Clotting Flashcards

1
Q

What causes the clotting cascade to start?

A

Injury to endothelium

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2
Q

What is primary hemostasis?

A

A localized platelet plug formed at endothelial injury

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3
Q

What is secondary hemostasis?

A

When more stuff is added to primary hemostasis, such as: fibrin (Factor 1) –> coagulum
Platelet plug + Coagulum = clot

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4
Q

What 2 things do you need to form a clot?

A

Platelet plug + Coagulum.

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5
Q

What is an antithrombiss?

A

Inhibition of clotting

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6
Q

What is Fibrinolysis?

A

Breakdown and removal of clot

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7
Q

What autonomic event happens when there’s an injury to the endothelium?

A

Vasoconstriction

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8
Q

What substance drastically accelerates production of fibrin 1000 fold?

A

Phospholipid platform formed during secondary hemostasis

sticky activated platelets

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9
Q

What starts off Extrinsic pathway?

What factors are in the extrinsic pathway?

A

7 being turned into 7a via injury. Injury lets off Tissue Factor (Thromboplastin/F).
7, 3, X (3=TF)

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10
Q

What is the overall goal of the extrinsic pathway?

A

To create Xa that goes in prothrombinase.

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11
Q

What enzyme must be created to form Xa from the extrinsic pathway?

A

The Complex of TF - 7a - Ca++

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12
Q

What enzyme must be created to form Xa from the intrinsic pathway?

A
Tenase. 
Contains: 
9a
8a
Ca++
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13
Q

What enzyme does the intrinsic and extrinisc pathway meet at?

A

Prothrombinase
Xa
Va
Ca

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14
Q

What does Prothrombinase do?

A

Makes thrombin from prothrombin via thrombine.

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15
Q

What is the overall goal of the clotting cascade?

A

To make stable, polymer fibrin (factor 1).

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16
Q

Once you have fibrin monomers, what final factor do you need to get your product?

A

13 –> 13a via thrombine.

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17
Q

Which factors are Vitamin K dependent?

A
2, --> (Thrombin)
7, 
9, 
X
Protein S and C

“1972”

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18
Q

How is the intrinsic pathway began?

A

Platelets conformational change to show the phospholipid- rich platform

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19
Q

How does the phospholipid platform initiate intrinsic cascade?

A

The Phospholipid platform is negatively charged, which attracts Factor 12 and HMWK

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20
Q

Factor 12 –> Factor 12a is accelerated by what 2 things?

A

HMWK & Kallikrein

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21
Q

If there’s a problem in your Factor 9 or Factor 8, what disease do you have?

A

Haemophilia

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22
Q

In general, what factors are used in what order of intrinsic?

A

12- 11- 9 - 8 -10.

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23
Q

What is the end product of the intrinsic pathway

A

Tenase
9a
8a
Ca++

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24
Q

What are thrombin’s 3 roles?

A
  • Activate downstream components (look at diagram)
  • Positive feedback upstream
  • Paracrine activity
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25
Q

What is the paracrine activity caused by Thrombin?

A

Causes endothelin cells to release NO, Prostacyclin, (Vasodilators) and TPA (Tissue plasminogen activator –> dissolves clots)

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26
Q

What part of the blood is used in Hemostasis testing?

What is the tube cap color?

A

Plasma

Blue

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27
Q

What are the most common causes of prolonged aPTT?

A

Med OD: heparin, oral anticog
Dilutional coagulopathy (Bleeding out)
Inherited: Haemophilia
DIC: Disseminated INtravascular Coagulation

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28
Q

What does Warfarin do?

A

Inhibit Vitamin K = Spontaneous bleeding b/c no clots

Warfarin: same.
More specifically inhibiting epoxide reductase

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29
Q

What are most common causes of prolonged PT?

A

Human error
Pt on Anticoagulants
Coagulation Factor deficiency from: Liver disease, hemorrhage, DIC, inherited.

30
Q

Common cause of Vit K deficiency?

A

Liver sucks

31
Q

What are the 4 components of hemostasis

A
  1. Vascular Spasm
  2. Formation of Platelet Plug
  3. Formation of blood clot
  4. Repair of damage
32
Q

What are platelets composed of?

A

Cell fragments of megakaryocytes.

  • Mitochondria
  • Actin/Myosin
  • COX1
  • Can secrete: thromboxane A-2, Serotonin = Vasoconstrictors
33
Q

How does TPO regulate platelet production?

A

Binds to cMPL on megakaryocytes. They activate and push out platelets

34
Q

What molecule regulates platelet production?

Where is this molecule secreted from?

A

TPO

Liver and Kidneys

35
Q

How is thrombopoiesis and erythropoiesis different?

A

Thrombopoiesis:
Increases all blood cell production
TPO from Liver and Kidneys
Always active

Erythropoisis:
Increases RBC production
EPO from kidneys
ONly released with low O2

36
Q

What is the function of vascular spasm? what is vascular spasm?

A

Vasoconstriction

Reduces blood flow ot lessen blood loss.

37
Q

How is vascular spasm initatied?

A

(myogenic response)

Platelets release thromboxane and serotonin

38
Q

Endothelial is damaged. What’s the initial response of the body? How is this made?

A
Make platelet plug
Damage to endothelial exposes collagen. 
Platelets bind to collagen via vWF
Platelets recruit more platelets via thromboxane and ADP
They stick together and form a plug.
39
Q

One of the platelet’s roles is to stabilize the clot (“retract the clot”). How does it do this?

A

Activates thrombin activator, thrombin,
Platelet clot (fibrin) squeezes out plasma
SEcretes fibrin stabilizing factor to generate and bring fibrin together.

40
Q

What does platelet derived growth factor do and what secretes it?

A

STimulates fibroblasts to repair smooth muscle

Platelets

41
Q

What main molecule is responsible for the lysis of clots?

How is it made?

A

Plasmin
Thrombin and Thrombomodulin bind –> ACtivates Protein C –> Inacitvates tPA inhibitor –> tPA converts plasminogen –> plasmin.

42
Q

If a patient is having a stroke, what would you give them?

A

tPA

43
Q
What is the MOA of these molecules:
Fibrin
Postacyclin
Antithrombin III
Heparin:
A

Fibrin: Inhibits thrombin.
Postacyclin: Vasodilation limits platelet aggregation
Antithrombin III: Antithrombin.
Heparin: Antithrombin efficacy

44
Q

In what form is Vitamin K Active?

In what form is dietary Vitamin K?

A

QUinol form

Dietary: Quinone

45
Q

What is the function of Protein C?

Protein C deficiency puts pts at an increased risk of?

A

Anticoagulation

DVT

46
Q

A young pt comes in bleeding a lot- - you suspect Haemophilia A. How can you test this? What are you looking for?

A

aPTT test will test for intrinsic pathway, which is where Factor 8 is. A deficiency in Factor 8 causes Haemophilia

47
Q

What is the mechanism of Haemophilia?

A

Factor 8 is deficient. Factor 8 helps cleave X into Xa which feeds into prothrombinase.

48
Q

What does a PT test evaluate?

Normal time?

A

Extrinsic and common pathway;
factors: 1, 2, 5, [3, 7, 10.]
10-13

49
Q

What does PTT test evaluate?

Normal time?

A

intrinsic and common;
[12, 11, 9, 8] [10, 13] and kallikrein, vWf
25-35

50
Q

WHere are the 3 sources of triacylglycerol?

A

Dietary processed in intestine
De novo from liver
De novo from adipocyte

51
Q

In intestinal synthesis of TG, what is the backbone molecule? What is the net result?

A

2 monoacylglycerol
Triacylglycerol +apolipoprotein + other lipids
=
Chylomicrons

52
Q

In liver synthesis of TG, what is the backbone molecule? What is the net result?

A

glycerol 3 phosphate
Triacylglycerol +apolipoprotein + other lipids
=
Forms VLDL

53
Q

In adipocyte synthesis of TG, what is the backbone molecule? What is the net result?

A

Glycerol 3 phosphate

Storage of TG in adipocytes

54
Q
Which exclusive system has glycerol kinase?
A. Liver
B. Kidney
C. Adipocytes
D. Intestine
What can glycerol kinase do?
A

Liver only man.

Use glycerol as fuel

55
Q

Where is the only place that TGs are broken down? What enzymes are responsible for lipolysis?

What molecules do they affect?

A
Adipocytes
HSL (Hormone sensitive lipase)
LPL (Lipoprotein lipase)
MAG Lipase
ATGL **Discovered in 2006

TAG to DAG via ATGL
DAG to MAG via HSL
MAG to fatty acid via MAG lipase

56
Q

When is lipolysis stimulated?

What inhibits lipolysis?

A

Hunger and exercise (glucagon and epinephrine)

Insulin inhibits.

57
Q

What are the functions of Apolipoproteins

A

Cofactors for enzymes
Structurally stable.
Transport of TG

58
Q

What apolipoprotein is located in
LDL?
HDL?
VLDL?

A

LDL: Apo B
HDL: ApoA-1
VLDL: Apo E

59
Q

What is Type I Familial hyperchylomicronemia caused by? What will you see in the blood?

A

Deficiency in lipoprotein lipase.
HIGH TAG

YOUNG - overnight plasma fridgeration thick creamy layer.
most people die
Xanthomas

60
Q

What is Type II familial hypercholesterolemia caused by? What will you see in the blood?

A

LDL receptor defective.
High cholesterol, high LDL , high VDL

Substernal tightness - 10 minutes
Xanthoma, rings around cornea
Elevated cholesterol in family
Given statins

Artherosclerosis
Most homozygous die.

61
Q

If a patient has high cholesterol, what sorta drugs will you give them?

A

Statins

62
Q

What are the benefits of high HDL?

A

Antioxidant
Reverse cholderserol transport
Reduced risk for CAD

63
Q

A pt presents with substernal tightness that lasted for 10 minutes. Multiple xanthomas, rings around cornea and family history of elevated cholesterol. Diagnosis? Drug?

A

Type 2 Familial Hypercholesteronemia

Statins

64
Q

A young pt comes in, you put his plasma in the fridge overnight. Next morning is a thick creamy layer. Diagnosis? What is the MOA

A

Type 1 Hypercholemia.

MOA: Deficient ApoC

65
Q

How can aspirin aid nicotinic acid’s (niacin) side effects?

MOA of Niacin?

A

Reduce cutaneous flushing

Antihyperlidemic agent. People think it involves PKA

66
Q

What do we use niacin for?

What can niacin side effects be?

A

Hepatotoxicity if over 6 grams.
Increases HDL
Lowers LDL
Cutaneous flushing

67
Q

Insulin is a positive regulator of what?

A

Triglyceride Syntehsis in adipocytes

68
Q

Where can adipocytes get glucose?

What does glucose become?

A

Glycolysis
DHAP –> Glycerol 3 P
add Fatty acyl CoA to make TG

69
Q

In what organ are there multiple paths to DHAP?
What are these paths?
Why can this organ do multiple?

A

Liver.
Glycolysis and Glycerol Kinase
Contains Glycerol Kinase

70
Q

What is the 7TM receptor?

A

Beginning of GPCR complex

71
Q

What is the GPCR complex pathway?

A

Hormone hits 7TM receptor –> ATP –> cAMP –> PKA –> Triacylglycerol lipase

72
Q

What is carnitine’s role in metabolism?

What is it’s biochemical role?

A

Best for long term exercise

Transfers carnitine into mitochondria