Malabsorption — etiopathogenesis, clinical features, diagnostic algorithm and management

Definitions. Maldigestion is impaired breakdown of nutrients within the lumen or at the brush border; malabsorption is impaired mucosal uptake and transport of digested nutrients. Both produce the clinical malabsorption syndrome, and the two frequently coexist.

Luminal (maldigestive) causes. Chronic pancreatitis and pancreatic exocrine insufficiency (also pancreatic carcinoma and post-pancreatectomy), bile salt deficiency from cholestasis or ileal resection, small intestinal bacterial overgrowth with bile salt deconjugation, post-gastrectomy states, and Zollinger-Ellison syndrome (acid inactivation of enzymes).

Mucosal causes. Coeliac disease — increasingly diagnosed in the elderly and often presenting with isolated anaemia or osteoporosis rather than diarrhoea; tropical sprue (important in India); Whipple's disease; Crohn's disease; radiation enteritis; amyloidosis; intestinal lymphoma; giardiasis; HIV enteropathy; and drugs — metformin, olmesartan, colchicine, NSAIDs, orlistat and neomycin.

Structural, lymphatic and vascular causes. Short bowel after resection, blind loops, fistulae and strictures; intestinal lymphangiectasia with protein-losing enteropathy; and chronic mesenteric ischaemia, which is particularly important in older vasculopaths and presents with postprandial abdominal pain, food fear and weight loss.

Pathogenesis. Reduced absorptive surface area, defective luminal digestion, impaired brush-border enzyme activity, bacterial deconjugation of bile salts and lymphatic obstruction lead to osmotic diarrhoea and steatorrhoea, with secondary deficiencies of fat, protein, carbohydrate, vitamins and minerals. Unabsorbed fatty acids and bile acids in the colon further stimulate secretion.

Clinical features. Chronic diarrhoea with pale, bulky, offensive, greasy stools that float and are difficult to flush (steatorrhoea), flatulence, borborygmi, abdominal distension, and weight loss despite an adequate appetite and intake. In the elderly the presentation is often subtle — unexplained weight loss, refractory anaemia, oedema, osteoporotic fracture or falls.

Deficiency syndromes (very high yield). Iron, folate and B deficiency anaemia (often dimorphic); 12 osteomalacia and osteoporosis from calcium and vitamin D deficiency — bone pain, proximal myopathy and fractures; bleeding and bruising from vitamin K deficiency; hypoproteinaemic oedema; night blindness from vitamin A deficiency; glossitis, cheilosis and dermatitis; tetany from hypocalcaemia and hypomagnesaemia; and peripheral neuropathy.

Diagnostic algorithm — Step 1: confirm malabsorption and screen for consequences. Complete blood count with indices and film, iron studies, B and folate, calcium, phosphate, magnesium, vitamin D, albumin, PT/INR, and 12 thyroid function. Confirm fat malabsorption with faecal fat estimation — qualitative Sudan III stain or quantitative 72-hour faecal fat >7 g/day; measure faecal calprotectin to separate inflammatory from non-inflammatory causes.

Diagnostic algorithm — Step 2: identify the specific cause. IgA anti-tissue transglutaminase with total IgA for coeliac disease, confirmed by duodenal biopsy showing villous atrophy (Marsh grading); faecal elastase-1 <200 µg/g for pancreatic exocrine insufficiency, with CT or MRCP of the pancreas; glucose or lactulose hydrogen breath test for bacterial overgrowth (or an empirical antibiotic trial); stool for ova, parasites and Giardia antigen; CT or MR enterography and capsule endoscopy for small bowel disease; and CT angiography if mesenteric ischaemia is suspected. Remember that coeliac serology is falsely negative in IgA deficiency and may be lower-titre in the elderly.

Management. Treat the specific cause — a lifelong strict gluten-free diet with dietitian supervision for coeliac disease; pancreatic enzyme replacement of 40,000–50,000 units of lipase with each main meal plus a PPI for exocrine insufficiency; rotating antibiotics (rifaximin, norfloxacin) for bacterial overgrowth; tetracycline with folic acid for tropical sprue; and revascularisation for mesenteric ischaemia. Replace deficiencies — iron, B , folate, calcium with vitamin D, fat-soluble vitamins A, D, E and K, zinc and magnesium; use medium-chain 12 triglycerides in severe steatorrhoea since they are absorbed without bile salts or lymphatics; monitor bone mineral density; and address weight, sarcopenia and quality of life.

ACG Clinical Guideline on Coeliac Disease 2023 (Am J Gastroenterol 2023;118:59) — IgA anti-tTG with a total IgA level remains the single best initial test; duodenal biopsy (one from the bulb and four from the distal duodenum) is still required in adults for diagnosis; HLA-DQ2/DQ8 typing is useful only to exclude the disease, not to confirm it. The guideline emphasises follow-up biopsy or serology for persistent villous atrophy, and routine screening for nutritional deficiency and metabolic bone disease — particularly relevant in older patients diagnosed late.

AGA Clinical Practice Update on exocrine pancreatic insufficiency (2023) — highlights that PEI is substantially under-diagnosed and, when diagnosed, systematically under-dosed. It occurs not only in chronic pancreatitis but also after gastric and pancreatic surgery, and in diabetes, coeliac disease and advanced age. Faecal elastase-1 should be checked in any patient with unexplained weight loss or steatorrhoea, and enzyme doses should be titrated upward against symptoms and nutritional markers rather than left at a fixed low dose.