Altered Hematologic Function: Erythrocytes

1. Altered Hematologic Function:Erythrocytes

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

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

5. Plasma • 92 % Water • 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 • Globulins – 38 % - antibodies synthesized by plasma cells • Clotting factors – fibrinogen – 4 %

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

7. Formed elements • 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 • 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 → • Stem cell is signaled to differentiate into the needed type of blood cell • Hematopoiesis / cell breakdown continue through life.

10. Erythrocytes (RBC’s) • Most abundant blood cell type • Transport gases • Shape is important • Large surface to volume ratio • Reversible deformability – can change shape • 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) • 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 CO2 is bound to globin portion • 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 • RBC’s are removed from circulation by the liver and spleen • Broken down into heme and globin portions • Globin is broken down into amino acids • Iron is removed from heme and stored or recycled • Heme is broken down into biliverdin and then into bilirubin

16. Usually eliminated in bile. • To produce more RBC’s, the body needs sufficient iron and amino acids as well as the vitamins folate (folic acid) and vitamin B12

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

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

19. Classification of Anemias • 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. • Additional terms: • Anisocytosis – various sizes • Poikilocytosis – various shapes

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.

21. These anemias are the result of: • Ineffective DNA synthesis • Commonly due to folate and B12 (cobalamin) deficiencies – malabsorption or malnutrition • These cells die prematurely, decreasing the numbers of RBC’s in circulation • DNA synthesis is blocked or delayed, but RNA replication and protein synthesis are normal.

22. Pernicious Anemia • Common megaloblastic anemia • Caused by a Vitamin B12 deficiency • Pernicious means highly injurious or destructive – this condition was once fatal

23. Can be congenital – baby born with a deficiency in a protein , intrinsic factor, necessary to absorb B12 from the stomach • 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 • Females are more prone to PA , and black females have an earlier onset.

24. 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

25. Develops slowly – over 20 - 30 years • 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. • Usually a degree of neuropathy occurs • Untreated, it is fatal, us. due to heart failure

26. Folate deficiency anemias • Folic acid also needed for DNA synthesis • Demands are increased in pregnant and lactating females • Absorbed from small intestine and does not require any other elements for absorption. • Folate deficiency is more common than B12 deficiency

27. Folate deficiency is more common than B12 deficiency , esp. in alcoholics and those who are malnourished because of fad diets or diets low in vegetables. • 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.

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

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

30. 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

31. Clinical manifestations: • Early symptoms are nonspecific • 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

34. Treatment • Stop blood loss • Iron replacement therapy

35. Sideroblastic Anemia • Due to inefficient iron uptake, resulting in abnormal hemoglobin synthesis • Characterized by the presence of ringed sideroblasts in the bone marrow – red cells containing iron granules that have not been synthesized into hemoglobin, but instead are arranged in a circle around the nucleus.

36. http://sickle.bwh.harvard.edu/sideroblast.jpg

37. Can be acquired or hereditary • Acquired SA is the most common • May be idiopathic or associated with other disorders • Reversible - secondary to alcoholism, drug reactions, copper deficiency and hypothermia • Hereditary SA –rare, almost always in males – probably X-linked recessive gene.

38. Clinical manifestations • Along with cardiovascular and respiratory manifestations of anemia, may also show signs of iron overload (hemosiderosis) • Enlargement of spleen and liver • Bronze tint to skin • Heart rhythm disturbances • Impaired growth and development in young children

39. Treatment • Drug therapy – pyridoxine • Iron overload requires repeated blood removal – phlebotomies • Iron chelating agents in anemic individuals who require transfusions

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

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

42. Aplastic anemia • 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; B12 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

43. Posthemorrhagic • Caused by sudden loss of blood. • 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.

44. Hemolytic Anemia • Red blood cells are formed, but are broken down. • 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.

45. 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.

46. 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. • Sickle crisis: episodes of acute sickling that block blood flow, posing the threat of widespread and possibly life-threatening ischemic organ damage.

47. http://www.sunyniagara.cc.ny.us/val/sicklecellhigh.html

48. 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. • Only when a person inherits two defective genes does sickle cell anemia occur.

49. 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. • Problem occurs when two defective genes are inherited; heterozygotes are essentially normal.

50. 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. http://www.nlm.nih.gov/medlineplus/ency/imagepages/1498.htm