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CVS & IBL - Physiology 🫁 > L2: Physiological basis of haemostatic mechanisms > Flashcards

L2: Physiological basis of haemostatic mechanisms Flashcards

1
Q

What is the definition of hemostasis?

A

Prevention of blood loss after injury.

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2
Q

What are the steps of hemostasis?

A
  • Vascular spasm: occurs immediately after the blood vessel has been cut
  • Formation of a platelet plug (temporary hemostatic plug).
  • Formation of a blood clot (definitive hemostatic plug).
  • Fibrosis of the blood clot to close the hole in the vessel permanently.
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3
Q

What does vascular constriction result from?

A
  • Nervous reflexes are initiated by the pain from the traumatized vessel.
  • Local myogenic contraction due to direct damage.
  • Local vasoconstrictor factors as serotonin and thromboxane A2 (from platelets).
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4
Q

What causes more constriction to the vascular walls?

A

Transverse cut & traumatized vessels “nervous reflex”

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5
Q

What is the function of vascular spasms in blood clotting?

A

The vascular spasm reduces the flow of blood from the vessel rupture.

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6
Q

What is the functional structure of the platelet membrane?

A

☺ It is extensively invaginated membrane with a complex canalicular system that allow contact with the ECF.

☺ Contain a coat of glycoprotein
• Repulses adherence to normal endothelium
• Allow adherence to the injured vessel wall.

☺ Contains large amounts of phospholipids
• Play several roles in the process of blood clotting.

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7
Q

What is the Functional structure of the platelets cytoplasm?

A

Contains many active structures as:
- Contractile proteins for platelet contraction as actin, myosin, and thrombosthenin

  • Residual of both endoplasmic reticulum and Golgi apparatus for synthesis of enzymes and storage of Ca2+.
  • Mitochondria
    • Can form ATP & ADP.
  • Enzyme system
    • Can synthesize prostaglandins
  • Clotting factors as fibrin-stabilizing & von Willebrand factors
  • A growth factor that helps repair damaged vessel walls.
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8
Q

What are the steps of the formation of the platelet plug?

A

Platelet adhesion
Platelet activation
Platelet aggregation

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9
Q

What is the adhesion of platelets potentiated by?

A

Such adhesion is potentiated by the von Willebrand factor (a glycoprotein presents in the plasma and subendothelial tissue) and the platelets membrane glycoprotein

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10
Q

When do platelets adhesion take place?

A

When a blood vessel is injured, the platelets adhere to the exposed subendothelial collagen.

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11
Q

What initiates platelet activation?

A

Initiated by platelet adhesion.

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12
Q

What happens in platelet activation?

A
  • The activated platelets swell, develop pseudopodia, become sticky, and discharge their granules mainly ADP.
  • Also, its enzyme system is activated to form thromboxane A2. “VC”
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13
Q

What happens in platelet aggregation?

A
  • The released ADP and thromboxane –A2 activate the nearby platelets, Making them stickier and adhere to the originally activated platelets and release ADP and thromboxane – A2 which, in turn, activates more and more platelets.
  • Thus, a vicious circle of platelets activation and aggregation is elicited leading to the formation of a loose platelet plug. “Purpura is due to non-formation or non-function of platelets”
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14
Q

What is the effect of salicylates (aspirin) on blood clotting?

A

Salicylates (aspirin) can inhibit the thromboxane –A2 formation and so inhibits platelets activation and aggregation.

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15
Q

What is the importance of platelet plugs?

A

Platelet plugs are extremely important for closing the minute ruptures occurring in the wall of vessels many thousand times daily

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16
Q

What is the duration of blood clot formation?

A

The active process occurs within 3-6 minutes.

17
Q

What does blood clot formation need?

A
  • The clotting process is initiated by active substances from the traumatized vascular wall, platelets, and coagulation factors.
  • The clotting process to occur, certain factors named clotting factors (plasma protein of beta globulin type) must be activated.
18
Q

What are the clotting factors?

A
  • Plasma proteins of beta globulin type, are proteolytic enzymes present in an inactive form
19
Q

Give examples of the clotting factors.

A

Factor I: Fibrinogen

Factor II: Prothrombin

Factor III: Tissue thromboplastin

Factor IV: Calcium ions (Ca++)

Factor V: Proaccelerin or labile factor

  • ——- Prekallikrein
  • ——- HMW kininogen
  • ——- Platelets F3

Factor VII: Proconvertin or stable factor

Factor VIII: Antihaemophilic factor

Factor IX: Christmas factor

Factor X: Stuart prewar factor

Factor XI: Plasma thromboplastin antecedent

Factor XII: Hegeman factor

Factor XIII: Fibrin stabilizing factor

20
Q

What are the steps of clot formation?

A

 Formation of prothrombin activator
 Conversion of prothrombin into thrombin
 Conversion of fibrinogen into fibrin

21
Q

What initiates the extrinsic pathway?

A

It is initiated by contact of blood with traumatized vascular walls or extra-vascular tissues.

22
Q

Mentions steps of the extrinsic pathway.

A

It is a rapid process and occurs according to the following steps:
- Traumatized tissues release a complex of several factors called tissue thromboplastin (composed of phospholipids and lipoprotein that functions as a proteolytic enzyme).

  • The lipoprotein of tissue thromboplastin activates factor VII and then complexes with it.
    • This complex in the presence of Ca2+ and tissue
    phospholipids act on factor X to form activated factor X
  • Formation of the prothrombin activator.
    • The activated factor X complexes immediately with the
    tissue phospholipids, Ca2+and with activated factor V to form the complex called prothrombin activator.
23
Q

What initiates the intrinsic pathway?

A

It begins with trauma to the blood itself or exposure of the blood to collagen from a traumatized vessel wall or contact of the blood with water – wettable surface e.g., glass.

24
Q

What are the steps of the intrinsic pathway?

A

It continues through the following series of cascading reactions:
1) Trauma to the blood or exposure of the blood to vascular wall collagen “slow blood flow, roughy intima”

2) leads to 2 effects; first, activation of factor XII; second, the release of platelet phospholipids (platelet factor 3 or PF3).

3) The activated factor XII activates factor XI.
• This reaction requires high molecular weight kininogen
(HMW) and is accelerated by prekallikrein

4) The activated XI acts on factor IX to activate it.
5) The activated factor IX together with factor VIIIa and platelet phospholipids (PF3) activate factor X.
6) The activated factor X combines with activated factor V, Ca2+, and platelets phospholipids to form the prothrombin activator

25
Q

Compare between the extrinsic and intrinsic pathway of blood clotting in terms of duration and site

A

In vivo, 15-20 sec

In vivo and vitro, 3-6 min

26
Q

What are the steps of conversion of prothrombin into thrombin?

A

After the prothrombin activator has been formed, it causes the conversion of prothrombin to thrombin in the presence of sufficient amounts of Ca2+.

27
Q

What are the steps of conversion of fibrinogen into fibrin?

A
  • Formed thrombin removes 4 low-molecular-weight peptides from each molecule of fibrinogen, forming a molecule of fibrin monomer.
  • Many fibrin monomer molecules polymerize within seconds into long fibrin threads that constitute the meshwork of the clot.
  • Within a few minutes after the clot is formed a substance called fibrin stabilizing factor, released from the platelets, strengthens the fibrin meshwork by adding more and more bonds between the fibrin monomer molecules and formation of multiple cross-linkages between the fibrin thread.
  • Finally, the firm blood clot is formed which is composed of a meshwork of fibrin threads running in all directions and entrapping blood cells, platelets, and plasma.
28
Q

What is the fate of the clot?

A
  • It can become invaded by fibroblasts, which subsequently form connective tissue till the clot is completely organized into fibrous tissue within about 1 to 2 weeks. “Permanent healing”
    • This course usually happened with the clot that is formed in a small hole in the vessel wall.
  • It can dissolve:
    • This usually occurs with the clots formed in the tissues.
29
Q

What is the role of calcium in clotting mechanisms?

A
  • Except for the first two steps in the intrinsic pathway, Ca2+ is required for acceleration of all the blood clotting reactions.
  • Therefore, in the absence of Ca2+, blood clotting by either pathway does not occur.
30
Q

How is blood removed from a person prevented from clotting?

A

either by de-ionizing the calcium by addition of citrates or by precipitating the calcium by oxalates.

31
Q

What is the importance of vitamin K in blood clotting?

A

Vitamin K “from the colon” is necessary for the liver formation of five important clotting factors, prothrombin, factor VII, Factor IX, Factor X, and protein C. “1972”

32
Q

What happens in cases of absence of vitamin K?

A

In the absence of vitamin K, deficiency of these coagulation factors results in serious bleeding tendencies (so it is called antihemorrhagic vitamin).

33
Q

Why are platelets important for clot retraction?

A
  • They become attached to the fibrin threads in a way that they bind different threads together.
  • Platelets secrete fibrin stabilizing factor (factor XII) which causes more cross-linking bonds between the fibrin threads.
  • Activation of the platelet contractile proteins by thrombin and Ca2+ cause strong contraction of the platelet attached to the fibrin.
34
Q

What is the importance of clot retraction?

A

the edges of the broken blood vessels are pulled together, thus contributing to the ultimate state of hemostasis.

35
Q

What happens after a clot is formed?

A

After a clot is formed, it begins to contract & a clear yellowish fluid is squeezed called serum

36
Q

What are the functions of platelets in hemostasis?

A

1) Induces vascular spasm (serotonin & thromboxane A2)
2) Formation of primary platelet plug
3) Release of platelets phospholipid (Pf 3) which is essential for clotting mechanism.
4) Stabilization of blood clot (fibrin – stabilizing factor)
5) Clot retraction (Ca2+).
6) Repair of damaged vessels wall (platelet-derived -growth factor)

CVS & IBL - Physiology 🫁 (12 decks)

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