1. 赖蒽茵 浙江大学医学院生理系 求是特聘教授 浙江省 “ 千人计划 ” 人才， 博导 laienyin@zju.edu.cn 13:15-14:00 ， May 12 ， 2014 ，基础医学导论 紫金港东 2-203 ， 2013 级五年制临床，共 150 人 Blood Physiology / 血液的主要功能

2. Body Fluid = 60% of Body Weight (BW) Intracellular Fluid 2/3, 40% of BW Extracellular Fluid 1/3, 20% of BW Plasma 5% of BW Interstitial Fluid 15% of BW 70 kg Male, 42 L Internal environment （内环境）

3. Extracellular Fluid 1/3, 20% of BW Plasma 5% of BW Interstitial Fluid 15% of BW Internal Environment

5. Homeostasis （稳态） Homeostasis (from the Greek words for “ same ” and “ steady ” ): maintenance of static or constant conditions in the internal environment Walter B. Cannon http://www.harvardsquarelib rary.org/unitarians/cannon_ walter.html

6. Components of Homeostasis: l Concentration of O 2 and CO 2 l pH of the internal environment l Concentration of nutrients and waste products l Concentration of salt and other electrolytes l Volume and pressure of extracellular fluid

7. Body's systems operate together to maintain homeostasis: Skin systemSkeletal and muscular system Circulatory systemRespiratory system Digestive systemUrinary system Nervous systemEndocrine system Lymphatic systemReproductive system How is homeostasis achieved?

8. 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）

13. Plasma includes water, ions, proteins, 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).

14. the volume of red blood cells as a percentage of centrifuged whole blood M: 40~50% F: 37~48% Hematocrit （ packed cell volume, 血细胞比容）

15. Properties of blood 1. Specific Gravity （比重） Depending on hematocrit & protein composition Whole blood ： 1.050~1.060 Plasma ： 1.025~1.035 Red blood cells ： 1.090

16. 2. Viscosity （粘度） Relative viscosity of whole blood 4~5 depending on hematocrit Relative viscosity of plasma 1.6~2.4 related to the protein composition of the plasma Properties of blood

17. 3. 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 blood

18. Plasma osmotic pressure (~300 mOsm/L ） –Crystalloid Osmotic Pressure （晶体渗透压） 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 capillaries Properties of blood

19. 4. Plasma pH Normal range: 7.35~7.45 Buffer systems （缓冲系统） : NaHCO 3 /H 2 CO 3, Pro-Na/Pro, Na 2 HPO 4 /NaH 2 PO 4 Hb-K/Hb, HbO 2 -K/HbO 2, K 2 HPO 4 /KH 2 PO 4, KHCO 3 /H 2 CO 3 Properties of blood

20. Functions of blood Transportation –O 2 and CO 2 –Nutrients (glucose, lipids, amino acids) –Waste products (e.g., metabolites) –Hormones Regulation –pH –Body temperature Protection –Blood coagulation –Immunity

21. Body Fluid = 60% of Body Weight (BW) Intracellular Fluid 2/3, 40% of BW Extracellular Fluid 1/3, 20% of BW Plasma 5% of BW Interstitial Fluid 15% of BW Plasma

22. Water (92% of plasma) serves as transport medium; carries heat proteins Nutrients glucose, amino acids, lipids & vitamins Waste products nitrogenous wastes like urea Dissolved gases O2 & CO2 Hormones Plasma composition

23. Plasma proteins

24. Albumins （白蛋白） (60-80% of plasma proteins) most important in maintenance of osmotic balance produced by liver Globulins （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

25. Erythrocytes Structure Biconcave No nucleus Few organelles Small Hemoglobin molecules

26. u Count RBC count M: 4.0~5.5×10 12 /L F: 3.5~5.0×10 12 /L Hemoglobin （血红蛋白） M: 120~160 g/L F: 110~150 g/L

27. Physiological properties Plastic deformability （可塑变形性）

28. Erythrocyte Sedimentation Rate (ESR) （红细胞沉降率） The distance that red blood cells settle in a tube of blood in one hour Normal value, M: 0~15 mm/h ， F: 0~20 mm/h An indication of inflammation which increases in many diseases, such as tuberculosis & rheumatoid arthritis… Suspension stability （悬浮稳定性）

29. Osmotic fragility （渗透脆性） the susceptibility of a red blood cell to break apart when exposed to saline solutions of a lower osmotic pressure than that of the human cellular fluid

30. u Function of RBCs 1. Transport of O 2 and CO 2 2. Buffering

31. Production of RBC (Erythropoiesis)

32. Hemocytoblast stem cell Stem cell becomes committed Early erythroblasts have ribosomes 早期的红细胞有核 糖体 Erythroblasts accumulate iron and hemoglobin 红细胞积聚铁和血红蛋白 Normoblasts eject organelles Released as erythrocyte

34. Regulation of Erythropoiesis 1. Erythropoietin （促红细胞生成素） 2. Hormones: Androgen( 雄激素 ) Hypoxia-inducible factor-1, HIF-1

35. average lifespan = about 120 days u Destruction of RBC  Macrophages engulf ( 吞噬 ) old RBCs  Iron is salvaged  Heme degrades into bilirubin

36. Anemia （贫血） Anemia is defined as a qualitative or quantitative 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 hematopoiesis)

37. Iron deficiency anemia 缺铁性贫血

38. Megaloblastic anemia 巨幼红细胞性贫血

39. 地中海贫血

40. Hemolysis （溶血） Red blood cells hemolysis

41. White blood cells (Leucocytes) （白细胞） u Types of WBC

42. WBC Count (  10 9 /L) % Granulocytes Neutrophils2.0~7.0 50~70 Eosinophils0.02~0.5 0.5~5 Basophils0~0.1 0~1 Monocytes0.12~0.8 3~8 Lymphocytes0.8~4.0 20~40 Total 4~10 WBC count

43. Leukopoiesis ( 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 lymphocytes

45. Platelets  Formed in the bone marrow from cells called megakaryocytes ( 巨核细胞 ) u Without nucleus, but can secrete a variety of substances u normal value: (100~300) x 10 9 /L u Average lifespan=7~14 days u Play an important role in hemostasis

46. 1. Adhesion Platelets adhere to the vessel wall at the site of injury Physiological properties of platelets von Willebrand factor, vWF

48. 2. Aggregation ( 聚合 ) Platelets adhere to one another

49. Phospholipid ( 磷脂 ) Arachidonic Acid ( 花生四烯酸 ) Phospholipase A 2 TXA 2 Cyclo-oxygenase PGG 2 & PGH 2 PGI 2 Prostacyclin synthase (Vascular endothelium) Thromboxane synthase (Platelets) Aggregation Anti-aggregation Contraction Relaxation

50. 4. Contraction Clot retraction ( 血块回缩 )

51. 5. Adsorption ( 吸附 ) Clotting factors: I, V, XI, XIII

52. Production of Platelets (Thrombocytes) Formation – Large multinucleated cells that pushes against the wall of the capillary – Cytoplasmic extensions stick through and separate

53. Hemostasis （止血） The arrest of bleeding following injury and the result of 3 interacting, overlapping mechanisms: Vascular spasm （血管收缩） Formation of a platelet plug （血小板血栓形成） Blood coagulation (clotting) （血液凝固）

54. Role of vascular endothelium in hemostasis oVasoconstriction: reduced blood flow facilitates contact activation of platelets and coagulation factors oExposure of sub-endothelial basement membrane and collagen oRelease of tissue thromboplastins ( 组织因子 ) oSynthesis of basement membrane components, tissue factor ( 组织因子 ), vWF, plasminogen activator ( 纤溶酶原激活物 ), antithrombin III ( 抗凝血酶 III), thrombomodulin ( 血栓调节蛋白 )

55. Clotting factors Clotting factorSynonyms Ifibrinogen 纤维蛋白原 II prothrombin 凝血酶原 III tissue thromboplastin 组织因子 IV Ca 2+ Vproaccelerin 前加速素易变因子 VII proconvertin 前转变素稳定因子 VIIIantihemophilic factor 抗血友病因子 IXplasma thromboplastin component 血浆凝血活酶 XStuart-Prower factor XI 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 u Blood coagulation

56. The liver plays a critical role in producing and modifying blood-borne proteins, including those used in the clotting 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.

57. Knowledge that thrombin plays a central role in clotting has generated detailed studies of the possible pathways resulting in its formation: the extrinsic pathway is the more important of the two under most circumstances.

58. Hemophilia ( 血友病 ) Rasputin

59. Serum （血清） serum = plasma – fibrinogen and some of the other clotting factors + substances released by vascular endothelial cells and platelets Clotting time (凝血时间)：4-12 min

60. oSerine Protease Inhibitor Antithrombin III （抗凝血酶 III ） inhibiting all serine proteases of the blood coagulation system, including: othrombin ofactor IX a, X a, XI a, XII a u Anticoagulants （抗凝物质）

61. Heparin （肝素）  A polysaccharide ( 多糖 ) produced by the tissue mast cells and the basophils of circulating blood  Interfering primarily with the action of thrombin after combining with antithrombin III

62. Fibrinolysis （纤维蛋白溶解） o2 processes oActivation of plasminogen oDegradation of fibrin o4 components of plasma fibrinolysis system oPlasminogen （纤维蛋白溶解酶原） oPlasmin （纤维蛋白溶解酶） oPlasminogen activator oPlasminogen inhibitor

63. Blood types oErythrocytes carry on their surfaces many antigens, but the most important and commonly recognized are the A and B substances and the Rhesus (Rh) factors

64. ABO blood types

66. Blood typeAntigenAntibody AAanti-B BBanti-A ABA & Bneither Oneitheranti-A & anti-B

67. inherited independent of ABO system Rh positive = antigen present (mainly D antigen) & no antibodies Rh negative = no antigen & antibodies will be produced if exposure occurs Rh group/type

68. Transfusion 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 transfusion Sterility, Viability, Quantity, Safety & Quality

69. Risk from Transfusion 1. Allergic reactions to the blood or one of its components 2. Hemolytic reaction 3. Diseases transmission, such as HIV, Hepatitis B, C virus

70. Guideline 1. Ensuring that transfusion recipients and donors have compatible blood group 2. Cross-match test 3. Tests screening for Hepatitis virus, HIV… in blood donated