Immunology and Haematology > Homeostasis > Flashcards

Homeostasis Flashcards

(40 cards)

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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?

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A

Formation of primary platelet clot

18
Q

Describe the process for the formation of the fibrin clot?

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

What is fibrinogen cleaved to form?

20
Q

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

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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?

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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?

Study These Flashcards
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?

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

What does protein C and protein S do?

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A
  • Binds to co-factor protein S
  • Which switches of factors Va and VIIIa to reduce thrombin formation
25
What does antithrombin (AT) do?
* Inhibits many coagulation factors: Xa and thombin most important
26
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
27
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
28
What are the activators of plasminogen and what are they secreted by?
* Endothelial cell secretes activators of plasminogen * t-PA * u-PA
29
What is formed when plasmin breaks down the clot?
* Plasmin breaks down clot * Forms fibrin degradation products (FDP) such as d-dimer
30
What does FDP stand for?
Fibrin degradation products
31
What are some inhibitors of plasminogen?
* PA1-1 * PA1-2
32
What are some inhibitors of plasmin?
* A2 – antiplasmin * A2 – macroglobulin
33
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
34
List some drugs that inhibit platelet activation?
35
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 * **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
What is warfarin?
* Vitamin K antagonist * Vitamin K required for post-translational modification of factors II, VII, IX and X
37
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
38
What does LMWH stand for?
Low molecular weight heparin
39
For factor Xa inhibitors: - drugs - mechanism
* Drugs * Rivaroxaban, edoxaban, apixaban * Mechanism * Sit on active site of factor Xa, preventing cleavage of prothrombin into thrombin
40
For direct thrombin inhibitors: - drugs - mechanism
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