Iron and its disorders, NAC in pediatrics, detail explanation, in simple language - mbbs final year , pedia
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Iron and Its Disorders + NAC in Pediatrics
MBBS Final Year - Pediatrics Focus
PART 1: IRON METABOLISM
What is Iron and Why Does the Body Need It?
Iron is one of the most important minerals in the body. Total body iron = 4-5 grams.
| Iron Pool | Form | Amount |
|---|---|---|
| Hemoglobin | Functional | ~65% |
| Myoglobin | Functional | ~4% |
| Enzymes (cytochromes, peroxidase, catalase) | Functional | ~1% |
| Transferrin (transport, plasma) | Transport | ~0.1% |
| Ferritin + Hemosiderin (liver, RES) | Storage | 15-30% |
Think of it simply: most iron is working (in Hb), a small bit is travelling (on transferrin), and the rest is stored (as ferritin).
Iron Metabolism Pathway
Iron metabolism flow - Goodman & Gilman's Pharmacological Basis of Therapeutics
Step-by-step in simple terms:
-
Absorption: Dietary iron (~14 mg/day eaten; only ~1 mg absorbed) enters through intestinal mucosa. Ferrous (Fe2+) is absorbed 3x better than ferric (Fe3+). Heme iron (from meat) is absorbed much better than non-heme iron.
- Enhancers: Vitamin C (ascorbic acid), meat/fish
- Inhibitors: Phytates (wheat bran), phosphates, tannins (tea), calcium
-
Transport in blood: Absorbed iron binds to apotransferrin → forms transferrin (a beta-globulin, 76 kDa glycoprotein) in plasma. Transferrin carries iron to where it's needed.
-
Delivery to marrow: Transferrin binds to transferrin receptors on erythroblasts → endocytosed → iron released inside the cell → goes to mitochondria → heme is synthesized.
-
Storage: Excess iron stored as:
- Ferritin - soluble, dispersed form (apoferritin shell + Fe inside; up to 4000 iron atoms per molecule)
- Hemosiderin - insoluble aggregate, visible under light microscope (seen in overload states)
-
Recycling: After ~120 days, old RBCs are destroyed by macrophages → iron released → stored as ferritin → recycled back to plasma. ~25 mg/day recycled this way (far more than the 1 mg absorbed daily).
-
Loss: Men lose ~0.6 mg/day (mostly in feces). Women lose ~1.3 mg/day (includes menstrual loss).
Iron Regulation - The Hepcidin Master Switch
Hepcidin (made by liver) is the key regulator:
- Iron overload / inflammation → hepcidin ↑ → blocks ferroportin → less iron exported from intestinal cells and macrophages → less iron in blood
- Iron deficiency / anemia / hypoxia → hepcidin ↓ → more iron released
IRPs (Iron Regulatory Proteins) control ferritin and transferrin receptor synthesis at the cellular level - when iron is low, cells make more transferrin receptors and less ferritin.
PART 2: IRON REQUIREMENTS IN PEDIATRICS
This is high-yield for finals!
| Age Group | Iron Requirement (µg/kg/day) |
|---|---|
| Infant | 67 (highest per kg - rapid growth!) |
| Child | 22 |
| Adolescent male | 21 |
| Adolescent female | 20 |
| Pregnant (2nd-3rd trimester) | 80 (very high!) |
Key exam point: Infants have a safety factor of 0.5-1 (barely meeting needs). If on a poor diet, infants are the most at-risk group.
PART 3: IRON DEFICIENCY ANEMIA (IDA)
Who Gets It?
- Children 6-24 months - Most vulnerable. Birth iron stores are exhausted after 4-6 months.
- Adolescent girls - Menstrual loss + rapid growth + poor diet
- Premature/low birth weight infants - Less iron stored before birth
- "Milk anemia" of infancy - Baby on only milk + carbs, no iron-containing foods
Why cow's milk is dangerous before 12 months: Causes intestinal blood loss (protein intolerance) + has very low iron content.
Pathophysiology - Three Stages
The body loses iron in sequence - think of it as emptying a bucket:
Stage 1: Iron Depletion
- Iron stores (ferritin) ↓
- Plasma ferritin ↓, TIBC (transferrin) ↑
- No anemia yet, Hb still normal
Stage 2: Iron-Deficient Erythropoiesis
- Serum iron ↓, transferrin saturation <15%
- RBC protoporphyrin ↑ (iron needed for heme synthesis, isn't there)
- Anemia mild or absent
- RBCs still normal size
Stage 3: IDA (frank anemia)
- Hb low, RBCs microcytic + hypochromic
- All the above abnormalities present
Clinical Features
General anemia symptoms:
- Pallor (especially conjunctival, palmar, nail bed)
- Fatigue, irritability
- Tachycardia, flow murmur
Iron-deficiency specific signs (iron in tissues):
- Pica - eating ice, dirt, clay (especially children)
- Koilonychia - spoon-shaped nails
- Angular stomatitis - fissures at mouth corners
- Glossitis - smooth, sore tongue
- Dysphagia - Plummer-Vinson syndrome (glossitis + koilonychia + dysphagia = this triad)
- Restless leg syndrome
- Developmental delay / poor school performance in children - iron deficiency in early childhood can cause irreversible cognitive delay
Lab Features
| Test | IDA |
|---|---|
| Hb | ↓ |
| MCV | ↓ (microcytic) |
| MCH/MCHC | ↓ (hypochromic) |
| RDW | ↑ (anisocytosis) |
| Serum Iron | ↓ |
| TIBC | ↑ |
| Transferrin saturation | ↓ (<15%) |
| Serum Ferritin | ↓ (first to fall) |
| Reticulocyte count | ↓ (before treatment) |
| Bone marrow Prussian blue stain | No stainable iron |
Blood film shows: microcytic, hypochromic RBCs, pencil cells (hypochromic elliptocytes), anisocytosis, poikilocytosis.
Treatment of IDA
Oral Iron (first choice):
- Ferrous sulfate - cheapest, most effective (ferrous salts absorbed 3x better than ferric)
- Pediatric dose: 3-6 mg/kg/day of elemental iron in 2-3 divided doses
- Adult: 150-200 mg elemental iron/day (e.g., ferrous sulfate 325 mg TDS)
- Give on empty stomach or with Vitamin C
- Response: Reticulocytosis in 4-7 days, Hb rise of ≥2 g/dL by 4 weeks = good response
- Continue for 3 months after Hb normalizes to replenish stores
Side effects of oral iron: Nausea, heartburn, constipation, black stools (tell parents!), abdominal discomfort. Start low and go up.
IV/Parenteral Iron - when oral fails, malabsorption, ongoing losses, non-compliance:
- Ferric carboxymaltose, iron sucrose, iron dextran
Blood transfusion - only if Hb very low (<5 g/dL) with symptoms, or before urgent surgery.
PART 4: IRON OVERLOAD / POISONING
Iron Poisoning in Children (Pediatric Emergency!)
Accidental iron tablet ingestion is a leading cause of toxic death in young children. As few as 20 mg/kg of elemental iron can cause toxicity; >60 mg/kg is potentially fatal.
4 Stages of Iron Poisoning:
| Stage | Time | Features |
|---|---|---|
| Stage 1 | 0-6 hours | Vomiting, diarrhea, hematemesis, abdominal pain (direct GI toxicity) |
| Stage 2 | 6-24 hours | Apparent improvement (deceptive "quiet phase") |
| Stage 3 | 12-48 hours | Shock, metabolic acidosis, liver failure, coagulopathy, CNS toxicity |
| Stage 4 | 2-6 weeks | GI scarring, pyloric stenosis, bowel obstruction |
Why is free iron toxic? When transferrin is fully saturated, free iron (NTBI = non-transferrin-bound iron) circulates → catalyzes free radical production (Fenton reaction) → oxidative damage to GI, liver, heart, brain.
Treatment of iron poisoning:
- Supportive care (IV fluids, correct acidosis)
- Deferoxamine - specific chelator for iron overload/poisoning. Binds free iron → forms ferrioxamine → excreted in urine (urine turns "vin rose" / reddish-brown color = sign it's working)
- Whole bowel irrigation if large ingestion
Hereditary Hemochromatosis
- Genetic iron overload (usually HFE gene mutation, autosomal recessive)
- Excess iron deposits in liver, heart, pancreas, joints, gonads
- "Bronze diabetes" - skin pigmentation + diabetes + cirrhosis
- Treatment: Phlebotomy (removing blood) is the mainstay
PART 5: NAC (N-ACETYLCYSTEINE) IN PEDIATRICS
What is NAC?
NAC is the antidote for paracetamol (acetaminophen/APAP) poisoning - the most common drug overdose presenting to pediatric emergency. It is also used as a mucolytic.
Why is Paracetamol Toxic?
In normal doses, paracetamol is safely metabolized by:
- Glucuronidation (~55%)
- Sulfation (~30%)
- Only ~5% goes through CYP2E1 → makes NAPQI (toxic metabolite), immediately detoxified by glutathione
In overdose, glucuronidation and sulfation get overwhelmed → more and more goes through CYP2E1 → NAPQI accumulates → glutathione stores depleted → NAPQI binds to liver cell proteins → hepatocellular necrosis
How does NAC work?
NAC works by three mechanisms:
- Replenishes glutathione - NAC is converted to cysteine → used to synthesize new glutathione → NAPQI is neutralized
- Directly detoxifies NAPQI - acts as a sulfhydryl donor
- Counteracts oxidative stress caused by NAPQI
The golden window: NAC is most effective within 8 hours of ingestion. Still useful beyond 8-16 hours but less hepatoprotective effect.
Dosing of NAC (High-Yield!)
| Route | Loading Dose | Maintenance |
|---|---|---|
| Oral | 140 mg/kg | 70 mg/kg q4h × 17 doses (72 hours total) |
| IV (FDA) | 150 mg/kg over 1 hour | 12.5 mg/kg/h × 4h, then 6.25 mg/kg/h × 16h |
| IV (one-bag method) | 150 mg/kg over 1 hour | 12.5 mg/kg/h × 20 hours |
Note: Same weight-based doses apply in children (per kg dosing). IV is preferred in pediatrics because the sulfur taste of oral NAC causes vomiting in children.
When to Give NAC?
- Paracetamol level plots above treatment line on the Rumack-Matthew nomogram (level drawn at ≥4 hours post-ingestion)
- If level cannot be obtained within 8 hours of ingestion → start empirically, stop if level is non-toxic
- Staggered/unknown time overdose → start NAC (safety first)
- Acute liver failure from APAP → continue NAC even if level undetectable (hepatoprotective mechanism beyond glutathione replenishment)
Side Effects of IV NAC (Anaphylactoid Reactions)
These are not true allergies - they are rate-related reactions:
- Flushing, pruritus, urticaria, nausea/vomiting
- Occasionally: bronchospasm, hypotension
- Management: Slow the infusion rate, give antihistamines/antiemetics; rarely need to stop
Minor interference with PT/INR assay - an elevated INR during NAC therapy does not mean liver failure unless INR >2.0.
When to Stop IV NAC?
Stop after the 21-hour protocol is complete IF:
- AST <50% of peak value, AND
- INR <2.0, AND
- Clinical improvement (no encephalopathy)
Otherwise continue until liver function recovers.
NAC as Mucolytic in Pediatrics
- NAC splits disulfide bonds of mucoproteins → reduces sputum viscosity
- Used in:
- Cystic fibrosis
- Bronchiectasis
- Chronic suppurative lung disease
- Meconium ileus equivalent (oral high dose)
- Given by nebulization or orally
QUICK EXAM SUMMARY TABLE
| Topic | Key Points |
|---|---|
| Most common age for IDA | 6-24 months |
| First lab to fall in IDA | Serum ferritin |
| Blood film in IDA | Microcytic, hypochromic, pencil cells, anisocytosis |
| Oral iron dose (peds) | 3-6 mg/kg/day elemental iron |
| Response monitoring | Reticulocytosis at 4-7 days; Hb +2 g/dL at 4 weeks |
| NAC antidote for | Paracetamol (APAP) poisoning |
| NAC mechanism | Replenishes glutathione, detoxifies NAPQI |
| Best window for NAC | Within 8 hours of ingestion |
| IV NAC loading | 150 mg/kg over 1 hour |
| Oral NAC loading | 140 mg/kg |
| Side effect of IV NAC | Anaphylactoid reaction (rate-related, not true allergy) |
| Iron poisoning antidote | Deferoxamine |
| Deceptive stage in iron poisoning | Stage 2 (6-24h) - "quiet phase" |
| Plummer-Vinson triad | Glossitis + koilonychia + dysphagia |
| Pica | Eating non-food (dirt, ice) - seen in IDA |
Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics; Guyton and Hall Medical Physiology; Henry's Clinical Diagnosis and Management by Laboratory Methods; The Washington Manual of Medical Therapeutics
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