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Medical Physiology > Lecture 8: Hemostasis/Coagulation > Flashcards

Lecture 8: Hemostasis/Coagulation Flashcards

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USMLE® Step 1 flashcards
1
Q

What are the ways in which we can achieve hemostasis?

A

Vascular constriction
Formation of a platelet plug
Formation of a blood clot as a result of blood coagulating
Eventual growth of fibrous tissue into the blood clot.

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2
Q

What causes our smooth muscle to contract? (in regards to hemostasis)

A

Trauma to the vessel wall

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3
Q

What causes smooth muscle wall contraction in our blood vessels?

A

Local myogenic spasm (aka responding to the physical trauma hitting the vessel)

Local autacoid factors (thromboxane A2)

Nervous reflexes (Pain)

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4
Q

What are platelets?

A

Little discs formed in the bone marrow.

NO NUCLEI
UNABLE TO REPRODUCE

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5
Q

If I do a CBC, how many platelets do I usually expect?

A

150k-450k

<150k = thrombocytopenia

> 450k = thrombocytosis

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6
Q

What can I find in the cytoplasm of a platelet?

A

Actin & myosin
Ca2+ and enzymes
Mitochondria
Enzyme systems for making prostaglandins
Fibrin-stabilizing factor
Growth factor (for endothelial cells)

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7
Q

What can I find on a platelet’s cell membrane?

A

Glycoproteins (repulse adherence to NORMAL endothelium, but adherence to INJURED endothelium)

Phospholipids (helps with blood-clotting)

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8
Q

What removes most of the platelets in our blood?

A

Macrophages in our spleen!

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9
Q

What is the half-life of a platelet?

A

8-12 days.

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10
Q

What do platelets specifically come into contact with on a damaged vessel wall?

A

Collagen fibers.

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11
Q

What happens when a platelet touches a collagen fiber?

A

It will start swelling and forming pseudopods.

Contractile proteins contract and release granules.

Platelets become sticky and adhere to the collagen fibers and von willebrand factor.

Secretes large quantities of ADP and thromboxane A2, causing vasoconstriction and activating nearby platelets.

This is also the process of a platelet plug.

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12
Q

What is thrombocytopenia?

A

Low levels of platelets in circulation.
Idiopathic.

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13
Q

What are the characteristics of thrombocytopenia?

A

Bleeding from SMALL vessels.

Note:
This is what makes it different from hemophilia, which is large vessels.

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14
Q

Our vessels are normally cut throughout the day, resulting in tiny holes. How are they fixed?

A

Platelet plugs.

Not blood clots!!!

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15
Q

What are the 5 stages of blood clotting?

A
  1. Severed vessel
  2. Platelets agglutinate
  3. Fibrin appears
  4. Fibrin clot forms
  5. Clot retraction occurs
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16
Q

How long does it take for a clot to start forming? Finish?

A

15-20 seconds to begin.

3-6 minutes is when the clot is fully filled.

20 minutes is when it actually retracts to close the vessel further.

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17
Q

What is a blood clot eventually replaced by?

A

Fibroblasts, which replace it with collagen.

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18
Q

Our blood contains pro and anticoagulants. Which one is generally more dominant?

A

Anticoagulants.

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19
Q

What are the two ways clotting is activated?

A

Rupture of the vessel
Damage to the blood itself.

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20
Q

What first occurs when clotting is activated?

A

Prothrombin activator is made (complex of substances)

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21
Q

What is the purpose of prothrombin activator?

A

Converts prothrombin to thrombin.

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22
Q

What is the purpose of thrombin?

A

Converts fibrinogen to fibrin.

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23
Q

What are the two pathways of clotting? What distinguishes them from one another?

A

Extrinsic = injury to the WALL

Intrinsic = injury to the BLOOD

24
Q

What is the rate limiting factor in blood clotting?

A

Prothrombin activator formation

25
Q

What does prothrombin activator need to actually convert prothrombin to thrombin?

A

The presence of calcium.

26
Q

What makes prothrombin?

A

The liver (continuously)

Note:
If the liver stops, it only takes a day for prothrombin concentrations to be low.

27
Q

What is prothrombin?

A

An unstable plasma protein made by the liver, which has a smaller compound in it called thrombin.

28
Q

What does the liver need to make prothrombin?

A

Vitamin K!

29
Q

What happens to someone with a vit K deficiency or liver disease?

A

Tendency to bleed.

30
Q

What is fibrinogen?

A

A plasma protein also made by the liver. It is cleaved by thombin into fibrin. Fibrins then bind to one another to make up the reticulum of the blood clot.

31
Q

What is the fluid expressed from a clot called?

A

Serum

32
Q

What do platelets trapped in a clot release?

A

Fibrin-stabilizing factor.

They also contribute their own actin and myosin, allowing for cross-linking of fibrin fibers.

33
Q

What kind of feedback loop is blood clotting?

A

Positive feedback.

Thrombin is proteolytic on its precursor, prothrombin, so it can make more thrombin itself.

34
Q

What are the 3 processes that can form prothrombin activator?

A

Trauma to the vessel wall (extrinsic)
Trauma to the blood (intrinsic)
Contact of blood with damaged endothelial cells or with collagen. (extrinsic?)

35
Q

Describe the extrinsic pathway.

A

Injured tissue wall releases tissue factor.

Tissue factor acts on F7 to make it F7a.

F7a + Ca + F10 = F10a.

10a + Ca = prothrombin activator.

Takes ~6 seconds.

36
Q

What are the tissue factors in the extrinsic pathway also called?

A

Thromboplastin

37
Q

What is the simplified extrinsic pathway?

A

Tissue factor = 3
Factor 7 = 7
Factor 10 = 10

3 + 7 = 10.

38
Q

Describe the intrinsic pathway.

A

F12 + HMW kininogen + prekallirein = F12a
F12a + F11 = F11a
F11a + F9 = F9a
F9a + F8 + thrombin + F10 = F10a

F8 + thrombin = F8a

39
Q

What is the simplified intrinsic pathway?

A

12 => 11 => 9 => 8 => 10

40
Q

What is the simplified clotting pathway after F10?

A

10 => 5 => 2 (2*5 = 10)

41
Q

What is PT used to measure?

A

Prothrombin time is used to measure EXTRINSIC.

Warfarin dosage
Liver damage
Vit K status

It measures factors 1, 2, 5, 7, and 10.

42
Q

What is aPTT used to measure?

A

Activated partial thromboplastin time measures factors:
1, 2, 5, 7, 9, 11, and 12.

Prolonged aPTT = heparin, Factor 8 deficiency (hemophilia), sepsis, antibodies against coagulation factors.

Note:
It is named after the LACK of factor 3.

43
Q

What affects clotting besides the factors?

A

Endothelial surface factors:
Smooth endothelium causes lack of contact.

Glycocalyx layer repels clotting factors and platelets.

Thrombomodulin protein can bind thrombin to remove it.

44
Q

What removes thrombin from the blood?

A

Thrombomodulin on the endothelium.

Fibrin fibers formed during clotting. (90%)

Antithrombin III, which blocks the effect of thrombin on fibrinogen. (10%) It will eventually inactivate the thrombin.

45
Q

What is heparin?

A

An anticoagulant made in our blood but in low concentrations. (mast cells and basophils)

It commonly combines with antithrombin III to boost its effectiveness at removing thrombin by 100x.

46
Q

How are blood clots broken down?

A

Plasminogen => plasmin.

It is a proteolytic enzyme like trypsin.

Digests fibrin and other clotting factors.

47
Q

Disease of what organ can heavily affect blood clotting?

A

Liver

Diseases such as hepatitis, cirrhosis, and acute yellow atrophy.

48
Q

What deficiency can cause excessive bleeding?

A

Vitamin K.

49
Q

What can cause a Vit K deficiency?

A

Liver failure.

Lack of bile = inadequate fat digestion/absorption.

50
Q

What are the characteristics of hemophilia?

A

Bleeding disorder in LARGE vessels, caused by a factor 8 deficiency.

Maternal inheritance.

1 in 10000 males have it.

51
Q

How do you treat thrombocytopenia?

A

Whole blood transfusions.
Splenectomy (so the spleen doesn’t get rid of platelets as much)

52
Q

What is the characteristic physical finding of thrombocytopenia?

A

Smallish purple blotches on skin.

53
Q

What is the difference between a thrombus and an embolus?

A

A thrombus is an abnormal clot in a blood vessel.

An emboli is a clot that BROKE AWAY and is flowing through the blood.

54
Q

If an embolus originates in the artery/left heart, where can it end up? What about a vein/right heart?

A

Artery/left heart => brain/kidney

Vein/Right heart => Lungs!!!! (pulmonary embolism)

55
Q

What is tPA? What is its purpose?

A

Tissue plasminogen activator.

Plasmin is what dissolve clots.

Must be administered within the first hour.

Note:
It is given for ischemic strokes and MIs caused by thrombotic occlusions of coronary arteries.

56
Q

What is disseminated intravascular coagulation?

A

Commonly known as DIC, it is caused lots of dying/traumatized tissue.

It releases a great amt of tissue factor.

Medical Physiology (14 decks)

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