Chapter 18: Blood

Explain what determines a person's ABO and Rh blood types and how this relates to transfusion compatibility.

•Blood types are based on interactions between antigens and antibodies -You do not form antibodies against your antigens •Antigens -Complex molecules on surface of cell membrane that activate an immune response •They are genetically unique to the individual •Used to distinguish self from foreign matter •Foreign antigens generate an immune response •Agglutinogens—antigens on the surface of the RBC that are the basis for blood typing •Antibodies -Proteins (gamma globulins) secreted by plasma cells •Part of immune response to foreign matter •Bind to antigens and mark them for destruction •Forms antigen-antibody complexes •Agglutinins—antibodies in the plasma that bring about transfusion mismatch •Agglutination -Antibody molecule binding to antigens -Causes clumping of red blood cells •RBC antigens called agglutinogens -Called antigen A and B -Determined by glycolipids on RBC surface •Antibodies called agglutinins -Found in plasma -Anti-A and anti-B •Your ABO blood type is determined by presence or absence of antigens (agglutinogens) on RBCs -Blood type A person has A antigens -Blood type B person has B antigens -Blood type AB has both A and B antigens -Blood type O person has neither antigen •Most common: type O •Rarest: type AB •Agglutination -Each antibody can attach to several foreign antigens on several different RBCs at the same time •Responsible for mismatched transfusion reaction -Agglutinated RBCs block small blood vessels, hemolyze, and release their hemoglobin over the next few hours or days -Hbblocks kidney tubules and causes acute renal failure

Describe the functions and major components of the circulatory system.

Circulatory system consists of the heart, blood vessels, and blood Functions of circulatory system -Transport •O2, CO2, nutrients, wastes, hormones, and stem cells -Protection •Inflammation, limit spread of infection, destroy microorganisms and cancer cells, neutralize toxins, and initiate clotting -Regulation •Fluid balance, stabilizes pH of ECF, and temperature control

Describe in general terms how blood is produced.

•Adult production of 400 billion platelets, 100-200 billion RBCs, and 10 billion WBCs every day •Hemopoiesis—production of blood, especially its formed elements •Hemopoietic tissues produce blood cells -Yolk sac produces stem cells for first blood cells •Colonize fetal bone marrow, liver, spleen, and thymus -Liver stops producing blood cells at birth -Spleen remains involved with lymphocyte production -Red bone marrow produces all seven formed elements •Pluripotent stem cells (PPSC) -Formerly called hemocytoblasts or hemopoietic stem cells •Colony-forming unit—specialized stem cells only producing one class of formed element of blood •Myeloid hemopoiesis—blood formation in the bone marrow •Lymphoid hemopoiesis—blood formation in the lymphatic organs (beyond infancy this only involves lymphocytes)

Describe the components and physical properties of blood.

•Adults have 4 to 6 L of blood •A liquid connective tissue consisting of cells and extracellular matrix -Plasma: matrix of blood •Clear, light yellow fluid -Formed elements: blood cells and cell fragments •Red blood cells, white blood cells, and platelets •Seven kinds of formed elements -1)Erythrocytes: red blood cells (RBCs) -2)Platelets •Cell fragments from special cell in bone marrow -Leukocytes: white blood cells (WBCs) •Five leukocyte types divided into two categories •Granulocytes (with granules) -3)Neutrophils -4)Eosinophils -5)Basophils •Agranulocytes(without granules) -6)Lymphocytes -7)Monocytes •Hematocrit—centrifuge blood to separate components -Erythrocytes are heaviest and settle first •37% to 52% total volume -White blood cells and platelets •1% total volume •Buffy coat -Plasma •The remainder of volume •47% to 63% •Complex mixture of water, proteins, nutrients, electrolytes, nitrogenous wastes, hormones, and gases

Explain what happens to blood clots when they are no longer needed.

•Clot retraction occurs within 30 minutes •Platelet-derived growth factor secreted by platelets and endothelial cells -Mitotic stimulant for fibroblasts and smooth muscle to multiply and repair damaged vessel •Fibrinolysis—dissolution of a clot -Factor XII speeds up formation of kallikrein enzyme -Kallikrein converts plasminogen into plasmin, a fibrin-dissolving enzyme that breaks up the clot

Describe some disorders of blood clotting.

•Deficiency of any clotting factor can shut down the coagulation cascade •Hemophilia—family of hereditary diseases characterized by deficiencies of one factor or another •Sex-linked recessive (on X chromosome) -Hemophilia A missing factor VIII (83% of cases) -Hemophilia B missing factor IX (15% of cases) •Hemophilia C missing factor XI (autosomal) •Thrombosis—abnormal clotting in unbroken vessel -Thrombus: clot •Most likely to occur in leg veins of inactive people -Pulmonary embolism: clot may break free, travel from veins to lungs •Embolus—anything that can travel in the blood and block blood vessels •Infarction (tissue death) may occur if clot blocks blood supply to an organ (MI or stroke) -650,000 Americans die annually of thromboembolism (traveling blood clots)

Describe the structure and function of hemoglobin.

•Each Hb molecule consists of: -Four protein chains—globins •Adult HB has two alpha and two beta chains •Fetal Hb contains two alpha and two gamma chains •Globins bind CO2(5% of CO2in blood) -Four heme groups •Heme groups -Nonprotein moiety that binds O2to ferrous ion (Fe) at its center •Gas transport—major function -Increased surface area/volume ratio •Due to loss of organelles during maturation •Increases diffusion rate of substances -33% of cytoplasm is hemoglobin (Hb) •280 million hemoglobin molecules on one RBC •O2delivery to tissue and CO2transport to lungs •Carbonic anhydrase (CAH) in cytoplasm -Produces carbonic acid from CO2and water -Important role in gas transport and pH balance

Describe the life cycle of erythrocytes.

•Erythropoiesis—RBC production •1 million RBCs are produced per second •Average lifespan of about 120 days •Development takes 3 to 5 days -Reduction in cell size, increase in cell number, synthesis of hemoglobin, and loss of nucleus •First committed cell—erythrocyte colony-forming unit -Has receptors for erythropoietin (EPO) from kidneys •Erythroblasts (normoblast) multiply and synthesize hemoglobin •Nucleus discarded to form a reticulocyte -Named for fine network of endoplasmic reticulum -0.5% to 1.5% of circulating RBCs are reticulocytes

Describe two reaction pathways that produce blood clots.

•Extrinsic pathway -Initiated by release of tissue thromboplastin (factor III) from damaged tissue -Cascade to factor VII, V, and X (fewer steps) •Intrinsic pathway -Initiated by platelets releasing Hageman factor (factor XII) -Cascade to factor XI to IX to VIII to X •Calcium required for either pathway Completion of Coagulation •Activation of factor X -Leads to production of prothrombin activator •Prothrombin activator -Converts prothrombin to thrombin •Thrombin -Converts fibrinogen into fibrin monomers -Monomers covalently bind to form fibrin polymer -Factor XIII cross links fibrin polymer strands •Positive feedback—thrombin speeds up formation of prothrombin activator •Overall efficiency in coagulation can be measured with bleeding time after a 1 mm deep incision

Describe the appearance and relative abundance of each type of leukocyte.

•Granulocytes -Neutrophils (60% to 70%): polymorphonuclear leukocytes •Barely visible granules in cytoplasm; three-to five-lobed nucleus -Eosinophils (2% to 4%) •Large rosy-orange granules; bilobed nucleus -Basophils (less than 1%) •Large, abundant, violet granules (obscure a large S-shaped nucleus) •Agranulocytes -Lymphocytes (25% to 33%) •Variable amounts of bluish cytoplasm (scanty to abundant); ovoid/round, uniform dark violet nucleus -Monocytes (3% to 8%) •Usually largest WBC; ovoid, kidney-, or horseshoe-shaped nucleus

Explain the function of leukocytes in general and the individual role of each leukocyte type.

•Least abundant formed element »5,000 to 10,000 WBCs/μL •Protect against infectious microorganisms and other pathogens •Conspicuous nucleus •Spend only a few hours in the bloodstream before migrating to connective tissue •Retain their organelles for protein synthesis •Granules -All WBCs have lysosomes called nonspecific (azurophilic) granules -Granulocytes (some WBCs) have specific granules that contain enzymes and other chemicals employed in defense against pathogens Granulocytes •Neutrophils—aggressively antibacterial -Neutrophilia—rise in number of neutrophils in response to bacterial infection •Eosinophils—increased numbers in parasitic infections, collagen diseases, allergies, diseases of spleen and CNS -Phagocytosis of antigen-antibody complexes, allergens, and inflammatory chemicals -Release enzymes to destroy large parasites •Basophils -Secrete histamine (vasodilator): speeds flow of blood to an injured area -Secrete heparin (anticoagulant): promotes the mobility of other WBCs in the area Agranulocytes •Lymphocytes—increased numbers in diverse infections and immune responses -Destroy cells (cancer, foreign, and virally infected cells) -"Present" antigens to activate other immune cells -Coordinate actions of other immune cells -Secrete antibodies and provide immune memory •Monocytes—increased numbers in viral infections and inflammation -Leave bloodstream and transform into macrophages •Phagocytize pathogens and debris •"Present" antigens to activate other immune cells—antigen-presenting cells (APCs)

Discuss the types, causes, and effects of leukocyte excesses and deficiencies.

•Leukopenia—low WBC count: below 5,000 WBCs/μL -Causes: radiation, poisons, infectious disease -Effects: elevated risk of infection •Leukocytosis—high WBC count: above 10,000 WBCs/μL -Causes: infection, allergy, disease -Differential WBC count: identifies what percentage of the total WBC count consist of each type of leukocyte •Leukemia—cancer of hemopoietic tissue usually producing a very high number of circulating leukocytes -Myeloid leukemia: uncontrolled granulocyte production -Lymphoid leukemia: uncontrolled lymphocyte or monocyte production -Acute leukemia: appears suddenly, progresses rapidly, death within months -Chronic leukemia: undetected for months, survival time 3 years -Effects: normal cell percentages disrupted; impaired clotting; opportunistic infections

Describe the formation and life history of leukocytes.

•Leukopoiesis—production of white blood cells -Hemopoietic stem cells (HSCs) differentiate into: •Myeloblasts—form neutrophils, eosinophils, basophils •Monoblasts—form monocytes •Lymphoblasts give rise to all forms of lymphocytes -T lymphocytes complete development in thymus •Red bone marrow stores and releases granulocytes and monocytes •Circulating WBCs do not stay in bloodstream -Granulocytes leave in 8 hours and live 5 days longer -Monocytes leave in 20 hours, transform into macrophages, and live for several years -Lymphocytes provide long-term immunity (decades), being continuously recycled from blood to tissue fluid to lymph and back to the blood

Describe the composition of blood plasma.

•Plasma—liquid portion of blood -Serum: remaining fluid when blood clots and solids are removed •Identical to plasma except for the absence of fibrinogen •Three major categories of plasma proteins -Albumins: smallest and most abundant •Contribute to viscosity and osmolarity; influence blood pressure, flow, and fluid balance -Globulins (antibodies) •Provide immune system functions •Alpha, beta, and gamma globulins -Fibrinogen •Precursor of fibrin threads that help form blood clots •Plasma proteins are formed by liver -Except gamma globulins (produced by plasma cells) •Nitrogenous compounds -Free amino acids from dietary protein or tissue breakdown -Nitrogenous wastes (urea) •Toxic end products of catabolism •Normally removed by the kidneys •Nutrients -Glucose, vitamins, fats, cholesterol, phospholipids, and minerals •Dissolved O2, CO2, and nitrogen •Electrolytes -Na+makes up 90% of plasma cations

List the functions of platelets.

•Platelet functions -Secrete vasoconstrictors that help reduce blood loss -Stick together to form platelet plugs to seal small breaks -Secrete procoagulants or clotting factors to promote clotting -Initiate formation of clot-dissolving enzyme -Chemically attract neutrophils and monocytes to sites of inflammation -Phagocytize and destroy bacteria -Secrete growth factors that stimulate mitosis to repair blood vessels

Explain what keeps blood from clotting in the absence of injury.

•Platelet repulsion -Platelets do not adhere to prostacyclin-coated endothelium •Thrombin dilution -By rapidly flowing blood •Heart slowing in shock can result in clot formation •Natural anticoagulants -Heparin (from basophils and mast cells) interferes with formation of prothrombin activator -Antithrombin (from liver) deactivates thrombin before it can act on fibrinogen

Name and describe the types, causes, and effects of RBC excesses and deficiencies.

•Polycythemia—an excess of RBCs -Primary polycythemia (polycythemia vera) •Cancer of erythropoietic cell line in red bone marrow -RBC count as high as 11 million RBCs/μL; hematocrit 80% -Secondary polycythemia •From dehydration, emphysema, high altitude, or physical conditioning -RBC count up to 8 million RBCs/μL •Dangers of polycythemia -Increased blood volume, pressure, viscosity •Can lead to embolism, stroke, or heart failure •Causes of anemia fall into three categories -Inadequate erythropoiesis or hemoglobin synthesis •Kidney failure and insufficient erythropoietin •Iron-deficiency anemia •Pernicious anemia—autoimmune attack of stomach tissue leads to inadequate vitamin B12absorption •Hypoplastic anemia—slowing of erythropoiesis •Aplastic anemia—complete cessation of erythropoiesis -Hemorrhagic anemias from bleeding -Hemolytic anemias from RBC destruction •Anemia has three potential consequences -Tissue hypoxia and necrosis •Patient is lethargic •Shortness of breath upon exertion •Life-threatening necrosis of brain, heart, or kidney -Blood osmolarity is reduced, producing tissue edema -Blood viscosity is low •Heart races and pressure drops •Cardiac failure may ensue Sickle-Cell Disease •Hereditary defects that occur mostly among people of African descent •Caused by recessive allele that modifies structure of Hb (makes HbS) -Differs only on the sixth amino acid of the beta chain -HbS does not bind oxygen well -RBCs become rigid, sticky, pointed at ends -Clump together and block small blood vessels -Can lead to kidney or heart failure, stroke, joint pain, or paralysis -Heterozygotes (only one sickle cell allele) are resistant to malaria

State and define some clinical measurements of RBC and hemoglobin quantities.

•RBC count and hemoglobin concentration indicate amount of O2blood can carry -Hematocrit (packed cell volume): percentage of whole blood volume composed of RBCs •Men 42% to 52% cells; women 37% to 48% cells -Hemoglobin concentration of whole blood •Men 13 to 18 g/dL; women 12 to 16 g/dL -RBC count •Men 4.6 to 6.2 million/μL; women 4.2 to 5.4 million/μL •Values are lower in women -Androgens stimulate RBC production -Women have periodic menstrual losses -Hematocrit is inversely proportional to percentage of body fat

List some blood groups other than ABO and Rh and explain how they may be useful; and describe the effect of an incompatibility between mother and fetus.

•Rh (C, D, E) agglutinogens discovered in rhesus monkey in 1940 -Rh D is the most reactive and a patient is considered blood type Rh+ if having D antigen (agglutinogens) on RBCs -Rh frequencies vary among ethnic groups •Anti-D agglutinins not normally present -Form in Rh−individuals exposed to Rh+blood •Rh−woman with an Rh+fetus or transfusion of Rh+blood •No problems with first transfusion or pregnancy •Hemolytic disease of the newborn (HDN) can occur if Rh−mother has formed antibodies and is pregnant with second Rh+child -Anti-D antibodies can cross placenta •Prevention -RhoGAM given to pregnant Rh−women •Binds fetal agglutinogens in her blood so she will not form anti-D antibodies

Discuss the structure and function of erythrocytes (RBCs).

•Two principal functions -Carry oxygen from lungs to cell tissues -Pick up CO2from tissues and bring to lungs •Disc-shaped cell with thick rim -7.5 μm diameter and 2.0 μm thick at rim -Lose nearly all organelles during development •Lack mitochondria -Anaerobic fermentation to produce ATP •Lack of nucleus and DNA -No protein synthesis or mitosis

Describe the body's mechanism for controlling bleeding.

•Vascular spasm—prompt constriction of a broken vessel -Most immediate protection against blood loss •Causes -Pain receptors •Some directly innervate blood vessels to constrict -Smooth muscle injury -Platelets release serotonin (vasoconstrictor) •Effects -Prompt constriction of a broken vessel •Pain receptors—short duration (minutes) •Smooth muscle injury—longer duration -Provides time for other two clotting pathways •Platelet plug formation -Intact vessels have a smooth endothelium coated with prostacyclin—a platelet repellant -Broken vessel exposes collagen -Platelet pseudopods stick to damaged vessel and other platelets -Pseudopods contract -draw together a platelet plug -Platelets degranulate releasing a variety of substances •Serotonin is a vasoconstrictor •ADP attracts and degranulates more platelets •Thromboxane A2, an eicosanoid, promotes platelet aggregation, degranulation, and vasoconstriction -Positive feedback cycle is active until break in small vessel is sealed •Coagulation (clotting)—last and most effective defense against bleeding -Conversion of plasma protein fibrinogen into insoluble fibrin threads to form framework of clot -Procoagulants (clotting factors)—usually produced by the liver; are present in plasma •Activate one factor and it will activate the next to form a reaction cascade -Extrinsic pathway •Factors released by damaged tissues begin cascade -Intrinsic pathway •Factors found in blood begin cascade (platelet degranulation)

Explain the significance of blood viscosity and osmolarity.

•Viscosity—resistance of a fluid to flow, resulting from the cohesion of its particles -Whole blood 4.5 to 5.5 times as viscous as water -Plasma is 2.0 times as viscous as water •Important in circulatory function •Osmolarityof blood—the total molarity of those dissolved particles that cannot pass through the blood vessel wall -If too high, blood absorbs too much water, increasing the blood pressure -If too low, too much water stays in tissue, blood pressure drops, and edema occurs -Optimum osmolarityis achieved by the body's regulation of sodium ions, proteins, and red blood cells