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ANEMIA

ANEMIA . IMS 423 BLOCK. Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College. Intended Learning Outcomes. Describe pathophysiology of anemia Enumerate the different types of anemia Describe the clinical features of anemia

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ANEMIA

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  1. ANEMIA IMS 423 BLOCK Dr. ShaikhMujeeb Ahmed Assistant Professor AlMaarefa College

  2. Intended Learning Outcomes • Describe pathophysiology of anemia • Enumerate the different types of anemia • Describe the clinical features of anemia • Interpret the lab results and correlate the findings with the type of anemia.

  3. ANEMIA • What is Anemia? • Anemia means - Decreased hemoglobin - Decreased RBC count - Decreased Hematocrit [PCV] • Therefore, decreased O2 carrying capacity of blood.

  4. BLOOD • Consists of 3 types of specialized cellular elements suspended in plasma (liquid portion of blood) • Erythrocytes • Red blood cells • Important in O2 transport • Leukocytes • White blood cells • Immune system’s mobile defense units • Platelets • Cell fragments • Important in hemostasis

  5. Blood Composition

  6. ERYTHROCYTES • Normal RBC count - 5 million per cubic millimeter (mm3) of blood. • Male – 5 – 5.5 / mm3 • Female 4.5 – 5 / mm3 • RBC contain hemoglobin which carries O2. • Main function of RBC – O2 transport, also CO2 transport.

  7. STRUCTURE OF RBC • RBC are biconcave discs 7.5 - 8 micrometer (µm) in diameter and 2µm thick at outer edge and 1µm thick at the center. • RBC membrane is flexible and can change as RBC pass through capillary with a narrow diameter of 5µm.

  8. HEMOGLOBIN • Hemoglobin is found only in RBC. • Normal Hemoglobin – 15 gram / dl . • Structure of Hemoglobin • It has two parts 1.Globin – protein has 4 polypeptide chain 2 αchain [141 amino acid in each chain] 2 β chain [146 amino acid in each chain] 2.Heme – 4 iron containing groups, each is bound to one polypeptide chain.

  9. HEMOGLOBIN[cont] • Each iron atom present in Heme [iron is in ferrous state] can combine reversibly with one molecule of O2, therefore, each hemoglobin molecule can take four O2 molecules in the lungs. • 98.5% of O2 is carried in the blood bound to hemoglobin. • Hemoglobin is a pigment naturally colored because of iron content.

  10. HEMOGLOBIN[cont] • It appears reddish when combine with O2, e.g. Arterial blood. • It appears bluish when deoxygenated, e.g. venous blood.

  11. HEMOGLOBIN FUNTIONS • Transports O2. • Also transports CO2. • Combines with H+ ion, therefore, plays part as buffer. • Combines with carbon monoxide (CO), therefore, can cause CO poisoning. • Nitric Oxide (NO) gas combines with hemoglobin and this NO is released at the tissues and causes vasodilation.

  12. IMPORTANT NOTE • RBC is mainly a plasma membrane having hemoglobin. • RBC has no nucleus and organelle. • Enzyme in RBC - Glycolytic enzyme, it generates energy ATP for active transport at membrane. - Carbon anhydrase enzyme for CO2 transport.

  13. ERYTHROPOIESIS • Formation and maturation of RBCs. • In adult RBC are formed in bone marrow. [Bone marrow is cellular tissue that fills the internal cavities of bones]. • Bone marrow normally generates new RBC to replace old ruptured cells. • In the fetus – RBC formation takes place in yolk sac during first 03 months of life then liver and spleen up to 7th month of intrauterine life. • Bone marrow starts from 4th month till birth of baby.

  14. ERYTHROPOIESIS • In children, most bones produce RBC by red bone marrow then red bone marrow is replaced by fatty yellow bone marrow that does not produce RBC. • In adults, red bone marrow remains in sternum, ribs, vertebrae, pelvis, upper end of long bones e.g. femur, humerus.

  15. IMPORTANT • If we need bone marrow sample for examination, we usually take from iliac crest or sternum.

  16. MAJOR STEPS IN ERYTHROPOIESIS

  17. ERYTHROPOIESIS • As RBC matures, it involves - reduction in size - disappearance of nucleus - acquiring of hemoglobin

  18. NUTRIONAL REQUIREMENT OF RBC PRODUCTION • 1. Amino Acids – for synthesis of globin of hemoglobin. • 2. Iron – If iron deficiency, it causes microcytic hypochromic anemia [small RBC with less Hb]. • 3. Vitamins – Vitamin B12 and folic acid for synthesis of nucleo protein. If less DNA metabolism affected and results in megloblastic anemia [mega means large]. • 4. Trace elements – e.g. copper, zinc, cobalt • 5. Hormones – Cortisol, growth hormone.

  19. CONTROL OF ERYTHROPOIESIS • It is done by Erythropoietin hormone. • Source of Erythropoietin – mainly kidney. • Erythropoietin is produced by the kidneys due to reduced O2 delivery to kidney. • Main stimulus for production of erythropoietin is hypoxia e.g. high altitude, anemia. • Hormone erythropoietin is secreted in blood and stimulates erythropoiesis in the bone marrow by acting on committed RBC.

  20. IMPORTANT • Normal RBC count 5 millions / mm3. • In every person, 25 trillion – 30 trillion RBC are moving through our blood vessels. • Average life of RBC is 120 days. • RBC are replaced at average rate of 2 millions to 3 millions / sec.

  21. RETICULOCYTES • It is immature erythrocyte. • Normal reticulocyte count 0.5 – 1.5% in blood. • Increased reticulocyte count in blood indicates high rate of erythropoietic activity.

  22. SYNTHETIC ERYTHROPOIETIN • Synthetic erythropoietin is given to kidney failure patients or those patients under going chemotherapy for cancer as chemotherapy affects bone marrow and developing RBC.

  23. RBC BREAKDOWN • Average life of RBC is 120 days then it is destroyed. • When RBC breakdown, they release hemoglobin. • Hemoglobin is taken by macrophages. • Hemoglobin is broken into heme + globin. • Globin is degraded into amino acids which are used. • From Hemoglobin, iron is released and passes back to blood. Porphyrin portion of hemoglobin molecule is converted into bilirubin. • Bilirubin is carried to liver [bound with albumin] and secreted in bile by liver.

  24. WHAT YOU SHOULD KNOW FROM THIS LECTURE ? • Normal RBC count, Size, Shape and Function • Life Span of RBC • Erythropoiesis in Adults & Children • Nutritional Requirement for Erythropoiesis • Erythropoietin • Functions of Hemoglobin • Importance of Reticulocyte count in blood • Hemoglobin Breakdown

  25. Classification of Anemia

  26. CLASSIFICATION OF ANEMIA • ON THE BASIS OF • Size of the RBCs • Normocytic • Microcytic • Macrocytic • Hemoglobin content • Normochromic • Hypochromic

  27. CLASSIFICATION OF ANEMIA We will define MCV, MCH, MCHC. • Mean Corpuscular Volume (MCV) it is the volume of average RBC - Normal MCV = 90 fL or 90 μ3 [MCV > 95 fL are called macrocyte] [MCV < 80 fL are called microcyte] • Mean Corpuscular Hemoglobin (MCH) – it is mean concentration of Hemoglobin in each RBC. - Normal MCH = 30 picogram [pg] • Mean corpuscular Hb concentration (MCHC) – it is hemoglobin present per 100ml of RBC. - Normal MCHC = 30 gram/100ml of RBC

  28. NORMAL VALUEs & FORMULAE FOR CALCULATION OF MCV, MCH, MCHC • Mean Corpuscular Volume (fl) • 78 – 98 (fl) • Mean Corpuscular Hemoglobin (pg) • 27 – 33 pg. • Mean corpuscular Hb concentration • 30 – 35%

  29. CAUSES OF ANEMIA

  30. EFFECTS OF ANEMIA

  31. CLINICAL FEATURES OF ANEMIA • Pallor • Tachycardia • Hyperbilirubinemia, Jaundice • Increase level of iron absorption – damage to endocrine glands

  32. BLOOD LOSS ANEMIA • Rate of hemorrhage • Bleeding is internal / external • Acute loss • Loss of intravascualr volume • Cardiovascular collapse • Normocytic normochromic type • Increase reticulocyte count • External bleeding • Iron loss – iron deficiency anemia • GI bleeding, menstrual bleeding • Chronic loss - Microcytic hypochromic anemia

  33. HEMOLYTIC ANEMIA • Characterized by; • Premature destruction of RBCs • Iron retention • Hb destruction products • Normocyticnormochromic anemia • Increase reticulocyte count • Presents with; • Fatigability • Dyspnea • Cause • Intrinsic • Cell membrane • Enzymes • Hemoglobin • Extrensic • Immune mechanism • Mechanical trauma • Infection

  34. Inherited Disorder of the Red Cell Membrane • Heredditaryspherocytosis • Autosomal dominant triat • Abnormality of spectrin & ankyrin membrane protein • Sphere shape cells • Mild hemolytic anemia • Jaundice • Spleenomegaly • Bilirubin & • Gall stone • Treated with; • Splenectomy • Blood transfusion

  35. Inherited Disorder of the Red Cell Membrane • Sickle cell disease • Abnormal Hb S • Chronic hemolytic anemia • Mean life span of RBCs is 20 days • Pain • Organ failure • HbS gene as recessive inheritance • Sickle cell trait • Sickle cell disease • 30% in African population;

  36. Definition • Autosomal recessive genetic disease: • β-globin gene (chromosome 11q) mutation GAGGTG at 6thcodon • Glutamic Acid  Valineat the 6th amino acid along the β-globin chain • α2β2 = normal hemoglobin • α2βS = heterozygote = Sickle trait • α2S2 = homozygous recessive = Sickle cell disease

  37. Effect of Sickling

  38. Sickling mechanism Hb SS • Precipitating Factors • Hypoxia • Acidosis • Dehydration • Infections Deoxygenated Polymerise Pseudocrystalline Tactoids

  39. Clinical course • Homozygous for HbS experiences • Severe hemolytic anemia • Hyperbilirubinemia • Jaundice • Gall stones • Vaso-occlusive crises

  40. Complication • Vaso-occlusive pain crises • Acute chest syndrome

  41. Vaso-occlusive pain crisis • Common sites • Abdomen • Chest • Bone • Joints • Infarction of • Liver • Spleen • Kidney • Heart • Retina

  42. Acute chest syndrome • Atypical pneumonia resulting from pulmonary infarction • Pulmonary infiltrates • Shortness of breath • Fever • Chest pain • Cough

  43. Aplastic crises • Infection with erythrovirus 19 • Severe red cell aplasia • Reduced reciculocyte count

  44. Diagnosis & treatment • Clinical findings + blood smear – sickle cells • Hemoglobin solubility result • RBCs + sodium dithionate = turbid solution • Hemoglobin electrophoresis Management • Prophylactic treatment with penicillin • Immunization for • H. influenzae • Hepatitis B • Pneumococcal vaccine

  45. Diagnosis & treatment • Vaso-occlusive crises • Rehydration, analgesics, antibiotics, transfusion • Hydroxyurea – to reduce pain crises • Bone marrow & stem cell transplantation • Gene therapy

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