BLOOD【血液】
Qiang XIA (夏强), PhD
Department of Physiology
Room C518, Block C, Research Building, School of Medicine
Tel: 88208252
Email: xiaqiang@zju.edu.cn
Internal environment （内环境）
Body Fluid = 60% of Body Weight (BW)
Plasma 5% of BW
Extracellular Fluid
1/3, 20% of BW
Interstitial Fluid
15% of BW
70 kg Male, 42 L
Intracellular Fluid
2/3, 40% of BW
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
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
How is homeostasis achieved?
----Regulation
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
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).
Hematocrit（packed cell volume, 血细胞比容）
the volume of red blood cells as a percentage of
centrifuged whole blood
M: 40~50%
F: 37~48%
International Council for Standardization in Haematology (ICSH)
Recommendations for "Surrogate Reference" Method for the Packed Cell Volume
Physical & chemical 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
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
 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
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
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
Plasma
Body Fluid = 60% of Body Weight (BW)
Plasma 5% of BW
Extracellular Fluid
1/3, 20% of BW
Interstitial Fluid
15% of BW
70 kg Male, 42 L
Intracellular Fluid
2/3, 40% of BW
 Composition
Water (92% of plasma)
serves as transport medium; carries heat
Proteins (6~8% of plasma)
Inorganic constituents (1% of plasma)
e.g., Na+, Cl-, K+, Ca2+…
Nutrients
glucose, amino acids, lipids & vitamins
Waste products
e.g., nitrogenous wastes like urea
Dissolved gases
O2 & CO2
Hormones
•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
Red blood cells (Erythrocytes)
（红细胞）
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
Plastic deformability
（可塑变形性）
properties
d
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 value [Westergren method（魏氏法，国际血液学标准化委员
会推荐魏氏法为标准法）]:
M: 0~15 mm/h，F: 0~20 mm/h
 An indication of inflammation which increases in many diseases,
such as tuberculosis & rheumatoid arthritis…
International Council for Standardization in Haematology (ICSH)
红细胞叠连（rouleaux formation）
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
Notice that hemolysis begins in the 0.45% tube and is complete in the 0.35% tube.
 Function
of RBCs
1. Transport of O2 and CO2
2. Buffering
White blood cells (Leucocytes)
（白细胞）
 Types
of WBC
 WBC
WBC
Granulocytes
Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes
Total
count
Count (109/L)
%
2.0~7.0
50~70
0.02~0.5
0.5~5
0~0.1
0~1
0.12~0.8
3~8
0.8~4.0
20~40
4~10
Platelets
(Thrombocytes)





Formed in the bone marrow
from cells called
megakaryocytes
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
 Physiological
properties of platelets
1. Adhesion
Platelets adhere to the vessel wall at the site of injury
von Willebrand factor, vWF
2. Aggregation
Platelets adhere to one another
 3. Release or secretion:
Platelets contain alpha and dense granules
 Dense granules: containing ADP or ATP, calcium, and serotonin
 α-granules: containing platelet factor 4, PDGF, fibronectin, B-
thromboglobulin, vWF, fibrinogen, and coagulation factors V
and XIII
Schematic drawing of the
platelet (top figure), showing its
alpha and dense granules and
canalicular system. The bottom
figure illustrates the platelet's
major functions, including
secretion of stored products,
as well as its attachment, via
specific surface glycoproteins
(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.
 4. Contraction
Clot retraction (血块回缩)
 5. Adsorption
Clotting factors: I, V, XI, XIII
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）
Bleeding time (出血时间)：<9 min
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 hemostasis
 Release of vasoconstricting substances
 Formation of the "platelet plug"
 Promotion of blood clotting
 Clot retraction
 Blood
coagulation
Clotting factors
Clotting factor
Synonyms
I
II
III
IV
V
VII
VIII
IX
X
XI
XII
XIII
fibrinogen纤维蛋白原
prothrombin凝血酶原
tissue thromboplastin组织因子
Ca2+
proaccelerin前加速素易变因子
proconvertin前转变素稳定因子
antihemophilic factor抗血友病因子
plasma thromboplastin component血浆凝血活酶
Stuart-Prower factor
plasma thromboplastin antecedent血浆凝血活酶前质
contact factor接触因子
fibrin-stabilizing factor纤维蛋白稳定因子
Coagulation factors and related substances
Number and/or name
I (fibrinogen)
II (prothrombin)
Tissue factor
Calcium
Function
Forms clot (fibrin)
Its active form (IIa) activates I, V, VII, VIII, XI, XIII, protein C, platelets
V (proaccelerin, labile factor)
Co-factor of VIIa (formerly known as factor III)
Required for coagulation factors to bind to phospholipid (formerly known as
factor IV)
Co-factor of X with which it forms the prothrombinase complex
VI
VII (stable factor)
VIII (antihemophilic factor)
IX (Christmas factor)
X (Stuart-Prower factor)
XI (plasma thromboplastin antecedent)
XII (Hageman factor)
XIII (fibrin-stabilizing factor)
von Willebrand factor
prekallikrein
high-molecular-weight kininogen (HMWK)
fibronectin
antithrombin III
heparin cofactor II
Unassigned – old name of Factor Va
Activates IX, X
Co-factor of IX with which it forms the tenase complex
Activates X: forms tenase complex with factor VIII
Activates II: forms prothrombinase complex with factor V
Activates IX
Activates factor XI and prekallikrein
Crosslinks fibrin
Binds to VIII, mediates platelet adhesion
Activates XII and prekallikrein; cleaves HMWK
Supports reciprocal activation of XII, XI, and prekallikrein
Mediates cell adhesion
Inhibits IIa, Xa, and other proteases;
Inhibits IIa, cofactor for heparin and dermatan sulfate ("minor antithrombin")
protein C
protein S
Protein Z-related protease inhibitor (ZPI)
Inactivates Va and VIIIa
Cofactor for activated protein C (APC, inactive when bound to C4b-binding
protein)
Mediates thrombin adhesion to phospholipids and stimulates degradation
of factor X by ZPI
Degrades factors X (in presence of protein Z) and XI (independently)
plasminogen
alpha 2-antiplasmin
tissue plasminogen activator (tPA)
urokinase
plasminogen activator inhibitor-1 (PAI1)
plasminogen activator inhibitor-2 (PAI2)
cancer procoagulant
Converts to plasmin, lyses fibrin and other proteins
Inhibits plasmin
Activates plasminogen
Activates plasminogen
Inactivates tPA & urokinase (endothelial PAI)
Inactivates tPA & urokinase (placental PAI)
Pathological factor X activator linked to thrombosis in cancer
protein Z
Exploration of the details of the clotting pathway has
yielded detailed information about the sequence,
only a portion of which is represented here.
Note thrombin’s influence in three different directions.
Coagulation cascade
3 processes
2 pathways
Structure of
Fibrinogen
Fibrin
Polymerization
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.
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
 Which of the following statements is correct?
A Damaged tissue releases a substance called tissue fibrinogen, which is mainly
composed of phospholipids
B Damage to the vessel wall initiates what is called the intrinsic pathway
C The activation of protein coagulation factor plus the release of platelet
thromboplastin eventually leads directly to the formation of thrombin
D The actual blood clotting is caused by a conversion of the plasma protein
prothrombin into another protein thrombin, which is the enzyme that causes
the polymerization of the plasma fibrinogen molecules into fibrin threads that
lead to blood clotting
E Damage to platelets causes the release of platelet thromboplastin, which has
an effect similar to tissue prothrombin
 Which of the following statements is correct?
A Damaged tissue releases a substance called tissue fibrinogen, which is mainly
composed of phospholipids
B Damage to the vessel wall initiates what is called the intrinsic pathway
C The activation of protein coagulation factor plus the release of platelet
thromboplastin eventually leads directly to the formation of thrombin
D The actual blood clotting is caused by a conversion of the plasma protein
prothrombin into another protein thrombin, which is the enzyme that causes
the polymerization of the plasma fibrinogen molecules into fibrin threads that
lead to blood clotting
E Damage to platelets causes the release of platelet thromboplastin, which has
an effect similar to tissue prothrombin
 Which of the following substances enzymatically causes the
polymerization of plasma fibrinogen?
A
B
C
D
E
Thromboplastin
Prothrombin
Prothrombin Activator
Thrombin
Phospholipids
 Which of the following substances enzymatically causes the
polymerization of plasma fibrinogen?
A
B
C
D
E
Thromboplastin
Prothrombin
Prothrombin Activator
Thrombin
Phospholipids
 Anticoagulants（抗凝物质）
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
o Protein C system（蛋白C系统）
Protein C, thrombomodulin, Protein S…
o Tissue factor pathway inhibitor (TFPI)（组织因子途径抑制物）
In an uninjured vessel,
thrombin bound to
thrombomodulin activates
protein C, which blocks the
clotting response.
o
Heparin（肝素）

A polysaccharide 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 processes
o Activation of plasminogen
o Degradation of fibrin
o 4 components of plasma fibrinolysis system
o Plasminogen（纤维蛋白溶解酶原）
o Plasmin（纤维蛋白溶解酶）
o Plasminogen activator
o Plasminogen inhibitor
Following tissue repair, fibrin clots are dissolved in a
process mediated by plasmin; synthetic plasminogen
activators can be used immediately after a stroke or
heart attack to help dissolve clots and restore blood flow.
o 2 pathways of plasminogen activation
Fibrin Degradation Products (FDP)
Thank you for your attention!