Blood-RBC&Anaemia I 2024.PDF

RBC and anaemia (I) Compositions of blood Haemopoiesis Anaemias – General – Iron deficiency – Vit B12 & folate deficiency Learning outcomes To describe the process of haemopoiesis To understand pathogenesis and clinical features of anaemias due to iron deficiency and Vit B12 & folate deficiency RBC...

RBC and anaemia (I) Compositions of blood Haemopoiesis Anaemias – General – Iron deficiency – Vit B12 & folate deficiency Learning outcomes To describe the process of haemopoiesis To understand pathogenesis and clinical features of anaemias due to iron deficiency and Vit B12 & folate deficiency RBC and anaemia (I) Compositions of blood Haemopoiesis Anaemias – General – Iron deficiency – Vit B12 & folate deficiency Blood and cellular components Blood – cells suspended in plasma Function: - transport O2 Nutrients CO2 & waste products - immune response Composition: Plasma ( 55% ) Cells (40-45%) Cell types − Red cells (erythrocytes, RBC) − White cells (leucocytes, WBC) − Platelets (thrombocytes) RBC and anaemia (I) Compositions of blood Haemopoiesis Anaemias – General – Iron deficiency – Vit B12 & folate deficiency Haemopoiesis – site of production Starts in yolk sac at 3rd wk of gestation 6 wks–6 mo: liver, spleen (extramedullary) 6 mo–birth: bone marrow taking over (medullary) In adult life: bone marrow Extramedullary haemopoiesis in disease Blood cell differentiation Pluripotential stem cells Myeloid or Lymphoid stem cells Committed stem cells Earliest recognisable precursors Mature cells RBC Average 7-8 µm Normal red cell values Male Female RBC Count (x1012 /l) 4.5 - 6.5 3.9 - 5.6 Haemoglobin (g/dl) 13.8 -17.5 11.3 -15.5 PCV% 40 - 52 36 - 48 Reticulocytes 1% of total RBC RBC - derived absolute values 1.Mean Cell Volume (MCV) fl - cell size 2.Mean Cell Hb (MCH) pg - Hb content per cell 3.Mean Cell Hb Conc. (MCHC) g/dl - average Hb conc. in RBC; independent of cell size PCV RBC Count/l (80-95 fl) Hb g/dl RBC Count/l (27-32 pg) Hb g/dl PCV (32-36 g/dl) Erythropoiesis – the process Stem cell Proerythroblast Erythroblast (early, late) Normoblast Reticulocyte (early, late) Erythrocyte Nucleus (change!) Bone marrow Peripheral blood Erythropoiesis – main features Several stages of mitosis & maturation reticulocytes Erythropoietin Essential dietary constituents - Iron - Vit B12 - Folic acid RBC and anaemia (I) Compositions of blood Haemopoiesis Anaemias – General – Iron deficiency – Vit B12 & folate deficiency Anaemia Anaemia: - Haemoglobin < reference level for age & gender - Reduction in red cell mass Classified in terms of the red cell indices (MCV) Three major types: - hypochromic microcytic with a low MCV - normochromic normocytic with a normal MCV - macrocytic with a high MCV Pathological consequences: tissue hypoxia Anaemia Clinical manifestations May be asymptomatic Symptoms (non-specific): fatigue headaches faintness Signs: pallor (eg conjunctiva) Anaemia Laboratory investigation: RBC  Hb  PCV  Blood film − Anisocytosis: variation in size eg VB12 ↓→megaloblastic anaemia − Poikilocytosis: variation in shape eg sickle cell − Anisochromasia: eg Fe↓ variation in haemoglobinisation Anaemia Causes Decreased production - Suppressed proliferation e.g. aplastic bone marrow - Defective maturation e.g. haematinic deficiency Increased destruction/loss: usually reticulocytes↑ - Haemorrhage - Haemolysis, e.g. defective Hb Fe Deficiency – Microcytic, hypochromic anaemia The commonest cause of anaemia Blood picture: microcytic, hypochromic Iron metabolism: - Iron status largely controlled by absorption - Absorption: Fe+++→ Fe++; gastric HCl required - Stored as ferritin and haemosiderin - Carried by transferrin Fe Deficiency anaemia Mechanisms of Fe deficiency - Increased demands - Chronic blood loss - Poor diet - Malabsorption Fe Deficiency – Microcytic, Hypochromic cells Fe deficiency Normal Fe deficiency anaemia Treatment Find & treat the underlying cause Fe to correct anaemia and replace stores Monitored by reticulocyte count & Hb Oral Fe in most case Fe deficiency anaemia Failure to respond to Fe therapy Non compliance Incorrect diagnosis (thalassaemia trait) Mixed deficiency e.g. thalassaemia Chronic inflammation: - Infectious (e.g. TB, malaria) - Non infectious (e.g. rheumatoid arthritis) Malignant disease (carcinoma, sarcoma, lymphoma) Megaloblastic Anaemia(Macrocytic, Normo/Hypochromic ) Characterised by megaloblasts in bone marrow - erythroblasts with delayed nucleus maturation Peripheral blood: - Large oval RBCs; Howell-Jolly bodies (nuclear DNA) - Hypersegmented neutrophils Causes of Megaloblastic Anaemia Deficiency of B12 and folate Abnormal metabolism of B12 and folate Other defects of DNA synthesis Biochemical basis – block of DNA synthesis Deoxyuridine monophosphate Methylation Methylene tetrahydrofolate Tetrahydrofolate B12 Methyl tetrahydrofolate Dietary folate Deoxythymidine monophosphate DNA B12 Deficiency Present in meat, fish, dairy produce, but not in plant; Absorbed in terminal ileum, Intrinsic Factor (IF) required; Function: methylation – essential for DNA synthesis methyl tetrahydrofolate B12 homocysteine tetrahydrofolate methionine Causes of B12 deficiency Low dietary intake Malabsorption: - Gastric pernicious anaemia (IF) congenital lack of IF gastrectomy - Intestinal Crohn’s blind loop syndrome ileal resection Folate Deficiency Source: meat, greens; present as polyglutamates (reduced dihydrofolate or tetrahydrofolate) Metabolism: - Converted to monoglutamate during absorption (methyl tetrahydrofolate) - Transported in the same form Causes of folate deficiency: Nutritional - poor diet; overcooking of food; Malabsorption - tropical sprue, coeliac disease, Crohn’s. Excess utilisation - pregnancy, lactation; malignancy; haemolytic anaemia Drugs - alcohol; anti-convulsants Which of the following regarding erythropoiesis is NOT true: a) It undergoes multiple stages of mitosis and maturation b) Erythropoietin serves as a growth factor c) Iron is an important dietary constituent d) Folic acid is required e) Vitamin B2 is essential Which of the following is a cause of anaemia? a) Suppression of red cell proliferation b) Maturation defect in red cells c) Chronic haemorrhage d) Haemolysis e) All of the above