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Blood!
About 8% of total body weight!
Average volume: 5 litres in women; 5.5 litres in men!
Consists of 3 types of specialized cellular elements suspended in plasma
(liquid portion of blood)!
Erythrocytes!
Red blood cells!
Important in O2 transport!
Leukocytes!
White blood cells!
Immune system’s mobile !
defense units!
Platelets !
Cell fragments!
Important in haemostasis!
A blood sample following centrifugation!
Composition of blood I: Plasma!
Constituent
Functions
Water (90% of plasma)
Transport medium, carries heat
Electrolytes
Membrane excitability; osmotic distribution of fluid between ECF
and ICF; buffer pH changes
Nutrients, wastes, gases,
hormones
Transported in blood; blood CO2 plays role in acid-base balance
Plasma proteins
6-8% of plasma
Albumins — most abundant
Contribute to the colloid osmotic pressure by virtue of their abundance (next lecture)
Transport molecules that are poorly soluble in plasma (eg) bilirubin, bile salts & many drugs.
Globulins (3 subclasses - α, β and γ)
-  α/β - Transport molecules (high specificity); blood clotting factors
-  α - Inactive precursors proteins e.g. Angiotensinogen: Converted to angiotensin
- γ - Immunoglobulins (antibodies) - Immunity
Fibrinogen - clotting factor; converted to fibrin
All produced by the liver - except for γ-globulins which are produced by lymphocytes
Serum is plasma from which fibrinogen and other clotting proteins have been removed. When
you centrifuge coagulated (clotted) blood the liquid portion is serum
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Composition of Blood II: Cells: Erythrocytes!
5 million per cubic millilitre
Lack nuclei, mitochondria, ribosomes
7µm diameter, 2µm thickness, biconcave
Transport O2 and CO2
Haemoglobin
Life cycle of 120 days
EPO (erythropoietin) produced by kidney
We make about 1012 (1 Trillion) new RBCs each day!
Haemopoiesis (production of blood cells)
Progressive differentiation:
Change from relatively undifferentiated pluripotent stem cell
Gradual acquisition of specific characteristics of ‘end-cells’
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Anemia!
Refers to a below-normal O2-carrying capacity of the blood!
Possible causes of anemia!
1.  Reduced Haemoglobin content of RBCs !
Iron deficiency!
2.  Reduced RBC Number!
Reduced cell production!
Increased cell loss!
•  Haemolysis (membrane changes)!
Pallor associated with anemia
Anaemia — Causes!
Nutritional anemia (eg) Iron deficiency (can’t make sufficient haemoglobin).
Pernicious anemia Inability to absorb Vitamin B12 from GIT due to deficiency of an intrinsic
factor
Aplastic anemia Failure of the bone marrow to produce enough RBCs eventhough all the
ingredients necessary for erythropoiesis are present (eg) Cancer chemotherapy,
radiation,
Renal anemia
Reduced RBC production due to impaired EPO synthesis due to Kidney disease
Hemorrhagic anemia Caused by losing a lot of blood
Hemolytic anemia Caused by rupture of RBCs
Malaria (parasite) invades RBCs and causes rupture
Sickle cell disease (Due to a genetic mutation in β-chain of haemoglobin)
Normal RBC
Sickled RBC
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Platelets (thrombocytes)!
Smallest of formed elements in the blood, lack nucleus
Are fragments of megakaryocytes
Constitute most of mass of blood clots
Release serotonin to vasoconstrict & reduce blood flow to clot area
Secrete growth factors to maintain integrity of blood vessel wall
Survive 5-9 days, and are removed from circulation by tissue
macrophages
Thrombopoietin Hormone produced by liver; increases number of
megakaryocytes and therefore increases platelet production
Haemostasis!
Process of keeping blood within a damaged blood vessel (the opposite of haemostasis is
haemorrhage)
Involves 2 major steps
1. Formation of a platelet plug
2. Blood coagulation (clotting): Transformation of blood from liquid into a solid gel
1. Formation of the Platelet Plug
2. Blood Clotting
Red blood cells trapped in a mesh of fibrin!
Platelets aggregate on contact with
exposed collagen in damaged wall of
the vessel
Platelets release ADP which causes
surface of nearby circulating
platelets to become sticky in order to
adhere to first layer of aggregated
platelets
Reinforces platelet plug & converts blood
in vicinity of vessel injury into a nonflowing gel
Clotting factors always present in blood
plasma in inactive precursor form. Vessel
damage that exposes collagen initiates
cascade of reactions that involve
successive activation of clotting factors
Convert fibrinogen  fibrin
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Blood clotting cascade: 2 pathways
Extrinsic: Shorter & faster
Intrinsic: Requires more upstream
factors
Points to note:!
Series of steps involving 12 clotting factors!
Ca2+ /PF3 required at several points!
Final common pathway!
Activation of Factor X!
Prothrombin to Thrombin!
Cleaves Fibrinogen to form Fibrin!
Limitation of clotting
Clotting is potentially dangerous!
Clot dissolution: Plasmin dissolves clots
Plasmin is produced from plasminogen by
many clotting factors (including XII).
Phagocytic WBCs remove the products of
clot dissolution
Clot prevention:
Tissue Plasminogen Activator (tPA)
Converts plasminogen in plasmin and
prevents inappropriate clot formation
tPA used clinically as a clot buster
Thrombomodulin
Binds thrombin (So no fibrinogen
1.  Intact endothelium releases NO and
conversion)
prostacyclin…!
Activates Protein C — anticoagulant
•  Inhibit platelet adhesion
(inactivates active factors V and VIII).
G&S Fig. 16.6
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Abnormal Blood Clotting!
Thrombus!
–  Abnormal intravasculaar clot attached to a vessel wall!
Emboli!
–  Freely floating clots!
Factors that can cause thromboembolism!
–  Roughened vessel surfaces associated with atherosclerosis!
–  Imbalances in the clotting-anticlotting systems!
–  Slow-moving blood !
–  Occasionally triggered by release of tissue thromboplastin into
blood from large amounts of traumatized tissue!
Haemophilia!
–  Excessive bleeding caused by deficiency of one of the factors in
the clotting cascade !
•  Haemophillia A: Clotting Factor XIII deficiency!
•  Haemophillia B: Clotting Factor IX deficiency!
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