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BLOOD PHYSIOLOGY
What will we discuss in this chapter?
I. Blood composition
                           OUTLINE
II. Physical and chemical characteristics of blood
III. Blood Cells
       1. Hemopoietic process and hemopoietic stem cells
       2. Hemopoietic microenvironment
       3. Erythrocyte Physiology
       4. Leukocyte Physiology
       5. Platelet or Thrombocyte Physiology
IV. Physiological Hemostasis
       1. Endocrine functions of vessel endothelial cells
       2. Physiological Characteristics of Platelet
       3. Blood Coagulation
       4. Fibrinolysis
V. Blood Group
       1. RBC Agglutination
       2. ABO blood group system
       3. Rh blood group system
       4. Relation between blood volume and clinic
       5. Principle of Transfusion and Cross-match test
BLOOD AND INTERNAL
    ENVIRONMENTAL HOMEOSTASIS
   Blood is that part of extracellular fluid within the cardiovascular system
   Blood formation
    During animals’ evolution, extracellular fluid was gradually shaped from the
    age-old time with ocean which was mainly salty solution. At last, extracellular
    fluid was differentiated into plasma and interstitial fluid and blood came from
    plasma and cells.
   The role of blood in internal environmental = homeostasis
    Blood, the most active component in extracellular fluid, display functions as
    follows:
      (1) transport;
      (2) pH buffer;
      (3) temperature or thermal maintenance;
      (4) immunity and defense
I. BLOOD COMPOSITION
 Blood composed of :
  plasma + blood cells
 Hematocrit:

  the percentage of total
  blood volume that blood
  cells occupy.
  normal value
  male: 40-50%
  female: 37-48%
  newborn: 55%
BLOOD   COMPONENT   (SUMMING-UP)
TERMINOLOGY AND NORMAL VALUE
CHEMICAL COMPONENT OF PLASMA
   H 2O    90 - 91%
             血浆
           Plasma       组织液
                      Interstitial     细胞内液
                                     Intracellular
                         fluid           fluid

   Na+       142          145             12
   Cl-       104          117             4
  Ca++       2.5          2.4          <0.001
   K+        4.3          4.4            139
  PO4-        2           2.3             29
 蛋白质
 Protein     14           0.4             54
                                     (Unit:mmol/L)
II. PHYSICAL           AND CHEMICAL
         CHARACTERISTICS OF BLOOD
 Specific gravity: total blood (1.050-1.060) more influenced by
  red blood cells; plasma (1.025-1.030) more influenced by
  plasma protein; RBC (1.090-1.092) more influenced by Hb.
 Viscosity:

   Blood relative viscosity (4~5) mainly depends on the
  numbers of red blood cells.
   Plasma relative viscosity (1.6~2.4) is mainly involved in plasma
  protein
 Plasma osmotic pressure is 300 mmol/L or 770kPa
   (1) Crystal osmotic pressure results from NaCl and
  modulates water distribution between inside and outside of
  cells.
   (2) Colloid osmotic pressure results from albumin and
  regulates water distribution between inside and outside of
  capillary.
 Plasma pH value is about 7.35~7.45, and usually buffer
  systems are NaHCO3/H2CO3 (20:1), protein salt/protein,
  Na2HPO4/ NaH2PO4, Hb salt/Hb, HbO salt/ HbO2,
  K2HPO4/ KH2PO4, KHCO3/H2CO3, etc [lungs and kidney
  mainly regulate Plasma pH value ].
OSMOSIS AND OSMOTIC PRESSURE


 Osmosis is the movement of water down its concentration
  gradient.
 Osmosis is determined by the number of impermeable
  molecules.
 Osmotic pressure is the force drawing water down its
  concentration gradient.
OSMOSIS AND OSMOTIC PRESSURE
             A                                                     B




                      Water



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

 The tonicity of a solution refers to the effect of the solution
  on cell volume.
 A hypertonic extracellular solution is one in which the
  water concentration is less outside the cell than inside;
  water leaves the cell; cell volume decreases.
 An isotonic extracellular solution is one in which the water
  concentration is the same inside and outside the cell; no
  water movement; cell volume does not change.
 A hypotonic solution is one in which the water
  concentration is greater outside than inside the cell; water
  enters the cell; cell volume increases.
 An isosmotic solution may not be an isotonic solution if the
  particles are permeable to the cell membrane.
III.BLOOD CELLS
Blood cells are erythrocyte (red blood cell, RBC),
leukocyte (white blood cell, WBC) and thrombocyte
(platelet, P).
BLOOD CELLS
   The forming processes of erythrocyte (red blood cell, RBC),
    leukocyte (white blood cell, WBC) and thrombocyte (platelet, P)
    originating from hematopoietic stem cells are hemopoiesis.
   Transfer of blood cells forming place:
    yolk sac hemopoiesis (early embryo period) → liver and spleen
    (second embryo month) → marrow↑and liver, spleen↓ (after
    fourth embryo month) → marrow (fetus birth time) and liver,
    spleen as complementary role.
    During adulthood (after 18), red marrow (flat bones, e.g.
    vertebra,ilium, sternum, rib, skull and long bone ending) rather
    than yellow marrow has hematopoietic functions.
1. HEMOPOIETIC PROCESS AND
          HEMOPOIETIC STEM CELLS


               Hemopoietic process
Stage one: Hemopoietic stem cells
self renewal, steady numbers, active differentiation.
Stage two: committed progenitors
directional differentiation (CFU-GEMM, CFU-E, CFU-
GM, CFU-MK, CFU-TB). [CFU: colony- forming unit
Stage three: precursors
morphologic occurrence of various original blood cells.
HEMOPOIETIC STEM CELLS
                             Basic characteristics
   Self renewal in high degree, constant from young to old age.
   Multi- directional differentiation
   Large potential proliferation, Hemopoietic stem cells produce about
    1×1011 blood cells releasing to blood for use.
   Surface sign
    According to CFU (colony forming unit), using fluorescence-
    activated cell sorting (FACS), its main surface sign is CD34+CD38-
    Lin-and CD34-CD38-Lin-.
    Note
    CD: cluster of differentiation of antigen on the white blood cells;
    Lin: systemic specific antigen on the hemopoietic cells.
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
①   Permeability: semipermeable membrane, gas and urea freely
    passing through, negative ions easily in or out of RBC, and
    positive ions not. There are Na-K ATPase as pump on the
    membrane of RBC and low-temperature-stored plasma
    easily has high kalium. Why?
②   Plasticity and metamorphose:




Plasticity and metamorphose depend on: 1) surface area-cubage
ratio, 2) viscosity of Hb, 3) membrane elasticity and viscosity.
PHYSIOLOGICAL
      CHARACTERISTICS AND
       FUNCTIONS OF RBC
                  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
                        Characteristics of RBC
④    Osmotic fragility: Changes in RBC put into
    lower osmotic salty solution.
    Osmotic fragility of aged RBC is large and
    easily results in rupture (hemolysis and ghost
    cell).
    Isosmotic solution, e.g. 0.85% NaCl,
         1.4%NaHCO3, 5% glucose, etc.
    Isotonic solution, e.g. 0.85% NaCl
    Isosmotic solution does not equal to isotonic
    solution.
    Isosmotic solution, isotonic solution and clinic
PHYSIOLOGICAL CHARACTERISTICS
    AND FUNCTIONS OF RBC
                Functions of RBC
   RBC can be used for transportation of
     O2 and CO2 in the blood.
   RBC can be served as pH buffer.
ERYTHROPOIESIS
   Hemopoietic material for erythropoiesis:
              iron (Fe++) and protein, [reason for anemia]
   Influencing factors of RBC maturity:
            Vitamin B12 and folic acid (DNA metabolism),
                            [clinic relation]
   Process of erythropoiesis:
    Hemopoietic stem cells→multi systemic hemopoietic progenitor
    cells→RBC-committed progenitor cells (BFU-E→CFU-E)→original RBC→
    earlier infantile RBC→medium-term infantile RBC→terminal infantile
    RBC→reticular RBC→mature RBC→blood for circulation.
    This process requires 6~7 days.
    [mitosis several times] [apoptosis]
PLACE FOR ERYTHROPOIESIS

Main place for Erythropoiesis is bone
marrow. Aother place is liver.
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)             Percentage (%)
Total numbers of leukocytes      4.0~10.0

Neutrophil (bacilliform nucleus) 0.04~0.5                    1~5

Neutrophil (foliiform nucleus)   2.0~7.0                 50~70

Eosinophil                       0.02~0.5                0.5~5

Basophil                         0.0~0.1                     0~1

Monocyte                         0.12~0.8                    3~8

Lymphocyte                       0.8~4.0                 20~40
                                            For Clinic Use
PHYSIOLOGICAL CHANGES IN
                NUMBERS
              OF LEUKOCYTE
   Newborn: Number is higher, 15×109/L, after birth 3 or 4 days to
    3 months, being about 10×109/L, mainly, neutrophil, 70%;
    secondarily, lymphocyte.
   Circadian changes: Number of WBC is more in the afternoon
    than in the morning.
   Food taking, ache and mood excitation: Number of WBC is
    remarkably higher.
   Heavy exercise and laboring: Increasing numbers, about
    35×109/L, return to original level after action stop.
   Terminal pregnancy of female: Numbers changes in
    12~17×109/L, and during parturition, 34×109/L, and after
    parturition 2~5 days, number return to original level.
PHYSIOLOGICAL CHARACTERISTICS AND
                FUNCTIONS OF WBC
                    Terminology
   Diapedisis: Metamorphosed WBCs pass
    through vessel wall getting into
    interstitial fluid.
   Chemotaxis: It is a process that WBCs     WBC
    shift to some chemical material




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




                                                       Metamorphose
PHYSIOLOGICAL CHARACTERISTICS
   AND FUNCTIONS OF WBC


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

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

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

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

   Normal value: 100×109 ~ 300×109, range from 6%~10%
   Normal changes: more number in the afternoon than in the morning,
    more in winter than in spring, more in the venous blood than
    capillary, after sport↑, pregnacy↑.
   *Functions:
     1. It maintains capillary endothelial cells smooth and
        integrated (repairing endothelium and providing
        nutrition).
     2. It is involved in physiological hemostasis.
   Platelet and clinic relation:
    decrease of platelet, abnormal immune reaction, will results in
    hemorrhage or bleeding, purpuric symptom.
PLATELET FORMING AND
               REGULATION
   Platelet forming:
    Birth place is bone marrow, originating from hemopoietic stem cells,
    and differentiating into burst forming unit- megakaryocyte, BFU-MK,
    then continuously into CFU-MK, and into megakaryocyte,
    demarcation membrane system, DMS, into fractionlet release to the
    blood requiring 8~10 days. (one megakaryocyte can produce
    200~7700 platelet).
   Regulation:
    Protein, Mpl, expressed by c-mpl (oncogene) exists in CD34+ located
    at hemopoietic stem cells/ committed progenitors, megakaryocyte
    and platelet, found by Methin in 1993, and its ligand named
    thrombopoietin, TPO was discovered in 1994 which promoted
    hemopoietic stem cells differentiating into megakaryocyte as
    hemopoietic stem cells positive regulating factor.
LIFE- SPAN AND BREAKAGE OF PLATELET


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

   *Definition: The process from vessel bleeding to automatic
    hemostasia.
   *Bleeding time: The time from vessel bleeding to automatic
    hemostasia. Normal time is 1~3 min and it is longer when
    platelet decrease.
   Process of hemostasis:
    1. Blood vessel contraction or convulsion (induced by
    neuroreflex; 5-hydroxytryptamine,5-HT; thromboxane A2,
    TXA2; endothelin, ET )
    2. Platelet thrombosis forming (made by platelet adhesion,
    aggregation, release and contraction)
    3. fibrin, clot forming and maintenance (made by blood
    coagulation activation)
PHYSIOLOGICAL HEMOSTASIS
1.ENDOCRINE FUNCTIONS OF VESSEL
                 ENDOTHELIAL CELLS
①   Material related to hemostasis are basal membrane, collagen (III, IV),
    microfibril, elastin, laminin, ectonectin, fibronectin, von Willebrand
    factor (vWF), protein enzyme, protein enzyme inhibitor, adhesive
    amylose, etc.
②   Anticoagulative material: They are prostacyclin (PGI2),
    endothelium-derived relaxing factor (EDRF or nitric oxide, NO),
    tissue-type plasminogen activator (tPA), uPA, ADPase, ATIII,
    heparin sulfate, protein C, thrombomomodulin (TM), plasminogen
    activator (PA).
③   Promoting coagulative material: Tissue factor, vWF, blood clotting
    factor V, plasminogen activator inhibitor (PAI-1, PAI-2, ATIII), TNFα,
    interleukin-1 (IL-1).
④   Vessel constricting and relaxing modulators: endothelin-1 (ET-1),
    EDRF (NO), PGI2, etc.
ROLES OF VESSEL ENDOTHELIAL
       CELLS IN PHYSIOLOGICAL
            HEMOSTASIS
     Roles are close related to its endocrine functions
①   Vessel endothelium serves as barrier between underendothelial
    structure (namely, collagen) and blood. As soon as collagen
    expose to blood, hemostasis of platelet is immediately activated
    to form thrombus blocking wounded vessels.
②   Platelet activation can releases constrictive factors (TXA2, ET-1, 5-
    HT, etc) making vessel convulsion, lasting about 60 sec.
③   Stimulated vessel endothelial cells release coagulative factors
    and Promoting coagulative material to realize, speed up blood
    coagulation. At the same time, cells also release anticoagulative
    factors and fibrinolysis material to modify blood coagulation.
INACTIVE PLATELET
Under the electronic microscope
ACTIVATED PLATELET FOR
HEMOSTASIS
     Under the electronic microscope
2.PHYSIOLOGICAL CHARACTERISTICS                                       OF
                     PLATELET
   Thrombocyte adhesion: its membrane glycoprotein (GP, GPIb/IX and GPIIa/IIIb),
    collagen (underendothelial structure), vWF (plasma component), fibrinogen are
    involved in adhesion.
    Mechanism: Exposed collagen+vWF →vWF changes →platelet membrane
    glycoprotein+changed vWF → Thrombocyte adhesion.
   Thrombocyte aggregation: induced by physiological factors such as ADP,
    thromboxane A2 (TXA2), epinephrine, 5-HT, histamine, collagen, thrombin,
    prostacyclin,etc and by pathological factors like bacteria, virus, immune complex,
    drugs, etc.
    The process can be separated into two phases: phase one is reversible aggregation
    and phase two irreversible aggregation. Two phases require Ca2+, fibrinogen and
    energy consumption.
    Mechanism : Various factors+corresponding receptors on the platelet →changes in the
    second messenger within platelet →cAMP↓, Ip3↑, Ca2+↑, cGMP↑→ platelet aggregation.
   Thrombocyte release: ADP, ATP, 5-HT, Ca2+ released from dense body, and β-platelet
    globin, PF4, vWF, fibrinogen, PFV, PDGF, thrombin sensitive protein from α-granule,
    and acid protein hydrolyzed enzyme, tissue hydrolyzed enzyme from lysosome.
   Thrombocyte contraction: Loose platelet thrombus could turn into compact platelet
    thrombus by Ca2+ release and cytoskeleton movement (filament/canaliculus) within
    platelet.
ROLES OF PLATELET IN
               HEMOSTASIS
   Activation of platelet: Stimulus brings about thrombocyte adhesion,
    aggregation, release and contraction.
   Loose platelet thrombus forming: First phase of hemostasis.
   Blood coagulation activation by platelet: Fibrin net forming, second
    phase of hemostasis.
   *Roles of platelet in hemostasis:
    1. Activated platelets supply lecithoid (phospholipid) surface for blood
     clotting factor and involve in activating factor X and prothrombin.
    2. Surface of platelet membrane combine with many blood clotting
     factor, such as fibrinogen, FV, FXI, FXIII to speed up coagulation.
    3. Activated platelets release α-granule which contains fibrinogen to
     intensify fibrin forming and blood coagulation.
    4. Activated platelets contract clot with its contractive protein to solidify
     blood coagulation.
TWO PHASES OF PHYSIOLOGICAL
         HEMOSTASIS


First Phase        Second Phase
MECHANISM1 OF PLATELET IN
      HEMOSTASIS
MECHANISM2 OF PLATELET IN HEMOSTASIS
3.BLOOD COAGULATION
         BLOOD CLOTTING FACTOR
   Definition: The process of blood flow from flowing liquid to gel or
    gelatin.
   Serum: Light yellow fluid after blood coagulation.
   Difference between serum and plasma mainly consists in no
    fibrinogen in serum.
   Blood coagulation is a series of complicated biochemical reactions
    with various enzymes.
   Blood clotting factor: Material which are directly involved in blood
    coagulation. There are 12 factors named Roman numerals, except
    Ca2+, phospholipid,other factors being protein, and except FIII (TF),
    others are in fresh plasma synthesized by liver with VitK .
   Blood clotting enzymes have two type: inactive and activated type [FII,
    FVII, FIX, Fx, FXI, FXII, FXIII].
Blood Clotting Factor
Factor Name                                   Plasma         Synthesizing                                Half life    Chromsome
                                       Concentration             site                                                      site
  I Fibrinogen                                  3000         Liver                                       4~5 d        4
  II Prothrombin                                100          Liver (with Vit K)                          3d           11
  III Tissue factor                             -           Endothelial cell                 -                -
  IV Ca2+                                       100          -                                            -           -
  V Proaccelerin                                10           Endothelial cell, platelet 12~15 h                   1
  Ⅶ Proconvertin                       0.5      Liver (with Vit K)             4~7 h             13
  Ⅷ Antihemophilic factor,AHF           0.1         Liver                         8~10 h             Ⅹ
  Ⅸ Plasma thromboplastic               5           Liver (with Vit K)            24 h               Ⅹ
    component,PTC(Christmas factor)
  Ⅹ Stuart-Prower Factor               10           Liver (with Vit K)            2d                 13
  Ⅺ Plasma thromoboplastin              5           Liver                         2~3 d              4
    antecedent,PTA
  Ⅻ Contact factor or Hageman factor    40           Liver                            24 h           5
  XIII Fibrin-stabilizing factor       10       Liver, platelet                   8d             6,1
   - High-molecular weight             80           Liver                         -              3
    kininogen,HMW-K
BLOOD COAGULATION
   Intrinsic pathway of blood coagulation: All blood clotting factors involved in
    blood coagulation come from blood. Eyewinker surface with negative charges
    (collagenin) on the endothelium of blood vessel activates blood FXII as
    beginning of coagulation named surface activation.
   Extrinsic pathway of blood coagulation: Stimulus activates tissue factor (FIII) as
    beginning of coagulation.
    Extrinsic pathway of blood coagulation is faster than intrinsic pathway of blood
    coagulation because its steps are more simple.
   *Basic steps of blood coagulation [typical positive feedback]:
    Prothrombin activator forming [FXa-Va-Ca2+-phospholipid]       Step 1


           Prothrombin          thrombin                          Step 2


                   Fibrinogen           fibrin (clot)             Step 3
   Hemophilia A, B, C in the clinic results from deficiency of FVIII, FIX,
     FXI in the blood, respectively.
Process of Blood Coagulation
       Extrinsic pathway                                Intrinsic pathway
     (Tissue Factor,TF)                            ( Eyewinker surface )
              TF+Ⅶ                                                 Ⅻ
                                                   Ⅺ      H              S
                    Ca2+
                                                          K              K       PK
                Ⅶ-TF                    Ⅸ                          Ⅻa
     Ⅹa                                     Ca2+
                           Ca2+ ,PL                Ⅺa
                Ⅶa-TF
                                        Ⅸa
                    Ca2+
                     PL                  Ca2+
                                      Ⅷa
                                         PL

          Ⅹ                                  Ⅹa
PL: phospholipid                               Ca2+                    ⅩⅢ
                                            Ⅴa
CL: cross linking fibrin                        PL
                                       Ⅱ                Ⅱa
HK: high molecular weight kininogen
                                                                       ⅩⅢa
S:   Subendothelium
                                                                         Ca2+
PK: prekallikrein                                  Ⅰ          Ⅰa                CLⅠa
K: kallikrein
MECHANISM OF BLOOD
COAGULATION
ANTICOAGULATIVE SYSTEM IN BLOOD
   Cellular anticoagulative system: Liver cell and reticular endothelial cell could engulf
    blood clotting factor, tissue factor, prothrombin complex and soluble fibrin
    monomer.
   Humoral anticoagulative system:
    1. Amino acid protease inhibitors in blood include antithrombin III, Cl-inhibitor, α1
    antitrypsin, α2 antiplasmin, α2 huge globin, heparin coenzyme II, protease nexin-1
    (PN-1) to combine with FIXa, FXa, FXIa, FXIIa and thrombin and then inactivate them
    for anticoagulation. Heparin can intensify functions of antithrombin III.
    2. Protein C system are protein C (PC), thrombomodulin (TM), protein S and Protein
    C inhibitors. Main functions of PC consist in ①It inactivates FVa, FVIIIa with
    phospholipid and Ca2+; ②It blocks FXa combining with platelet phospholipid
    membrane to reduce prothrombin activation; ③It stimulates plasminogen activators
    release to trigger fibrinolysis; ④ Protein S is a coenzyme of PC and greatly intensify
    functions of PC.
    3. Tissue factor pathway inhibitor (TFPI) mainly coming from vessel endothelial cells
    inhibits FXa and inactivates FVIIa-TF complex to block extrinsic pathway of
    coagulation with negative feed back.
    4. Heparin used in the clinic widely is due to ①It combines with antithrombin III to
    increase functions of antithrombin III; ②It stimulates vessel endothelial cell greatlu
    releasing TFPI and other anticoagulative material; ③It intensifies PC activation and
    stimulates vessel endothelial cell releasing plasminogen activators to increase
    fibrinolysis. [lower molecular weight heparin is less hemorrhage]
4.FIBRINOLYSIS
   Fibrinolytic system is involved in fibrinolysis, tissue repair
    and vessel rebirth.
   Two fibrinolytic systems: cellular one and plasma one. The
    former is leucocyte, macrophage, endothelial cell, mesothelial
    cell and platelet to engulf and digest fibrin. The latter is
    plasminogen activators (PA) and its inhibitors (PAI),
    plasminogen, plasmin.
   Basic steps:
                                            Kallikrein (Intrinsic pathway)
    Endothelial cells (Extrinsicpathway )
                         (Urokinase, uPA)             Cl-inhibitors
        tPA                         uPA              uPAG
                        PAI-1
    Plasminogen                                    Plasmin
                 α2-antiplasmin
                α2-huge globin                                  Fibrin
                          Fibrin or fibrinogen               dissolution
BLOOD COAGULATION   AND
     FIBRINOLYSIS
ANTIFIBRINOLYSIS:
       FIBRINOLYTIC INHIBITORS AND ITS
                  FUNCTIONS
   Main fibrinolytic inhibitors: They are plasminogen activator inhibitor
    type-1 (PAI-1, in platelet), α2-antiplasmin (in liver), α2-huge globin,
    α1-antitrypsin, antithrombin III, alexin C1 inhibitor.
   PAI-1 synthesis and release: PAI-1 made by endothelial cell, smooth
    muscular cell, mesothelial cell, megakaryocyte is stored in platelet
    with inactive form. Some factors such as thrombin, IL-1, TNFα, etc
    stimulate its release from platelet.
   PAI-1 function: It inhibits tPA (tissue-type plasminogen activator)
    limiting local fibrinolysis of thrombus.
   α2-antiplasmin characteristics: (1) Quick effect, (2) Inhibit
    plasminogen adhering to fibrin; (3) Combine with fibrin αchain and
    block fibrinolysis
   Clinic relation: Innate deficiency of α2-antiplasmin often brings
    about serious hemorrhage.
V. BLOOD GROUP
   History: ABO blood group system was firstly found by Landsteiner
    in 1901.
   Definition for blood group*: Types of specific antigens on the blood
    cell.
   Agglutination: Combination of the same antigen (or named
    agglutinogen, glycoprotein/glycolipid on the membrane of blood
    cell) and antibody (or named agglutinin, r-globin in serum) results
    in harmful immune reactions showing hemolysis.
   Human leukocyte antigen, HLA have widespread distribution in the
    body and involves in immune repulsive reaction of organ transplant.
   Platelet antigens such as PI, Zw, Ko, etc may bring about fever heat
    when transfusion occur.
1. RBC Agglutination

Antigen-Antibody Harmful immune Reaction




Blood Coagulation       RBC Agglutination
ANTIGEN OF BLOOD GROUP

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


   Crude antibody: It is the unexposed antibody to
    correlative RBC, e.g., IgM in ABO blood group system
    which can not pass through placenta for the sake of big
    molecule.
   Immune antibody: Various extraordinary RBC antigens
    (transfusion or parturition) sensitize lymphatic cells
    producing antibody such as Rh, Kell, Duffy, kidd, which
    belong to IgG (small molecule) and IgM (big molecule).
BLOOD GROUP OF RBC
   Number: 23 types, 193 antigens, more important
    blood groups are ABO, Rh, MNSs, Lutheran, kell,
    Lewis, duff, kidd, etc and all of them could result in
    hemolysis during transfusion.
   ABO blood group system:

Blood group     Antigen on the RBC   Antibody in the serum

     A                   A                  Anti-B
     B                   B                  Anti-A
     AB                 A+B
     O                                      Anti-A+Anti-B
2. ABO BLOOD GROUP SYSTEM

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

    A   A1              A+ A1                Anti-B
        A2               A               Anti-B+ Anti-A1
    B                    B                  Anti-A
    AB A1B            A+ A1 +B
        A2B             A+B                 Anti-A1
    O                                    Anti-A+Anti-B
ABH Antigen chemical structure in ABO
                 blood group system
Antigen of blood group
  Ushering material


     O(H)-antigen




         A-antigen




         B-Antigen




                         N-acetamide   N-acetamide
         Galactose         Glucose      galactose
           Sugar          Glucose
INHERITANCE OF ABO BLOOD
                      GROUP

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



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

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


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

 China Han nationality: Type A 31.31%,

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

Anti-B   Anti-A   Anti-A, B
Serum    Serum     Serum
3. RH BLOOD GROUP SYSTEM

   Rh antigen (Rh factor) is about 40 kinds and Rh factors
    related to clinic are D, E, C, c, e and most important is D
    antigen.
   Membrane of RBC has D antigen meaning Rh Positive,
    otherwise, Rh negative. Most of people (99%) are Rh
    Positive and less than 1% persons are Rh negative.
   Rh blood group characteristics: Immune antobody and
    incomplete antibody, IgG; while ABO blood group, crude
    antibody and complete antibody,IgM.
   Rh blood group system and clinic work
     Transfusion and pregnacy [Clinic meaning]
QUANTIFICATION OF BLOOD
             VOLUME
 Blood volume is an important determinant of systemic
  arterial pressure.
 Circulatory system is essentially a closed container
  including a volume of blood equal to approximately 5
  liters or 70-80mL/Kg of the body weight (in kilograms).
4. RELATION BETWEEN BLOOD VOLUME
                         AND CLINIC
 When you donate 10 % of total blood volume, your body
  compensates so that blood pressure does not change, and the
  volume is replaced through the normal ingestion of fluids.
 Volume loss up to 30-40 % of total blood volume can be tolerated
  if the loss is corrected within 30 min (e.g. artery contraction
  increases peripheral resistance but artery blood pressure can
  not maintain the normal levels which occur in symptoms such as
  light-headed, dazzled, force-lacked, etc)
 Blood loss more than 40 % of total blood volume will threaten
  the life, results in shock and the measures in the hospital should
  be immediately taken for life survival [Transfusion].
5. PRINCIPLE OF TRANSFUSION
 Transfusion is widely used in clinic treatment.
 Principle of transfusion*:

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


   供
 Donator
                                                      受
                                                 Receiver

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

       -                     -            相合,可以输血
                                         Perfect match, transfusion

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

       -                    +             应急情况下输血
                                         Transfusion under emergency
  +: Agglutination; -: No agglutination
TYPES OF TRANSFUSION
   According to source of transfusion, allogenetic
    transfusion (more use), autologous transfusion.
   According to component of transfusion, whole blood
    transfusion, transfusion of blood components
   Autologous transfusion has some advantages:
    ①    It decreases infection.
    ②    It blocks syndrome (fever, hemolysis) induced by
      allogenetic transfusion.
    ③    It stimulates bone marrow hemopoiesis towards RBC.
   Transfusion of blood components is good.
Summarization


PLEASE TAKE DOWN
Consideration after class
                     【本章节问题思考】
1. Please describe classification and main effects of
 leucocyte.
2. What is the elementary process of blood coagulation and
 main factors which have participated in blood coagulation?
3. Please describe the principle of classification and blood
 transfusion of ABO blood group system.
GUIDE OF REFERENCE
                         【本章节学习参考书单】
1. 姚泰主编. 生理学. 第五版. 北京: 人民卫生出版社, 2000.
2. 范少光, 汤浩, 潘伟丰主编. 人体生理学(二版). 北京: 北京医科大学出版社, 2000.
3. 贺石林, 李俊成, 秦晓群主编. 临床生理学. 北京: 科学出版社, 2001.
4. 王庭槐主编. 生理学. 全国高等学校医学规划教材, 北京: 高等教育出版社, 2005.
5. 吴祖泽, 贺福初, 裴雪涛主编. 造血调控. 上海: 上海医科大学出版社, 2000.
6. 李勇, 杨贵贞主编. 人类红细胞血型学实用理论与实验技术. 北京: 中国科学技术出版社, 1999.
7. Ding L, Lu S, Batchu R, et al. Bone marrow stromal cells as a vehicle for gene transfer.
   Gene Ther, 1999, 6(9): 1611-1616.
8. Humeau L, Bardin F, Maroc C, et al. Phenotypic, molecular, and functional
   characterization of human peripheral blood, CD34+/Thy1+ cells. Blood, 1996, 87(3):
   949-955.
9. Kaushansky K. Thrombopoietin: accumulating evidence for an important biological
   effect on the hematopoietic stem cell. Ann N Y Acad Sci, 2003, 996: 39-43.
10.     Berne RM, Levy MN, Koeppen BMI, Stanton BA. Physiology, 5th ed, St Louis:
   Mosby Electronic Production, 2004.
11.Guyton AC, Hall JE. TEXTBOOK OF MEDICAL PHYSIOLOGY, 10th ed, Philadelphia:
   W.B. Saunders Co, 2000.
12.      Berardi AC, Wang A, Levine JD, et al. Functional isolation and characterization
   of human hematopoietic stem cells. Science, 1995, 267(5194): 104-108.
13.      Fox SI. Human physiology, 7th ed, New York: McGraw-Hill Co Inc, 2002.
NAVIGATION FOR WEB ADDRESS
             【本章节课后学习导航网站】
1.http://bioresearch.ac.uk/browse/mesh/detail/c0005811L000
     5811.html
2.http://www.inform.umd.edu/EdRes/Colleges/HONR/HONR2
     69U/Jenn/
3.http://www.ohsu.edu/cliniweb/G9/G9.188.html
4.http://www.mednote.co.kr/PHYSIOLOGY%20BLUE.htm
5.http://www.fpnotebook.com/HEM38.htm
BLOOD PHYSIOLOGY




QUESTIONS


  ANSWERS
THANK YOU FOR YOUR ATTENTION




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Blood physiology

  • 2. What will we discuss in this chapter? I. Blood composition OUTLINE II. Physical and chemical characteristics of blood III. Blood Cells 1. Hemopoietic process and hemopoietic stem cells 2. Hemopoietic microenvironment 3. Erythrocyte Physiology 4. Leukocyte Physiology 5. Platelet or Thrombocyte Physiology IV. Physiological Hemostasis 1. Endocrine functions of vessel endothelial cells 2. Physiological Characteristics of Platelet 3. Blood Coagulation 4. Fibrinolysis V. Blood Group 1. RBC Agglutination 2. ABO blood group system 3. Rh blood group system 4. Relation between blood volume and clinic 5. Principle of Transfusion and Cross-match test
  • 3. BLOOD AND INTERNAL ENVIRONMENTAL HOMEOSTASIS  Blood is that part of extracellular fluid within the cardiovascular system  Blood formation During animals’ evolution, extracellular fluid was gradually shaped from the age-old time with ocean which was mainly salty solution. At last, extracellular fluid was differentiated into plasma and interstitial fluid and blood came from plasma and cells.  The role of blood in internal environmental = homeostasis Blood, the most active component in extracellular fluid, display functions as follows: (1) transport; (2) pH buffer; (3) temperature or thermal maintenance; (4) immunity and defense
  • 4. I. BLOOD COMPOSITION  Blood composed of : plasma + blood cells  Hematocrit: the percentage of total blood volume that blood cells occupy. normal value male: 40-50% female: 37-48% newborn: 55%
  • 5. BLOOD COMPONENT (SUMMING-UP)
  • 7. CHEMICAL COMPONENT OF PLASMA H 2O 90 - 91% 血浆 Plasma 组织液 Interstitial 细胞内液 Intracellular fluid fluid Na+ 142 145 12 Cl- 104 117 4 Ca++ 2.5 2.4 <0.001 K+ 4.3 4.4 139 PO4- 2 2.3 29 蛋白质 Protein 14 0.4 54 (Unit:mmol/L)
  • 8. 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
  • 9.  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 ].
  • 10. 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.
  • 11. 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.
  • 12. 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.
  • 13. III.BLOOD CELLS Blood cells are erythrocyte (red blood cell, RBC), leukocyte (white blood cell, WBC) and thrombocyte (platelet, P).
  • 14. 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.
  • 15. 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.
  • 16. HEMOPOIETIC STEM CELLS Basic characteristics  Self renewal in high degree, constant from young to old age.  Multi- directional differentiation  Large potential proliferation, Hemopoietic stem cells produce about 1×1011 blood cells releasing to blood for use.  Surface sign According to CFU (colony forming unit), using fluorescence- activated cell sorting (FACS), its main surface sign is CD34+CD38- Lin-and CD34-CD38-Lin-. Note CD: cluster of differentiation of antigen on the white blood cells; Lin: systemic specific antigen on the hemopoietic cells.
  • 20. 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.
  • 21. REASON FOR SHAPE OF RBC biconcave disc like
  • 22. 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).
  • 23. PHYSIOLOGICAL CHARACTERISTICS AND FUNCTIONS OF RBC Characteristics of RBC ① Permeability: semipermeable membrane, gas and urea freely passing through, negative ions easily in or out of RBC, and positive ions not. There are Na-K ATPase as pump on the membrane of RBC and low-temperature-stored plasma easily has high kalium. Why? ② Plasticity and metamorphose: Plasticity and metamorphose depend on: 1) surface area-cubage ratio, 2) viscosity of Hb, 3) membrane elasticity and viscosity.
  • 24. 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.
  • 25. PHYSIOLOGICAL CHARACTERISTICS AND FUNCTIONS OF RBC Characteristics of RBC ④ Osmotic fragility: Changes in RBC put into lower osmotic salty solution. Osmotic fragility of aged RBC is large and easily results in rupture (hemolysis and ghost cell). Isosmotic solution, e.g. 0.85% NaCl, 1.4%NaHCO3, 5% glucose, etc. Isotonic solution, e.g. 0.85% NaCl Isosmotic solution does not equal to isotonic solution. Isosmotic solution, isotonic solution and clinic
  • 26. 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.
  • 27. 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]
  • 28. PLACE FOR ERYTHROPOIESIS Main place for Erythropoiesis is bone marrow. Aother place is liver.
  • 30. 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.
  • 31. 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.
  • 32. CLASSIFICATION AND NUMBERS OF LEUKOCYTE TABLE. Classification and normal value of Leukocyte Absolute Value (×109/L) Percentage (%) Total numbers of leukocytes 4.0~10.0 Neutrophil (bacilliform nucleus) 0.04~0.5 1~5 Neutrophil (foliiform nucleus) 2.0~7.0 50~70 Eosinophil 0.02~0.5 0.5~5 Basophil 0.0~0.1 0~1 Monocyte 0.12~0.8 3~8 Lymphocyte 0.8~4.0 20~40 For Clinic Use
  • 33. 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.
  • 34. PHYSIOLOGICAL CHARACTERISTICS AND FUNCTIONS OF WBC Terminology  Diapedisis: Metamorphosed WBCs pass through vessel wall getting into interstitial fluid.  Chemotaxis: It is a process that WBCs WBC shift to some chemical material Diapedisis (metabolic production, antigen-antibody complex, bacteria, toxin, etc).  Phagocytosis: It is a process that WBCs enclose and engulf exotic or extraneous material, and use intracellular enzyme Blood digesting them. Vessel Metamorphose
  • 35. PHYSIOLOGICAL CHARACTERISTICS AND FUNCTIONS OF WBC ① Neutrophil  Another name, polymorphonuclear, PMN, 6~8 h in the vessels, diapedisis, chemotaxis and phagocytosis (using its hydrolyzed enzyme)  Function: It plays a very important role in nonspecific cellular immunity system which is against pathogenic microorganism, such as bacteria, virus, parasite, etc.  Clinic relation: Number of neutrophil greatly increase occurring in acute inflammation and earlier time of chronic inflammation. number decrease of neutrophil will result in poor resistibility and easily suffering from infection.
  • 36. 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.
  • 37. 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.
  • 38. 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.
  • 39. 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
  • 40. LEUKOPOIESIS, REGULATION AND BREAKAGE  Birth place: bone marrow, originating from hemopoietic stem cells, and leukopoiesis process is similar to RBC.  Leukopoiesis, differentiation and growth are influenced by hemopoietic growth factor, HGF which are glycoprotein secreted by lymphocyte, monocyte- macrophage, fibrous cell and endothelial cell.  Colony stimulating factor, CSF, such as GM-CSF, G-CSF, M-CSF, Multi-CSF (IL-3) also influence Leukopoiesis.  Life span: several hours to 3 or 4 days.  Leukocyte breakage: site are liver, spleen and lymphatic node.  Pus or purulence forming
  • 41. 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.
  • 42. 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.
  • 43. PLATELET FORMING AND REGULATION  Platelet forming: Birth place is bone marrow, originating from hemopoietic stem cells, and differentiating into burst forming unit- megakaryocyte, BFU-MK, then continuously into CFU-MK, and into megakaryocyte, demarcation membrane system, DMS, into fractionlet release to the blood requiring 8~10 days. (one megakaryocyte can produce 200~7700 platelet).  Regulation: Protein, Mpl, expressed by c-mpl (oncogene) exists in CD34+ located at hemopoietic stem cells/ committed progenitors, megakaryocyte and platelet, found by Methin in 1993, and its ligand named thrombopoietin, TPO was discovered in 1994 which promoted hemopoietic stem cells differentiating into megakaryocyte as hemopoietic stem cells positive regulating factor.
  • 44. 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.
  • 45. 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)
  • 47. 1.ENDOCRINE FUNCTIONS OF VESSEL ENDOTHELIAL CELLS ① Material related to hemostasis are basal membrane, collagen (III, IV), microfibril, elastin, laminin, ectonectin, fibronectin, von Willebrand factor (vWF), protein enzyme, protein enzyme inhibitor, adhesive amylose, etc. ② Anticoagulative material: They are prostacyclin (PGI2), endothelium-derived relaxing factor (EDRF or nitric oxide, NO), tissue-type plasminogen activator (tPA), uPA, ADPase, ATIII, heparin sulfate, protein C, thrombomomodulin (TM), plasminogen activator (PA). ③ Promoting coagulative material: Tissue factor, vWF, blood clotting factor V, plasminogen activator inhibitor (PAI-1, PAI-2, ATIII), TNFα, interleukin-1 (IL-1). ④ Vessel constricting and relaxing modulators: endothelin-1 (ET-1), EDRF (NO), PGI2, etc.
  • 48. ROLES OF VESSEL ENDOTHELIAL CELLS IN PHYSIOLOGICAL HEMOSTASIS Roles are close related to its endocrine functions ① Vessel endothelium serves as barrier between underendothelial structure (namely, collagen) and blood. As soon as collagen expose to blood, hemostasis of platelet is immediately activated to form thrombus blocking wounded vessels. ② Platelet activation can releases constrictive factors (TXA2, ET-1, 5- HT, etc) making vessel convulsion, lasting about 60 sec. ③ Stimulated vessel endothelial cells release coagulative factors and Promoting coagulative material to realize, speed up blood coagulation. At the same time, cells also release anticoagulative factors and fibrinolysis material to modify blood coagulation.
  • 49. INACTIVE PLATELET Under the electronic microscope
  • 50. ACTIVATED PLATELET FOR HEMOSTASIS Under the electronic microscope
  • 51. 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.
  • 52. 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.
  • 53. TWO PHASES OF PHYSIOLOGICAL HEMOSTASIS First Phase Second Phase
  • 54. MECHANISM1 OF PLATELET IN HEMOSTASIS
  • 55. MECHANISM2 OF PLATELET IN HEMOSTASIS
  • 56. 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].
  • 57. Blood Clotting Factor Factor Name Plasma Synthesizing Half life Chromsome Concentration site site I Fibrinogen 3000 Liver 4~5 d 4 II Prothrombin 100 Liver (with Vit K) 3d 11 III Tissue factor - Endothelial cell - - IV Ca2+ 100 - - - V Proaccelerin 10 Endothelial cell, platelet 12~15 h 1 Ⅶ Proconvertin 0.5 Liver (with Vit K) 4~7 h 13 Ⅷ Antihemophilic factor,AHF 0.1 Liver 8~10 h Ⅹ Ⅸ Plasma thromboplastic 5 Liver (with Vit K) 24 h Ⅹ component,PTC(Christmas factor) Ⅹ Stuart-Prower Factor 10 Liver (with Vit K) 2d 13 Ⅺ Plasma thromoboplastin 5 Liver 2~3 d 4 antecedent,PTA Ⅻ Contact factor or Hageman factor 40 Liver 24 h 5 XIII Fibrin-stabilizing factor 10 Liver, platelet 8d 6,1 - High-molecular weight 80 Liver - 3 kininogen,HMW-K
  • 58. 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.
  • 59. Process of Blood Coagulation Extrinsic pathway Intrinsic pathway (Tissue Factor,TF) ( Eyewinker surface ) TF+Ⅶ Ⅻ Ⅺ H S Ca2+ K K PK Ⅶ-TF Ⅸ Ⅻa Ⅹa Ca2+ Ca2+ ,PL Ⅺa Ⅶa-TF Ⅸa Ca2+ PL Ca2+ Ⅷa PL Ⅹ Ⅹa PL: phospholipid Ca2+ ⅩⅢ Ⅴa CL: cross linking fibrin PL Ⅱ Ⅱa HK: high molecular weight kininogen ⅩⅢa S: Subendothelium Ca2+ PK: prekallikrein Ⅰ Ⅰa CLⅠa K: kallikrein
  • 61. ANTICOAGULATIVE SYSTEM IN BLOOD  Cellular anticoagulative system: Liver cell and reticular endothelial cell could engulf blood clotting factor, tissue factor, prothrombin complex and soluble fibrin monomer.  Humoral anticoagulative system: 1. Amino acid protease inhibitors in blood include antithrombin III, Cl-inhibitor, α1 antitrypsin, α2 antiplasmin, α2 huge globin, heparin coenzyme II, protease nexin-1 (PN-1) to combine with FIXa, FXa, FXIa, FXIIa and thrombin and then inactivate them for anticoagulation. Heparin can intensify functions of antithrombin III. 2. Protein C system are protein C (PC), thrombomodulin (TM), protein S and Protein C inhibitors. Main functions of PC consist in ①It inactivates FVa, FVIIIa with phospholipid and Ca2+; ②It blocks FXa combining with platelet phospholipid membrane to reduce prothrombin activation; ③It stimulates plasminogen activators release to trigger fibrinolysis; ④ Protein S is a coenzyme of PC and greatly intensify functions of PC. 3. Tissue factor pathway inhibitor (TFPI) mainly coming from vessel endothelial cells inhibits FXa and inactivates FVIIa-TF complex to block extrinsic pathway of coagulation with negative feed back. 4. Heparin used in the clinic widely is due to ①It combines with antithrombin III to increase functions of antithrombin III; ②It stimulates vessel endothelial cell greatlu releasing TFPI and other anticoagulative material; ③It intensifies PC activation and stimulates vessel endothelial cell releasing plasminogen activators to increase fibrinolysis. [lower molecular weight heparin is less hemorrhage]
  • 62. 4.FIBRINOLYSIS  Fibrinolytic system is involved in fibrinolysis, tissue repair and vessel rebirth.  Two fibrinolytic systems: cellular one and plasma one. The former is leucocyte, macrophage, endothelial cell, mesothelial cell and platelet to engulf and digest fibrin. The latter is plasminogen activators (PA) and its inhibitors (PAI), plasminogen, plasmin.  Basic steps: Kallikrein (Intrinsic pathway) Endothelial cells (Extrinsicpathway ) (Urokinase, uPA) Cl-inhibitors tPA uPA uPAG PAI-1 Plasminogen Plasmin α2-antiplasmin α2-huge globin Fibrin Fibrin or fibrinogen dissolution
  • 63. BLOOD COAGULATION AND FIBRINOLYSIS
  • 64. 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.
  • 65. 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.
  • 66. 1. RBC Agglutination Antigen-Antibody Harmful immune Reaction Blood Coagulation RBC Agglutination
  • 67. 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.
  • 68. 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).
  • 69. BLOOD GROUP OF RBC  Number: 23 types, 193 antigens, more important blood groups are ABO, Rh, MNSs, Lutheran, kell, Lewis, duff, kidd, etc and all of them could result in hemolysis during transfusion.  ABO blood group system: Blood group Antigen on the RBC Antibody in the serum A A Anti-B B B Anti-A AB A+B O Anti-A+Anti-B
  • 70. 2. ABO BLOOD GROUP SYSTEM Antigen (agglutinogen) and antibody (agglutinin) in ABO blood subgroup system Blood group Antigen on the RBC Antibody in the serum A A1 A+ A1 Anti-B A2 A Anti-B+ Anti-A1 B B Anti-A AB A1B A+ A1 +B A2B A+B Anti-A1 O Anti-A+Anti-B
  • 71. ABH Antigen chemical structure in ABO blood group system Antigen of blood group Ushering material O(H)-antigen A-antigen B-Antigen N-acetamide N-acetamide Galactose Glucose galactose Sugar Glucose
  • 72. 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
  • 73. INHERITANCE OF ABO BLOOD GROUP Genetic relationship of ABO blood group Parents’ Offspring possible Offspring impossible blood group blood group blood group O×O O A, B, AB A×A O, A B, AB A×O O, A B, AB B×B O, B A, AB B×O O, B A, AB B×A O, A, B, AB ____ AB×O A,B O, AB AB×A A , B, AB O AB×B A , B, AB O AB×AB A , B, AB O
  • 74. 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
  • 75. Mensuration of ABO blood group Anti-B Anti-A Anti-A, B Serum Serum Serum
  • 76. 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]
  • 77. 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).
  • 78. 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].
  • 79. 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.
  • 80. CROSS-MATCH TEST FOR TRANSFUSION 红细胞 RBC 红细胞 RBC 供 Donator 受 Receiver 血 血 者 者 Serum Serum 血清 血清 主侧凝集反应 Main side of 次侧凝集反应 Subordinary side Decision agglutination of agglutination - - 相合,可以输血 Perfect match, transfusion + +, - 不合,不能输血 × No match, transfusion - + 应急情况下输血 Transfusion under emergency +: Agglutination; -: No agglutination
  • 81. TYPES OF TRANSFUSION  According to source of transfusion, allogenetic transfusion (more use), autologous transfusion.  According to component of transfusion, whole blood transfusion, transfusion of blood components  Autologous transfusion has some advantages: ① It decreases infection. ② It blocks syndrome (fever, hemolysis) induced by allogenetic transfusion. ③ It stimulates bone marrow hemopoiesis towards RBC.  Transfusion of blood components is good.
  • 83. Consideration after class 【本章节问题思考】 1. Please describe classification and main effects of leucocyte. 2. What is the elementary process of blood coagulation and main factors which have participated in blood coagulation? 3. Please describe the principle of classification and blood transfusion of ABO blood group system.
  • 84. GUIDE OF REFERENCE 【本章节学习参考书单】 1. 姚泰主编. 生理学. 第五版. 北京: 人民卫生出版社, 2000. 2. 范少光, 汤浩, 潘伟丰主编. 人体生理学(二版). 北京: 北京医科大学出版社, 2000. 3. 贺石林, 李俊成, 秦晓群主编. 临床生理学. 北京: 科学出版社, 2001. 4. 王庭槐主编. 生理学. 全国高等学校医学规划教材, 北京: 高等教育出版社, 2005. 5. 吴祖泽, 贺福初, 裴雪涛主编. 造血调控. 上海: 上海医科大学出版社, 2000. 6. 李勇, 杨贵贞主编. 人类红细胞血型学实用理论与实验技术. 北京: 中国科学技术出版社, 1999. 7. Ding L, Lu S, Batchu R, et al. Bone marrow stromal cells as a vehicle for gene transfer. Gene Ther, 1999, 6(9): 1611-1616. 8. Humeau L, Bardin F, Maroc C, et al. Phenotypic, molecular, and functional characterization of human peripheral blood, CD34+/Thy1+ cells. Blood, 1996, 87(3): 949-955. 9. Kaushansky K. Thrombopoietin: accumulating evidence for an important biological effect on the hematopoietic stem cell. Ann N Y Acad Sci, 2003, 996: 39-43. 10. Berne RM, Levy MN, Koeppen BMI, Stanton BA. Physiology, 5th ed, St Louis: Mosby Electronic Production, 2004. 11.Guyton AC, Hall JE. TEXTBOOK OF MEDICAL PHYSIOLOGY, 10th ed, Philadelphia: W.B. Saunders Co, 2000. 12. Berardi AC, Wang A, Levine JD, et al. Functional isolation and characterization of human hematopoietic stem cells. Science, 1995, 267(5194): 104-108. 13. Fox SI. Human physiology, 7th ed, New York: McGraw-Hill Co Inc, 2002.
  • 85. NAVIGATION FOR WEB ADDRESS 【本章节课后学习导航网站】 1.http://bioresearch.ac.uk/browse/mesh/detail/c0005811L000 5811.html 2.http://www.inform.umd.edu/EdRes/Colleges/HONR/HONR2 69U/Jenn/ 3.http://www.ohsu.edu/cliniweb/G9/G9.188.html 4.http://www.mednote.co.kr/PHYSIOLOGY%20BLUE.htm 5.http://www.fpnotebook.com/HEM38.htm
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