structure and function of the hematologic system chapter 25 mosby items and derived items © 2010,...
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Cellular BiologyMosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Structure and Function of the Hematologic System
Chapter 25
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Components of the
6 quarts (5.5 L)
Organic and inorganic elements
Serum
Plasma that has been allowed to clot to remove fibrinogen (may interfere with diagnostic tests)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Components of the
The majority are synthesized in the liver
Except immunoglobulins (made by plasma cells)
Albumins
Globulins
Clotting factors
Mainly fibrinogen
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Components of the
Clotting
Enzymatic inhibitors
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Components of the
Responsible for tissue oxygenation
Biconcavity and reversible deformity
120-day life cycle
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Granulocytes
The granules contain enzymes capable of destroying microorganisms
Inflammatory and immune functions
Capable of ameboid movement (diapedesis)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Neutrophils, eosinophils, basophils, mast cells
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Induced by IgE hypersensitivity
Increase in parasitic infections
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Basophils (<1%)
Precise function not understood
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Monocytes and macrophages make up the mononuclear phagocyte system (MPS)
Monocytes (precursor to macrophage)
Remove old and damaged cells and large molecules from circulation
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Essential for blood coagulation and control of bleeding
Incapable of mitotic division
Live 10 days and then removed by spleen
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Lymphoid Organs
Fetal hematopoiesis
Venous sinuses
Blood storage (300 ml)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Lymphoid Organs
Lymph nodes
Facilitate maturation of lymphocytes
Cleanse the lymphatic fluid of microorganisms and foreign particles
First site of contact between circulating antigen and nodal lymphocytes
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hematopoiesis
The process of blood cell production in adult bone marrow
Humans need 100 billion new blood cells per day
Two stages
Maturation
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hematopoiesis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hematopoiesis
Adult active bone marrow
Pelvic bones, vertebrae, cranium and mandible, sternum and ribs, humerus, and femur
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Colony-Stimulating Factors
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Erythropoiesis
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Erythropoiesis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Regulation of Erythropoiesis
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemoglobin Synthesis
A single erythrocyte contains as many as 300 hemoglobin molecules
Two pairs of polypeptide chains
Globulins
Two α-chains and two β-chains
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemoglobin Synthesis
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemoglobin Synthesis
Nutritional requirements
Building blocks
Vitamins
Vitamins B12, B6, B2, E, and C, folic acid, pantothenic acid, and niacin
Minerals
Iron and copper
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemoglobin Synthesis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Senescent Erythrocytes
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
Heme
Globin
Iron
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Iron Cycle
Hemosiderin
Precursor apotransferrin
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Iron Cycle
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Development of Leukocytes
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Development of Platelets
Endomitosis
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
Platelet levels are maintained by thrombopoietin and IL-11
Platelets circulate for 10 days before losing their functional capacity
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Requirements
Platelets
Endothelial cells
Fibrinolysis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Sequence
Vasoconstriction
Formation of a platelet plug
Activation of the coagulation cascade
Formation of a blood clot
Clot retraction and clot dissolution
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Platelet function
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)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Activation
Aggregation
Secretion
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Extrinsic pathway
Activated when tissue factor (TF) (tissue thromboplastin) is released by damaged endothelial cells
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Control of Hemostatic Mechanisms
Tissue factor pathway inhibitor (TFPI)
Protein C and protein S
Thrombomodulin system
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
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 actin-like contractile proteins in the platelets
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Control of Hemostatic Mechanisms
Lysis of blood clots
D-dimers
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Fibrinolytic System
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Evaluation of the
Bone marrow aspiration
Bone marrow biopsy
Differential cell count
Large variety of tests
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Pediatrics and the
Hematologic System
Blood cell counts increase above adult levels at birth; decline during childhood
Trauma of birth and cutting the umbilical cord
The hypoxic intrauterine environment stimulates erythropoietin production
Results in polycythemia
Children have more atypical lymphocytes due to frequent viral infections
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Aging and the Hematologic System
Erythrocyte life span is normal but erythrocytes are replaced more slowly
Possible causes
Iron depletion
Lymphocyte function decreases with age
The humoral immune system is less responsive
Structure and Function of the Hematologic System
Chapter 25
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Components of the
6 quarts (5.5 L)
Organic and inorganic elements
Serum
Plasma that has been allowed to clot to remove fibrinogen (may interfere with diagnostic tests)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Components of the
The majority are synthesized in the liver
Except immunoglobulins (made by plasma cells)
Albumins
Globulins
Clotting factors
Mainly fibrinogen
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Components of the
Clotting
Enzymatic inhibitors
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Components of the
Responsible for tissue oxygenation
Biconcavity and reversible deformity
120-day life cycle
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Granulocytes
The granules contain enzymes capable of destroying microorganisms
Inflammatory and immune functions
Capable of ameboid movement (diapedesis)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Neutrophils, eosinophils, basophils, mast cells
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Induced by IgE hypersensitivity
Increase in parasitic infections
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Basophils (<1%)
Precise function not understood
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Monocytes and macrophages make up the mononuclear phagocyte system (MPS)
Monocytes (precursor to macrophage)
Remove old and damaged cells and large molecules from circulation
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Composition of Blood
Essential for blood coagulation and control of bleeding
Incapable of mitotic division
Live 10 days and then removed by spleen
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Lymphoid Organs
Fetal hematopoiesis
Venous sinuses
Blood storage (300 ml)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Lymphoid Organs
Lymph nodes
Facilitate maturation of lymphocytes
Cleanse the lymphatic fluid of microorganisms and foreign particles
First site of contact between circulating antigen and nodal lymphocytes
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hematopoiesis
The process of blood cell production in adult bone marrow
Humans need 100 billion new blood cells per day
Two stages
Maturation
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hematopoiesis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hematopoiesis
Adult active bone marrow
Pelvic bones, vertebrae, cranium and mandible, sternum and ribs, humerus, and femur
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Colony-Stimulating Factors
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Erythropoiesis
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Erythropoiesis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Regulation of Erythropoiesis
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemoglobin Synthesis
A single erythrocyte contains as many as 300 hemoglobin molecules
Two pairs of polypeptide chains
Globulins
Two α-chains and two β-chains
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemoglobin Synthesis
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemoglobin Synthesis
Nutritional requirements
Building blocks
Vitamins
Vitamins B12, B6, B2, E, and C, folic acid, pantothenic acid, and niacin
Minerals
Iron and copper
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemoglobin Synthesis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Senescent Erythrocytes
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
Heme
Globin
Iron
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Iron Cycle
Hemosiderin
Precursor apotransferrin
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Iron Cycle
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Development of Leukocytes
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Development of Platelets
Endomitosis
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
Platelet levels are maintained by thrombopoietin and IL-11
Platelets circulate for 10 days before losing their functional capacity
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Requirements
Platelets
Endothelial cells
Fibrinolysis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Sequence
Vasoconstriction
Formation of a platelet plug
Activation of the coagulation cascade
Formation of a blood clot
Clot retraction and clot dissolution
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Platelet function
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)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Activation
Aggregation
Secretion
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Hemostasis
Extrinsic pathway
Activated when tissue factor (TF) (tissue thromboplastin) is released by damaged endothelial cells
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Control of Hemostatic Mechanisms
Tissue factor pathway inhibitor (TFPI)
Protein C and protein S
Thrombomodulin system
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
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 actin-like contractile proteins in the platelets
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Control of Hemostatic Mechanisms
Lysis of blood clots
D-dimers
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Fibrinolytic System
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Evaluation of the
Bone marrow aspiration
Bone marrow biopsy
Differential cell count
Large variety of tests
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Pediatrics and the
Hematologic System
Blood cell counts increase above adult levels at birth; decline during childhood
Trauma of birth and cutting the umbilical cord
The hypoxic intrauterine environment stimulates erythropoietin production
Results in polycythemia
Children have more atypical lymphocytes due to frequent viral infections
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Aging and the Hematologic System
Erythrocyte life span is normal but erythrocytes are replaced more slowly
Possible causes
Iron depletion
Lymphocyte function decreases with age
The humoral immune system is less responsive