Human Pathophysiology

1. Denver School of Nursing Human Pathophysiology Bio 206 / 308 – ch 19 & 20 Hemo PATH

2. Hematology • Chapter 19 & 20 Image Source: http://www.beliefnet.com

3. Hematology Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

4. Components of the Hematologic System • Composition of blood • 90% water and 10% solutes • 6 quarts (5.5 L = “about 6 liters”) • Plasma • 55% to 60% of the blood volume • Organic and inorganic elements

5. Components of the Hematologic System • Chief Function • Delivery of substances needed for cellular metabolism • Removal of wastes • Defense against microorganisms and injury • Maintenance of acid-base balance

6. Components of the Hematologic System • Composition of blood • Plasma proteins • Albumins • Function as carriers and control the plasma oncotic pressure • Globulins • Carrier proteins and immunoglobulins (antibodies) • Clotting factors • Mainly fibrinogen

7. Components of the Hematologic System • Composition of blood • Cellular components • Erythrocytes • Most abundant cell in the body • Responsible for tissue oxygenation • Biconcavity and reversible deformity • 120-day life cycle

9. Composition of Blood • Cellular components • Leukocytes (white blood cells) • Defend the body against infection and remove debris • Granulocytes • Membrane-bound granules in their cytoplasm • The granules contain enzymes capable of destroying microorganisms • Inflammatory and immune functions • Capable of ameboid movement (diapedesis)

10. Composition of Blood • After all of your immuno studies what blood cells would you consider to be granulocytes??

11. Composition of Blood • Granulocytes • Neutrophils • Polymorphonuclear neutrophil (PMN) • Phagocytes in early inflammation • Eosinophils • Eosinophils ingest antigen-antibody complexes • Induced by IgE hypersensitivity • Increase in parasitic infections

12. Composition of Blood • Granulocytes- basophils • Mast cells • Central cell in inflammation • Found in vascularized connective tissue • Basophils • Structurally and functionally similar to mast cells

13. Composition of Blood • Agranulocytes • Monocytes and macrophages make up the mononuclear phagocyte system (MPS) • Monocytes • Macrophages • Lymphocytes-T & B • Natural killer (NK) cells

15. Composition of Blood • Platelets • Disk-shaped cytoplasmic fragments • Essential for blood coagulation and control of bleeding • Thrombopoietin • Main regulator of platelets

17. Lymphoid Organs • Spleen • Largest secondary lymphoid organ • Splenic pulp • Masses of lymphoid tissue containing macrophages and lymphoid tissue • Venous sinuses • Phagocytosis of old, damaged, and dead blood cells • Blood storage

18. Lymphoid Organs • Lymph nodes • Part of the immune and hematologic systems • Facilitates maturation of lymphocytes • Transports lymphatic fluid back to the circulation • Cleanses the lymphatic fluid of microorganisms and foreign particles

19. Lymphoid Organs

20. Mononuclear Phagocyte System (MPS) • The MPS consists of a line of cells that originate in the bone marrow, are transported into the bloodstream, differentiate into monocytes, and settle in the tissues as mature macrophages • Cells of the MPS ingest and destroy microorganisms and foreign material • The MPS is mostly the liverand spleen

21. Hematopoiesis • Hematopoiesis is the process of blood cell production • Two stages • Mitosis • Mitosis stops before the cell enters the peripheral blood • Maturation and differentiation

22. Hematopoiesis • Stem cell system • Pluripotent stem cells • Colony-stimulating factors • Bone marrow • Also called myeloid tissue • Red and yellow bone marrow • Adult active bone marrow • Pelvic bones, vertebrae, cranium and mandible, sternum and ribs, humerus, and femur

23. Hematology – Which Filter is this?? Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

24. Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

26. Erythropoiesis • Erythrocytes are derived from erythroblasts (normoblasts) • Maturation is stimulated by erythropoietin

27. Erythropoiesis • Sequence • Uncommitted pluripotent stem cell, committed proerythroblast, normoblast, basophilic normoblast, polychromatophilicnormoblast, orthochromicnormoblast, reticulocyte (nucleus is lost), erythrocyte • In each step the quantity of hemoglobinincreases and the nucleus decreases in size

28. Erythropoiesis

30. Regulation of Erythropoiesis • Numbers of circulating red cells in healthy individuals remain constant • The peritubular cells of the kidney produce erythropoietin • Hypoxia stimulates the production and release of erythropoietin

31. Regulation of Erythropoiesis • Erythropoietin causes an increase in red cell production and release from bone marrow

32. Red Blood Cells Source: googleimages.com

33. Hemoglobin Synthesis • Oxygen-carrying protein of the erythrocyte • A single erythrocyte contains as many as 300 million hemoglobin molecules • Two pairs of polypeptide chains • Globulins

34. Hemoglobin Synthesis • Four colorful iron-protoporphyrin complexes • Adult hemoglobin • Two alpha chains and two beta chains

35. Hemoglobin Synthesis Source: Huether: Understanding Pathophysiology, 4th Edition, 2008

36. Hemoglobin Source: Huether: Understanding Pathophysiology, 4th Edition, 2008

37. Hemoglobin Synthesis • Nutritional requirements • Building blocks • Proteins • Amino acids • Vitamins • Vitamins B12, B6, B2, E, and C; folic acid; pantothenic acid; and niacin • Minerals • Iron and copper • Folate

38. Hemoglobin Synthesis • Iron cycle • Total body iron is bound to heme or stored bound to ferritin or hemosiderin mononuclear phagocytes and hepatic parenchymal cells • Less than 1 mg per day is lost in the urine, sweat, epithelial cells, or from the gut • Transferrin • Apotransferrin-w/o Oxygen

39. Iron Cycle Source: Huether: Understanding Pathophysiology, 4th Edition, 2008

40. Normal Destruction of Senescent Erythrocytes • Aged red cells are sequestered and destroyed by macrophages of the MPS, primarily in the spleen • The liver takes over if the spleen is absent • Globin chains are broken down into amino acids • Role of B12 & Folate in RBC life span

41. Normal Destruction of Senescent Erythrocytes • Porphyrin is reduced to bilirubin, transported to the liver, and secreted in the bile

42. Hematology Path • What is the most common cause of hypocalcemia? • What is the largest protein molecule in blood? Source: Robbins Pathologic Basis of Disease 8th Edition 2010

43. Hematology – Iron Cycle Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008 (Fig 19-13)

44. Hematology –Metabolism of Bilirubin Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008 (Fig 19-14)

45. Development of Leukocytes • Leukocytes arise from stem cells in the bone marrow • Granulocytes mature in the bone marrow • Agranulocytes and monocytes are released into the bloodstream before they fully mature

46. Development of Leukocytes • Growth factors and colony-simulating factors encourage production and maturation of leukocytes

47. White Blood Cells

48. Development of Platelets • Endomitosis • The megakaryocyte undergoes the nuclear phase of cell division but fails to undergo cytokinesis • The megakaryocyte expands due to the doubling of the DNA and breaks up into fragments

49. Development of Platelets • Platelet levels are maintained by thrombopoietinand IL-11 • Platelets circulate for 10 days before losing their functional capacity

50. Hemostasis • Hemostasis means arrest of bleeding • Requirements • Platelets • Clotting factors • Blood flow and shear forces • Endothelial cells • Fibrinolysis