Malabsorption B&B

Question 1

how does malabsorption of fat vs carbs vs proteins present?

Answer 1

fat malabsorption —> steatorrhea, pale and voluminous stools which float, greasy/foul smelling

carb malabsorption —> watery diarrhea (osmotic effect of sugars)

protein malabsorption —> edema (loss of albumin)

Question 2

what is the immunogenic component of Celiac Disease?

Answer 2

gluten = gliadin + glutenin (both proteins in wheat)

when gliadin is deamidated via tissue transglutaminase (tTG), it becomes immunogenic

[NH2 group is removed and replaced by COOH]

Question 3

what type of hypersensitivity is Celiac Spure (aka Celiac Disease)?

Answer 3

type IV hypersensitivity mediated by T cells!

deamidated gliadin (wheat protein) is consumed by APCs

[note Abs are present but not known to contribute to disease]

Question 4

with which HLA genes is Celiac Disease associated? (2)

Answer 4

1. HLA-DQ2
2. HLA-DQ8

Question 5

what are the key histological features (3) of Celiac Disease? (in GI tract)

Answer 5

1. blunting of villi
2. crypt hyperplasia
3. lymphocytes in lamina propria

Question 6

which 3 antibodies can be detected in patients with Celiac Disease? what type of Abs are detected? What is their relevance in pathology?

Answer 6

1. anti-gliadin (wheat protein that is immunogenic to these patients)
2. IgA anti-tissue transglutaminase (tTG) (enzyme that deamidates gliadin to make it immunogenic) - used for screening
3. IgA anti-endomysial (part of smooth muscle connective tissue, idk just go with it)

note, IgG testing can also be done in patients with IgA deficiency (remember this is relatively common)

HOWEVER, remember Celiac’s is caused by Type IV (T cell) hypersensitivity - Abs are present but do not contribute (we think)

Question 7

which area of the GI tract is most affected by Celiac Disease, and why does this make sense?

Answer 7

duodenum - this is first part exposed to gluten for absorption

—> steatorrhea, flatulence/bloating, chronic diarrhea, iron deficiency (malabsorption due to inflammation)

Question 8

to which types of cancer (2) are patients with Celiac Disease predisposed?

Answer 8

small increased risk for small bowel malignancy, which is typically rare

1. adenocarcinoma
2. T-cell lymphoma (enteropathy-associated T-cell lymphoma, EATL) - this makes sense bc the pathology is Type IV (T cell) hypersensitivity

classic scenario is patient adhering to gluten-green diet who now presents with worsening symptoms

Question 9

what is the cause of dermatitis herpetiformis? what is the treatment?

Answer 9

herpes-like lesions on skin due to IgA deposition in the dermal papillae

associated with Celiac Disease, resolves with gluten-free diet

Question 10

contrast Celiac Disease and tropical sprue

Answer 10

Celiac disease affects duodenum, may cause iron deficiency (malabsorption)

tropical sprue affects entire small bowel and is associated with folate/B12 deficiency

both cause blunting of villi and chronic diarrhea w/ steatorrhea

Question 11

how does tropical sprue present?

Answer 11

malabsorption due to unknown infectious cause (can be treated with antibiotics), occurs in tropics (esp. Caribbean)

causes blunting of villi similar to Celiac’s, but affects entire small bowel (not just duodenum) —> can cause B12/folate deficiency, steatorrhea, watery diarrhea (sugar malabsorption is osmotic)

Question 12

Your patient returned from a vacation in the Caribbean and now complains of chronic, watery diarrhea. They did not drink local water or eat any undercooked foods. A biopsy is taken from the jejunum which shows blunting of villi. Their condition is successfully treated with tetracycline and folate supplementation. What is the dx? (hint: not looking for infectious agent)

Answer 12

tropical sprue: malabsorption due to unknown infectious agent, occurs in tropics

similar blunting of villi as in Celiac’s, but affects entire small bowel —> folate/B12 malabsorption (—> megaloblastic anemia), steatorrhea, water diarrhea (sugar malabsorption is osmotic)

Question 13

what is the cause of Whipple’s Disease?

Answer 13

infection with Tropheryma whipplei: Gram + rod, related to actinomycetes

causes systematic infection involving small intestine (diarrhea, abdominal pain, weight loss), joints (migratory arthralgia), brain, heart (endocarditis, culture negative)

occurs in white males, ~50yo

Question 14

what are the clinical features of Whipple’s Disease? (4)

Answer 14

infection with Tropheryma whipplei: Gram + rod, related to actinomycetes

4 cardinal features: diarrhea (malabsorption), abdominal pain, weight loss, migratory arthralgia of large joints

can also cause mesenteric lymphadenopathy (abdominal distention), hyperpigmentation, confusion (CNS), culture negative endocarditis (heart)

occurs in white males, ~50yo

biopsy of small intestine shows PAS+ foamy macrophages

Question 15

what is the characteristic histology finding in Whipple’s Disease?

Answer 15

infection with Tropheryma whipplei: Gram + rod, related to actinomycetes

4 cardinal features: diarrhea (malabsorption), abdominal pain, weight loss, migratory arthralgia of large joints

biopsy of small intestine shows PAS+ foamy macrophages in lamina propria

Question 16

PAS+ foamy macrophages in small intestine lamina propria =

Answer 16

Whipple’s Disease: infection with Tropheryma whipplei: Gram + rod, related to actinomycetes

4 cardinal features: diarrhea (malabsorption), abdominal pain, weight loss, migratory arthralgia of large joints

can also cause mesenteric lymphadenopathy (abdominal distention), hyperpigmentation, confusion (CNS), culture negative endocarditis (heart)

Question 17

Pt is a 49yo white M presenting with chronic diarrhea, abdominal pain, weight loss, and migratory joint pain. PE is notable for a distended abdomen and areas of hyperpigmentation. Workup also reveals endocarditis, which is culture negative. He is successfully treated with ceftriaxone. What is the dx, and what would you expect to see on biopsy of the small intestine?

Answer 17

Whipple’s Disease: infection with Tropheryma whipplei: Gram + rod, related to actinomycetes

4 cardinal features: diarrhea (malabsorption), abdominal pain, weight loss, migratory arthralgia of large joints

can also cause mesenteric lymphadenopathy (abdominal distention), hyperpigmentation, confusion (CNS), culture negative endocarditis (heart)

occurs in white males, ~50yo

biopsy of small intestine shows PAS+ foamy macrophages

Question 18

what is the most common cause of lactose intolerance? (in principle)

Answer 18

lactase non-persistence - enzyme levels fall with aging, can fall to such a low level that lactose intolerance occurs

[congenital lactase deficiency is rare]

Question 19

how do the lactose breath hydrogen test and lactose tolerance test work?

Answer 19

lactose breath hydrogen test - patient ingests lactose, if they can’t break it down (intolerant), bacteria will ferment it and produce hydrogen, which is exhaled and detected

lactose tolerance test - patient ingests lactose and blood glucose levels are monitored… should rise if lactose can be broken down to galactose + glucose, but will not rise very much in intolerant patients (less than 20mg/dL)

Question 20

what type of malabsorption is caused by pancreatic insufficiency?

Answer 20

may be caused by cystic fibrosis, chronic pancreatitis, obstruction —> loss of pancreatic lipase, colipase, etc —> fat malabsorption (steatorrhea, deficiency of DAKE vitamins)

Question 21

what is the clinical use of the D-xylose test?

Answer 21

D-xylose is a monosaccharide that is absorbed in intestine but does not require an enzyme to break it down - tests carbohydrate absorption in small intestine

D-xylose is consumed, then levels are measured in serum and urine - should rise in serum in patients with intact absorption, abnormal results seen in bacterial overgrowth, Whipple’s Disease, other causes of malabsorption