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PY2.1-13 | Haematology — Part 2

Iron Metabolism — Absorption, Transport, Storage & Recycling (PY2.6)

Iron is essential for haemoglobin synthesis — 70% of body iron is in haemoglobin. Total body iron: ~3–5 g (more in males).

Distribution of body iron:
• Haemoglobin iron: 70% (~2.5 g) — in circulating RBCs
• Storage iron: 25% (~1 g) — as ferritin (soluble, readily available) and haemosiderin (insoluble, long-term storage) in liver, spleen, and bone marrow
• Myoglobin iron: 4% — in muscle
• Transport iron: ~0.1% — bound to transferrin in plasma
• Enzyme iron: ~1% — in cytochromes, catalase, peroxidase

Iron absorption (in the duodenum and upper jejunum):
• Dietary iron comes in two forms:
- Haem iron (from meat, fish) — absorbed directly by haem carrier protein. More efficiently absorbed (15–35%)
- Non-haem iron (from vegetables, grains) — must be reduced from Fe³⁺ to Fe²⁺ by duodenal cytochrome b (Dcytb) and vitamin C, then absorbed via DMT1 (divalent metal transporter 1)

• Inside the enterocyte, iron either:
• Binds to ferritin (stored, lost when the enterocyte is shed) — this is how the body limits absorption when iron is sufficient
• Exits via ferroportin (the only known iron exporter) into the blood

• In the blood, Fe²⁺ is oxidised to Fe³⁺ by hephaestin (on enterocyte) or ceruloplasmin (in plasma), then binds transferrin for transport to bone marrow and storage sites

Hepcidin — the master regulator:
Produced by the liver, hepcidin controls iron homeostasis. It works by degrading ferroportin on enterocytes and macrophages:
• High iron stores / inflammation → ↑ hepcidin → ↓ ferroportin → ↓ iron absorption and release → iron stays locked inside cells
• Iron deficiency / hypoxia / erythropoietic demand → ↓ hepcidin → ↑ ferroportin → ↑ iron absorption and release

Think of hepcidin as the 'iron gatekeeper' — it slams the door shut when there's enough iron.

Iron deficiency anaemia (IDA) — the most common anaemia worldwide, especially in India:
• Causes: poor dietary intake, malabsorption (coeliac disease), chronic blood loss (menstruation, hookworm, GI bleeding)
• Lab: ↓ serum iron, ↓ ferritin, ↑ TIBC (total iron-binding capacity), ↓ transferrin saturation
• Blood film: microcytic hypochromic RBCs (small, pale cells — not enough iron to fill them with Hb)
• Treatment: oral iron (ferrous sulphate) with vitamin C to enhance absorption

Classification of Anaemias (PY2.7)

Anaemia = reduction in haemoglobin concentration below normal for age and sex (WHO: < 13 g/dL in males, < 12 g/dL in non-pregnant females, < 11 g/dL in pregnancy).

Anaemias are classified by red cell size (MCV) — this is the most clinically useful classification:

1. Microcytic anaemias (MCV < 80 fL) — small RBCs
• Iron deficiency anaemia — most common worldwide. Microcytic hypochromic.
• Thalassaemia — defective globin chain synthesis (α or β). Common in India, especially in Gujarat, Maharashtra, and the tribal belt.
• Anaemia of chronic disease — often normocytic but can be microcytic. Hepcidin-mediated iron trapping.
• Sideroblastic anaemia — defective haem synthesis. Ring sideroblasts in marrow.
• Mnemonic: TAILS (Thalassaemia, Anaemia of chronic disease, Iron deficiency, Lead poisoning, Sideroblastic)

2. Normocytic anaemias (MCV 80–100 fL) — normal-sized RBCs
• Acute blood loss — RBCs are normal, just fewer of them
• Anaemia of chronic disease — most common in hospitalised patients
• Haemolytic anaemias — RBCs destroyed prematurely (sickle cell, hereditary spherocytosis, autoimmune)
• Aplastic anaemia — bone marrow failure
• Chronic kidney disease — EPO deficiency

3. Macrocytic anaemias (MCV > 100 fL) — large RBCs
• Megaloblastic (caused by impaired DNA synthesis):
- Vitamin B₁₂ deficiency — pernicious anaemia (autoimmune destruction of parietal cells → no intrinsic factor → no B₁₂ absorption), strict veganism, ileal disease
- Folate deficiency — poor diet, pregnancy (increased demand), drugs (methotrexate, phenytoin)
• Non-megaloblastic: liver disease, hypothyroidism, alcohol, reticulocytosis

Peripheral blood smear findings that help diagnosis:
• Target cells → thalassaemia, liver disease
• Sickle cells → sickle cell disease
• Spherocytes → hereditary spherocytosis, autoimmune haemolytic anaemia
• Schistocytes (fragmented RBCs) → microangiopathic haemolytic anaemia (DIC, TTP/HUS)
• Hypersegmented neutrophils → megaloblastic anaemia (B₁₂ or folate deficiency)

White Blood Cells — Types and Functions (PY2.8)

White blood cells (leucocytes) are your immune defence force. Total WBC count: 4,000–11,000/µL. Unlike RBCs, WBCs have nuclei, can leave blood vessels (diapedesis), and can move through tissues.

Differential WBC count — the five types and their functions:

Granulocytes (contain cytoplasmic granules, multilobed nuclei):

• Neutrophils (60–70%) — the most abundant WBCs and the first responders to bacterial infection.
Function: phagocytosis of bacteria. They engulf, kill (using reactive oxygen species, myeloperoxidase), and die — forming pus.
Lifespan: 6–12 hours in blood, 1–2 days in tissues
A high neutrophil count (neutrophilia) = think bacterial infection

• Eosinophils (1–4%) — bilobed nucleus, bright orange-red granules
Function: defence against parasitic infections (release major basic protein onto parasites), modulation of allergic reactions
Eosinophilia = think parasites or allergy

• Basophils (0–1%) — rarest WBC, bilobed nucleus, large dark blue granules
Function: release histamine and heparin. Involved in allergic and inflammatory responses. Tissue counterpart: mast cells.

Agranulocytes (no prominent granules, round/indented nuclei):

• Lymphocytes (20–30%) — round nucleus, thin rim of cytoplasm
- T lymphocytes (70%) — cell-mediated immunity. Types: helper T cells (CD4⁺), cytotoxic T cells (CD8⁺), regulatory T cells
- B lymphocytes (20%) — humoral immunity. When activated, differentiate into plasma cells that produce antibodies (immunoglobulins)
- NK (natural killer) cells (10%) — innate immunity, kill virus-infected cells and tumour cells without prior sensitisation
Lymphocytosis = think viral infection

• Monocytes (3–8%) — largest WBC, kidney-shaped nucleus
Function: leave the blood and become macrophages in tissues (Kupffer cells in liver, alveolar macrophages in lungs, microglia in brain). Phagocytose bacteria, dead cells, and debris. Also act as antigen-presenting cells (APCs) — they process antigens and present them to T lymphocytes to initiate adaptive immunity.
Lifespan: 1–3 days in blood, weeks to months as tissue macrophages

Leucocytosis (↑ WBC count): physiological (exercise, pregnancy) or pathological (infection, leukaemia)
Leucopenia (↓ WBC count): viral infections, bone marrow suppression, drugs