Y khoa, y dược - Chapter 17: Blood

CHAPTER 17 Blood BLOOD COMPOSITIONBlood: a fluid connective tissue composed ofPlasma Formed elementsErythrocytes (red blood cells, or RBCs) Leukocytes (white blood cells, or WBCs) Platelets BLOOD COMPOSITIONHematocritPercent of blood volume that is RBCs 47% ± 5% for males42% ± 5% for femalesConsider 45 % as an averageFigure 17.11 Withdrawblood and placein tube.2 Centrifuge theblood sample.Plasma• 55% of whole blood• Least dense componentBuffy coat• Leukocytes and platelets• 97% hemoglobin (not counting water)No mitochondria; ATP production is anaerobic; no O2 is used in generation of ATPA superb example of complementarity of structure and function! ERYTHROCYTE FUNCTIONRBCs are dedicated to respiratory gas transportHemoglobin binds reversibly with oxygen ERYTHROCYTE FUNCTIONHemoglobin structureProtein globin: two alpha and two beta chainsHeme pigment bonded to each globin chainIron atom in each heme can bind to one O2 moleculeEach Hb molecule can transport four O2Figure 17.4Hemegroup(a) Hemoglobin consists of globin (two alpha and two beta polypeptide chains) and four heme groups.(b) Iron-containing heme pigment.a Globin chainsb Globin chainsHEMOGLOBIN (HB)O2 loading in the lungsProduces oxyhemoglobin (ruby red)O2 unloading in the tissuesProduces deoxyhemoglobin or reduced hemoglobin (dark red) CO2 loading in the tissuesProduces carbaminohemoglobin (carries 20% of CO2 in the blood)HEMATOPOIESISHematopoiesis (hemopoiesis): blood cell formation Occurs in red bone marrow of axial skeleton, girdles and proximal epiphyses of humerus and femurHEMATOPOIESISHemocytoblasts (hematopoietic stem cells)Give rise to all formed elementsHormones and growth factors push the cell toward a specific pathway of blood cell developmentNew blood cells enter blood sinusoids ERYTHROPOIESISErythropoiesis: red blood cell productionA hemocytoblast is transformed into a proerythroblastProerythroblasts develop into early erythroblastsREGULATION OF ERYTHROPOIESISToo few RBCs leads to tissue hypoxiaToo many RBCs increases blood viscosityBalance between RBC production and destruction depends onHormonal controls Adequate supplies of iron, amino acids, and B vitaminsHORMONAL CONTROL OF ERYTHROPOIESISErythropoietin (EPO)Direct stimulus for erythropoiesis Released by the kidneys in response to hypoxiaHORMONAL CONTROL OF ERYTHROPOIESISCauses of hypoxia Hemorrhage or increased RBC destruction reduces RBC numbersInsufficient hemoglobin (e.g., iron deficiency)Reduced availability of O2 (e.g., high altitudes)HORMONAL CONTROL OF ERYTHROPOIESISEffects of EPOMore rapid maturation of committed bone marrow cellsIncreased circulating reticulocyte count in 1–2 daysTestosterone also enhances EPO production, resulting in higher RBC counts in malesFigure 17.6, step 5 Kidney (and liver toa smaller extent)releaseserythropoietin. Erythropoietinstimulates redbone marrow. Enhancederythropoiesisincreases RBCcount. O2- carryingability of bloodincreases.Homeostasis: Normal blood oxygen levels Stimulus:Hypoxia (low bloodO2- carrying ability)due to• DecreasedRBC count• Decreased amountof hemoglobin• Decreasedavailability of O212345IMBALANCEIMBALANCEDIETARY REQUIREMENTS FOR ERYTHROPOIESISNutrients— amino acids, lipids, and carbohydratesIronStored in Hb (65%), the liver, spleen, and bone marrowStored in cells as ferritin and hemosiderinTransported loosely bound to the protein transferrinVitamin B12 and folic acid —necessary for DNA synthesis for cell divisionFATE AND DESTRUCTION OF ERYTHROCYTESLife span: 100–120 daysOld RBCs become fragile, and Hb begins to degenerateMacrophages engulf dying RBCs in the spleen FATE AND DESTRUCTION OF ERYTHROCYTESHemoglobin is separated into heme and globinIron from heme is salvaged for reuseNon iron part of heme is degraded to yellow the pigments bilirubin and biliverdinLiver incorporated the pigments in bile as bile pigments.Bile is secreted into the small intestinesBile pigments are broken down and excreted in feces as stercobilin and in urine as urobilinGlobin is broken down into amino acids. Amino acids are recycled for protein synthesisFigure 17.7, step 4 Low O2 levels in blood stimulatekidneys to produce erythropoietin.1 Erythropoietin levels risein blood.2 Erythropoietin and necessaryraw materials in blood promoteerythropoiesis in red bone marrow.3 New erythrocytesenter bloodstream;function about 120 days.4Figure 17.7, step 6 Aged and damaged redblood cells are engulfed bymacrophages of liver,spleen, and bonemarrow; thehemoglobin isbroken down.5 Raw materials aremade available in bloodfor erythrocyte synthesis.6HemoglobinAminoacidsGlobinIron is bound totransferrin and releasedto blood from liver asneeded for erythropoiesis.Food nutrients,including amino acids,Fe, B12, and folic acid,are absorbed fromintestine and enterblood.HemeCirculationIron storedas ferritin,hemosiderinBilirubinBilirubin is picked up from bloodby liver, secreted into intestine inbile, metabolized to stercobilin bybacteria, and excreted in feces.Figure 17.7 Low O2 levels in blood stimulate kidneys to produce erythropoietin.1 Erythropoietin levels risein blood.2 Erythropoietin and necessaryraw materials in blood promoteerythropoiesis in red bone marrow.3 Aged and damagedred blood cells areengulfed by macrophagesof liver, spleen, and bonemarrow; the hemoglobinis broken down.5 New erythrocytesenter bloodstream;function about 120 days.4 Raw materials aremade available in bloodfor erythrocyte synthesis.6HemoglobinAminoacidsGlobinIron is bound totransferrin and releasedto blood from liver asneeded for erythropoiesis.Food nutrients,including amino acids,Fe, B12, and folic acid,are absorbed fromintestine and enterblood.HemeCirculationIron storedas ferritin,hemosiderinBilirubinBilirubin is picked up from bloodby liver, secreted into intestine inbile, metabolized to stercobilin bybacteria, and excreted in feces.ERYTHROCYTE DISORDERSAnemia: blood has abnormally low O2-carrying capacityA sign rather than a disease itselfBlood O2 levels cannot support normal metabolismAccompanied by fatigue, paleness, shortness of breath, and chills CAUSES OF ANEMIAInsufficient erythrocytesHemorrhagic anemia: acute or chronic loss of bloodHemolytic anemia: RBCs rupture prematurelyAplastic anemia: destruction or inhibition of red bone marrowCAUSES OF ANEMIALow hemoglobin contentIron-deficiency anemia Secondary result of hemorrhagic anemia orInadequate intake of iron-containing foods orImpaired iron absorptionCAUSES OF ANEMIAPernicious anemia ( a hereditory condition)Deficiency of vitamin B12Lack of intrinsic factor needed for absorption of B12Treated by intramuscular injection of B12 or application of NascobalCAUSES OF ANEMIAAbnormal hemoglobinThalassemias (a hereditory condition)Absent or faulty globin chain RBCs are thin, delicate, and deficient in hemoglobinCAUSES OF ANEMIASickle-cell anemia (a hereditory condition)Defective gene codes for abnormal hemoglobin (HbS)Causes RBCs to become sickle shaped in low-oxygen situationsFigure 17.812345671461234567146(a) Normal erythrocyte has normal hemoglobin amino acid sequence in the beta chain.(b) Sickled erythrocyte results from a single amino acid change in the beta chain of hemoglobin.ERYTHROCYTE DISORDERSPolycythemia: excess of RBCs that increase blood viscosity Results from:Polycythemia vera—bone marrow cancerSecondary polycythemia—when less O2 is available (high altitude) or when EPO production increasesBlood dopingLEUKOCYTES Make up <1% of total blood volumeCan leave capillaries via diapedesisMove through tissue spaces by ameboid motion and positive chemotaxisLeukocytosis: WBC count over 11,000/mm3Normal response to bacterial or viral invasionFigure 17.9FormedelementsPlateletsLeukocytesErythrocytesDifferentialWBC count(All total 4800 –10,800/l)Neutrophils (50 – 70%)Lymphocytes (25 – 45%)Eosinophils (2 – 4%)Basophils (0.5 – 1%)Monocytes (3 – 8%)AgranulocytesGranulocytesGRANULOCYTESGranulocytes: neutrophils, eosinophils, and basophilsCytoplasmic granules stain specifically with Wright’s stainLarger and shorter-lived than RBCsLobed nucleiPhagocytic NEUTROPHILSMost numerous WBCsPolymorphonuclear leukocytes (PMNs)Fine granules take up both acidic and basic dyesGive the cytoplasm a lilac colorGranules contain hydrolytic enzymes or defensins Very phagocytic—“bacteria slayers”EOSINOPHILSRed-staining, bilobed nuclei Red to crimson (acidophilic) coarse, lysosome-like granulesDigest parasitic worms that are too large to be phagocytizedModulators of the immune response BASOPHILSRarest WBCsLarge, purplish-black (basophilic) granules contain histamineHistamine: an inflammatory chemical that acts as a vasodilator and attracts other WBCs to inflamed sitesAre functionally similar to mast cellsFigure 17.10 (a-c)(a) Neutrophil; multilobed nucleus(b) Eosinophil; bilobed nucleus, red cytoplasmic granules(c) Basophil; bilobed nucleus, purplish-black cytoplasmic granulesAGRANULOCYTESAgranulocytes: lymphocytes and monocytesLack visible cytoplasmic granulesHave spherical or kidney-shaped nucleiLYMPHOCYTESLarge, dark-purple, circular nuclei with a thin rim of blue cytoplasmMostly in lymphoid tissue; few circulate in the bloodCrucial to immunityLYMPHOCYTESTwo types T cells act against virus-infected cells and tumor cellsB cells give rise to plasma cells, which produce antibodiesMONOCYTESThe largest leukocytesAbundant pale-blue cytoplasmDark purple-staining, U- or kidney-shaped nucleiMONOCYTESLeave circulation, enter tissues, and differentiate into macrophagesActively phagocytic cells; crucial against viruses, intracellular bacterial parasites, and chronic infectionsActivate lymphocytes to mount an immune responseFigure 17.10d, e(d) Small lymphocyte; large spherical nucleus(e) Monocyte; kidney-shaped nucleusTable 17.2 (1 of 2)Table 17.2 (2 of 2)LEUKOPOIESISProduction of WBCsStimulated by chemical messengers from bone marrow and mature WBCs All leukocytes originate from hemocytoblastsLEUKOCYTE DISORDERSLeukopenia Abnormally low WBC count—drug inducedLeukemiasCancerous conditions involving WBCsNamed according to the abnormal WBC clone involvedAcute leukemia and primarily affects childrenChronic leukemia is more prevalent in older peopleLEUKEMIABone marrow totally occupied with cancerous leukocytesImmature nonfunctional WBCs in the bloodstream Death caused by internal hemorrhage and overwhelming infectionsTreatments include irradiation, antileukemic drugs, and stem cell transplantsPLATELETSSmall fragments of megakaryocytesFormation is regulated by thrombopoietinBlue-staining outer region, purple granulesGranules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF)PLATELETSForm a temporary platelet plug that helps seal breaks in blood vesselsCirculating platelets are kept inactive and mobile by NO and prostacyclin from endothelial cells of blood vesselsFigure 17.12Stem cellDevelopmental pathwayHemocyto-blastMegakaryoblastPromegakaryocyteMegakaryocytePlateletsHEMOSTASISFast series of reactions for stoppage of bleedingVascular spasm Platelet plug formation (this is not clotting)Coagulation (blood clotting)VASCULAR SPASMVasoconstriction of damaged blood vesselTriggersDirect injuryChemicals released by endothelial cells and platelets Pain reflexesPLATELET PLUG FORMATIONPositive feedback cycleAt site of blood vessel injury, plateletsStick to exposed collagen fibers with the help of von Willebrand factor, a plasma proteinSwell, become spiked and sticky, and release chemical messengersADP causes more platelets to stick and release their contents Serotonin and thromboxane A2 enhance vascular spasm and more platelet aggregationFigure 17.13CollagenfibersPlateletsFibrinStep Vascular spasm• Smooth muscle contracts, causing vasoconstriction.Step Platelet plugformation• Injury to lining of vessel exposes collagen fibers; platelets adhere. • Platelets release chemicals that make nearby platelets sticky; platelet plug forms.Step Coagulation• Fibrin forms a mesh that traps red blood cells and platelets, forming the clot.123COAGULATIONA set of reactions in which blood is transformed from a liquid to a gelReinforces the platelet plug with fibrin threadsCOAGULATIONThree phases of coagulationProthrombin activator is formed (intrinsic and extrinsic pathways)Prothrombin is converted into thrombinThrombin catalyzes the joining of fibrinogen to form a fibrin meshFigure 17.14 (1 of 2)Vessel endothelium ruptures,exposing underlying tissues(e.g., collagen)PF3released byaggregatedplateletsXIIXIIXXIIaCa2+Ca2+XIaIXaIntrinsic pathwayPhase 1Tissue cell traumaexposes blood toPlatelets cling and theirsurfaces provide sites formobilization of factorsExtrinsic pathwayTissue factor (TF)VIIVIIaVIIIVIIIaCa2+XXaProthrombinactivatorPF3TF/VIIa complexIXa/VIIIa complexVVaFigure 17.14 (2 of 2)Ca2+Phase 2 Phase 3 ProthrombinactivatorProthrombin (II)Thrombin (IIa)Fibrinogen (I)(soluble)Fibrin(insolublepolymer)XIII XIIIa Cross-linkedfibrin meshCOAGULATION PHASE 1: TWO PATHWAYS TO PROTHROMBIN ACTIVATORInitiated by either the intrinsic or extrinsic pathway (usually both)Triggered by tissue-damaging eventsInvolves a series of procoagulantsEach pathway cascades toward factor XFactor X complexes with Ca2+, PF3, and factor V to form prothrombin activatorCOAGULATION PHASE 1: TWO PATHWAYS TO PROTHROMBIN ACTIVATORIntrinsic pathway Is triggered by negatively charged surfaces (activated platelets, collagen, glass)Uses factors present within the blood (intrinsic)Extrinsic pathwayIs triggered by exposure to tissue factor (TF) or factor III (an extrinsic factor)Bypasses several steps of the intrinsic pathway, so is fasterCOAGULATION PHASE 2: PATHWAY TO THROMBINProthrombin activator catalyzes the transformation of prothrombin to the active enzyme thrombinCOAGULATION PHASE 3: COMMON PATHWAY TO THE FIBRIN MESHThrombin converts soluble fibrinogen into fibrinFibrin strands form the structural basis of a clotFibrin causes plasma to become a gel-like trap for formed elements Thrombin (with Ca2+) activates factor XIII which:Cross-links fibrinStrengthens and stabilizes the clotFigure 17.15FACTORS PREVENTING UNDESIRABLE CLOTTINGPlatelet adhesion is prevented bySmooth endothelial lining of blood vesselsAntithrombic substances nitric oxide and prostacyclin secreted by endothelial cellsDISORDERS OF HEMOSTASISThromboembolytic disorders: undesirable clot formationBleeding disorders: abnormalities that prevent normal clot formationTHROMBOEMBOLYTIC CONDITIONSThrombus: clot that develops and persists in an unbroken blood vesselMay block circulation, leading to tissue deathEmbolus: a thrombus freely floating in the blood streamPulmonary emboli impair the ability of the body to obtain oxygenCerebral emboli can cause strokesTHROMBOEMBOLYTIC CONDITIONS Prevented byAspirinAntiprostaglandin that inhibits thromboxane A2HeparinAnticoagulant used clinically for pre- and postoperative cardiac careWarfarinUsed for those prone to atrial fibrillationBLEEDING DISORDERSThrombocytopenia: deficient number of circulating plateletsPetechiae appear due to spontaneous, widespread hemorrhage Due to suppression or destruction of bone marrow (e.g., malignancy, radiation)Platelet count <50,000/mm3 is diagnostic Treated with transfusion of concentrated plateletsBLEEDING DISORDERSImpaired liver functionInability to synthesize procoagulants Causes include vitamin K deficiency, hepatitis, and cirrhosisLiver disease can also prevent the liver from producing bile, impairing fat and vitamin K absorptionBLEEDING DISORDERSHemophilias include several similar hereditary bleeding disorders Symptoms include prolonged bleeding, especially into joint cavitiesTreated with plasma transfusions and injection of missing factorsTRANSFUSIONSWhole-blood transfusions are used when blood loss is substantial Packed red cells (plasma removed) are used to restore oxygen-carrying capacityTransfusion of incompatible blood can be fatalBLOOD GROUPSHumans have 30 varieties of naturally occurring RBC antigensAntigens of the ABO and Rh blood groups cause vigorous transfusion reactions ABO BLOOD GROUPSTypes A, B, AB, and OBased on the presence or absence of two antigens (agglutinins), A and B on the surface of the RBCs Blood also contain anti-A or anti-B antibodies (agglutinins) in the plasma that act against transfused RBCs with ABO antigens not normally present Anti-A or anti-B form in the blood at about 2 months of age Table 17.4RH BLOOD GROUPSAnti-Rh antibodies are not spontaneously formed in Rh– individualsAnti-Rh antibodies form if an Rh– individual receives Rh+ blood A second exposure to Rh+ blood will result in a typical transfusion reactionHOMEOSTATIC IMBALANCE: HEMOLYTIC DISEASE OF THE NEWBORNAlso called erythroblastosis fetalisRh– mother becomes sensitized when exposure to Rh+ blood causes her body to synthesize anti-Rh antibodiesAnti-Rh antibodies cross the placenta and destroy the RBCs of an Rh+ babyHOMEOSTATIC IMBALANCE: HEMOLYTIC DISEASE OF THE NEWBORNThe baby can be treated with prebirth transfusions and exchange transfusions after birthRhoGAM serum containing anti-Rh can prevent the Rh– mother from becoming sensitizedTRANSFUSION REACTIONSOccur if mismatched blood is infusedDonor’s cellsAre attacked by the recipient’s plasma agglutininsAgglutinate and clog small vesselsRupture and release free hemoglobin into the bloodstream Result inDiminished oxygen-carrying capacityHemoglobin in kidney tubules and renal failureBLOOD TYPINGWhen serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogensPositive reactions indicate agglutinationABO BLOOD TYPINGFigure 17.16SerumAnti-ARBCsAnti-BType AB (containsagglutinogens A and B;agglutinates with bothsera)Blood being testedType A (containsagglutinogen A;agglutinates with anti-A)Type B (containsagglutinogen B;agglutinates with anti-B)Type O (contains noagglutinogens; does notagglutinate with eitherserum)RESTORING BLOOD VOLUME Death from shock may result from low blood volumeVolume must be replaced immediately withNormal saline or multiple-electrolyte solution that mimics plasma electrolyte compositionPlasma expanders (e.g., purified human serum albumin, hetastarch, and dextran) Mimic osmotic properties of albuminMore expensive and may cause significant complicationsDIAGNOSTIC BLOOD TESTSHematocritBlood glucose testsMicroscopic examination reveals variations in size and shape of RBCs, indications of anemiasDIAGNOSTIC BLOOD TESTSDifferential WBC countProthrombin time and platelet counts assess hemostasisSMAC, a blood chemistry profileComplete blood count (CBC)