Blood Physiology 血液生理. Ying-ying Chen, PhD Zhejiang University School of Medicine

Transcription

1 Blood Physiology 血液生理 Ying-ying Chen, PhD Zhejiang University School of Medicine

2 Functions of blood Transportation (gases, nutrients, hormones, wastes) Regulation (ph, fluid and ion balance, thermoregulation ) Protection (immune response, clotting)

3 (I) Body Fluid & Internal Environment 体液和内环境 Body Fluid = 60% of Body Weight (BW) Extracellular Fluid 1/3, 20% of BW Plasma 4% of BW Interstitial Fluid 16% of BW Intracellular Fluid 2/3, 40% of BW 70 kg Male, 42 L

4 Extracellular Fluid 1/3, 20% of BW Plasma 4% of BW Interstitial Fluid 16% of BW Internal Environment External Environment

5 Homeostasis 稳态 (from the Greek words for same and steady ): maintenance of static or constant conditions in the internal environment Why? W. Cannon

6 Components of Homeostasis Concentration of O 2 and CO 2 ph of the internal environment Concentration of nutrients and waste products Concentration of salt and other electrolytes temperature Volume and pressure of extracellular fluid

7 (II) Components of blood Plasma 血浆 Formed elements Blood cells

8 Hematocrit 血细胞比容 : the volume of red blood cells as a percentage of centrifuged whole blood M: 45% F: 42%

9 Plasma mostly water (90% by volume) proteins (8% by weight) small solutes: electrolytes, lactic acid, urea

10 Formed elements Red Blood Cells (RBC) White Blood Cells (WBC) Platelets

11 Physical & chemical properties of blood 血液的理化特性 1. Specific Gravity 血液的比重 Depending on hematocrit & protein composition Whole blood: 1.050~1.060 Plasma: 1.025~1.035 Red blood cells: 1.090

12 2. Viscosity 粘滞性 internal friction of adjacent fluid layers fluid and the wall of the vessel relative viscosity whole blood 4~5 (depending on hematocrit) plasma 1.6~2.4 (related to the protein composition of the plasma)

13 3. Osmotic Pressure 渗透压 ability of a fluid to hold or attract water Solute molecules Selectively permeable memebrane blocks solute High osmotic pressure Low osmotic pressure Direction of water movement

14 Osmotic pressure depends only on the number of solute molecules or ions, NOT on their chemical composition and size 1M glucose=1 Osm 1M NaCl =2 Osm

15 Plasma osmotic pressure (~310 mosm/l) Crystalloid Osmotic Pressure 晶体渗透压 Colloid Osmotic Pressure 胶体渗透压 (0.5% of the total osmotic pressure ) plasma

16 Crystalloid Osmotic Pressure: important in maintaining fluid balance across cell membranes Colloid Osmotic Pressure: important in fluid transfer across capillaries

17 Only substances which act as impermeant molecules can be used to make isotonic solutions ( 等张溶液 )

18 4. Plasma ph Normal range: 7.35~7.45 Buffer systems: 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 /H2CO 3

19 (III) Red blood cells (Erythrocytes) RBC count M: 4.5~ /L F: 3.8~ /L

20 Morphology 形态 can be deformed Biconcave discs 双凹圆碟形

21 Morphology Biconcave discs Without a nucleus cannot perform repairs average lifespan = about 120 days

22 Morphology Biconcave discs Without a nucleus Without mitochondria anaerobic metabolism

23 Properties of erythrocytes 1. Permeability 通透性 2. Deformability 可塑变形性

24 3. Suspension stability 悬浮稳定性 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 values: M: less than 15 mm/h F: less than 20 mm/h

25 4. 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 plasma

26 Functions 功能 1. Transport of O 2 and CO 2

27 Functions 1. Transport of O 2 and CO 2 2. Buffering 缓冲 : hemoglobin

28 Production of RBC (Erythropoiesis) 红细胞生成

29 Iron balance

30 Regulation of Erythropoiesis 红细胞生成的调节 1. Erythropoietin 促红细胞生成素 2. Androgen 雄激素

31 White blood cells (Leukocytes) Types of WBC 白细胞

32 WBC count 白细胞计数

33 Platelets (Thrombocytes) 血小板 Formed in the bone marrow from cells called megakaryocytes ( 巨核细胞 )

34 Platelets (Thrombocytes) normal value: (150~350) x 10 9 /L Average lifespan=7~14 days

35 Morphology 形态 without a nucleus contain numerous granules 颗粒 contain actin and myosin

36 Function of platelets Play an important role in hemostasis ( 生理性止血 )

37 (IV) Physiological hemostasis 生理性止血 the arrest of bleeding following injury Three major events: 1. Vascular constriction 血管收缩 2. Formation of a platelet plug 血小板血栓形成 3. Blood coagulation (clotting) 凝血

38 1. Vascular constriction

39 changes occur in the endothelium at the injury site: Expose collagen ( 胶原 ) Release chemical factors (ADP and tissue factor) and local hormones (endothelins) Become "sticky"

40 2. Formation of a platelet plug Platelet Adhesion Platelet Activation Fibrinogen receptor Platelet Aggregation

41 Physiological properties of platelets (1) Adhesion 粘附 : Platelets adhere to the vessel wall at the site of injury Resting Platelets Platelet Adhesion vwf von Willebrand factor (vwf) is a plasma protein that is secreted by endothelial cells and platelets.

42 collagen fibrils vwf acts as a bridge between platelets and collagen fibrils

43 (2) Aggregation 聚集 Platelets stick to each other at the site of injury Platelet Aggregation Activation of platelets is required

44 Platelet Activation shape changed Typical smooth discoid shape of resting platelets Typical spiny spheric shape of activated platelets

45 Platelet Activation shape changed release secondary platelet agonists TXA 2, ADP, Serotonin, Fibrinogen, Thrombospondin

46 Mechanism of aggregation Fibrinogen receptors are activated and allow platelets to become cross-linked by fibrinogen Fibrinogen Fibrinogen receptors

47 (3) Contractile property 收缩的特性 Contractile proteins largely consist of myosin and actin filaments Compression and strengthening of the platelet plug

48 Formation of a platelet plug Platelet Adhesion Platelet Activation Fibrinogen receptor Platelet Aggregation

49 Positive feedback ( 正反馈 ) NO Why does the platelet plug not continuously expand?

50 3. Blood coagulation 血液凝固 transformation of blood from a liquid into a solid gel by changing fibrinogen to an insoluble polymer (fibrin 纤维蛋白 )

51 Clotting factors ( 凝血因子 )

52 Coagulation cascade

53 Two pathways of coagulation cascade intrinsic pathway 内源性途径 extrinsic pathway 外源性途径

54 Damaged endothelial cells The Extrinsic Pathway Initiated by the generation of the tissue factor-factor VIIa complex Requires factor III and VII Short and fast VIIa TF Xa Ca 2+ Thrombin

55 Exposed collagen Contact activation The Intrinsic Pathway Initiated by the activation of factor XII Requires factor XII, XI, IX, and VIII Long and Slow XIIa Xa Active factor cascade Thrombin

56 The Common Pathway ( 共同通路 ) Xa Va Prothrombin phospholide Ca 2+ X V Thrombin XIII XIIIa Fibrinogen Fibrin Cross-linked Fibrin

57 prothrombinase complex 凝血酶原酶复合物 conversion of prothrombin ( 凝血酶原 ) to thrombin ( 凝血酶 ) Va Xa Ca 2+ II Phospholipid membrane Va Xa Ca 2+ F1.2 Phospholipid membrane IIa

58 Thrombin ( 凝血酶 ) converts Fibrinogen( 纤维蛋白原 )to Fibrin ( 纤维蛋白 ) Feedback Control of Blood Clotting Activates XIII V XI VIII + Prothrombin Thrombin XIII XIIIa Fibrinogen Fibrin Cross-linked Fibrin

59 Factors affect Blood Clotting Concentration of plasma calcium ions Deficiency of Vitamin K: factors II, VII, IX, and X Inherited disorders : hemophilia( 血友病 )

60 Role of platelets in hemostasis formation of the platelet plug release of vasoconstricting substances promotion of blood coagulation clot retraction

61 4. Anticlotting systems 抗凝系统 Three groups: Inhibitors of clotting factor synthesis Inhibitors of thrombin Antiplatelet

62 (1) Antithrombin III ( 抗凝血酶 Ⅲ,ATIII) Inhibits Factors IXa, Xa, and Thrombin a a Fibrin Fibrin Fibrin Fibrin Fibrin Fibrin

63 The presence of heparin( 肝素 ) increases the activity of ATIII by

64 (2) Protein C synthesized in the liver as an inactive form

65 The activity of Protein C is markedly enhanced by its cofactor Protein S

66 (3) Tissue factor pathway inhibitor ( 组织因子途径抑制物,TFPI) Extrinsic Pathway VIIa TF Xa TFPI Thrombin

67 X Mechanism Actived complex VIIa TF Xa Thrombin TFPI VIIa Xa TF Inactived complex TFPI Xa Inactived complex

68 5. The Fibrinolytic System 纤维蛋白溶解系统 Fibrinolysis ( 纤维蛋白溶解 ): the fibrin clot is removed from the site of vascular injury during the healing process

69 Processes of Fibrinolysis Activation of plasminogen ( 纤溶酶原 ) Degradation of fibrin

70 Plasminogen activators Tissue plasminogen activator ( 组织型纤溶酶原激活物,t-PA) Urokinase( 尿激酶 ),. PLG: Plasminogen FDPs: Fibrin degradation products

71 6. Anticlotting drugs 抗凝药物 Aspirin: an important inhibitor of platelet activation Phospholipid Phospholipase A 2 Arachidonic Acid Cyclooxygenase (COX) Aspirin Thromboxane synthase (Platelets) TXA 2 PGG 2 & PGH 2 Prostacyclin synthase (Vascular endothelium) PGI 2 Aggregation Contraction Anti-aggregation Relaxation

72 Heparin EDTA (ethylene diamine tetroacetic acid) : removes Ca 2+ from plasma CPD (citrate phosphate dextrose) : ties up plasma Ca 2+

73 A physiological balance Anti-coagulation Fibrinolysis Coagulation

74 (V) Blood groups 血型 created by antigens present on the surface of red blood cells ABO type Rhesus type

75 ABO Blood Group System Blood Type A B AB O RBC Antigens A B A and B none Serum Antibodies anti-b anti-a none anti-a and anti-b

76 Rh (Rhesus) Blood Group System Blood Type Rh positive Rh negative RBC Antigens Rh factor (or D ) none none Serum Antibodies none (develop Rh antibody only after exposed to Rh + blood)

77 Blood typing O AB A B

78 Cross-matching ( 交叉配血试验 ) Donor Recipient RBC RBC Plasma Plasma