1. Altered Hematologic Function: Erythrocytes

2. Physical Characteristics of Blood Heavier, thicker, and 3-4 X more viscous than water Heavier, thicker, and 3-4 X more viscous than water 38 o C (100.4 o F) 38 o C (100.4 o F) pH : 7.35 – 7.45 pH : 7.35 – 7.45 4-6 liters in an adult 4-6 liters in an adult Varies with electrolyte concentration and amount of adipose tissue Varies with electrolyte concentration and amount of adipose tissue

3. Blood Volume Blood volume is about 8% of body weight. Blood volume is about 8% of body weight. 1 kg of blood ≈ 1 L of blood 1 kg of blood ≈ 1 L of blood 70 kg X 0.08 = 5.6 Kg = 5.6 L 70 kg X 0.08 = 5.6 Kg = 5.6 L 45 % is formed elements 45 % is formed elements 55% plasma 55% plasma

5. Plasma 92 % Water 92 % Water 8% Solutes – organic and inorganic 8% Solutes – organic and inorganic –Plasma proteins – largest proportion of solutes Albumins – 58 % of the proteins – maintain osmotic (oncotic) pressure – hold water in the blood Albumins – 58 % of the proteins – maintain osmotic (oncotic) pressure – hold water in the blood Globulins – 38 % - antibodies synthesized by plasma cells Globulins – 38 % - antibodies synthesized by plasma cells Clotting factors – fibrinogen – 4 % (Serum without) Clotting factors – fibrinogen – 4 % (Serum without)

6. Other components of plasma Nutrients Nutrients Hormones Hormones Electrolytes Electrolytes Waste products Waste products Dissolved gases Dissolved gases

7. Formed elements Three types: Three types: Erythrocytes – red blood cells- RBC’s Leukocytes – white blood cells – WBC’s Thrombocytes – platelets – cell fragments

8. Hemopoiesis (Hematopoiesis) All blood cells common from a common stem cell – Hemocytoblast All blood cells common from a common stem cell – Hemocytoblast These are in the bone marrow (red) and develop into blood cells as needed by the body These are in the bone marrow (red) and develop into blood cells as needed by the body Mitosis is signaled by biochemicals released from the body → Mitosis is signaled by biochemicals released from the body → Stem cell is signaled to differentiate into the needed type of blood cell Stem cell is signaled to differentiate into the needed type of blood cell Hematopoiesis / cell breakdown continue through life. Hematopoiesis / cell breakdown continue through life.

10. Erythrocytes (RBC’s) Most abundant blood cell type Most abundant blood cell type Transport gases Transport gases Shape is important Shape is important –Large surface to volume ratio –Reversible deformability – can change shape Development is called erythopoiesis Development is called erythopoiesis –Erythropoietin is a hormone produced by the kidneys in response to low blood oxygen levels; signals bone marrow to increase RBC production

12. Cytoplasm is mostly hemoglobin (lacks organelles, no nucleus) Cytoplasm is mostly hemoglobin (lacks organelles, no nucleus) Made up of 4 peptide chains that form the globin portion and four molecules of the pigment heme which contains an atom of iron Made up of 4 peptide chains that form the globin portion and four molecules of the pigment heme which contains an atom of iron –Oxygen binds to iron in heme (also CO) –23 % of CO 2 is bound to globin portion If there is a problem with any part of the molecule it may not be functional. If there is a problem with any part of the molecule it may not be functional.

14. RBC breakdown Healthy RBC’s live about 120 days; we break down about 174 million per minute Healthy RBC’s live about 120 days; we break down about 174 million per minute RBC’s are removed from circulation by the liver and spleen RBC’s are removed from circulation by the liver and spleen Broken down into heme and globin portions Broken down into heme and globin portions Globin is broken down into amino acids Globin is broken down into amino acids Iron is removed from heme and stored or recycled Iron is removed from heme and stored or recycled Heme is broken down into biliverdin and then into bilirubin Heme is broken down into biliverdin and then into bilirubin

16. Usually eliminated in bile. Usually eliminated in bile. If liver insufficiency, bilirubin accumulates in blood  Jaundice  too much  kernicterus If liver insufficiency, bilirubin accumulates in blood  Jaundice  too much  kernicterus To produce more RBC’s, the body needs sufficient iron and amino acids as well as the vitamins folate (folic acid) and vitamin B 12 To produce more RBC’s, the body needs sufficient iron and amino acids as well as the vitamins folate (folic acid) and vitamin B 12

17. Abnormalities Anemias Anemia is the inability of the blood to carry sufficient oxygen to the body. Anemia is the inability of the blood to carry sufficient oxygen to the body. low #’s of RBCs low #’s of RBCs lack of hemoglobin lack of hemoglobin

18. Clinical Manifestations Pallor Pallor Fatigue Fatigue Weakness; exercise intolerance Weakness; exercise intolerance Dyspnea Dyspnea Syncope (fainting) and dizziness Syncope (fainting) and dizziness Angina Angina Tachycardia (increased heart rate) Tachycardia (increased heart rate) Organ dysfunctions Organ dysfunctions

19. Classification of Anemias Identified by their causes or by the changes that affect the size, shape or substance of the erythrocyte Identified by their causes or by the changes that affect the size, shape or substance of the erythrocyte Terms that end with –cytic refer to cell size, and those that end in –chromic refer to hemoglobin content. Terms that end with –cytic refer to cell size, and those that end in –chromic refer to hemoglobin content.

20. Macrocytic / Megaloblastic Anemia Characterized by abnormally large stem cells (megaloblasts) in the marrow that mature into erythrocytes that are unusually large in size, thickness and volume. The hemoglobin content is normal, so these are normochromic anemias. Characterized by abnormally large stem cells (megaloblasts) in the marrow that mature into erythrocytes that are unusually large in size, thickness and volume. The hemoglobin content is normal, so these are normochromic anemias.

21. These anemias are the result of: These anemias are the result of: –Ineffective DNA synthesis Commonly due to folate and B 12 (cobalamin) deficiencies – mal-absorption or malnutrition Commonly due to folate and B 12 (cobalamin) deficiencies – mal-absorption or malnutrition These cells die prematurely, decreasing the numbers of RBC’s in circulation These cells die prematurely, decreasing the numbers of RBC’s in circulation

22. Pernicious Anemia Common megaloblastic anemia Common megaloblastic anemia Caused by a Vitamin B 12 deficiency Caused by a Vitamin B 12 deficiency Pernicious means highly injurious or destructive – this condition was once fatal Pernicious means highly injurious or destructive – this condition was once fatal

24. Can be congenital – baby born with a deficiency in a protein, intrinsic factor, necessary to absorb B 12 from the stomach Can be congenital – baby born with a deficiency in a protein, intrinsic factor, necessary to absorb B 12 from the stomach Adult onset – one example is an autoimmune dysfunction - type A chronic atrophic gastritis – where there is destruction of the gastric mucosa Adult onset – one example is an autoimmune dysfunction - type A chronic atrophic gastritis – where there is destruction of the gastric mucosa Most commonly affects people over 30 Most commonly affects people over 30 Females are more prone to pernicious anemia, and black females have an earlier onset. Females are more prone to pernicious anemia, and black females have an earlier onset.

25. Pernicious Anemia is also associated with: Heavy alcohol consumption Hot tea Cigarette smoking Other autoimmune conditions Complete or partial removal of the stomach can cause intrinsic factor deficiency

26. Develops slowly – over 20 - 30 years Develops slowly – over 20 - 30 years Usually severe by the time individual seeks treatment Usually severe by the time individual seeks treatment Early symptoms ignored because they are nonspecific and vague- infections, mood swings, and gastrointestinal, cardiac or kidney ailments. Early symptoms ignored because they are nonspecific and vague- infections, mood swings, and gastrointestinal, cardiac or kidney ailments. Usually a degree of neuropathy occurs Usually a degree of neuropathy occurs Untreated, it is fatal, due to heart failure Untreated, it is fatal, due to heart failure

27. Folate deficiency anemia Folic acid also needed for DNA synthesis Folic acid also needed for DNA synthesis Demands are increased in pregnant and lactating females Demands are increased in pregnant and lactating females Absorbed from small intestine and does not require any other elements for absorption. Absorbed from small intestine and does not require any other elements for absorption. Folate deficiency is more common than B 12 deficiency Folate deficiency is more common than B 12 deficiency

28. Folate deficiency is more common than B 12 deficiency, esp. in alcoholics and those who are malnourished because of fat diets or diets low in vegetables. Folate deficiency is more common than B 12 deficiency, esp. in alcoholics and those who are malnourished because of fat diets or diets low in vegetables. Estimated that 10 % of North Americans are folate deficient. Estimated that 10 % of North Americans are folate deficient. Specific manifestations include cheilosis, (scales and fissures of the mouth), inflammation of the mouth, and ulceration of the buccal mucosa and tongue. Specific manifestations include cheilosis, (scales and fissures of the mouth), inflammation of the mouth, and ulceration of the buccal mucosa and tongue.

31. Microcytic – Hypochromic Anemias Characterized by abnormally small RBC’s that contain reduced amounts of hemoglobin. Characterized by abnormally small RBC’s that contain reduced amounts of hemoglobin. Possible causes: Possible causes: –Disorders of iron metabolism –Disorders of porphyrin and heme synthesis –Disorders of globin synthesis

32. Iron Deficiency Anemia Most common type of anemia throughout the world. Most common type of anemia throughout the world. High risk: High risk: –Individuals living in poverty –Females of childbearing age –Children Common causes Common causes –Insufficient iron intake –Chronic blood loss – even 2- 4 ml/ day –In men –gastrointestinal bleeding –In women – profuse menstruation, pregnancy

34. Other causes: Other causes: –Use of medications that cause GI bleeding –Surgical procedures that decrease stomach acidity, intestinal transit time, and absorption –Eating disorders such as pica

35. Clinical manifestations: Early symptoms are nonspecific Early symptoms are nonspecific Later - changes in epithelial tissue: Later - changes in epithelial tissue: –Fingernails become brittle and concave (koilonychia) –Tongue papillae atrophy and cause soreness, redness and burning –Corners of mouth become dry and sore –Difficulty in swallowing due to web of mucus and inflammatory cells at opening of esophagus

38. Treatment Stop blood loss Stop blood loss Iron replacement therapy Iron replacement therapy

39. Normocytic – Normochromic Anemias RBC’s are normal in size and hemoglobin content, but are too few in number. RBC’s are normal in size and hemoglobin content, but are too few in number. Less common than the macrocytic and microcytic anemias Less common than the macrocytic and microcytic anemias

40. Several types that do not have anything else in common: Several types that do not have anything else in common: –Aplastic –Posthemorrhagic –Hemolytic –Sickle cell –Anemia of chronic inflammation

41. Aplastic anemia Fortunately, this condition is rare; it means the RBC’s are not being produced. Bone marrow stem cells are not functioning. Fortunately, this condition is rare; it means the RBC’s are not being produced. Bone marrow stem cells are not functioning. Can result from disorders of the bone marrow, such as cancer; autoimmune diseases; renal failure due to lack of erythropoietin; B 12 or folate deficiency; congenital problems; or it may be induced by radiation, toxins or the use of some drugs, such as chloramphenicol. Can result from disorders of the bone marrow, such as cancer; autoimmune diseases; renal failure due to lack of erythropoietin; B 12 or folate deficiency; congenital problems; or it may be induced by radiation, toxins or the use of some drugs, such as chloramphenicol. Treatment – treat the underlying disorder, blood transfusions, and possibly bone marrow transplant Treatment – treat the underlying disorder, blood transfusions, and possibly bone marrow transplant

42. Posthemorrhagic Caused by sudden loss of blood. Caused by sudden loss of blood. Can be fatal if loss exceeds 40- 50 % of plasma volume. Can be fatal if loss exceeds 40- 50 % of plasma volume. Treatment is to restore blood volume by intravenous administration of saline, dextran, albumin, plasma or whole blood. Treatment is to restore blood volume by intravenous administration of saline, dextran, albumin, plasma or whole blood.

43. Hemolytic Anemia Red blood cells are formed, but are broken down. Red blood cells are formed, but are broken down. May be acquired or hereditary. May be acquired or hereditary. Acquired hemolytic anemia is extrinsic, due to factors outside the red blood cell, such as an abnormal autoimmune response that targets red cells, or by improper matches during transfusions; or due to infection, systemic diseases, or drugs or toxins. Acquired hemolytic anemia is extrinsic, due to factors outside the red blood cell, such as an abnormal autoimmune response that targets red cells, or by improper matches during transfusions; or due to infection, systemic diseases, or drugs or toxins.

44. Hereditary or intrinsic hemolytic anemias: Sickle cell anemia – due to a change in one amino acid in each of the beta-chains in the globin, under conditions of low oxygen the hemoglobin forms insoluble threads that change the shape of the erythrocyte into a crescent. This shape is not as flexible and tend to be trapped in the capillaries, where they obstruct blood flow and cause ischemic injury. Sickle cell anemia – due to a change in one amino acid in each of the beta-chains in the globin, under conditions of low oxygen the hemoglobin forms insoluble threads that change the shape of the erythrocyte into a crescent. This shape is not as flexible and tend to be trapped in the capillaries, where they obstruct blood flow and cause ischemic injury.

45. The life span of a sickled cell is only 20 days rather than 120, and is removed from circulation by the spleen. The life span of a sickled cell is only 20 days rather than 120, and is removed from circulation by the spleen. Either mechanism causes a chronic anemia. Either mechanism causes a chronic anemia. Sickle crisis: episodes of acute sickling that block blood flow, posing the threat of widespread and possibly life- threatening ischemic organ damage. Sickle crisis: episodes of acute sickling that block blood flow, posing the threat of widespread and possibly life- threatening ischemic organ damage.

47. This is an inheritable condition. This is an inheritable condition. If a person has only one defective gene, it is called sickle cell trait, and the person is essentially normal. This condition tends to persist because it protects against malaria. When a cell becomes infected by the parasite, the cell sickles and is removed from circulation, preventing reproduction of the parasite. If a person has only one defective gene, it is called sickle cell trait, and the person is essentially normal. This condition tends to persist because it protects against malaria. When a cell becomes infected by the parasite, the cell sickles and is removed from circulation, preventing reproduction of the parasite. Only when a person inherits two defective genes does sickle cell anemia occur. Only when a person inherits two defective genes does sickle cell anemia occur.

48. Thalassemia is another hemolytic disorder where the alpha or beta chains of the globin are defective, or the beta chain is not produced. When the beta protein is lacking, the alpha protein accumulates and causes destructive membrane effects, causing these cells to be rapidly removed from the circulation. Thalassemia is another hemolytic disorder where the alpha or beta chains of the globin are defective, or the beta chain is not produced. When the beta protein is lacking, the alpha protein accumulates and causes destructive membrane effects, causing these cells to be rapidly removed from the circulation. Highest incidence in populations around the Mediterranean and Southeast Asia. Highest incidence in populations around the Mediterranean and Southeast Asia. Problem occurs when two defective genes are inherited; heterozygotes are essentially normal. Problem occurs when two defective genes are inherited; heterozygotes are essentially normal.

49. Thalassemia major is an inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. This is the most severe form of anemia, and the oxygen depletion in the body becomes apparent within the first 6 months of life. If left untreated, death usually results within a few years. Note the small, pale (hypochromic), abnormally-shaped red blood cells associated with thalassemia major. Thalassemia major is an inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. This is the most severe form of anemia, and the oxygen depletion in the body becomes apparent within the first 6 months of life. If left untreated, death usually results within a few years. Note the small, pale (hypochromic), abnormally-shaped red blood cells associated with thalassemia major.

51. Myeloproliferative Disorders The opposite of anemias – here we have too many RBC’s. The opposite of anemias – here we have too many RBC’s. Polycythemia – excessive production of RBC’s Polycythemia – excessive production of RBC’s –Primary polycythemia – cause is unknown, but is in effect, a benign tumor of the marrow, leading to increased numbers of stem cells and therefore RBC’s, and splenomegally. –Polycythemia vera – rare, mostly Northern European Jewish males between 60 – 80 yrs.

53. Secondary Polycythemia Due to the overproduction of erythropoietin caused by hypoxia. This is more common. Due to the overproduction of erythropoietin caused by hypoxia. This is more common. Seen in: Seen in: –Persons living at high altitudes –Smokers –COPD patients –Congestive heart failure patients

54. Polcythemia leads to : Polcythemia leads to : –Increased blood volume and viscosity –Congestion of liver and spleen –Clotting –Thrombus formation –(last two may be due increased numbers of platelets along with the increase in RBC’s due to bone marrow dysfunction.)

55. Clinical manifestation of Polycythemia Headache Headache Dizziness Dizziness Weakness Weakness Increased blood pressure Increased blood pressure Itching / sweating Itching / sweating

56. Treatment of polycythemia Reduce blood volume by phlebotomy – 300-500 ml. Reduce blood volume by phlebotomy – 300-500 ml. Treat underlying condition - Stop smoking Treat underlying condition - Stop smoking Radioactive phosphorus injections Radioactive phosphorus injections Prevent thrombosis Prevent thrombosis