Explain source of rda , functions, disorders of iron for 10 mark

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IRON: RDA, Sources, Functions, and Disorders

1. Recommended Dietary Allowance (RDA) of Iron

Iron requirements vary based on physiological state:

Population Group	RDA
Adult men	10 mg/day
Postmenopausal women	10 mg/day
Premenopausal women	15 mg/day
Pregnant women	27 mg/day (increased demand for fetal supply)
Infants / growing children	Increased needs (relative to body weight)

The average daily US diet contains 10-50 mg of iron, but only 10-15% is normally absorbed. Daily iron loss in adult men is approximately 1 mg/day (via desquamation, bile, feces, urine, and sweat).

Basic Medical Biochemistry, 6e, p.1526

2. Sources of Iron

Dietary Sources

Iron exists in two forms in the diet:

a) Heme Iron (animal sources - readily absorbed)

Red meat (beef, pork, lamb)
Poultry and fish
Organ meats (liver, kidney)
Heme iron is directly absorbed in the gut and is not affected by dietary inhibitors.

b) Non-Heme Iron (plant sources - less bioavailable)

Leafy green vegetables (spinach, fenugreek)
Legumes (lentils, beans, chickpeas)
Cereals and fortified grains
Dried fruits (raisins, apricots)
Seeds and nuts

Factors Affecting Iron Absorption

Enhancers of absorption:

Vitamin C (ascorbic acid) - converts Fe³⁺ to Fe²⁺ and increases uptake of non-heme iron
Heme iron itself
Acidic gastric environment (HCl)

Inhibitors of absorption:

Oxalates, phytates, tannins (tea, coffee), and other phenolic compounds in plants - these chelate iron or form insoluble precipitates
Antacids, achlorhydria
Phosphates, carbonates

Absorption Mechanism

Iron is absorbed in the ferrous (Fe²⁺) state by intestinal epithelial cells via the divalent metal transporter-1 (DMT-1). Inside the cell, it is oxidized to Fe³⁺ by the ferroxidase ceruloplasmin (a copper-containing enzyme) for transport through the blood.

Iron metabolism diagram showing absorption from diet, transport by transferrin, storage in ferritin, and use in tissues

Iron metabolism: absorbed from the diet, transported by transferrin, stored in ferritin/hemosiderin, used for cytochromes, iron-containing enzymes, hemoglobin, and myoglobin - Basic Medical Biochemistry, 6e

3. Functions of Iron

Iron is an essential trace mineral with wide-ranging biochemical roles:

3.1 Oxygen Transport - Hemoglobin

Iron (Fe²⁺) is the core of the heme moiety in hemoglobin in red blood cells.
It binds and transports oxygen from the lungs to the tissues.
Each hemoglobin molecule contains 4 heme groups, each with one iron atom.

3.2 Oxygen Storage - Myoglobin

Iron in myoglobin stores oxygen in muscle tissue.
Myoglobin releases oxygen during intense muscular activity.

3.3 Electron Transport Chain - Cytochromes

Iron-containing cytochromes (cytochrome a, b, c, cytochrome P450) are essential components of the mitochondrial electron transport chain.
They enable ATP synthesis via oxidative phosphorylation.

3.4 Enzymatic Functions

Iron is a cofactor or component of many enzymes:

Catalase and peroxidase - antioxidant enzymes that decompose hydrogen peroxide
Ribonucleotide reductase - essential for DNA synthesis
Aconitase - TCA cycle enzyme
Succinate dehydrogenase - links TCA cycle to ETC
Various oxidase and hydroxylase enzymes

3.5 Transport in Blood

Iron is transported in blood as transferrin (Fe³⁺ bound to apotransferrin).
Transferrin is normally only one-third saturated; total iron-binding capacity (TIBC) is ~300 µg/dL.
Transferrin-iron complex binds to transferrin receptors on cells and is internalized by receptor-mediated endocytosis.

3.6 Storage

Ferritin: primary storage form - apoferritin binds Fe²⁺ in the liver, spleen, and bone marrow. Serum ferritin is the most sensitive indicator of body iron stores.
Hemosiderin: when iron is in excess, it forms this less-mobilizable storage complex (ferritin + additional iron).

3.7 Immune Function and Cognitive Performance

Adequate iron is required for normal immunocompetence and lymphocyte proliferation.
Iron deficiency impairs cognitive performance and work capacity.

4. Disorders of Iron

A. Iron Deficiency and Iron Deficiency Anemia (IDA)

Causes:

Chronic blood loss (most common in higher-resource countries): GI bleeding (peptic ulcers, colon cancer, hemorrhoids), menorrhagia, metrorrhagia
Inadequate dietary intake: vegetarian diets, food insecurity, exclusively milk-fed infants, elderly
Increased demand: pregnancy, infancy, adolescence
Malabsorption: celiac disease, gastritis, post-gastrectomy

Pathogenesis (sequential stages):

Stage 1 - Iron depletion: Iron stores depleted; serum ferritin falls; no stainable iron in bone marrow macrophages
Stage 2 - Iron-deficient erythropoiesis: Serum iron falls; TIBC rises; transferrin saturation falls below 20%
Stage 3 - Iron deficiency anemia: Hemoglobin synthesis fails; microcytic, hypochromic anemia develops

Lab findings in IDA:

Test	Normal	IDA
Serum ferritin	50-200 µg/dL	Decreased (<15)
Serum iron	50-150 µg/dL	Decreased (<30)
TIBC	300-360 µg/dL	Increased (>400)
Transferrin saturation	30-50%	Decreased (<10%)
RBC morphology	Normal	Microcytic, hypochromic

Clinical Features:

Mild cases: asymptomatic
Severe cases: weakness, fatigue, pallor, dyspnea on exertion
Koilonychia (spoon-shaped nails): thinning, flattening of fingernails
Pica: compulsion to eat non-food items (dirt, clay, ice) - a curious neurobehavioral complication
Angular stomatitis, glossitis
Reduced immunocompetence and cognitive performance
Robbins & Kumar Basic Pathology, p.1971-1977

B. Anemia of Chronic Disease (ACD)

Most common anemia in hospitalized patients
Occurs in chronic infections (osteomyelitis, endocarditis), chronic immune disorders (rheumatoid arthritis, Crohn's disease), and cancers
Pathogenesis: Pro-inflammatory cytokines (IL-6) elevate hepcidin, which blocks ferroportin and traps iron in marrow macrophages, preventing its transfer to erythroid precursors
Laboratory: low serum iron but normal/elevated ferritin (iron stores are present but inaccessible)

C. Iron Overload - Hemochromatosis

Hereditary Hemochromatosis is an autosomal recessive condition caused most often by mutations in the HFE gene (C282Y homozygosity accounts for 80-90% of cases in northern European descent). Other genetic causes include mutations in TFR2, ferroportin, hemojuvelin, and hepcidin itself.

Pathophysiology: Defective hepcidin regulation leads to uncontrolled iron absorption, with progressive iron deposition in:

Liver (cirrhosis)
Pancreas ("bronze diabetes")
Heart (cardiomyopathy, arrhythmias)
Pituitary/gonads (hypogonadism)
Joints (arthropathy)
Skin (bronze discoloration)

Classic triad: Cirrhosis + Diabetes mellitus + Skin bronzing ("bronze diabetes")

Secondary Hemochromatosis causes include:

Repeated blood transfusions (transfusional iron overload)
Ineffective erythropoiesis (e.g., thalassemia major)
Excessive parenteral iron therapy

D. DMT-1 Mutation (Rare)

An inherited mutation in SLC11A2 (encoding DMT-1) leads to iron being trapped in endosomal vesicles, unable to reach cytoplasm. Result: refractory hypochromic microcytic anemia despite normal or elevated tissue iron. - Basic Medical Biochemistry, 6e

Summary Table

Aspect	Key Points
RDA	10 mg (men/postmenopausal women); 15 mg (premenopausal women)
Best dietary source	Heme iron from red meat; enhanced by vitamin C
Major function	O₂ transport (Hb), O₂ storage (Mb), ETC cytochromes, enzymes
Transport protein	Transferrin (Fe³⁺); stored as ferritin/hemosiderin
Deficiency disorder	IDA - microcytic, hypochromic anemia; koilonychia; pica
Excess disorder	Hemochromatosis - cirrhosis, diabetes, bronzing
Key regulatory hormone	Hepcidin (blocks ferroportin, reduces iron release)

Sources: Basic Medical Biochemistry - A Clinical Approach, 6e; Robbins & Kumar Basic Pathology; Harper's Illustrated Biochemistry, 32nd ed.

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