Pathology

Question 1

Clot or Thrombus?

Answer 1

Clot- developed outside of a vessel e.g. wound

Thrombus- intravascular

Question 2

Virchow’s Triad

Answer 2

Favoured locations of thrombosis;

1. site of endothelial injury
2. turbulent blood flow (stasis)
3. Hypercoagulable blood

Question 3

A thrombus is formed by…

Answer 3

intravascular coagulation;

1. platelet activation
2. fibrin production via coagulation cascade

Question 4

Platelet Activation

Answer 4

Endothelium lost - underlying collagen exposed
Collagen binds to glycoprotein Ia/IIb on platelets
von Willebrand Factor also binds platelets and collagen
Increase in platelet integrins
Glycoprotein IIb/IIIa binds fibrinogen
Activated platelets release granules to attract other platelets

Question 5

Activated platelets release granules…

Answer 5

to attract other platelets;
vWF
Platelet activating factor (PAF)
Thromboxane A2 (TXA2)
ADP

Question 6

Intrinsic Pathway of Coagulation Cascade

Answer 6

XII (hageman factor) + kallikrein. 
XI 
IX 
VIII 
Common pathway

Question 7

How is the intrinsic pathway of the coagulation cascade measured in the lab?

Answer 7

Prothrombotic Time (PT)

Question 8

The extrinsic pathway of Coagulation Cascade.

Answer 8

Tissue Factor (thromboplastin) + FVII = Tissue Factor VIIa 
Common pathway

Question 9

How is the extrinsic pathway of the coagulation cascade measured in the lab?

Answer 9

Activated Partial Thromboplastin Time (APTT)

Question 10

The common pathway of the Coagulation Cascade

Answer 10

X
V
II
IIa (thrombin) and XIIa activate fibrinogen and turn into Fibrin.

Question 11

Role of Vitamin K in the Coagulation Cascade

Answer 11

makes factors II, VII, IX and X.

Vitamin K is a fat soluble vitamin stored in the liver (in liver disease- the factors above not produced).

Question 12

Warfarin is an inhibitor of…

Answer 12

Vitamin K. Therefore it blocks the production of factors II, VII, IX and X in the coagulation cascade.

Question 13

How to treat warfarin overdose?

Answer 13

give vitamin K

Question 14

Why does thrombosis not occur in the arterial system (de novo)?

Answer 14

the arterial system is high flow therefore pro-coagulant materials are washed along before being able to do anything.
Requires underlying atherosclerosis.

Question 15

Complications of atherosclerosis

Answer 15

Thrombosis
Narrowed coronary artery
Stable Angina
Unstable Angina

Question 16

Poiseuille’s Law

Answer 16

changes to the vessel affect the flow rate to the power of four, aka small narrowing of vessel radius induces large change in flow.

Question 17

Causes of endothelial injury

Answer 17

toxins 
infectious agents 
smoking 
autoimmune diseases e.g. primary vasculitis 
previous DVT

Question 18

Turbulent flow produces…

Answer 18

endothelial damage (swirling blood) and stasis

Question 19

Stasis is where…

Answer 19

blood flow is no longer laminar causing platelets to increase contact with the vessel wall (margination like process) with no washing out.

Question 20

Stasis/slowing of blood flow most commonly occurs in…

Why?

Answer 20

Deep venous system. 
Gravity 
Inactivity 
Faulty valves 
Venous insufficiency

Question 21

Hypercoagulability

Answer 21

anything that causes an increase in viscosity of the blood

Question 22

Clot buster

Answer 22

Plasmin

Question 23

Anti-clot proteins

Answer 23

Protein C, protein S (degrade factor V and VIII) and antithrombin III (degrades FII, IX and X).

Question 24

Primary causes of Hypercoagulation

Answer 24

Genetic disorders e.g. FV Leiden

Deficiency of protein C, protein S or antithrombin III.

Question 25

Secondary causes of Hypercoagulation

Answer 25

Prolonged immobility 
Significant tissue injury e.g. burns, RTA 
Antiphospholipid syndrome 
MI 
Atrial fibrilation 
Cancer 
Therapy 
Marantic Endocarditis

Question 26

Low risk secondary causes of Hypercoagulation

Answer 26

Smoking
The contraceptive pill
Renal disease (nephrotic syndrome)
Cardiomyopathy

Question 27

Embolism (def)

Answer 27

where a thrombus dislodges and travels round the vascular system until becoming stuck and therefore blocking the vessel.

Question 28

Other causes of embolism, other than thrombus.

Answer 28

air, amniotic fluid, fat, septic, tumour.

Question 29

Ischaemia vs Infarction

Answer 29

Ischaemia- insufficient blood supply

Infarction- death of tissue as a result of ischaemia

Question 30

When calcium channels are not working appropriately and calcium increases, this can stimulate…

Answer 30

The ATPase 
Phospholipase 
Proteases 
Endonuclease 
Mitochondrial permeability 
(see notes for what each does)

Question 31

Common area of atheroma and thrombosis (endothelial damage + turbulence)

Answer 31

Branching vessels, examples;
The coronary vessels
The bifurcation of the aorta 
Origin and division of the carotids 
Renal arteries 
Superior mesenteric arteries