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 Eosinophils
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 Basophils
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 Bone marrow 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 Aggregation
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