Download Blood Physiology

BLOOD PHYSIOLOGY
What will we discuss in this chapter?
(Outline)
I. Blood composing
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
Outline
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
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
 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
H2O
90 - 91%
Plasma
Interstitial
fluid
Intracellular
fluid
Protein
(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 fluorescenceactivated 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
 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.
Hemopoietic process
Hemopoietic process
Hemopoietic process
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
①Permeability: 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 lowtemperature-stored plasma easily has high kalium.
Why?
②Plasticity 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
③Suspension 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
Characteristics of RBC
④Osmotic 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.
Regulation of Erythropoiesis
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.

Regulation of Erythropoiesis
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)
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





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
WBC
Diapedisis
Terminology
 Diapedisis: Metamorphosed WBCs
pass through vessel wall getting
into interstitial fluid.
 Chemotaxis: It is a process that
WBCs shift to some chemical
material (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 digesting
them.
BloodV
essel
Metamorphose
Physiological Characteristics
and Functions of WBC
①Neutrophil
 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
chronic inflammation and late time of infection.
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, 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




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 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

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)
Physiological Hemostasis
1.Endocrine functions of vessel endothelial cells
①Material 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.
②Anticoagulative 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).
③Promoting coagulative material: Tissue factor, vWF, blood
clotting factor V, plasminogen activator inhibitor (PAI-1, PAI2, ATIII), TNFα, interleukin-1 (IL-1).
④Vessel 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
①Vessel 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.
②Platelet activation can releases constrictive factors (TXA2,
ET-1, 5-HT, etc) making vessel convulsion, lasting about
60 sec.
③Stimulated 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 βplatelet globin, PF4, vWF, fibrinogen, PFV, PDGF, thrombin sensitive protein from αgranule, 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
Concentration
I
Fibrinogen
Synthesizing
Half life
Chromsome
site
site
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
Ⅹ Stuart-Prower Factor
10
Liver (with Vit K)
2d
13
Ⅺ Plasma thromoboplastin
5
Liver
2~3 d
4
Ⅻ Contact factor or Hageman factor
40
Liver
24 h
5
XIII Fibrin-stabilizing factor
10
Liver, platelet
8d
6,1
80
Liver
-
3
35
Liver
-
4
component,PTC(Christmas factor)
antecedent,PTA
- High-molecular weight
kininogen,HMW-K
- Prekallikrein,Pre-K or Fletcher factor
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 ）
Ⅻ
TF+Ⅶ
Ⅺ
Ca2+
Ⅶ-TF
Ⅹa
Ⅶa-TF
S
K
Ⅸ
PL
Ca2+
Ⅷa
PL
Ⅹa
PL: phospholipid
HK: high molecular weight kininogen
Ⅺa
Ⅸa
Ⅹ
CL: cross linking fibrin
Ⅴa
Ⅱ
Ca2+
PL
ⅩⅢ
Ⅱa
Subendothelium
PK: prekallikrein
K: kallikrein
PK
Ⅻa
Ca2+
Ca2+ ，PL
Ca2+
S:
H
K
Ⅰ
Ⅰa
ⅩⅢa
Ca2+
CLⅠa
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, 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
uPA
tPA
Plasminogen
PAI-1
α2-antiplasmin
α2-huge globin
Fibrin or fibrinogen
(Intrinsic pathway)
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), 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
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
ABH Antigen chemical structure in ABO
blood group system
Antigen of blood group
Ushering material
O(H)-antigen
A-antigen
B-Antigen
Galactose
N-acetamide
Glucose
Sugar
Glucose
N-acetamide
galactose
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
OO
AA, AO
BB, BO
AB
phenotype
O
A
B
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
Mensuration of ABO blood group
Anti-B
Serum
Anti-A
Serum
Anti-A, B
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
RBC
RBC
Donator
Receiver
Serum
Main side of
agglutination
Serum
Subordinary side
of agglutination
Decision
Perfect match, transfusion
×
No match, transfusion
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:
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.
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.