What is the regulatory mechanism of iron absorption at the level of intestine? What is the role of TIBC in iron metabolism? How does the body conserve iron?

Regulatory Mechanism of Iron Absorption at the Level of Intestine

Iron absorption primarily occurs in the duodenum and proximal jejunum. The process is complex and involves several key players:

• Dietary Iron Forms: Iron exists in two main forms in food: heme iron (from animal sources) and non-heme iron (from plant sources). Heme iron is absorbed more efficiently.
• Luminal Phase: Gastric acid and pepsin in the stomach release iron from food. Reducing agents like Vitamin C enhance the absorption of non-heme iron by converting ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), the form readily absorbed by intestinal cells.
• Enterocyte Absorption: Fe²⁺ is transported across the apical membrane of enterocytes by the Divalent Metal Transporter 1 (DMT1). Heme iron is absorbed via Heme Carrier Protein 1 (HCP1).
• Intracellular Regulation: Inside the enterocyte, iron can be:
  • Stored as ferritin, a storage protein.
  • Transported across the basolateral membrane into the circulation via Ferroportin, the only known iron exporter.
  • Trapped within the enterocyte and eventually sloughed off with the intestinal cells.
• Hepcidin Regulation: Hepcidin, a peptide hormone produced by the liver, is the master regulator of iron homeostasis. It binds to ferroportin, causing its internalization and degradation, thereby inhibiting iron export from enterocytes, macrophages, and hepatocytes. Hepcidin production is increased by inflammation, iron overload, and erythropoietic stress (in certain contexts).

Role of TIBC in Iron Metabolism

Total Iron Binding Capacity (TIBC) measures the blood’s capacity to bind iron with transferrin. Transferrin is the primary iron transport protein in the plasma. TIBC is an indirect measure of transferrin levels.

• Inverse Relationship with Serum Iron: TIBC is typically elevated in iron deficiency anemia because the liver increases transferrin production to scavenge for available iron. Conversely, TIBC is decreased in conditions of iron overload (e.g., hemochromatosis) or chronic inflammation.
• Diagnostic Utility: TIBC, along with serum iron and transferrin saturation (serum iron/TIBC x 100), helps differentiate between different types of anemia. A low serum iron with a high TIBC suggests iron deficiency anemia.
• Clinical Significance: Changes in TIBC can also be seen in conditions like nephrotic syndrome (increased transferrin synthesis) and liver disease (decreased transferrin synthesis).

How the Body Conserves Iron

Given the lack of a dedicated iron excretion pathway, the body employs several mechanisms to conserve iron:

• Enterocyte Regulation: As mentioned earlier, the regulation of ferroportin by hepcidin minimizes iron loss from the intestine.
• Macrophage Recycling: Macrophages phagocytose senescent red blood cells and recycle the iron from hemoglobin. This recycled iron is stored as ferritin or released back into the circulation via ferroportin (regulated by hepcidin).
• Hepatocyte Storage: The liver stores iron as ferritin, providing a readily available reserve.
• Minimal Excretion: Small amounts of iron are lost through skin shedding, sweat, urine, and feces. Menstrual blood loss in women also contributes to iron loss.
• Erythropoiesis: During periods of increased erythropoiesis (red blood cell production), the body prioritizes iron utilization for hemoglobin synthesis, reducing iron stores.

The interplay between hepcidin, ferroportin, transferrin, and ferritin ensures a tightly regulated iron balance, preventing both deficiency and overload.