Chapter 19 Blood Functions of blood: 1. transportation functions 1. oxygen delivery 2. nutrient delivery 3. transportation of metabolic wastes (urine formation) 4. transportation of hormones (part of the immune system?) 2. regulatory functions 1. maintaining appropriate body temperature 2. maintaining normal ph of body tissues 3. maintaining adequate fluid volume in the circulatory system salts and proteins attract water into the circulatory system 3. protective functions 1. prevent fluid loss (clotting) 2. prevent infections (wbc) characteristics of blood 1. is a viscous liquid with both solid and liquid components viscosity is 5 X greater then water 2. is slightly alkaline; ph 7.35 to 7.45 venous blood is more acidic 3. temp is 100.4 degrees 4. 5-6 liters of blood in a male 4-5 liter of blood in a female normovolemic hypovolemic hypervolemic Components of blood is a specialized type of connective tissue made of: formed elements plasma is connective tissue matrix 1
centrifugation of a blood sample 1. bottom layer of red blood cells called erythrocytes is 45% of total blood volume called the hematocrit also called the volume of packed red cells (VPRC) 2. small middle layer the buffy coat is a layer of leukocytes and platelets is less 1% of blood volume 3. top layer of plasma 55% of blood fluid layer contains ions and dissolved proteins and fats and glucose top and middle layers contain the formed elements blood plasma 1. 92% of volume is water 2. plasma proteins (less then 8%) albumin are 60% of proteins are the smallest plasma proteins important in holding in water contribute to osmotic pressure of blood carrier molecules ph buffer made in liver changes in concentration effects blood pressure and fluid balance globulins (35%) 1. transport proteins bind small ions and hormones so what be lost in kidney made by liver 2. immunoglobulins (antibodies) largest group only major plasma protein not made by liver clotting proteins (4%) mostly fibrinogen is triggered to become insoluble strands of fibrin the framework of a clot fibrinogen is made by liver if clotting proteins are removed plasma is called serum 2
others peptide hormones metabolic enzymes 3. others ions gases various wastes etc. formed elements erythrocytes leukocytes, and platelets most are short-lived being renewed by stem cells in bone marrow formation of formed elements formed elements are produced through the process of hemopoiesis also called hematopoiesis site of hemopoiesis blood islands in the yolk sac (at third week of development) here stem cells called hemocytoblast first form and are release to colonize the other sites within the embryo liver starts at fifth month stops production around time of birth spleen starts at fifth month stops producing red blood cells shortly after birth continues WBC production thymus produces white blood cells only (T-lymphocytes) starts about fifth month stops producing WBC as an early child red bone marrow is major site after seventh month only site in adults 3
hematopoietic stem cells hemocytoblast (from blood islands) 1. lymphoid stem cell lymphocytes 2. myeloid stem cell a) proerythroblast erythrocytes b) Granulocyte-macrophage colony-forming unit neutrophils eosinophils basophils monocytes c) megakaryoblast platelets Types of formed elements Erythrocytes (RBC) most abundant blood cell 99.9% of formed elements 260 million RBC in a drop of hole blood 25 trillion in the adult one third of all cells in the adult body Structure of RBCs 1. size 7.8 microns in diameter 2.6 microns thick at thickest.8 microns thick at thinnest 2. biconcave discs advantages a) increases surface area 3800 square meters b) can easily change shape if necessary c) can form stacks like dinner plates called rouleaux (roo-lo) a rouleaux can pass early through capillary 3. during differentiation the red blood cells loss their organelles have no nucleus and few organelles no mitochondria so consume no oxygen for ATP production don t steal oxygen they are carrying to peripheral tissue can not synthesize proteins for repair 4
live 120 days 4. are bags of hemoglobin (97% of dry weight) 14 to 18 grams per 100ml of blood in male (g/dl) 12 to 16 g/dl in females functions in gas transport Hemoglobin 5. function of RBC transport of respiratory gases oxygen and carbon dioxide and ph regulation 1. hemoglobin is made up of the protein globin is actually four polypeptide chains two alpha two beta red pigment heme there are four heme groups per hemoglobin each polypeptide chain of globin has a heme each can bind to one oxygen molecule each heme contains one iron molecule have 280 million hemoglobin molecules per RBC one RBC can carry one billion O2 molecules forms of hemoglobin oxyhemoglobin is bound to O2 this form is bright red in color deoxyhemoglobin unbound this form is dark red in color carbaminohemoglobin bound to CO2 this form is dark red the fetus contains a different type of fetal hemoglobin globin contains two alpha chains and two gamma chains (no beta) has higher affinity for oxygen can steal oxygen from mother 5
production of erythrocytes a RBC makes a round trip in less than a minute in their 120 day life they will travel 700 miles eventually the cell membrane will rupture because there is no repair mechanism must replace 1% of the RCB each day make 3 million erythrocytes per second red blood cell formation hematopoiesis (blood cell formation) occurs in the red bone marrow events that occur during erythropoiesis 1.stem cell called proerythroblast divides forming a erythroblast 2. erythroblast produce huge # of ribosomes ribosomes produces hemoglobin (each cells has 250 million hemoglobin molecules) 3. maturing erythroblasts ejects its nucleus and is called reticulocyte reticulocyte continues to make hemoglobin from stored mrna 24 hours after reticulocytes appear they are released in to the blood where they eject other organelles and mature into erythrocytes Regulation of erythropoiesis there is a very tightly controlled balance between RBC production and destruction hormonal control erythropoiesis requires the hormone erythropoietin 1) stimulates rate of cell division of proerythroblast 2) speeds up maturation of erythroblast by stimulating hemoglobin production can increase to 30 million per second (from 3 million) normally small amounts are released from the kidneys 6
dietary requirements high levels are released when oxygen levels to the cells of the kidneys drop results from 1. reduced number of RBC 2. reduced availability of oxygen 3. increase tissue demands for oxygen 4. reduced lung function emphysema = polycythemia also released in response to a drop in renal blood pressure high levels of blood oxygen results in inhibition of erythropoietin release negative feedback iron for heme production vitamin C and copper mainly for globin production B12 and folic acid are required for DNA synthesis Erythrocyte death and disposal have no nucleus so lose their function quickly life span is 100 to 120 days rbcs have a protein called spectrin in the plasma membrane which makes the plasma membrane very flexible spectrin cant be replaced as cell ages so loose flexibility inflexible rbcs usually trapped in the spleen, liver, and bone marrow and destroyed by macrophages hemolysis macrophages split the cell releasing the hemoglobin heme is split off from the globin globin is broken down into amino acids most released back into circulation iron is removed from the heme and stored in liver and spleen for reuse iron is bond to a protein called apoferritin will in these tissues when released into the blood the iron is bound to transferrin 7
rest of heme is degraded to biliverdin has a green color gives a bruise its green color biliverdin in the macro is converted to bilirubin which is yellowish is then released into the circulation carried on albumin picked up by liver stored in gall bladder as part of bile which is secreted into intestines during a meal blockage of bile duct prevents removal from blood = jaundice leukocytes or white blood cells 1. are complete cells 2. important in defense against disease from bacteria, viruses, parasites, toxins, and tumor cells 3. most leukocytes are in the connective tissue proper or organs of the lymphatic system circulation leukocytes are a small fraction of total types of leukocytes: granulocytes agranulocytes granulocytes 1. neutrophils: are most common usually first at injury site so attracts others live only 10 hours in blood stream phagocytize bacteria that have been marked with antibodies or with complement after internializing the bacteria the cell produces hydrogen peroxide and supperoxice anions (O2 - ) which kill bacteria release defensins which form holes in cell walls 8
2. eosinophils: Attack objects coated with antibodies like bacteria protozoa and multicellular parasites Can phagocytises but normally releases toxic compounds like Nitric oxide, cytotoxic enzymes Also attracted to site of injury to limit the spread of inflammation 3. basophils: release histamines and other mediators of inflammation release heparin to prevent blood clots agranulocytes 1. lymphocytes: T cells: responsible for cell-mediated immunity B cells: responsible for humoral immunity NK cells: responsible for immune surveillance and attach cancer cells 2. monocytes: leave the blood stream and differentiate into macrophages phagocytize viral infected cells and bacteria very important in fighting chronic infection platelets 1. are fragments of a large cell called megakaryocytic is multinucleated most live in bone marrow a few in the lungs 2. survive about 10 days removed by spleen, liver and bone marrow 3. 25 to 40% are stored in the spleen 4. formation is regulated by hormone thrombopoietin from kidneys and liver platelet functions 9
transport chemicals important to the clotting process form a temporary patch in the wall of damaged blood vessels contract after clot formation has occurred hemostasis: stoppage of bleeding also establishes the framework for tissue repair three phases 1. vascular spasm phase 2. platelet phase 3. coagulation or blood clot formation 1. vascular spasm phase constriction of the blood vessels to slow blood flow and loss contraction results from 1. direct damage to smooth muscle 2. chemicals from the endothelial cells and platelets serotonin 3. relaxes from pain receptors larger the area, the stronger the spasm controls bleeding for about 20-30 minutes until other mechanisms to control bleeding take over 2. platelet phase platelets are normally repelled by prostacyclin on intact endothelium platelets adhere to exposed collagen of damaged vessel triggering platelet adhesion platelets swell forming spiked processes and release granules granules contain 1) serotonin to enhance spasms 2) ADP to attract more platelets to the area 3) thromboxane A2 does both 2 and 3 lead to platelet aggregation 4) platelet thromboplastin coagulates blood 5) platelet-derived growth factor 10
promotes vessel repair by stimulating fibroblasts endothelial cells smooth muscle cells 6) calcium required for platelet aggregation and blood coagulation 7) Hageman factor Involved in blood clotting regulation of the platelet phase prostacyclin a prostaglandin (PGI2) produced by health endothelial cells limit the plug size inhibitory compounds from the WBC in the area circulation enzymes that breakdown ADP 3. coagulation phase (blood clotting) results in the transformation of liquid blood into a gel is a complex sequence of steps that leads to the conversion of circulating fibrinogen into insoluble fibrin involves over 30 chemical reactions four steps of coagulation step one: activate prothrombin activator (PF) present in the blood there are two ways 1. intrinsic mechanism binding of platelets to collagen fibers cause the release of Hageman factor (VII) Hageman factor (VII) through several steps activates factor X in the blood. Factor X activates prothrombin activator (PA) 2. extrinsic mechanism thromboplastin (tissue factor) released from damaged perivascular tissue. thromboplastin activates factor X in the blood. Factor X activates prothrombin activator 11
step two: prothrombin activator converts prothrombin to thrombin step three: thrombin catalyzes the conversation of fibrinogen to fibrin fibrin is insoluble and forms a web the web traps formed elements thus have coagulation and clot formation step four: clot retraction after forming this fibrin web around the platelets, the contractile protein complex called actomyosin contracts pulling the clot tight drawing the damaged edges of the vessel together after clot retraction platelet-derived growth factor (PDGF) released from the platelets stimulates smooth muscle, fibroblast and endothelial cell growth and repair limiting clot growth and preventing inappropriate coagulation 1. dilution: swift removal of coagulation factors by the blood must reach a critical concentration for clot formation dilution in blood if not trapped in the clot 2. platelet repulsion: prostacyclin-coated endothelium prevents adhesion of platelets 3. anticoagulants: inhibition of activated clotting factors by plasma anticoagulants 1. thrombin formation is suppressed by plasma protein antithrombin 2. heparin: is released from basophils and mast cells works by inactivating thrombin and activating antithrombin clot removal (fibrinolysis) plasminogen from the plasma is incorporated in to the growing clot and is converted to plasmin by Hageman factor (VII) same Hageman factor released from the platelets during coagulation 12
this occurs much slower plasmin converts more plasminogen to plasmin positive feed back loop plasmin digests the fibrin strands of the clot preventing coagulation heparin activates antithrombin coumandin (warfarin) and coumarin depress the synthesis of several clotting factors they are vitamin K antagonists aspirin blocks production of thromboxane A2 platelet aggregation factor hirudin from medical leech inhibits thrombin clot -busters streptokinase or urokinase convert plasminogen to plasmin but also has nonspecific effects on other proteins plasminogen activator convert plasminogen to plasmin 13