Blood physiology

What will we discuss in this chapter?
I. Blood composition
OUTLINE
II. Physical and chemical characteristics of blood
III. Blood Cells
1. Hemopoietic process and hemopoietic stem cells
2. Hemopoietic microenvironment
3. Erythrocyte Physiology
4. Leukocyte Physiology
5. Platelet or Thrombocyte Physiology
IV. Physiological Hemostasis
1. Endocrine functions of vessel endothelial cells
2. Physiological Characteristics of Platelet
3. Blood Coagulation
4. Fibrinolysis
V. Blood Group
1. RBC Agglutination
2. ABO blood group system
3. Rh blood group system
4. Relation between blood volume and clinic
5. Principle of Transfusion and Cross-match test

BLOOD AND INTERNAL
ENVIRONMENTAL HOMEOSTASIS
 Blood is that part of extracellular fluid within the cardiovascular system
 Blood formation
During animals’ evolution, extracellular fluid was gradually shaped from the
age-old time with ocean which was mainly salty solution. At last, extracellular
fluid was differentiated into plasma and interstitial fluid and blood came from
plasma and cells.
 The role of blood in internal environmental = homeostasis
Blood, the most active component in extracellular fluid, display functions as
follows:
(1) transport;
(2) pH buffer;
(3) temperature or thermal maintenance;
(4) immunity and defense

I. BLOOD COMPOSITION
 Blood composed of :
plasma + blood cells
 Hematocrit:

the percentage of total
blood volume that blood
cells occupy.
normal value
male: 40-50%
female: 37-48%
newborn: 55%

BLOOD COMPONENT (SUMMING-UP)

CHEMICAL COMPONENT OF PLASMA
H 2O 90 - 91%
血浆
Plasma 组织液
Interstitial 细胞内液
Intracellular
fluid fluid

Na+ 142 145 12
Cl- 104 117 4
Ca++ 2.5 2.4 <0.001
K+ 4.3 4.4 139
PO4- 2 2.3 29
蛋白质
Protein 14 0.4 54
(Unit：mmol/L)

II. PHYSICAL AND CHEMICAL
CHARACTERISTICS OF BLOOD
 Specific gravity: total blood (1.050-1.060) more influenced by
red blood cells; plasma (1.025-1.030) more influenced by
plasma protein; RBC (1.090-1.092) more influenced by Hb.
 Viscosity:

Blood relative viscosity (4~5) mainly depends on the
numbers of red blood cells.
Plasma relative viscosity (1.6~2.4) is mainly involved in plasma
protein

 Plasma osmotic pressure is 300 mmol/L or 770kPa
(1) Crystal osmotic pressure results from NaCl and
modulates water distribution between inside and outside of
cells.
(2) Colloid osmotic pressure results from albumin and
regulates water distribution between inside and outside of
capillary.
 Plasma pH value is about 7.35~7.45, and usually buffer
systems are NaHCO3/H2CO3 (20:1), protein salt/protein,
Na2HPO4/ NaH2PO4, Hb salt/Hb, HbO salt/ HbO2,
K2HPO4/ KH2PO4, KHCO3/H2CO3, etc [lungs and kidney
mainly regulate Plasma pH value ].

OSMOSIS AND OSMOTIC PRESSURE

 Osmosis is the movement of water down its concentration
gradient.
 Osmosis is determined by the number of impermeable
molecules.
 Osmotic pressure is the force drawing water down its
concentration gradient.

OSMOSIS AND OSMOTIC PRESSURE
A B

Water

[Water] > [Water]
[Salt] < [Salt]
Osmotic Pressure < Osmotic Pressure
Osmosis is the movement of water from a high concentration to a low concentration. In
this illustration, two compartments (A and B) are separated by a semipermeable
membrane (broken vertical line). The water concentration in compartment A is greater
than the concentration in compartment B because of the presence of salt (X) in B.
Therefore, water will move down its concentration gradient from A to B. The force
needed to prevent this water movement is called osmotic pressure.

TONICITY

 The tonicity of a solution refers to the effect of the solution
on cell volume.
 A hypertonic extracellular solution is one in which the
water concentration is less outside the cell than inside;
water leaves the cell; cell volume decreases.
 An isotonic extracellular solution is one in which the water
concentration is the same inside and outside the cell; no
water movement; cell volume does not change.
 A hypotonic solution is one in which the water
concentration is greater outside than inside the cell; water
enters the cell; cell volume increases.
 An isosmotic solution may not be an isotonic solution if the
particles are permeable to the cell membrane.

III.BLOOD CELLS
Blood cells are erythrocyte (red blood cell, RBC),
leukocyte (white blood cell, WBC) and thrombocyte
(platelet, P).

BLOOD CELLS
 The forming processes of erythrocyte (red blood cell, RBC),
leukocyte (white blood cell, WBC) and thrombocyte (platelet, P)
originating from hematopoietic stem cells are hemopoiesis.
 Transfer of blood cells forming place:
yolk sac hemopoiesis (early embryo period) → liver and spleen
(second embryo month) → marrow↑and liver, spleen↓ (after
fourth embryo month) → marrow (fetus birth time) and liver,
spleen as complementary role.
During adulthood (after 18), red marrow (flat bones, e.g.
vertebra,ilium, sternum, rib, skull and long bone ending) rather
than yellow marrow has hematopoietic functions.

1. HEMOPOIETIC PROCESS AND
HEMOPOIETIC STEM CELLS

Hemopoietic process
Stage one: Hemopoietic stem cells
self renewal, steady numbers, active differentiation.
Stage two: committed progenitors
directional differentiation (CFU-GEMM, CFU-E, CFU-
GM, CFU-MK, CFU-TB). [CFU: colony- forming unit
Stage three: precursors
morphologic occurrence of various original blood cells.

HEMOPOIETIC STEM CELLS
Basic characteristics
 Self renewal in high degree, constant from young to old age.
 Multi- directional differentiation
 Large potential proliferation, Hemopoietic stem cells produce about
1×1011 blood cells releasing to blood for use.
 Surface sign
According to CFU (colony forming unit), using fluorescence-
activated cell sorting (FACS), its main surface sign is CD34+CD38-
Lin-and CD34-CD38-Lin-.
Note
CD: cluster of differentiation of antigen on the white blood cells;
Lin: systemic specific antigen on the hemopoietic cells.

3.ERYTHROCYTE PHYSIOLOGY

Shape and number of red blood cells (RBC)
 Shape of RBC: like biconcave disc

Its diameter is about 7~8 µm, peripheral thickness about
2.5 µm, central thickness about 1 µm and cubage about
90 µm3.

REASON FOR SHAPE OF RBC

biconcave disc like

ERYTHROCYTE PHYSIOLOGY
Number of RBC: It is most numbers in the blood.
Normal value about RBC
Male adult, 4.5~5.5×1012/L; average, 5.0×1012/L
Female adult, 3.8~4.6× 1012/L; average, 4.2×1012/L
Newborn, ≥ 6.0×1012/L
Protein within RBC is hemoglobin (Hb).
Hb in male adult, 120~160 g/L;
Hb in female adult, 110~150 g/L;
Hb in newborn (within 5 days), ≥ 200 g/L
Pregnant female, numbers of RBC and Hb are relatively less (because of
more plasma).
Dweller lived in plateau, numbers of RBC and Hb are relatively more
(because of compensation for anoxia).

PHYSIOLOGICAL CHARACTERISTICS AND
FUNCTIONS OF RBC
Characteristics of RBC
① Permeability: semipermeable membrane, gas and urea freely
passing through, negative ions easily in or out of RBC, and
positive ions not. There are Na-K ATPase as pump on the
membrane of RBC and low-temperature-stored plasma
easily has high kalium. Why?
② Plasticity and metamorphose:

Plasticity and metamorphose depend on: 1) surface area-cubage
ratio, 2) viscosity of Hb, 3) membrane elasticity and viscosity.

PHYSIOLOGICAL
CHARACTERISTICS AND
FUNCTIONS OF RBC
③ Suspension stability: it cab be described by
erythrocyte sedimentation rate (ESR) which is RBC
descending distance per hour and suspension
stability is inverse proportion to ESR.
Normal value of ESR: male, 0~15 mm/h; female, 0~20
mm/h.
ESR and clinic: some diseases bring about rouleaux
formation (mainly involved in plasma component, e.g.
globulin, fibrinogen, cholesterol) and speed up ESR.

PHYSIOLOGICAL
CHARACTERISTICS AND
FUNCTIONS OF RBC
④ Osmotic fragility: Changes in RBC put into
lower osmotic salty solution.
Osmotic fragility of aged RBC is large and
easily results in rupture (hemolysis and ghost
cell).
Isosmotic solution, e.g. 0.85% NaCl,
1.4%NaHCO3, 5% glucose, etc.
Isotonic solution, e.g. 0.85% NaCl
Isosmotic solution does not equal to isotonic
solution.
Isosmotic solution, isotonic solution and clinic

PHYSIOLOGICAL CHARACTERISTICS
AND FUNCTIONS OF RBC
Functions of RBC
 RBC can be used for transportation of
O2 and CO2 in the blood.
 RBC can be served as pH buffer.

ERYTHROPOIESIS
 Hemopoietic material for erythropoiesis:
iron (Fe++) and protein, [reason for anemia]
 Influencing factors of RBC maturity:
Vitamin B12 and folic acid (DNA metabolism),
[clinic relation]
 Process of erythropoiesis:
Hemopoietic stem cells→multi systemic hemopoietic progenitor
cells→RBC-committed progenitor cells (BFU-E→CFU-E)→original RBC→
earlier infantile RBC→medium-term infantile RBC→terminal infantile
RBC→reticular RBC→mature RBC→blood for circulation.
This process requires 6~7 days.
[mitosis several times] [apoptosis]

PLACE FOR ERYTHROPOIESIS

Main place for Erythropoiesis is bone
marrow. Aother place is liver.

LIFE AND BREAKAGE OF RBC

 Life-span: 120 days, about 4 months, each RBC
circulates 27 km averagely in vessels, short life-span for
aged RBC
 Breakage: places are liver, spleen and lymphatic node,
and after breakage, Hb released from RBC immediately
combine with plasma α2-globulin (Hb touched protein)
which is taken in by liver for iron reuse.
 Hb, very toxic if it get into blood, normally, it can be
metabolized into bile pigment in liver.
 Clinic relation.

4.LEUKOCYTE PHYSIOLOGY
CLASSIFICATION AND NUMBERS OF
LEUKOCYTE

 Number of Leukocyte (white blood cells, WBC):
(4.0~10)×109/L
 Classification: It is granulocyte (neutrophil,
eosinophil, basophil), monocyte and lymphocyte.

CLASSIFICATION AND NUMBERS OF
LEUKOCYTE
TABLE. Classification and normal value of Leukocyte
Absolute Value (×109/L) Percentage (%)
Total numbers of leukocytes 4.0~10.0

Neutrophil (bacilliform nucleus) 0.04~0.5 1~5

Neutrophil (foliiform nucleus) 2.0~7.0 50~70

Eosinophil 0.02~0.5 0.5~5

Basophil 0.0~0.1 0~1

Monocyte 0.12~0.8 3~8

Lymphocyte 0.8~4.0 20~40
For Clinic Use

PHYSIOLOGICAL CHANGES IN
NUMBERS
OF LEUKOCYTE
 Newborn: Number is higher, 15×109/L, after birth 3 or 4 days to
3 months, being about 10×109/L, mainly, neutrophil, 70%;
secondarily, lymphocyte.
 Circadian changes: Number of WBC is more in the afternoon
than in the morning.
 Food taking, ache and mood excitation: Number of WBC is
remarkably higher.
 Heavy exercise and laboring: Increasing numbers, about
35×109/L, return to original level after action stop.
 Terminal pregnancy of female: Numbers changes in
12~17×109/L, and during parturition, 34×109/L, and after
parturition 2~5 days, number return to original level.

PHYSIOLOGICAL CHARACTERISTICS AND
FUNCTIONS OF WBC
Terminology
 Diapedisis: Metamorphosed WBCs pass
through vessel wall getting into
interstitial fluid.
 Chemotaxis: It is a process that WBCs WBC
shift to some chemical material

Diapedisis
(metabolic production, antigen-antibody
complex, bacteria, toxin, etc).
 Phagocytosis: It is a process that WBCs
enclose and engulf exotic or extraneous
material, and use intracellular enzyme Blood
digesting them. Vessel

Metamorphose

AND FUNCTIONS OF WBC

① Neutrophil
 Another name, polymorphonuclear, PMN, 6~8 h in the vessels,
diapedisis, chemotaxis and phagocytosis (using its hydrolyzed
enzyme)
 Function: It plays a very important role in nonspecific cellular
immunity system which is against pathogenic microorganism,
such as bacteria, virus, parasite, etc.
 Clinic relation:
Number of neutrophil greatly increase occurring in
acute inflammation and earlier time of chronic
inflammation.
number decrease of neutrophil will result in poor
resistibility and easily suffering from infection.


② Eosinophil
 Circadian changes: Its number is lower in the morning
and higher at night.
 Function:
1. It limits and modulates the effects of basophil on fast
allergic reaction.
2. It is involved in immune reaction against worm with
opsonization.
 Clinic relation: Its number increase when person suffers
from parasite infection or allergic reaction.


③ Basophil
 Circulatory time: 12 hours
 Basogranules contain heparin, histamine, chemotactic
factors and chronic reactive material for allergic reaction.
 Function: It is also involved in allergic reaction.
1. Heparin serves as lipase cobase and speeds up fatty
decomposition.
2. Histamine and chronic reactive material increase
permeability of capillary and contract bronchia smooth
muscle, and result in allergic reaction such as measles,
asthma.
3. Eosinophil chemotactic factor A released by basophil
can attract eosinophil collection and modify eosinophil
function.

④ Monocyte
Its body is large, diameter about 15~30 µm without granule
Function:
1. It contains many nonspecific lipase and displays the
powerful phagocytosis.
2. As soon as monocytes get into tissue from blood , it change
name called macrophage activating monocyte- macrophage
system to release many cytokins, such as colony stimulating
factor (CSF), IL-1, IL-3, IL-6, TNFα, INF-α,β ,etc.
3. Cytokins induced by monocyte may modulate other cells
growth.
4. Monocyte- macrophage system plays a very important role in
specific immune responsive induction and regulation.


⑤ Lymphocyte
 Classification: It can be separated into T- Lymphocyte
and
B- Lymphocyte.
 Function:
1. Lymphocytes serve as a nuclear role in immune
responsive reaction.
2. T- Lymphocytes involved in cellular immunity.
3. B- Lymphocytes involved in humoral immunity.
 Clinic relation: Numbers increase of lymphocytes occur
in

LEUKOPOIESIS, REGULATION AND
BREAKAGE

 Birth place: bone marrow, originating from hemopoietic stem cells,
and leukopoiesis process is similar to RBC.
 Leukopoiesis, differentiation and growth are influenced by
hemopoietic growth factor, HGF which are glycoprotein secreted
by lymphocyte, monocyte- macrophage, fibrous cell and
endothelial cell.
 Colony stimulating factor, CSF, such as GM-CSF, G-CSF, M-CSF,
Multi-CSF (IL-3) also influence Leukopoiesis.
 Life span: several hours to 3 or 4 days.
 Leukocyte breakage: site are liver, spleen and lymphatic node.
 Pus or purulence forming

5.PLATELET OR THROMBOCYTE
PHYSIOLOGY

 Shape: Biconvex disk like,
diameter about 2~4 µm, average
cubage 8 µm3.
 Complicated structure: under the
electronic microscope, there are α-
granule, dense body, lysin
peroxide enzyme, opening tubular
system, dense tubular system,
canaliculus,etc.

 Dense body: It contains ADP, ATP, 5-HT, Ca2+, epinephrine,etc.
 Source: Platelet comes from megakaryocyte fractionlet release
in the marrow.

NORMAL VALUE AND FUNCTION OF
PLATELET

 Normal value: 100×109 ~ 300×109, range from 6%~10%
 Normal changes: more number in the afternoon than in the morning,
more in winter than in spring, more in the venous blood than
capillary, after sport↑, pregnacy↑.
 *Functions:
1. It maintains capillary endothelial cells smooth and
integrated (repairing endothelium and providing
nutrition).
2. It is involved in physiological hemostasis.
 Platelet and clinic relation:
decrease of platelet, abnormal immune reaction, will results in
hemorrhage or bleeding, purpuric symptom.

PLATELET FORMING AND
REGULATION
 Platelet forming:
Birth place is bone marrow, originating from hemopoietic stem cells,
and differentiating into burst forming unit- megakaryocyte, BFU-MK,
then continuously into CFU-MK, and into megakaryocyte,
demarcation membrane system, DMS, into fractionlet release to the
blood requiring 8~10 days. (one megakaryocyte can produce
200~7700 platelet).
 Regulation:
Protein, Mpl, expressed by c-mpl (oncogene) exists in CD34+ located
at hemopoietic stem cells/ committed progenitors, megakaryocyte
and platelet, found by Methin in 1993, and its ligand named
thrombopoietin, TPO was discovered in 1994 which promoted
hemopoietic stem cells differentiating into megakaryocyte as
hemopoietic stem cells positive regulating factor.

LIFE- SPAN AND BREAKAGE OF PLATELET

 Life-span: Averagely, 7~14 days in the blood. It can
be consumed when it displays physiological
functions.
 Breakage: Aged platelet can be processed by
phagocytosis in liver, spleen and lymphatic node.

IV. PHYSIOLOGICAL HEMOSTASIS

 *Definition: The process from vessel bleeding to automatic
hemostasia.
 *Bleeding time: The time from vessel bleeding to automatic
hemostasia. Normal time is 1~3 min and it is longer when
platelet decrease.
 Process of hemostasis:
1. Blood vessel contraction or convulsion (induced by
neuroreflex; 5-hydroxytryptamine,5-HT; thromboxane A2,
TXA2; endothelin, ET )
2. Platelet thrombosis forming (made by platelet adhesion,
aggregation, release and contraction)
3. fibrin, clot forming and maintenance (made by blood
coagulation activation)

1.ENDOCRINE FUNCTIONS OF VESSEL
ENDOTHELIAL CELLS
① Material related to hemostasis are basal membrane, collagen (III, IV),
microfibril, elastin, laminin, ectonectin, fibronectin, von Willebrand
factor (vWF), protein enzyme, protein enzyme inhibitor, adhesive
amylose, etc.
② Anticoagulative material: They are prostacyclin (PGI2),
endothelium-derived relaxing factor (EDRF or nitric oxide, NO),
tissue-type plasminogen activator (tPA), uPA, ADPase, ATIII,
heparin sulfate, protein C, thrombomomodulin (TM), plasminogen
activator (PA).
③ Promoting coagulative material: Tissue factor, vWF, blood clotting
factor V, plasminogen activator inhibitor (PAI-1, PAI-2, ATIII), TNFα,
interleukin-1 (IL-1).
④ Vessel constricting and relaxing modulators: endothelin-1 (ET-1),
EDRF (NO), PGI2, etc.

ROLES OF VESSEL ENDOTHELIAL
CELLS IN PHYSIOLOGICAL
HEMOSTASIS
Roles are close related to its endocrine functions
① Vessel endothelium serves as barrier between underendothelial
structure (namely, collagen) and blood. As soon as collagen
expose to blood, hemostasis of platelet is immediately activated
to form thrombus blocking wounded vessels.
② Platelet activation can releases constrictive factors (TXA2, ET-1, 5-
HT, etc) making vessel convulsion, lasting about 60 sec.
③ Stimulated vessel endothelial cells release coagulative factors
and Promoting coagulative material to realize, speed up blood
coagulation. At the same time, cells also release anticoagulative
factors and fibrinolysis material to modify blood coagulation.

INACTIVE PLATELET
Under the electronic microscope

ACTIVATED PLATELET FOR
HEMOSTASIS
Under the electronic microscope

2.PHYSIOLOGICAL CHARACTERISTICS OF
PLATELET
 Thrombocyte adhesion: its membrane glycoprotein (GP, GPIb/IX and GPIIa/IIIb),
collagen (underendothelial structure), vWF (plasma component), fibrinogen are
involved in adhesion.
Mechanism: Exposed collagen+vWF →vWF changes →platelet membrane
glycoprotein+changed vWF → Thrombocyte adhesion.
 Thrombocyte aggregation: induced by physiological factors such as ADP,
thromboxane A2 (TXA2), epinephrine, 5-HT, histamine, collagen, thrombin,
prostacyclin,etc and by pathological factors like bacteria, virus, immune complex,
drugs, etc.
The process can be separated into two phases: phase one is reversible aggregation
and phase two irreversible aggregation. Two phases require Ca2+, fibrinogen and
energy consumption.
Mechanism : Various factors+corresponding receptors on the platelet →changes in the
second messenger within platelet →cAMP↓, Ip3↑, Ca2+↑, cGMP↑→ platelet aggregation.
 Thrombocyte release: ADP, ATP, 5-HT, Ca2+ released from dense body, and β-platelet
globin, PF4, vWF, fibrinogen, PFV, PDGF, thrombin sensitive protein from α-granule,
and acid protein hydrolyzed enzyme, tissue hydrolyzed enzyme from lysosome.
 Thrombocyte contraction: Loose platelet thrombus could turn into compact platelet
thrombus by Ca2+ release and cytoskeleton movement (filament/canaliculus) within
platelet.

ROLES OF PLATELET IN
HEMOSTASIS
 Activation of platelet: Stimulus brings about thrombocyte adhesion,
aggregation, release and contraction.
 Loose platelet thrombus forming: First phase of hemostasis.
 Blood coagulation activation by platelet: Fibrin net forming, second
phase of hemostasis.
 *Roles of platelet in hemostasis:
1. Activated platelets supply lecithoid (phospholipid) surface for blood
clotting factor and involve in activating factor X and prothrombin.
2. Surface of platelet membrane combine with many blood clotting
factor, such as fibrinogen, FV, FXI, FXIII to speed up coagulation.
3. Activated platelets release α-granule which contains fibrinogen to
intensify fibrin forming and blood coagulation.
4. Activated platelets contract clot with its contractive protein to solidify
blood coagulation.

TWO PHASES OF PHYSIOLOGICAL
HEMOSTASIS

First Phase Second Phase

MECHANISM1 OF PLATELET IN
HEMOSTASIS

MECHANISM2 OF PLATELET IN HEMOSTASIS

3.BLOOD COAGULATION
BLOOD CLOTTING FACTOR
 Definition: The process of blood flow from flowing liquid to gel or
gelatin.
 Serum: Light yellow fluid after blood coagulation.
 Difference between serum and plasma mainly consists in no
fibrinogen in serum.
 Blood coagulation is a series of complicated biochemical reactions
with various enzymes.
 Blood clotting factor: Material which are directly involved in blood
coagulation. There are 12 factors named Roman numerals, except
Ca2+, phospholipid，other factors being protein, and except FIII (TF),
others are in fresh plasma synthesized by liver with VitK .
 Blood clotting enzymes have two type: inactive and activated type [FII,
FVII, FIX, Fx, FXI, FXII, FXIII].

Blood Clotting Factor
Factor Name Plasma Synthesizing Half life Chromsome
Concentration site site
I Fibrinogen 3000 Liver 4~5 d 4
II Prothrombin 100 Liver (with Vit K) 3d 11
III Tissue factor - Endothelial cell - -
IV Ca2+ 100 - - -
V Proaccelerin 10 Endothelial cell, platelet 12~15 h 1
Ⅶ Proconvertin 0.5 Liver (with Vit K) 4~7 h 13
Ⅷ Antihemophilic factor,AHF 0.1 Liver 8~10 h Ⅹ
Ⅸ Plasma thromboplastic 5 Liver (with Vit K) 24 h Ⅹ
component,PTC(Christmas factor)
Ⅹ Stuart-Prower Factor 10 Liver (with Vit K) 2d 13
Ⅺ Plasma thromoboplastin 5 Liver 2~3 d 4
antecedent,PTA
Ⅻ Contact factor or Hageman factor 40 Liver 24 h 5
XIII Fibrin-stabilizing factor 10 Liver, platelet 8d 6,1
- High-molecular weight 80 Liver - 3
kininogen,HMW-K

BLOOD COAGULATION
 Intrinsic pathway of blood coagulation: All blood clotting factors involved in
blood coagulation come from blood. Eyewinker surface with negative charges
(collagenin) on the endothelium of blood vessel activates blood FXII as
beginning of coagulation named surface activation.
 Extrinsic pathway of blood coagulation: Stimulus activates tissue factor (FIII) as
beginning of coagulation.
Extrinsic pathway of blood coagulation is faster than intrinsic pathway of blood
coagulation because its steps are more simple.
 *Basic steps of blood coagulation [typical positive feedback]:
Prothrombin activator forming [FXa-Va-Ca2+-phospholipid] Step 1

Prothrombin thrombin Step 2

Fibrinogen fibrin (clot) Step 3
 Hemophilia A, B, C in the clinic results from deficiency of FVIII, FIX,
FXI in the blood, respectively.

Process of Blood Coagulation
Extrinsic pathway Intrinsic pathway
（Tissue Factor，TF）（ Eyewinker surface ）
TF+Ⅶ Ⅻ
Ⅺ H S
Ca2+
K K PK
Ⅶ-TF Ⅸ Ⅻa
Ⅹa Ca2+
Ca2+ ，PL Ⅺa
Ⅶa-TF
Ⅸa
Ca2+
PL Ca2+
Ⅷa
PL

Ⅹ Ⅹa
PL: phospholipid Ca2+ ⅩⅢ
Ⅴa
CL: cross linking fibrin PL
Ⅱ Ⅱa
HK: high molecular weight kininogen
ⅩⅢa
S: Subendothelium
Ca2+
PK: prekallikrein Ⅰ Ⅰa CLⅠa
K: kallikrein

MECHANISM OF BLOOD
COAGULATION

ANTICOAGULATIVE SYSTEM IN BLOOD
 Cellular anticoagulative system: Liver cell and reticular endothelial cell could engulf
blood clotting factor, tissue factor, prothrombin complex and soluble fibrin
monomer.
 Humoral anticoagulative system:
1. Amino acid protease inhibitors in blood include antithrombin III, Cl-inhibitor, α1
antitrypsin, α2 antiplasmin, α2 huge globin, heparin coenzyme II, protease nexin-1
(PN-1) to combine with FIXa, FXa, FXIa, FXIIa and thrombin and then inactivate them
for anticoagulation. Heparin can intensify functions of antithrombin III.
2. Protein C system are protein C (PC), thrombomodulin (TM), protein S and Protein
C inhibitors. Main functions of PC consist in ①It inactivates FVa, FVIIIa with
phospholipid and Ca2+; ②It blocks FXa combining with platelet phospholipid
membrane to reduce prothrombin activation; ③It stimulates plasminogen activators
release to trigger fibrinolysis; ④ Protein S is a coenzyme of PC and greatly intensify
functions of PC.
3. Tissue factor pathway inhibitor (TFPI) mainly coming from vessel endothelial cells
inhibits FXa and inactivates FVIIa-TF complex to block extrinsic pathway of
coagulation with negative feed back.
4. Heparin used in the clinic widely is due to ①It combines with antithrombin III to
increase functions of antithrombin III; ②It stimulates vessel endothelial cell greatlu
releasing TFPI and other anticoagulative material; ③It intensifies PC activation and
stimulates vessel endothelial cell releasing plasminogen activators to increase
fibrinolysis. [lower molecular weight heparin is less hemorrhage]

4.FIBRINOLYSIS
 Fibrinolytic system is involved in fibrinolysis, tissue repair
and vessel rebirth.
 Two fibrinolytic systems: cellular one and plasma one. The
former is leucocyte, macrophage, endothelial cell, mesothelial
cell and platelet to engulf and digest fibrin. The latter is
plasminogen activators (PA) and its inhibitors (PAI),
plasminogen, plasmin.
 Basic steps:
Kallikrein (Intrinsic pathway)
Endothelial cells (Extrinsicpathway )
(Urokinase, uPA) Cl-inhibitors
tPA uPA uPAG
PAI-1
Plasminogen Plasmin
α2-antiplasmin
α2-huge globin Fibrin
Fibrin or fibrinogen dissolution

BLOOD COAGULATION AND
FIBRINOLYSIS

ANTIFIBRINOLYSIS:
FIBRINOLYTIC INHIBITORS AND ITS
FUNCTIONS
 Main fibrinolytic inhibitors: They are plasminogen activator inhibitor
type-1 (PAI-1, in platelet), α2-antiplasmin (in liver), α2-huge globin,
α1-antitrypsin, antithrombin III, alexin C1 inhibitor.
 PAI-1 synthesis and release: PAI-1 made by endothelial cell, smooth
muscular cell, mesothelial cell, megakaryocyte is stored in platelet
with inactive form. Some factors such as thrombin, IL-1, TNFα, etc
stimulate its release from platelet.
 PAI-1 function: It inhibits tPA (tissue-type plasminogen activator)
limiting local fibrinolysis of thrombus.
 α2-antiplasmin characteristics: (1) Quick effect, (2) Inhibit
plasminogen adhering to fibrin; (3) Combine with fibrin αchain and
block fibrinolysis
 Clinic relation: Innate deficiency of α2-antiplasmin often brings
about serious hemorrhage.

V. BLOOD GROUP
 History: ABO blood group system was firstly found by Landsteiner
in 1901.
 Definition for blood group*: Types of specific antigens on the blood
cell.
 Agglutination: Combination of the same antigen (or named
agglutinogen, glycoprotein/glycolipid on the membrane of blood
cell) and antibody (or named agglutinin, r-globin in serum) results
in harmful immune reactions showing hemolysis.
 Human leukocyte antigen, HLA have widespread distribution in the
body and involves in immune repulsive reaction of organ transplant.
 Platelet antigens such as PI, Zw, Ko, etc may bring about fever heat
when transfusion occur.

1. RBC Agglutination

Antigen-Antibody Harmful immune Reaction

Blood Coagulation RBC Agglutination

ANTIGEN OF BLOOD GROUP

 Antigen: Its genes are located at allele on
euchromosome, namely, expressed gene.
 Genotpye is genetic gene in blood group system and
phenotype is antigen produced by corresponding
genetic gene and amorph is noneffective allele.
 Genes in the blood system decide differential specific
antigen on the membrane with control of enzymatic
activity.

ANTIBODY OF BLOOD GROUP

 Crude antibody: It is the unexposed antibody to
correlative RBC, e.g., IgM in ABO blood group system
which can not pass through placenta for the sake of big
molecule.
 Immune antibody: Various extraordinary RBC antigens
(transfusion or parturition) sensitize lymphatic cells
producing antibody such as Rh, Kell, Duffy, kidd, which
belong to IgG (small molecule) and IgM (big molecule).

BLOOD GROUP OF RBC
 Number: 23 types, 193 antigens, more important
blood groups are ABO, Rh, MNSs, Lutheran, kell,
Lewis, duff, kidd, etc and all of them could result in
hemolysis during transfusion.
 ABO blood group system:

Blood group Antigen on the RBC Antibody in the serum

A A Anti-B
B B Anti-A
AB A+B
O Anti-A+Anti-B

2. ABO BLOOD GROUP SYSTEM

Antigen (agglutinogen) and antibody (agglutinin)
in ABO blood subgroup system
Blood group Antigen on the RBC Antibody in the serum

A A1 A+ A1 Anti-B
A2 A Anti-B+ Anti-A1
B B Anti-A
AB A1B A+ A1 +B
A2B A+B Anti-A1
O Anti-A+Anti-B

ABH Antigen chemical structure in ABO
blood group system
Antigen of blood group
Ushering material

O(H)-antigen

A-antigen

B-Antigen

N-acetamide N-acetamide
Galactose Glucose galactose
Sugar Glucose

INHERITANCE OF ABO BLOOD
GROUP

 Inheritance: The A, B, H agglutinogen in ABO blood
group system controlled by gene which is located at
allele on No.9 chromosome (9q34.1-q34.2).
 Genotype and Phenotype:

Genotype and Phenotype in ABO blood group system
Genotype phenotype
OO O
AA, AO A
BB, BO B
AB AB

INHERITANCE OF ABO BLOOD
GROUP

Genetic relationship of ABO blood group
Parents’ Offspring possible Offspring impossible
blood group blood group blood group
O×O O A, B, AB
A×A O, A B, AB
A×O O, A B, AB
B×B O, B A, AB
B×O O, B A, AB
B×A O, A, B, AB ____
AB×O A,B O, AB
AB×A A , B, AB O
AB×B A , B, AB O
AB×AB A , B, AB O

DISTRIBUTION OF ABO BLOOD
GROUP

 Mid Europe: Type A 40%, Type O 40%, Type B 10%, Type
AB 6%.
 America aborigines: Type O 90%.

 China Han nationality: Type A 31.31%,

Type B 28.06%, Type AB 9.77%, Type O 30.86%.
Other chinese minority is different.
 Bloog group can be used in research on anthropology

Mensuration of ABO blood group

Anti-B Anti-A Anti-A, B
Serum Serum Serum

3. RH BLOOD GROUP SYSTEM

 Rh antigen (Rh factor) is about 40 kinds and Rh factors
related to clinic are D, E, C, c, e and most important is D
antigen.
 Membrane of RBC has D antigen meaning Rh Positive,
otherwise, Rh negative. Most of people (99％) are Rh
Positive and less than 1% persons are Rh negative.
 Rh blood group characteristics: Immune antobody and
incomplete antibody, IgG; while ABO blood group, crude
antibody and complete antibody,IgM.
 Rh blood group system and clinic work
Transfusion and pregnacy [Clinic meaning]

QUANTIFICATION OF BLOOD
VOLUME
 Blood volume is an important determinant of systemic
arterial pressure.
 Circulatory system is essentially a closed container
including a volume of blood equal to approximately 5
liters or 70-80mL/Kg of the body weight (in kilograms).

4. RELATION BETWEEN BLOOD VOLUME
AND CLINIC
 When you donate 10 % of total blood volume, your body
compensates so that blood pressure does not change, and the
volume is replaced through the normal ingestion of fluids.
 Volume loss up to 30-40 % of total blood volume can be tolerated
if the loss is corrected within 30 min (e.g. artery contraction
increases peripheral resistance but artery blood pressure can
not maintain the normal levels which occur in symptoms such as
light-headed, dazzled, force-lacked, etc)
 Blood loss more than 40 % of total blood volume will threaten
the life, results in shock and the measures in the hospital should
be immediately taken for life survival [Transfusion].

5. PRINCIPLE OF TRANSFUSION
 Transfusion is widely used in clinic treatment.
 Principle of transfusion*:

1. Identification of blood group must be taken before
transfusion.
2. Cross-match test must be done before transfusion.
3. The same tpyes of blood group for transfusion should
be firstly considered.
4. The different tpyes of blood group for transfusion
should be very careful, small amount and slow import
and if condition is better, changes in the same tpyes of
blood group for transfusion.

CROSS-MATCH TEST FOR
TRANSFUSION
红细胞
RBC 红细胞
RBC

供
Donator
受
Receiver

血血
者
者
Serum Serum
血清血清
主侧凝集反应
Main side of 次侧凝集反应
Subordinary side
Decision
agglutination of agglutination

- - 相合，可以输血
Perfect match, transfusion

+ +, - 不合，不能输血 ×
No match, transfusion

- + 应急情况下输血
Transfusion under emergency
+: Agglutination; -: No agglutination

TYPES OF TRANSFUSION
 According to source of transfusion, allogenetic
transfusion (more use), autologous transfusion.
 According to component of transfusion, whole blood
transfusion, transfusion of blood components
 Autologous transfusion has some advantages:
① It decreases infection.
② It blocks syndrome (fever, hemolysis) induced by
allogenetic transfusion.
③ It stimulates bone marrow hemopoiesis towards RBC.
 Transfusion of blood components is good.

Summarization

PLEASE TAKE DOWN

Consideration after class
【本章节问题思考】
1. Please describe classification and main effects of
leucocyte.
2. What is the elementary process of blood coagulation and
main factors which have participated in blood coagulation?
3. Please describe the principle of classification and blood
transfusion of ABO blood group system.

GUIDE OF REFERENCE
【本章节学习参考书单】
1. 姚泰主编. 生理学. 第五版. 北京: 人民卫生出版社, 2000.
2. 范少光, 汤浩, 潘伟丰主编. 人体生理学（二版）. 北京: 北京医科大学出版社, 2000.
3. 贺石林, 李俊成, 秦晓群主编. 临床生理学. 北京: 科学出版社, 2001.
4. 王庭槐主编. 生理学. 全国高等学校医学规划教材, 北京: 高等教育出版社, 2005.
5. 吴祖泽, 贺福初, 裴雪涛主编. 造血调控. 上海: 上海医科大学出版社, 2000.
6. 李勇, 杨贵贞主编. 人类红细胞血型学实用理论与实验技术. 北京: 中国科学技术出版社, 1999.
7. Ding L, Lu S, Batchu R, et al. Bone marrow stromal cells as a vehicle for gene transfer.
Gene Ther, 1999, 6(9): 1611-1616.
8. Humeau L, Bardin F, Maroc C, et al. Phenotypic, molecular, and functional
characterization of human peripheral blood, CD34+/Thy1+ cells. Blood, 1996, 87(3):
949-955.
9. Kaushansky K. Thrombopoietin: accumulating evidence for an important biological
effect on the hematopoietic stem cell. Ann N Y Acad Sci, 2003, 996: 39-43.
10. Berne RM, Levy MN, Koeppen BMI, Stanton BA. Physiology, 5th ed, St Louis:
Mosby Electronic Production, 2004.
11.Guyton AC, Hall JE. TEXTBOOK OF MEDICAL PHYSIOLOGY, 10th ed, Philadelphia:
W.B. Saunders Co, 2000.
12. Berardi AC, Wang A, Levine JD, et al. Functional isolation and characterization
of human hematopoietic stem cells. Science, 1995, 267(5194): 104-108.
13. Fox SI. Human physiology, 7th ed, New York: McGraw-Hill Co Inc, 2002.

NAVIGATION FOR WEB ADDRESS
【本章节课后学习导航网站】
1.http://bioresearch.ac.uk/browse/mesh/detail/c0005811L000
5811.html
2.http://www.inform.umd.edu/EdRes/Colleges/HONR/HONR2
69U/Jenn/
3.http://www.ohsu.edu/cliniweb/G9/G9.188.html
4.http://www.mednote.co.kr/PHYSIOLOGY%20BLUE.htm
5.http://www.fpnotebook.com/HEM38.htm

BLOOD PHYSIOLOGY

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