1. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 27 Disorders of Red Blood Cells

2. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Red Blood Cell Development Erythroblasts are continuously being formed from the pluripotent stem cells in the bone marrow. –They move through a series of divisions to develop into mature red blood cells. –Normoblast to reticulocyte, the red blood cell accumulates hemoglobin as the nucleus condenses and is lost. –The red cell loses its mitochondria and ribosomes.

3. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Function of the Red Blood Transportation of oxygen to the tissues –Hemoglobin binds some carbon dioxide and carries it from the tissues to the lungs. –The hemoglobin molecule is composed of two pairs of structurally different polypeptide chains. Each of the four polypeptide chains consists of a globin (protein) portion and a heme unit, which surrounds an atom of iron that binds oxygen.

4. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Function of the Red Blood (cont.) –Each molecule of hemoglobin can carry four molecules of oxygen. The production of each type of globin chain is controlled by individual structural genes with five different gene loci. –Mutations can occur anywhere in these five loci.

5. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Erythropoiesis Red cells are produced in the red bone marrow after birth. Until 5 years of age, almost all bones produce red cells to meet growth needs; after 5 years, bone marrow activity gradually declines. After 20 years, red cell production takes place mainly in the membranous bones of the vertebrae, sternum, ribs, and pelvis. With this reduction in activity, the red bone marrow is replaced with fatty yellow bone marrow.

6. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hemoglobin Structure Globin chains –α –β Heme –Iron –Porphyrin Oxygen binding

7. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Red Blood Cell Destruction The red blood cell has a life span of approximately 120 days. –It is broken down in the spleen. –The degradation products (iron and amino acids) are recycled. The heme molecule is converted to bilirubin and transported to the liver. –It is removed and rendered water soluble for elimination in the bile.

8. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Bilirubin The heme unit is converted to bilirubin. Bilirubin is insoluble in plasma and attaches to plasma proteins for transport. –Unconjugated Removed from the blood by the liver and conjugated with glucuronide to render it water soluble –Conjugated Jaundice

9. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Bilirubin is an important indicator of which of the following: –A. Rate of RBC production –B. Rate of hemoglobin production –C. Rate of RBC breakdown –D. Rate of hemoglobin oxidation

10. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer C: Rate of RBC breakdown Rationale: Bilirubin is a product of RBC breakdown and will be elevated if breakdown is accelerated (hemolytic anemia).

11. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Laboratory Tests for Red Blood Cells Red blood cell count (RBC) –Measures the total number of red blood cells in 1 mm 3 of blood Percentage of reticulocytes (normally approximately 1%) –Provides an index of the rate of red cell production

12. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Laboratory Tests for Red Blood Cells (cont.) Hemoglobin (grams per 100 mL of blood) –Measures the hemoglobin content of the blood Hematocrit –Measures the volume of red cell mass in 100 mL of plasma volume

13. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Transfusion Therapy Provides the means for replacement of red blood cells and other blood components Four major ABO blood types are determined by the presence or absence of two red cell antigens: A and B. –The presence of D antigen determines the Rh- positive type. –The absence of the D antigen determines the Rh- negative type.

14. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Red Blood Cell Components Used in Transfusion Therapy Whole blood Red blood cells Leukocyte-reduced blood cells Washed red blood cells Frozen red blood cells

15. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Signs and Symptoms of Transfusion Reactions Sensation of heat along the vein where the blood is being infused Flushing of the face Urticaria, headache, pain in the lumbar area Chills, fever, constricting pain in the chest Cramping pain in the abdomen Nausea, vomiting Tachycardia, hypotension, and dyspnea

16. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Anemia Definition –An abnormally low number of circulating red blood cells or level of hemoglobin, or both –Results in diminished oxygen-carrying capacity Causes –Excessive loss or destruction of red blood cells –Deficient red blood cell production because of a lack of nutritional elements or bone marrow failure

17. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Manifestations of Anemia Impaired oxygen transport with the resulting compensatory mechanisms Reduction in red cell indices and hemoglobin levels Signs and symptoms associated with the pathologic process that is causing the anemia

18. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Anemias of Deficient Red Cell Production Iron deficiency anemia Megaloblastic anemias –Cobalamin deficiency anemia –Folic acid deficiency anemia Aplastic anemia Chronic disease anemia

19. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Manifestations of Anemia are dependent upon the causative factor in the initiation of the disease. True or False

20. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer False Rationale: Regardless of the causation, the main detrimental effect is systemic hypoxia.

21. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Which of the following disease etiologies may be directly related to dietary insufficiencies? –A. Erythroblastosis fetalis –B. Sickle cell anemia –C. Polycythemia vera –D. Iron deficiency anemia

22. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins D. Iron deficiency anemia Rationale: Iron deficiency anemia can be caused by a decreased iron intake. Answer

23. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins G6PD A hereditary deficiency of glucose-6-phosphate dehydrogenase predisposes to oxidative denaturation of hemoglobin, with resultant red cell injury and lysis.

24. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Intravascular and Extravascular Hemolysis Extravascular hemolysis occurs when red cells become less deformable, making it difficult for them to traverse the splenic sinusoids. Intravascular hemolysis occurs as a result of complement fixation in transfusion reactions, mechanical injury, or toxic factors.

25. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Sickle Cell Disease and Thalassemias Sickle cell disease is an inherited disorder in which an abnormal hemoglobin (hemoglobin S [HbS]) leads to chronic hemolytic anemia, pain, and organ failure. The thalassemias are a group of inherited disorders of hemoglobin synthesis leading to decreased synthesis of either the α- or β-globin chains of HbA.

26. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Cause of Sickling in Sickle Cell Disease The abnormal structure of HbS results from a point mutation in the β chain of the hemoglobin molecule, with an abnormal substitution of a single amino acid, valine, for glutamic acid.

27. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Iron-Deficiency Anemia Iron deficiency is a common worldwide cause of anemia affecting people of all ages. The anemia results from dietary deficiency, loss of iron through bleeding, or increased demands. Because iron is a component of heme, a deficiency leads to decreased hemoglobin synthesis and consequent impairment of oxygen delivery.

28. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Vitamin B 12 Deficiency The hallmark of vitamin B 12 deficiency is megaloblastic anemia. When vitamin B 12 is deficient, the red cells that are produced are abnormally large because of excess cytoplasmic growth and structural proteins.

29. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Causes of Aplastic Anemia Among the causes of aplastic anemia are exposure to high doses of radiation, chemicals, and toxins that suppress hematopoiesis directly or through immune mechanisms.

30. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Polycythemia Definition –A condition in which the red blood cell mass is increased. Types –Relative polycythemia: results from a loss of vascular fluid and is corrected by replacing the fluid

31. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Polycythemia (cont.) –Primary polycythemia: a proliferative disease of the bone marrow with an absolute increase in total red blood cell mass accompanied by elevated white cell and platelet counts –Secondary polycythemia: results from increased erythropoietin levels caused by hypoxic conditions such as chronic heart and lung disease

32. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Polycythemia Manifestations Variable and related to an increase in RBCs, hemoglobin level, and hematocrit with increased blood volume and viscosity –Splenomegaly –Depletion of iron –Disrupted cardiac output –Hypertension –Decreased cerebral blood flow –Venous stasis –Thromboembolism and hemorrhage

33. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Neonatal Blood Hemoglobin concentrations at birth are high, reflecting the high synthetic activity in utero to provide adequate oxygen delivery. –HbF versus HbA Affinity of F versus A Hyperbilirubinemia –Unconjugated versus conjugated –Phototherapy Hemolytic disease

34. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Aging and Red Blood Cells Age-associated decline in the hematopoietic reserve –Reduction in hematopoietic progenitors –Reduced production of hematopoietic growth factors –Inhibition of erythropoietin –Inflammatory cytokines interfere with erythropoietin interaction with its receptors.

35. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Aging and Red Blood Cells (cont.) Anemia –Hb decreases with age. –RBC production decreases with age. –Complete blood count Peripheral blood smear and a reticulocyte count and index –Studies to rule out comorbid conditions such as malignancy, gastrointestinal conditions that cause bleeding, and pernicious anemia