Transcript FUNCTIONS OF THE BLOOD

Haemostasis
Prof. K. Sivapalan
Thrombocytes
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2 – 4 μm in diameter.
Half life – 4 days.
300,000 / μL.
Break off from
megakaryocytes.
• Colony stimulating
factors and
thrombopoietin- liver and
kidney.
• 60 – 70 % in circulating
blood - balance in
spleen.
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Properties of Platelets
• A ring of microtubules in periphery.
• Extensively invaginated membrane.
• Membrane contains receptors for:
– Collagen, von Willebrand factor and fibrin.
• Dense granules in cytoplasm:
– Serotonin, ADP, other nuclear tides.
• α – granules in cytoplasm :
– Clotting factors and platelet-derived growth factor
[PDGF – stimulates wound healing and mitogen for
vascular smooth muscle.]
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Platelet activation.
• Binds to exposed collagen and von
Willebrand factor (when damage to blood
vessel). This is platelet adhesion.
• This activates platelets [ADP]
• Platelets change shape, put out
psudopodia and release granules and
causes platelet aggregation.
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Changes in the platelet.
• Platelet activation results in change in shape, putting out
psseudopodia, release of granules and aehesion to other
platelets.
• Platelet Activating Factor secreted by neutrophils and
monocytes stimulates G protein which activates
phospholipase C to form diacylglycerol. This also
causes release of granules.
• Increased cytoplasmic calcium and diacylglycerol
activate Phospholipase A2. This causes release of
arachidonic acid from membrane phospholipids which is
converted into Thromboxan A2
• Thromboxan and other substances released cause
vasoconstriction, platelet aggregation, clot formation
• Aspirin prevents the above reaction and alters the
balance between thromboxan and prostacycline and
prevents clotting in low doses.
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Effects of platelet aggregation.
• Repair of the blood
vessels.
• Block damaged
capillaries.
• Vasoconstriction.
• Clotting.
• [Test for platelet
function: bleeding
time.]
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Thrombocytopenia.
• Results in capillary
bleeding [purpura].
• Caused by– Marrow disorders.
– Alcohol, cytotoxic drugs,
viral infections.
– Hereditary.
– Immunologically mediated
destruction.
– Increased consumption of
platelets.
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Thrombocytosis.
Causes:
• Spleanectomy.
• Postoperatively, delivery.
• Haemorrhage or haemolysis.
• Extreme exercise.
Risk:
• Thrombotic diseases- deep vein
thrombosis.
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Hemostasis.
• Vascular spasm: local myogenic, serotonin
– lasts for about 20 – 30 minutes.
• Platelet plug.
• Clotting of blood.
• Organization by fibrous tissue.
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Coagulation of blood – clotting.
• Fibrinogen → Fibrin.
• Polymerization of
fibrin with branching.
• Loose mesh of
interlacing strands.
• Formation of covalent
bonds → dense, tight
aggrigate.
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Clot
retraction.
Stabilization. [platelets]
30 – 60 min.
Fibrin.
Important reactions.
Fibrinogen
Activated XIII
Thrombin
Platelet Factor, Ca++,
Activated Factor V.
Factor x
(activated)
Prothrombin
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Factor XIII
Intrinsic system.
2 – 5 minutes.
Extrinsic system.
15 – 30 Seconds.
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Coagulation cascade.
Tissue factor –
Extrinsic system.
Contact with wettable,
negatively charged surface –
Intrinsic system.
Prekallikerin
Kallikerin.
HMW Kilinogen
XII
XIIa.
XI
XIIa
IX
IXa
[Tissue ThromboplastinTPL+TFI]
Activated VIII,
Ca++
TPL+TFI
Platelet factor
(PL),
Ca++
VIIa
VII
Ca++, PL, TPL
X
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Xa
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Role of liver in clotting.
• Synthesizes:
– Fibrinogen.
– Prothrombin.
– Other clotting factors.
• Needs:
– Vitamin K.
• Removes activated clotting factors.
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Propagation of clot formation.
• Clot formation can be initiated at any
vessel by damage to endothelium by
platelet plug.
• Activated clotting factors on the surface
of the clot can cause further clotting.
• Platelet plug can form on the surface of
the clot which can initiate further clotting
• Rapid flow wash off the factors which
are diluted and removed in liver.
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Clotting and Anti clotting
mechanisms.
• Clotting and anti clotting mechanisms are
balanced under normal circumstances.
• It is essential to maintain blood in liquid
form but prevent loss if the vessels are
damaged.
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Anti clotting mechanisms.
• Anti thrombin III [circulating protease]
inactivates activated factors IX,X,XI and
XII. Heparin facilitates it.
• Prostacycline of Endothelium antagonizes
thromboxane A2 of platelets. (aggregation)
• Endothelium has thrombomodulin. It’s
reaction with thrombin leads to fibrinolysis,
inactivation of factor V and VIII.
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Fibrinolytic system.
Thrombomodulin
in endothelium.
Binds to Thrombin
Prtotein C.
VIIIa
Inactive VIIIa
Va
Inactive Va
Activated protein C.[APC]
Inhibitor of tissue
plasminogen activator
inhibited.
Plasmin.
Plasminogen
Lyses of fibrin.
Tissue plasminogen activator
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Abnormalities of clotting.
Defective clotting:
• Abnormalities of platelet function.
• Congenital deficiency of clotting factors– Hemophelia A – factor VIII [ X linked].
– Hemophelia B – factor IX.
• Von Willebrand factor deficiency.
• Vitamin K deficiency and Liver diseases.
Enhanced clotting:
 Increased platelets.
 Absent Protein C.
Intravascular Clotting is thrombosis and if carried in blood it
is embolism. Both can obstruct blood vessels and cause
ischemia to organs.
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Anticoagulants.
• Heparin promotes antithrombin III which
inactivates factors IX, X, XI and XII.
Warfarin inhibits Vitamin K.
Streptokinase activates plasminogen and
disolves fibrin. [snake, bacteria]
Aspirin reduces thromboxan A2 formation.
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