PA14.1-2 | Iron Metabolism: Absorption, Transport, Storage, Regulation — Summary & Reflection

REFLECT

Before moving to the next module, consolidate this system in your mind by tracing one iron atom from your last meal to a haemoglobin molecule:

1. You ate dal (lentils — non-haem iron, Fe³⁺). Gastric acid and Dcytb reduced it to Fe²⁺. DMT1 transported it into the duodenal enterocyte.
2. Iron was exported across the basolateral surface via ferroportin, oxidised to Fe³⁺ by hephaestin, and bound to apotransferrin in the portal blood.
3. Diferric transferrin reached the bone marrow, bound TfR1 on a pro-erythroblast, was endocytosed, released its iron in the acidified endosome, and Fe²⁺ entered the cytoplasm.
4. In the mitochondria, Fe²⁺ was inserted into protoporphyrin IX by ferrochelatase to form haem. Haem combined with α and β globin chains to form haemoglobin.
5. The reticulocyte matured and entered the circulation. 120 days later, the spleen's macrophages broke it down. The iron was released, bound to ferritin temporarily, re-exported via ferroportin, and picked up by transferrin again — ready for the next cycle.

Now ask yourself: at which step in this chain could iron deficiency most plausibly develop in your patient population in India? Which step does inflammation target? This reflection will guide your differential diagnosis in the next module.

KEY TAKEAWAYS

Iron Metabolism: The System in Brief

Total body iron (~3–4 g) is distributed across three pools: functional (haemoglobin 65%, myoglobin, enzymes), storage (ferritin > hemosiderin, in liver, macrophages), and transport (transferrin, only ~4 mg but the clinically measured fraction). Daily turnover is 25 mg, almost entirely from RBC recycling; only 1–2 mg is absorbed from food.

Absorption occurs exclusively in the duodenum and proximal jejunum. Non-haem iron (the majority of dietary iron) requires: gastric acid and Dcytb for Fe³⁺→Fe²⁺ reduction, DMT1 for enterocyte entry, and ferroportin + hephaestin for basolateral export. Haem iron follows a separate, higher-efficiency pathway. Vitamin C enhances, and phytates/polyphenols/calcium inhibit, non-haem absorption.

Transport occurs as transferrin-bound Fe³⁺. TIBC measures the total transferrin capacity; transferrin saturation = serum iron ÷ TIBC × 100. Cells acquire iron via TfR1-mediated endocytosis. Storage is in ferritin (soluble, mobilisable) and hemosiderin (insoluble, Perls-blue positive).

Regulation is governed by hepcidin (hepatocyte-derived), which degrades ferroportin → blocks iron export from enterocytes and macrophages. Hepcidin rises with ↑ iron stores and ↑ inflammation (IL-6); falls with ↓ iron stores and ↑ erythropoietic demand. This is the molecular mechanism of anaemia of chronic disease.

Progressive iron depletion follows three stages: (1) ↓ ferritin only, (2) ↓ ferritin + ↓ transferrin saturation + ↑ TIBC (no anaemia yet), (3) IDA — ↓ Hb + ↓ MCV + microcytic hypochromic smear. Ferritin falls first and is the best single marker of stores — but is unreliable in inflammation.

Bridge to SDL 2: You now know the physiology. Every parameter in an iron-study panel — the low serum iron, the high TIBC, the low transferrin saturation, the rock-bottom ferritin — maps to a specific step in the system you've just traced. In the next module, we turn pathophysiology into diagnosis: what happens when this system fails, why iron deficiency is the world's most common nutritional cause of anaemia, and how you work through the clinical and laboratory diagnosis of IDA.