Malabsorption Syndromes
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Direct answer
Weight loss with chronic diarrhoea, steatorrhoea (pale, bulky, floating stools) and deficiencies of iron, folate, B12 or fat-soluble vitamins defines the malabsorption syndromes, divided mechanistically into luminal causes (bile salt deficiency, pancreatic exocrine failure), mucosal causes (coeliac disease, tropical sprue, giardiasis, Whipple disease) and post-mucosal causes (lymphangiectasia, lymphoma). The two-test sieve separates them: D-xylose is abnormal in mucosal disease but normal with pancreatic or biliary causes, while 72-hour faecal fat (over 7 g/day on a 100 g daily fat diet) confirms steatorrhoea from any cause. Treatment is cause-specific — gluten-free diet, enzymes, antibiotics — layered on universal nutritional repletion.
What you must remember
- The sieve to recite: D-xylose (a pentose absorbed across intact mucosa without enzymes) falls in mucosal disease; pancreatic causes give a normal D-xylose but abnormal faecal fat and a faecal elastase below 200 µg/g.
- Site-specific deficiency patterns: iron and folate deficiency suggest proximal jejunal disease (coeliac); B12 deficiency suggests terminal ileal disease (Crohn's, resection, tropical sprue, fish tapeworm); vitamin K malabsorption gives a raised INR with cholestasis.
- Tropical sprue: the Indian postgraduate's default mucosal cause — megaloblastic anaemia from combined folate and B12 deficiency, patchy villous atrophy, and dramatic response to folic acid 5 mg daily with tetracycline for three to six months; the exam answer for "megaloblastic anaemia with steatorrhoea in the tropics".
- Giardia trophozoites: the commonest small-intestinal parasite in India — foul-smelling fatty stools without blood, seen on duodenal biopsy or string test, cured by metronidazole or tinidazole; it causes secondary lactase deficiency, and IgA deficiency increases risk.
- Coeliac serology pathway: IgA anti-tTG with a total IgA level (10-15 percent selective IgA deficiency in some series), duodenal biopsies with villous atrophy and crypt hyperplasia before starting the gluten-free diet.
- Whipple disease: a PAS-positive macrophage-infiltrated mucosa, Tropheryma whipplei on PCR, arthralgia preceding diarrhoea by years, weight loss, dementia and ophthalmoplegia — treated with ceftriaxone then co-trimoxazole for a year.
- Short-bowel arithmetic: ileal resection under 100 cm causes bile-salt diarrhoea treated with cholestyramine; beyond 100 cm the bile salt pool depletes, true steatorrhoea develops, and cholestyramine worsens it — give medium-chain triglycerides instead.
- Zollinger-Ellison: inappropriately low pH inactivates lipase, so refractory peptic ulcer disease with unexplained steatorrhoea is the exam pattern; gastrin over 1,000 pg/mL with a gastric pH below 2 clinches it.
The three-compartment workup
A 34-year-old man from Bihar presents with six months of bulky greasy stools, 8 kg weight loss, glossitis and a haemoglobin of 8.5 g/dL with an MCV of 110 fL. The first step places the lesion: a megaloblastic picture pulls tropical sprue, fish-tapeworm or ileal Crohn's to the top, while iron deficiency would pull coeliac. D-xylose absorption is impaired, pointing at the mucosa rather than the pancreas; coeliac serology is negative, faecal elastase normal. Upper gastrointestinal endoscopy with distal duodenal biopsy shows partial villous atrophy, and no Giardia trophozoites are seen, while PAS-positive macrophages are absent, excluding Whipple. The composite — residence in the tropics, folate-B12 deficiency, patchy villous atrophy, no alternative — supports tropical sprue. Folic acid 5 mg daily begins; reticulocytes rise within a week and the glossitis clears within two, the folate-first response being itself diagnostic. Tetracycline 250 mg four times daily is added for a three-to-six month course because relapse without antibiotics is common.
Had D-xylose been normal with a low elastase, the pathway moves to chronic pancreatitis; had the biopsy shown dilated lacteals with lymphopenia and hypoalbuminaemia, it moves to lymphangiectasia and a medium-chain triglyceride diet.
The examiner's favourite trap
The most-tested confusion is coeliac versus tropical sprue on a duodenal biopsy: both show villous atrophy, but coeliac has strongly positive tTG-IgA, HLA-DQ2/DQ8 association and subtotal atrophy with crypt hyperplasia, whereas tropical sprue is seronegative, involves the terminal ileum with B12 deficiency, and responds to folate within days — geography or folate response is the discriminator the stem hides. The second trap is the D-xylose question in pancreatic disease: candidates wrongly call it abnormal; pancreatic insufficiency leaves mucosa intact, so xylose absorption is preserved. Third, remember that bacterial overgrowth can deconjugate bile salts and produce a mixed picture — a course of rifaximin with repeat testing unmasks the underlying diagnosis.
Frequently asked questions
How does the D-xylose test differentiate malabsorption causes?
D-xylose needs no digestion and is absorbed directly by jejunal mucosa, so impaired excretion points to mucosal disease (coeliac, sprue) while pancreatic insufficiency and bile salt deficiency leave it normal.
What distinguishes tropical sprue from coeliac disease?
Tropical sprue occurs in tropical residents, is tTG-negative, frequently causes B12 deficiency from terminal ileal involvement, and responds dramatically to folate; coeliac is gluten-driven, serology-positive and needs a lifelong gluten-free diet.
Which deficiencies localise the malabsorbing segment?
Iron and folate point to proximal jejunum, B12 to terminal ileum, and fat-soluble vitamins A, D, E and K with a rising INR to cholestasis or diffuse mucosal disease.
How does ileal resection length change management?
Resections under about 100 cm cause secretory bile-salt diarrhoea responsive to cholestyramine; longer resections deplete the bile salt pool, causing true steatorrhoea where cholestyramine worsens fat loss and medium-chain triglycerides are needed.
Which infection produces malabsorption with PAS-positive macrophages?
Whipple disease, caused by Tropheryma whipplei — PAS-positive foamy macrophages in the lamina propria, preceded by arthritis, treated with prolonged antibiotics.