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Iron

Iron is a part of the structure of many very important body constituents, e.g. hemoglobin, myoglobin, enzymes like cytochromes, catalase, xanthine oxidase, etc. (xanthine oxidase contains iron–sulfur clusters indirectly involved in electron transfer rather than iron as the main catalytic metal.)

Iron is an essential trace element required for oxygen transport, energy production (cellular respiration), and many enzymatic reactions involving oxidation–reduction processes.

  Dietary Sources of Iron

Animal sources are the best and include liver, meat, and egg yolk. Of the vegetables, spinach and other leafy vegetables are good sources. Dried fruits also contain appreciable amounts of iron. A fact of great importance is that milk is very low in iron (1 mg per liter). Cooking in iron utensils increases iron content of the foods.

Additional important points:

Iron in food exists in two forms:

  • Heme iron (animal sources): meat, liver, fish
    → Easily absorbed (better bioavailability)
  • Non-heme iron (plant sources): vegetables, grains, fruits
    → Poorer absorption and more affected by dietary factors

  Factors increasing absorption:

  • Vitamin C (ascorbic acid)
  • Meat proteins (“meat factor”)
  • Gastric acid (helps solubility)

  Factors decreasing absorption:

  • Phytates (grains, cereals)
  • Oxalates (spinach)
  • Tannins (tea, coffee)
  • Calcium (in high amounts)

  Recommended Daily Dietary Allowance

This differs according to the age and sex of the person.

Sex & Age New born Infant Child 8-10 years Adult male 22-35 Years Adult female 22-35 years Pregnancy Lactation
Amount of Iron(mg) 6 10 10 18 18 18

Physiological requirement understanding:

  • Adult male requirement is usually lower (~8 mg/day) due to no menstrual loss
  • Adult female requirement remains higher due to menstrual blood loss
  • Pregnancy requirement increases significantly due to:
    • expansion of maternal blood volume
    • fetal needs
    • placenta formation
      → total requirement rises to ~27 mg/day in many guidelines
  • Lactation requirement decreases compared to pregnancy because menstruation is often suppressed

  Iron Distribution in the Body

Total Iron = 3 to 5 grams

  • 66% in hemoglobin
  • 25% stored as ferritin present mainly in liver, spleen, bone marrow and small intestinal mucosal cells
  • 3% in myoglobin
  • 5% in other body cells
  • 1% in heme-containing enzymes

Additional important clarification:

  • Iron in blood is transported bound to transferrin
  • Iron storage occurs mainly in two forms:
    • Ferritin (readily available storage form)
    • Hemosiderin (insoluble storage, seen in iron overload)

  Iron Absorption

Iron is mainly absorbed in the duodenum and upper jejunum.

Step-by-step process:

  1. Reduction step
    • Dietary iron (Fe³⁺) is reduced to Fe²⁺ in the stomach and duodenum
    • This is helped by gastric acid and vitamin C
  2. Entry into intestinal cells
    • Fe²⁺ enters enterocytes via DMT1 (Divalent Metal Transporter-1)
  3. Intracellular fate
    • Iron is either:
      • stored as ferritin in enterocytes, OR
      • transported into blood
  4. Exit into blood
    • Iron leaves enterocytes via ferroportin
    • It is then oxidized back to Fe³⁺ and binds to transferrin
  5. Transport in blood
    • Iron is carried by transferrin, which delivers it to:
      • bone marrow (for RBC production)
      • liver (storage)
      • other tissues

  Regulation of Iron Balance

The most important regulator of iron metabolism is hepcidin (a hormone produced by the liver).

Role of hepcidin:

  • High hepcidin → decreases iron absorption and release
  • Low hepcidin → increases iron absorption

Mechanism:

  • Hepcidin binds to ferroportin → causes its degradation
  • This prevents iron from entering blood from:
    • intestinal cells
    • macrophages
    • liver stores

Conditions affecting hepcidin:

  • Increased in:
    • inflammation (anemia of chronic disease)
    • iron overload
  • Decreased in:
    • iron deficiency
    • hypoxia
    • increased erythropoiesis

  Iron Recycling in the Body

A major portion of iron is recycled rather than newly absorbed.

  • Old RBCs are broken down in spleen and liver macrophages
  • Hemoglobin is degraded into:
    • globin → amino acids
    • heme → iron + porphyrin
  • Iron is:
    • reused for new RBC production
    • or stored as ferritin/hemosiderin

👉 This recycling system supplies most daily iron needs; only a small fraction is absorbed from diet.

  Iron Loss from Body

Iron is lost mainly through:

  • Desquamation of skin and intestinal cells
  • Sweat
  • Minor bleeding

Average loss:

  • Males: ~1 mg/day
  • Females: ~1.5–2 mg/day (higher due to menstruation)

  Iron Storage

Iron is stored mainly as:

1. Ferritin

  • Soluble, readily mobilizable
  • Found in liver, spleen, bone marrow

2. Hemosiderin

  • Insoluble aggregate form
  • Seen in iron overload conditions

  Clinical Importance of Iron

1. Iron Deficiency Anemia (most common deficiency anemia)
Causes:

  • poor diet
  • chronic blood loss (especially gastrointestinal or menstrual)
  • increased requirement (pregnancy, growth)

Features:

  • microcytic hypochromic anemia
  • fatigue, pallor
  • brittle nails, koilonychia (spoon nails)
  • pica (craving non-food substances)

2. Iron Overload
Causes:

  • repeated blood transfusions
  • excessive supplementation

Effects:

  • deposition in liver, heart, pancreas
  • organ damage

3. Hemochromatosis

  • Genetic disorder causing excessive iron absorption
  • Leads to:
    • liver cirrhosis
    • diabetes mellitus
    • skin pigmentation (“bronze diabetes”)

  Laboratory Assessment of Iron Status

Important tests include:

  • Serum ferritin → best indicator of iron stores
  • Serum iron
  • Total iron binding capacity (TIBC)
  • Transferrin saturation
  • Peripheral blood smear

Typical pattern in iron deficiency:

  • ↓ serum iron
  • ↑ TIBC
  • ↓ ferritin
  • ↓ transferrin saturation