1. Anemia Premed 2 Pathophysiology

2. Normal blood smear

3. Anemia Decrease in whole red cell mass Decrease in whole red cell mass Causes: Causes: 1.Excessive blood loss 1.Excessive blood loss 2. decreased in RBC production 2. decreased in RBC production 3. increased RBC loss 3. increased RBC loss

4. Anemia Caused by Blood Loss Anemia Caused by Blood Loss Red blood cells can be lost through bleeding, which can occur slowly over a long period of time, and can often go undetected. This kind of chronic bleeding commonly results from the following: Red blood cells can be lost through bleeding, which can occur slowly over a long period of time, and can often go undetected. This kind of chronic bleeding commonly results from the following:

5. Gastrointestinal conditions such as ulcers, hemorrhoids, gastritis (inflammation of the stomach) and cancer Gastrointestinal conditions such as ulcers, hemorrhoids, gastritis (inflammation of the stomach) and cancerulcers hemorrhoidsgastritis stomachcancerulcers hemorrhoidsgastritis stomachcancer Use of nonsteroidal anti-inflammatory drugs (NSAIDS) such as aspirin or Motrin Use of nonsteroidal anti-inflammatory drugs (NSAIDS) such as aspirin or Motrindrugsaspirindrugsaspirin Menstruation and childbirth in women, especially if menstrual bleeding is excessive and if there are multiple pregnancies Menstruation and childbirth in women, especially if menstrual bleeding is excessive and if there are multiple pregnancieschildbirth

6. Anemia Caused by Decreased or Faulty Red Blood Cell Production Anemia Caused by Decreased or Faulty Red Blood Cell Production The body may produce too few blood cells or the blood cells may not work properly. In either case, anemia can result. Red blood cells may be faulty or decreased due to abnormal red blood cells or the a lack of minerals and vitamins needed for red blood cells to work properly. Conditions associated with these causes of anemia include the following: The body may produce too few blood cells or the blood cells may not work properly. In either case, anemia can result. Red blood cells may be faulty or decreased due to abnormal red blood cells or the a lack of minerals and vitamins needed for red blood cells to work properly. Conditions associated with these causes of anemia include the following:

7. Sickle cell anemia Sickle cell anemia Sickle cell Sickle cell Iron deficiency anemia Iron deficiency anemia Vitamin deficiency Vitamin deficiency Bone marrow and stem cell problems Bone marrow and stem cell problems Other health conditions Other health conditions

8. Sickle cell anemia is an inherited disorder that affects African-Americans. Red blood cells become crescent-shaped because of a genetic defect. They break down rapidly, so oxygen does not get to the body's organs, causing anemia. The crescent-shaped red blood cells also get stuck in tiny blood vessels, causing pain. Sickle cell anemia is an inherited disorder that affects African-Americans. Red blood cells become crescent-shaped because of a genetic defect. They break down rapidly, so oxygen does not get to the body's organs, causing anemia. The crescent-shaped red blood cells also get stuck in tiny blood vessels, causing pain.pain

9. Iron-deficiency anemia Major cause in adults: chronic blood loss Major cause in adults: chronic blood loss menorrhagia ( heavy menses) bleeding from GIT Dietary deficiency is common after 6 months of age in infants Dietary deficiency is common after 6 months of age in infants Pallor, fatigue, dyspnea on exertion Pallor, fatigue, dyspnea on exertion

10. Iron-deficiency anemia Low hemoglobin Low hemoglobin Low hematocrit Low hematocrit Low RBC count Low RBC count Hypochromic, microcytic RBC on smear Hypochromic, microcytic RBC on smear Low serum iron Low serum iron High total iron binding capacity(TIBC) High total iron binding capacity(TIBC) Low iron store; low ferritin Low iron store; low ferritin

11. Iron deficiency anemia

12. Vitamin deficiency anemia may occur when vitamin B-12 and folate are deficient. These two vitamins are needed to make red blood cells. Conditions leading to anemia caused by vitamin deficiency include the following: Vitamin deficiency anemia may occur when vitamin B-12 and folate are deficient. These two vitamins are needed to make red blood cells. Conditions leading to anemia caused by vitamin deficiency include the following:

13. Megaloblastic anemia Presence of large, abnormal-looking erythroid precursor cells or MEGALOBLASTS in the bone marrow Presence of large, abnormal-looking erythroid precursor cells or MEGALOBLASTS in the bone marrow Cause: low vitamin B12 or folic acid Cause: low vitamin B12 or folic acid Decrease DNA synthesis  decrease DNA replication and nuclear division Decrease DNA synthesis  decrease DNA replication and nuclear division Impaired RBC production Impaired RBC production

14. Megaloblastic anemia Pancytopenia Pancytopenia low RBC low platelets low WBC Oval macrocytosis (“ big RBC”) Oval macrocytosis (“ big RBC”) Hypersegmented neutrophils (more than 5 lobes) Hypersegmented neutrophils (more than 5 lobes) Megaloblastic hyperplasia of the bone marrow Megaloblastic hyperplasia of the bone marrow

15. Hypersegmented neutrophils

16. Megaloblast

17. Megaloblastic anemia Vitamin B12 deficiency Vitamin B12 deficiency Pernicious anemia Pernicious anemia Lemon-yellow skin Lemon-yellow skin Stomatitis Stomatitis Glossitis Glossitis Demyelination of the posterior and lateral columns of the spinal cord Demyelination of the posterior and lateral columns of the spinal cord Ataxic gait, hyperreflexia, impaired position and vibration reflexes Ataxic gait, hyperreflexia, impaired position and vibration reflexes Labs: Antibodies against Intrinsic factor Abnormal Schilling test

18. Megaloblastic anemia Folate deficiency Folate deficiency Seen in alcoholics Seen in alcoholics Pregnancy Pregnancy Fad dieters Fad dieters Contraceptive pills Contraceptive pills Dilantin Dilantin Chemotherapy agents Chemotherapy agents Same presentation as B12 deficiency NO NEUROLOGIC DEFICITS

19. Anemia of Chronic disease Second most common form Second most common form May be due to rheumatoid arthritis, kidney disease, chronic infection May be due to rheumatoid arthritis, kidney disease, chronic infection Normochromic, normocytic Normochromic, normocytic In chronic disease: it may be similar to IDA, but the TIBC is low In chronic disease: it may be similar to IDA, but the TIBC is low

20. Aplastic anemia Most common cause: toxic exposure Most common cause: toxic exposureradiation chemicals – benzene antibiotics – chloramphenicol cancer drugs viruses – hepatitis C and Parvovirus

21. Aplastic anemia Hypocellular bone marrow Hypocellular bone marrow Loss of hematopoietic cells Loss of hematopoietic cells Peripheral pancytopenia Peripheral pancytopenia

22. Hemolytic anemias Immune hemolytic anemias Immune hemolytic anemias cold agglutinin disease Hemolytic disease of the newborn Membrane skeletal protein abnormalities Membrane skeletal protein abnormalities Hereditary spherocytosis Enzyme deficiency HA Enzyme deficiency HA G6PD deficiency Pyruvate kinase deficiency Hemoglobinopathies Hemoglobinopathies Hemoglobin S disorder : Sickle cell anemia Thalassemias: alpha and beta

23. Hemolytic anemias Shortened life span of RBC Shortened life span of RBC Increased destruction Increased destruction Increased unconjugated bilirubin Increased unconjugated bilirubin Pigment-containing stones Pigment-containing stones Increased urobilinogen Increased urobilinogen Hemoglobinemia, hemoglobinuria Hemoglobinemia, hemoglobinuria Disappearance of serum haptoglobulins Disappearance of serum haptoglobulins Hemosiderosis Hemosiderosis Increased erythropoiesis Increased erythropoiesis reticulocytosis reticulocytosis

24. IHA: Hemolytic disease of the newborn Erythroblastosis fetalis Erythroblastosis fetalis Maternal antibodies attack the D antigen of the Rh blood group Maternal antibodies attack the D antigen of the Rh blood group Mom: Rh (-) or “ d” Baby: Rh (+) or “D” Also seen in ABO incompatibility Also seen in ABO incompatibility Mom O, Baby A or B Mom A, Baby B or AB Mom B, Baby A or AB

25. Hemolytic disease of the newborn Kernicterus: unconjugated bilirubin accumulates in the basal ganglia and the CNS Kernicterus: unconjugated bilirubin accumulates in the basal ganglia and the CNS Hydrops fetalis Hydrops fetalis stillbirth stillbirth

26. Enzyme deficiency HA Most common form Most common form X-linked X-linked Common in 10% of African Americans; Mediterrenean Common in 10% of African Americans; Mediterrenean Acute, self-limited Acute, self-limited Hemoglobinemia, hemoglobinuria Hemoglobinemia, hemoglobinuria Triggering factors: Triggering factors:infectionsprimaquinesulfonamides

27. Heinz bodies

28. Enzyme deficiency HA Pyruvate kinase deficiency Pyruvate kinase deficiency Anemia is chronic and sustained Anemia is chronic and sustained Autosomal recessive Autosomal recessive No spherocytes seen No spherocytes seen

29. Hemoglobinopathies Abnormal hemoglobin structure Abnormal hemoglobin structure Most commonly involved: Hemoglobin S Most commonly involved: Hemoglobin S Point mutation in codon 6 of the beta-globin gene Point mutation in codon 6 of the beta-globin gene Valine is substituted for glutamic acid Valine is substituted for glutamic acid

30. Hemoglobinopathies Result: Hemoglobin S polymerizes at low oxygen tension  sickle cells  RBC membranes stiffen  hemolysis/ obstruction of the blood vessels Result: Hemoglobin S polymerizes at low oxygen tension  sickle cells  RBC membranes stiffen  hemolysis/ obstruction of the blood vessels Severe Hemolytic anemia Severe Hemolytic anemia Chronic leg ulcers Chronic leg ulcers Painful crises: limbs, back, chest, abdomen Painful crises: limbs, back, chest, abdomen Infarctions: lungs and spleen  autosplenectomy Infarctions: lungs and spleen  autosplenectomy Aplastic crisis: fall in hemoglobin Aplastic crisis: fall in hemoglobin Salmonella osteomyelitis Salmonella osteomyelitis

32. Thalassemia occurs when the red cells can't mature and grow properly. Thalassemia is an inherited condition that typically affects people of Mediterranean, African, Middle Eastern, and Southeast Asian descent. This condition can range in severity from mild to life-threatening; the most severe form is called Cooley's anemia Thalassemia occurs when the red cells can't mature and grow properly. Thalassemia is an inherited condition that typically affects people of Mediterranean, African, Middle Eastern, and Southeast Asian descent. This condition can range in severity from mild to life-threatening; the most severe form is called Cooley's anemia

33. Thalasemias Deficient production of either alpha or beta- globin chains Deficient production of either alpha or beta- globin chains Beta-thalasemia: most common form; defect in the genes coding for Beta-globin gene Beta-thalasemia: most common form; defect in the genes coding for Beta-globin gene

34. Beta-thalassemia major (Mediterrenean or Cooley anemia) Decrease hgb synthesis Decrease hgb synthesis Short rbc lifespan (due to insoluble, excess alpha- chains) Short rbc lifespan (due to insoluble, excess alpha- chains) Ineffective RBC production Ineffective RBC production Enlarged spleen Enlarged spleen Skull, facial bones and long bones distortion Microcytosis, hypochromic anemia Hemosiderosis Increase Hgb F throughout life

35. Beta-thalassemia major: target cells

36. Other forms of thalassemias Beta-thalassemia minor Beta-thalassemia minor Increase in Hgb A2 Increase in Hgb A2 Alpha-thalassemia Most common in Southeast Asia May be asymptomatic or fatal.