Chapter 25
Structure and Function of the
Hematologic System
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Components of the
Hematologic System
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Composition of blood
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90% water and 10% solutes
6 quarts (5.5 L)
Plasma
• 50% to 55% of the blood volume
• Organic and inorganic elements
Serum
• Plasma that has been allowed to clot to remove
fibrinogen (may interfere with diagnostic tests)
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Components of the
Hematologic System
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Composition of blood
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Plasma proteins
• 7% of the plasma total weight
• The majority are synthesized in the liver

Except immunoglobulins (made by plasma cells)
• Albumins
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Function as carriers; control plasma oncotic pressure
• Globulins
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Carrier proteins and immunoglobulins (antibodies)
• Clotting factors

Mainly fibrinogen
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Components of the
Hematologic System
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Plasma proteins classification by function
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Clotting
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Fibrinogen and fibrin
Defense
• Antibodies
• Complement
Transport
• Proteins
Regulation
• Enzymatic inhibitors
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Components of the
Hematologic System
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Composition of blood
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Cellular components
• Erythrocytes
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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
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Cellular components
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Leukocytes (white blood cells)
• Defend body against infection and remove debris
• Granulocytes
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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
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Granulocytes
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Cells with membrane-bound granules
Inflammatory mediators
Enzymes
Neutrophils, eosinophils, basophils, mast cells
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Composition of Blood
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Granulocytes
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Neutrophils (most numerous, 55%)
• Polymorphonuclear neutrophils (PMNs)
• Phagocytes in early inflammation
Eosinophils (1%–4%)
• Ingest antigen-antibody complexes
• Induced by IgE hypersensitivity
• Increase in parasitic infections
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Composition of Blood
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Granulocytes
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Mast cells
• Central cell in inflammation
• Found in vascularized connective tissue
Basophils (<1%)
• Structurally similar to mast cells
• Precise function not understood
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Composition of Blood
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Agranulocytes
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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
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Composition of Blood
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Agranulocytes
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Lymphocytes (36% of lymphocytes)
• Major cells of immune system
• Life span: days, months, years, depending on type
Natural killer (NK) cells (5%-10%)
• Kill tumor cells and virally infected cells
• Produce cytokines involved in immune responses
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Composition of Blood
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Platelets
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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
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Lymphoid Organs
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Spleen
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Largest secondary lymphoid organ
Splenic pulp
• Masses of lymphoid tissue containing macrophages and
lymphoid tissue
• Fetal hematopoiesis
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Venous sinuses
• Phagocytosis of old, damaged, dead blood cells
• Blood storage (300 ml)
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Lymphoid Organs
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Lymph nodes
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Part of the immune and hematologic systems
• Facilitate maturation of lymphocytes
• Transport lymphatic fluid back to circulation
• Cleanse the lymphatic fluid of microorganisms and
foreign particles
• First site of contact between circulating antigen and
nodal lymphocytes
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Hematopoiesis
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The process of blood cell production in adult
bone marrow
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Humans need 100 billion new blood cells per day
Two stages
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Mitosis
• Stops before the cell enters the peripheral blood
 Maturation
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Hematopoiesis
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Hematopoiesis
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Stem cell system
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Pluripotent stem cells
Colony-stimulating factors
Bone marrow
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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
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Erythrocytes derived from erythroblasts
(normoblasts)
Maturation is stimulated by erythropoietin
Sequence
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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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Regulation of Erythropoiesis
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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
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Hemoglobin Synthesis
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Oxygen carrying protein of the erythrocyte
A single erythrocyte contains as many as 300
hemoglobin molecules
Two pairs of polypeptide chains
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Globulins
4 colorful iron-protoporphyrin complexes
Adult hemoglobin
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Two α-chains and two β-chains
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Hemoglobin Synthesis
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Total body iron cycle (most recycled)
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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
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Hemoglobin Synthesis
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Nutritional requirements
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Building blocks
• Proteins
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Amino acids
• Vitamins
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Vitamins B12, B6, B2, E, and C, folic acid, pantothenic acid,
and niacin
• Minerals

Iron and copper
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Hemoglobin Synthesis
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Senescent Erythrocytes
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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
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Heme
Globin
Iron
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Iron Cycle
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Ferritin
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Hemosiderin
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Major intracellular iron storage protein
Precursor apoferritin (ferritin without iron)
Ferritin micelles
Transferrin
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Transfers iron in circulation
Precursor apotransferrin
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Iron Cycle
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Development of Leukocytes
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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
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Development of Platelets
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Endomitosis
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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
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Platelet levels are maintained by
thrombopoietin and IL-11
Platelets circulate for 10 days before losing
their functional capacity
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Hemostasis
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Hemostasis means arrest of bleeding
Requirements
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Platelets
Clotting cascade
Blood flow and shear forces
Endothelial cells
Fibrinolysis
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Hemostasis
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Sequence
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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
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Platelet function
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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)
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Hemostasis
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Platelet plug formation
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Adhesion
• von Willebrand factor (vWF)
Activation
Aggregation
Secretion
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Hemostasis
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Function of clotting factors
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Intrinsic pathway
• Activated when Hageman factor (factor XII) contacts
subendothelial substances exposed by vascular injury
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Extrinsic pathway
• Activated when tissue factor (TF) (tissue thromboplastin)
is released by damaged endothelial cells
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Control of Hemostatic
Mechanisms
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Antithrombotics
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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
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Clot retraction
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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
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Control of Hemostatic
Mechanisms
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Lysis of blood clots
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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
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Tests of bone marrow function
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Bone marrow aspiration
Bone marrow biopsy
Measurement of bone marrow iron stores
Differential cell count
Blood tests
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Large variety of tests
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Pediatrics and the
Hematologic System
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Blood cell counts increase above adult levels
at birth; decline during childhood
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The hypoxic intrauterine environment
stimulates erythropoietin production
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Trauma of birth and cutting the umbilical cord
Results in polycythemia
Children have more atypical lymphocytes due
to frequent viral infections
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Aging and the Hematologic
System
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Erythrocyte life span is normal but
erythrocytes are replaced more slowly
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Possible causes
• Iron depletion
• Decreased total serum iron, iron-binding capacity, and
intestinal iron absorption
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Lymphocyte function decreases with age
The humoral immune system is less
responsive
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