Atheroma, embolism Flashcards
What is meant by atherosclerosis?
Degeneration of arterial walls, characterised by fibrosis, lipid deposition and inflammation which limits blood circulation and predisposes to thrombosis
What in general are the common sights affected by atherosclerosis?
Bifurcations of vessels (sights of turbulent flow)
Name 5 vessels commonly affected by atherosclerosis?
1) Abdominal aorta
2) Coronary arteries
3) Popliteal arteries
4) Carotid vessels
5) Circle of Willis
Name 4 non-modifiable risk factors for atherosclerosis?
1) Age
2) Male
3) Family history
4) Genetic
Name 5 modifiable risk factors for atherosclerosis?
1) Hyperlipidaemia (LDL:HDL)
2) Hypertension
3) Smoking
4) Diabetes
5) Other - CRP, increased homocysteine, stress
What is the first step in the pathophysiology of atheroma formation and what are the possible causes of this?
First step = endothelial injury
Causes = haemodynamic injury, chemicals, immune complex deposition, irradiation
After endothelial injury what 2 steps follow in the pathophysiology of atherosclerosis to lead to the formation of a fatty streak?
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
Which further steps occur in the pathophysiology of atherosclerosis to move from a fatty streak to an atherosclerotic plaque?
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
The structure of a plaque contains which 3 parts?
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
What 3 things can lead on from atherosclerosis?
1) Occlusion
2) Weakening of vessel wall - aneurysm formation
3) Erosion - thrombus formation
What is the difference between a clot and a thrombus?
Clot - stagnant blood, enzymatic process, elastic, adopts shape of vessel
Thrombus - within the body during life, dependent on patelets, firm
Thrombus formation is dependent on platelets, what are they and what do they secrete?
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
What substances are found within the alpha and dense granules of platelets?
Alpha granules = fibrinogen, fibronectin, PDGF
Dense granules = Chemotactic chemicals
What does Virchow’s triad state?
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
Show how arterial thrombus formation adheres to Virchow’s triad?
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
What are ‘lines of zahn’?
When you view a thrombus microscopically there are alternating lines of pale fibrin and pink RBCs - this striped formation is the lines of zahn
Show how a venous thrombus formation adheres to Virchow’s triad?
Change to intimal surface = valves
Change in blood flow = immobile
Change in blood constituents = Inflammatory mediators (infection, malignancy), Factor V Leiden, Oestrogen
Why can infection or malignancy be significant in the formation of a venous thrombus?
Inflammatory mediators raised in these conditions are pro-thrombotic
What are thrombi that form within the heart termed, and where do they form?
Known as mural thrombi
Form over areas of endomyocardial injury
This may occur in MI or myocarditis
Other than with endomyocardial injury why else could a mural thrombus form? 2
Can also occur with
1) arrhythmias
2) cardiomyopathy
What are the 5 possible things that could lead on from thrombus formation?
1) Occlusion of a vessel
2) Resolution
3) Incorporation into vessel wall
4) Recanalisation
5) Embolisation
What is meant by an embolus?
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
What is the most common type of embolus?
Pulmonary
Name 9 aquired risk factors for a VTE (venous thrombosis embolism)?
1) Immobility
2) Malignancy
3) Previous VTE
4) Heart failure
5) Oestrogens
6) Obesity
7) Pregnancy
8) Renal disease
9) Smokers
Name 2 genetic disorders which are risk factors for VTE?
Thrombotic disorders
1) FV Leiden
2) Protein S deficiency
What are the differences in clinical effects of a small, medium and large pulmonary embolism?
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)
Where do systemic embolisms arise?
In the heart with MI or AF
In the arterial circulation - with atheroma
Where does an infective embolism occur?
Usually from vegetations on infected heart valves
Effects are compounded by the infective nature - may lead to mycotic aneurysm formation
How does a tumour embolism occur, does it cause any problems?
Bits of tumour may break off as tumours penetrate vessels
Do not usually cause any immediate problems
Major route of dissemination
What are the 2 types of gas embolism and why can they occur?
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
Why does an amniotic fluid embolism occur, what does it cause and how do we know its that?
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
What is a fat embolism, why does it occur, what does it lead to?
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%
What is a foreign body embolism and what does it lead to?
Particles injected IV
eg. talc in IVDUs
Leads to granulomatous reaction
