Malabsorption Syndromes

Malabsorption is the defective uptake of one or more dietary nutrients across the small-intestinal mucosa, distinct from maldigestion (defective intraluminal breakdown). For NEET PG, this topic is a dense, fact-rich cluster — coeliac disease, tropical sprue, Whipple disease, lactase deficiency and the steatorrhoea workup — where antibody profiles, biopsy histology, the investigation of choice and drug of choice are repeatedly tested.

Definition & Classification

Maldigestion = failure to break down nutrients in the lumen (e.g., pancreatic exocrine insufficiency, bile-salt deficiency). Malabsorption = failure of mucosal uptake/transport despite adequate digestion (e.g., coeliac disease, short bowel). The two overlap clinically and both produce steatorrhoea (faecal fat > 7 g/day on a 100 g/day fat diet).

A clean classification divides causes by the phase of nutrient handling disrupted:

Phase	Mechanism	Classic examples
Luminal (maldigestion)	Defective hydrolysis	Chronic pancreatitis, cystic fibrosis, bile-salt deficiency (cholestasis, bacterial overgrowth, terminal ileal disease)
Mucosal	Damaged absorptive surface / enterocyte defect	Coeliac disease, tropical sprue, Whipple disease, lactase deficiency, abetalipoproteinaemia
Post-mucosal	Impaired transport from enterocyte	Intestinal lymphangiectasia, Whipple disease (lymphatic block), congestive states

High-yield: Selective malabsorption (one nutrient) vs global malabsorption (all classes). Pernicious anaemia = selective B12 malabsorption; lactase deficiency = selective lactose. Coeliac disease and tropical sprue cause global malabsorption because they damage the whole proximal mucosa.

Clinical Features Common to Malabsorption

The syndrome reflects which nutrients are lost. Use the deficiency to reason backwards to the cut surface affected.

• Steatorrhoea — bulky, pale, foul, floating, difficult-to-flush stools (fat malabsorption).
• Weight loss despite adequate intake; growth failure in children.
• Iron / folate deficiency → microcytic or megaloblastic anaemia. Iron and folate are absorbed in the duodenum and jejunum — hence prominent in proximal disease (coeliac, tropical sprue).
• Vitamin B12 absorbed in terminal ileum — deficiency in ileal disease (Crohn, resection) and tropical sprue (which affects whole small bowel).
• Fat-soluble vitamins (A, D, E, K): night blindness (A), osteomalacia/tetany (D + calcium), neuropathy/ataxia (E), bleeding/prolonged PT (K).
• Hypoproteinaemia → oedema; hypocalcaemia/hypomagnesaemia → tetany, Chvostek/Trousseau signs.
• Glossitis, angular stomatitis, cheilosis (B-complex/iron).

High-yield: A prolonged prothrombin time that corrects with parenteral vitamin K points to fat malabsorption rather than hepatocellular failure (where it does not correct).

Coeliac Disease (Gluten-Sensitive Enteropathy)

An immune-mediated enteropathy triggered by gliadin (the alcohol-soluble fraction of gluten in wheat, barley, rye). Oats are usually tolerated unless contaminated.

Pathophysiology

Tissue transglutaminase (tTG) deaminates gliadin peptides → these bind HLA-DQ2 (≈90–95%) or HLA-DQ8 on antigen-presenting cells → CD4⁺ T-cell activation → mucosal damage. The lesion is maximal in the proximal small bowel (duodenum/jejunum) where gluten exposure is highest.

High-yield: Absence of HLA-DQ2 and DQ8 has a very high negative predictive value — it essentially rules out coeliac disease. But their presence is non-diagnostic (common in the general population).

Clinical clues

Classic: chronic diarrhoea, steatorrhoea, weight loss, iron-deficiency anaemia refractory to oral iron. Atypical/silent forms are now commoner. Associations to memorise:

• Dermatitis herpetiformis — intensely pruritic vesicles on extensors; IgA deposits at dermal papillae; treat with a gluten-free diet ± dapsone.
• Type 1 diabetes, autoimmune thyroiditis, IgA deficiency, Down syndrome.
• Hyposplenism (Howell-Jolly bodies on smear).

Diagnosis & investigation of choice

Test	Comment
Anti-tissue transglutaminase IgA (anti-tTG IgA)	First-line serology — best combination of sensitivity & specificity
Anti-endomysial antibody (EMA) IgA	Most specific (~near 100%); confirmatory
Anti-deamidated gliadin peptide (DGP)	Useful in young children / IgA deficiency
Total serum IgA	Always check — selective IgA deficiency gives false-negative IgA serology; then use IgG-based tests (IgG-tTG/DGP)
Duodenal biopsy (gold standard)	Take ≥4 biopsies from second part of duodenum + bulb, while patient is still on gluten

Histology (Marsh classification): intraepithelial lymphocytosis → crypt hyperplasia → villous atrophy (blunted/absent villi). Villous atrophy is the hallmark but is not specific (also in tropical sprue, etc.).

Diagnostic flow: Suspicion → anti-tTG IgA + total IgA → if positive → duodenal biopsy (on gluten) → start gluten-free diet → antibodies fall / mucosa recovers confirms diagnosis.

Management

• Lifelong strict gluten-free diet (GFD) — drug/treatment of choice; correct iron, folate, calcium, vitamin D, B12.
• Pneumococcal vaccination (hyposplenism).
• Refractory coeliac disease: no response to GFD → consider steroids/immunosuppression and exclude complications.

High-yield: Most feared complication is enteropathy-associated T-cell lymphoma (EATL); also increased small-bowel adenocarcinoma. Suspect when a previously controlled patient relapses on a strict diet.

Tropical Sprue

An acquired malabsorption of unknown infective aetiology (postulated coliform/bacterial overgrowth) affecting residents of and visitors to tropical regions (Indian subcontinent, Caribbean, South-East Asia). Highly relevant in the Indian context.

Features

• Chronic diarrhoea, weight loss, glossitis.
• Megaloblastic anaemia from combined folate and vitamin B12 deficiency — because tropical sprue, unlike coeliac, affects the entire small bowel including the terminal ileum (site of B12 absorption).
• Biopsy: villous atrophy, but typically less severe / partial and involving distal bowel too; with eosinophilic and lymphocytic infiltrate.

Diagnosis & treatment

High-yield: Treatment (and drug of choice) = tetracycline (or doxycycline) + folic acid for 3–6 months. The dramatic response to this combination is itself supportive of the diagnosis.

Feature	Coeliac disease	Tropical sprue
Trigger	Gluten (gliadin)	? Infective; tropics
Bowel involved	Proximal (duodenum/jejunum)	Whole small bowel
Anaemia	Iron / folate (proximal)	Folate + B12 (megaloblastic)
Serology	Anti-tTG / EMA positive	Negative
Treatment	Gluten-free diet	Tetracycline + folic acid
Response to GFD	Yes	No

Whipple Disease

A rare, multisystem chronic infection by the actinomycete Tropheryma whipplei. Classically a middle-aged white male.

Clinical tetrad

Think "WHIPPLE" systemically: Weight loss, Heart (endocarditis, culture-negative), migratory arthralgia (often precedes GI symptoms by years), diarrhoea/abdominal pain, lymphadenopathy, hyperpigmentation, and CNS involvement (dementia, oculomasticatory myorhythmia — pathognomonic).

Diagnosis

High-yield: Small-bowel (duodenal) biopsy showing PAS-positive (periodic acid–Schiff) foamy macrophages in the lamina propria containing the bacilli — investigation of choice. Confirm/clinch with PCR for T. whipplei. PAS positivity can be mimicked by MAC (Mycobacterium avium) in HIV — distinguished because MAC is also acid-fast (Ziehl-Neelsen positive), whereas T. whipplei is acid-fast negative.

Treatment

• Induction: IV ceftriaxone (or penicillin) for ~2 weeks, then
• Maintenance: oral co-trimoxazole (TMP-SMX) for ~1 year (crosses blood-brain barrier — prevents CNS relapse).

High-yield: Untreated Whipple disease is fatal; relapse is common, especially neurological, hence the prolonged CNS-penetrating maintenance.

Lactase Deficiency (Lactose Intolerance)

The commonest disaccharidase deficiency and a classic example of selective carbohydrate malabsorption.

• Primary (adult-type hypolactasia): genetically programmed decline of lactase after weaning — very common in Asians and Africans.
• Secondary: transient, after mucosal injury (gastroenteritis, coeliac, giardiasis) — reversible.

Mechanism: unhydrolysed lactose is osmotically active → osmotic diarrhoea; colonic bacterial fermentation → bloating, flatulence, cramps, acidic stool.

Diagnosis:

• Lactose hydrogen breath test — rise in breath H₂ after a lactose load (investigation of choice, non-invasive).
• Stool: acidic pH (< 5.5), positive reducing substances, increased osmotic gap.
• Lactose tolerance test (flat glucose curve) — older method.

Treatment: lactose restriction, lactase enzyme supplements, calcium/vitamin D replacement. (Diarrhoea is osmotic — stops with fasting, unlike secretory diarrhoea.)

Steatorrhoea Workup — The Investigations

This is the single most examinable "approach" theme. Learn the sequence and what each test localises.

Stepwise approach: Confirm steatorrhoea → confirm/quantify malabsorption → localise (mucosal vs pancreatic vs ileal) → specific cause.

1. Qualitative fat — Sudan III stain of stool (screening, fat globules).
2. Quantitative fat (gold standard for steatorrhoea) — 72-hour faecal fat on a 100 g/day fat diet; > 7 g/day = steatorrhoea.
3. D-xylose absorption test — the key localiser (below).
4. Schilling test — localises B12 malabsorption (pernicious anaemia vs ileal disease vs bacterial overgrowth vs pancreatic).
5. Faecal elastase / faecal chymotrypsin ↓ in pancreatic exocrine insufficiency.
6. Imaging/endoscopy: duodenal biopsy, CT/MRCP for pancreas, capsule/enteroscopy.

D-xylose test — interpret it precisely

D-xylose is a pentose absorbed passively in the proximal small bowel without needing pancreatic enzymes or bile, then excreted in urine. So it isolates mucosal integrity.

D-xylose result	Interpretation
Low (low urinary/blood xylose)	Mucosal disease (coeliac, tropical sprue) or bacterial overgrowth (bacteria consume xylose)
Normal	Mucosa intact → think pancreatic insufficiency or bile-salt deficiency as the cause of fat malabsorption

High-yield: Low D-xylose that corrects after antibiotics = small-intestinal bacterial overgrowth (SIBO); low and uncorrected = primary mucosal disease. Normal D-xylose in a patient with steatorrhoea redirects you to the pancreas.

High-yield: In pancreatic exocrine insufficiency, fat-soluble vitamin and fat malabsorption occur, but D-xylose is normal and there is no anaemia of iron/folate type initially — a favourite distinguishing point.

Other Mucosal Causes Worth a Line

• Abetalipoproteinaemia: absent apoB → cannot form chylomicrons; acanthocytes on smear, fat-laden enterocytes, retinitis pigmentosa, neuro signs; treat with vitamin E.
• Intestinal lymphangiectasia: dilated lacteals → protein-losing enteropathy, lymphocytopenia, low immunoglobulins, oedema.
• Bile acid malabsorption (terminal ileal disease/resection): watery diarrhoea responding to cholestyramine.

Complications

• Profound malnutrition, growth/developmental failure in children.
• Metabolic bone disease — osteomalacia, osteoporosis, hypocalcaemic tetany.
• Bleeding diathesis (vitamin K), anaemia (iron/folate/B12).
• Coeliac: EATL lymphoma, small-bowel adenocarcinoma, refractory disease, hyposplenism-related sepsis.
• Whipple: CNS relapse, culture-negative endocarditis, death if untreated.
• Oxalate renal stones (enteric hyperoxaluria) in fat malabsorption/short bowel — unabsorbed fatty acids bind calcium, freeing oxalate for absorption.

Key Differentials

When a patient presents with chronic diarrhoea + weight loss, separate the big four:

Clue	Points to
Anti-tTG positive, proximal villous atrophy, responds to GFD	Coeliac disease
Tropical residence, B12 + folate deficiency, responds to tetracycline + folate	Tropical sprue
Arthralgia + dementia + PAS⁺ macrophages	Whipple disease
Symptoms only with milk, acidic stool, ↑breath H₂	Lactase deficiency
Normal D-xylose, ↓faecal elastase, calcified pancreas	Pancreatic insufficiency
Diarrhoea stops on fasting, high stool osmotic gap	Osmotic (e.g., lactose)
Diarrhoea persists on fasting, normal osmotic gap	Secretory

Recently asked / exam angle

• Investigation of choice / single best test questions: anti-tTG IgA (first serology) and duodenal biopsy (gold standard) for coeliac; PAS-positive macrophages + PCR for Whipple; lactose hydrogen breath test for lactose intolerance; 72-hour faecal fat for steatorrhoea.
• D-xylose interpretation (mucosal vs pancreatic; correction after antibiotics = SIBO) is a recurring single-line MCQ.
• HLA association: DQ2/DQ8 with coeliac; negative result rules out.
• Drug of choice: tetracycline + folic acid (tropical sprue); ceftriaxone then long-term co-trimoxazole (Whipple); dapsone for dermatitis herpetiformis skin lesions.
• Image/buzzword: villous atrophy (coeliac/sprue), PAS-positive foamy macrophages (Whipple), acanthocytes (abetalipoproteinaemia), Howell-Jolly bodies (coeliac hyposplenism).
• A common trap: MAC vs Whipple — both PAS-positive, but MAC is acid-fast positive and seen in HIV.
• "Why B12 deficiency in tropical sprue but not classic coeliac?" — sprue affects the terminal ileum; coeliac is proximal.

Rapid revision

1. Maldigestion = luminal defect; malabsorption = mucosal/transport defect; both cause steatorrhoea (>7 g fat/day).
2. Coeliac: gliadin in wheat/barley/rye; HLA-DQ2/DQ8; anti-tTG IgA screen, EMA most specific, duodenal biopsy gold standard.
3. Always check total IgA — IgA deficiency causes false-negative coeliac serology; switch to IgG-based tests.
4. Coeliac lesion is proximal → iron + folate deficiency; dermatitis herpetiformis (IgA at dermal papillae) treated with GFD + dapsone.
5. Coeliac complication = EATL lymphoma; treatment = lifelong gluten-free diet.
6. Tropical sprue: whole small bowel → folate + B12 megaloblastic anaemia; treat tetracycline/doxycycline + folic acid 3–6 months.
7. Whipple = Tropheryma whipplei; arthralgia precedes GI; PAS-positive macrophages + PCR; oculomasticatory myorhythmia is pathognomonic.
8. Whipple therapy: IV ceftriaxone → oral co-trimoxazole ~1 year (CNS cover).
9. Lactase deficiency: osmotic diarrhoea, acidic stool, lactose hydrogen breath test; diarrhoea stops with fasting.
10. D-xylose low = mucosal disease/SIBO; normal = pancreatic/bile cause; correction after antibiotics = SIBO.
11. 72-hour faecal fat = gold standard to quantify steatorrhoea; faecal elastase low in pancreatic insufficiency.
12. Fat malabsorption → fat-soluble vitamin deficiency (A,D,E,K), prolonged PT correcting with parenteral vitamin K, and enteric hyperoxaluria (oxalate stones).