Transcript BLOOD PHYSIOLOGY

Chapter 3
BLOOD PHYSIOLOGY
What will we discuss in this chapter?
(Outline)
Blood composing
Outline
I.
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 forming
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) transportation;

(2) pH value buffer;
(3) temperature or thermal maintenance;
(4) immunity and defence
I. Blood composing
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Blood composing:
plasma + blood cells
Hematocrit:
blood cells occupies
the percentage of
total blood volume.
normal value
male: 40-50%
female: 37-48%
newborn: 55%
Blood component (summing-up)
Terminology and normal value
Chemical component of plasma
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Water: > 90%
Small molecule: 2%, it is electrolytes, nutriment, metabolic
products, hormone, enzyme,etc.
Protein: 60-80 g/L, plasma protein include albumin (40-50
g/L), globulin (20-30 g/L,α1-, α2, β-, γ- ) and fibrinogen. Most
of albumin and globulin made from liver. A/G and clinic.
Function of plasma protein:
(1) transportation, (2) nutrition, (3) forming colloid osmotic
pressure, (4) coagulation and anticoagulation, (5) pH value
buffer, (6) immunity (globulin)
Chemical component of plasma
H 2O
90 - 91%
Plasma
血浆
Interstitial
组织液
fluid
Intracellular
细胞内液
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
Protein
蛋白质
14
0.4
54
(Unit：mmol/L)
II. Physical and chemical
characteristics of blood
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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.
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Osmosis and Osmotic Pressure
A
B
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Water
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  
 
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[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
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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
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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, CFUGM, CFU-MK, CFU-TB). [CFU: colony- forming unit
Stage three: precursors
morphologic occurrence of various original blood
cells.
Hemopoietic stem cells
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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.
2.Hemopoietic microenvironment
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Hemopoietic microenvironment:
It includes stromal cell secreting extracellular matrix (ECM),
multihemopoietic regulating factor, hemopoietic nerves and
blood vessels.
Stromal cells in the marrow come from fibrocyte, reticulocyte,
endothelial cell, ectoblast cell, monocyte, engulfing cell,
osteoblast and osteoclast.
Stromal cells supply two material: one is soluble hemopoietic
growth factor, another is membrane-combined adhesive
molecule.
Extracellular stroma synthesized and secreted by marrow
stromal cell filling cellular interstice contains big molecules,
such as collagen (typeI, II, III, IV), glycoprotein (fibronectin,
laminin, hemopoieticnectin ) and protein amylose (sulfate
cartilagetin, sulfate heparin, hyaluronic acid and sulfate
dermatin, etc).
Hemopoietic cells must adhere to stromal cell and is in the
hemopoietic microenvironment for survival.
3.Erythrocyte Physiology
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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.
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
①
②
Characteristics of RBC
Permeability: semipermeable membrane, gas and
urea freely passing through, negative ions easily in
or out of RBC, and positive ions not. There are NaK ATPase as pump on the membrane of RBC and
low-temperature-stored plasma easily has high
kalium. Why?
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
Characteristics 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
Characteristics of RBC
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
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RBC can be used for transportation of
O2 and CO2 in the blood.
RBC can be served as pH buffer.
Erythropoiesis
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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→CFUE)→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.
Regulation of Erythropoiesis
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0.8% of total RBCs has self renewal, that is to
say, 160×106 RBC production every minute.
Burst forming unit-erythroid, BUF-E, important
to earlier erythropoiesis, depends on
stimulation of burst promoting activity, BPA
outside body. BPA made by leucocyte is a
glycoprotein whose molecular weight is about
25000~40000
Colony forming unit-erythroid, CFU-E,
important to terminal erythropoiesis, depends
on erythropoietin, EPO which is also a
glycoprotein, molecular weight, 34000, plasma
concentration 10 pmol/L, half life 5 hours,
increasing release when anoxia.
Life and breakage of RBC
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Life-span: 120 days, about 4 months, each RBC
circulates 27 km averagely in vessels, short
life-span for aged RBC
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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.
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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)
Total numbers of leukocytes
Percentage (%)
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
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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
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Diapedisis: Metamorphosed WBCs pass through vessel
wall getting into interstitial fluid.
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Chemotaxis: It is a process that WBCs shift to some
chemical material (metabolic production, antigenantibody complex, bacteria, toxin, etc).
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Phagocytosis: It is a process that WBCs enclose and
engulf exotic or extraneous material, and use
intracellular enzyme digesting them.
Physiological Characteristics
and Functions of WBC
① Neutrophil
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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.
Physiological Characteristics
and Functions of WBC
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.
Physiological Characteristics
and Functions of WBC
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.
Physiological Characteristics
and Functions of WBC
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.
Physiological Characteristics
and Functions of WBC
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
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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, monocytemacrophage, 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
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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
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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
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Platelet forming:
Birth place is bone marrow, originating from hemopoietic
stem cells, and differentiating into burst forming unitmegakaryocyte, 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
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Life-span: Averagely, 7~14 days in
the blood. It can be consumed when it
displays physiological functions.
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Breakage: Aged platelet can be
processed by phagocytosis in liver,
spleen and lymphatic node.
IV. Physiological Hemostasis
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*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)
Physiological Hemostasis
1.Endocrine functions of vessel
endothelial cells
①
②
③
④
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.
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).
Promoting coagulative material: Tissue factor, vWF,
blood clotting factor V, plasminogen activator inhibitor
(PAI-1, PAI-2, ATIII), TNFα, interleukin-1 (IL-1).
Vessel constricting and relaxing modulators: endothelin1 (ET-1), EDRF (NO), PGI2, etc.
Roles of Vessel Endothelial Cells in
Physiological Hemostasis
Roles are close related to its endocrine functions
①
②
③
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.
Platelet activation can releases constrictive factors
(TXA2, ET-1, 5-HT, etc) making vessel convulsion,
lasting about 60 sec.
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
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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
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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.
3.Blood Coagulation
Blood Clotting Factor
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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
Concentration
I Fibrinogen
3000
II Prothrombin
100
III Tissue factor
IV Ca2+
100
V Proaccelerin
10
Ⅶ Proconvertin
0.5
Ⅷ Antihemophilic factor,AHF
0.1
Ⅸ Plasma thromboplastic
5
component,PTC(Christmas factor)
Ⅹ Stuart-Prower Factor
10
Ⅺ Plasma thromoboplastin
5
antecedent,PTA
Ⅻ Contact factor or Hageman factor
40
XIII Fibrin-stabilizing factor
10
- High-molecular weight
80
kininogen,HMW-K
- Prekallikrein,Pre-K or Fletcher factor 35
Synthesizing
Half life
Chromsome
site
Liver
Liver (with Vit K)
Endothelial cell
Endothelial cell, platelet
Liver (with Vit K)
Liver
Liver (with Vit K)
site
4~5 d
3d
12~15 h
4~7 h
8~10 h
24 h
4
11
1
13
Ⅹ
Ⅹ
Liver (with Vit K)
Liver
2d
2~3 d
13
4
Liver
Liver, platelet
Liver
24 h
8d
-
5
6,1
3
Liver
-
4
Blood Coagulation
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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 ）
Ⅻ
TF+Ⅶ
Ⅺ
Ca2+
Ⅶ-TF
Ⅹa
Ⅶa-TF
Ⅸ
Ca2+ ，PL
Ca2+
PL
S:
Ⅺa
Ca2+
Ⅷa
PL
PL: phospholipid
HK: high molecular weight kininogen
Ⅻa
Ⅱ
Ⅹa
Ca2+
Ⅴa
PL
ⅩⅢ
Ⅱa
Subendothelium
PK: prekallikrein
K: kallikrein
PK
Ⅸa
Ⅹ
CL: cross linking fibrin
Ca2+
S
K
HK
Ⅰ
Ⅰa
ⅩⅢa
Ca2+
CLⅠa
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, Clinhibitor, 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:
Endothelial cells (Extrinsic
pathway )
(Urokinase, uPA)
Kallikrein (Intrinsic pathway)
uPA
tPA
Plasminogen
PAI-1
α2-antiplasmin
α2-huge globin
Fibrin or fibrinogen
Cl-inhibitors
uPAG
Plasmin
Fibrin
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), α2antiplasmin (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
O
A+B
Anti-A+Anti-B
2. ABO blood group system
Antigen (agglutinogen) and antibody
(agglutinin) in ABO blood subgroup system
Blood group
A
A1
A2
B
A+ A1
A
B
AB A1B
A2B
O
Antigen on the RBC
Antibody in the serum
Anti-B
Anti-B+ Anti-A1
Anti-A
A+ A1 +B
A+B
Anti-A1
Anti-A+Anti-B
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’
blood group
Offspring possible
blood group
Offspring impossible
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
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
RBC
红细胞
RBC
红细胞
Donator
Receiver
受
血
者
供
血
者
Serum
Serum
血清
血清
Main side of
主侧凝集反应
agglutination
Subordinary
side
次侧凝集反应
of agglutination
-
-
+
+, -
-
+
Decision
Perfect
match, transfusion
相合，可以输血
×
No
match, transfusion
不合，不能输血
Transfusion
under emergency
应急情况下输血
+: 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:
It decreases infection.
It blocks syndrome (fever, hemolysis) induced by
allogenetic transfusion.
③
It stimulates bone marrow hemopoiesis towards
RBC.
①
②

Transfusion of blood components is good.
Summarization
PLEASE TAKE DOWN
Consideration after class
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.
Thank You for Your Attention