Homeostasis Flashcards
What produces the substances that ensures blood stays liquid?
Endothelium
What substances does the endothelium produce to keep blood liquid?
- Heparins
- Tissue factor pathway inhibitor (TFPI)
- Thrombomodulin
- Nitric oxide
- Prostacyclin
What does TFPI stand for?
Tissue factor pathway inhibitor
What can become activated to turn blood solid when required?
Platelets and coagulation factors
Describe the process after you injure yourself and bleed?
- Bleed at site of injury
- Bleeding then stops when clot is formed
- Platelets, Von Willebrand Factor (vWF), coagulation factors
- Clot remains confined to site of injury
- Natural anticoagulants
- 1 week later clot gone
- Fibrinolytic system
Describe the process that follows the endothelium becoming damaged?
When blood vessel walls is damaged resting platelets and coagulation factors become activated, initiated by:
- Platelets and vWF binding to collagen (below endothelium) and become activated
- Forming primary haemostatic (platelet) plug
- Physiological activator (tissue factor) released from blood vessel initiating coagulation cascade
- Allows formation of following fibrin plug
What do platelets and vWF bind to to become activated?
Collagen (below endothelium)
Of the platelet and fibrin plug, which is formed first?
Platelet plug and then fibrin plug
What is found on the surface of platelet cells?
- Cell surface receptors – these attach on trauma and activate platelet
- ADP receptor
- Epinephrine receptor
- Thrombin receptor
- Platelet glycoproteins
- Bind to ligands such as fibrinogen and vWF and collagen
What system is found inside platelet cells?
- Open canalicular system
- Allows granules to open and excrete onto surface of platelets
- Alpha granules – release vWF and thrombin
- Dense granules – release ADP/ATP, calcium and serotonin
- This makes it ‘sticky’
- Allows granules to open and excrete onto surface of platelets
What do alpha granules in platelets release?
- Alpha granules – release vWF and thrombin
What do dense granules inside platelets release?
- Dense granules – release ADP/ATP, calcium and serotonin
The open canalicular system makes platelets sticky, what does this allow?
This allows platelets to bind to:
- Firstly the collagen and vWF
- vWF also binded to collagen
- Then changes conformation, allowing fibrinogen to bind which binds red cells
Summarise platelets role in homeostasis?
- Adhere
- To collagen and vWF
- Activation
- ADP pathway
- COX pathway
- Aggregation
- Enzyme scramblase allows phosphides to be exposed on cell external surface instead of normal internal
What does vWF stand for?
von Willebrand factor
What is vWF?
Sticky molecule that binds to:
- FVIII
- Heparin
- Collagen
- Platelet
What does formation of the fibrin clot occur after?
Formation of primary platelet clot
Describe the process for the formation of the fibrin clot?
- Fibrinogen is attached to platelet
- Fibrinogen cleaved to form fibrin
What is fibrinogen cleaved to form?
Fibrin
What is done to allow fibrinogen to be cleaved to fibrin?
This is achieved by coagulation cascade:
- Uses clotting agents
- Factor XII
- Factor XI
- Factor IX
- Factor VIII
- Prothrombin
- Fibrinogen
List some important clotting agents?
This is achieved by coagulation cascade:
- Uses clotting agents
- Factor XII
- Factor XI
- Factor IX
- Factor VIII
- Prothrombin
- Fibrinogen
What are the most important anticoagulants?
- TFPI
- Inhibits factor VIIa and Xa to stop formation of thrombin
- Protein C and S
- Binds to co-factor protein S
- Which switches of factors Va and VIIIa to reduce thrombin formation
- Antithrombin (AT)
- Inhibits many coagulation factors: Xa and thombin most important
What does TFPI do?
- Inhibits factor VIIa and Xa to stop formation of thrombin
What does protein C and protein S do?
- Binds to co-factor protein S
- Which switches of factors Va and VIIIa to reduce thrombin formation
What does antithrombin (AT) do?
- Inhibits many coagulation factors: Xa and thombin most important
When the clots purpose is done, what happens to it?
When purpose is done, clot later broken down by fibrinolysis:
- Endothelial cell secretes activators of plasminogen
- t-PA
- u-PA
- These cleave plasminogen to make plasmin (makes has action)
- Plasmin breaks down clot
- Forms fibrin degradation products (FDP) such as d-dimer
- Inhibitors of plasminogen
- PA1-1
- PA1-2
- Inhibitors of plasmin
- A2 – antiplasmin
- A2 – macroglobulin
Describe the mechanism of fibrinolysis?
- Endothelial cell secretes activators of plasminogen
- t-PA
- u-PA
- These cleave plasminogen to make plasmin (makes has action)
- Plasmin breaks down clot
- Forms fibrin degradation products (FDP) such as d-dimer
- Inhibitors of plasminogen
- PA1-1
- PA1-2
- Inhibitors of plasmin
- A2 – antiplasmin
- A2 – macroglobulin
What are the activators of plasminogen and what are they secreted by?
- Endothelial cell secretes activators of plasminogen
- t-PA
- u-PA
What is formed when plasmin breaks down the clot?
- Plasmin breaks down clot
- Forms fibrin degradation products (FDP) such as d-dimer
What does FDP stand for?
Fibrin degradation products
What are some inhibitors of plasminogen?
- PA1-1
- PA1-2
What are some inhibitors of plasmin?
- A2 – antiplasmin
- A2 – macroglobulin
What are some methods drugs use to inhibit platalet activation?
-
Inhibit ADP (also called P2Y12) pathway
- Clopidogrel
- Prasugrel
- Ticagrelo
-
Inhibits production of thromboxane – preventing aggregation
- Aspirin
-
Inhibits glycoprotein IIb/IIIa receptor (normally binds to fibrinogen)
- Abciximab
- Tirofaban
- Eptifibatide
List some drugs that inhibit platelet activation?
List some drugs that inhibit coagulation?
-
Warfarin
- Vitamin K antagonist
- Vitamin K required for post-translational modification of factors II, VII, IX and X
-
Heparins
- Drugs
- Fracturated heparins
- Low molecular weight heparin (LMWH)
- Same molecule but with side chain cleaved off
- Mechanism
- Binds to antithrombin, allowing antithrombin to cleave thrombin and activated factor Xa quicker
- Drugs
-
Factor Xa inhibitors
- Drugs
- Rivaroxaban, edoxaban, apixaban
- Mechanism
- Sit on active site of factor Xa, preventing cleavage of prothrombin into thrombin
- Drugs
-
Direct thrombin inhibitors
- Drugs
- Dabigatran
- Bivalirudin/argatroban
- Mechanism
- Inhibits thrombin, preventing cleavage of fibrinogen to fibrin and preventing clot formation
- Drugs
What is warfarin?
- Vitamin K antagonist
- Vitamin K required for post-translational modification of factors II, VII, IX and X
For heparin:
- drugs
- mechanism
- Drugs
- Fracturated heparins
- Low molecular weight heparin (LMWH)
- Same molecule but with side chain cleaved off
- Mechanism
- Binds to antithrombin, allowing antithrombin to cleave thrombin and activated factor Xa quicker
What does LMWH stand for?
Low molecular weight heparin
For factor Xa inhibitors:
- drugs
- mechanism
- Drugs
- Rivaroxaban, edoxaban, apixaban
- Mechanism
- Sit on active site of factor Xa, preventing cleavage of prothrombin into thrombin
For direct thrombin inhibitors:
- drugs
- mechanism
