Structure and Function of the Hematologic System Chapter

Structure and Function of the Hematologic System Chapter 25 1

Components of the Hematologic System o Composition of blood n n n 90% water and 10% solutes 6 quarts (5. 5 L) Plasma o o 55% to 60% of the blood volume Organic and inorganic elements 2 Mosby items and derived items © 2006 by Mosby, Inc.

Components of the Hematologic System o Composition of blood n Plasma proteins o o o 7% of the plasma total weight The majority are synthesized in the liver Albumins n o Globulins n o Function as carriers and control the plasma oncotic pressure Carrier proteins and immunoglobulins (antibodies) Clotting factors n Mainly fibrinogen 3 Mosby items and derived items © 2006 by Mosby, Inc.

Components of the Hematologic System o Composition of blood n Cellular components o Erythrocytes n n Most abundant cell in the body Responsible for tissue oxygenation Biconcavity and reversible deformity 120 -day life cycle 4 Mosby items and derived items © 2006 by Mosby, Inc.

Composition of Blood o Cellular components n Leukocytes (white blood cells) o o Defend the body against infection and remove debris Granulocytes n n Membrane-bound granules in their cytoplasm The granules contain enzymes capable of destroying microorganisms Inflammatory and immune functions Capable of ameboid movement (diapedesis) 5 Mosby items and derived items © 2006 by Mosby, Inc.

Composition of Blood o Granulocytes n Neutrophils o o n Polymorphonuclear neutrophil (PMN) Phagocytes in early inflammation Eosinophils o o o Eosinophils ingest antigen-antibody complexes Induced by Ig. E hypersensitivity Increase in parasitic infections 6 Mosby items and derived items © 2006 by Mosby, Inc.

Composition of Blood o Granulocytes n Mast cells o o n Central cell in inflammation Found in vascularized connective tissue Basophils o o Structurally similar to mast cells Precise function not understood 7 Mosby items and derived items © 2006 by Mosby, Inc.

Composition of Blood o Agranulocytes n n n Monocytes and macrophages make up the mononuclear phagocyte system (MPS) Monocytes Macrophages Lymphocytes Natural killer (NK) cells 8 Mosby items and derived items © 2006 by Mosby, Inc.

Composition of Blood o Platelets n n n Disk-shaped cytoplasmic fragments Formed by fragmentation of megakaryocytes Essential for blood coagulation and control of bleeding 9 Mosby items and derived items © 2006 by Mosby, Inc.

Lymphoid Organs o Spleen n n Largest secondary lymphoid organ Splenic pulp o n Masses of lymphoid tissue containing macrophages and lymphoid tissue Venous sinuses o o Phagocytosis of old, damaged, and dead blood cells Blood storage 10 Mosby items and derived items © 2006 by Mosby, Inc.

Lymphoid Organs o Lymph nodes n Part of the immune and hematologic systems o o o Facilitates maturation of lymphocytes Transports lymphatic fluid back to the circulation Cleanses the lymphatic fluid of microorganisms and foreign particles 11 Mosby items and derived items © 2006 by Mosby, Inc.

Lymphoid Organs 12 Mosby items and derived items © 2006 by Mosby, Inc.

Mononuclear Phagocyte System (MPS) o o o 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 13 Mosby items and derived items © 2006 by Mosby, Inc.

Hematopoiesis o o Hematopoiesis is the process of blood cell production Two stages: n Mitosis o n Mitosis stops before the cell enters the peripheral blood Maturation 14 Mosby items and derived items © 2006 by Mosby, Inc.

Hematopoiesis 15 Mosby items and derived items © 2006 by Mosby, Inc.

Hematopoiesis o Stem cell system n n o Pluripotent stem cells Colony-stimulating factors Bone marrow n n n Also called myeloid tissue Red and yellow bone marrow Adult active bone marrow o Pelvic bones, vertebrae, cranium and mandible, sternum and ribs, humerus, and femur 16 Mosby items and derived items © 2006 by Mosby, Inc.

Colony-Stimulating Factors 17 Mosby items and derived items © 2006 by Mosby, Inc.

Erythropoiesis o o o Erythrocytes are derived from erythroblasts (normoblasts) Maturation is stimulated by erythropoietin Sequence n n 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 18 Mosby items and derived items © 2006 by Mosby, Inc.

Erythropoiesis 19 Mosby items and derived items © 2006 by Mosby, Inc.

Hemoglobin Synthesis o o o Oxygen carrying protein of the erythrocyte A single erythrocyte contains as many as 300 hemoglobin molecules Two pairs of polypeptide chains n o o Globulins Four colorful iron-protoporphyrin complexes Adult hemoglobin n Two α chains and two β chains 20 Mosby items and derived items © 2006 by Mosby, Inc.

Hemoglobin Synthesis 21 Mosby items and derived items © 2006 by Mosby, Inc.

Hemoglobin Synthesis o Nutritional requirements n Building blocks o Proteins n o Vitamins n o Amino acids Vitamins B 12, B 6, B 2, E, and C, folic acid, pantothenic acid, and niacin Minerals n Iron and copper 22 Mosby items and derived items © 2006 by Mosby, Inc.

Hemoglobin Synthesis o Iron cycle n n 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 23 Mosby items and derived items © 2006 by Mosby, Inc.

Iron Cycle 24 Mosby items and derived items © 2006 by Mosby, Inc.

Regulation of Erythropoiesis o o 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 25 Mosby items and derived items © 2006 by Mosby, Inc.

Regulation of Erythropoiesis 26 Mosby items and derived items © 2006 by Mosby, Inc.

Normal Destruction of Senescent Erythrocytes o o 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 27 Mosby items and derived items © 2006 by Mosby, Inc.

Development of Leukocytes o o 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 28 Mosby items and derived items © 2006 by Mosby, Inc.

Development of Platelets o Endomitosis n n o o 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 29 Mosby items and derived items © 2006 by Mosby, Inc.

Hemostasis o o Hemostasis means arrest of bleeding Requirements n n n Platelets Clotting cascade Blood flow and shear forces Endothelial cells Fibrinolysis 30 Mosby items and derived items © 2006 by Mosby, Inc.

Hemostasis o Sequence n n n Vasoconstriction Formation of a platelet plug Activation of the coagulation cascade Formation of a blood clot Clot retraction and clot dissolution 31 Mosby items and derived items © 2006 by Mosby, Inc.

Hemostasis o Platelet plug formation n n Activation Adhesion o n n von Willebrand factor (v. WF) Aggregation Secretion 32 Mosby items and derived items © 2006 by Mosby, Inc.

Hemostasis o Function of clotting factors n Intrinsic pathway o n Activated when factor XII contacts subendothelial substances exposed by vascular injury Extrinsic pathway o Activated when tissue factor (TF) (tissue thromboplastin) is released by damaged endothelial cells 33 Mosby items and derived items © 2006 by Mosby, Inc.

Coagulation Cascade 34 Mosby items and derived items © 2006 by Mosby, Inc.

Control of Hemostatic Mechanisms o Antithrombotics n Antithrombin III o n n Protease inhibitor; inhibits thrombin and factor Xa Tissue factor pathway inhibitor (TFPI) Protein C and protein S o Thrombomodulin system 35 Mosby items and derived items © 2006 by Mosby, Inc.

Control of Hemostatic Mechanisms o Clot retraction n n 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 36 Mosby items and derived items © 2006 by Mosby, Inc.

Control of Hemostatic Mechanisms o Lysis of blood clots n Fibrinolytic system o o o Plasminogen and plasmin Tissue plasminogen activator (t-PA) Fibrin degradation products n D-dimers 37 Mosby items and derived items © 2006 by Mosby, Inc.

Fibrinolytic System 38 Mosby items and derived items © 2006 by Mosby, Inc.

Evaluation of the Hematologic System o Tests of bone marrow function n n o Bone marrow aspiration Bone marrow biopsy Measurement of bone marrow iron stores Differential cell count Blood tests n Large variety of tests 39 Mosby items and derived items © 2006 by Mosby, Inc.

Pediatrics and the Hematologic System o Blood cell counts increase above adult levels at birth n o The hypoxic intrauterine environment stimulates erythropoietin production n o Trauma of birth and cutting the umbilical cord Results in polycythemia Children tend to have more atypical lymphocytes due to frequent viral infections 40 Mosby items and derived items © 2006 by Mosby, Inc.

Aging and the Hematologic System o Erythrocyte life span is normal but erythrocytes are replaced more slowly n Possible causes: o o 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 41 Mosby items and derived items © 2006 by Mosby, Inc.