Arteriosclerosis and Cholesterol

Question 1

What are the three types of arteriosclerosis?

Answer 1

1. Monkeberg medial sclerosis: calcification of media, incidental
2. Arteriolosclerosis: thickening of small vessels
3. Atherosclerosis: thickening of medium/large vessels

Question 2

Where in the blood vessel wall does atherosclerotic thickening occur?

Answer 2

Intima

Question 3

What are the four vessels most commonly effected by atherosclerosis?

Answer 3

1. Coronary
2. Abdominal Aorta
3. Popliteal
4. Internal Carotid

Question 4

What are the four modifiable risk factors of atherosclerotic disease?

Answer 4

HTN
Hypercholesterolemia
Smoking
Diabetes

Question 5

What are the three non modifiable risks of atherosclerotic disease?

Answer 5

Age
Gender
Genetics

Question 6

What is the pathogenesis of atherosclerosis?

Answer 6

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

Question 7

What is the earliest sign of atherosclerosis and when does it occur?

Answer 7

Fatty streaks, can occur in a large number of people as early as teen years

Question 8

What are the four pathologic results of atherosclerosis?

Answer 8

1. Stenosis of medium sized vessels: (politeal -PVD; coronary -angina; mesenteric: ischemic bowel disease)
2. Rupture and thrombosis: plaque rupture exposures coags and thrombus formation, MI and CVA( middle cerebral a)
3. Rupture and embolism: cholesterol clefts in emboli
4. Weakening of vessel wall and aneurysm : thickening of wall causes a diffusion barrier, atrophy and weakening of wall; aneurysm

Question 9

How much of the vessel lumen has to be narrowed in stenosis to cause symptoms?

Answer 9

more than 70%

Question 10

What are the two types of arteriolosclerosis?

Answer 10

1. Hyaline

2. Hyperplastic

Question 11

What are the causes of hyaline arteriolosclerosis?

Answer 11

1. Benign HT: plasma proteins pushed out of lumen by increased pressure, deposit in vessel wall, thicken
2. Diabetes: non-enzymatic glycosylation of basement membrane makes vessels leaky, protein leaks into wall, thickening

Question 12

What is the end result of hyaline arteriolosclerosis? in the kidney?

Answer 12

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

Question 13

What is the cause(s) of hyperplastic arteriolosclerosis?

Answer 13

Malignant HT cause hyperplasia of smooth muscle cells of vessel wall
Onion skin appearance

Question 14

What is the end result of hyperplastic arteriolosclerosis?

Answer 14

Fibrinoid necrosis

Acute renal failure with flea bite appearance from pin point hemorrhage

Question 15

Malignant HT

Answer 15

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

Question 16

What BP constitutes a HT emergency?

Answer 16

> 180/110

Question 17

When do you often see Monkeburg medial sclerosis?

Answer 17

on mamogram (looking for calcifications)
Monkeberg vessel calcifications follow the path of the vasculature

Question 18

What is a normal cholesterol levels?

Answer 18

less than or equal to 200 mg/dl

Question 19

Where are chylomicrons assembled?

Answer 19

Intestinal mucosal cells
Core of TAGs, cholesterol, fat soluble vitamens DEAK, cholesterol esters
Capsule of apo B-48

Question 20

Where do chylomicrons go after they are assembled?

Answer 20

Travel into lymph to lymphatic duct to dump out in the left subclavian vein

Question 21

What do chylomicrons pick up in the blood?

Answer 21

Apo C (CII activates LPL lipoprotein lipase on endothelial cells)
Apo E ( recognized by hepatic receptors) 
Both from HDL

Question 22

What regulates LPL?

Answer 22

Increases in fed states by insulin in adipose
Increases in fasting states in skeletal muscle
Highest expression in cardiac muscle

Question 23

What does LPL do?

Answer 23

Extracellular enzyme bound to heparin sulfate on endothelial cells that cleaves chylomicron and VLDL contents like TAG into FAs and glycerol

Question 24

What happens after chylomicrons are digested by LPL?

Answer 24

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)

Question 25

What is the apolipoprotein of VLDL/LDL?

Answer 25

ApoB100

Question 26

What is the role of VLDL?

Answer 26

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

Question 27

Where does HDL come from?

Answer 27

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)

Question 28

What is the function of HDL?

Answer 28

1. Provides apo e and c to chylomicrons and VLDL/LDL

2. Takes up cholesterol and returns it to the liver

Question 29

What is lipoprotein A and what is its role in disease?

Answer 29

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