Nutrient Absorption & Post-Surgical Deficiencies
Where each nutrient crosses, and what surgery takes away
Carbohydrates and proteins
The absorptive engine. About 9 L of fluid enters the small intestine daily (roughly 2 L ingested and 7 L secreted); the small bowel reclaims most of it, the colon most of the rest, and only about 100–200 mL leaves in stool. The basolateral Na+/K+-ATPase keeps enterocyte Na+ low, powering the Na+-coupled transporters that drive much of nutrient uptake.
Carbohydrate digestion. Salivary α-amylase starts on starch and is inactivated by gastric acid; pancreatic α-amylase finishes the luminal phase. Amylase cuts only α-1,4 bonds, yielding maltose, maltotriose, and α-limit dextrins; it cannot cut α-1,6 branch points or the β-linkages of cellulose. Brush-border enzymes complete digestion: lactase (lactose → glucose + galactose), sucrase-isomaltase (sucrose → glucose + fructose; the isomaltase domain removes α-1,6 branches), and maltase-glucoamylase. Only monosaccharides are absorbed.
Monosaccharide transport. Glucose and galactose enter through apical SGLT1, which couples each sugar to 2 Na+ (secondary active transport). Fructose enters by facilitated diffusion through GLUT5. All three leave through basolateral GLUT2 into portal blood.
Oral rehydration solution works because secretory toxins such as cholera toxin block NaCl absorption but spare SGLT1: glucose carries Na+ in, and water follows. SGLT1 mutations cause congenital glucose-galactose malabsorption, with severe neonatal diarrhea that stops on a fructose-based formula.
Protein digestion. Pepsin, activated by gastric acid, begins proteolysis but is not essential. The key step is in the duodenum: brush-border enteropeptidase (enterokinase) converts trypsinogen to trypsin, which activates chymotrypsinogen, proelastase, procarboxypeptidases A and B, procolipase, prophospholipase A2, and more trypsinogen. Congenital enteropeptidase deficiency causes severe protein malabsorption with edema and failure to thrive. Brush-border peptidases then yield free amino acids plus di- and tripeptides.
Amino acid and peptide uptake. Free amino acids enter through several transporter families, most of them Na+-coupled. Di- and tripeptides enter faster through PepT1, driven by an H+ gradient, and are split by cytosolic peptidases; amino acids exit basolaterally to portal blood. In Hartnup disease, a defective neutral amino acid transporter in gut and kidney causes tryptophan loss and pellagra-like symptoms, but dietary peptides still enter through PepT1, so a high-protein diet helps.
Fats
- EmulsificationBile salts and gastric churning break fat into small droplets
- LipolysisColipase anchors pancreatic lipase to the droplet; triglyceride → 2-monoglyceride + free fatty acids; cholesterol esterase and phospholipase A2 act alongside
- Micelle transportMixed micelles carry lipids and vitamins A, D, E, K across the unstirred water layer
- Re-esterificationSmooth ER rebuilds triglyceride, cholesterol esters, and phospholipids
- Chylomicron exportMTP loads ApoB-48; chylomicrons enter lacteals → thoracic duct → blood, bypassing the liver
Key players. Bile salts are amphipathic, which lets them both emulsify fat and form micelles; they are not absorbed with the lipids but stay in the lumen for reuptake in the terminal ileum. Colipase, activated from procolipase by trypsin, is required because bile salts coating the droplet would otherwise keep lipase off its substrate. Steatorrhea follows failure at any step: pancreatic insufficiency (lipase), bile salt deficiency (cholestasis, ileal loss), mucosal disease, or lymphatic obstruction.
Medium-chain triglycerides. Fatty acids of 6–12 carbons need neither micelles nor chylomicrons and enter portal blood directly, which makes MCT oil a useful calorie source in fat malabsorption and short bowel syndrome.
Abetalipoproteinemia (MTP deficiency) traps fat inside enterocytes: steatorrhea, acanthocytes, very low plasma lipids, and fat-soluble vitamin deficiency, with vitamin E loss causing ataxia.
Where each nutrient is absorbed
| Site | Key nutrients | Mechanism |
|---|---|---|
| Duodenum | Iron, calcium | Fe2+ via DMT1; calcitriol-driven active Ca2+ uptake |
| Jejunum | Folate; most sugars, amino acids, and fat | Proton-coupled folate transporter; SGLT1, PepT1, micelles |
| Terminal ileum | Vitamin B12, bile salts | Cubilin takes up IF-B12; Na+-coupled ASBT reclaims bile salts |
| Colon | Water, Na+, short-chain fatty acids | Aldosterone-sensitive Na+ uptake; butyrate fuels colonocytes |
Iron. Dietary Fe3+ is reduced to Fe2+ by duodenal cytochrome b, a step helped by gastric acid and vitamin C, and enters through apical DMT1; heme iron uses a separate carrier. Iron is stored as ferritin or exported through basolateral ferroportin, re-oxidized by hephaestin, and bound to transferrin. Hepcidin from the liver degrades ferroportin, shutting absorption down when stores are full or inflammation is present.
Calcium. Active transcellular uptake in the duodenum depends on calcitriol, which induces calbindin; passive paracellular uptake continues along the rest of the small bowel. Acid helps dissolve calcium salts, so achlorhydria and duodenal bypass both impair absorption.
Folate. Dietary polyglutamates are trimmed to monoglutamates by a brush-border conjugase and absorbed in the proximal jejunum by the proton-coupled folate transporter. Stores last only about 3–4 months, so jejunal disease such as celiac disease or poor intake produces deficiency quickly.
Vitamin B12. Acid and pepsin free B12 from food proteins, and it binds haptocorrin (R-binder) from saliva. In the duodenum, pancreatic proteases degrade haptocorrin so B12 can bind intrinsic factor from parietal cells. Cubilin receptors in the terminal ileum absorb the IF-B12 complex; transcobalamin II carries B12 in blood, and liver stores last years. Deficiency can therefore follow loss of acid, parietal cells, pancreatic proteases, or ileum, or bacterial overgrowth that consumes B12.
Bile salts. About 95% of conjugated bile salts are reclaimed in the terminal ileum by the apical sodium-dependent bile acid transporter (ASBT) and returned to the liver in portal blood. The small fraction lost in stool is replaced by hepatic synthesis from cholesterol, rate-limited by 7α-hydroxylase.
After gastric surgery
Deficiencies. Total gastrectomy removes all parietal cells and intrinsic factor, guaranteeing B12 deficiency without supplementation; Roux-en-Y gastric bypass leaves a small pouch with little acid or intrinsic factor. Reduced acid plus bypass of the duodenum impairs iron absorption (microcytic anemia) and calcium and vitamin D absorption (bone loss, secondary hyperparathyroidism). Lifelong B12, iron, calcium citrate (which does not need acid to dissolve), and vitamin D are routine.
Persistent vomiting after bariatric surgery can precipitate thiamine deficiency and Wernicke encephalopathy; copper deficiency can mimic B12 deficiency with anemia and myeloneuropathy.
| Feature | Early dumping | Late dumping |
|---|---|---|
| Timing | 10–30 minutes after eating | 1–3 hours after eating |
| Mechanism | Hyperosmolar chyme pulls fluid into the small bowel; vasoactive peptides released | Rapid glucose absorption → exaggerated incretin (GLP-1)-driven insulin surge |
| Symptoms | Cramps, bloating, diarrhea, palpitations, flushing, lightheadedness | Reactive hypoglycemia: sweating, tremor, confusion |
| Management | Small frequent meals; liquids separate from solids | Avoid simple sugars; acarbose if refractory |
Ileal resection and short bowel syndrome
| Feature | Under ~100 cm | Over ~100 cm |
|---|---|---|
| Bile acid pool | Maintained by increased hepatic synthesis | Depleted; losses outstrip synthesis |
| Diarrhea | Watery bile acid diarrhea: bile acids stimulate colonic Cl− and water secretion | Steatorrhea with loss of vitamins A, D, E, K |
| Treatment | Bile acid sequestrant (cholestyramine) | Low-fat diet, MCT, vitamin replacement; sequestrants worsen it |
Enteric hyperoxaluria. Unabsorbed fatty acids bind luminal calcium (saponification), leaving dietary oxalate free. The colon absorbs it, and the kidney excretes it as calcium oxalate stones. This requires an intact colon and is treated with hydration, a low-fat, low-oxalate diet, and calcium taken with meals to bind oxalate.
Gallstones. A shrunken bile acid pool leaves bile supersaturated with cholesterol, so cholesterol gallstones are common after ileal resection or with ileal Crohn disease.
Short bowel syndrome. Malabsorption from too little functional small bowel, usually under about 200 cm in adults. Causes include mesenteric ischemia, Crohn disease, volvulus, and trauma in adults, and necrotizing enterocolitis, midgut volvulus, and gastroschisis in children. Consequences:
- Diarrhea, dehydration, and loss of sodium, potassium, magnesium, and zinc
- Malnutrition with B12 and fat-soluble vitamin deficiency
- Transient gastric acid hypersecretion after massive resection
- Cholesterol gallstones and calcium oxalate kidney stones
- D-lactic acidosis with confusion, when colonic bacteria ferment excess carbohydrate
- Bacterial overgrowth, and liver disease from long-term parenteral nutrition
Adaptation. Over 1–2 years the remnant adapts with villous hyperplasia and dilation. The ileum can take over jejunal functions but not the reverse, because B12 and bile salt receptors are ileal. A retained colon absorbs water and salvages calories from short-chain fatty acids. Teduglutide, a GLP-2 analog, enhances adaptation and can reduce dependence on parenteral nutrition.