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Lecture 2-3 Flashcards

1
Q

What is hemostasis?

A

The prevention of blood loss when a vessel is severed or ruptured

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2
Q

What are several mechanisms to limit blood loss in hemostasis?

A
  1. Vascular constriction
  2. Formation of a platelet plug
  3. Formation of a blood clot
  4. Clot retraction
  5. Removal of the clot (dissolved after repair)
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3
Q

Local factors released from damaged tissues causes platelets to release ___________ which contributes to ____________.

A
  1. Thromboxane A2 (TXA2), [synthesized from arachidonic acid formed by PLA2]
  2. Vasoconstriction, (nervous reflexes initiated principally by pain receptors also contributes)
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4
Q

What releases prostaglandin I2 (aka PGI2 or prostacyclin)?

A

Adjacent undamaged endothelium and platelets

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5
Q

What is the purpose of prostacyclin (aka PGI2 or prostaglandin)?

A

Inhibits platelet aggregation from spreading inappropriately and vasodilator.

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6
Q

What are thrombocytes?

A

platelets

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7
Q

Thrombocytes contain contractile proteins including _____, ______ and __________ which allow the platelets to rapidly release intracellular granules as necessary.

A

actin, myosin, and thrombosthenin

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8
Q

What do platelets contain that stimulates endothelial cells, vascular smooth muscle cells and fibroblasts to multiply and grow?

A

Prostaglandins, fibrin-stabilizing factor, and a growth factor. (Necessary for repair)

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9
Q

________ is on the external face of the platelet cell membrane which prevents them from adhering to the normal undamaged endothelial surface.

A

Glycoproteins

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10
Q

Platelets contain high concentration of __________ that are involved in blood clotting.

A

phospholipids

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11
Q

T or F? Platelets has a short half-life of 8-12 days and are removed by macrophages in the liver.

A

False, spleen

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12
Q

T or F? Platelets begin to swell and assume irregular shapes and radiating pseudopodia as they come in contact with damaged endothelium or exposed collagen.

A

True

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13
Q

During the formation of the platelet plug, the platelets become “sticky” and adhere to _____ and a protein called __________ from the blood.

A

damaged endothelium and/or collagen; von Willebrand factor

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14
Q

During the formation of the platelet plug, platelet secrete large amounts of _______ and ______ which activate nearby platelets which themselves adhere to the original ones in a positive feedback loop.

A

ADP; TXA2

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15
Q

How quickly can a blood clot form?

A

15-20 seconds if trauma is significant
1-2 minutes if minor.
After 3-6 minutes most reasonable holes are plugged by the clot.
(After 20-60 mins the clot retracts due to platelets and close the hole even more/more tightly)

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16
Q

What are the 2 options after a clot has formed?

A
  1. It can be invaded by fibroblasts (which form fibrous connective tissue throughout the clot)
  2. It can be dissolved
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17
Q

T or F? There are more than 50 substances found to affect or cause clotting.

A

True. (Anticoagulants dominate but when there is damage procoagulants dominate at the site)

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18
Q

What are the 3 simplified essential steps to clotting/coagulation?

A
  1. Trauma stimulating either of 2 enzyme cascades resulting in formation complex called Prothrombin activator.
  2. Conversion of Prothrombin into the active enzyme Thrombin.
  3. Conversion of soluble plasma protein Fibrinogen into insoluble Fibrin.
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19
Q

T or F? Fibrinogen enmesh platelets, RBC’s and plasma to form the clot.

A

False, Fibrin fibers not Fibrinogen.

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20
Q

What are the 2 different enzyme cascades?

A

Extrinsic pathway; initiated by trauma to the endothelium and surrounding/supporting tissues.
Intrinsic pathway; originates in the blood itself or exposure to collagen.

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21
Q

T or F? During the intrinsic pathway, platelets are activated and release phospholipids including Tissue factor III, and factor XII is activated

A

False, lipoprotein platelet factor III not tissue factor III

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22
Q

Intrinsic pathway: factor XIIa together with ____ ____ ___ ____, (accelerated by Prekallikrein), activates XI.

A

High Molecular Weight Kininogen

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23
Q

Intrinsic pathway could be blocked by deficiency in either factor VIII or platelets, what are these conditions called?

A

Deficiency in factor VIII is the primary cause of “classic” hemophilia.
Deficiency in number of platelets is termed Thrombocytopenia.

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24
Q

Which enzyme cascade is faster?

A

Extrinsic (as fast as 15 seconds, intrinsic taking 1-6 mins to clot)

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25
What protein is expressed on the endothelial surface which binds to Thrombin and inhibits its function as a procoagulant?
Thrombomodulin
26
What acts as an anticoagulant by inactivating factors Va and VIIIa?
Activated Protein C (activated by Thrombomodulin + Thrombin)
27
Name 2 important anticoagulants found in blood itself.
``` Fibrin fibers (absorbs Thrombin) Antithrombin III (alpha-globulin) (combines and inactivates thrombin) ```
28
Heparin + Antithrombin III complex removes which activated factors?
IIa, IXa, Xa, XIa, and XIIa
29
Heparin is secreted by many cell types but especially by _____ cells in connective tissues and _____ in blood.
Mast ; basophils
30
How are prothrombin levels estimated?
By measuring the clotting time in the presence of excess Ca2+ and tissue factor.
31
What are 3 conditions that are particularly significant in excessive bleeding?
1. Vitamin K defciency 2. Hemophilia (deficiency of factor XIII) 3. Thrombocytopenia (low platelet counts)
32
Vitamin K (synthesized by symbiotic gut bacteria) is important in the production of which clotting factors?
II, VII, IX, X.
33
T or F? Hemophilia is primarily inherited as "sex-linked" and is almost exclusively found in males.
True
34
A thrombus is loose in the blood vessel it is called a(n) ______
embolus
35
What are 2 main reasons for inappropriate clotting?
Arteriosclerotic plaque Disseminated intravascular coagulation (caused by traumatized or necrotic tissue that can result in increase amounts of tissue factors into the blood where it can cause widespread clotting)
36
What "digests" fibrin fibers, fibrinogen, prothrombin and factors V, VIII and XII?
Plasmin (forms from plasminogen found in plasma)
37
Tissue plasminogen activator (t-PA) is released very slowly (so repairs can be done) from the ______ ______.
damage tissue (plasminogen are trapped inside the clot)
38
Fibrinogen is which factor?
factor 1
39
Prothrombin is which factor?
factor 2
40
Tissue Factor is which factor?
Factor III | Tissue Thromboplastin
41
Calcium is which factor?
Factor IV
42
What is the synonym for factor V?
Proaccelerin
43
What is the synonym for factor VII?
Serum prothrombin conversion accelerator (SPCA)
44
What is the synonym for factor VIII?
Antihemophilic factor (AHF)
45
What is the synonym for factor IX?
Plasma thromboplastin component (PTC)
46
What is the synonym for High-molecular-weight kininogen?
Fitzgerald factor | HMWK
47
T or F? Any situation that produces hypoxia in tissues inhibits Erythropoietin production?
false, it stimulates!
48
Sickle cell anemia is due to what?
A single base-pair mutation in the beta-globin chain
49
What mechanism/s are employed initially (before activation of the clotting cascades) to limit blood loss from a severed vessel?
vascular constriction and platelet plugs
50
What protein is required in the GI tract for absorption of Fe and what mechanism is employed?
apotransferrin helping absorption of Fe via signal-mediated endocytosis
51
What is Iron (Fe) used for besides making Hb?
Cytochromes for both ETC and drug metabolizing enzymes
52
Thromboxane A2 (TXA2) and prostaglandin I2 (PGI2) are synthesized from?
AA via PLA2
53
Heparin acts how?
Removes activated factors IIa, IXa, Xa, XIa, and XIIa
54
LMW heparin acts how?
Increases the actions Anti-thrombin III to increase its actions on removing Xa
55
How do you measure clotting times?
Prothrombin levels are estimated by measuring the clotting time in the presence of excess Ca2+ and tissue factor.
56
Any situation that produces hypoxia in tissues inhibits Erythropoietin production?
false, it stimulates!
57
Sickle cell anemia is due to what?
a single base-pair mutation in the beta-globin chain
58
What protein is required in the GI tract for absorption of Fe and what mechanism is employed?
apotransferrin helping absorption of Fe via signal-mediated endocytosis
59
Apart from hemoglobin and myoglobin, what is a very significant use of Fe in our bodies? (clue; ~1% total Fe)
cytochromes for both ETC and p450 drug metabolizing enzymes
60
Factor I(a)
Fibrinogen/fibrin
61
Factor II(a)
Prothrombin/thrombin
62
Factor III
Tissue Factor
63
Factor IV
Calcium
64
Factor V
Proaccelerin
65
Factor VII
Serum prothrombin conversion accelerator (SPCA)
66
Factor VIII
Antihemophilic factor (AHF)
67
Factor IX
Plasma thromboplastin component (PTC)
68
Factor X
Stuart Prower factor
69
Factor XI
Plasma thromboplastin antecedent (PTA)
70
Factor XII
Hageman factor
71
Factor XIII
Fibrin stabilizing factor
72
Prekallikrein
Fletcher factor
73
High molecular weight kininogen (HMWK)
Fitzgerald factor
74
Vitamin K is necessary for the synthesis of?
factors II, VII, IX and X (not Protein C)
75
Warfarin acts how? (remember to check slide #15 as ALL information is on slide only and NOT in the SHORT notes!- ALWAYS have slides available when using the SHORT notes please).
vitamin K antagonist (note similar structures).
76
How do you measure clotting times? (‘cos I forgot to mention it!)
relative clotting times can be used to see if a clotting factor/s is/are missing. If you suspect a factor is missing, a clotting assay is set up with everything in excess but for the suspect factor; that has to be supplied by the patient’s plasma. If the clotting time, compared to the standard with everything present, is significantly longer then that suggests that the suspect is indeed missing (VERY low level?)
77
Heparin and AT iii removes which factors?
Factors 2a, 9a, 10a, 11a and 12a
78
The Coumarins like warfarin cause decrease plasma levels of which factors?
Factor 2,7,9 and 10
79
Heparins, LMWHs and hirusin inhibits which factors?
Factor 9,10,11 and 12
80
Removal of clot activate plasminogen to plasmin by degrade or digest which factors?
Fibrin fibers, fibrogen, factor 2,5,8 and 12

BSI 2 (22 decks)

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