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Haematology and Transfusion Science > Homeostasis > Flashcards

Homeostasis Flashcards

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1
Q

What are the main functions of homeostasis regarding haematology?

A
  • blood in fluid state
  • confine blood to vascular bed.
  • arrest bleeding (haemostatic plug)
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2
Q

What does normal haemostasis involve?

A

Normal haemostasis physiology constitutes a delicate balance where any deficit or exaggeration could lead to either thrombosis or hemorrhage.

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3
Q

What are the 5 components of normal haemostasis?

A
  1. blood vessels (vascular system)
  2. Platelets
  3. Plasma coagulation factors
  4. Plasma coagulation inhibitors.
  5. Fibrinolytic system
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4
Q

What is the general role of the endothelium cell?

A

The prevention of blood clotting in vivo

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5
Q

What is the endothelium cell?

A

This is a single layer of cells on the lumen of vascular tissue.
blood clotting is controlled by the vascular endothelial cells and some of the substances present on these cells.

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6
Q

What are some of the substances on the endothelium cell which promote an anticoagulant environment?

A

Thrombomodulin and heparan sulphate.

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7
Q

What are some of the natural anticoagulants in the blood?

A

Antithrombin, protein C , protein S

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8
Q

Which enzyme inhibits platelet aggregation?

A

ADPase - breaks down ADP which is a platelet agonist.

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9
Q

Which two substances are platelet inhibitors?

A

Prostacyclin and nitric oxide.

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10
Q

Why is ADPase effective as an inhibitor of platelet aggregation?

A

As when platelets are activated aka coagulation, to be kept neutral (coagulation not needed) ADPase prevents the platelets from using ADP for aggregation.

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11
Q

Name a vasoconstrictor:

A

Serotonin

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12
Q

What is the first factor which is released from the exposure of the sub endothelial after vessel damage?

A

Tissue factor is released from the blood vessel into the area that is damaged

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13
Q

How is the physiological coagulation cascade activated?

A

When the tissue factor released by the damaged vessel is in the presence of phospholipid released from platelets this leads to the formation of the physiological blood coagulation cascade.

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14
Q

What is the role of thrombin and when is it released?

A

When the blood coagulation cascade begins, a large amount of it is produced. It has mainly enzymatic functions including converting soluble fibrin to insoluble fibrinogen which can aid and reinforce the development of the primary haemostatic plug = leading to a stable hemostatic plug.

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15
Q

What is the role of vasoconstrictors?

A

To minimise the blood going to a site of injury.

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16
Q

How to platelets adhere to the damaged vessel?

A

They adhere to the glycoprotein receptors in the sub endothelial cells of the damaged vessel. Join to collagen.

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17
Q

What does the aggregation of platelets lead to?

A

Primary haemostatic plug.

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18
Q

How do the coagulation factors from the tissue factor cascade interact with the platlets?

A

Coagulation factors use the laid down platelets as a membrane to lay down fibrin.

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19
Q

What is the role of the physiological coagulation cascade?

A

Their role involves activated coagulation factors that function in the generation of thrombin and formation of the fibrin clot. This is coagulation

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20
Q

What type of muscle do muscular arteries have?

A

Smooth muscle.

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21
Q

What type of muscle do elastic arteries have?

A

Collagen and elastic fibres.

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22
Q

What are vessels with muscular coats able to do after injury?

A

Contract, helping to arrest bleeding.
Release vasoconstrictores such as angiotensin II, this ensures that there is reduced blood flow which will assist in the eventual formation of a stable haemostatic plug.

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23
Q

What do endothelial cells contain that that helps in attempting to arrest bleeding?

A

Procoagulants and anticoagulant proteins that when released will play a balancing act in attempting to arrest bleeding.

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24
Q

What do the endothelial cells synthesis upon damage to the their vessel?

A

Tissue factor - which initiates coagulation.

Protein S and C

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25
Q

What are protein S and C examples of?

A

These are natural anticoagulants.

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26
Q

What is heparin sulphate and which cells synthesis it?

A

Endothelial cells synthesis it, it is a natural anticoagulant/antithrombin.

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27
Q

Which factor does the endothelial tissue produce?

A

Von Willebrand Factor.

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28
Q

What is Von Willebrand Factor?

A

It is essential for platelets for adhesion to the sub endothelial glycoprotein receptors.

29
Q

What is the sub endothelium consisting of?

A

Connective tissue, collage, elastic tissues, proteoglycans, non collagenous glycoproteins and VWF - after damage = exposed ….. available to enable platelet adherence.

30
Q

What are platelets made up of?

A

They are produced in the marrow by fragmentation of the cytoplasm of megakaryocytes.

31
Q

Which precursor did thrombocytes arise from in thrombopoiesis? How long does differentiation take?

A

CFU - GEMM

10 days

32
Q

How many platelets does one megakaryocyte give rise to?

A

1000-5000

33
Q

What is thrombopoietin?

A

It is a platelet growth factor and is a major growth regulator of platelet production and is mainly found in the liver and kidneys.

34
Q

What do platelets contain?

A
  • granules (pro coagulant and anticoagulant factors)
  • thromboxane A2 = powerful vasoconstrictor.
  • glycoprotein receptors (activated coagulation factors bind - thrombin )
35
Q

What is thromboxane A2?

A

A powerful vasoconstrictor.

36
Q

What does platelet function consist of?

A

Adhesion, activation and aggregation (triple a)

37
Q

What two components lead to normal circulatory platelet function?

A

Nitric oxide, prostacylin

38
Q

What is step one of platelet function in homeostasis?

A

adhesion - platelets adhere to collagen fires at the site of injury

39
Q

What is the second step of platelet function in homeostasis?

A

activation - change in platelet shape - activation, release of procoagulant molecules from granules

40
Q

What are some examples of procoagulant granule molecules?

A

TXA2, ADP, VWF, serotonin, phospholipid, platelet factor 3

41
Q

What do the procoagulant granules provide for the platelets?

A

A surface for the reactions of the coagulation factors in the physiological coagulation cascade

42
Q

What is step three of the platelet function in homeostasis?

A

Platelet aggregation - this is where a primary aggregation (reversible) and secondary aggregation (irreversible) take place

43
Q

What is the product of the platelet aggregation step?

A

A primary haemostatic plug.

44
Q

What do activated platelets produce and what is its function?

A

Thromboxane A2 which is a powerful vasoconstrictor.

45
Q

What reduces the level of platelet aggregation?

A

Aspirin and clonotril

46
Q

Upon vessel injury and exposure of the sub endotherlium, circulating platelets bind to which blood vessel surface glycoproteins?

A

Gp 1a

Gp 1b

47
Q

What happens to platelets when they bind to the blood vessel surface glycoproteins?

A

They undergo shape change, become spherical, extending pseudopods.
Intracellular granules are moved to surface and release of content into microenvironment.
Mediated by mobilization of calcium and activation of platelets.

48
Q

What helps binding of the surface glycoproteins, present on the platelet membrane ?

A
  • collagen
  • VWF
  • fibrinogen
49
Q

What is the function of VWF?

A
  • binds platelets to sub endothelial

- carries coagulation factor 8 (haemophilia A)

50
Q

What does soluble fibrinogen convert to?

A

Fibrin.

51
Q

What are the advantages to the platelet surface membrane being invaginated?

A
  • increases surface area for release of contents of intracellular granules.
52
Q

What do alpha granules contain?

A

A variety of haemostatic proteins including PDGF, vWF, fibrinogen and fibrinolytic proteins.

53
Q

What is PDGF?

A

Platelet derived growth factor

54
Q

Which glycoprotein binds directly to collagen?

A

Glycoprotein 1a.

Permits direct adhesion.

55
Q

What are the glycoproteins which when attached to the vWF adhere to the subendothelium?

A

1b, 2b, 3a

56
Q

Where is vWF synthesised and stored?

A

It is synthesised in the endothelial cells and megakaryocytes.
Stored in Weibel Palade bodies and platelet alpha granules.

57
Q

Who discovered the blood coagulation factors?

A

Morawitz

58
Q

What is the simple equation of blood clot development?

A

Prothrombin + calcium + tissue thromboplastin = Thrombin, Thrombin + fibrinogen = fibrin clot.

59
Q

What is the role of thrombin?

A

Converts fibrinogen to fibrin.

60
Q

What is the coagulation pathway dependent on ?

A

Activated coagulation factors (enzymes), some are known as serine proteases or serine endopeptidases.

61
Q

What are serine proteases or serine endopeptidases?

A

These are a class of peptidase enzymes that cleave peptide bonds in proteins, they are characterized by the presence of a serine residue in the active centre o f the enzyme.

62
Q

What are some examples of serine proteases in coagulation?

A

Factor: II, IX, X

63
Q

What is factor III?

A

Calcium

64
Q

What is the lacking factor in haemophilia B?

A

Factor 9 or the Christmas Factor.

65
Q

What is factor 15?

A

Fibrin Stabilising factor.

66
Q

What stages are involved in the generation of thrombin following vascular injury?

A

Initiation
Amplification
Propagation
IAP

67
Q

What happens during the initiation phase of post thrombin formation?

A

Small amounts of thrombin are generated which prepares the coagulation cascade for the amplification and propagation phases which sees a thrombin burst and conversion of fibrinogen to fibrin.

68
Q

Which factor strengthens the thrombin?

A

By the transamidase which crosslinks fibrin clot = action of factor 13, fibrin stabilising factor - reinforces the clot

69
Q

What activated factor 15?

A

Thrombin.

Haematology and Transfusion Science (18 decks)

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