Atheroma, embolism

Question 1

What is meant by atherosclerosis?

Answer 1

Degeneration of arterial walls, characterised by fibrosis, lipid deposition and inflammation which limits blood circulation and predisposes to thrombosis

Question 2

What in general are the common sights affected by atherosclerosis?

Answer 2

Bifurcations of vessels (sights of turbulent flow)

Question 3

Name 5 vessels commonly affected by atherosclerosis?

Answer 3

1) Abdominal aorta
2) Coronary arteries
3) Popliteal arteries
4) Carotid vessels
5) Circle of Willis

Question 4

Name 4 non-modifiable risk factors for atherosclerosis?

Answer 4

1) Age
2) Male
3) Family history
4) Genetic

Question 5

Name 5 modifiable risk factors for atherosclerosis?

Answer 5

1) Hyperlipidaemia (LDL:HDL)
2) Hypertension
3) Smoking
4) Diabetes
5) Other - CRP, increased homocysteine, stress

Question 6

What is the first step in the pathophysiology of atheroma formation and what are the possible causes of this?

Answer 6

First step = endothelial injury

Causes = haemodynamic injury, chemicals, immune complex deposition, irradiation

Question 7

After endothelial injury what 2 steps follow in the pathophysiology of atherosclerosis to lead to the formation of a fatty streak?

Answer 7

1) In the presence of hyperlipidaemia, lipid will accumulate in the inner most part of the vessel - the intima
2) Monocytes will migrate into the intima (due to lipid and endothelial injury (VCAM1)) and injest the fat to become foam cells
This stage is a fatty streak

Question 8

Which further steps occur in the pathophysiology of atherosclerosis to move from a fatty streak to an atherosclerotic plaque?

Answer 8

1) Foam cells secrete chemokines attracting more monocytes/macrophages, lymphocytes and smooth muscle cells
2) Smooth muscle cells proliferate and smooth muscle cells and fibroblasts secrete connective tissue
This mixture of fat, extracellular material and leukocytes and smooth muscle cells form the atherosclerotic plaque

Question 9

The structure of a plaque contains which 3 parts?

Answer 9

1) Shoulder area - may contain some small blood vessels
2) Necrotic center - cell debris, cholesterol crystals, foam cells calcium
3) Fibrous cap - depth is important in whether it ruptures or not

Question 10

What 3 things can lead on from atherosclerosis?

Answer 10

1) Occlusion
2) Weakening of vessel wall - aneurysm formation
3) Erosion - thrombus formation

Question 11

What is the difference between a clot and a thrombus?

Answer 11

Clot - stagnant blood, enzymatic process, elastic, adopts shape of vessel
Thrombus - within the body during life, dependent on patelets, firm

Question 12

Thrombus formation is dependent on platelets, what are they and what do they secrete?

Answer 12

They are fragments of megakaryocytes in the bone marrow
Bind to collagen exposed by endothelial damage and become activated
They then secrete contents of alpha granules and dense granules

Question 13

What substances are found within the alpha and dense granules of platelets?

Answer 13

Alpha granules = fibrinogen, fibronectin, PDGF

Dense granules = Chemotactic chemicals

Question 14

What does Virchow’s triad state?

Answer 14

Platelet adhesion and subsequent thrombus formation requires changes in:

1) The intimal surface of the vessel
2) The pattern of blood flow
3) Blood constituents

Question 15

Show how arterial thrombus formation adheres to Virchow’s triad?

Answer 15

Plaque rupture - change in intimal surface of vessel and creates turbulence, ie. a change to the pattern of blood flow
Hyperlipidaemia = change to blood constituents

Question 16

What are ‘lines of zahn’?

Answer 16

When you view a thrombus microscopically there are alternating lines of pale fibrin and pink RBCs - this striped formation is the lines of zahn

Question 17

Show how a venous thrombus formation adheres to Virchow’s triad?

Answer 17

Change to intimal surface = valves
Change in blood flow = immobile
Change in blood constituents = Inflammatory mediators (infection, malignancy), Factor V Leiden, Oestrogen

Question 18

Why can infection or malignancy be significant in the formation of a venous thrombus?

Answer 18

Inflammatory mediators raised in these conditions are pro-thrombotic

Question 19

What are thrombi that form within the heart termed, and where do they form?

Answer 19

Known as mural thrombi
Form over areas of endomyocardial injury
This may occur in MI or myocarditis

Question 20

Other than with endomyocardial injury why else could a mural thrombus form? 2

Answer 20

Can also occur with

1) arrhythmias
2) cardiomyopathy

Question 21

What are the 5 possible things that could lead on from thrombus formation?

Answer 21

1) Occlusion of a vessel
2) Resolution
3) Incorporation into vessel wall
4) Recanalisation
5) Embolisation

Question 22

What is meant by an embolus?

Answer 22

A mass of material in the vascular system able to lodge in a vessel and block it
May be endo or exo genous
May be solid, liquid or gas

Question 23

What is the most common type of embolus?

Answer 23

Pulmonary

Question 24

Name 9 aquired risk factors for a VTE (venous thrombosis embolism)?

Answer 24

1) Immobility
2) Malignancy
3) Previous VTE
4) Heart failure
5) Oestrogens
6) Obesity
7) Pregnancy
8) Renal disease
9) Smokers

Question 25

Name 2 genetic disorders which are risk factors for VTE?

Answer 25

Thrombotic disorders

1) FV Leiden
2) Protein S deficiency

Question 26

What are the differences in clinical effects of a small, medium and large pulmonary embolism?

Answer 26

Small = initially asymptomatic, if multiple may result in pulmonary hypertension
Medium = Cause acute respiratory and cardiac failure (V/Q mismatch and RV strain)
Large = death = saddle emboli (blocks branching point of vessels)

Question 27

Where do systemic embolisms arise?

Answer 27

In the heart with MI or AF

In the arterial circulation - with atheroma

Question 28

Where does an infective embolism occur?

Answer 28

Usually from vegetations on infected heart valves

Effects are compounded by the infective nature - may lead to mycotic aneurysm formation

Question 29

How does a tumour embolism occur, does it cause any problems?

Answer 29

Bits of tumour may break off as tumours penetrate vessels
Do not usually cause any immediate problems
Major route of dissemination

Question 30

What are the 2 types of gas embolism and why can they occur?

Answer 30

1) Air (vessel opening in the air)
Obstetric procedures/chest wall injury
>100ml needed to cause clinical effects
2) Nitrogen
Decompression sickness
Divers, tunnels
In high pressure nitrogen forced into blood, as pressure decreases this exits as small bubbles which enter the bones, joints and lungs

Question 31

Why does an amniotic fluid embolism occur, what does it cause and how do we know its that?

Answer 31

Occurs due to increased pressure during labour which forces AF into maternal uterine veins
Lodge in lungs and get respiratory distress
Know its AF as can see shed foetal skin cells histologically

Question 32

What is a fat embolism, why does it occur, what does it lead to?

Answer 32

Microscopic fat emboli found in 80% of patients with significant trauma (get fat accumulation in bone marrow with age)
Sudden onset of respiratory distress
Thought to be fatal in ~15%

Question 33

What is a foreign body embolism and what does it lead to?

Answer 33

Particles injected IV
eg. talc in IVDUs
Leads to granulomatous reaction