Arteriosclerosis and Cholesterol Flashcards
What are the three types of arteriosclerosis?
- Monkeberg medial sclerosis: calcification of media, incidental
- Arteriolosclerosis: thickening of small vessels
- Atherosclerosis: thickening of medium/large vessels
Where in the blood vessel wall does atherosclerotic thickening occur?
Intima
What are the four vessels most commonly effected by atherosclerosis?
- Coronary
- Abdominal Aorta
- Popliteal
- Internal Carotid
What are the four modifiable risk factors of atherosclerotic disease?
HTN
Hypercholesterolemia
Smoking
Diabetes
What are the three non modifiable risks of atherosclerotic disease?
Age
Gender
Genetics
What is the pathogenesis of atherosclerosis?
Damage to intima causes lipid entry
Lipids oxidize
Picked up by macrophage scavenger receptors that bind apoB receptors from oxidized LDL
Cholesterol esters accumulate in macrophages that are called foam cells
Foam cells release cytokines and growth factors that cause smooth muscle cells recruitment and a cycle of inflammation, injury, and repair that results in a necrotic cholesterol core covered by a fibrotic cap
What is the earliest sign of atherosclerosis and when does it occur?
Fatty streaks, can occur in a large number of people as early as teen years
What are the four pathologic results of atherosclerosis?
- Stenosis of medium sized vessels: (politeal -PVD; coronary -angina; mesenteric: ischemic bowel disease)
- Rupture and thrombosis: plaque rupture exposures coags and thrombus formation, MI and CVA( middle cerebral a)
- Rupture and embolism: cholesterol clefts in emboli
- Weakening of vessel wall and aneurysm : thickening of wall causes a diffusion barrier, atrophy and weakening of wall; aneurysm
How much of the vessel lumen has to be narrowed in stenosis to cause symptoms?
more than 70%
What are the two types of arteriolosclerosis?
- Hyaline
2. Hyperplastic
What are the causes of hyaline arteriolosclerosis?
- Benign HT: plasma proteins pushed out of lumen by increased pressure, deposit in vessel wall, thicken
- Diabetes: non-enzymatic glycosylation of basement membrane makes vessels leaky, protein leaks into wall, thickening
What is the end result of hyaline arteriolosclerosis? in the kidney?
Cause lumen to narrow and end organ damage
Glomerular scarring = arteriolonephrosclerosis due to thickening of afferent arteriole
Reason for renal failure in diabetics and people with chronic HT
Grossly kidney because small with cortex scarring
What is the cause(s) of hyperplastic arteriolosclerosis?
Malignant HT cause hyperplasia of smooth muscle cells of vessel wall
Onion skin appearance
What is the end result of hyperplastic arteriolosclerosis?
Fibrinoid necrosis
Acute renal failure with flea bite appearance from pin point hemorrhage
Malignant HT
Malignant hypertension is an accelerated, severe hypertensive disorder characterized by rapidly rising BP, usually in excess of 140 mm diastolic and may be accompanied by encephalopathy, nephropathy, retinopathy, heart failure and/or myocardial ischemia
What BP constitutes a HT emergency?
> 180/110
When do you often see Monkeburg medial sclerosis?
on mamogram (looking for calcifications) Monkeberg vessel calcifications follow the path of the vasculature
What is a normal cholesterol levels?
less than or equal to 200 mg/dl
Where are chylomicrons assembled?
Intestinal mucosal cells
Core of TAGs, cholesterol, fat soluble vitamens DEAK, cholesterol esters
Capsule of apo B-48
Where do chylomicrons go after they are assembled?
Travel into lymph to lymphatic duct to dump out in the left subclavian vein
What do chylomicrons pick up in the blood?
Apo C (CII activates LPL lipoprotein lipase on endothelial cells) Apo E ( recognized by hepatic receptors) Both from HDL
What regulates LPL?
Increases in fed states by insulin in adipose
Increases in fasting states in skeletal muscle
Highest expression in cardiac muscle
What does LPL do?
Extracellular enzyme bound to heparin sulfate on endothelial cells that cleaves chylomicron and VLDL contents like TAG into FAs and glycerol
What happens after chylomicrons are digested by LPL?
Apo C dissipates back to HDL, smaller (almost no TAGs) chylomicron reminant goes to liver where Apo E receptor allows for receptor mediated endocytosis, fuses with lysosome, digests the rest of the chylomicron (aas, cholesterol, fatty acids)
What is the apolipoprotein of VLDL/LDL?
ApoB100
What is the role of VLDL?
Made in liver to carry lipid to peripheral tissue
Gains Apo E and C in blood like chylomicrons
Digested by LPL and lose TAGs
Becomes LDL (higher cholesterol and cholesterol ester content)
Uptake of LDL in tissues mediated by LDLR that recognizes ApoB100 and ApoE
Where does HDL come from?
Made in blood (but also can be made in liver and intestines)
Esterifies cholesterols so that it can maintain a good gradient for uptake (sink)
What is the function of HDL?
- Provides apo e and c to chylomicrons and VLDL/LDL
2. Takes up cholesterol and returns it to the liver
What is lipoprotein A and what is its role in disease?
Lp(A) has the same structure as LDL by with an apo(a) molecule linked to apoB100
ApoA is a structural analog of plasminogen so competes with plasminogen for fibrin binding and induces a hypercoagulable state by slowing the degredation of clots and increase risk of heart disease
