Pathology of Anemia fsm.ac

“The future belongs to those who believe in the beauty of their dreams.” –Eleanor Roosevelt “No doubt knowledge is valuable..”, but above it are power, goodness & most important Character” HEMATOLOGY Anemia Dr. Venkatesh M. Shashidhar Associate Professor of Pathology Fiji School of Medicine Anemia - 4 Normal Blood Cells: Shashi-May 04 Anemia - 5 Blood Smear - Normal Shashi-May 04 Anemia - 6 Shashi-May 04 Anemia - 7 Haemopoiesis: Shashi-May 04 Anemia - 8 Steps in Erythropoisis Early Intermediate Late Proerythroblast (Pronormoblast) Polychromatophilic Normoblast Reticulocyte Erythrocyte Basophilic Normoblast Orthochromatophilic Normoblast Shashi-May 04 Anemia - 10 RBC disorders (Anemias) : “Anemia is decreased red cell mass affecting tissue oxygenation” • Practical - Low Hb* or Low Hematocrit* Shashi-May 04 Anemia - 11 C.B.C • Haemoglobin - 15±2.5, 14 ±2.5 - g/dl • PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%) – Haematocrit, effective RBC volume - better • RBC count - 5.5 ±1, 4.8 ± 1 x1012/l • MCHC - Hb/PCV - 30-36 - g/dl – Hb synthesis within RBC • MCH - Hb/RBC - 29.5 ± 2.5 pg/l – Average Hb in RBC • MCV - PCV/RBC 85 ± 8 - fl Shashi-May 04 Anemia - 12 Mechanism of Anemia : • Decreased Production: – Nutrient Deficiency. • Iron, B12/Folate – Hemopoietic cell damage: • Aplastic, Hypoplastic – Neoplasms, radiation, drugs • Increased loss / destruction: – Blood loss anemias - parasites, bleeding – Hemolytic anemias – Autoimmune, mechanical, drugs, parasites. Shashi-May 04 Anemia - 13 Iron Deficiency Anemia: • Most abundant metal but most common deficiency..! • Common in developing world, • Parasitic Worm infestation + Malnutrition • Chronic blood loss  only Iron Deficiency • not other deficiency….. Why ? Shashi-May 04 Anemia - 15 Iron Metabolism • • • • Limited absorption* and no proper excretory mech*. Recycling of iron – dead cells to new cells 1mg/day  3-6G body  1mg/day 10% of the 10 to 20 mg of dietary iron. • Iron is absorbed in Jejunum. • Stored as Ferritin & Hemosiderin. • Laboratory tests: • Serum iron(1mg/l) • Serum iron binding capacity (3mg) • Serum ferritin (>20ug) Shashi-May 04 Anemia - 16 Transferrin Transport Protein For Iron In Blood Fully Saturated Transferrin = TIBC 300 - 350ug/dl Fe Normal Transferrin - 1/3 Filled With Iron 100 - 120ug/dl Fe (Serum Iron) Shashi-May 04 Anemia - 17 IDA - Etiology • Blood loss – Bleeding – Parasites, Gynecologic, ulcers… • Increased need – Pregnancy, children • Poor diet / poor absorption – Malnutrition (greens & meat), malabsorption, intestinal surgery, gastric atrophy. Shashi-May 04 Anemia - 18 IDA - Pathogenesis: • Decreased Iron stores • Decreased Hb Synthesis • Delayed maturation of erythroblasts (cytoplasmic) • Decreased cytoplasm, more division (microcytes) • Decreased hb content (hypochromia) • Anemia. Shashi-May 04 Microcytic Anemia (IDA) Anemia - 20 Clinical Features: • General features of Anemia – Pallor, Weakness, Lethargy, – Breathlessness on exertion – Palpitations  heart failure  pedal edema • Special features in IDA: – Angular cheilitis, atrophic glossitis, – Oesophageal atrophy/web  dysphagia, – Koilonychia, brittle nails, gastric atrophy. Shashi-May 04 Anemia - 21 Angular cheilitis Shashi-May 04 Anemia - 22 Angular cheilitis & Glossitis …Why? Shashi-May 04 Anemia - 23 Koilonychia in Iron def. …Why? Shashi-May 04 Anemia - 24 Koilonychia in Iron def. Shashi-May 04 Anemia - 25 Hypochromic Microcytic RBC Shashi-May 04 Anemia - 26 Iron Deficiency Anemia: Shashi-May 04 Anemia - 27 IDA on Treatment : Shashi-May 04 Anemia - 28 “Seeing much, suffering much and studying much are the three pillars of learning.” –Benjamin Disraeli Shashi-May 04 Anemia - 29 Megaloblastic anemia: • Vitamin B12/Folic acid deficiency • Second most common type of anemia. • Multi System disease – All organs with increased cell division. • Macrocytic anemia, pancytopenia. • Pernicious anaemia – – autoimmune, Gastric atrophy, VitB12 def. Shashi-May 04 Anemia - 30 Megaloblastic anemia - Etiology • • • • • • Malnutrition Intrinsic factor Ab - Pernicious anemia Gastrectomy, Ileal resection Inflammatory bowel disease Malabsorption syndromes - Sprue Blind loop syndrome Shashi-May 04 Anemia - 31 Megalobl - Pathogenesis: • • • • • • • • Decreased Vit B12 / Folate Decreased DNA Synthesis Delayed maturation of erythroblasts (Nucleus) Increased cell size (macrocytes) Normal hb content (Normochromia) Decreased RBC number Decreased WBC number (pancytopenia) Anemia & Pancytopenia. Shashi-May 04 Anemia - 32 Vitamin B12 Absorption B12 B12 IF BIF 12+IF Stomach Parietal cells produce IF Ileum IF receptors IF B12 B12 Shashi-May 04 Anemia - 33 Macrocytic Anemia (Meg.): Shashi-May 04 Anemia - 34 CWM-20353-Meg.An Shashi-May 04 Anemia - 35 Macroovalocytes & Macropoly Shashi-May 04 Anemia - 36 Megaloblastic Anemia : Shashi-May 04 Anemia - 37 CWM-20353-Meg.An Shashi-May 04 Anemia - 38 “The only person who never makes a mistake is a person who never does anything” - Theodore Roosevelt Shashi-May 04 Anemia - 39 Congenital RBC Disorders: • Membrane Disorders: – Spherocytosis, Elliptocytosis • Hemoglobin Disorders: – Hemoglobinopathies - Sickle cell, HbC etc. – Thalassemia Syndromes - , ,  • Enzyme disorders: – G6PD, PK deficiency Shashi-May 04 Differential diagnosis of Anemia Low Hb=Anemia MCV Low microcytic Measure Ferritin Low Iron def Anemia Normal/high Normal normocytic High macrocytic Measure B12 + folate Normal Anemia of chronic disease/ Congenital Hb dis. Reticulocyte count Low Megaloblastic anemia Hemolytic anemia or blood loss high low Anemia of chronic disease Renal failure Marrow failure Anemia - 42 Anemia with Low MCV and Low Retics • • • • • • Differential diagnosis Iron deficiency (Micro Hypo - severe) Anemia of chronic disease (mild micro/hypo) Laboratory evaluation Iron, iron-binding capacity, and ferritin Blood smear – Micro/hypo, Pencil cells. Shashi-May 04 Anemia - 43 Anemia with High MCV • • • • • • • • Differential diagnosis Megaloblastic anemia – B12, Folate Nonmegaloblastic anemia – No def. High retics – bleeding, hemolysis * Laboratory evaluation Serum B12, RBC folate levels. Blood film – macroovalocytes, pancytopenia Bone marrow – dysplasia, neoplasia. Shashi-May 04 Anemia - 44 Anemia with Normal MCV • Differential diagnosis • Primary bone marrow failure – Aplastic anemia, drugs, chemotherapy • Secondary bone marrow failure – Uremia, Endocrine disorders, AIDS, – Anemia of chronic disease • Laboratory evaluation • Blood smear & Iron, TIBC, Ferritin. • Bone marrow smear and iron stores • Kidney, Thyroid & liver function tests, Cortisol levels • Erythropoietin level Shashi-May 04 Anemia - 45 Anemia with high Retics • Differential diagnosis: – Bleeding – blood loss internal/external – Hemolysis – immune, mechanical, toxic, inf. • Laboratory evaluation • Blood film, nRBC, spherocytes, Parasites, Retics. • Hemolysis – indirect Bilirubin, Haptoglobin, • Direct and indirect Coombs test • Hemoglobin electrophoresis, G6PD screen etc. Shashi-May 04 Anemia - 46 Bone Marrow Cellularity: Normal Hypercellular Hypocellular Shashi-May 04 Anemia - 47 ß Thalassemia Major: Shashi-May 04 Anemia - 48 Sickle Cell Disease: Shashi-May 04 Anemia - 49 Polychromasia - Hemolytic An. Shashi-May 04 Anemia - 50 Warm Ab IHA: Shashi-May 04 Anemia - 51 Microangiopathic Hemolytic A. Shashi-May 04 Anemia - 52 Thalassemia Trait: Shashi-May 04 Anemia - 53 Thalassemia Major: Shashi-May 04 Anemia - 54 Her. Spherocytosis: Shashi-May 04 Anemia - 55 Hereditary Elliptocytosis: Shashi-May 04 Anemia - 56 G6PD Deficiency Anemia: Shashi-May 04 Anemia - 57 Causes of High Hct/polycythemia • Relative or spurious erythrocytosis – Hemoconcentration secondary to dehydration – (diarrhea, diaphoresis, diuretics, deprivation of water, emesis, ethanol, etc.) • Absolute erythrocytosis (True ): – Tissue hypoxia – Smoking (Co), High altitude, Pumonary disease, respiratory def. Cardiac shunts, High oxygen-affinity Hb. – High EPO - Tumors eg. HCC. – Androgen therapy – Primary - Polycythemia vera Shashi-May 04 The only person who never makes a mistake is the person who never does anything…! - Theodore Roosevelt