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Chapter 3 Blood Physiology

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Title: Chapter 3 Blood Physiology


1
Chapter 3 Blood Physiology
  • Blood composition and properties
  • Blood cells
  • Hematopoiesis
  • RBC function, anemia.
  • WBC
  • Platelet function, coagulation and fibrinolysis.
  • Blood grouping and transfusion

2
Introduction
  • Blood volume 78 (70-80ml/kg B.W)
  • Plasma (60) and cells (40).
  • Types of blood cells
  • RBC (Erythrocytes), WBC (Leukocytes) and
    Platelets (Thrombocytes)
  • Main function
  • Maintain homeostasis
  • Buffering pH
  • Humoral regulation
  • Body temperature regulation
  • Transportation
  • Gases, nutrients, hormones, and so on.
  • Host defense
  • Immune reaction, coagulation.

3
Section 1 Components and Characteristic
  • Water 93-95
  • Plasma 50-60
  • Solutes 5-7
    Proteins

  • Nutrients

  • Products

  • Electrolytes

  • Others urea, gases.
  • WBC, Platelet 1
  • RBC 40-50 (male)
  • 37-48 (female)

Whole blood
4
Blood Components
  • Water
  • 9395 (plasma) 6568 (RBC) 8186 (whole
    blood).
  • Solvent, humoral balance, osmotic pressure.
  • Electrolytes
  • Na, K, Mg2, Cl-, HCO3-, etc. Cell shape, pH.
  • Proteins
  • Albumin 40-48g/L. Colloidal osmotic pressure
    carrier buffer pH.
  • Globulin 15-30g/L. Immune reaction antibody
    carrier.
  • Fibrinogen 2-4g/L. Blood coagulation.

5
  • Hemoglobin (Hb)
  • 120-160g/L (male), 110-150g/L (female)
  • Function carry gases.
  • Others
  • carbohydrates, lipids, amino acid, pigments,
    hormones, gas (O2, CO2), and others like urea,
    uric acid.

6
Physical and chemical properties
  • Blood pH
  • Normal interval 7.357.45.
  • Regulated by lung and kidney.
  • Viscosity
  • Friction of molecules and cells in blood.
  • Relative viscosity
  • Whole blood 45 times to water (RBC).
  • Plasma 1.62.4 times to water (Proteins).
  • Anemia or body fluid loss.

7
  • Osmotic pressure
  • Definition
  • An ability of a liquid to attract and retain
    water. It drives osmosis. 300mmol/L
  • Composition and roles
  • Crystal osmotic pressure 298.7 mmol/L.
  • Maintain shape and size of cells.
  • Colloid osmotic pressure 1.3 mmol/L.
  • Retain blood volume
  • Decide distribution of water between blood and
    interstitial fluid.

8
Section 2 Blood Cells
  • Red blood cell
  • White blood cell
  • Platelet

9
Hemopoiesis
  • The process of blood generation.

Cell Lineage Lifespan Daily Production Rate
RBC 120 days 2.5 ? 109/L
Neutrophil 7 hours 0.85 ? 109/L
Platelet 10 days 2. 5 ? 109/L
10
  • Ontogeny of Hematopoiesis
  • Prenatal stages
  • First month yolk sac.
  • Third month liver
  • Fourth month bone marrow
  • Postnatal stages
  • Bone marrow of almost any bone, predominatantly
    by flat bones and long bones.

11
100
100
Hemopoitic activity ()
Bone morrow
Yolk Sac
Liver
Lymph nodes
Spleen
0
2
3
4
5
6
7
8
9
1
Prenatal age (months)
100
100
Vertebrate
Proportion of Red Morrow ()
Tibia
Sternum
Femur
Ribs
birth
20
30
40
50
60
70
80
90
10
Postnatal age (years)
12
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13
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14
  • Stage 1, hemopoietic stem cells pluripotent
    uncommitted stem cells.
  • Stage 2, committed progenitor cell unipotent
    committed stem cells. Includes
  • Erythrocytic progenitor cell
  • Megakaryocytic progenitor cell
  • Granulocytic progenitor cell
  • Lymphocytic progenitor cell
  • Stage 3, precursors (cell) immature cells,
    differentiate functional cells. Including
  • Ery. progenitor?? erythrocytes.
  • Mega. progenitor ? platelets.
  • Gran. progenitor ? granulocytes and monocytes.
  • Lym. progenitor ? T and B lymphocytes.

15
  • Hematopoietic growth factor and related molecules
  • Necessary for proliferation and differentation of
    hematopoietic cells in the marrow.
  • Colony-stimulating factors (CSF) see a table in
    next slide.
  • Cytokines
  • IL-1, stem cell factor (SCF), etc.
  • Extracellular matrix proteins
  • Sulfated glycosamimoglycans and heparin sulfate,
    may concentrate hematopoitic growth factors in
    local micro environment
  • Fibronectin and hemonectin, mediate adhension of
    cells, and may serve a growth promoting function.

16
Hematopoietic growth factors
17
Red blood cells (erythrocytes)
  • Circular, biconcave discs without nuclei. ?78?m,
    thickness 12.5 ?m.

18
  • Cell count and volume
  • Hematocrit Percentage of blood volume occupied
    by packed cell volume.

19
  • Volume
  • 4.55.5?1012/L, average 5.0?1012/L (male).
  • 3.84.6?1012/L, average 4.2?1012/L (female).
  • Physical properties
  • Permeability
  • Deformation
  • Fragility and hemolysis
  • Isosmotic solution and lower osmotic solution
  • Suspension stability
  • The erythrocytes are very stable in suspension.
  • Cause repelling force of same charge and bigger
    surface area.

20
  • Erythrocytes Sedimentation Rate (ESR)
    Sedimentated distance of RBC after one hour.
  • 015 mm/h (male), 020 mm/h (female).
  • Ratio of Surface area/Volume of RBC.
  • Albumin, globulin, fibrinogen, and cholesterol.
  • Rouleaux RBC aggregate.
  • Function of RBC
  • The main constituent of RBC is hemoglobin.
  • To deliver O2 to tissues by hemoglobin.

21
Hemoglobin (HB)
  • HB is made up of two polypeptide ? chains and ?
    chains.
  • Each polypeptide has alpha helical segments
    folded and bent into a globular configuration,
    with a heme ring within a pocket where the iron
    molecule can interact with oxygen.

22
  • Hb formation materials
  • Protein enough intake from food.
  • Iron 3-4g/person. Mainly in Hb (70).
  • Degrading Hb 95.
  • Absorbed from small intestine 1mg/d, 5.
  • Microcytic hypochromic anemia Lack of iron.

23
  • RBC Maturation factors
  • Vitamin B12
  • Cobalamine, 25?g/d.
  • Produced by gut bacteria (esp. in ruminants).
    Good sources include meat, liver, fish, eggs and
    milk.
  • Absorbed in terminal ileum with intrinsic factor
    help.
  • Function Improve utilization of FA.
  • Folic acid
  • FA is essential for the synthesis DNA.
  • Synthesized by microorganisms and higher plants.
  • Good sources are green leafy vegetables, yeast
    and organ meats.
  • Absorbed in the proximal jejunum.

24
  • Lack of folic acid and vitb12 give rise to
    immature cells due to DNA synthesis derangement.
  • Megaloblast anemia.

25
Regulation of erythropoiesis Hypoxia ? EPO? RBC
Hemopoitic stem cell (uncommitted
progenitor) ? Erythrocytic progenitor (committed
progenitor) ? Pronormblast (precursor) ? Normobla
st, Reticulocyte ? Mature RBC (without nucleus)
EPO
26
  • Erythropoietin (EPO)
  • A glycoprotein, 34kd. Produced in interstitial
    cells in cortical kidney such as fibroblast,
    endothelial cells.
  • Roles
  • Erythrocytic progenitor proliferate and
    differentiate to precursor.
  • Accelerate precursor proliferation and
    differentiation.
  • Promote bone marrow release reticulocytes.
  • Renal type anemia EPO production decrease
  • Other hormones
  • Androgen, thyroid hormone, parathyroid
    hormone,etc.
  • RBC destruction
  • Life span of RBC is about 120 days. Older cells

27
White blood cells (leucocyte)
  • WBC
  • 410?109/L, average is 7?109/L.
  • Include
  • neutrophil, eosinophil, basophil
  • monocyte, lymphocyte.
  • Protection, execute specific and non-specific
    immune reaction.
  • Physical and chemical properties
  • Chemotaxis attracted by chemical substances
    released by bacteria and foreign substances.
  • Movement Move to chemotaxic source
  • Phagocytosis engulf and digest

28
Composition and functions
  • Neutrophil
  • 1012?m, 2.07.0?109/L, 60-70.
  • Function
  • Phagocytosis older cells, becteria, dead
    tissues, and other foreign substances.
  • To execute non-specific immune activity in first
    front.

29
  • Monocytes
  • 1530?m, 0.12 0.8?109/L, 3 8.
  • Monocytes-macrophages system
  • Monocytes (in blood) wander into tissues and
    become macrophages (50 80 ?m). Stronger
    phagocytosis.
  • Contain many kinds of cytokines such as CSF, ILs,
    TNF?, INF-a,b.
  • Roles
  • Engulf and clear bacteria, vermins, older,
    necrotic tissues, dead neutrophils, dead cells
    and fragments.
  • Activate lymphocytes to execute specific immune
    response.
  • Recognize and kill cancer cells.
  • Produce CSF, Ils, TNF?, INF-?, ?, regulate growth
    of granulocytes.

30
  • Lymphocytes
  • 0.84.0?109/L, 20 40.
  • Development of lymphocyte
  • T lymphocyte
  • lymphocytic stem cells ? T lymphocytes (thymus
    gland).
  • B lymphocyte
  • lymphocytic stem cells ? B lymphocytes (lymphoid
    tissue).
  • Functions
  • T lymphocytes cellular type of immunity
  • B lymphocytes humoral immunity

31
  • Eosinophils
  • 0.020.5? 109/L, 0.55.
  • Functions
  • Inhibit allergic reaction induced by basophils
  • Produce PGE to inhibit secretion of basophils
  • Engulf substances secreted by basophils
  • Secrete matters to hydrolyze histamine and 5-HT.
  • Phagocytic action to some worms.

32
  • Basophils
  • 0.01.0 ? 109/L, 01.
  • Large cytoplastmic granules contain heparin,
    5-hydroxytryptamine and histamine.
  • Function
  • Secrete heparin blood to prevent coagulation.
  • Wander into tissue and become mast cell.
  • Induce allergy.

33
Platelet
  • Hemostasis
  • The process of blood clotting and then the
    subsequent dissolution of the clot.

Platelet ? activation ? adhension ? aggregation ?
clot ? thrombus ? FDP
thrombin
fibrin
plasmin
ADP and TXA2
vWF
fibrinogen
Blood Coagulation
Fibrinolysis
34
  • Anatomic physiology of platelet
  • 24 ?m, thickness 1?m.

35
Fibrinogen
GP IIb/III a
Phospholipid
Va
Ca2
Receptor
X
GPI
vWF
36
  • Membrane
  • Receptor For adhension, aggregation and
    coagulation.
  • Phospholipid provides the lipid cofactors needed
    for coagulation reactions.
  • Granules in platelet
  • ?-granules coagulation factors, growth factors
    (e.g. PDGF).
  • ?-granules (dense bodies) Ca2, ADP and
    serotonin.
  • Volume 100300 ?109/L in adult.
  • Thrombocytopenia lt50 ?109/L, ? hemorrhage
  • Thrombocytosis gt1000?109/L, ? Thrombosis

37
  • Physical properties
  • Adhesion
  • Mediated by von Willebrand factor (vWF).
  • vWF is producted and stored in a-granules of
    platelets. Also synthesized by megakaryocytes.
  • Function of vWF
  • To act as a bridge between glycoprotein on the
    surface of platelets (GPIb/IX) and collagen
    fibrils.
  • Serves as a carrier protein for factor VIII.
  • von Willebrand Disease (vWD) deficiency in vWF a
    patient with long bleeding time, a low level of
    factor vWF/VIII complex.
  • Bernard-Soulier Syndromedeficiency of
    glycoprotein Ib/IX.

38
  • Aggregation
  • Activated platelets aggregate together.
  • Activation of platelets induced by thrombin.
  • Thrombin receptor ? initiate signal cascade.
  • G-protein, and phospholipase C(PLC-g).
  • PLC-g ? IP3 and DAG formation.
  • IP3 ? Ca2 , and DAG ? PKC.
  • Mechanisms
  • Ca2 ? phospholipase A2 (PLA2) ?arachidonic acid
    ? thromboxane A2 (TXA2)
  • PKC? ADP ? fibrinogen to adhere to two platelet
    surface glycoproteins (GPIIb and GPIIIa) ?
    fibrinogen-induced platelet aggregation.
  • Glanzmann-Thrombasthenia, deficiency of
    glycoprotein IIb/IIIa.

39
  • Contractile function
  • PLC-g ? Ca2 ? myosin light chain kinase (MLCK)
  • MLCK ? phosphorylation of light chain of myosin
  • Myosin interacts with actin
  • Platelet morphology, motility, and clot
    retraction.

40
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41
  • Roles of platelet
  • Platelet clot formation at the site of vessel
    injury (primary hemostasis)
  • Enhance activation of coagulation factors to
    solidify platelet clot by interlacing with fibrin
    (secondary hemostasis).

42
  • Platelet function disorders
  • Disorders of platelet adhesion
  • Bernard-Soulier Syndrome deficiency of
    glycoprotein Ib/IX.
  • Disorders of platelet aggregation
  • Glanzmann-Thrombasthenia, deficiency of
    glycoprotein IIb/IIIa.
  • Disorders of platelet secretion
  • Alpha or Dense Granules Deficiency.
  • Disorders of platelet procoagulant activity
  • Platelets fail to promote activation of the blood
    clotting proteins.
  • Acquired platelet function disorders
  • Drugs like aspirin, non-steroidal
    anti-inflammatory drugs like indomethacin,
    ibuprofen.

43
Blood coagulation
  • A process of blood from liquid to colloid. A
    serious of enzymes reactions.
  • Coagulation factors
  • Factors involved in the blood coagulation
  • Attentions
  • FIII come from tissue, others from plasma.
  • FIV is Ca2, and others are proteins.
  • FII, VII, IX, XII exist as proenzymes.

44
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45
clotting cascade
Stage 1 Formation of prothrombin activator.
Stage 2 Conversion of prothrombin to thrombin.
Stage 3 conversion of fibrinogen to fibrin
46
  • Difference of stage 1
  • Prothrombin-converting enzyme Xa, Ca2, V, PL.
  • Difference of factor Xa
  • Intrinsic stage
  • Start from XII. The intrinsic pathway requires
    factors VIII, IX, X, XI, and XII. Also required
    are the proteins prekallikrein and
    high-molecular-weight kininogen, as well as Ca2
    and phospholipids secreted from platelets.
  • Extrinsic stage
  • Start from FIII (TF), is initiated at the site of
    injury in response to the release of TF.
  • TF is a cofactor in the factor VIIa
  • Factor VIIa, cleaves factor X to factor Xa

47
Prevention of coagulation
  • Plasma inhibitors
  • Fibrinolysis
  • Role of the endothelial cells

48
Plasma inhibitors
49
  • Antithrombin III
  • Nonspecific protease inhibitors
  • Produced in liver and endothelial cells
  • Inhibit active sites of FIXa,FXa,FXIa,FXIIa,
    thrombin.
  • Protein C
  • Vitamin K-dependent protein
  • Is activated to activited protein C (aPC) by
    thrombin in presence of endothelial cell-derived
    cofactor thrombomodulin.
  • aPC inactivates FV and FVIII in presence of
    another vitamin K-dependent cofactor protein S.
  • See next slide.

50
Anticoagulation pathway
VIII
VIIIa
VIIIi
PS
aPC
PC
X
X Va
PS
V
Vi
FII
Thrombin
FI
Fibrin
51
  • Heparin
  • A polysaccharide produced in basophilic mast
    cells
  • Distributed in the pericapillary tissue.
  • Abundant in lung, heart, liver, muscle tissues.
  • Inhibit thrombin conversion.
  • Promote antithrombin III activity.
  • Calcium ions precipitants
  • Sodium citrate

52
Fibrinolysis
  • Fibrinolysis
  • Process of liquefaction of fibrin

Activator
plasminogen
plasmin
Inhibitor
fibrin degradation products
fibrin
Activator Tissue plasminogen activator (tPA),
urokinase. Plasmin, a serine protease, is
inhibited by ?2-antiplasma.
53
  • tPA
  • Released from vascular endothelial cells
    following injury
  • Binds to fibrin and is consequently activated.
  • Urokinase
  • Produced as the precursor, prourokinase by
    epithelial cells lining excretory ducts.
  • Role to activate the dissolution of fibrin
    clots.
  • plasminogen activator-inhibitors
  • PAI-1 and PAI-2

54
Endothelial cells
  • Endothelium produces several inhibitors of
    hemostasis
  • Prostaglandin I2
  • secreted by endothelial cells and is a potent
    inhibitor of platelet aggregation.
  • Thrombomodulin
  • Enhances the activiation of protein C by thrombin
    and results in the inactivation of factor V and
    VIII.
  • Heparans
  • a heparin-like molecule, produced by endothelial
    cells. Increase the anticoagulant effect of
    antithrombin III.
  • Plasminogen activator
  • necessary for dissolution of fibrin clots, such
    as tPA.

55
Coagulation disorders
  • Hemophilia A
  • Deficiency of FVIII. The disease severity usually
    parallels the factor VIII levels.
  • Serve (lt 1 VIII) with spontaneous bleeding
  • Moderate (1-5 VIII) with occasional bleeding,
    usually with trauma
  • Mild (6-30 VIII) with bleeding only after
    surgery or trauma.
  • Therapy administration of FVIII.

56
  • Hemophilia B (Christmas Disease)
  • FIX deficiency.
  • Treatment requires IX-rich material fresh frozen
    plasma (FFP) or lyophilized concentrates
    proagulatant proteins.
  • Decreased production of coagulation factors
  • E.g. Liver disease, vitamin K malabsorption,
    dietary deficiency of vitamin K.
  • Inactivation of coagulation factors
  • e.g. specific inhibitors, excessive activation of
    coagulation (DIC) and/or enzymatic destruction of
    coagulation factors.

57
Blood grouping and transfusion
  • The discovery of blood groups
  • 1901, Austrian Karl Landsteiner discovered human
    blood groups.
  • Blood agglutination was an immunological
    reaction.
  • Awarded the Nobel Prize in Physiology or Medicine
    in 1930.

58
  • Agglutination
  • Agglutinogen antigen on membrane of RBC.
  • Agglutinin antibody in the plasma.
  • RBC grouping
  • ABO, Rh, MnSs, lewis
  • The differences in human blood are due to the
    presence or absence of certain protein molecules
    called antigens and antibodies.

59
ABO grouping
Blood group AA antigens on the surface of RBC,
B antibodies in blood plasma.
Blood group BB antigens on the surface of RBC,
A antibodies in blood plasma.
Blood group ABboth A and B antigens on the
surface of RBC, no A or B antibodies at all in
blood plasma.
Blood group Oneither A or B antigens on the
surface of RBC, but you have both A and B
antibodies in blood plasma
60
  • Antigens and antibodies
  • Antigens
  • A, B.
  • Carbohydrate
  • Antibodies Antibody A and B.
  • Ig M congenital,
  • Bigger Mr.

61
Rh grouping
  • Original discovery
  • Rhesus monkey Red cells ? injected into rabbits
    ? got serum ? injected back to Rhesus monkey, or
    human ? agglutination happens.
  • Rh antigen and antibody
  • Antigen D, E, C, c, e.
  • 99 Chinese people are Rh
  • Minority in China 2-5 is Rh-
  • 15 western people are Rh-
  • Antibody IgG

62
Which blood group do you belong to?
63
Blood Transfusion
  • Clinical significance
  • ABO and Rh blood groups must be compatible
    between the donor blood and the patient blood.
  • Agglutinated RBC clog blood vessels or crack to
    becomes toxic when HB outside the cell.
  • Cross-match test
  • Main lateral donors RBC and recipients serum.
  • Co-lateral donors serum and recipients RBC.

64
  • Principle of blood transfusion
  • Agglutination of main lateral absolutely no.
  • Both of main and co-lateral do not agglutinate
  • Co-lateral agglutinates but Main lateral
  • slow and less amount of blood transfusion could
    be recommended.

People with blood group O are called universal
donors. People with blood group AB are called
universal receivers.
65
  • Clinical importance for Rh group
  • Blood transfusion between Rh and Rh- persons.
  • A mother who is Rh- woman give birth a baby who
    is Rh.
  • Preventive measure given an injection of
    anti-Rh antibodies.

66
Donor
Recipient
RBC
RBC (co-lateral)
Serum (main lateral)
Serum
Cross match test
67
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