Atherosclerosis Flashcards
What is atherosclerosis ?
Gruel; hardness to elastic and medium-large arteries
What is an atheroma ?
Intimal fibrous cap
Central core rich in lipids
Clinical Significance of Atherosclerosis
IN 2016 - atherosclerosis was related to the top 2 causes of death
Although death rates from heart and circulatory diseases have fallen and plateoud from 1969 to 2017.
Describe features of symptomatic atherosclerosis
Contributes to 1/2 of all deaths (western world)
State some clinical conditions linked to atherosclerosis
MI
Stroke
Aneurysm
Peripheral Vascular Disease
How has the peak of deaths from atherosclerosis reduced from 1963 to the 2000’s ?
Improved methods of treatment
Prevention of recurrences
Prevention of atherosclerosis
50% decreased death rate heart attack
70% decreased death rate stroke
Risk Factors for atherosclerosis
Age
Sex
Genetics
Hyperlipidaemia
Hypertension
Smoking
Diabetes Mellitus
Hyperlipidaemia
Elevated concentrations of lipids/fats in the blood. (LDL)
One of the most prevalent risk factors contributing to the evolution of atherosclerosis.
What does hyperlipidaemia cause ?
Impairs endothelial function
Accumulates within intima
Causes oxidative modification of LDL
Describe oxidative modification of LDL
Inhibits the motility of macrophages
Stimulates the release of cytokines
Cytotoxic to endothelial and smooth muscle cells
Chemotactic centre for monocytes
State the stages of atherosclerosis
Initiation/ Formation Stage (subclinical)
Adaptation stage (subclinical)
Clinical Stage
How is atherosclerosis developed ?
Chronic endothelial injury/ dysfunction
Role of Lipids -
Role of macrophages
Smooth muscle proliferation
Formation of a fibro-lipid plaque
Injury to the plaque - thrombus formation
Describe chronic endothelial injury / dysfunction risk factors
Haemodynamic disturbances
Hypercholesterolemia
Hypertension
Smoking
Toxins
Viruses
Immune Reactions
What happens when endothelial cells are injured ?
This creates gaps in between endothelial cells
IN these gaps you get monocytes
Monocytes adhere to the endothelium
State the steps leading to atherosclerosis
Chronic Endothelial injury
Endothelial dysfunction (monocyte adhesion and immigration)
Smooth muscle emigration from media to intima
(macrophage activation)
Macrophages and smooth muscle cells engulf lipid
Smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid
What does endothelial dysfunction lead to ?
Increased endothelial permeability
Increased leukocyte adhesion
Increased monocyte adhesion and migration
Yellow dots
Low density cholesterol
Monocytes
Monocytes pass through the endothelium and change themselves into macrophages, eating away oxidised LDL.
Function of macrophages
Macrophages eat away, phagocyte oxidised LDL
Role of macrophages
What do they secrete ?
Engulf oxidised LDL = foam cells
Secrete :
- IL1 (interleukin 1)
- TNF (tumor necrosis factor)
- MCP1
- Growth factors
- INterferon
Fatty streak
Accumulation of LDL
Raised streak of yellow
Foam cells
Macrophages that phagocytes oxidised LDL
Role of smooth muscles proliferation
Collagen and ECM deposition
Fatty streak —> Mature fibro-fatty atheroma
What happens once macrophages / foam cells die ?
The LDL cholesterol in the cytoplasm will form crystals.
All cholesterol forms a lipid debris centre.
Summary of atheroma formation
Monocytes adhere and emigrate into the tunica intima.
Monocytes change into macrophages
In addition to monocytes, LDL also goes into the tunica intima and becomes oxidised .
Macrophages phagocytose, oxidise LDL
This forms foam cells and these cells produce granules which further attracts more monocytes.
Foam cells and granules cause migration of smooth muscle cells from the tunica media to the intima.
These muscle cells produce collagen, forming the fibrous caps.
Eventually the foam cells die and form cholesterol crystals in the centre
Describe the morphology of atheromatous plaque
Patchy and raised white to yellow
0.3-1.5 cm
Core of lipid
Fibrous cap
Where are atheroma commonly found ?
Abdominal aorta
Coronary Arteries
Popliteal arteries - back of leg
Descending thoracic aorta
Internal carotid arteries
Vessels of the circle of Willis
Most common site of atheroma ?
Abdominal aorta
Atheroma in coronary artery
Contributes to heart attacks
Vessels of the Circle of Willis
Circuit of the blood vessels in the brain
Patient could have a stroke due to blockage
How do complicated lesions look like ?
Calcification
Rupture or ulceration
Haemorrhage
Thrombosis
Aneurysmal dilation
What are fatty streaks precursors to ?
Plaques
Fatty streaks morphology
Foam cells and T lymphocytes
Elongated streaks 1cm or longer
Fatty dots <1mm
Where are fatty dots found ?
IN the aorta, present before the age of 1 in everyone
In coronary artery from adolescence
If there are complications, what can atherosclerosis lead to ?
Thrombosis
Calcification
Aneurysmal dilation
Ischaemic Events
Describe what happens in the preclinical phase
Normal artery
Fatty streak
Fibrofatty plaque
Advanced/ vulnerable plaque
Describe what happens in the clinical phase
Aneurysm and Rupture
Occlusion by thrombosis
Critical stenosis (progressive plaque growth)
Primary prevention of atherosclerosis
Stop smoking
Control hypertension
Weight reduction
Lowering total LDL
Reduce calories intake
Secondary prevention of atherosclerosis
Prevent complication
Antiplatelet drugs in thrombosis
Lower blood lipid levels
What do smooth muscle cells produce ?
Collagen
What is the white parts found in the left ventricle ?
Fibrous scar tissue - could be due to myocardial infarction.
Why may the thyroid appear white ?
Auto-immune thyroiditis
