Absorption of iron, calcium and vitamin B12 !

Mechanism
Exam priority: medium

Iron and calcium are absorbed mainly in the duodenum; vitamin B12 needs intrinsic factor from the stomach and is absorbed at the end of the ileum.

Updated 2026-11-01

Also called: Hepcidin, Intrinsic factor

See it in 3D: Stomach · Duodenum · Jejunum · Ileum · Liver

Key points

Non-heme iron: Fe³⁺ is reduced to Fe²⁺ (duodenal cytochrome b, vitamin C) and enters via DMT1; it leaves via ferroportin and hephaestin oxidizes it for transferrin.
Hepcidin (liver) degrades ferroportin: when it rises (inflammation, overload) absorption falls; when it falls (deficiency, active erythropoiesis) absorption rises.
Heme iron is absorbed better than non-heme iron; phytates, tannins, calcium and lack of acid reduce non-heme uptake.
Calcium: a transcellular duodenal route (TRPV6, calbindin, Ca²⁺ pump) driven by calcitriol, and a passive paracellular route in the jejunum and ileum.
B12: freed from food by acid and pepsin → binds haptocorrin → pancreatic proteases release it → binds intrinsic factor → cubilin receptor in the terminal ileum.
Liver B12 stores last for years, so anemia appears long after gastrectomy or ileal resection.

What it is

Three nutrients with their own routes, and all heavily tested. Iron is absorbed in the duodenum and its entry into the blood is controlled by hepcidin from the liver, because the body has no active way to excrete it. Calcium is absorbed in the duodenum by an active, calcitriol-dependent route and along the whole gut paracellularly. Vitamin B12 has a long journey: acid and pepsin, haptocorrin, pancreatic proteases, intrinsic factor and a terminal ileal receptor.

How it works, step by step

Gastric acid solubilizes iron and frees B12 from food proteins.
In the duodenum, Fe³⁺ is reduced to Fe²⁺ and enters the enterocyte via DMT1; heme enters by another route and iron is released inside the cell.
Iron is stored as ferritin (and lost when the enterocyte is shed) or exported via ferroportin to plasma transferrin.
Calcitriol induces TRPV6 and calbindin: Ca²⁺ enters, is ferried across the cytosol and leaves via the Ca²⁺ pump and the Na⁺/Ca²⁺ exchanger.
Haptocorrin-bound B12 passes into the duodenum, where pancreatic proteases degrade haptocorrin.
Free B12 binds intrinsic factor, which protects it to the terminal ileum, where the complex enters by endocytosis.
In blood, B12 travels bound to transcobalamin II and is stored in the liver.

Where and how they are absorbed

Nutrient	Main site	What it needs	When it fails
Iron	Duodenum	Acid, Fe²⁺, DMT1, ferroportin; regulated by hepcidin	Microcytic anemia (celiac disease, bleeding, low intake)
Calcium	Duodenum (active); jejunum and ileum (passive)	Calcitriol (active vitamin D)	Hypocalcemia, osteomalacia or rickets
Vitamin B12	Terminal ileum	Acid, pepsin, pancreatic proteases, intrinsic factor, cubilin	Megaloblastic anemia and nerve damage
Folate	Jejunum	Brush-border deconjugation and a folate transporter	Megaloblastic anemia without nerve damage

Clinical notes

In Colombia iron deficiency anemia is common in children, adolescents and pregnant women; intestinal parasites (hookworm) add blood loss.
Pernicious anemia: antibodies against parietal cells and intrinsic factor → megaloblastic anemia and subacute combined degeneration of the cord.
Hereditary hemochromatosis: hepcidin is inappropriately low → excess absorption and iron deposits in the liver, pancreas and heart.
Long-term metformin or proton pump inhibitor use can lower vitamin B12.

Test yourself

Think of the answer, then tap the question to see it.

Why does chronic inflammation reduce intestinal iron absorption?

Interleukin 6 raises hepatic hepcidin; hepcidin degrades ferroportin in enterocytes and macrophages, so iron is trapped and does not reach the blood.

Why does terminal ileal resection cause B12 deficiency even with a healthy stomach?

The intrinsic factor–B12 complex is absorbed only in the terminal ileum via the cubilin receptor; without that segment the vitamin is lost in stool.

Why does celiac disease usually cause iron deficiency before B12 deficiency?

Celiac disease mainly damages the proximal gut (duodenum), where iron is absorbed; the terminal ileum, where B12 is taken up, is usually spared.

Which hormone increases active calcium absorption in the duodenum, and how?

Calcitriol (1,25-dihydroxyvitamin D). It acts on its nuclear receptor and induces TRPV6, calbindin and the basolateral Ca²⁺ pump.

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The structures of Durgical's 3D anatomy where it happens.

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 23.7 Chemical Digestion and Absorption: A Closer Look (OpenStax (Rice University), 2022); Iron Deficiency and Microcytic Hypochromic Anemia (StatPearls (NCBI Bookshelf), 2024); Pernicious anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 66). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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