STEPTRACKERGASTROINTESTINAL | PATHOLOGY + IMMUNOLOGY + BIOCHEMISTRY | HIGH-YIELD REVIEW

Malabsorption

When nutrients reach the gut but don't get absorbed: the mucosa, the enzymes, the bugs and the lipoproteins.

FOCUS ON
Malabsorption gives diarrhea, steatorrhea, weight loss and deficiencies (ADEK, B12, folate, iron). Celiac disease is the headline: HLA-DQ2/DQ8, anti-tTG IgA, villous atrophy in the distal duodenum, dermatitis herpetiformis. The D-xylose test separates mucosal disease (abnormal) from pancreatic insufficiency (normal).
DISORDER
MECHANISM
FEATURES · HISTOLOGY
CLUE · TREATMENT
Celiac disease
Gliadin deamidated by tissue transglutaminase → presented on HLA-DQ2/DQ8 → T-cell injury
Villous atrophy, crypt hyperplasia, ↑ intraepithelial lymphocytes; distal duodenum, proximal jejunum
IgA anti-tTG, anti-endomysial, anti-DGP · gluten-free diet
Celiac — associations
Systemic consequences of the immune response and malabsorption
Dermatitis herpetiformis, iron-deficiency anemia, osteoporosis, hyposplenism, ↓ fertility
↑ risk of EATL (T-cell lymphoma), small bowel adenocarcinoma · IgA deficiency (false-negative IgA tests)
Lactase deficiency
Primary (age-related decline, common in Asian/African ancestry) or secondary (after gastroenteritis, celiac)
Bloating, gas, osmotic diarrhea after dairy; normal villi
↓ stool pH, ↑ breath H₂, ↑ stool osmotic gap
Pancreatic insufficiency
↓ lipase, protease: CF, chronic pancreatitis, obstructing tumor
Steatorrhea, ADEK and B12 deficiency (needs pancreatic proteases to free B12 from R-binder)
↓ fecal elastase · normal D-xylose · enzyme replacement
Tropical sprue
Probably infectious; residents/visitors of the tropics
Villous atrophy across the whole small bowel; B12 and folate deficiency → megaloblastic anemia
Responds to antibiotics + folate
Whipple disease
Tropheryma whipplei (gram⁺ actinomycete)
PAS⁺ foamy macrophages in the lamina propria; distended villi; older White men
Arthralgia, cardiac, neuro (oculomasticatory myorhythmia), lymphadenopathy
Abetalipoproteinemia
Autosomal recessive MTTP defect → no apoB-48 or apoB-100 → no chylomicrons, VLDL, LDL
Lipid-laden enterocytes; failure to thrive, steatorrhea in infancy; acanthocytes
Vitamin E deficiency → ataxia, retinitis pigmentosa
Small intestinal bacterial overgrowth
Stasis: blind loop, strictures, scleroderma, diabetic neuropathy, ↓ acid
Bacteria deconjugate bile acids and consume B12
↓ B12 with ↑ folate (bacteria make folate)
Giardiasis
Giardia trophozoites attach to the duodenal mucosa
Foul-smelling fatty diarrhea, bloating after camping (stream water)
Common in IgA deficiency · metronidazole
Terminal ileal disease
Crohn disease, ileal resection
↓ bile acid reabsorption → fat malabsorption; ↓ B12
Calcium oxalate kidney stones (fat binds Ca²⁺) · gallstones

Mechanism — celiac disease

Gluten (gliadin)
→
tTG deamidationFits HLA-DQ2/8 better
→
CD4 T cells + IELsIFN-γ, IL-15
→
Villous atrophy↓ absorptive surface
→
MalabsorptionIron, folate, Ca²⁺, ADEK

Site follows exposure: gluten is highest proximally, so the duodenum is hit hardest — the same site where iron is absorbed.

Sorting malabsorption by test

TEST
RESULT
MEANING
Sudan stain of stool
Fat ⁺
Steatorrhea
D-xylose absorption
↓ (abnormal)
Mucosal disease (celiac, sprue, Whipple)
D-xylose absorption
Normal
Pancreatic insufficiency
Fecal elastase
↓
Pancreatic insufficiency
Hydrogen breath test
↑ H₂
Lactase deficiency or SIBO
Duodenal biopsy
Villi, PAS⁺ cells
Celiac vs Whipple

How it's tested

COMMON CONFUSIONLactose intolerance has normal histology and an osmotic diarrhea that stops with fasting. Celiac disease has abnormal villi and positive antibodies.
THE TRAPA celiac patient with IgA deficiency will have negative IgA anti-tTG. Check total IgA, then use IgG-based tests (IgG anti-DGP).
YOUR APPROACHConfirm steatorrhea → D-xylose (mucosa vs pancreas) → antibodies/biopsy → look for clues (travel, camping, atopy, joints, acanthocytes).

If you see… think…

Itchy vesicles on elbows + iron deficiency + diarrhea → celiac disease
Villous atrophy, crypt hyperplasia, intraepithelial lymphocytes → celiac disease
Treated celiac with new weight loss and abdominal pain → EATL (T-cell lymphoma)
Bloating after milk, normal biopsy, ↑ breath H₂ → lactase deficiency
Arthralgia + diarrhea + PAS⁺ foamy macrophages → Whipple disease
Infant with steatorrhea, acanthocytes, ataxia → abetalipoproteinemia
Steatorrhea with normal D-xylose test → pancreatic insufficiency
Megaloblastic anemia after living in the Caribbean → tropical sprue
Low B12 + high folate after a blind loop → bacterial overgrowth
Foul greasy diarrhea after drinking stream water → Giardia