MoD S6 - Atherosclerosis Flashcards
(26 cards)
What is an atheroma?
Accumulation of intracellular and extracellular lipid in the intima and media of large to medium sized arteries
Outline the differences between atherosclerosis and arteriosclerosis
Atherosclerosis is the thickening and hardening of arterial walls as a consequence of atheroma whereas arteriosclerosis is the thickening of walls of arteries and arterioles due to hypertension and diabetes mellitus
Outline the events leading to the formation of atherosclerotic lesions
- Chronic endothelial injury
- Endothelial dysfunction with platelet adhesion and monocyte accumulation
- Release of cytokines and growth factors
- Smooth muscle emigration from tunica media to intima
- Macrophages and smooth muscle cells engulf lipids to form foam cells
- Smooth muscle proliferation, collagen and matrix deposition
What are the three different macroscopic appearances of atherosclerosis?
Fatty streaks, simple plaque and complicated plaque
Describe the differences in appearance of fatty streak, simple and complicated plaque
Fatty streak - yellow lipid deposits in intima, raised
Simple - Raised, white/yellow, widely distributed, irregular outline, enlarge and coalesce
Complicated - Thrombosis, haemorrhage, calcification, aneurysm formation
What are the early microscopic changes seen in atherosclerosis?
- Proliferation of smooth muscle
- Accumulation of foam cells
- Extracellular lipid
List some possible consequences of ischaemic heart disease
Sudden death, MI, angina pectoris, arrhythmias, cardiac failure
List some possible consequences of cerebral ischaemia
Transient ischaemic attacks, cerebral infarction, Multi‐infarct dementia
What are the later microscopic changes seen in atherosclerosis?
Fibrosis, necrosis, cholesterol clefts, disruption of internal elastic lamina, damage extends to media, ingrowth of blood vessels, plaque fissuring
How does multi‐infarct dementia differ from Alzheimer’s?
Due to vascular problems opposed to neurological
List some possible consequences of mesenteric ischaemia
Ischaemic colitis, malabsorption, intestinal infarction
How would a patient with peripheral vascular disease present and how may this progress if left untreated?
Intermittent claudication
Develops into gangrene
How does intermittent claudication differ from Leriche syndrome?
IC‐ pain in the calf muscles
LS‐ pain in buttocks, may also present with impotence
How can abdominal aortic aneurysm result in death?
Ruptures causing haemorrhage resulting in hypovolemic shock
What are the potential genetic risk factors for atherosclerosis?
Apolipoprotein E genotype, familial hyperlipidaemia
Outline the main concepts involved in the insudation theory?
Endothelial injury occurs causing inflammation and subsequent increased permeability to lipid from the plasma
What is the monoclonal hypothesis? (Benditt and Benditt)
Smooth muscle cells proliferate and each plaque that forms is monoclonal
Example of abnormal growth control
Each plaque is a benign tumour
What possible aetiology for atherogenesis does the monoclonal hypothesis lead to?
Possible viral link
List the main cells involved in atherogenesis and their roles
Endothelial‐ haemostasis, altered permeability to lipoproteins, secretion of collagen, stimulation of proliferation and migration of SMC
Macrophages‐ oxidise LDL, take up lipids and become foam cells, secrete proteases which modify extracellular matrix, stimulate proliferation and migration of SMC
Platelets‐ haemostasis, stimulate proliferation and migration of SMC
Lymphocytes‐ TNF interferes with lipid metabolism, stimulation of proliferation and migration of SMC
Neutrophils‐ secrete proteases leading to continued local damage and inflammation
SMC‐ take up LDL to make foam cells, synthesise collagen and proteoglycans
Outline the main concepts of the Reaction to Injury Hypothesis (Aka insudation)
- Plaque forms due to endothelial injury
- Hyperlipidaemia causes endothelial damage
- Results in increased permeability to lipid and platelet aggregation
- Monocytes migrate in and form foam cells
- SMC migrate and proliferate
What later additions were made to the Reaction to Injury hypothesis?
Endothelial damage may be subtle and hard to see, oxidised LDL may be responsible for endothelial damage
Outline the unifying hypothesis and what theories contribute to this one overall hypothesis
Thrombogenic theory, insudation theory, monoclonal hypothesis and response to injury hypothesis
Endothelial injury occurs due to:
● toxins, hypertension, raised LDL, haemodynamic stress
Endothelial injury then results in:
● platelet aggregation, PDGF production, SMC migration and proliferation
● Insudation of lipids, oxidation of LDL, foam cells form from SMC and macrophages
● Migration of monocytes into intima
Stimulated SMC produced intercellular matrix
Foam cells secrete cytokines causing:
● further SMC stimulation, recruitment of other inflammatory cells
What interventions would be used in atherosclerosis?
Stop smoking, modify diet, lipid lowering drugs, treat hypertension, treat diabetes
Why is cigarette smoking a risk factor for atheroma?
Increased risk of IHD
Believed to be due to coagulation system (decreased PGI2, increased platelet aggregation)
