can be repaired surgically

Question 17

What type of diverticulum is a Meckel diverticulum and what causes it?

Answer 17

A true diverticulum - all layers of the abdominal wall

Caused by a failure of the regression of the vitelline duct, which normally communicates with the yolk sac during development

Question 18

What are the rules of 2’s for Meckel’s?

Answer 18

2 inches long, 2 feet from ileocecal valve, in 2% of the population, occurring in first two years of life

Most common congenital anomaly of the GI tract

Question 19

Why do Meckel’s diverticula sometimes cause problems?

Answer 19

1. Often contains heterotopic gastric mucosa which secretes acid, causing bleeding
2. Volvulus, intussusception, or obstruction can occur
3. Can present as a fistula which drains into umbilicus

Question 20

How is are mucoid cells of the ectopic gastric mucosa in a Meckl’s detected?

Answer 20

Pertechnetate scan (Actively uptaken and secreted by mucosal epithelial cells of gastric tissue)

Question 21

How can malabsorptive syndromes cause anemia?

Answer 21

Failure to absorb B12 in ileum
Failure to absorb iron in duodenum
Failure to absorb vitamin K due to steatorrhea -> bleeding

Question 22

What happens to exocrine pancreas in cystic fibrosis? What will this do to vitamin absorption?

Answer 22

Mucous plugs form in ducts due to increased water reabsorption (Cl- can’t leave)

• > duct dilatation and cystic change, leading to acinar atrophy and fibrosis because of inappropriate enzyme activation
• > decreases fat and fat-soluble vitamin absorption

Question 23

What is one complication of CF only seen in infants?

Answer 23

Meconium ileus -> thick secretions obstruct the bowel. Only seen when small bowel is small enough for this to still happen (infancy)

Question 24

What happens rarely to the liver and often to the vas deferens in CF?

Answer 24

Liver - secondary biliary cirrhosis due to mucosal plugs blocking bile secretion

Vas deferens - congenital bilateral absence causing obstructive azoospermia. CFTR is thought to be required for development of vas deferens

Question 25

What is seen pathologically in lactose intolerance and what happens?

Answer 25

Absolutely nothing Lack of lactase in brush border enzymes -> osmotic diarrhea

Question 26

What is the pathogenesis of Celiac disease?

Answer 26

Gliadin is a soluble portion of grains, is absorbed into GI tract and deaminated by tissue transglutaminase (tTG) Deaminated gliadin is presented by MHC class II and activates CD4 T cells -> T cell mediated damage of intestinal mucosa

Question 27

Who is susceptible to Celiac disease?

Answer 27

Caucasians with HLA-DQ2 and HLA-DQ8 -> MHC Class II which can present the deaminated gliadin on their APCs

Question 28

What is seen on anatomic pathology of Celiac disease? Where is the damage worst?

Answer 28

Villous atrophy / blunting with crypt hyperplasia for regeneration, and chronic inflammation surrounding Worst in proximal small intestine

Question 29

What antibodies are detected by serology in Celiac disease?

Answer 29

IgA antibodies: 1. Anti-tissue transglutaminase 2. Anti-deaminated gliadin 3. Anti-endomysial antibodies - connective tissue which ensheaths muscle fibers, thought to be cross-reactive to a tissue transglutaminase

Question 30

What skin condition is associated with Celiac disease?

Answer 30

Dermatitis herpetiformis - > intensely itchy, grouped vesicles on extensor surfaces of extremities and back - > thought to be caused by IgA antibodies and microabscesses within the papillary dermis

Question 31

What malignancies is Celiac disease associated with?

Answer 31

T-cell lymphoma - due to lymph hyperplasia / inflammation Small intestinal adenocarcinoma (rare, associated with the crypt hyperplasia)

Question 32

What is Tropical sprue and what is the treatment?

Answer 32

Infectious disease within unknown cause which is responsive to antibiotics, seen in tropics. Pathologic and clinical findings are identical to Celiac disease

Question 33

What is abetalipoproteinemia and what are the clinical presenting symptoms?

Answer 33

Autosomal recessive disorder of apoplipoprotein B synthesis -> failure to make chylomicrons, VLDL, and LDL Presenting symptoms are of malabsorption and failure to thrive

Question 34

What is seen pathologically and on peripheral smear of abetalipoproteinemia?

Answer 34

Pathologically - vacuolization of enterocytes due to accumulation of fats which cannot be packaged into chylomicrons Peripheral smear - acanthocytes (spur cells) - spiky RBCs due to abnormal lipoproteins in their membrane

Question 35

What causes Whipple disease and who tends to get it? How is it treated?

Answer 35

Typically found in older men, it is a systemic bacterial infection caused by Tropheryma whipplei -> intracellular gram + bacteria normally cleared by immune system, but some people are unable to It is responsive to antibiotics

Question 36

How is Whipple disease detected pathologically?

Answer 36

Numerous, distended foamy macrophages in lamina propria as well as mesenteric lymph nodes which stain PAS+. They can only be seen by EM since they are so small

Question 37

What are the symptoms of Whipple disease?

Answer 37

Foamy Whipped cream in a CAN Foamy - macrophages Whipped - Whipple disease CAN: Cardiac symptoms - invade heart valves Arthralgias - also live in joint synovial membranes Neurologic symptoms - invade brain, cause psychiatric complaints

Question 38

What are the viral causes of acute gastroenteritis, and what does the intestinal pathology look alot like acutely?

Answer 38

Rotavirus, Norovirus, adenovirus, astrovirus Looks alot like Celiac disease -> loss of brush border with compensatory hyperplasia of crypts and shortening of villi with lymph infiltration

Question 39

What intolerance is characteristic of postenteritis syndrome?

Answer 39

Diary intolerance - loss of brush border due to intestinal damage depletes lactase and causes a secondary lactose intolerance until cells heal

Question 40

What are the etiologies of transmural infarcts of the bowel due to low oxygen (ischemic bowel disease)?

Answer 40

Only severe infarcts 1. Arterial thrombosis - i.e. atherosclerosis, polyarteritis nodosa 2. Arterial embolism - i.e. mural thrombi or plaque rupture 3. Venous thrombosis - due to hypercoagulability 4. Vascular compression

Question 41

What are some causes of vascular compression in ischemic bowel disease?

Answer 41

Extrinsic mechanical factors - herniation, volvulus, intussusception Intrinsic vascular disease - amyloidosis

Question 42

What is the typical etiology of a mucosal infarction in ischemic bowel?

Answer 42

Marked hypotension, i.e. cardiogenic or septic shock

Question 43

What causes the majority of the injury in ischemic bowel, and what area is particularly susceptible?

Answer 43

Secondary reperfusion injury -> due to oxygen-derived free radicals Splenic flexure is most vulnerable - watershed area between SMA / IMA

Question 44

How does acute ischemic bowel appear grossly and microscopically?

Answer 44

Grossly - purplish-red region with intraluminal hemorrhage, wall may be edematous or thin and attenuated, about to burst Microscopic - coagulative necrosis with hemorrhage (red infarct) with some acute inflammation

Question 45

What is the clinical presentation of ischemic bowel disease?

Answer 45

Abdominal pain (especially postprandial) with some bloody diarrhea -> often suspected as a diagnosis of exclusion in older adults

Question 46

Why does necrotizing enterocolitis happen?

Answer 46

Happens usually in premature infants due to intestinal ischemia during neonatal RDS, followed by presence of oral bacteria from oral feedings, and increased workload of gut -> immature mucosa with increased permeability leads to infection and increased ROS damage

Question 47

What is seen in anatomic pathology of necrotizing enterocolitis?

Answer 47

Hemorrhagic infarct of small and/or large intestines with possible perforation Air can also seep into the wall -> "pneumatosis intestinalis"

Question 48

Where does gastrointestinal carcinoid tumor tend to appear and how does it appear grossly / microscopically?

Answer 48

Ileum (remember this is the only common primary malignancy of small bowel, per pathoma), appendix, rectum Grossly - yellow-to-white mass with variable degree of wall inflammation and fibrosis which may lead to kinking Microscopic - Small round cells with salt and pepper chromatin and high vascularization

Question 49

How are carcinoid tumor cells identified cytochemically?

Answer 49

Dense-core secretory granules due to presence of chromogranins

Question 50

What are the differences in presentation between the locations of carcinoid tumors of the GI tract?

Answer 50

Small bowel - may cause obstruction due to prominent desmoplasia, and can metastasis Appendix / rectal - Usually found incidentally, almost never metastasize

Question 51

When will you actually get the symptoms of carcinoid syndrome with carcinoid tumor? Why?

Answer 51

Tumor must metastasize to liver first -> all portal blood going to the liver will metabolize the serotonin to inactive 5-hydroxyindoleacetic acid (5-HIAA)

Question 52

What are the symptoms of carcinoid syndrome?

Answer 52

Bronchospasm, diarrhea, wheezing, flushing worsened by emotional stress which stimulate serotonin release from the tumor Damage includes: right-sided valvular fibrosis, tricuspid regurg, and pulmonary valve stenosis. Left-sided valves not affected due to MAO in the lung.

Question 53

What is the most common kind of lymphoma of the GI tract in terms of cell type? Most common subtype?

Answer 53

B cell lymphomas MALT lymphoma - marginal zone lymphoma associated with chronic gastritis due to H. pylori

Question 54

What is Mediterranean lymphoma and what is the treatment?

Answer 54

Immunoproliferative small-intestinal disease - > a B cell lymphoma of children and young adults, preceded by malabsorption - > may be due to infection because it is treatable with antibiotics

Question 55

What aggressive B cell lymphoma is often found in the abdomen or pelvis and is often not associated with EBV?

Answer 55

Burkitt lymphoma - sporadic form seen here in the U.S. t(8;14) which happens independent of EBV

Question 56

Who gets Intestinal T-cell lymphoma?

Answer 56

Enteropathy-associated | -> associated with long-standing malabsorption, i.e. Celiac disease

Question 57

How do all Primary GI lymphomas appear grossly?

Answer 57

Start as superficial plaques and then can assume any form -> need biopsy to distinguish from adenocarcinoma

Question 58

What is a leiomyosarcoma?

Answer 58

A malignancy of smooth muscle cells, most commonly found in muscularis propria of small intestine

Question 59

What neoplasm is derived from the interstitial cells of Cajal and what mutation is commonly associated with it? What tumor does it look similar to and what is the treatment?

Answer 59

Gastrointestinal stromal tumor - tyrosine kinase mutations, specifically c-KIT -> treated well with imatinib - looks very similar to leiomyosarcoma (grows outward and will not cause symptoms unless obstructing lumen)