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

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

[email protected]

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

Body Fluid = 60% of Body Weight (BW)

Intracellular Fluid2/3, 40% of BW

Extracellular Fluid1/3, 20% of BW

Plasma 5% of BW

Interstitial Fluid15% of BW

70 kg Male, 42 L

Internal environment （内环境）

Extracellular Fluid1/3, 20% of BW

Plasma 5% of BW

Interstitial Fluid15% of BW

Internal Environment

Homeostasis（稳态）

Homeostasis (from the

Greek words for “same” and

“steady”):

maintenance of static or

constant conditions in the

internal environment

Walter B. Cannonhttp://www.harvardsquarelibrary.org/unitarians/cannon_walter.html

Components of Homeostasis:

Concentration of O2 and CO2

pH of the internal environment

Concentration of nutrients and waste products

Concentration of salt and other electrolytes

Volume and pressure of extracellular fluid

Body's systems operate together to

maintain homeostasis:

Skin system Skeletal and muscular system

Circulatory system Respiratory system

Digestive system Urinary system

Nervous system Endocrine system

Lymphatic system Reproductive system

How 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, 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).

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）

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

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

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

• 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

4. Plasma pH

• Normal range: 7.35~7.45

• Buffer systems（缓冲系统） :

NaHCO3/H2CO3, Pro-Na/Pro, Na2HPO4/NaH2PO4

Hb-K/Hb, HbO2-K/HbO2, K2HPO4/KH2PO4, KHCO3/H2CO3

Properties of blood

Functions of blood• Transportation

– O2 and CO2 – Nutrients (glucose, lipids, amino acids) – Waste products (e.g., metabolites) – Hormones

• Regulation– pH– Body temperature

• Protection– Blood coagulation– Immunity

Body Fluid = 60% of Body Weight (BW)

Intracellular Fluid2/3, 40% of BW

Extracellular Fluid1/3, 20% of BW

Plasma 5% of BW

Interstitial Fluid15% of BW

Plasma

Water (92% of plasma)serves as transport medium; carries heat proteins Nutrients glucose, amino acids, lipids & vitamins

Waste products nitrogenous wastes like urea

Dissolved gasesO2 & CO2

Hormones

Plasma composition

• Plasma proteins

•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

Erythrocytes Structure

• Biconcave• No nucleus• Few organelles• Small• Hemoglobin molecules

Count

RBC count

M:

4.0~5.5×1012/L

F: 3.5~5.0×1012/L

Hemoglobin（血红蛋白）M: 120~160 g/L

F: 110~150 g/L

Physiological 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 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）

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

Function of RBCs

1. Transport of O2 and CO2

2. Buffering

Production of RBC (Erythropoiesis)

• 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

Regulation of Erythropoiesis

1. Erythropoietin（促红细胞生成素）

2. Hormones: Androgen(雄激素 )

Hypoxia-inducible factor-1, HIF-1

average lifespan = about 120 days

Destruction of RBC

Macrophages engulf( 吞噬 )old RBCs Iron is salvaged Heme degrades into bilirubin

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)

Iron deficiency anemia缺铁性贫血

Megaloblastic anemia巨幼红细胞性贫血

地中海贫血

Hemolysis（溶血） Red blood cells hemolysis

White blood cells (Leucocytes)（白细胞）

Types of WBC

WBC Count (109/L) %Granulocytes

Neutrophils 2.0~7.0 50~70Eosinophils 0.02~0.5 0.5~5Basophils 0~0.1 0~1

Monocytes 0.12~0.8 3~8Lymphocytes 0.8~4.0 20~40

Total 4~10

WBC count

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

Platelets

Formed in the bone marrow from cells called megakaryocytes (巨核细胞 )

Without nucleus, but can secrete a variety of substances

normal value:

(100~300) x 109/L Average lifespan=7~14 days Play an important role in

hemostasis

1. Adhesion

Platelets adhere to the vessel wall at the site of injury

Physiological properties of platelets

von Willebrand factor, vWF

2. Aggregation (聚合 )

Platelets adhere to one another

Phospholipid ( 磷脂 )

Arachidonic Acid ( 花生四烯酸 )

Phospholipase A2

TXA2

Cyclo-oxygenase

PGG2 & PGH2

PGI2

Prostacyclin synthase(Vascular endothelium)

Thromboxane synthase(Platelets)

Aggregation Anti-aggregationContraction Relaxation

• 4. ContractionClot retraction (血块回缩 )

• 5. Adsorption (吸附 )

Clotting factors: I, V, XI, XIII

Production of Platelets (Thrombocytes)

• Formation– Large multinucleated cells that pushes against the

wall of the capillary– Cytoplasmic extensions stick through and separate

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）

Role of vascular endothelium in hemostasis

o Vasoconstriction: reduced 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 )

o Synthesis 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 )

Clotting factors

Clotting factor SynonymsI fibrinogen纤维蛋白原II prothrombin凝血酶原III tissue thromboplastin组织因子IV Ca2+

V proaccelerin前加速素易变因子VII proconvertin前转变素稳定因子VIII antihemophilic factor抗血友病因子IX plasma thromboplastin component血浆凝血活酶X Stuart-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

Blood coagulation

The liver plays a critical role in producing andmodifying blood-borne proteins, including those used in the clottingpathway.

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.

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.

Hemophilia (血友病 )

Rasputin

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

o Serine Protease Inhibitor

Antithrombin III （抗凝血酶 III ）inhibiting all serine proteases of the blood coagulation

system, including:

o thrombin

o factor IXa, Xa, XIa, XIIa

Anticoagulants （抗凝物质）

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

Fibrinolysis （纤维蛋白溶解）

o 2 processeso Activation of plasminogen

o Degradation of fibrin

o 4 components of plasma fibrinolysis systemo Plasminogen （纤维蛋白溶解酶原）o Plasmin （纤维蛋白溶解酶）o Plasminogen activator

o Plasminogen inhibitor

Blood types

o 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 types

Blood type Antigen Antibody

A A anti-B

B B anti-A

AB A & B neither

O neither anti-A & anti-B

• 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

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

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

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