Blood Physiology

• Blood is define as a connective tissue in fluid form.

• It is regarded as fluid of life-due to its ability to carry oxygenated blood from lungs
to different parts of the body and CO2 from body tissues to the lungs.
• It is regarded as fluid of growth- due to its ability to carry digested nutrients from
GIT and endocrine hormones to all tissues of the body.
• It is known as fluid of health- due to its function to protect the body from disease
invasion and remove unwanted substances and waste product via excretory organs
like kidney, skin, anus etc.
• Blood composition and properties
• Blood cells
– RBC: contains oxygen (red in color).
– WBC: protect the body against disease
– Platelet: function in coagulation and fibrinolysis.
• Blood grouping and transfusion

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 Blood composition and properties
• Blood volume: 7~8% (70-80ml/kg Body Weight)
– 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:
oxygen and carbon dioxide (Gases)
nutrients, hormones, metabolic wastes
heat.
– Host defense:
• Immune reaction, coagulation.
– Note that the volume of red blood cells expressed in percentage is called the
hematocrit value or packed cell volume (PCV). S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)
 Components and Characteristic
Water: 93-95%
Plasma: 50-60%
Solutes: 5-7% Proteins:
Nutrients
Products
Whole Electrolytes:
blood Others: urea, gases.
WBC, Platelet: 1%
RBC: 40-50% (male)
37-48% (female)

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 Blood Components
• The blood contains
• Water:
– 93~95% (plasma); 65~68% (RBC); 81~86% (whole blood).
– Solvent, humoral balance, osmotic pressure.
• Electrolytes:
– Na+, K+, Mg2+, Cl-, HCO3-, etc. Cell shape, pH.
• Plasma 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.

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 – 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.
The plasma

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

The Plasma
 Physical and chemical properties of blood
• Blood pH:
– Normal interval: 7.35~7.45.
• Regulated by lung and kidney.

• Viscosity: blood is more viscous than water due

to its RBC and plasma proteins composition.
– Friction of molecules and cells in blood.
– Relative viscosity:
• Whole blood: 4~5 times more than water (RBC).
• Plasma: 1.6~2.4 times more than water (Proteins).
• Reduced RBC count result to Anemia.
S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)
• 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.

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 Blood Cells
• The redness of RBC is due to it hemoglobin and
oxygen content
• Red blood cell
• White blood cell
• Platelet

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 Hemopoiesis
• The process of blood production.

Cell Lineage Lifespan Daily Production Rate

RBC 120 days 2.5  109/L

Neutrophil (WBC) 7 hours 0.85  109/L

Platelet 10 days 2. 5  109/L

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

• Ontogeny of Hematopoiesis
– Prenatal stages: (before birth)
• First month: yolk sac produces blood.
• Third month: liver produces blood
• Fourth month: bone marrow begins to produce blood
– Postnatal stages: (after birth)
• Within 20 years -bone marrow of all bone, predominatantly
by flat bones and long bones.
• After 20 years membranous bones like vertebra, sternum,
ribs, scapula, iliac bones and skull bones and from the ends
of long bones.
• Liver and spleen can also produce blood if there is bone
marrow destruction.

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 100 100

Yolk Sac Liver Bone morrow

activity (%)
Hemopoitic

Lymph nodes
Spleen

0 1 2 3 4 5 6 7 8 9

Prenatal age (months)

100 100
Vertebrate
Proportion of Red
Morrow (%)

Tibia Sternum
Femur Ribs

birth 10 20 30 40 50 60 70 80 90

Postnatal age (years) S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)
S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)
Hematopoiesis

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 Stages of hemopoiesis
– 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.
S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)
• Hematopoietic growth factor and related molecules
– Necessary for proliferation and differentiation of
hematopoietic cells in the marrow.
– Colony-stimulating factors (CSF): see a table in next slide.
– Cytokines:
• (Interlukin-1) 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.

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 Hematopoietic growth factors
Growth Factors Function: stimulate progenitor of the
followings:

GM-CSF (granulocyte-macrophage CSF) Granulocyte-monocyte

G-CSF (granulocyte CSF) Granulocyte

M-CSF (macrophage CSF) Monocyte

EPO (Erythropoietin) Erythrocyte

IL-1,3,6 (Interleukin-3, 1, 6) Myeloid lineage

TPO (Thrombopoietin) Platelet

S.K. MOBISSON (B.Sc, M.Sc) &Ph.D (in view)

 Red blood cells (erythrocytes)
• Circular, biconcave discs without nuclei. 7~8m,
thickness 1~2.5 m.
• Cell count and volume:
– Hematocrit: Percentage of blood volume occupied by packed cell volume.
 – Volume:
• 4.5~5.51012/L, average 5.01012/L (male).
• 3.8~4.6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.
 • Erythrocytes Sedimentation Rate (ESR):
Sedimentated distance of RBC after one hour.
– 0~15 mm/h (male), 0~20 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.
 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.
• 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.
• RBC Maturation factors:
– Vitamin B12:
• Cobalamine, 2~5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.
– Lack of folic acid and vitb12: give rise to immature
cells due to DNA synthesis derangement.
– Megaloblast anemia.
•Regulation of erythropoiesis: Hypoxia:  EPO RBC

Hemopoitic stem cell (uncommitted progenitor)


Erythrocytic progenitor (committed progenitor)
EPO 
Pronormblast (precursor)

Normoblast, Reticulocyte

Mature RBC (without nucleus)
• 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 that aid in erythropoiesis:
– Androgen (testosterone), thyroid hormone, parathyroid
hormone,etc.
• RBC destruction:
– Life span of RBC is about 120 days. Older cells
 White blood cells (leucocyte)
• WBC:
– 4~10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
 Composition and functions
• Neutrophil:
– 10~12m, 2.0~7.0109/L, 60-70%.
– Function:
• Phagocytosis: older cells, becteria, dead tissues, and
other foreign substances.
• To execute non-specific immune activity in first front.
• Monocytes:
– 15~30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 cells, 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.
• Lymphocytes:
– 0.8~4.0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 functions in cellular mediated immunity
• B lymphocytes functions in humoral immunity
• Eosinophils
– 0.02~0.5 109/L, 0.5~5%.
– Functions:
• Inhibit allergic reaction induced by basophils:
– Produce prostaglandin E (PGE) to inhibit secretion of
basophils;
– Engulf substances secreted by basophils;
– Secrete matters to hydrolyze histamine and serotonin (5-
hydroxytryptamine).
• Phagocytic action to some worms.
• Basophils
– 0.0~1.0  109/L, 0~1%.
– It has large cytoplastmic granules that contains heparin,
5-hydroxytryptamine (serotonin) and histamine.
– Function:
• Secrete heparin blood to prevent coagulation.
• Wander into tissue and become mast cell.
• Induce allergy (hypersensitivity reaction).
 Platelet

• Hemostasis:
– The process of blood clotting and then the subsequent
dissolution of the clot.

Platelet  activation  adhension  aggregation  clot  thrombus  FDP

thrombin vWF ADP and TXA2 fibrin plasmin

fibrinogen

Blood Coagulation Fibrinolysis

• Anatomic physiology of platelet:
– 2~4 m, thickness 1m.
 Fibrinogen

GP IIb/III a

Phospholipid

Va

Ca2+
Receptor
X

GPI

vWF
– 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: 100~300 109/L in adult.
• Thrombocytopenia: <50 109/L,  hemorrhage
• Thrombocytosis: >1000109/L,  Thrombosis
• Physical properties
– Adhesion:
• Mediated by von Willebrand factor (vWF).
• vWF is produced 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 Syndrome:deficiency of glycoprotein
Ib/IX.
– 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.
• 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.
• 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).
• 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.
 Blood coagulation
• A process of blood from liquid to colloid. A series 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.
 Factor Trivial Name(s) Pathway Characteristic

Intrinsi  
Prekallikrein Fletcher factor
c

High molecular weight kininogen Intrinsi  

contact activation cofactor; Fitzgerald, Flaujeac Williams factor
(HMWK) c

-
I Fibrinogen Both

II Prothrombin Both Contains N-term. gla segment

Extrinsi -
III Tissue Factor
c

-
IV Calcium Both

V Proaccelerin, labile factor, accelerator (Ac-) globulin Both Protein cofactor

This is Va, redundant to

VI (Va) Accelerin
Factor V

Proconvertin, serum prothrombin conversion accelerator (SPCA), Extrinsi Endopeptidase with gla
VII
cothromboplastin c residues

Intrinsi
VIII Antihemophiliac factor A, antihemophilic globulin (AHG) Protein cofactor
c

Christmas Factor, Intrinsi Endopeptidase with gla

IX
antihemophilic factor B,plasma thromboplastin component (PTC) c residues

Endopeptidase with gla

X Stuart-Prower Factor Both
residues

Intrinsi
XI Plasma thromboplastin antecedent (PTA) Endopeptidase
c

Intrinsi
XII Hageman Factor Endopeptidase
c

Protransglutaminase,
XIII Both Transpeptidase
fibrin stabilizing factor (FSF), fibrinoligase
 clotting cascade

Stage 1: Formation
of prothrombin
activator.

Stage 2:
Conversion of
prothrombin
to thrombin.

Stage 3: conversion of
fibrinogen to fibrin
• 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
 Prevention of coagulation
• Plasma inhibitors
• Fibrinolysis
• Role of the endothelial cells
 Plasma inhibitors

Inhibitor Mol. Weight Action Plasma Conc.

(kD) (mg/ml)

Antithrombin 50 Antiserine 240

III protease

2- 70 Antiplasmin 70
antiplasma
2- 725 Antiprotease 2500
macroglobulin
Protein c 56 Anti-factor V 5
and Viii
• 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.
 Anticoagulation pathway

VIII VIIIa VIIIi

PS

X X aPC PC
PS
+
V Va Vi

FII Thrombin

FI Fibrin
• 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
 Fibrinolysis
• Fibrinolysis:
– Process of liquefaction of fibrin

Activator
plasminogen plasmin
Inhibitor

fibrin fibrin degradation products

Activator: Tissue plasminogen activator (tPA), urokinase.

Plasmin, a serine protease, is inhibited by 2-antiplasma.
• tPA:
– Released from vascular endothelial cells following
injury;
– Binds to fibrin and is consequently activated.
• Urokinase:
– Produced as the precursor, pro-urokinase by
epithelial cells lining excretory ducts.
– Role: to activate the dissolution of fibrin clots.
• plasminogen activator-inhibitors (PAI):
– PAI-1 and PAI-2
 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.
 Coagulation disorders
• Hemophilia A:
– Deficiency of FVIII. The disease severity usually
parallels the factor VIII levels.
– Serve (< 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.
• 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.
 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 /Medicine in 1930.
• 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.
 ABO grouping

Blood group A ： A antigens on the surface of RBC,

B antibodies in blood plasma.

Blood group B ： B antigens on the surface of RBC,

A antibodies in blood plasma.

Blood group AB ： both A and B antigens on the

surface of RBC, no A or B antibodies at all in blood
plasma.

Blood group O ： neither A or B antigens on the

surface of RBC, but you have both A and B antibodies
in blood plasma
• Antigens and antibodies:
– Antigens:
• A, B.
• Carbohydrate
– Antibodies: Antibody A and B.
(immunoglobulins)
• Ig M: congenital,
• Bigger Mr.
 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
Which blood group do you belong to?

A Rh+ B Rh+ AB Rh+ O Rh+

A Rh- B Rh- AB Rh- O Rh-

 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: donor’s RBC and recipient’s serum.
– Co-lateral: donor’s serum and recipient’s RBC.
• 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”.
• 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.
Donor Recipient

RBC RBC (co-lateral)

Serum Serum (main lateral)

Cross match test