Haematology Revision: Haematopoiesis, OmpathStudy

MOUNT KENYA UNIVERSITY School of Medicine Department of Pathology### Bachelor of Medicine and Bachelor of Surgery — Year 3 Unit Code: MBML 3200 Unit Title: HAEMATOLOGY Examination: University Examination 2024/2025 — Main Exam Date: 14th July, 2025 Time: 2 Hours 30 Minutes Sections: A — 60 MCQs B — 7 SAQs C — 1 LAQ --- COMPREHENSIVE REVISION NOTES BATCH 1 Topics 1 – 5--- TOPIC 1: HAEMATOPOIESIS Etymology: Haema (Greek) = blood Poiesis = making/production Definition: Continuous process of blood cell production from pluripotent stem cells (★) Replaces cells lost through senescence, destruction, or haemorrhage Produces ~200 billion RBCs and ~100 billion WBCs daily --- SITES OF HAEMATOPOIESIS — BY DEVELOPMENTAL STAGE (★) Phase Site Period --- --- --- Mesoblastic Yolk sac 0–2 months fetal Hepatic Liver (primary), spleen, lymph nodes 2–7 months fetal Myeloid Bone marrow 5 months → adult life In healthy adults: bone marrow is the sole site (★) Active marrow in adults: sternum, vertebrae, pelvis, ribs, skull, proximal femur and humerus Extramedullary haematopoiesis = reactivation of liver/spleen in disease states (e.g. myelofibrosis, thalassaemia major) (★) --- THE HAEMATOPOIETIC STEM CELL (HSC) Pluripotent and self-renewing Surface marker: CD34+ (★) — also CD38−, CD117+, HLA-DR+ Differentiates into two main progenitors: Common Myeloid Progenitor (CMP) → RBCs, platelets, neutrophils, eosinophils, basophils, monocytes Common Lymphoid Progenitor (CLP) → T-cells, B-cells, NK cells Common CD markers — know the difference: (★) CD34 = HSC marker CD3 = T-cell marker CD4 = T-helper cell CD19, CD20 = B-cell markers CD33 = myeloid marker --- GROWTH FACTORS & CYTOKINES (★) Factor Primary Target Clinical Use --- --- --- Erythropoietin (EPO) RBC production (erythroid line) Anaemia of CKD Thrombopoietin (TPO) Platelet production via megakaryocytes (★) — G-CSF (Filgrastim) Neutrophil production and recovery (★) Post-chemotherapy neutropenia GM-CSF Neutrophils + monocytes Stem cell mobilisation IL-3 Multi-lineage stimulation — SCF (Stem cell factor) HSC survival and proliferation — G-CSF = Granulocyte Colony-Stimulating Factor → promotes neutrophil recovery after chemotherapy (★) Thrombopoietin → acts on megakaryocytes → platelets (★) --- TOPIC 2: ANAEMIA — GENERAL + IRON DEFICIENCY ANAEMIA (IDA) Etymology: An- = without haima = blood Definition of Anaemia: Reduction in haemoglobin concentration below normal for age and sex WHO thresholds: Hb <13 g/dL (adult male) <12 g/dL (adult non-pregnant female) <11 g/dL (pregnant) --- CLASSIFICATION OF ANAEMIA BY MCV (★) Type MCV Causes --- --- --- Microcytic (<80 fL) ↓ IDA, thalassaemia, anaemia of chronic disease, sideroblastic Normocytic (80–100 fL) Normal Aplastic anaemia, haemolytic anaemia, acute blood loss, CKD Macrocytic ( 100 fL) ↑ B12/folate deficiency, liver disease, hypothyroidism, drugs (zidovudine, hydroxyurea, methotrexate) --- IRON DEFICIENCY ANAEMIA (IDA) (★) Definition: Most common anaemia worldwide — due to negative iron balance leading to insufficient haem synthesis Iron Metabolism — The Pathway: Dietary iron: haem iron (meat) absorbed 20–30% non-haem iron (plant) absorbed 5–10% Absorbed in duodenum and proximal jejunum as Fe²⁺ (ferrous form) Carried in blood bound to transferrin Stored as ferritin (soluble, reflects body stores — best early marker) and haemosiderin (insoluble) Regulated by hepcidin — liver hormone that blocks ferroportin → ↓ iron absorption and release Stages of IDA: (★) Stage 1: ↓ ferritin (depleted stores) — no anaemia yet Stage 2: ↓ serum iron, ↑ TIBC, ↓ transferrin saturation — iron-deficient erythropoiesis Stage 3: ↓ Hb, microcytic hypochromic anaemia — overt IDA Causes: ↑ Loss: heavy menstrual bleeding (commonest in premenopausal women), GI bleeding (peptic ulcer, colorectal Ca, hookworm) ↓ Intake: poor diet, malnutrition ↓ Absorption: coeliac disease, gastrectomy, achlorhydria, H. pylori ↑ Demand: pregnancy, infancy, adolescent growth spurt Clinical Features: General anaemia: fatigue, pallor, dyspnoea on exertion, palpitations, headache, dizziness IDA-specific signs: (★) Koilonychia — spoon-shaped nails Angular cheilitis — cracking at corners of mouth Glossitis — smooth, beefy-red, painful tongue Pica — craving non-food substances (ice, soil, clay, paper) Plummer-Vinson syndrome — IDA + dysphagia + post-cricoid oesophageal web (★) Laboratory Findings: (★) Test IDA Result --- --- Hb ↓ MCV ↓ (<80 fL) — microcytic MCH ↓ — hypochromic Serum ferritin ↓ ← earliest and most sensitive indicator Serum iron ↓ TIBC (transferrin capacity) ↑ Transferrin saturation ↓ (<15%) Reticulocyte count ↓ or normal PBF Microcytes, hypochromia, pencil/cigar cells, anisocytosis, poikilocytosis Serum soluble transferrin receptor ↑ (useful in pregnancy) Confirmatory Tests: Serum ferritin — most sensitive and specific Serum iron + TIBC Bone marrow aspirate with Prussian blue stain — absent iron stores (gold standard, rarely done) Treatment: Oral ferrous sulphate (FeSO₄) — first