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Shashidhar Venkatesh Murthy A/Prof & Head of Pathology College of Medicine & Dentistry ….. foundation of clinical medicine Clinical Pathology: RBC Disorders: Deficiency Anemia
Pathogenetic Classification of Anemia: Decreased Production: Nutrient Deficiency. Iron def (IDA) / Megaloblastic (MBA) Hemopoietic cell defect: Anemia of chronic disorders (ACD) Aplastic anemia (AA). Dysplastic anemia. Myelodysplastic Syndromes Increased loss / destruction: Blood loss anemia – Acute / Chronic - bleeding. Hemolytic anemia – Congenital / Acquired. Acquired / External injury. Immune AIHA (Warm/Cold) Mechanical, Drugs & Parasites Congenital / Internal RBC defect Defective Membrane (Spherocytic an) Defective Hemoglobin (Sickle cell an.) Deficient Enzyme (G6PD) Top 6 Anemias: 1. Iron Def. A 2. Megaloblastic 3. Anem. Of Chronic Dis. 4. Aplastic An. 5. Immune Hemolytic – Warm 6. Immune Hemolytic - Cold 2 2 3
Anemia Pathogenesis: B12/Folate Metabolism: R Binders, Stomach, IF, Colon, Methionine, Homocysteine – DNA synthesis – cell division. Megaloblastic anemia DNA: B12, Folate BLAST Early Intermediate Late Retic. RBC Aplastic anemia Dysplastic anemia Hemolytic anemia Immune Mech. Infection Proerythroblast (Pronormoblast) Polychromatophilic Normoblast Reticulocyte Basophilic Normoblast Orthochromatophilic Normoblast Erythrocyte Iron Deficiency anemia Hb: Iron Iron Metabolism: “limited”,10%, Recycle, Ferritin, Transferrin, Hepcidin, forms Hb in cytoplasm. 4
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Iron Deficiency - Megaloblastic Causes: • Causes: Bleeding, Nutrition, Increased needs. Pathogenesis: Iron - Hb - MCV Morphology: Microcytic, Hypochromic Pencil cells. Clinical Features: glossitis, chelitis, stomatitis. koilonychia, dysphagia Nutrition, gastritis, intestinal disorders, Cancer therapy. Pathogenesis: • DNA Cells - all cells. Morphology: • Macrocytic, Normochromic • Pancytopenia* Clinical Features: • glossitis, chelitis, stomatitis. • Mild Jaundice & Bruising 6
Microcytic Anemia (IDA) Normal 7
Iron Deficiency Anemia: L 1.Microcytic, Hypochromic – excess cell division, low Hb. 2.Anisopoikilocytosis. – varying supply, abnormal hemopoiesis. 3.Pencil forms. - ? cause 8
Macrocytic Anemia (Meg.): H H N Normal 9
Megaloblastic Anemia: Megaloblastic Bone Marrow Normal Macrocyte Megaloblast Hypersegmented Neutrophils 1. Oval Macrocytes, Pancytopenia: cell division. 2. Anisopoikilocytosis: Hemolysis. 3. Hypersegmented neutrophils: Large cells / Megaloblasts (in bone marrow). 10
Pernicious Anemia: Vit B12 Autoimmune atrophic gastritis in aged. IF & Parietal cell antibody (Type I,II,III) Reduced Tetra-hydrofolate (FH4) Decreased DNA synthesis. Other causes of Vit B12 def. (not pernicious) Gastrectomy Achlorhydria Chronic Pancreatitis Ileal resection Mal absorption syndromes. Tapeworm infestation Malignancy, pregnancy, hyperthyroidism etc. Clinical: MBA+ neurological deficits (spinal dorsal tract) Loss of proprioception. B12 Folate Green Veg Animal/bacteria
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Haemopoiesis in deficiency anemias Macrocytic, pancytopenia Megaloblastic Microcytic hypochromic Iron Deficiency Normal 13
Anemia of Chronic Disease: Etiology: Chronic Infections, inflammations, malignancy & anemia of renal disease*. Pathogenesis: IFN, TNF, IL block iron transfer from macrophage store to RBC. Erythropoietin*. Morphology: Mild Microcytic, Hypochromic. Clinical Features: Mild anemia, resistant to iron therapy.
Aplastic Anemia: BM Failure Stem Cell Cancer: Myelodysplastic Sy. Leukemia Stem cell damage • Drugs, Immune • Viral Infections. Dysplasia Normal BM Aplasia Clinical Features: 1. RBC - Anemia, 2. WBC - Infections 3. PLT - Bleeding Normocytic Pancytopenia 15
Learning Objectives: Diseases of RBC Anaemia: Overview, Classification, pathogenesis, diagnosis, clinical features & complications. - common Study TOP 10 ANEMIA Major (detailed) Iron Deficiency anemia. Megaloblastic anemia. Imm. Hemolytic (Warm/Cold) Anemia of Chronic Disease. Aplastic Anemia Minor (brief note) Myelodysplastic Syndrome Sickle Cell Anemia Thalassemia syndromes. G6PD deficiency anemia. Hereditary Spherocytosis. 1. 2. 3. 4. 5. 1. 2. 3. 4. 5.