1. Structure and Function of the Hematologic System Chapter 25 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2. 2 Components of the Hematologic System  Composition of blood  90% water and 10% solutes  6 quarts (5.5 L)  Plasma 50% to 55% of the blood volume 50% to 55% of the blood volume Organic and inorganic elements Organic and inorganic elements  Serum Plasma that has been allowed to clot to remove fibrinogen (may interfere with diagnostic tests) Plasma that has been allowed to clot to remove fibrinogen (may interfere with diagnostic tests)

3. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Components of the Hematologic System  Composition of blood  Plasma proteins 7% of the plasma total weight 7% of the plasma total weight The majority are synthesized in the liver The majority are synthesized in the liver  Except immunoglobulins (made by plasma cells) Albumins Albumins  Function as carriers; control plasma oncotic pressure Globulins Globulins  Carrier proteins and immunoglobulins (antibodies) Clotting factors Clotting factors  Mainly fibrinogen

4. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Components of the Hematologic System  Plasma proteins classification by function  Clotting  Fibrinogen and fibrin  Defense Antibodies Antibodies Complement Complement  Transport Proteins Proteins  Regulation Enzymatic inhibitors Enzymatic inhibitors

5. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Components of the Hematologic System  Composition of blood  Cellular components Erythrocytes Erythrocytes  Most abundant cell in the body  Responsible for tissue oxygenation  Biconcavity and reversible deformity  120-day life cycle

6. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Composition of Blood  Cellular components  Leukocytes (white blood cells) Defend body against infection and remove debris Defend body against infection and remove debris Granulocytes Granulocytes  Membrane-bound granules in their cytoplasm  The granules contain enzymes capable of destroying microorganisms  Inflammatory and immune functions  Capable of ameboid movement (diapedesis)

7. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Composition of Blood  Granulocytes  Cells with membrane-bound granules  Inflammatory mediators  Enzymes  Neutrophils, eosinophils, basophils, mast cells

8. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Composition of Blood  Granulocytes  Neutrophils (most numerous, 55%) Polymorphonuclear neutrophils (PMNs) Polymorphonuclear neutrophils (PMNs) Phagocytes in early inflammation Phagocytes in early inflammation  Eosinophils (1%–4%) Ingest antigen-antibody complexes Ingest antigen-antibody complexes Induced by IgE hypersensitivity Induced by IgE hypersensitivity Increase in parasitic infections Increase in parasitic infections

9. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Composition of Blood  Granulocytes  Mast cells Central cell in inflammation Central cell in inflammation Found in vascularized connective tissue Found in vascularized connective tissue  Basophils (<1%) Structurally similar to mast cells Structurally similar to mast cells Precise function not understood Precise function not understood

10. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Composition of Blood  Agranulocytes  Monocytes and macrophages make up the mononuclear phagocyte system (MPS)  Monocytes (precursor to macrophage)  Macrophages Remove old and damaged cells and large molecules from circulation Remove old and damaged cells and large molecules from circulation

11. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Composition of Blood  Agranulocytes  Lymphocytes (36% of lymphocytes) Major cells of immune system Major cells of immune system Life span: days, months, years, depending on type Life span: days, months, years, depending on type  Natural killer (NK) cells (5%-10%) Kill tumor cells and virally infected cells Kill tumor cells and virally infected cells Produce cytokines involved in immune responses Produce cytokines involved in immune responses

12. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Composition of Blood  Platelets  Disk-shaped cytoplasmic fragments  Formed by fragmentation of megakaryocytes  Essential for blood coagulation and control of bleeding  Incapable of mitotic division  Live 10 days and then removed by spleen

13. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Lymphoid Organs  Spleen  Largest secondary lymphoid organ  Splenic pulp Masses of lymphoid tissue containing macrophages and lymphoid tissue Masses of lymphoid tissue containing macrophages and lymphoid tissue Fetal hematopoiesis Fetal hematopoiesis  Venous sinuses Phagocytosis of old, damaged, dead blood cells Phagocytosis of old, damaged, dead blood cells Blood storage (300 ml) Blood storage (300 ml)

14. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Lymphoid Organs  Lymph nodes  Part of the immune and hematologic systems Facilitate maturation of lymphocytes Facilitate maturation of lymphocytes Transport lymphatic fluid back to circulation Transport lymphatic fluid back to circulation Cleanse the lymphatic fluid of microorganisms and foreign particles Cleanse the lymphatic fluid of microorganisms and foreign particles First site of contact between circulating antigen and nodal lymphocytes First site of contact between circulating antigen and nodal lymphocytes

15. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Hematopoiesis  The process of blood cell production in adult bone marrow  Humans need 100 billion new blood cells per day  Two stages  Mitosis Stops before the cell enters the peripheral blood Stops before the cell enters the peripheral blood  Maturation

16. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Hematopoiesis

17. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 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 Pelvic bones, vertebrae, cranium and mandible, sternum and ribs, humerus, and femur

18. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Colony-Stimulating Factors

19. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Erythropoiesis  Erythrocytes 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

20. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Erythropoiesis

21. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Regulation of Erythropoiesis  Numbers of circulating RBCs in healthy individuals remain constant  Peritubular cells of the kidney produce erythropoietin  Hypoxia stimulates the production and release of erythropoietin  Erythropoietin causes increase in RBC production and release from bone marrow

22. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Hemoglobin Synthesis  Oxygen carrying protein of the erythrocyte  A single erythrocyte contains as many as 300 hemoglobin molecules  Two pairs of polypeptide chains  Globulins  4 colorful iron-protoporphyrin complexes  Adult hemoglobin  Two α-chains and two β-chains

23. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Hemoglobin Synthesis  Total body iron cycle (most recycled)  Bound to heme (67%)  Bound to ferritin or hemosiderin mononuclear phagocytes (30%) and hepatic parenchymal cells  Less than 1 mg per day is lost in the urine, sweat, epithelial cells, or from the gut (3%)  Transferrin  Apotransferrin

24. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Hemoglobin Synthesis  Nutritional requirements  Building blocks Proteins Proteins  Amino acids Vitamins Vitamins  Vitamins B 12, B 6, B 2, E, and C, folic acid, pantothenic acid, and niacin Minerals Minerals  Iron and copper

25. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Hemoglobin Synthesis

26. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Senescent Erythrocytes  Older RBCs removed from circulation by macrophages after 120 days  Usually occurs in the spleen  If spleen unable or absent, removed by Kupffer cells in liver  Heme  Globin  Iron

27. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Iron Cycle  Ferritin  Major intracellular iron storage protein  Precursor apoferritin (ferritin without iron)  Hemosiderin  Ferritin micelles  Transferrin  Transfers iron in circulation  Precursor apotransferrin

28. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Iron Cycle

29. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Development of Leukocytes  Leukocytes (lymphocytes, granulocytes, monocytes) arise from stem cells in the bone marrow  Granulocytes mature in the bone marrow  Agranulocytes and monocytes released into bloodstream before they fully mature  Growth factors and colony-simulating factors encourage production and maturation of leukocytes

30. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Development of Platelets  Endomitosis  Megakaryocyte undergoes nuclear phase of cell division but fails to undergo cytokinesis  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

31. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Hemostasis  Hemostasis means arrest of bleeding  Requirements  Platelets  Clotting cascade  Blood flow and shear forces  Endothelial cells  Fibrinolysis

32. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Hemostasis  Sequence  Vasoconstriction  Formation of a platelet plug  Activation of the coagulation cascade  Formation of a blood clot  Clot retraction and clot dissolution

33. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 33 Hemostasis  Platelet function  Help regulate blood flow into a damaged site by inducing vasoconstriction  Initiate platelet-to-platelet interactions resulting in formation of a platelet plug  Activate the coagulation (or clotting) cascade to stabilize the platelet plug  Initiate repair processes including clot retraction and clot dissolution (fibrinolysis)

34. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 34 Hemostasis  Platelet plug formation  Adhesion von Willebrand factor (vWF) von Willebrand factor (vWF)  Activation  Aggregation  Secretion

35. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Hemostasis  Function of clotting factors  Intrinsic pathway Activated when Hageman factor (factor XII) contacts subendothelial substances exposed by vascular injury Activated when Hageman factor (factor XII) contacts subendothelial substances exposed by vascular injury  Extrinsic pathway Activated when tissue factor (TF) (tissue thromboplastin) is released by damaged endothelial cells Activated when tissue factor (TF) (tissue thromboplastin) is released by damaged endothelial cells

36. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Control of Hemostatic Mechanisms  Antithrombotics  Antithrombin III Protease inhibitor; inhibits thrombin and factor Xa Protease inhibitor; inhibits thrombin and factor Xa  Tissue factor pathway inhibitor (TFPI)  Protein C and protein S Thrombomodulin system Thrombomodulin system

37. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 37 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 actin-like contractile proteins in the platelets

38. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Control of Hemostatic Mechanisms  Lysis of blood clots  Fibrinolytic system Plasminogen and plasmin Plasminogen and plasmin Tissue plasminogen activator (t-PA) Tissue plasminogen activator (t-PA) Fibrin degradation products Fibrin degradation products  D-dimers

39. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Fibrinolytic System

40. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 40 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

41. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 41 Pediatrics and the Hematologic System  Blood cell counts increase above adult levels at birth; decline during childhood  Trauma of birth and cutting the umbilical cord  The hypoxic intrauterine environment stimulates erythropoietin production  Results in polycythemia  Children have more atypical lymphocytes due to frequent viral infections

42. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 42 Aging and the Hematologic System  Erythrocyte life span is normal but erythrocytes are replaced more slowly  Possible causes Iron depletion Iron depletion Decreased total serum iron, iron-binding capacity, and intestinal iron absorption Decreased total serum iron, iron-binding capacity, and intestinal iron absorption  Lymphocyte function decreases with age  The humoral immune system is less responsive