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Immunology and Haematology > Homeostasis > Flashcards

Homeostasis Flashcards

1
Q

What produces the substances that ensures blood stays liquid?

A

Endothelium

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2
Q

What substances does the endothelium produce to keep blood liquid?

A
  • Heparins
  • Tissue factor pathway inhibitor (TFPI)
  • Thrombomodulin
  • Nitric oxide
  • Prostacyclin
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3
Q

What does TFPI stand for?

A

Tissue factor pathway inhibitor

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4
Q

What can become activated to turn blood solid when required?

A

Platelets and coagulation factors

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5
Q

Describe the process after you injure yourself and bleed?

A
  • 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
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6
Q

Describe the process that follows the endothelium becoming damaged?

A

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
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7
Q

What do platelets and vWF bind to to become activated?

A

Collagen (below endothelium)

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8
Q

Of the platelet and fibrin plug, which is formed first?

A

Platelet plug and then fibrin plug

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9
Q

What is found on the surface of platelet cells?

A
  • 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
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10
Q

What system is found inside platelet cells?

A
  • 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’
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11
Q

What do alpha granules in platelets release?

A
  • Alpha granules – release vWF and thrombin
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12
Q

What do dense granules inside platelets release?

A
  • Dense granules – release ADP/ATP, calcium and serotonin
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13
Q

The open canalicular system makes platelets sticky, what does this allow?

A

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
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14
Q

Summarise platelets role in homeostasis?

A
  • 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
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15
Q

What does vWF stand for?

A

von Willebrand factor

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16
Q

What is vWF?

A

Sticky molecule that binds to:

  • FVIII
  • Heparin
  • Collagen
  • Platelet
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17
Q

What does formation of the fibrin clot occur after?

A

Formation of primary platelet clot

18
Q

Describe the process for the formation of the fibrin clot?

A
  1. Fibrinogen is attached to platelet
  2. Fibrinogen cleaved to form fibrin
19
Q

What is fibrinogen cleaved to form?

A

Fibrin

20
Q

What is done to allow fibrinogen to be cleaved to fibrin?

A

This is achieved by coagulation cascade:

  • Uses clotting agents
    • Factor XII
    • Factor XI
    • Factor IX
    • Factor VIII
    • Prothrombin
    • Fibrinogen
21
Q

List some important clotting agents?

A

This is achieved by coagulation cascade:

  • Uses clotting agents
    • Factor XII
    • Factor XI
    • Factor IX
    • Factor VIII
    • Prothrombin
    • Fibrinogen
22
Q

What are the most important anticoagulants?

A
  • 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
23
Q

What does TFPI do?

A
  • Inhibits factor VIIa and Xa to stop formation of thrombin
24
Q

What does protein C and protein S do?

A
  • Binds to co-factor protein S
  • Which switches of factors Va and VIIIa to reduce thrombin formation
25
Q

What does antithrombin (AT) do?

A
  • Inhibits many coagulation factors: Xa and thombin most important
26
Q

When the clots purpose is done, what happens to it?

A

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
27
Q

Describe the mechanism of fibrinolysis?

A
  • 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
28
Q

What are the activators of plasminogen and what are they secreted by?

A
  • Endothelial cell secretes activators of plasminogen
    • t-PA
    • u-PA
29
Q

What is formed when plasmin breaks down the clot?

A
  • Plasmin breaks down clot
    • Forms fibrin degradation products (FDP) such as d-dimer
30
Q

What does FDP stand for?

A

Fibrin degradation products

31
Q

What are some inhibitors of plasminogen?

A
  • PA1-1
  • PA1-2
32
Q

What are some inhibitors of plasmin?

A
  • A2 – antiplasmin
  • A2 – macroglobulin
33
Q

What are some methods drugs use to inhibit platalet activation?

A
  • 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
34
Q

List some drugs that inhibit platelet activation?

A
35
Q

List some drugs that inhibit coagulation?

A
  • 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
  • Factor Xa inhibitors
    • Drugs
      • Rivaroxaban, edoxaban, apixaban
    • Mechanism
      • Sit on active site of factor Xa, preventing cleavage of prothrombin into thrombin
  • Direct thrombin inhibitors
    • Drugs
      • Dabigatran
      • Bivalirudin/argatroban
    • Mechanism
      • Inhibits thrombin, preventing cleavage of fibrinogen to fibrin and preventing clot formation
36
Q

What is warfarin?

A
  • Vitamin K antagonist
  • Vitamin K required for post-translational modification of factors II, VII, IX and X
37
Q

For heparin:

  • drugs
  • mechanism
A
  • 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
38
Q

What does LMWH stand for?

A

Low molecular weight heparin

39
Q

For factor Xa inhibitors:

  • drugs
  • mechanism
A
  • Drugs
    • Rivaroxaban, edoxaban, apixaban
  • Mechanism
    • Sit on active site of factor Xa, preventing cleavage of prothrombin into thrombin
40
Q

For direct thrombin inhibitors:

  • drugs
  • mechanism
A

Immunology and Haematology (23 decks)

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