Lecture 13

Question 1

Describe haemostasis?

Answer 1

It is a physiological process. it stops leakage of blood from injured vessels (by plugging the leaks and sets up the vessel to be repaired). Response of vessels to injury.

Question 2

Describe the process of haemostasis?

Answer 2

In healthy vessels, haemostasis is actively switched off, however it is ready to go and be of use. Endothelial cells inhibit (actively) haemostasis in a healthy vessel. Endothelial cells physically insulate the tissues underneath them from the blood on top of them. As soon as your blood comes into contact with the tissues underlying the endothelium it initiates haemostasis very rapidly. The endothelial cells produce both chemical and enzymatic inhibitors (NO and prostacyclin).

Question 3

What happens when a blood vessel becomes injured?

Answer 3

Haemostasis actively and rapidly turns on. It is a cooperation effort between: endothelial cells, platelets and the clotting cascade. The endothelial cells are the initiator of haemostasis.

Question 4

what do the endothelial cells do?

Answer 4

Normally they prevent haemostasis from being turned on. But when a vessel is injured then the cells switch, and they actively turn on haemostasis. They produce endothelin, a substance which causes vasoconstriction (less blood lost through a damaged vessel and easier time to repair a leak). The underlying tissues are exposed, especially CT proteins which activate platelets and coagulation cascade. Endothelial cells also produce von Willebrand Factor which promotes platelet adhesion to ECM proteins that have been exposed. And they produce a substance called thromboplasitn (which directly activates coagulation cascade).

Question 5

What do the platelets do?

Answer 5

They are produced by megakaryocytes in the bone marrow (fragment their cytoplasm). They last about a week in the cytoplasm. The alpha and dense granules contain chemical mediators of paltelet activation and activity. Once the platelets become activated, then the alpha and dense granules start to degranulate and secrete substances such as: Thromoxane A2, vasoactive amines, ADP. This allows haemostasis to be turned on rapidly. These substances cause further vasoconstriction and for the platelets to aggregate towards each other.

Question 6

What happens when a person does not have enough platelets?

Answer 6

There is bleeding from skin capillaries or spontaneous haemorrhage.

Question 7

Describe the coagulation cascade?

Answer 7

There are several different pathways which can activate this coagulation cascade. It turns on a series of enzymatic cleavage events. This ends up with a fibrin web which stabilises the platelets in a plug. It is a proteolytic cascade (cleaving one another). Once zymogens have been cleaved, this enzyme then cleaves the zymogen below it and so forth. Gradually build up a series of cleavage events.

Question 8

What initiates the coagulation cascade? and describe the process of the coagulation cascade?

Answer 8

Lots of different factors: tissue factor that is produced when the vessel wall is damaged. The activation of thrombin, which catalyses the conversion of fibrinogen into fibrin monomers which turn into fibrin strands, which stabilise the platelet plug. Thrombin activates and catalyses some of the earlier events in the cascade. So the fibrin strands form a dense network.

Question 9

When does thrombosis occurs?

Answer 9

When the physiological process of haemostasis are turned on inappropriately.

Question 10

What is the formal definition of thrombosis?

Answer 10

Mass formed from blood constituents within the circulation during life.

Question 11

What are thrombi composed of?

Answer 11

Fibrin and platelets with red blood cells trapped in their.

Question 12

Where can thrombi form?

Answer 12

In both arteries and veins. Thrombi prevent blood form getting to the tissues downstream.

Question 13

what is an embolus?

Answer 13

When a piece of the thrombus breaks off to obstruct a vessel downstream.

Question 14

What is a clot?

Answer 14

A clot is formed from static blood and involves the coagulation system. It is jelly like, and it is different to thrombus.

Question 15

Describe Virchow’s Triad?

Answer 15

There are three things that are predisposing factors for thrombosis:

1. Endothelial injury - changes in the vessel wall.
2. Hypercoagulability - changes in blood flow.
3. Abnormal blood flow - changes in constituents of blood.

Question 16

Describe what happens when there is a change in the vessel wall?

Answer 16

1. Atherosclerosis can cause endothelial injury - turns on inflammation and turns on haemostasis inappropriately. That’s why atherosclerotic plaques can be complicated by a thrombis.
2. Hypoxia.
3. Infection.
4. Inflammation.
5. Physical damage (crushing of veins of stress of hypertension).
6. Chemical damage.
   Thrombi can also form on parts of a blood vessel that don’t have the normal inhibitors of haemostasis. If you have vascular implants, then the artificial surfaces can activate the intrinsic activation cascade - activate platelets. Artificial heart valves or stents can activate thrombosis - so non-thrombotic materials are used to coat these vessels/stents sometimes.

Question 17

Describe what happens in abnormal blood flow?

Answer 17

An atherosclerotic plaque could narrow the lumen. This could cause turbulence, which will increase sheer stress is going to activate and injure the endothelium. Thus endothelium can turn on haemostasis. Aneurysms, or normal cardiac rhythms after a heart attack can all cause abnormal blood flow. In veins it is slow blood flow, or right sided heart failure (slower flow in the periphery), varicose veins, sickle cell disease - it is stasis of blood.
The platelets may come more in contact with endothelium, impaired removal of coagulation factors, change in blood flow may indirectly injure endothelial cells.

Question 18

Describe what happens in hypercoagulability?

Answer 18

This is increased blood clotting, makes the blood constituents a bit more likely to participate in haemostasis. There could be genetic causes (deficiency of anti-thrombin 3 family, which is found on the surface of endothelial cells), acquired causes, pro-inflammatory substances, malignancy or after surgery. Anything where your body is sensing that there has been a massive injury. A range of changes can cause an inappropriate activation of haemostasis.

Question 19

What limits coagulation?

Answer 19

There are natural-coagulants: protein C and S, tissue factor pathway inhibitor protein (natural molecules that are secreted to control and limit the normal haemostatic response).

Question 20

Describe arterial thrombosis?

Answer 20

Atherosclerosis is building up a plaque which narrows the lumen, and is predominantly silent. Suddenly the disease will manifest if there is a thrombus that forms on top of the injured endothelial cells in narrowed vessels. There are vulnerable plaques on top of which arterial thrombosis occurs. Thrombi can form inside the chambers of the heart (mural thrombosis) - can cause turbulence.

Question 21

Describe venous thrombosis?

Answer 21

Stasis is the main change in blood flow. The triad still applies. DVT - long thrombi that start to propagate to the sight that they were formed in and break off as emboli (move in the circulation up into the lungs - infarction of lung tissue, as they’re blocking part of the lungs). Venous thrombi can embolise - flows to a distant site.

Question 22

What is an embolus?

Answer 22

It is an intravascular mass that is carried by the blood flow to a distant site (from air, fat embolus, debris from a plaque, or bone marrow or fluid).

Question 23

Describe what happens when there is an emboli from the left side of the heart?

Answer 23

This can flow up to the brain, leading to a stroke (the emboli will enter the systemic circulation).