MOD 6 Flashcards
What is an atherosclerosis
Thickening and hardening of the vessel walls due to an atheroma
What’s an atheroma
accumulation of intra and extracellular lipid in the intima and media of large-medium sized vessels
What’s an arteriosclerosis and name one cause
Thickening and hardening of vessel wall NOT due to an atheroma. E.g; calcification with age
What would you see histologically in an atherosclerosis
- Pale - fat
2. Asymmetrically narrowed lumen
Name the normal layers of an artery from lumen out
ESIMEA
- Endothelium
- Sub-endothelial CT
- Internal elastic lamina
- Muscular media
- external elastic lamina
- adventitia
Name the 5 steps leading up to an Atherosclerosis and which mechanism they fall under
Mechanism 1 = step 1: Chronic endothelial injury
-hemodynamic stress, hypertension, toxins, high LDLs
Mechanism 2 = Step 2,3,4
2. Endothelial dysfunction: platelet adhesion and release of PDGF, monocyte accumulation in the intima, T lymphocytes join the party
- Smooth muscle emigrates from media –> intima, narrowing the vessels
- Smooth muscle cells and macrophages engulf oxidized LDLs producing foam cells
Mechanism 3: step 5:
-smooth muscle cells proliferate in response to cytokines, GFs, collagen and ECM, and neovascularisation
Name the three stages in which plaques develop and their characteristics
- Fatty Streak: normal in adolescence, no disturbance to blood flow, yellow lipid deposits in the intima
- Simple Plaque: endothelium still intact but vessel lumen is impinged, plaque often occurs around the Ostia and are irregularly outlined, widely distributed and raised about 1 cm in diameter
- Complicated Plaque: endothelial surface has broken and released TF. Next steps can be hemorrhage, thrombosis and calcification
What can occur as a result of hemorrhage to a plaque? Name one example of a consequence
Thromboemboli/microemboli if the plaque ruptures.
(The plaque can also expand)
e.g cholesterol emboli could reach the kidneys and cause renal failure
What three could occur as a result of degeneration of surrounding elastic tissue and muscle due to an atherosclerosis
Weakening of the vessel walls, can cause dilation of the vessel (aneurysmal dilation), inflammation and arthritis
What could become exposed as a result of ulceration or erosion to the luminal surface of the plaque
Highly thrombogenic substances, encourages the formation of a superimposed thrombus
What is the clinical term for what progressive plaque growth causes
Critical Stenosis; critical narrowing of an artery
Name 4 early microscopic changes of an atherosclerosis
- foam cells
- lymphocytes
- smooth muscle cells
- extracellular lipid deposition
Name 6 late microscopic changes of an atherosclerosis
- fibrosis
- necrosis
- cholesterol clefts
- disruption of internal elastic lamina that could extend into the media
- ingrowth of blood vessels
- plaque rupture
Name 5 common sites for an atherosclerosis
- coronary arteries - ischemic damage
- carotid
- cerebral - stroke
- arteries of the legs
- abdominal aorta
Why do you get an edema when the heart weakens?
Blood is pumped less efficiently and can back up and increase pressure in the veins, fluid can then be pushed into any air spaces including the lungs and peripheral tissues
How much of the lumen has to be blocked for blood flow in an artery to be significantly reduced?
70-80%
What is a coronary thrombosis
formation of a blood clot inside a vessel of the heart, usually occurs over ruptured atheromatous plaques resulting in an MI
What does a survived infarction look like, and why can it be dangerous?
White as there is old fibrous scarring, the scarring disrupts the electricity of the heart and can cause an arrhythmia - leading to sudden death
Provide 6 things that can happen in a timeline of Cerebral Ischemia
- Atherosclerosis of carotid arteries
- Thrombus forms over a plaque
- Thromboembolism to cerebral arteries
- Transient ischemic attacks: brief episodes of neurological dysfunction
- Stroke
- Multi-infarct dementia: a major stroke, one of many causes of dementia
What kind of necrosis can form as a result of a stroke, and what would it cause?
Liquefactive necrosis, may cause an absess filled with CSF
What is an AAA, list one major risk factor and a current preventative step in place?
Abdominal Aortic Aneurysm
- continuous smoking
- ultrasound scans at 65
Why can an AAA cause terrible abdominal pain?
Because the atheroma has gone on for decades and caused constant endothelial damage, resulting in chronic abdominal pain
How does an AAA usually form, and what are some of its characteristics
Due to weakening of the large abdominal artery wall causing local dilation, almost always due to atherosclerosis,
- can be 10-15 cm in diameter
- lined/filled by thrombus
- may rupture and produce an emboli
What colour is dead muscle?
yellow
What happens if you have a blockage to your superior mesenteric artery?
Lose blood supply to the …
a) intestine: causes malabsorption and intestinal infarction
b) bowel: will die within a day or so with no oxygen, when the mucosal lining starts dying the bacteria in the feces can enter the bloodstream causing septic shock
Name 3 consequences as a result of peripheral vascular disease and what other disease it is particularly associated with?
- intermittent claudication
- ischemic rest pain
- gangrene
Diabetes
What’s Leriche syndrome?
Atherosclerosis of the abdominal aorta as it bifurcates into the common iliac arteries
Name 6 cells involved in atherogenesis
- macrophages
- lymphocytes
- smooth muscle cells
- platelets
- endothelial cells
- foam cells
Name the 4 steps of a plaque rupture leading to a blood clot
- Plaque forms lining an artery, takes many years and is a silent disease
- Plaque grows
- plaque ruptures - causing the release of TF from the endothelium
- Blood clot forms as a result of coagulation activation
What are the 3 roles of endothelial cells
Secrete collage, stimulate proliferation/migration of smooth muscle cells, alter permeability to lipoproteins
What do platelets do other than form a platelet plug?
stimulate proliferation/migration of smooth muscle cells through releasing PDGF
What are the 2 roles of smooth muscle cells
phagocytose oxidized LDLs to form foam cells, secrete collagen and ECM
What are the 3 roles of macrophages
phagocytose oxidized LDLs to form foam cells, stimulate proliferation and migration of smooth muscle cells, secrete proteases that modify the matrix
Name 8 risk factors for an atherosclerosis
- age (increases with age)
- premenopausal women are protected due to estrogen
- Familial hyperlipidemia and cholesterolemia
- smoking
- alcohol - an independent risk factor
- hypertension
- geography - less-developed nations
- diabetes
What is the main defect in familial hyperlipidemia and 3 clinical signs
Abnormal lipoproteins
- corneal arcus
- tendon xanthoma
- xanthelasma
What is the main defect in familial cholesterolemia
Defect in LDL receptor on hepatocytes, making it more difficult to take up oxidized LDLs so they remain in the circulation for longer
What can hypertension form a strong link between
Ischemic heart disease and high diastolic and systolic BP
Why is smoking a risk factor for atherosclerosis and ischemic heart disease?
It’s a procoagulant that inhibits prostacyclin
Why is diabetes a risk factor for atherosclerosis
Amino acids react with glucose derivatives to form advanced glycation end products (AGE). AGE cross-links collagen in large vessels - leading to decreased endothelial elasticity (changing the protein properties of the vessel wall) and increased LDLs get trapped - more cholesterol in the intima
What is the clinical relevance of LDLs
Have a very long half-life (and liver has less of an affinity for them) so they’re more susceptible to oxidative damage
Why is aspirin not the best treatment for atherosclerosis
Since aspirin is a blood thinner you’re less likely to die of atherosclerosis but more likely to have a hemorrhagic stroke :(
