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Iron Deficiency & Related Disorders - Pediatrics MBBS

1. Iron Metabolism (Physiology)

Body Iron Distribution

• Robbins & Kumar, p. 612

Iron Cycle

• Harrison's 22E, p. 806

Hepcidin - The Master Regulator

• Hepcidin = peptide produced by liver; inhibits ferroportin (the iron exporter) in enterocytes, macrophages, and hepatocytes
• When iron stores are replete: hepcidin is HIGH → ferroportin is degraded → iron export blocked
• When iron deficient: hepcidin is LOW (suppressed by TMPRSS6 and erythroferrone) → ferroportin active → more iron absorption
• Erythroferrone (secreted by erythroblasts after EPO stimulation) is a powerful hepcidin inhibitor

Intestinal Absorption

• Nonheme iron (Fe³⁺) → reduced to Fe²⁺ by ferrireductase DCYTB → imported by DMT-1 across apical membrane
• Heme iron (from red meat) → directly absorbed; highly bioavailable (~20%)
• Nonheme iron bioavailability: only 1-5%
• Fe²⁺ exits basolateral membrane via ferroportin → oxidized by hephaestin/ceruloplasmin → binds transferrin

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2. Stages of Iron Deficiency

• Park's Textbook of Preventive and Social Medicine, p. 3146-3157

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3. Etiology / Causes of Iron Deficiency

1. Dietary lack - Common in:
   • Infants (breast milk gives only ~0.3 mg/L; cow's milk bioavailability is poor)
   • Low-resource countries where diet is mostly plant-based (nonheme iron)
   • Vegans, the elderly, the impoverished
2. Impaired absorption - Sprue, celiac disease, gastrectomy (reduces duodenal acidity), chronic diarrhea
3. Increased requirement - Growing infants, children, adolescents (rapid tissue expansion); pregnancy; premenopausal females
4. Chronic blood loss - Most common cause in developed countries; GI bleeds (must rule out occult malignancy in adult males and postmenopausal females); menstruation; parasites (hookworm - significant in India)

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4. WHO Hemoglobin Cut-offs for Anemia Diagnosis

• Park's PSM, p. 3180

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5. Laboratory Diagnosis

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6. Peripheral Blood Smear Findings (Morphology)

• Microcytic hypochromic red cells
• Central pallor > 1/3 of cell diameter (zone of pallor enlarged)
• Pencil cells (elongated poikilocytes) - characteristic
• Mild poikilocytosis
• Bone marrow: absence of stainable iron on Prussian blue stain (diagnostic gold standard for iron stores)
• Robbins & Kumar, p. 1389

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7. Clinical Features

• Pallor, fatigue, exertional dyspnea, palpitations

• Koilonychia (spoon-shaped nails)
• Alopecia
• Atrophic glossitis (smooth, pale tongue)
• Pica - craving for non-food items (clay, ice/pagophagia, flour)
• Gastric mucosal atrophy → intestinal malabsorption
• Plummer-Vinson syndrome (rare triad): microcytic hypochromic anemia + esophageal webs + atrophic glossitis

• Impaired cognitive development, behavioral problems, poor scholastic achievement
• Reduced motor and language development
• Impaired cell-mediated immunity, increased susceptibility to infections
• Increased morbidity and mortality
• Diminished work performance

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8. Treatment of Iron Deficiency Anemia

Therapeutic Doses

• Oral iron (ferrous sulfate): 3-6 mg/kg/day of elemental iron in children (divided doses)
• Response: reticulocytosis in 5-7 days, followed by steady rise in Hb
• Continue for 3 months after Hb normalizes to replenish stores

Monitoring

• Therapeutic response confirms the diagnosis retrospectively
• Check reticulocyte count at day 7-10

When to use parenteral iron:

• Malabsorption (celiac, bowel surgery)
• Non-compliance
• Severe anemia requiring rapid correction

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9. NACP / National Iron Plus Initiative (NACP) - The PSM Component

Historical Context

Anemia Mukt Bharat (Current Programme)

1. Prophylactic IFA (Iron Folic Acid) supplementation
2. Periodic deworming
3. Behavior Change Communication (BCC)
4. Appropriate infant and young child feeding (IYCF)
5. Dietary diversification and food fortification
6. Delayed cord clamping

IFA Supplementation Schedule (Current National Guidelines)

• Source: Anemia Mukt Bharat, National Health Mission (nhm.gov.in)

Key NACP Epidemiology Points

• ~74% children 6-35 months were anemic (NFHS-II data)
• ~80% children under 2 years in India are anemic
• ~58% pregnant women, 50% non-pregnant women, 56% adolescent girls are anemic
• IDA is both a result and cause of poverty (vicious cycle)

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10. Iron Deficiency vs. Anemia of Chronic Disease (Comparison)

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11. Quick MCQ Points (MBBS Exam Highlights)

• Earliest indicator of iron deficiency = Serum ferritin
• Most sensitive test for iron stores = Serum ferritin
• Diagnostic gold standard for absent iron stores = Bone marrow Prussian blue stain
• Central pallor in normal RBC = 1/3 of cell diameter
• Pencil cells = seen in IDA
• Pica/pagophagia = iron deficiency
• Plummer-Vinson = IDA + esophageal webs + atrophic glossitis
• Most common cause of anemia worldwide = Iron deficiency
• Most common nutritional disorder globally = Iron deficiency
• Hepcidin inhibitor in iron deficiency = TMPRSS6 (and erythroferrone)
• Iron transporter across apical membrane = DMT-1 (divalent metal transporter 1)
• Iron exporter (basolateral) = Ferroportin
• Oxidases = Hephaestin (enterocyte), Ceruloplasmin (plasma)
• Stage most prevalent in India = Stage 2 (Latent IDA)
• NACP launched = 1970
• AMB target group = 6 beneficiary groups (6 months to 49 years)
• 6-59 months dose = 1 ml syrup biweekly (20 mg iron/ml)
• Reticulocytosis after iron therapy = 5-7 days

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IRON & ITS DEFICIENCY DISORDERS

Complete Simple Explanation for MBBS Pediatrics

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PART 1: WHAT IS IRON AND WHY DOES THE BODY NEED IT?

• No iron → No hemoglobin → Red blood cells become small and pale → Cannot carry enough oxygen → Body suffers

• Myoglobin - oxygen store in muscles (that's why muscles need iron)
• Enzymes - like catalase, cytochrome (needed for energy production in cells)
• DNA synthesis (cell division needs iron)

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PART 2: WHERE IS IRON STORED IN THE BODY?

Locker 1: Functional Pool (Iron that is WORKING)

Locker 2: Storage Pool (Iron in RESERVE)

Simple rule: Most iron is in RBCs doing its job. A reserve is stored in the liver and spleen. Females have less reserve because they lose iron every month in menstruation.

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PART 3: HOW DOES THE BODY HANDLE IRON? (Iron Cycle)

The Big Picture: Iron is RECYCLED, not excreted

Food → Absorbed in duodenum (1-2 mg/day)
         ↓
    Plasma Transferrin (carries iron in blood)
         ↓
    Bone Marrow (iron used to make Hb in RBCs)
         ↓
    RBCs circulate for 120 days
         ↓
    Old RBCs eaten by macrophages (in spleen, liver, bone marrow)
         ↓
    Iron recovered → back to Transferrin → Bone marrow again

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PART 4: HOW IS IRON ABSORBED? (From Food to Blood)

Two types of dietary iron:

• Already in the right form (Fe²⁺ inside heme molecule)
• Absorbed directly and easily
• ~20% is absorbed - very bioavailable
• Absorption is NOT affected much by other foods

• Comes as Fe³⁺ (ferric form) which cannot be absorbed
• Must be converted to Fe²⁺ (ferrous form) first
• Only 1-5% is absorbed - very poorly bioavailable
• Affected A LOT by other foods in the diet

Step-by-step absorption:

Fe³⁺ in food
    ↓ (reduced by DCYTB - Duodenal Cytochrome B)
Fe²⁺
    ↓ (enters duodenal cell via DMT-1 transporter)
Inside duodenal cell:
    ↓ Either stored as Ferritin (if enough iron already)
    ↓ Or exits cell via FERROPORTIN
Fe²⁺ oxidized to Fe³⁺ by HEPHAESTIN (enzyme)
    ↓
Binds TRANSFERRIN in blood
    ↓
Transported to bone marrow, liver, other tissues

Remember these transporters for MCQs:

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PART 5: HEPCIDIN - THE BOSS OF IRON

• Duodenal cells (less iron absorbed from food)
• Macrophages (less iron recycled from old RBCs)
• Liver cells (less iron released from stores)

Simple Logic:

What suppresses hepcidin (when iron is needed)?

• TMPRSS6 - a liver enzyme that breaks down the hepcidin-stimulating pathway
• Erythroferrone - released by bone marrow when EPO is high (after blood loss, hypoxia) - tells liver "make more RBCs, send iron!"

What stimulates hepcidin (when iron is excessive)?

• High iron stores
• Inflammation (via IL-6) - this is why anemia of chronic disease happens!

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PART 6: FOODS THAT HELP AND HURT IRON ABSORPTION

Things that INCREASE absorption (eat these with iron-rich foods):

Things that DECREASE absorption (avoid with iron):

Practical tip for patients: Take iron tablet with lemon juice or orange juice. Do NOT take with tea or milk.

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PART 7: STAGES OF IRON DEFICIENCY

Stage 1 - Pre-latent (Depletion)

• Iron stores (ferritin) start falling
• Serum ferritin decreases - this is the FIRST thing to fall
• Everything else (Hb, serum iron, TIBC) is still NORMAL
• No symptoms
• Person doesn't even know they are iron deficient

Stage 2 - Latent Iron Deficiency (Iron-deficient erythropoiesis)

• Iron stores are NOW EMPTY (ferritin very low)
• Transferrin saturation falls below 15% (normally ~30%)
• Serum iron falls
• But hemoglobin is STILL NORMAL - no anemia yet!
• This is the most common stage in India - most Indians are here
• Can detect only by blood tests, not by looking at the patient

Stage 3 - Iron Deficiency Anemia (Overt IDA)

• Now hemoglobin falls
• RBCs become small (microcytic) and pale (hypochromic)
• Symptoms appear - pallor, tiredness, breathlessness
• This is what we clinically diagnose as "Iron Deficiency Anemia"

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PART 8: WHO GETS IRON DEFICIENCY? (Causes)

In CHILDREN (most relevant for Pediatrics):

• Breast milk has very little iron (~0.3 mg/L)
• Cow's milk has even worse absorption
• Babies fed only milk beyond 6 months (no weaning foods) are at HIGH RISK
• Vegetarian diet = mostly non-heme iron = poorly absorbed

• Iron is mainly transferred from mother to baby in the LAST TRIMESTER (3rd trimester)
• Premature baby misses this transfer = born with low iron stores
• Also grows faster = higher iron demand

• Children, adolescents have rapidly expanding blood volume
• Need more iron but diet often can't keep up

• Hookworms attach to intestinal wall and suck blood
• Each worm can take 0.03-0.15 mL blood/day
• Heavy infestation = significant iron loss
• Very common in India - this is why deworming is part of NACP

• Each pregnancy needs extra iron
• Mother in India who has 3-4 children closely spaced = very likely to be iron deficient

• Celiac disease, Crohn's disease
• After bowel surgery

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PART 9: CLINICAL FEATURES - WHAT DO YOU SEE IN THE PATIENT?

Group A: Symptoms of Anemia (less oxygen delivery)

• Pallor - pale skin, pale conjunctiva, pale tongue, pale nails
• Fatigue and weakness - muscles not getting enough oxygen
• Breathlessness on exertion - heart working harder
• Palpitations - heart beating faster to compensate
• Dizziness, headache
• Tachycardia

Group B: Specific Signs of Iron Deficiency (tissue iron depletion)

Pica - Special Mention:

• Clay eating (geophagia)
• Ice eating (pagophagia) - most specific for IDA
• Paper eating
• Flour/chalk eating

Plummer-Vinson Syndrome (Rare but high-yield MCQ):

1. Microcytic hypochromic anemia (IDA)
2. Esophageal webs (thin membranes in esophagus → difficulty swallowing)
3. Atrophic glossitis (smooth pale tongue)

Effects in Children (IMPORTANT for Pedia):

• Impaired cognitive development - Iron is needed for brain myelination and neurotransmitter synthesis
• Poor scholastic performance - Children cannot concentrate or learn well
• Behavioral problems - Irritability, short attention span
• Delayed motor development - Sitting, standing, walking delayed
• Impaired immunity - More infections, more sick days
• Increased mortality - In severe cases

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PART 10: LABORATORY DIAGNOSIS

Blood Tests in IDA:

• Low (but remember, this is a LATE finding)
• Cut-offs to diagnose anemia (WHO):
  • Children 6 months - 6 years: Hb < 11 g/dL
  • Children 6-14 years: Hb < 12 g/dL
  • Adult males: Hb < 13 g/dL
  • Non-pregnant females: Hb < 12 g/dL
  • Pregnant females: Hb < 11 g/dL

• Microcytic = small RBCs (MCV < 80 fL)
• Hypochromic = pale RBCs (central pallor >1/3 of cell diameter)
• Pencil cells (cigar cells) = elongated thin RBCs, characteristic of IDA
• Mild poikilocytosis (variation in shape)

• Reflects iron stores
• First lab value to fall in iron deficiency (even before anemia)
• Normal: >12-20 µg/L
• IDA: <12 µg/L = iron stores are gone
• Single most sensitive and specific test for iron deficiency
• MCQ favourite: "Most sensitive indicator of iron stores" = Serum Ferritin

• Measures iron bound to transferrin in plasma
• Normal: 80-180 µg/dL
• In IDA: LOW (<50 µg/dL)

• Measures how much transferrin is available to carry iron
• When iron is low → liver makes MORE transferrin → TIBC goes UP
• Normal: 250-370 µg/dL
• In IDA: HIGH (>350-400 µg/dL)
• Simple logic: Empty shelves (low iron) → body makes more shelves (high TIBC)

• = (Serum Iron / TIBC) × 100
• Normal: ~30%
• In IDA: <15% (diagnostic)

• Falls in IDA (body trying to maximize iron absorption)

Summary Table:

Gold Standard for Confirming Absent Iron Stores:

Reticulocyte response after treatment:

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PART 11: TREATMENT OF IDA

Oral Iron (first choice):

• Ferrous sulfate - cheapest, most used (but causes GI upset)
• Ferrous gluconate - better tolerated
• Ferrous fumarate

• Continue until Hb is normal, THEN give 3 more months to replenish iron stores
• Most students forget this - it's not just until Hb normalizes!

• Black stool (harmless, expected)
• Nausea, vomiting, constipation
• Abdominal cramps

Parenteral Iron (IV/IM - only when oral doesn't work):

• Can't absorb oral iron (malabsorption)
• Won't take oral iron (non-compliance)
• Need rapid correction (severe anemia before surgery)
• Inflammatory bowel disease

Blood Transfusion:

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PART 12: NACP - NATIONAL NUTRITIONAL ANEMIA CONTROL PROGRAMME

Why is this needed?

• ~80% of children under 2 years are anemic
• 74% of children aged 6-35 months are anemic (NFHS-II data)
• 58% of pregnant women are anemic
• 50% of non-pregnant women are anemic
• 56% of adolescent girls are anemic

History of the Programme:

1970: NACP launched (National Nutritional Anemia Control Programme)
      ↓
      Focused on pregnant women, lactating mothers, children
      ↓
National Iron Plus Initiative
      ↓
Anemia Mukt Bharat (AMB) - Current programme
      (Part of National Health Mission)

Anemia Mukt Bharat - Target Groups (Life Cycle Approach)

1. Children 6-59 months
2. Children 5-9 years
3. Adolescents 10-19 years
4. Pregnant and lactating women
5. Women of reproductive age (non-pregnant, non-lactating)
6. Women 20-49 years

The 6 Interventions under Anemia Mukt Bharat:

1. IFA supplementation (Iron Folic Acid tablets/syrup)
2. Periodic deworming (to eliminate hookworm and other intestinal parasites)
3. Behaviour Change Communication (BCC) - educating people
4. Appropriate IYCF (Infant and Young Child Feeding - promoting breastfeeding + complementary foods)
5. Dietary diversification and food fortification
6. Delayed cord clamping (allows more blood/iron from placenta to reach newborn)

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IFA SUPPLEMENTATION SCHEDULE (Most Important for MCQs)

Delayed Cord Clamping - Why is it done?

• Normally the umbilical cord is cut immediately after birth
• If you wait 1-3 minutes before cutting, extra blood (rich in iron and stem cells) flows from placenta to baby
• This gives the newborn an additional 30-50 mg of iron
• Reduces the risk of IDA in the first year of life
• Now recommended as a routine practice

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PART 13: IRON DEFICIENCY vs. ANEMIA OF CHRONIC DISEASE (High-yield comparison)

• In IDA: body is SCREAMING for iron (high TIBC = lots of empty transferrin waiting for iron), but there's none
• In ACD: iron is LOCKED AWAY (high ferritin = iron stored and not released) because inflammation causes high hepcidin that blocks ferroportin

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PART 14: KEY MCQ POINTS - ONE-LINERS

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Everything here ties together: Iron goes in through DMT-1, travels on transferrin, is regulated by hepcidin, stored as ferritin, and when deficient - causes a cascade from empty stores (ferritin falls first) → latent deficiency → microcytic hypochromic anemia with all its tissue signs. The NACP/Anemia Mukt Bharat programme addresses this at the population level through IFA supplementation, deworming, and behavior change. Know the doses, know the stages, know the lab patterns - and you're exam-ready.