IRON METABOLISM

HEAMOSTASIS & FIBRINOLYSIS

HAEMOSTASIS &FIBRINOLYSISHAEMOSTASIS &FIBRINOLYSIS

DR B L MtinangiDR B L Mtinangi

DEPARTMENT OF PHYSIOLOGYDEPARTMENT OF PHYSIOLOGY

Hubert Kairuki Memorial UniversityHubert Kairuki Memorial University

December 3, 2015December 3, 2015

A SUMMARY OF PLATELETSFORMATIONA SUMMARY OF PLATELETSFORMATION

HEAMOSTASIS & FIBRINOLYSIS

SUMMARY OF BLOOD COAGULATION

BV Injury

PlateletPlatelet

Aggregation

Platelet

Activation

Blood VesselBlood Vessel

Constriction

CoagulationCoagulation

Cascade

Stable Hemostatic Plug

Fibrinformation

Reduced

Blood flow

Contact/TissueFactor

Primary hemostatic plug

Neural

HEAMOSTASIS & FIBRINOLYSIS

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HEAMOSTASIS & FIBRINOLYSIS

HAEMOSTATISHAEMOSTATIS

Haemostasis is prevention ofblood loss after rupture orinjury/trauma of blood vesselsHaemostasis is prevention ofblood loss after rupture orinjury/trauma of blood vessels

It is achieved through:It is achieved through:

–Vascular spasms–Vascular spasms

–Formation of platelet plug formation–Formation of platelet plug formation

–Blood coagulation i.e. Developmentof insoluble fibrin clot–Blood coagulation i.e. Developmentof insoluble fibrin clot

–Clot retraction–Clot retraction

–Clot dissolution–Clot dissolution

HEAMOSTASIS & FIBRINOLYSIS

Vascular spasms (vasoconstriction)Vascular spasms (vasoconstriction)

Vascular spasms is due to:Vascular spasms is due to:

–Nervious reflex due to pain–Nervious reflex due to pain

–Effects of local and humoralmechanism–Effects of local and humoralmechanism

–Thromboxane A2 (prostaglandin)cause vasoconstrition–Thromboxane A2 (prostaglandin)cause vasoconstrition

All generate an Action Potentialand cause Myogenic spasm(constriction) and REDUCE bloodflowAll generate an Action Potentialand cause Myogenic spasm(constriction) and REDUCE bloodflow

The spasm last less than 1 minThe spasm last less than 1 min

HEAMOSTASIS & FIBRINOLYSIS

FORMATION OF PLATELET PLUGFORMATION OF PLATELET PLUG

Initiated when the platelet come intocontact with damaged vascular surfaceor collagen fibersInitiated when the platelet come intocontact with damaged vascular surfaceor collagen fibers

Platelets adhere and aggregate to thedamaged sitePlatelets adhere and aggregate to thedamaged site

Platelets secrete large quantity of ADPand Thromboxane A2 (prostaglandin)Platelets secrete large quantity of ADPand Thromboxane A2 (prostaglandin)

Endothetal cells secrete a VonWillebrands factor (a small proteinmolecule)Endothetal cells secrete a VonWillebrands factor (a small proteinmolecule)

–Usually attached to factor VIII–Usually attached to factor VIII

–Bridges the platelets to exposed collagen–Bridges the platelets to exposed collagen

HEAMOSTASIS & FIBRINOLYSIS

CONT.CONT.

Aggregated platelets activatecoagulation factorsAggregated platelets activatecoagulation factors

Finally convert FIBRINOGEN toFIBRINFinally convert FIBRINOGEN toFIBRIN

–Stabilizing the PLATELET PLUG–Stabilizing the PLATELET PLUG

Platelets normal count 150,000-400,000/µlPlatelets normal count 150,000-400,000/µl

Platelets maintain normal vascularintegrityPlatelets maintain normal vascularintegrity

HEAMOSTASIS & FIBRINOLYSIS

MECHANISMS OF BLOOD COAGULATIONMECHANISMS OF BLOOD COAGULATION

Two mechanismsTwo mechanisms

1.Procoagulant-promote coagulation1.Procoagulant-promote coagulation

Predominate during injuryPredominate during injury

2.Anti coagulant – inhibit coagulation2.Anti coagulant – inhibit coagulation

In normal condition it ispredominatIn normal condition it ispredominat

HEAMOSTASIS & FIBRINOLYSIS

CLOTTING FACTORS ANDTHEIR ROMANS SYNONYMSCLOTTING FACTORS ANDTHEIR ROMANS SYNONYMS

Fibrinogen: factor IFibrinogen: factor I

Prothrombin: factor IIProthrombin: factor II

Tissue thromboplastin: factor IIITissue thromboplastin: factor III

Calcium: factor IVCalcium: factor IV

Proaccelerin: (labile factor V)Proaccelerin: (labile factor V)

Prothrombin: factor VIIProthrombin: factor VII

Antihaemophilic: factor (AHF VIII)Antihaemophilic: factor (AHF VIII)

Plasma thromboplastin componentPTC: factor IXPlasma thromboplastin componentPTC: factor IX

HEAMOSTASIS & FIBRINOLYSIS

CONT.CONT.

Stuart: factor XStuart: factor X

Plasma thromboplastinantecedent PTA: factor XIPlasma thromboplastinantecedent PTA: factor XI

Hegman factor XII (contact factor) Hegman factor XII (contact factor)

Fibrin stabilizing: factor XIIIFibrin stabilizing: factor XIII

NB: Factor II, VII, IX & X requiresvit K for their synthesis IN THELIVER, therefore NB: Factor II, VII, IX & X requiresvit K for their synthesis IN THELIVER, therefore

Vit K deficiency & liver diseasesleads to bleeding tendenciesVit K deficiency & liver diseasesleads to bleeding tendencies

HEAMOSTASIS & FIBRINOLYSIS

Factor

Trivial Name(s)

Pathway

Characteristic

Prekallikrein

Fletcher factor

Intrinsic

High molecular weightkininogen (HMWK)

contact activation cofactor; Fitzgerald, Flaujeac Williamsfactor

Intrinsic

Fibrinogen

Both

Prothrombin

Both

Contains N-term. glasegment

III

Tissue Factor

Extrinsic

Calcium

Both

Proaccelerin, labile factor, accelerator (Ac-)globulin

Both

Protein cofactor

VI (Va)

Accelerin

This is Va, redundant toFactor V

VII

Proconvertin, serum prothrombin conversionaccelerator (SPCA), cothromboplastin

Extrinsic

Endopeptidase with glaresidues

VIII

Antihemophiliac factor A, antihemophilic globulin(AHG)

Intrinsic

Protein cofactor

Christmas Factor,antihemophilic factor B,plasma thromboplastin component(PTC)

Intrinsic

Endopeptidase with glaresidues

Stuart-Prower Factor

Both

Endopeptidase with glaresidues

Plasma thromboplastin antecedent (PTA)

Intrinsic

Endopeptidase

XII

Hageman Factor

Intrinsic

Endopeptidase

XIII

Protransglutaminase,fibrin stabilizing factor (FSF), fibrinoligase

Both

Transpeptidase

HEAMOSTASIS & FIBRINOLYSIS

INITIATION OF COAGULATIONINITIATION OF COAGULATION

Initiation of coagulation by either:Initiation of coagulation by either:

1.Trauma/injury to the tissue –extrinsic pathway1.Trauma/injury to the tissue –extrinsic pathway

2.Trauma/injury to the blood –intrinsic pathway2.Trauma/injury to the blood –intrinsic pathway

3.Contact of blood with damagedendothelial and collagen3.Contact of blood with damagedendothelial and collagen

A SUMMARY OF COAGULATION PATHWAYA SUMMARY OF COAGULATION PATHWAY

HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS

COAGULATION is also regulated byseveral natural anticoagulantsCOAGULATION is also regulated byseveral natural anticoagulants

Antithrombin III inactivate coagulationfactors& it neutralizes thrombinAntithrombin III inactivate coagulationfactors& it neutralizes thrombin

Antithrombin III activity is enhanced byheparinAntithrombin III activity is enhanced byheparin

Protein C receptor combinethrombomodulin – inhibits thrombin andseveral coagulation factorsProtein C receptor combinethrombomodulin – inhibits thrombin andseveral coagulation factors

Protein S accelerate the action ofprotein CProtein S accelerate the action ofprotein C

Deficiency of the above factors leadsto HYPERCOAGULOPATHY statesleading to increasedTHROMBOEMBOLISMDeficiency of the above factors leadsto HYPERCOAGULOPATHY statesleading to increasedTHROMBOEMBOLISM

HEAMOSTASIS & FIBRINOLYSIS

CLOT RETRACTIONCLOT RETRACTION

Clot retraction requires largenumbers of platelets ieconsolidate the clotClot retraction requires largenumbers of platelets ieconsolidate the clot

This contributes to haemostasisby joining the edges of the brokenvesselsThis contributes to haemostasisby joining the edges of the brokenvessels

HEAMOSTASIS & FIBRINOLYSIS

SUMMARY OF FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS

FIBRINOLYSIS (CLOT DISSOLUTION)FIBRINOLYSIS (CLOT DISSOLUTION)

Dissolution of a blood clot beginsshortly after its formationDissolution of a blood clot beginsshortly after its formation

Plasma – contains a globulinPLASMINOGEN incooperated in alarge amount in the CLOTPlasma – contains a globulinPLASMINOGEN incooperated in alarge amount in the CLOT

PLASMINOGEN is activated byPLASMINOGEN is activated by

Thrombin, factor XIII, and somelysosomal enzymes to PLASMIN withA PROTEOLYTIC like action Thrombin, factor XIII, and somelysosomal enzymes to PLASMIN withA PROTEOLYTIC like action

HEAMOSTASIS & FIBRINOLYSIS

PLASMINPLASMIN

Plasmin digest formed fibrin thread/clotPlasmin digest formed fibrin thread/clot

(FIBRINOLYSIS) (FIBRINOLYSIS)

Plasmin also digest a number of clottingfactors like Factor I, II, V & VIIPlasmin also digest a number of clottingfactors like Factor I, II, V & VII

alpha2 antiplasmin is always present inblood whichalpha2 antiplasmin is always present inblood which

Binds with plasmin and inhibit its actionBinds with plasmin and inhibit its action

Fibrinolysis system is therefore importantfor removing small clot from tiny peripheralvessels-preventing occlusion or blockageand thromboembolismFibrinolysis system is therefore importantfor removing small clot from tiny peripheralvessels-preventing occlusion or blockageand thromboembolism

Thank you

HEAMOSTASIS & FIBRINOLYSIS