Structure and Function of the Hematologic System

1. Structure and Function of the Hematologic System Chapter 25

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

3. Components of the Hematologic System • Composition of blood • Plasma proteins • 7% of the plasma total weight • The majority are synthesized in the liver • Albumins • Function as carriers and control the plasma oncotic pressure • Globulins • Carrier proteins and immunoglobulins (antibodies) • Clotting factors • Mainly fibrinogen

4. 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

5. 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)

6. 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

7. Composition of Blood • Granulocytes • Mast cells • Central cell in inflammation • Found in vascularized connective tissue • Basophils • Structurally similar to mast cells • Precise function not understood

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

9. Composition of Blood • Platelets • Disk-shaped cytoplasmic fragments • Formed by fragmentation of megakaryocytes • Essential for blood coagulation and control of bleeding

10. 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

11. 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

12. Lymphoid Organs

13. 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 liver and spleen

14. Hematopoiesis • Hematopoiesis is the process of blood cell production • Two stages: • Mitosis • Mitosis stops before the cell enters the peripheral blood • Maturation

15. Hematopoiesis

16. 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

17. Colony-Stimulating Factors

18. Erythropoiesis • Erythrocytes are derived from erythroblasts (normoblasts) • Maturation is stimulated by erythropoietin • Sequence • Uncommitted pluripotent stem cell, committed proerythroblast, normoblast, basophilic normoblast, polychromatophilic normoblast, orthochromic normoblast, reticulocyte (nucleus is lost), erythrocyte • In each step the quantity of hemoglobin increases and the nucleus decreases in size

19. Erythropoiesis

20. Hemoglobin Synthesis • Oxygen carrying protein of the erythrocyte • A single erythrocyte contains as many as 300 hemoglobin molecules • Two pairs of polypeptide chains • Globulins • Four colorful iron-protoporphyrin complexes • Adult hemoglobin • Two α chains and two β chains

21. Hemoglobin Synthesis

22. 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

23. 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

24. Iron Cycle

25. 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 • Erythropoietin causes an increase in red cell production and release from bone marrow

26. Regulation of Erythropoiesis

27. 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 • Porphyrin is reduced to bilirubin, transported to the liver, and secreted in the bile

28. 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 • Growth factors and colony-simulating factors encourage production and maturation of leukocytes

29. 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 • Platelet levels are maintained by thrombopoietin and IL-11 • Platelets circulate for 10 days before losing their functional capacity

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

31. Hemostasis • Sequence • Vasoconstriction • Formation of a platelet plug • Activation of the coagulation cascade • Formation of a blood clot • Clot retraction and clot dissolution

32. Hemostasis • Platelet plug formation • Activation • Adhesion • von Willebrand factor (vWF) • Aggregation • Secretion

33. Hemostasis • Function of clotting factors • Intrinsic pathway • Activated when factor XII contacts subendothelial substances exposed by vascular injury • Extrinsic pathway • Activated when tissue factor (TF) (tissue thromboplastin) is released by damaged endothelial cells

34. Coagulation Cascade

35. Control of Hemostatic Mechanisms • Antithrombotics • Antithrombin III • Protease inhibitor; inhibits thrombin and factor Xa • Tissue factor pathway inhibitor (TFPI) • Protein C and protein S • Thrombomodulin system

36. Control of Hemostatic Mechanisms • Clot retraction • Fibrin strands shorten; become denser and stronger to approximate the edges of the injured vessel and site of injury • Facilitated by large numbers of platelets within the clot and actinlike contractile proteins in the platelets

37. Control of Hemostatic Mechanisms • Lysis of blood clots • Fibrinolytic system • Plasminogen and plasmin • Tissue plasminogen activator (t-PA) • Fibrin degradation products • D-dimers

38. Fibrinolytic System

39. Evaluation of the Hematologic System • Tests of bone marrow function • Bone marrow aspiration • Bone marrow biopsy • Measurement of bone marrow iron stores • Differential cell count • Blood tests • Large variety of tests

40. Pediatrics and the Hematologic System • Blood cell counts increase above adult levels at birth • Trauma of birth and cutting the umbilical cord • The hypoxic intrauterine environment stimulates erythropoietin production • Results in polycythemia • Children tend to have more atypical lymphocytes due to frequent viral infections

41. Aging and the Hematologic System • Erythrocyte life span is normal but erythrocytes are replaced more slowly • Possible causes: • Iron depletion • Decreased total serum iron, iron binding capacity, and intestinal iron absorption • Lymphocyte function decreases with age • The humoral immune system is less responsive