Atherosclerosis Flashcards
define atherosclerosis
Atherosclerosis is the accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
Common sites
- Aorta- especially abdominal (AAA- Abdominal aortic aneursym)
- Coronary arteries
- Carotid arteries
- Cerebral arteries
- Leg arteries
normal arterial structure
- Endothelium
- Subendothelial connective tissue
- Internal elastic lamina
- Muscular media
- External elastic lamina
- Adventitia
macroscopic features of atherosclerosis
- Fatty streak
- Simple plaque
- Complicated plaque
fatty streak
early age of atheroma
- Lipid deposits in intima
- Yellow
- Relationship to atherosclerosis somewhat debatable
Simple plaque
- Raised yellow/white
- Irregular outline
- Widely distributed
Complicated plaque
- Thrombosis
- Haemorrhage into plaque
- Calcification- degenerate lipid material
- Aneurysm formation
microscopic features: early changes
1) Proliferation of smooth muscle cells
2) Accumulation of foam cells
3) Extracellular lipid
microscopic features: later changes
4) Fibrosis
5) Necrosis
6) Cholesterol cleft- where cholesterol used to be
7) +/- inflammatory cells
8) Disruption of internal elastic lamina
9) Damage extends into media
10) Ingrowth of blood vessels
11) Plaque fissuring
clinical effects of atherosclerosis
ischaemic heart disease
cerebral ischameia
mesenteric ischaemia
abdominal aortic aneurysm (AAA)
peripheral vascular disease
ischaemic heart disease
- Sudden death
- MI
- Angina pectoris
- Arrhythmias- irregular heart beats
- Tachycardia
- Bradycardia
- Atrial fibrillation
- Ventricular fibrillation
- Cardiac failures
Cerebral ischaemia
- Transient ischaemic attack
- Cerebral infarction (stroke)
- Multi-infarct dementia
Mesenteric ischaemia
in which injury to the small intestine occurs due to not enough blood supply
- Ischaemic colitis
- Malabsorption
- Intestinal infarction
Abdominal aortic aneurysm (AAA)
is a localized enlargement of the abdominal aorta such that the diameter is greater than 3 cm or more than 50% larger than normal. They usually cause no symptoms, except during rupture.
peripheral vascular disease
- Intermittent claudication
- Leriche syndrome
- Ischaemic rest pain
- Gangrene
intermittent claudication
painful to walk
- pain onset for a given distance gets shorter overtime
Leriche syndrome
- pain the buttock on exercise (erectile dysfunction)
Ischaemic rest pain
risk factors of atherosclerosis pathogenesis
age
gender
hyperlipidaemia
cigarette smoking
hypertension
DM
alcohol consumption
infection
Age
- Slowly progressive throughout adult life
- Risk factors operate over years
Gender
- Women protected relatively before menopause
- Presumed hormonal basis
Hyperlipidaemia
- High plasma cholesterol associated with atherosclerosis
- LDL most significant
- HDL protective
lipid in the blood is carried on
lipoproteins
lipoproteins carry
cholesterol and TAG
lipoprotein structure
Lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids, primarily cholesterol esters and triglycerides. This hydrophobic core is surrounded by a hydrophobic membrane consisting of phospholipids, free cholesterol, and apolipoproteins (A-E)
chylomicrons
transport lipids from the intestine to the liver
VLDL
carry cholesterol and TAG from the liver
- TAG get sremoved leaving LDL
LDL
rich in choelsterol
carry cholesterol to non-liver cells (formation of foam cells)
HDL
carries cholesterol back to the liver
Apolopoprotein E and atherosclerosis
- Genetic variation in ApoE are associated with changes in LDL levels
- Polymorphisms of genes involved lead to at least 6 Apo E phenotypes
- Polymorphisms can be used as risk markers for atherosclerosis
Familial hyperlipidaemia
- Genetically determined abnormalities of lipoprotein
- Lead to early development of atherosclerosis
physical signs of hyperlipidaemia
corneal arcus
tendon xanthomas
xanthelasma
corneal arcus
deposition of lipid in the peripheral cornea and is generally considered a concomitant of normal ageing process and expected in the elderly patient.
tendon xanthomas
Appears as slowly enlarging subcutaneous nodules related to a tendon or ligament; Most commonly found on the hands, feet and knees
Xanthelasma
yellowish deposit of cholesterol underneath the skin. It usually occurs on or around the eyelids
genetic predisposition to familial hyperlipidaemia
- Possibly due to
- Variation in apolipoprotein metabolism
- Variation in apolipoprotein receptors
Other risk factors for hyperlipidaemia
- Lack of exercise
- Obesity
- Soft water
- Oral contraceptives
- Stress
- Personality type
Cigarette smoking
- Powerful risk factor for IHD
- Risk falls after giving up
- Mode of action uncertain
Hypertension
*
- Strong link between IHD and high systolic blood pressure
- Mechanism uncertain
- Endothelial damage caused by raised pressure?
DM
- Double risk of IHD
- Protective effect tin premenopausal women lost
- DM also associated with high risk of cerebrovascular and peripheral vascular disease
- Related to hyperlipidaemia and hypertension
Alcohol consumption
- More than 5 units a day associated with increased IHD
- Alcohol consumption associated with other risk factors
- Smaller amount of alcohol may be protective
Infection
- Chlamydia pneumonia
- Helicobacter pylori
- Cytomegalovirus
pathogenesis theories
- thrombogenic theory
- insudation theory
- monoclonal hypothesis
- reaction to injury hypothesis
thrombogenic thoery
due to repeated thrombosis
insudation theory
lipid leaked out of vessel into vessel wall due to endothelial injury such as inflammation hat made the vessel more permeable.
Monoclonal hypothesis
- Smooth muscle proliferation
- Each plaque monoclonal
- Might represent abnormal growth control
- Is each plaque a benign tumour?
- Viral aetiology?
Reaction to injury hypothesis
- Endothelial injury
- Hypercholesterolaemia leads to endothelial damage (LDL)
- Injury increases permeability and allows platelet adhesion
- Monocytes penetrate endothelium
- Smooth muscle cells proliferate and migrate
which cells become foam cells
smooth muscle cells and macrophages
summary of atherosclerosis
- Thrombosis
- Lipid accumulation
- Production of intercellular matrix
- Interaction between cell types
- Endothelial cells
- Key role in haemostasis
- Altered permeability to lipoproteins
- Production of collagen
- Stimulation of proliferation and migration of smooth muscle cells
- Platelets
- Key role in haemostasis
- Stimulate proliferation and migration of smooth muscle cells (PDGF)
- Smooth muscle cells
- Take up LDL and other lipid to become foam cells
- Synthesise collagen and proteoglycans
- Endothelial cells
- Macrophages
- Oxidise LDL
- Take up lipids to become foam cells
- Secrete proteases which modify matrix
- Stimulate proliferation and migration of smooth muscle cell
- Lymphocytes
- TNF may affect lipoprotein metabolism
- Stimulation proliferation and migration of smooth muscle cells
- Neutrophils (often no inflammation)
- Secrete proteases leading to continued local damage and inflammation
atheroscelrosis prevention
- No smoking
- Reduce fat intake
- Treat hypertension
- Not too much alcohol
- Regular exercise/ weight control
- but some people will still develop atherosclerosis
atheroscleorsis intervention
- stop smoking
- modify diet
- treat hypertension
- treat diabetes
- lipid lowering drugs
