基础医学各论I：Blood Physiology

1、Blood PhysiologyBody Fluid = 60% of Body Weight (BW)Intracellular Fluid2/3, 40% of BWExtracellular Fluid1/3, 20% of BWPlasma 5% of BWInterstitial Fluid15% of BW70 kg Male, 42 LInternal environment （内环境）Extracellular Fluid1/3, 20% of BWPlasma 5% of BWInterstitial Fluid15% of BWInternal EnvironmentHom

2、eostasis（稳态）Homeostasis (from the Greek words for “same” and “steady”):maintenance of static or constant conditions in the internal environmentWalter B. Cannon/unitarians/cannon_walter.htmlComponents of Homeostasis:lConcentration of O2 and CO2 lpH of the internal en

3、vironment lConcentration of nutrients and waste products lConcentration of salt and other electrolytes lVolume and pressure of extracellular fluid Bodys systems operate together to maintain homeostasis:Skin systemSkeletal and muscular systemCirculatory system Respiratory systemDigestive systemUrinar

4、y systemNervous systemEndocrine systemLymphatic systemReproductive systemHow is homeostasis achieved?Components of blood Plasma（血浆） Blood Cells Red Blood Cells (RBC) or Erythrocytes（红细胞） White Blood Cells (WBC) or Leucocytes（白细胞） Platelets (PLT) or Thrombocytes（血小板）Plasma includes water, ions, prote

5、ins, nutrients, hormones, wastes, etc.The hematocrit（血细胞比容） is a rapid assessment of blood composition.It is the percent of the blood volume that is composed of RBCs (red blood cells).the volume of red blood cells as a percentage of centrifuged whole bloodM: 4050%F: 3748% Hematocrit（packed cell volu

6、me, 血细胞比容）血细胞比容）Properties of blood1. Specific Gravity（比重）Depending on hematocrit & protein composition Whole blood：1.0501.060Plasma：1.0251.035Red blood cells：1.0902. Viscosity（粘度）Relative viscosity of whole blood 45 depending on hematocritRelative viscosity of plasma 1.62.4 related to the prote

7、in composition of the plasmaProperties of blood3. Osmotic Pressure（渗透压） The osmotic pressure of a solution depends on the number of solute particles in the solution, not on their chemical composition and size Properties of bloodPlasma osmotic pressure (300 mOsm/L） Crystalloid Osmotic Pressure（晶体渗透压）

8、 Pressure generated by all crystal substances, particularly electrolytes Important in maintaining fluid balance across cell membranes Colloid Osmotic Pressure（胶体渗透压） Osmotic pressure generated by plasma proteins, particularly albumin. Approximately 25 mmHg, but important in fluid transfer across cap

9、illariesProperties of blood4. Plasma pH Normal range: 7.357.45 Buffer systems（缓冲系统）:NaHCO3/H2CO3, Pro-Na/Pro, Na2HPO4/NaH2PO4Hb-K/Hb, HbO2-K/HbO2, K2HPO4/KH2PO4, KHCO3/H2CO3Properties of bloodFunctions of blood Transportation O2 and CO2 Nutrients (glucose, lipids, amino acids) Waste products (e.g.,

10、metabolites) Hormones Regulation pH Body temperature Protection Blood coagulation ImmunityBody Fluid = 60% of Body Weight (BW)Intracellular Fluid2/3, 40% of BWExtracellular Fluid1/3, 20% of BWPlasma 5% of BWInterstitial Fluid15% of BWPlasmaWater (92% of plasma)serves as transport medium; carries hea

11、t proteins Nutrients glucose, amino acids, lipids & vitamins Waste products nitrogenous wastes like urea Dissolved gasesO2 & CO2 Hormones Plasma composition Plasma proteinsAlbumins （白蛋白）(60-80% of plasma proteins) most important in maintenance of osmotic balance produced by liver Globulins （

12、球蛋白）(1-, 2-, -, -)important for transport of materials through the blood (e.g., thyroid hormone & iron) clotting factors produced by liver except -globulins which are immunoglobulins (antibodies) produced by lymphocytes Fibrinogen（纤维蛋白原） important in clotting produced by liver Erythrocytes Struc

13、ture Biconcave No nucleus Few organelles Small Hemoglobin moleculesuCountRBC countM: 4.05.51012/LF: 3.55.01012/LHemoglobin（血红蛋白）M: 120160 g/LF: 110150 g/LPhysiological properties Plastic deformability（可塑变形性）Erythrocyte Sedimentation Rate (ESR)（红细胞沉降率） The distance that red blood cells settle in a tu

14、be of blood in one hour Normal value, M: 015 mm/h，F: 020 mm/h An indication of inflammation which increases in many diseases, such as tuberculosis & rheumatoid arthritis Suspension stability（悬浮稳定性）红细胞叠连（rouleaux formation）Osmotic fragility （渗透脆性）the susceptibility of a red blood cell to break ap

15、art when exposed to saline solutions of a lower osmotic pressure than that of the human cellular fluiduFunction of RBCs 1. Transport of O2 and CO22. BufferingProduction of RBC (Erythropoiesis) Hemocytoblast stem cell Stem cell becomes committed Early erythroblasts have ribosomes早期的红细胞有核糖体 Erythrobla

16、sts accumulate iron and hemoglobin红细胞积聚铁和血红蛋白 Normoblasts eject organelles Released as erythrocyte Nutritional Requirements for Erythropoiesis1. Many vitamins, minerals, and proteins are necessary for normal RBC production2. Clinically, folic acid（叶酸）, VitB12, and iron （铁） are the most important. De

17、ficiencies of these factors lead to characteristic anemias（贫血）Diagram of iron kinetics from iron stores to developing red blood cell (RBC)Iron stores include the bone marrow, reticuloendothelial system (liver and spleen) and RBCs. Transferrin (total iron-binding capacity TIBC) transports iron (Fe) t

18、o developing erythrocytes. Iron is deposited in the RBC, and transferrin returns to storage sites to bind more Fe for transport. Lactoferrin is a competitor of transferrin; it takes Fe that is free and returns it to storage sites. Lactoferrin levels are elevated in anemia of chronic disease. Increas

19、es in interleukin-1 increase the sequestration of Fe in storage sites. (Hb=hemoglobin)Regulation of Erythropoiesis1. Erythropoietin（促红细胞生成素）2. Hormones: Androgen(雄激素)Hypoxia-inducible factor-1, HIF-1Erythropoiesis is hormonally regulated:decreased oxygen delivery to the kidney causes the secretion o

20、f erythropoietin, which activates receptors in bone marrow, leading to an increase in the rate of erythropoiesis.average lifespan = about 120 daysuDestruction of RBC Macrophages engulf(吞噬)old RBCsIron is salvagedHeme degrades into bilirubinAnemia（贫血） Anemia is defined as a qualitative or quantitativ

21、e deficiency of hemoglobin, a protein found inside red blood cells (RBCs) The three main classes of anemia： excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss) excessive blood cell destruction (hemolysis) deficient red blood cell production (ineffective hematop

22、oiesis)Iron deficiency anemia缺铁性贫血Megaloblastic anemia巨幼红细胞性贫血地中海贫血地中海贫血 Hemolysis（溶血）Red blood cells hemolysisWhite blood cells (Leucocytes)（白细胞）（白细胞）uTypes of WBC WBC Count (109/L) %GranulocytesNeutrophils2.07.0 5070Eosinophils0.020.5 0.55Basophils00.1 01Monocytes0.120.8 38Lymphocytes0.84.0 2040To

23、tal 410WBC countLeukopoiesis (白细胞生成) Myeloblasts (原始粒细胞) become all of the granular leukocytes (白细胞) Monoblasts become monocytes Lymphoblasts become lymphocytesPlatelets uFormed in the bone marrow from cells called megakaryocytes (巨核细胞)uWithout nucleus, but can secrete a variety of substances unorma

24、l value: (100300) x 109/LuAverage lifespan=714 days uPlay an important role in hemostasis1. AdhesionPlatelets adhere to the vessel wall at the site of injuryPhysiological properties of plateletsvon Willebrand factor, vWF2. Aggregation (聚合)Platelets adhere to one another Inducers of platelet aggregat

25、ion ADP Low dose1st reversible phase High dose 2nd irreversible phase Thromboxane A2 (TXA2) Collagen (胶原) Thrombin (凝血酶)Phospholipid (磷脂磷脂)Arachidonic Acid (花生四烯酸花生四烯酸)Phospholipase A2 TXA2Cyclo-oxygenasePGG2 & PGH2PGI2Prostacyclin synthase(Vascular endothelium)Thromboxane synthase(Platelets)Agg

26、regation Anti-aggregationContraction RelaxationPlatelet interactions with agonists and antagonists of platelet aggregation, the vessel wall, other platelets, and adhesive macromolecules. Agents in parentheses prevent the formation or inhibit the function of the adjacent agonists of platelet aggregat

27、ion. ADP = adenosine diphosphate, VWF = von Willebrand factor, cAMP = cyclic adenosine monophosphate, GP = glycoprotein. 3. Release or secretion: Platelets contain alpha and dense granules Dense granules: containing ADP or ATP, calcium, and serotonin -granules: containing platelet factor 4, PDGF, fi

28、bronectin, B-thromboglobulin, vWF, fibrinogen, and coagulation factors V and XIII Platelet (top figure)Showing its alpha and dense granules and canalicular system. (bottom figure) Platelets major functions, including secretion of stored products, as well as its attachment, via specific surface glyco

29、proteins (GP), to denuded epithelium (bottom) and other platelets (left).VWF: von Willebrand factor; TSP: thrombospondin; PF4: platelet factor 4; PDGF: platelet derived growth factor; TG: beta thromboglobulin; ADP: adenosine diphosphate; ATP: adenosine triphosphate. Platelet responses to activation

30、and the congenital disorders of platelet functionAC = adenylyl cyclase; BSS = BernardSoulier syndrome; CO = cyclooxygenase; DG = diacylglycerol; G = GTP-binding protein; IP3 = inositol trisphosphate; MLC = myosin light chain; MLCK = myosin light chain kinase; P2Y1, P2Y12 = G-protein-coupled ADP rece

31、ptors; PAF = platelet activating factor; PGG2/PGH2 = prostaglandin arachidonic pathway intermediates; PIP2 = phosphatidylinositol bisphosphate; PKC = protein kinase C; PLA2 = phospholipase A2; TK = tyrosine kinase; PLC = phospholipase C; TS = thromboxane synthase; TxA2 = thromboxane A2; vWD = von Wi

32、llebrand disease; vWF = von Willebrand factor. 4. ContractionClot retraction (血块回缩) 5. Adsorption (吸附) Clotting factors: I, V, XI, XIIIProduction of Platelets (Thrombocytes) Formation Large multinucleated cells that pushes against the wall of the capillary Cytoplasmic extensions stick through and se

33、parate Hemostasis（止血） The arrest of bleeding following injury and the result of 3 interacting, overlapping mechanisms: Vascular spasm（血管收缩）（血管收缩） Formation of a platelet plug（血小板血栓形成）（血小板血栓形成） Blood coagulation (clotting)（血液凝固）（血液凝固）Role of vascular endothelium in hemostasiso Vasoconstriction: reduc

34、ed blood flow facilitates contact activation of platelets and coagulation factors o Exposure of sub-endothelial basement membrane and collagen o Release of tissue thromboplastins (组织因子组织因子) o Synthesis of basement membrane components, tissue factor (组织因子组织因子), vWF, plasminogen activator (纤溶酶原激活物纤溶酶原

35、激活物), antithrombin III (抗凝血酶抗凝血酶III), thrombomodulin (血栓调节蛋白血栓调节蛋白)Signaling mediates responses to damage in a blood vessel:adjacent endothelial cells are a source of signals that influence platelet aggregation and alter blood flow and clot formation at the affected site.Role of platelets in hemosta

36、sis Release of vasoconstricting substances Formation of the platelet plug Promotion of blood clotting Clot retraction Clotting factorsClotting factorSynonymsIfibrinogen纤维蛋白原II prothrombin凝血酶原III tissue thromboplastin组织因子IV Ca2+Vproaccelerin前加速素易变因子VII proconvertin前转变素稳定因子VIIIantihemophilic factor抗血友

37、病因子IXplasma thromboplastin component血浆凝血活酶XStuart-Prower factorXI plasma thromboplastin antecedent血浆凝血活酶前质XII contact factor接触因子XIII fibrin-stabilizing factor纤维蛋白稳定因子uBlood coagulationThe liver plays a critical role in producing andmodifying blood-borne proteins, including those used in the clotting

38、pathway. Moreover, bile salts from the liver facilitate the absorption of lipids in the diet, including vitamin K, which is required for the synthesis of prothrombin.Coagulation factors and related substancesNumber and/or nameFunctionI (fibrinogen)Forms clot (fibrin)II (prothrombin)Its active form (

39、IIa) activates I, V, VII, VIII, XI, XIII, protein C, plateletsTissue factorCo-factor of VIIa (formerly known as factor III)CalciumRequired for coagulation factors to bind to phospholipid (formerly known as factor IV)V (proaccelerin, labile factor)Co-factor of X with which it forms the prothrombinase

40、 complexVIUnassigned old name of Factor VaVII (stable factor)Activates IX, XVIII (antihemophilic factor)Co-factor of IX with which it forms the tenase complexIX (Christmas factor)Activates X: forms tenase complex with factor VIIIX (Stuart-Prower factor)Activates II: forms prothrombinase complex with

41、 factor VXI (plasma thromboplastin antecedent)Activates IXXII (Hageman factor)Activates factor XI and prekallikreinXIII (fibrin-stabilizing factor)Crosslinks fibrinvon Willebrand factorBinds to VIII, mediates platelet adhesionprekallikreinActivates XII and prekallikrein; cleaves HMWKhigh-molecular-w

42、eight kininogen (HMWK)Supports reciprocal activation of XII, XI, and prekallikreinfibronectinMediates cell adhesionantithrombin IIIInhibits IIa, Xa, and other proteases;heparin cofactor IIInhibits IIa, cofactor for heparin and dermatan sulfate (minor antithrombin)protein CInactivates Va and VIIIapro

43、tein SCofactor for activated protein C (APC, inactive when bound to C4b-binding protein)protein ZMediates thrombin adhesion to phospholipids and stimulates degradation of factor X by ZPIProtein Z-related protease inhibitor (ZPI)Degrades factors X (in presence of protein Z) and XI (independently)plas

44、minogenConverts to plasmin, lyses fibrin and other proteinsalpha 2-antiplasminInhibits plasmintissue plasminogen activator (tPA)Activates plasminogenurokinaseActivates plasminogenplasminogen activator inhibitor-1 (PAI1)Inactivates tPA & urokinase (endothelial PAI)plasminogen activator inhibitor-

45、2 (PAI2)Inactivates tPA & urokinase (placental PAI)cancer procoagulantPathological factor X activator linked to thrombosis in cancerExploration of the details of the clotting pathway has yielded detailed information about the sequence, only a portion of which is represented here. Note thrombins

46、influence in three different directions.Knowledge that thrombin plays acentral role in clottinghas generated detailedstudies of the possiblepathways resulting inits formation:the extrinsic pathway is the more important of the two under most circumstances.Coagulation cascade3 processes2 pathwaysFibri

47、n Polymerization Structure of Fibrinogen A deficiency of a clotting factor can lead to uncontrolled bleeding. Vitamin K is a cofactor needed for the synthesis of factors II, VII, IX, & X in the liver. So a deficiency of Vitamin K predisposes to bleeding. Hemophilia (血友病)RasputinSerum （血清）（血清）ser

48、um = plasma fibrinogen and some of the other clotting factors + substances released by vascular endothelial cells andplateletsClotting time (凝血时间)：4-12 mino Serine Protease InhibitorAntithrombin III（抗凝血酶（抗凝血酶III）inhibiting all serine proteases of the blood coagulation system, including: o thrombin o

49、 factor IXa, Xa, XIa, XIIauAnticoagulants（抗凝物质）（抗凝物质）o Protein C system（蛋白（蛋白C系统）系统）Protein C, thrombomodulin, Protein So Tissue factor pathway inhibitor (TFPI)（组织因子途径抑制物）（组织因子途径抑制物）In an uninjured vessel,thrombin bound to thrombomodulin activatesprotein C, which blocks theclotting response. Heparin

50、（肝素）（肝素）A polysaccharide (多糖) produced by the tissue mast cells and the basophils of circulating bloodInterfering primarily with the action of thrombin after combining with antithrombin III Fibrinolysis（纤维蛋白溶解）（纤维蛋白溶解）o 2 processesoActivation of plasminogenoDegradation of fibrino 4 components of pla

51、sma fibrinolysis systemoPlasminogen（纤维蛋白溶解酶原）（纤维蛋白溶解酶原）oPlasmin（纤维蛋白溶解酶）（纤维蛋白溶解酶）oPlasminogen activatoroPlasminogen inhibitorFollowing tissue repair, fibrin clots are dissolved in a process mediated by plasmin; synthetic plasminogenactivators can be used immediately after a stroke orheart attack to

52、help dissolve clots and restore blood flow. pathways of plasminogen (纤维蛋白溶酶原) activationFibrin Degradation Products (FDP)oExtrinsic Plasminogen activatorTissue-type plasminogen activator (tPA)Urokinase oPlasminogen inhibitorPlasminogen activator inhibitor type-1 (PAI-1) 2-antiplasminAntithrombin III

53、 Blood typeso Erythrocytes carry on their surfaces many antigens, but the most important and commonly recognized are the A and B substances and the Rhesus (Rh) factors ABO blood typesBlood typeAntigenAntibodyAAanti-BBBanti-AABA & BneitherOneitheranti-A & anti-BO ABA B inherited independent o

54、f ABO system Rh positive = antigen present (mainly D antigen) & no antibodies Rh negative = no antigen & antibodies will be produced if exposure occursRh group/type Blood volume The total blood volume is 7 8% of body weight. For a 70 Kg male, it is 5.0 5.5 L. Blood volume & blood transfu

55、sionTransfusion is the process of replacing blood or blood component which a body has lost in surgery, through an accident or as a result of medical treatment such as chemotherapy. Blood transfusionSterility, Viability, Quantity, Safety & Quality Risk from Transfusion1.Allergic reactions to the

56、blood or one of its components2.Hemolytic reaction3.Diseases transmission, such as HIV, Hepatitis B, C virus Basic principles1.Unexpected, emergency blood transfusion is rarely required. It is needed only in situations of massive hemorrhage like severe trauma, gynecologic and obstetric emergency, or

57、 gastrointestinal bleeding. 2.In many cases, resuscitation can be achieved by use of colloid or crystalloid plasma expanders instead of blood. 3.Blood transfusion is not free of risk, even in the best of conditions. Guideline1.Ensuring that transfusion recipients and donors have compatible blood gro

58、up2.Cross-match test3.Tests screening for Hepatitis virus, HIV in blood donatedRBCRBCPlasmaPlasmaDonorRecipientCross-match TestOptionDefinitionAdvantageDisadvantagePre-operative Autologous DonationA patients blood is collected and stored until neededDisease transmission and allergic reactions are el

59、iminatedMust be planned in advance May delay surgery Certain medical conditions disqualifyPerioperative Autologous TransfusionBlood lost during or after surgery is collected, processed and returnedDisease transmission and allergic reactions are eliminatedMust be planned in advance Certain medical co

60、nditions disqualifyVolunteer Blood DonationBlood voluntarily donated to a community blood centerAvailability in emergenciesRisk of disease transmission and allergic reactionDirected Donor Blood DonationPatient selects blood donorPatient feels safe with donors selectedMay be higher risk of disease transmission and allergic reaction Blood type must be co