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Structure and Function of the Hematologic SystemChapter 25

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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

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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

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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

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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)

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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

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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

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Composition of Blood Agranulocytes

Monocytes and macrophages make up the mononuclear phagocyte system (MPS)

Monocytes Macrophages Lymphocytes Natural killer (NK) cells

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Composition of Blood Platelets

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

bleeding

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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

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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

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Lymphoid Organs

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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

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Hematopoiesis Hematopoiesis is the process of blood cell

production Two stages:

Mitosis Mitosis stops before the cell enters the peripheral

blood

Maturation

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Hematopoiesis

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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

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Colony-Stimulating Factors

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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

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Erythropoiesis

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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

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Hemoglobin Synthesis

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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

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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

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Iron Cycle

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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

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Regulation of Erythropoiesis

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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

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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

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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

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Hemostasis Hemostasis means arrest of bleeding Requirements

Platelets Clotting cascade Blood flow and shear forces Endothelial cells Fibrinolysis

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Hemostasis Sequence

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

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Hemostasis Platelet plug formation

Activation Adhesion

von Willebrand factor (vWF)

Aggregation Secretion

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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

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Coagulation Cascade

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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

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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

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Control of Hemostatic Mechanisms Lysis of blood clots

Fibrinolytic system Plasminogen and plasmin Tissue plasminogen activator (t-PA) Fibrin degradation products

D-dimers

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Fibrinolytic System

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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

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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

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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