---

Iron and Iron Deficiency Disorders - Pediatrics MBBS

---

1. Iron in the Body - Normal Metabolism

Distribution of Iron

• ~65% as hemoglobin, ~4% as myoglobin, ~1% in heme enzymes, ~0.1% as plasma transferrin, 15-30% in storage

Iron Transport and Storage

• Transferrin (beta-globulin, synthesized in liver): transports iron in plasma; normally ~1/3 saturated; serum iron ~120 µg/dL males, ~100 µg/dL females
• Ferritin: major storage form; iron bound to apoferritin protein shell (mol wt ~460 kDa, up to 4000 atoms/molecule); highest in hepatocytes and RES cells; plasma ferritin correlates with body iron stores (normal: >12 µg/L; iron deficiency: <12 µg/L)
• Hemosiderin: insoluble aggregates of partially degraded ferritin within lysosomes; stains blue-black with Prussian blue (potassium ferrocyanide); predominates in iron overload
• Transferrin delivers iron to erythroid precursors via receptor-mediated endocytosis; iron then goes to mitochondria where heme is synthesized

Iron Absorption (Duodenum)

• Daily diet contains 10-20 mg iron; only 10-15% absorbed
• Heme iron (from animal products): ~20% absorbed, transported by separate heme transporter
• Non-heme iron: Fe³⁺ reduced to Fe²⁺ by ferrireductases (b cytochromes), then taken up by DMT1 (divalent metal transporter 1); only 1-5% absorbed
• Fe²⁺ crosses the basolateral membrane via ferroportin, oxidized to Fe³⁺ by hephaestin/ceruloplasmin, then binds plasma transferrin
• Enhancers: ascorbic acid (Vit C), citric acid, amino acids, sugars
• Inhibitors: phytates (cereals), tannins (tea), calcium, phosphates

Hepcidin - The Master Regulator

• Peptide synthesized by liver
• When iron stores are high OR inflammation → hepcidin ↑ → binds ferroportin → ferroportin degraded → iron trapped in enterocytes as mucosal ferritin (lost when cells slough) → ↓ iron absorption; also blocks iron release from macrophages
• When iron stores are low → hepcidin ↓ → ferroportin intact → ↑ iron absorption
• Anemia of chronic disease = ↑ hepcidin → functional iron deficiency
• Hemochromatosis = ↓ hepcidin → excess absorption

Daily Iron Loss

• Males: ~0.6 mg/day (shed cells)
• Females: ~1-2 mg/day (+ menstrual losses)
• Net requirement: 1 mg must be absorbed daily

---

2. Iron Deficiency Anemia (IDA)

Causes (Etiology)

• Exclusive breastfeeding beyond 6 months without complementary feeding
• Cow's milk as main diet (low iron + inhibits absorption + causes occult GI blood loss)
• Predominantly plant-based diet (low bioavailability)
• Premature/low birth weight infants (depleted fetal stores)

• Rapid growth: infants (6 months-2 years), adolescent growth spurt
• Pregnancy and lactation

• Celiac disease, post-gastric surgery, achlorhydria
• Malabsorption syndromes

• GI: hookworm, Meckel's diverticulum, IBD, peptic ulcer
• Urinary: hematuria
• Menstrual losses (adolescent girls)

Stages of Iron Deficiency (Important for MCQs)

Clinical Features

• Pallor (conjunctival, palmar, nail beds), fatigue, exertional dyspnea, tachycardia

• Pica - craving for non-food substances (mud/clay = geophagia, ice = pagophagia, starch = amylophagia) - common in children
• Koilonychia (spoon-shaped nails)
• Angular stomatitis (cracking at corners of mouth)
• Glossitis (smooth, sore tongue)
• Brittle hair and nails
• Blue sclerae
• Plummer-Vinson syndrome (in adults): IDA + dysphagia + esophageal web
• Behavioral/developmental effects in children: irritability, poor attention span, impaired cognitive development, reduced school performance (may not be fully reversible even after iron treatment)
• Increased susceptibility to lead toxicity (pica + increased absorption of heavy metals)
• Breath-holding spells in toddlers

Lab Findings (IDA)

Peripheral Blood Smear - IDA

• Microcytic, hypochromic RBCs
• Anisocytosis, poikilocytosis
• Pencil (cigar) cells
• Target cells
• Thrombocytosis (reactive - in chronic blood loss)

Differential Diagnosis

---

3. WHO Hb Cutoffs for Anemia Diagnosis

---

4. Treatment of IDA

Oral Iron (First Line)

• Ferrous salts (ferrous sulfate, ferrous gluconate, ferrous fumarate) - ferrous (Fe²⁺) absorbed better than ferric (Fe³⁺)
• Therapeutic dose in children: 3-6 mg/kg/day of elemental iron in 2-3 divided doses
• Best absorbed on empty stomach, but can give with food to reduce GI side effects
• Vitamin C (ascorbic acid) with iron enhances absorption
• Avoid with milk, tea, antacids
• Duration: Continue for 3 months after Hb normalizes to replenish stores
• Response monitoring:
  • Reticulocyte count rises in 4-7 days (earliest response)
  • Hb rises by ~1 g/dL/week
  • Decision on effectiveness at 4 weeks (expect ≥2 g/dL rise)

Parenteral Iron

• Indications: malabsorption, non-compliance, severe ongoing blood loss exceeding oral absorption capacity, intolerance to oral iron
• Options: iron sucrose, ferric carboxymaltose, iron dextran
• Risk: anaphylaxis (especially iron dextran)

Blood Transfusion

• Only in severe symptomatic anemia (Hb <5-6 g/dL) with hemodynamic compromise or cardiac failure
• Use packed RBCs (10-15 mL/kg slowly)

Dietary advice

• Increase iron-rich foods: red meat, poultry, fish (heme iron); dark green leafy vegetables, legumes (non-heme iron)
• Cook in iron vessels (increases iron content of food)
• Vitamin C-rich foods with meals
• Reduce tea/coffee consumption with meals
• Delayed cord clamping at birth (2-3 min) - increases iron stores in newborn by ~50-75 mg

---

5. NACP / NNACP and Related Government Programs (India)

Evolution of the Program

Anemia Mukt Bharat (AMB) - 2018 - The Current Program

• 6 target beneficiary groups: Preschool children (6-59 months), School children (5-9 years), Adolescents (10-19 years), Pregnant women, Lactating women, Women of reproductive age (WRA, 15-49 years)
• 6 interventions:
  1. Prophylactic IFA supplementation
  2. Deworming (biannual)
  3. Intensified year-round behavior change communication (BCC)
  4. Testing for anemia using digital hemoglobinometers
  5. Non-nutritional anemia management (malaria, hemoglobinopathies)
  6. Fortified rice distribution via PDS
• 6 delivery platforms: AWCs (Anganwadi), ASHA, Schools, PHCs/CHCs, BPHUs, digital monitoring

NIPI / AMB - Iron Supplementation Schedule

Prophylactic IFA Supplementation:

Key MCQ: Preschool children (6-59 months) receive IFA biweekly | School children (5-9 yr) receive IFA weekly

Treatment Doses Under NIPI:

IFA Syrup Dose for Anemic Children 6 months-5 years (NIPI):

WIFS (Weekly Iron and Folic Acid Supplementation)

• Specifically for school-going adolescents
• 100 mg iron + 500 µg folic acid weekly for boys and girls aged 10-19 years (school/non-school)
• Implemented through teachers (in-school) and AWC/ASHA (out-of-school)
• Combined with biannual deworming

---

6. Prevention of IDA - Summary

---

Key MCQ Pearls

1. Most common nutritional deficiency worldwide = Iron deficiency
2. Most sensitive test for iron depletion = Serum ferritin (first to fall, last to normalize)
3. Gold standard for tissue iron = Bone marrow Prussian blue stain (absent stainable iron)
4. Earliest response to iron therapy = Reticulocyte count rises in 4-7 days
5. Pica is pathognomonic of iron deficiency (not just anemia)
6. Mentzer index = MCV/RBC count: >13 favors IDA, <13 favors thalassemia trait
7. Hepcidin = master regulator of iron absorption; ↑ in inflammation (ACD), ↓ in IDA and hemochromatosis
8. Koilonychia = spoon-shaped nails, specific to IDA
9. NIPI introduced the life cycle approach in 2013; AMB (2018) uses 6×6×6 strategy
10. IFA for children 6-59 months = 20 mg iron + 100 µg folate, biweekly
11. IFA for 5-10 years = 45 mg iron + 400 µg folate, weekly
12. IFA for adolescents = 100 mg iron + 500 µg folate, weekly
13. Therapeutic dose of iron in children = 3-6 mg/kg/day (treatment); prophylactic = 1-2 mg/kg/day
14. Cow's milk anemia: exclusively cow's milk fed infants develop IDA due to low iron content + GI blood loss from cow's milk protein intolerance

---