13. Atheroma and thrombosis Flashcards
Define atherosclerosis
Degeneration of arterial walls characterised by fibrosis, lipid deposition, and inflammation, which limits blood circulation and predisposes to thrombosis
Where in the vessels is endothelial injury/atherosclerosis most likely to occur?
Where the vessels bifurcate, as this is where the blood flow is most turbulent
Less likely where the blood flow is more laminar
Why does atherosclerosis occur?
Due to chronic injury and repair of the endothelium (first step = endothelial injury)
Why is hyperlipidaemia a risk factor for atherosclerosis?
In hyperlipidaemia, lipid will accumulate in the innermost part of the vessel wall (the intima)
Monocytes (or macrophages when they are in the tissue ) will migrate into the intima due to lipid endothelial injury and ingest the lipid becoming foam cells
= FATTY STREAK
In which layer of the vessel wall does lipid accumulate at the begging of atherosclerosis?
In the intima (innermost layer)
Which type of cell ingests deposited lipid?
Monocytes (called macrophages when they are in the tissue)
After macrophages have ingested lipid, what do they become?
Foam cells
What is a fatty streak?
Early stage of atherosclerosis (first grossly visible lesion)
It is when the macrophages are ingesting lipid deposits and becoming foam cells
What do foam cells do?
They secrete chemokines, attracting more monocytes/macrophages, lymphocytes and smooth muscle cells
Foam cells secrete chemokines which attract smooth muscle cells as well as other cells. What do smooth cells do?
Proliferate and secrete connective tissue
What does an atherosclerotic plaque consist of?
Fat, extracellular material and leukocytes and smooth muscle
What is another name for a white blood cell?
A leukocyte
An atherosclerotic plaque has a specific structure. What does it consist of?
- dead central CORE
- SHOULDER region which might contain some new blood vessels
- thin CAP which might be unstable and rupture
- fibrous CAP which consists of collagen and smooth muscle
What is the sequelae of atherosclerosis?
- occlusion
- block a blood vessel
- tissue dies
- could lead to gangrene
- weakening of vessel wall
- aneurysm formation
- haemorrhage
- erosion (due to turbulence of blood e.g.)
- possible thrombus formation on top of atherosclerotic plaque
What is an embolus?
A mass of material in the vascular system able to lodge in a vessel and block it
What is the most common embolus?
A thrombus (a thromboembolus)
What is thrombosis?
Solidification of blood contents formed in the vessel during life
How is thrombosis different to a blood clot?
Different in pathogenesis and morphology
Thrombosis = within body during life, dependent on platelets, firm
Clot = stagnant blood, enzymatic process, elastic, adopts shape of vessel
Do platelets have a nucleus?
No
`What are platelets activated by?
Collagen exposed by endothelial damage
What two types of secretory granules do platelets contain?
- alpha granules
- dense granules
What do platelet alpha granules secrete?
- fibrinogen
- fibronectin
- PDGF
What do platelet dense granules secrete?
- chemotactic chemicals
Where are megakaryocytes located and what are they responsible for?
In the bone marrow
Responsible for the production of platelets
Where are platelets?
They circulate in the blood stream
What is subsequent to platelet adhesion?
Thrombus formation
What are the 3 aspects of Virchow’s triad?
- endothelial injury
- stasis
- hypercoagulabilty
What does Virchow’s triad describe?
The three broad categories of factors that are thought to contribute to thrombosis
Change in blood constituents is part of Virchow’s triad. Give an example of this
Hyperlipidaemia
How would a plaque rupture increase chance of thrombosis?
- creates turbulent flow
- intimal change
(Virchow’s triad)
What do lines of Zahn show?
They are lines of alternating pale pink bands of platelets and fibrin and red bands of RBCs
They are characteristic of thrombi
In lines of Zahn, what do the pale pink bands contain?
Platelets mixed with fibrin
Lines of Zahn are characteristic of thrombi, particular when formed where?
In the heart or aorta
In lines of Zahn, what do the darker pink/red layers contain?
Red blood cells
What are the characteristics of venous thrombosis?
- intimal change = valves
- change in blood flow = immobile
- change in blood constituents = prothrombotic effect of inflammatory mediators (infection malignancy)
What is the most common inherited disorder of blood clotting?
Factor V Leiden thrombophilia
What type of clot are you more at risk of if you have Factor V Leiden?
Deep vein thrombosis (DVT)
What are thrombi in the heart known as?
A mural thrombi
Where do mural thrombi (cardiac thrombi) occur?
Over areas of endomyocardial injury
- MI
- myocarditis
Can also occur with arrhythmias and cardiomyopathy
What is the sequelae of thrombosis?
- occlusion of vessel
- resolution
- incorporation into vessel wall
- recanalisation
- EMBOLISATION!
How can a thrombus turn into an embolus?
Thrombus might detach and embolise
What is a paradoxical embolism?
A kind of arterial thrombosis caused by embolism of a thrombus (blood clot) of venous origin through a lateral opening in the heart, such as a patent foramen ovale (RARE)
What is a saddle embolus?
Saddle pulmonary embolism (PE) is a form of large pulmonary thrombo-embolism that straddles the main pulmonary arterial trunk at its bifurcation. Its incidence among patients diagnosed with PE was found to be approximately 2.6%.
What are the clinical effects of a small pulmonary embolism?
Initially asymptomatic, if multiple it may result in pulmonary hypertension
What are the clinical effects of a medium-sized pulmonary embolism?
Cause acute respiratory and cardiac failure (V/Q mismatch, RV strain)
What are the clinical effects of a large pulmonary embolism?
Death
saddle emboli
Where do systemic emboli go?
Anywhere in circulation
Where do systemic emboli normally arise?
- within the heart (MI or AF)
- or within arterial circulation (atheroma)
Where do infective emboli arise?
Usually from the vegetations on infected heart valves
What may infective embolism lead to?
Mycotic aneurysm formation
the effects are compounded by the infective nature
Who is infective embolism common in?
People with prosthetic valves
Intravenous drug users
What is a tumour embolism?
When bits break off a tumour as they penetrate vessels
Do not usually cause intermediate physical problems
What is a major route of dissemination (spread) of tumours?
Tumour embolism
What are the 2 types of gas embolism?
- air
- nitrogen
How is air embolism caused?
When vessels are opened into the air during obstetric procedures/chest wall injury
How much air is needed to enter in an air embolism to cause clinical effects?
> 100ml
What is nitrogen embolism commonly known as?
Decompression sickness (“the bends”)
Who is affected by decompression sickness/ nitrogen embolism?
Divers
Tunnel workers
What happens in nitrogen embolism?
Increased pressure at depth - blood absorbs more nitrogen - come back up and the nitrogen is forced out of the blood
Nitrogen bubbles enter bones, joints and the lungs
How does amniotic fluid embolism occur?
Increased uterine pressure during labour forces amniotic fluid into maternal uterine veins
How common is amniotic fluid embolism?
1 in 50,000 deliveries
Why is amniotic fluid embolism a medial emergency?
Can lodge in the lungs and cause respiratory distress
What can you see histologically in an amniotic fluid embolism?
Shed skin cells
What is fat embolism caused by?
Trauma
Mainly fractures but also seen in severe burns
What does fat embolism cause?
Sudden onset of respiratory distress
How is foreign body embolism caused?
Particles injected intravenously
Eg, talc in intravenous drug users
What does foreign body embolism lead to?
A granulomatous reaction
