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BLOOD PHYSIOLOGYBLOOD PHYSIOLOGY
OutlineOutlineI. Blood composingI. Blood composingII. Physical and chemical characteristics of bloodII. Physical and chemical characteristics of bloodIII. Blood CellsIII. Blood Cells
1. Hemopoietic process and hemopoietic stem cells1. Hemopoietic process and hemopoietic stem cells2. Hemopoietic microenvironment2. Hemopoietic microenvironment3. Erythrocyte Physiology3. Erythrocyte Physiology4. Leukocyte Physiology4. Leukocyte Physiology5. Platelet or Thrombocyte Physiology5. Platelet or Thrombocyte Physiology
IV. Physiological HemostasisIV. Physiological Hemostasis1. Endocrine functions of vessel endothelial cells 1. Endocrine functions of vessel endothelial cells 2. Physiological Characteristics of Platelet2. Physiological Characteristics of Platelet3. Blood Coagulation3. Blood Coagulation4. Fibrinolysis4. Fibrinolysis
V. Blood GroupV. Blood Group1. RBC Agglutination1. RBC Agglutination2. ABO blood group system2. ABO blood group system3. Rh blood group system3. Rh blood group system4. Relation between blood volume and clinic4. Relation between blood volume and clinic5. Principle of Transfusion and Cross-match test 5. Principle of Transfusion and Cross-match test
What will we discuss in this chapter?What will we discuss in this chapter?(Outline)(Outline)
Blood and Internal Environmental Blood and Internal Environmental HomeostasisHomeostasis
Blood is that part of extracellular fluid within the cardiovascular systemBlood 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 composingI. Blood composingBlood composing: plasma + blood cellsHematocrit: blood cells occupies the percentage of total blood volume. normal value male: 40-50% female: 37-48% newborn: 55%
Blood component (summing-up)Blood component (summing-up)
Terminology and normal valueTerminology and normal value
Chemical component of plasmaChemical component of plasmaWater: > 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 plasmaChemical component of plasma
(Unit : mmol/L)
H2O 90 - 91%
Plasma Interstitial fluid
Intracellular fluid
Protein
II. Physical and chemical II. Physical and chemical characteristics of blood 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 PressureOsmosis 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 PressureOsmosis and Osmotic Pressure
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A B
[Water] > [Water][Salt] < [Salt]
Osmotic Pressure < Osmotic PressureOsmosis 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.
TonicityTonicity
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 CellsIII.Blood Cells Blood cells are erythrocyte (red blood cell, Blood cells are erythrocyte (red blood cell, RBC), leukocyte (white blood cell, WBC) and RBC), leukocyte (white blood cell, WBC) and thrombocyte (platelet, P).thrombocyte (platelet, P).
Blood CellsBlood CellsThe forming processes of erythrocyte (red blood cell, The forming processes of erythrocyte (red blood cell, RBC), leukocyte (white blood cell, WBC) and RBC), leukocyte (white blood cell, WBC) and thrombocyte (platelet, P) originating from thrombocyte (platelet, P) originating from hematopoietic stem cells are hematopoietic stem cells are hemopoiesishemopoiesis..
Transfer of blood cells forming place:Transfer of blood cells forming place: yolk sac hemopoiesisyolk sac hemopoiesis (early(early embryo period) embryo period) →→ liver liver and spleenand spleen (second embryo month) (second embryo month) → marrow↑and liver, → marrow↑and liver, spleen↓ spleen↓ (after fourth embryo month) (after fourth embryo month) → marrow → marrow (fetus (fetus birth time) birth time) and liver, spleen as complementary role.and liver, spleen as complementary role.
During adulthood (after 18), red marrow During adulthood (after 18), red marrow (flat bones, (flat bones, e.g. vertebra,ilium, sternum, rib, skull and long bone e.g. vertebra,ilium, sternum, rib, skull and long bone ending)ending) rather than yellow marrow has hematopoietic rather than yellow marrow has hematopoietic functions. functions.
1. Hemopoietic process and 1. Hemopoietic process and hemopoietic stem cells hemopoietic stem cells
Hemopoietic processHemopoietic process Stage one:Stage one: Hemopoietic stem cells Hemopoietic stem cells
self renewal, steady numbers, active differentiation. self renewal, steady numbers, active differentiation.
Stage two:Stage two: committed progenitors committed progenitors
directionaldirectional differentiation (CFU-GEMM, CFU-E, CFU-differentiation (CFU-GEMM, CFU-E, CFU-
GM, CFU-MK, CFU-TB). [CFU: colony- forming unitGM, CFU-MK, CFU-TB). [CFU: colony- forming unit
Stage three:Stage three: precursors precursors
morphologic occurrence of various original blood cells. morphologic occurrence of various original blood cells.
Hemopoietic stem cellsHemopoietic stem cellsBasic 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 microenvironment2.Hemopoietic microenvironmentHemopoietic 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 processHemopoietic process
Hemopoietic processHemopoietic process
Hemopoietic processHemopoietic process
3.Erythrocyte Physiology3.Erythrocyte PhysiologyShape 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 RBCReason for shape of RBC
biconcave disc likebiconcave disc like
Erythrocyte PhysiologyErythrocyte PhysiologyNumber 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 Physiological Characteristics and Functions of RBCFunctions of RBC
Characteristics of RBCCharacteristics of RBC①① Permeability:Permeability: semipermeable membrane, gas and semipermeable membrane, gas and
urea freely passing through, negative ions easily in urea freely passing through, negative ions easily in or out of RBC, and positive ions not. There are Na-K or out of RBC, and positive ions not. There are Na-K ATPase as pump on the membrane of RBC and low-ATPase as pump on the membrane of RBC and low-temperature-stored plasma easily has high kalium. temperature-stored plasma easily has high kalium. Why?Why?
②② Plasticity and metamorphose:Plasticity and metamorphose:
Plasticity and metamorphose depend on: 1) surface area-cubage Plasticity and metamorphose depend on: 1) surface area-cubage ratio, 2) viscosity of Hb, 3) membrane elasticity and viscosity. ratio, 2) viscosity of Hb, 3) membrane elasticity and viscosity.
Characteristics of RBCCharacteristics of RBC③③Suspension stability: it cab be described by Suspension stability: it cab be described by erythrocyte sedimentation rate (ESR) which is erythrocyte sedimentation rate (ESR) which is RBC descending distance per hour and RBC descending distance per hour and suspension stability is inverse proportion to suspension stability is inverse proportion to ESR.ESR.
Normal value of ESR: male, 0~15 mm/h; Normal value of ESR: male, 0~15 mm/h; female, 0~20 mm/h.female, 0~20 mm/h.
ESR and clinic: some diseases bring about ESR and clinic: some diseases bring about rouleaux formation (mainly involved in plasma rouleaux formation (mainly involved in plasma component, e.g. globulin, fibrinogen, component, e.g. globulin, fibrinogen, cholesterol) and speed up ESR. cholesterol) and speed up ESR.
Physiological Characteristics and Physiological Characteristics and Functions of RBCFunctions of RBC
Physiological Characteristics and Physiological Characteristics and Functions of RBCFunctions of RBC
Characteristics of RBCCharacteristics of RBC
④④Osmotic fragility: Changes in RBC put intoOsmotic fragility: Changes in RBC put into
lower osmotic salty solution.lower osmotic salty solution.
Osmotic fragility of aged RBC is large andOsmotic fragility of aged RBC is large and
easily results in rupture (hemolysis and ghosteasily results in rupture (hemolysis and ghost
cell).cell).
Isosmotic solution, e.g. 0.85% NaCl, Isosmotic solution, e.g. 0.85% NaCl,
1.4%NaHCO1.4%NaHCO33, 5% glucose, etc. , 5% glucose, etc.
Isotonic solution, e.g. 0.85% NaCl Isotonic solution, e.g. 0.85% NaCl
Isosmotic solution does not equal to isotonicIsosmotic solution does not equal to isotonic
solution.solution.
Isosmotic solution, isotonic solution and clinicIsosmotic solution, isotonic solution and clinic
Physiological Characteristics and Physiological Characteristics and Functions of RBCFunctions of RBC Functions of RBCFunctions of RBC
RBC can be used for transportation ofRBC can be used for transportation of OO22 and CO and CO22 in the blood. in the blood. RBC can be served as pH buffer. RBC can be served as pH buffer.
ErythropoiesisErythropoiesisHemopoietic 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 ErythropoiesisPlace for Erythropoiesis
Main place for Erythropoiesis is bone Main place for Erythropoiesis is bone marrow. Aother place is liver.marrow. Aother place is liver.
Regulation of ErythropoiesisRegulation of Erythropoiesis0.8% of total RBCs has self renewal, that is to 0.8% of total RBCs has self renewal, that is to
say, 160×10say, 160×1066 RBC production every minute. RBC production every minute.Burst forming unit-erythroid, BUF-E, important Burst forming unit-erythroid, BUF-E, important
to earlier erythropoiesis, depends on stimulation to earlier erythropoiesis, depends on stimulation of burst promoting activity, BPA outside body. of burst promoting activity, BPA outside body. BPA made by leucocyte is a glycoprotein whose BPA made by leucocyte is a glycoprotein whose molecular weight is about 25000~40000molecular weight is about 25000~40000
Colony forming unit-erythroid, CFU-E, important Colony forming unit-erythroid, CFU-E, important to terminal erythropoiesis, depends on to terminal erythropoiesis, depends on erythropoietin, EPO which is also a glycoprotein, erythropoietin, EPO which is also a glycoprotein, molecular weight, 34000, plasma concentration molecular weight, 34000, plasma concentration 10 pmol/L, half life 5 hours, increasing release 10 pmol/L, half life 5 hours, increasing release when anoxia. when anoxia.
Regulation of ErythropoiesisRegulation of Erythropoiesis
Life and breakage of RBCLife and breakage of RBC
Life-span: 120 days, about 4 months, each RBC Life-span: 120 days, about 4 months, each RBC circulates 27 km averagely in vessels, short circulates 27 km averagely in vessels, short life-span for aged RBClife-span for aged RBC
Breakage: places are liver, spleen and Breakage: places are liver, spleen and lymphatic node, and after breakage, Hb lymphatic node, and after breakage, Hb released from RBC immediately combine with released from RBC immediately combine with plasma αplasma α22-globulin (Hb touched protein) which -globulin (Hb touched protein) which
is taken in by liver for iron reuse.is taken in by liver for iron reuse.Hb, very toxic if it get into blood, normally, it Hb, very toxic if it get into blood, normally, it
can be metabolized into bile pigment in liver. can be metabolized into bile pigment in liver. Clinic relation. Clinic relation.
4.Leukocyte Physiology4.Leukocyte PhysiologyClassification and numbers of LeukocyteClassification 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 Classification and numbers of LeukocyteLeukocyte
TABLE. Classification and normal value of LeukocyteTABLE. Classification and normal value of Leukocyte
Absolute Value (×10Absolute Value (×1099/L) Percentage (%)/L) Percentage (%)
Total numbers of leukocytes 4.0~10.0 Total numbers of leukocytes 4.0~10.0 Neutrophil (bacilliform nucleus) 0.04~0.5 1~5 Neutrophil (bacilliform nucleus) 0.04~0.5 1~5 Neutrophil (foliiform nucleus) 2.0~7.0 50~70 Neutrophil (foliiform nucleus) 2.0~7.0 50~70 Eosinophil 0.02~0.5 0.5~5 Eosinophil 0.02~0.5 0.5~5 Basophil 0.0~0.1 0~1 Basophil 0.0~0.1 0~1 Monocyte 0.12~0.8 3~8 Monocyte 0.12~0.8 3~8 Lymphocyte 0.8~4.0 20~40 Lymphocyte 0.8~4.0 20~40
For Clinic Use
Physiological Changes in Numbers Physiological Changes in Numbers of Leukocyteof Leukocyte
Newborn: Number is higher, 15×10Newborn: Number is higher, 15×1099/L, after birth 3 or 4 /L, after birth 3 or 4 days to 3 months, being about 10×10days to 3 months, being about 10×1099/L, mainly, /L, mainly, neutrophil, 70%; secondarily, lymphocyte.neutrophil, 70%; secondarily, lymphocyte.
Circadian changes: Number of WBC is more in the Circadian changes: Number of WBC is more in the afternoon than in the morning.afternoon than in the morning.
Food taking, ache and mood excitation: Number of Food taking, ache and mood excitation: Number of WBC is remarkably higher.WBC is remarkably higher.
Heavy exercise and laboring: Increasing numbers, Heavy exercise and laboring: Increasing numbers, about 35×10about 35×1099/L, return to original level after action /L, return to original level after action stop.stop.
Terminal pregnancy of female: Numbers changes in Terminal pregnancy of female: Numbers changes in 12~17×1012~17×1099/L, and during parturition, 34×10/L, and during parturition, 34×1099/L, and /L, and after parturition 2~5 days, number return to original after parturition 2~5 days, number return to original level. level.
Physiological Characteristics and Physiological Characteristics and Functions of WBCFunctions of WBC
TerminologyDiapedisis: 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.
Dia
ped
isis
Chemota
xis
Metamorphose
BloodVessel
WBC
Physiological CharacteristicsPhysiological Characteristics and Functions of WBC and Functions of WBC
①①NeutrophilNeutrophilAnother name, polymorphonuclear, PMN, 6~8 h in the Another name, polymorphonuclear, PMN, 6~8 h in the
vessels, diapedisis, chemotaxis and phagocytosis (using vessels, diapedisis, chemotaxis and phagocytosis (using its hydrolyzed enzyme)its hydrolyzed enzyme)
Function: It plays a very important role in nonspecific Function: It plays a very important role in nonspecific cellular immunity system which is against pathogenic cellular immunity system which is against pathogenic microorganism, such as bacteria, virus, parasite, etc. microorganism, such as bacteria, virus, parasite, etc.
Clinic relation: Clinic relation: Number of neutrophil greatly increase occurring in Number of neutrophil greatly increase occurring in acute inflammation and earlier time of chronicacute inflammation and earlier time of chronic inflammation. inflammation. number decrease of neutrophil will result in poornumber decrease of neutrophil will result in poor resistibility and easily suffering from infection.resistibility and easily suffering from infection.
Physiological CharacteristicsPhysiological Characteristics and Functions of WBC and Functions of WBC
②② EosinophilEosinophil Circadian changes: Its number is lower in the morning Circadian changes: Its number is lower in the morning
and higher at night.and higher at night. Function: Function:
1. It limits and modulates the effects of basophil on fast1. It limits and modulates the effects of basophil on fast
allergic reaction.allergic reaction.
2. It is involved in immune reaction against worm with2. It is involved in immune reaction against worm with
opsonization.opsonization.
②② Clinic relation: Its number increase when person suffers Clinic relation: Its number increase when person suffers
from parasite infection or allergic reaction. from parasite infection or allergic reaction.
Physiological CharacteristicsPhysiological Characteristics and Functions of WBC 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 CharacteristicsPhysiological Characteristicsand Functions of WBCand 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 CharacteristicsPhysiological Characteristicsand Functions of WBCand Functions of WBC
⑤⑤ LymphocyteLymphocyte Classification: It can be separated into T- Lymphocyte andClassification: It can be separated into T- Lymphocyte and
B- Lymphocyte.B- Lymphocyte. Function:Function:
1. Lymphocytes serve as a nuclear role in immune1. Lymphocytes serve as a nuclear role in immune
responsive reaction.responsive reaction.
2. T- Lymphocytes involved in cellular immunity.2. T- Lymphocytes involved in cellular immunity.
3. B- Lymphocytes involved in humoral immunity.3. B- Lymphocytes involved in humoral immunity.
⑤⑤ Clinic relation: Numbers increase of lymphocytes occur inClinic relation: Numbers increase of lymphocytes occur in
chronic inflammation and late time of infection. chronic inflammation and late time of infection.
Leukopoiesis, Regulation and BreakageLeukopoiesis, 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 Physiology5.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 PlateletNormal 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 RegulationPlatelet Forming and RegulationPlatelet 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 PlateletLife- Span and Breakage of Platelet
Life-span:Life-span: Averagely, 7~14 days in the Averagely, 7~14 days in the
blood. It can be consumed when it blood. It can be consumed when it
displays physiological functions.displays physiological functions.Breakage:Breakage: Aged platelet can be Aged platelet can be
processed by phagocytosis in liver, processed by phagocytosis in liver,
spleen and lymphatic node. spleen and lymphatic node.
IV. Physiological HemostasisIV. 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 HemostasisPhysiological Hemostasis
1.Endocrine functions of vessel endothelial cells1.Endocrine functions of vessel endothelial cells① 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 Roles of Vessel Endothelial Cells in Physiological HemostasisPhysiological Hemostasis
Roles are close related to its endocrine functionsRoles are close related to its endocrine functions①① Vessel endothelium serves as barrier between Vessel endothelium serves as barrier between
underendothelial structure (namely, collagen) and blood. underendothelial structure (namely, collagen) and blood. As soon as collagen expose to blood, hemostasis of As soon as collagen expose to blood, hemostasis of platelet is immediately activated to form thrombus platelet is immediately activated to form thrombus blocking wounded vessels.blocking wounded vessels.
②② Platelet activation can releases constrictive factors (TXAPlatelet activation can releases constrictive factors (TXA22, , ET-1, 5-HT, etc) making vessel convulsion, lasting about ET-1, 5-HT, etc) making vessel convulsion, lasting about 60 sec.60 sec.
③③ Stimulated vessel endothelial cells release coagulative Stimulated vessel endothelial cells release coagulative factors and Promoting coagulative material to realize, factors and Promoting coagulative material to realize, speed up blood coagulation. At the same time, cells also speed up blood coagulation. At the same time, cells also release anticoagulative factors and fibrinolysis material to release anticoagulative factors and fibrinolysis material to modify blood coagulation.modify blood coagulation.
Inactive Platelet Inactive Platelet Under the electronic microscope
Activated Platelet for Hemostasis Activated Platelet for Hemostasis
Under the electronic microscope
2.Physiological Characteristics of Platelet 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 HemostasisRoles of Platelet in HemostasisActivation 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 PhysiologicalTwo Phases of Physiological HemostasisHemostasis
First Phase Second Phase
Mechanism1 of Platelet in HemostasisMechanism1 of Platelet in Hemostasis
Mechanism2 of Platelet in HemostasisMechanism2 of Platelet in Hemostasis
3.Blood Coagulation3.Blood CoagulationBlood Clotting FactorBlood 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 Blood coagulation is a series of complicated biochemical
reactions with various enzymes.reactions with various enzymes.Blood clotting factor: Material which are directly involved in Blood clotting factor: Material which are directly involved in
blood coagulation. There are 12 factors named Roman blood coagulation. There are 12 factors named Roman numerals, except Canumerals, except Ca2+2+, phospholipid, phospholipid ,, other factors being other factors being protein, and except FIII (TF), others are in fresh plasma protein, and except FIII (TF), others are in fresh plasma synthesized by liver with VitK .synthesized by liver with VitK .
Blood clotting enzymes have two type: inactive and activated Blood clotting enzymes have two type: inactive and activated type [FII, FVII, FIX, Fx, FXI, FXII, FXIII].type [FII, FVII, FIX, Fx, FXI, FXII, FXIII].
I Fibrinogen 3000 Liver 4~5 d 4
II Prothrombin 100 Liver (with Vit K) 3 d 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) 2 d 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 8 d 6,1
- High-molecular weight 80 Liver - 3
kininogen,HMW-K
- Prekallikrein,Pre-K or Fletcher factor 35 Liver - 4
Factor Name Plasma Synthesizing Half life Chromsome
Concentration site site
Blood Clotting FactorBlood Clotting Factor
Blood CoagulationBlood CoagulationIntrinsic 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 3Hemophilia A, B, C in the clinic results from deficiency of FVIII, FIX,
FXI in the blood, respectively.
Extrinsic pathway (Tissue Factor , TF )
TF+Ⅶ
Ⅶ-TF
Ⅶa-TF
Ca2+
Ca2+ , PL
Ca2+
Ⅹa
Ca2+
Ⅹ
Ⅺ
Ⅸ
Ⅸa
Ⅹa
Ca2+
Ⅷa
PLPL
Ⅴa
Ⅻ
Ⅱ
Ⅰ
ⅩⅢ
Ⅻa
HK
SK PK
Ⅺa
Ⅰa CLⅠa
Ca2+
PLCa2+
Ⅱa
ⅩⅢa
Intrinsic pathway ( Eyewinker surface )
PL: phospholipid
CL: cross linking fibrin
HK: high molecular weight kininogen
S: Subendothelium
PK: prekallikrein
K: kallikrein
Process of Blood CoagulationProcess of Blood Coagulation
Mechanism of Blood CoagulationMechanism of Blood Coagulation
Anticoagulative system in bloodAnticoagulative system in bloodCellular 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 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
tPA
Plasminogen
Kallikrein
Cl-inhibitorsuPAGuPA
PlasminPAI-1
Fibrin or fibrinogen Fibrin
dissolution
α2-antiplasminα2-huge globin
(Urokinase, uPA)(Extrinsic pathway )
(Intrinsic pathway)
Blood Coagulation and FibrinolysisBlood Coagulation and Fibrinolysis
Antifibrinolysis: Antifibrinolysis: Fibrinolytic Inhibitors and Its FunctionsFibrinolytic 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 GroupV. Blood GroupHistory: 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.
Antigen-Antibody Harmful immune Reaction
1. RBC Agglutination
Blood Coagulation RBC Agglutination
Antigen of Blood GroupAntigen of Blood Group
Antigen:Antigen: Its genes are located at allele on Its genes are located at allele on euchromosome, namely, expressed gene.euchromosome, namely, expressed gene.
GenotpyeGenotpye is genetic gene in blood group is genetic gene in blood group system and system and phenotypephenotype is antigen produced by is antigen produced by corresponding genetic gene and corresponding genetic gene and amorphamorph is is noneffective allele.noneffective allele.
Genes in the blood system decide differential Genes in the blood system decide differential specific antigen on the membrane with control specific antigen on the membrane with control of enzymatic activity. of enzymatic activity.
Antibody of Blood GroupAntibody 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 RBCBlood Group of RBC
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
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:
2. ABO blood group system2. 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
Ushering material
O(H)-antigen
A-antigen
B-Antigen
GalactoseN-acetamide
GlucoseN-acetamide
galactose
GlucoseSugar
Antigen of blood group
ABH Antigen chemical structure in ABO ABH Antigen chemical structure in ABO blood group systemblood group system
Inheritance of ABO blood groupInheritance of ABO blood groupInheritance: 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 phenotype
OO OAA, AO ABB, BO BAB AB
Genotype and Phenotype in ABO blood group system
Inheritance of ABO blood groupInheritance 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
Genetic relationship of ABO blood group
Distribution of ABO blood groupDistribution 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 groupMensuration of ABO blood group
Anti-BSerum
Anti-ASerum
Anti-A, BSerum
3. Rh blood group system3. 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 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. 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 Transfusion5. Principle of TransfusionTransfusion 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 transfusionRBC RBC
Donator ReceiverM
ain side
Subordin
ate
side
Serum Serum
Main side of agglutination
Perfect match, transfusion
No match, transfusion
Transfusion under emergency
×
Subordinary side of agglutination Decision
+: Agglutination; -: No agglutination
Types of TransfusionTypes of Transfusion According to source of transfusion, allogenetic According to source of transfusion, allogenetic
transfusion (more use), autologous transfusion.transfusion (more use), autologous transfusion. According to component of transfusion, whole According to component of transfusion, whole
blood transfusion, transfusion of blood blood transfusion, transfusion of blood componentscomponents
Autologous transfusion has some advantages:Autologous transfusion has some advantages:①① It decreases infection.It decreases infection.②② It blocks syndrome (fever, hemolysis) induced by It blocks syndrome (fever, hemolysis) induced by
allogenetic transfusion.allogenetic transfusion.③③ It stimulates bone marrow hemopoiesis towards RBC.It stimulates bone marrow hemopoiesis towards RBC.
Transfusion of blood components is good. Transfusion of blood components is good.
Consideration after classConsideration after class
1. Please describe classification and main effects of leucocyte.1. Please describe classification and main effects of leucocyte.
2. What is the elementary process of blood coagulation and 2. What is the elementary process of blood coagulation and
main factors which have participated in blood coagulation?main factors which have participated in blood coagulation?
3. Please describe the principle of classification and blood 3. Please describe the principle of classification and blood
transfusion of ABO blood group system.transfusion of ABO blood group system.