📚 Hematology — L2: Iron Deficiency Anemia

📚 Lecture Overview

This lecture covers normal iron metabolism, the etiology and clinical consequences of iron deficiency, and its management. Understanding these concepts is critical because iron deficiency anaemia is the most common hematological disorder encountered in clinical practice.

🎯 Key Concepts & Definitions

• Ferrous vs. Ferric Iron: Ferrous (Fe++) is biologically active and easily absorbed, while ferric (Fe+++) requires reduction via gastric acidity and Vitamin C before absorption.
• Transferrin: The primary iron transport protein in the blood.
• Ferritin: The main intracellular protein that stores iron, reflecting body iron stores.
• Pica: A neuropsychiatric symptom of iron deficiency characterized by cravings for non-food items like ice (pagophagia) or clay (geophagia).
• Koilonychia: Spooning of the fingernails, a classic epithelial tissue change seen in chronic iron deficiency.

📖 Main Content

1- Normal Iron Metabolism & Distribution

• Iron is the most abundant trace element; total body content is roughly 2500 mg (two-thirds bound to haem).
• Daily erythropoiesis requires 20-25 mg of iron:
• 95% is recycled from normal RBC turnover and haemoglobin catabolism.
• 5% (1 mg/day) is newly absorbed to balance minimal daily losses (faeces, urine, sweat, skin).
• The remaining one-third of body iron is stored in the liver, spleen, and bone marrow, or utilized in myoglobin and cytochromes.
• Haem vs. Non-Haem: Non-haem compounds include sulfur-iron bonding proteins (respiratory chain), transferrin, lactoferrin, and ferritin.

2- Iron Absorption & Requirements

• Intestinal absorption normally accounts for 10% of a 10-20 mg/day dietary intake, occurring primarily in the duodenum and upper jejunum.
• In severe deficiency, absorption can upregulate up to 30%.
• Factors enhancing absorption: Acidic pH (favors ferrous state), ascorbic acid (Vitamin C), low molecular weight chelators (amino acids, fructose), and cooking.
• Factors decreasing absorption: Phytates and phosphates (e.g., in spinach), neutral/alkaline pH, and pancreatic secretions.
• Daily requirements:
• Adult men: 1 mg/day.
• Menstruating women: Additional 1-1.5 mg/day to cover monthly blood loss (60-80 ml).
• Infancy, adolescence, and pregnancy: Requirements significantly increase; absorption increases up to 20% during pregnancy.

3- Aetiology & Phases of Iron Deficiency

• Causes: Poor intake, diminished absorption (coeliac disease, gastrectomy, achlorhydria), increased requirements, and excessive blood loss (most common cause globally, especially heavy menstruation and GI bleeding).
• Three Phases of Iron Deficiency:
• Phase 1 (Iron depletion): Ferritin and haemosiderin stores are depleted.
• Phase 2 (Iron-deficient erythropoiesis): Serum iron falls, and iron-binding capacity rises.
• Phase 3 (Iron-deficiency anaemia): Haemoglobin falls as iron deficiency affects haem synthesis.

4- Clinical Consequences & Management

• Clinical Manifestations: Fatigue, lethargy, dizziness, pallor, immune deficiency (diminished phagocytosis, T-cell dysfunction), splenomegaly, neuropsychiatric symptoms, and epithelial changes (koilonychia, lingual papillary atrophy, angular stomatitis, and gastric atrophy).
• Two Core Management Principles:
  1. Correction of the underlying disorder.
  2. Replenishment of iron stores.
• Oral Iron Preparations:
• Ferrous sulphate (200 mg tab = 60 mg elemental iron).
• Ferrous gluconate (300 mg tab = 35 mg elemental iron).
• Ferrous fumarate (200 mg tab = 65 mg elemental iron).
• Standard dosing: 1 tablet 3 times daily with/after meals (provides 100-200 mg elemental iron).
• Monitoring Response:
• Reticulocytosis starts on day 4 and lasts for 12 days.
• Haemoglobin rises by 0.15 gm/dl/day starting after one week.
• Continue treatment for 3-6 months post-correction to replenish stores.
• Parenteral Iron:
• Indications: Oral intolerance, severe GI disease, chronic blood loss exceeding absorption, malabsorption, or rapid correction needed before surgery.
• Formulas/Routes: Intramuscular (iron-dextran, iron-sorbitol-citrate) or Intravenous (iron-dextran).
• Total Dose Formula: Total dose (mgs) = 0.3 x Weight (lb) x Hb deficit (%) (taking 14.6 gm as 100%).

📊 Visual Learning

💡 Important Points to Remember

• Recycling dominance: 95% of daily iron used for erythropoiesis comes from recycled RBC turnover; only 5% (1 mg) is newly absorbed.
• Site of absorption: Maximum absorption occurs in the duodenum and upper jejunum.
• Ferrous vs Ferric: Iron must be reduced to the ferrous (Fe++) state via gastric acidity and Vitamin C for optimal absorption.
• Dietary traps: Spinach is rich in iron, but it is bound to phytates and phosphates, making it a poor bioavailable source.
• Three Phases: Remember the sequence: 1) Store depletion, 2) Iron-deficient erythropoiesis, 3) Overt anaemia.
• Epithelial signs: Look out for koilonychia (spoon nails), angular stomatitis, and lingual papillary atrophy.
• Pica: Involuntary craving for ice (pagophagia) or clay (geophagia) is a hallmark neuropsychiatric sign.
• Therapy timeline: Reticulocytosis peaks starting on day 4, and Hb rises by 0.15 gm/dl/day.
• Storage replenishment: Continue iron treatment for 3 to 6 months after the hemoglobin normalizes to refill stores.
• Common pitfall: Treating only the anaemia without investigating the underlying cause (e.g., missed GI malignancy in men or post-menopausal women).

⚠️ Common Exam Questions

• MCQ Trick: Examiners often ask about dietary iron sources and trick students by listing spinach as the "best" source. Remember: while spinach has high iron content, its poor bioavailability due to phytates makes it a poor source compared to red meat and liver.
• Calculation traps: Questions involving the parenteral total dose formula 0.3 x W x D. Ensure weight is converted to pounds (lb) and hemoglobin deficit is expressed as a percentage (with 14.6 gm = 100%).
• Clinical scenario application: A post-menopausal male presenting with microcytic hypochromic anaemia. Examiners will test if you immediately jump to iron supplementation versus investigating GI blood loss (peptic ulcers, malignancy, diverticulosis) as the primary etiology.

📝 Quick Review Checklist

I can explain the normal distribution and daily recycling versus absorption of body iron.
I understand the factors affecting iron absorption and why the duodenum/jejunum is the primary site.
I can define the three phases of iron progression from depletion to overt anaemia.
I know the daily iron requirements for men, menstruating women, and pregnant individuals.
I can list the key epithelial and neuropsychiatric manifestations of iron deficiency.
I know the standard oral iron salts, their elemental iron content, and how to manage side effects.
I can calculate the parenteral total dose using the provided formula.
I understand how to monitor therapeutic response via reticulocytosis and Hb recovery rates.