Structure and Function of the Hematologic System Chapter 25

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

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

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

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)

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

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

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

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

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

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

Lymphoid Organs

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

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

Hematopoiesis

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

Colony-Stimulating Factors

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

Erythropoiesis

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

Hemoglobin Synthesis

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

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

Iron Cycle

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

Regulation of Erythropoiesis

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

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

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

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

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

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

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

Coagulation Cascade

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

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

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

Fibrinolytic System

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

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

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