Atheroma Flashcards
What is atherosclerosis?
- Thickening and hardening of arterial walls as a consequence of atheroma
What is the definition of an atheroma?
- Accumulation of Intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is arteriosclerosis?
- Thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes
What is a fatty streak?
- Lipid deposits in intima
- Yellow in colour and slightly raised
What causes acute inflammation in the blood vessels?
- Endothelial damage possibly due to oxidised LDLs
- Platelets build up, platelet activating factor to produce ADP which drugs attach to.
- e.g drugs: TXA2 (turned off by aspirin)
What is produced due to acute inflammation?
Neutrophils which can phagocytose
What is then produced in chronic inflammation?
- Macrophages which also phagocytose
- Lymphocytes
How do foam cells form?
- Macrophages have receptors for LDLs as they mop up the LDLs they form foam cells
What type of growth factors are produced from platelets?
- Platelet derived growth factor
What does PDGF lead to?
- Proliferation and migration of smooth muscle cells into the position of the platelets
- Causing atheroma plaque inducing fibrotic tissue
What is meant by simple plaque?
- When a new epithelium forms over the proliferated smooth muscle cells
- Has an irregular outline
- Typically raised an yellow/white in colour.
What is the effect of the simple plaque forming?
- Reduces luminal area (stenosis) and increased resistance as a result
- This leads to more damage to epithelium so is a recurrent problem.
What is complicated plaque?
- More unstable than simple plaque due to calcification
- Rupture leads to thrombosis use to release of cells from atheroma
- Haemorrhage into plaque
- If occurs in a coronary artery -> MI
What are the possible results of complicated plaque?
- Thrombosis
- Dissection of blood vessels
- Aneurysm
What causes an aneurysm and what is it?
- Blood vessel wall has become weakened
- Ballooning of blood vessel wall which if ruptures can lead to extensive bleeding
What is a dissection of a blood vessel and what can it lead to?
- When blood forces it’s way through blood vessel wall
- Blood in pericardium -> tampernarde -> acute failure
What are the possible drugs used to help with IHD?
- Beta blockers: anti-hypertensives
- Statins: lower cholesterol levels
- ACE inhibitors: allow for better remodelling of plaques
Where are the common sites for atheroma?
- Aorta (especially abdominal)
- Coronary arteries
- Carotid arteries
- Cerebral arteries
- Leg arteries
What are the possible later changes to a blood vessel due to atheroma?
- Fibrosis
- Necrosis
- Cholesterol changes
- Disrupted internal elastic lamina
- Plaque fissuring
What can atheroma lead to in a clinical sense?
- Ischaemic heart disease
- Cerebral ischaemia
- Mesenteric ischaemia
- Peripheral vascular disease
What can ischaemic heart disease lead to?
- MI
- Angina pectoris
- Arrhythmias
- Cardiac failure
What can cerebral ischaemia lead to?
- Transient ischaemic attack (mini stroke)
- Cerebral infarction (stroke)
- Multi-infarct dementia
What can mesenteric ischaemia lead to?
- Ischaemic colitis
- Malabsorption
- Intestinal infarction
What can peripheral vascular disease lead to?
- Intermittent claudication (calf pain on exercise)
- Leriche syndrome (aortoilliac occlusion disease)
- Ischaemic rest pain
- Gangrene
What is the pathogensis for atheroma?
- Age: risk factors operate over years
slowly progressive throughout adult life - Gender: women relatively protected premenopausal
hormone basis - Hyperlipidaemia: high plasma cholesterol
LDL most significant, HDL protective
What is the role of apoprotein E in establishing whether someone’s at a higher risk of atheroma?
- Genetic variations of Apo E are associated with changes in LDL levels
What is familial hyperlipidaemia?
- Genetically determined abnormalities of lipoproteins leads to early development of atheroma
What are the signs of familial hyperlipidaemia?
- Arcus
- Tendon xanthomas
- Xanthelasma
What are the risk factors for atheroma?
- Smoking
- Hypertension
- Diabetes
- Alcohol
- Infection
- Lack of exercise
- Obesity
- Soft water
- Oral contraceptives
- Stress
- Genetic predisposition
How is smoking a risk factor?
- Coagulation system affected
- Reduces PG12
- Increases platelet aggregation
How is hypertension a risk factor?
- Strong link to IHD
- Endothelial damage due to increased pressure
How is diabetes a risk factor?
- Doubles IHD risk
- Increases cerebrovascular and peripheral vascular disease
What level of alcohol is considered a risk for IHD?
- x>5 units per day
What infections are particularly associated with IHD?
- Chlamydia pneumoniae
- Helicobacter pylori
- Cytomegalovirus
Why may there be endothelial injury?
- Increased LDL
- Toxins
- Hypertension
- Haemodynamic stress
