Hemostasis Physiology.pdf

HEMOSTASIS   •  Click  to  edit  Master  text  styles   –  Second  PHYSIOLOGY   level   •  Third  level   –  Fourth  level   »  Fi8h  level  

FIFTEEN  APRILA  FAJRIN   BAGIAN  FKK-­‐FFUJ  

Outlines… •  Click  to  edit  Master  text  styles   –  Second  level   •  Third  level   –  Fourth  level   »  Fi8h  level  

①  Definition   ②  Normal  hemostasis   ③  Functions  of  vessel  wall,   platelets  and  coagulation   factors  in  bleeding   ④  Coagulation  and  Fibrinolysis  

Definition? • þ Drives   Click  tfrom   o  edit   Mreek   aster  text  styles   the  G -  Heme   :  Bllood   –  Second   evel   -  Stasis   :  to   halt   •  Third   level   –  Fourth   evel   þ Hemostasis   à  “lThe   stoppage  of  » bFi8h   lood  level   flow”   þ Repairs  injury  to  blood   vessels   þ Stops  or  prevents  blood   loss  

Hemostasis??? •  Click  to  edit  Master  text  styles   à  Hemostasis  is  a  balancing  act  

à Balance  of  bleeding  (hemorrhaging)  and  clotting  (thrombosis)  

–  Second  level  

à  Imbalance  in  one  direction  can  lead  to  :   •  Third   level   –  Bleeding   :  hypocoagulable   –  Fourth   level   –  Thrombosis   :  hypercoagulable   »  Fi8h  level  

Hemostasis??? •  Click  to  edit  Master  text  styles   –  Second  level   •  Third  level   –  Fourth  level   »  Fi8h  level  

Hemostasis Component Coagulation   System  

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ystem   • Platelet   Third  Slevel  

•  Forms  a  stable   insoluble  plug   (i.e)  fibrin   forming  

•  Interaction  of   –  Fourth   vascular   and   level   platelets   orm  al  evel   » fFi8h   temporary  plug  

Vascular  System   •  Controls  rate  of   blood  flow  

HEMOSTASIS COMPONENT

Fibrinolytic   System   •  Fibrin  lysing  

Coagulation   Inhibition  System   •  Natural  inhibitors   •  Control  fibrin   formation  and  fibrin   lysis  

NORMAL HEMOSTASIS -  It  is  a  complex  process  depending  on  interaction  between   •  vessel   Click  wto   epdit   Master   text  styles   all,   latelets   and  coagulation   factors.     –  Second  level   BV  Injury   •  Third  level   Tissue  Factor  

Neural   –  Fourth  level   »  Fi8h  level  

Blood  Vessel    

Platelet  

Constriction  

Activation   Primary  hemostatic  plug  

Reduced   blood  flow  

Plt-­‐Fusion  

Stable    Hemostatic  Plug  

Coagulation  

Activation  

Thrombin,   Fibrin  

NORMAL HEMOSTASIS STAGES •  Click  to  edit  Master  text  styles   –  Second  level   •  Third  level   –  Fourth  level   »  Fi8h  level  

NORMAL HEMOSTASIS Primary  

•  Click  to  eàplatelet   dit  Master   text  styles   and  vascular   response  to  vessel  injury   –  Second  level  

•  Third  level   –  Fourth  level   »  Fi8h  level  

Secondary  

àthe  coagulation  factors   response  to  such  injury  

1.  Together,  platelets,   vessels,  and   coagulation  factors  à   combine  to  stop  

bleeding  

2.  Allow  for  vessel  repair   through  formation  of  a  

stable  fibrin-­‐platelet   plug  at  the  site  of   injury.  

NORMAL HEMOSTASIS •  Click  to  edit  Master  text  styles   –  Second  level   •  Third  level   –  Fourth  level   »  Fi8h  level  

Vessel Wall-Endhotelium

Action?  

Intact  endothelial  cells    

–  maintain   liquid   blood   flaster   ow  by   text  styles   •  Click   t o   e dit   M actively  inhibiting  platelet   adherence   –  Second  level   –  preventing  coagulation  factor  

activation   •  Third  level   –  lysing  blood  clot  that  may  form  

–  Fourth  level   Endothelial  cells  can  be  stimulated   »  Fi8h  level   by     –  direct  injury   –  by  various  cytokines  that  are   produced  during  inflammation.  

Stimulation  à  expression  of   procoagulant  proteins  e.g.  tissue   factor  and  vWf   -  contribute  to  platelet   aggregation  and  local  thrombus   formation  

In  a  normal  individual,   coagulation  is  initiated  within   20  seconds  after  an  injury   occurs  to  the  blood  vessel   damaging  the  endothelial  cells.    

Vessel Wall-Endhotelium à FIRST  RESPONSE   • à Goal:   Click  to  edit  Master  text  styles  

Second  bllood   evel   • – Minimizes   flow  

Third   level   to  i• njured   area   –  Fourth  level   •  Prevents  blood  loss   »  Fi8h  level   •  Delivers  platelets  and   plasma  proteins  to   the  vessel  wall   •  Immediate  and  short-­‐ lived  

Action?  

Primary Hemostasis? •  Click  to  edit  Master  text  styles   –  Second  level   •  Third  level   –  Fourth  level   »  Fi8h  level  

After  injury  platelets   come  in  contact  with   collagen  and  vWF   and  undergo  three   changes   –  Adhesion  and  shape   change   –  Secretion  or  release   reaction   –  aggregation  

Primary Hemostasis-Role

of Platelets

?  

¤  glycoproteins  Ia  (GP-­‐Ia)   which  binds  directly  to   collagen  and  (GP-­‐Ib)  which   binds  to  Von-­‐Willebrand   factor  (vWF)  in  plasma  

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¤  vWF  in  turn  adheres  to   collagen  à  following   adhesion  à  shape  change   from  disc  to  sphere   ¤  release  of  content  of   platelets  granules  (platelet   release):  ADP  &  serotonin   and  TXA2,  Platelet  derived   growth  factor,  Platelet   factor  4  

Primary Hemostasis-Role

of Platelets

?  

•  Click  to  edit  Master  text  styles   –  Second  level   •  Third  level   –  Fourth  level   »  Fi8h  level  

à ADP  leads  binding  of  fibrinogen  to  platelet  à  platelet  aggregation  à  forming  plug   at  site  of  injury.     à Also  of  normal  platelet  function  is  platelet  prostaglandin  synthesis  which  is  induced   by  platelet  activation  and  leads  to  formation  of  TXA2à  powerful  vasoconstrictor    

Primary Hemostasis-Role

of Platelets

?  

¤  As  a  result  of  platelet  aggregation;   platelet  factor-­‐3  is  released  which   intiates  blood  coagulation  ground   platelets  ,  thrombin  encourage  fusion   of  platelet  and  fibrin  formation   reinforce    stability  platelet  plug  

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¤  Contraction  of  protein  thrombosthenin   which  together  with  fibrin  around  form   hemostatic  plug.   ¤  Prostacyclin  (PGI2)  is  synthesized  in   vascular  endothelium  and  oppose  the   action  of  TXA2à  increase  level  of  cyclic   AMPà  preventing  platelet  aggregation   on  normal  vessel  wall  as  well  as  limiting   the  extent  of  platelet  plug  after  injury.  

Secondary Hemostasis-Coagulation Cascade? The  coagulation   •  Click  of  tso  econdary   edit  Master  text  styles   cascade   hemostasis  has  two   –  Second  level   pathways:   þ  the   ontact   level   • CThird   Activation  pathway   –  Fourth  level   (formerly  known  as   the  Intrinsic  »  Fi8h  level   Pathway)     þ  And  the  Tissue  Factor   pathway  (formerly   known  as  the   Extrinsic  pathway)   that  lead  to  fibrin   formation.  

Coagulation Cascade-Coagulation Factors

•  Click  to  eFactor   dit  M text  styles    I   aster    =  Fibrinogen   –  Second  Factor   level  II   • 

 =  Prothrombin   Factor  III    =  Tissue  thromboplastin   Third  level   Factor  IV    =  Ionisable  calcium     –  Fourth  level   Factor  V    =  Proaccelerin  or  labile  factor   »  Fi8h  level   Facto  VII    =  Proconvertin  or  stable  factor   Factor  VIII  =    Antihemophilic  factor  (hemophilia      A)  .   Factor  IX    =  Christmas  factor  (hemophilia  B)   Factor  X    =  Stuart  –  Power  factor     Factor  XI    =  Plasma  thromboplastin  antecedent   Factor  XII    =  Hageman  factor   Factor  XIII  =  Fibrin  Stablizing  factor.    

Coagulation Cascade-Coagulation Factors

•  Click  to  edit  Master  text  styles   –  Second  level   •  Third  level   –  Fourth  level   »  Fi8h  level  

Secondary Hemostasis-Coagulation Cascade?

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FIBRINOLYSIS -  Fibrinolytic  system  is  involved   in  fibrinolysis,  tissue  repair   and  vessel  rebirth.  

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-  It  helps  to  restore  vessel   •  Third   level  of   potency   by  dissolution   –  Fourth  level   fibrin.  

» rotein   Fi8h  level   -  Normal  plasma  p Plasminogen  (formed  in  the   liver)  is  converted  by   Plasminogen  activators   derived  from  plasma   endothelial  cells,  platelets,   leukocytes  and  urine  into   plasmin  

Blood coagulation and fibrinolysis

FIBRINOLYSIS Activation  by:  Plasminogen   activator  (extrinsic),  intrinsic,   exogenous.  

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2  types   Plasminogen   – of  Second   level   activator:  

•  Third  level  

•  Tissue  Plasminogen   Fourth   evel   activator  f– ormed   in  tlhe   vascular  endothelium   »  Fi8h  (lt-­‐PA).   evel   •  Tissue  Plasminogen   activator  formed  in  the   kidney  (Urokinase/u-­‐PA).   •  t-­‐PA  is  inactivated    by   Plasminogen  activator   inhibitor  I.     Intrinsic  à  factor  XIIa,  HMWK,   Kallikrein   Exogenous  à  Streptokinase  

(a). Process of hemostasis •  Click  to  edit  Master  text  styles   –  Second  level  

(b). The•  Third  level   synthesis – ofFourth  level   »  Fi8h  level   fibrin in blood clots

Secondary Hemostasis-Anti Intrinsic

Coagulant?

Extrinsic

thrombin

•  Click  to  edit  Master  text  styles   exposed TF –  Second   level   XI XIa •  Third   level   IX

–  Fourth  level   VIII VIIIa »  Fi8h  level  

TF VIIa

IXa

X protein C V

TFPI

Va

VII

ATIII Xa

prothrombin

thrombin

fibrinogen

fibrin

clot

THROMBOSIS à  Hemostasis  is  normally  beneficial  BUT  if  inappropriately  

•  Click  to  edit  Master  text  styles   activated  can  be  harmful  

–  Second  level  

à  Distinguish   etween  these  words   •  Third  lbevel   à  Thrombosis   (pathological)   :  A  solid  mass  of  blood  constituents   –  Fourth   level   [thrombus]   formed   within  the  a  vascular  lumen  during  life   »  Fi8h   level   à  Clot  :  A  solid  mass  of  blood  constituents  occurring  outside  the   vascular  tree  OR  after  death  within  the  vascular  tree  

angan

ekuan •  Click  to  edit  Master  text  styles  

uan/ kit

–  Second  level   •  Third  level   –  Fourth  level   »  Fi8h  level  

•  Click  to  edit  Master  text  styles   –  Second  level   •  Third  level  

Thank You –  Fourth  level   »  Fi8h  level