semester 2: L6: Blood- Mechanisms of Homeostasis Flashcards

1
Q

What is Haemostasis?

A

process of stopping bleeding

keep blood within the damaged vessel

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2
Q

What are the three steps of Haemostasis?

A

Vasoconstriction
Formation of platelet plug
Blood coagulation

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3
Q

What occurs in endothelium damage?

A

Collagen becoming exposed is the trigger for the platelets to come
The platelets activate and come to the site
The platelets aggregate and activation of Coagulation occurs
Thrombin is formed, which works with fibrinogen to form fibrin
Fibrin is a mesh which is constructed to form fibrin polymers
it is then retracted (ripped apart) forming fibrin fragments

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4
Q

What are platelets?

A

Produced in the bone marrow from megakaryocytes
Cytoplasmic extensions on the cell surface break off
anucleate
Smaller than red blood cells, colourless
Cytoplasm contains mitochondria, SER,
Granules (dense, alpha and lysosomal)

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5
Q

what role does serotonin and 5-HT receptors play in platelet aggregation?

A

vasoconstrictor

platelet activation and aggregation

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6
Q

What is platelet activating factor involved in?

A
platelet activation and aggregation
converts memb phospholipids to thromboxane A2
thromboxane A2 vasoconstrictor
increases capillary permeability
inflammation
also from monocytes and neutrophils
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7
Q

How is ADP involved in platelet activation?

A

from platelet mitochondria
platelet activation and aggregation
Vasoconstriction and platelet plug formation

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8
Q

How is the platelet plug formed?

A

all the factors involved in the activation of platelets lead to the production of loose platelet clumping, which causes vasoconstriction at the same time
This results in the temporary haemostatic plug
The temporary haemostatic plug is formed before the definitive haemostatic plug

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9
Q

What is the von Willebrand factor?

A

primary function is to bind to other proteins, mainly factor VIII (8)

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10
Q

What is Weibel palade?

A

These are bodies in endothelial cells that release von Willebrand Factor

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11
Q

Why don’t all platelets clump?

A

This is due to Nitric oxide
Nitric Oxide inhibits the platelet activation,
It also is a potent vasodilator

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12
Q

Which factors is Calcium involved in helping?

A

Factors; VII (7),
X (10),
IX (11),
II (prothrombin)

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13
Q

How does the Extrinsic Pathway of coagulation begin?

A

Set off by the tissue factor released in the endothelial cells, due to endothelial damage

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14
Q

How does the Intrinsic Pathway of coagulation begin?

A

Set off by the exposure of collagen due to endothelial damage, in which activates factor XII (12)

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15
Q

Where do the two pathways meet?

A

At Thrombin

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16
Q

What does Thrombin convert Fibrinogen into?

A

Fibrin Polymers

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17
Q

What do factors 2, 7, 9, 10 contain?

A

Contain vitamin K-dependent g-carboxyglutamate (Gla) residues

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18
Q

How do zymogens become active factors?

A

This is through the binding of calcium to the Gla residues

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19
Q

How do factors V, and VIII (8) become activated?

A

By thrombin

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20
Q

How does factor II change when activated?

A

Inactive factor II is Prothrombin, and when activated by Xa it becomes Thrombin

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21
Q

What things have to come together in order to activate factor 2?

A

Ca2+, factor Va, factor Xa and prothrombin

Prothrombinase complex

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22
Q

What does the prothrombinase complex combine with in order to drive Thrombin?

A

Complexes with Phosphatidylserine (PS) and Phosphatidylinositol (PI) on platelet surface

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23
Q

How does factor V play a part?

A

If body senses low concentrations of thrombin, factor V will activate

If the body senses there is enough thrombin concentration, Factor V will be cleaved

24
Q

What exactly converts prothrombin to Thrombin?

A

Factor Xa and Factor Va and Ca2+ ions

25
What does Thrombin regulate?
Clot formation
26
How is a clot (thrombus) formed?
Platelet plug forms rapidly Exposed collagen activates intrinsic pathway Tissue factor in exposed sub-endothelial tissues activates extrinsic pathway Thrombin activates platelets, factors XI, VIII and V Fibrin forms clot, enmeshing platelets and erythrocytes
27
What is Tissue factor pathway inhibitor (TFPI)?
Plasma protein | Binds to TF/factor VIIa complex
28
What is Thrombomodulin?
Endothelial surface receptor protein Binds thrombin Complex activates protein C, which complexes with protein S and inactivates factor Va and factor VIIIa
29
What is Antithrombin III?
Plasma protein Binds to heparin on endothelial surface Blocks factors IX (9), X (10), X1 (11), XII (12), Thrombin, Kallikrein
30
What is fibrinolysis?
Clot dissolution
31
What is a fibrin clot removed by?
fibrinolytic system
32
What is Plasminogen?
Plasma protein | Cleaved by tissue plasminogen activator (tPA) to form plasmin
33
What is tPA (tissue plasminogen activator)?
Secreted by endothelium | Activated by fibrin
34
How does Thrombosis develop?
Blood clotting occurs within intact vessels Activated by atheroma Can result from hypercoagulability or bacterial infection
35
What diseases can thrombosis lead to?
Coronary thrombosis=myocardial infarction Stroke Pulmonary embolism Deep vein thrombosis (DVT)
36
What is the treatment for thrombosis?
Aspirin (inhibits TxA^2 formation) Anti-platelet drugs (prevent aggregation/activation) Anticoagulants (heparin; vitamin K antagonists, e.g. warfarin) Thrombolytic agents (recombinant tPA, streptokinase)
37
What is von Willebrand’s disease?
Abnormal bruising and mucosal bleeding | Due to genetic deficiency of von Willebrand factor
38
What is Haemophilia?
Soft tissue bleeding and bleeding into joints | Due to genetic deficiency of factor VIII (haemophilia A) or factor IX (haemophilia B)
39
What is severe liver disease?
Deficiency of coagulation factors, reduced absorption of vitamin K
40
What treatments are there for Severe liver disease, Haemophilia, and von Willebrand’s disease?
Treat with procoagulants; | Vitamin K, desmopressin
41
What is Inflammation?
Response to injury or infection Eliminate pathogen Repair tissue
42
What are cell derived mediators of inflammation?
``` Prostaglandins Leukotrienes Histamine Platelet-activating factor ATP 5-HT (serotonin) ```
43
What is plasma derived mediators of inflammation?
Bradykinin | Complement fragments
44
What are neurotransmitter mediators of inflammation?
Substance P | Calcitonin gene-related peptide (CGRP)
45
What is arachidonic acid important in?
The formation Prostoglandin, and Thromboxane A^2, and Leukotriene
46
How is bradykinin formed?
Prekalikrein is activated by factor 12 to form kalikrein. Kalikrein is involved in formation Bradykinin Bradykinin is a Vasodilator and allows the WBC in to help the inflammatory process Bradykinin is inactivated by angiotensin-converting enzyme
47
What are Substance P and CGRP?
they are localised in sensory nerves innervating blood vessels vasoactive neuropeptides roles in inflammatory and cardiovascular disease effects on microvascular tone and permeability recovery of microcirculation during wound healing phases
48
What is Tissue injury?
Injury due to trauma or immune hypersensitivity reactions Damage to blood vessels therefore, contact of blood with sub-endothelial and extravascular tissues Damaged endothelium and activated platelets ATP, 5-HT (serotonin) and TxA2 Damaged cells produce prostaglandins Bradykinin formed
49
What do sensory neuropeptides release?
Substance P | Calcitonin gene-related peptide (CGRP)
50
Give examples of tissue mast cells in which neuropeptides stimulate degranulation of?
Histamine (vasodilator) | PGD2, LTD4 (leukocyte chemoattractants)
51
What is complement system activated by?
contact of blood with tissues | The blood contains C3a and C5a (leukocyte chemoattractants)
52
What issues can arise from bradykinin and postglandins sensitising sensory nerves?
Hyperalgesia Pain response Itch response
53
What happens in Rubor?
Vasodilation leads to increased local blood flow | histamine, PGE2
54
What happens with a disorder like Calor?
Vasodilation | Stimulation of sensory nerves (ATP, PGs, 5-HT, bradykinin)
55
What happens within a Tumor?
Increased vascular permeability (histamine, LTD4, bradykinin, CGRP)
56
What happens within a Dolor?
Stimulation of sensory nerves (ATP, PGs, 5-HT, bradykinin)
57
What is the end result of inflammation?
Increased blood flow, vascular permeability and chemoattractants bring in leukocytes Stimulate proliferation of fibroblasts and production of extracellular matrix (=scar) Stimulate proliferation of muscle and epithelial cells