foundations hyperlipidemia/cholesterolemia

Question 1

morbidity vs mortality

Answer 1

morbidity = bad things that come out of a disease that dont actually kill you (vs mortality, which do)

Question 2

artery layers (3)

Answer 2

tunica intima
tunica media
tunica adventitia/externa

Question 3

atheroma

Answer 3

accumulation of degenerative material in tunica intima

debris = macros, lipids, chol, FAs, Ca2+, fibrous CT

Question 4

hemodynamic pressure: laminar vs turbulent flow

Answer 4

laminar = normal flow

turbulent flow = causes damage to endothelium. caused by HTN, atherosclerosis

Question 5

hypercholesterolemia

Answer 5

incr LDL & abnormal lipids; decr HDL
due to 1) LDL Rs on liver decreased
or 2) defective ApoB100 (can’t take up VLDLs, give more cholesterol)

Question 6

foamy cells

Answer 6

macrophages ‘eat’ excess cholesterol and become foamy cells, the lipids not ‘eaten’ can get deposited in intima > intimal thickening

Question 7

familial hypercholesterolemia

Answer 7

defective/absent LDL Rs (cant remove LDL chol from circulation) or defective ApoB100 (cant uptake VLDL)
high LDL and overall cholesterol

Question 8

xanthelasma palpebrarum

Answer 8

yellow patches of cholesterol above eyelids, iris margin, achilles
s/s of hypercholesterolemia
commonly leads to CAD

Question 9

stenosis definition

Answer 9

occlusion of bv
can rupture, ulcerate, or erode b/c of weakened bv walls
if chronic damage: can hemmorhage (new vessels formed attempting to restore flow)

Question 10

embolism vs thrombosis

Answer 10

thrombosis = block that forms locally
embolism = piece of material breaks away and blocks a vessel elsewhere

Question 11

dissecting aneurysm (definition, causes)

Answer 11

splitting of wall (tear in tunica intima)
always due to structural weakness/damage
most commonly caused by HTN, atherosclerosis

Question 12

aneurysm definition

false aneurysm vs true aneurysms (saccular, fusiform)

Answer 12

aneurysm - abnormal wall dilation
false - hematoma (blood extravasation into extravascular CT)
true: saccular - one side, outpouching
true: fusiform - diffuse dilation

Question 13

debakey classification of aortic aneurysms

type I, II, III

Answer 13

type I - asc, desc, and arch (all)
type II - asc
type III - desc

Question 14

vessel compliancy (definition, what happens when lost)

Answer 14

compliancy - elasticity, ability to modify BP

if lost: can’t modify BP > HTN

Question 15

NASH (non alcoholic steatohepatitis) def & cause

Answer 15

NASH - inflammation, danger of cirrhosis

due to fatty liver (liver has no storage limit for lipids/glycogen)

Question 16

HSL (H sensitive lipase) action & control

Answer 16

HSL: hydolyses TAGs (triacylglycerols) > release FAs to bloodstream (some bind albumin, others = FFAs)
HSL activated by epi, glucagon
HSL inhibited by insulin

Question 17

obesity and FFA uptake

Answer 17

normally: need high [FA transporters]=ACAT and high [FFAs] to get best uptake
with obesity: increased FFA uptake! much higher than normal levels

Question 18

FA transporters in cellular uptake:
pm
outer mito
inner mito

Answer 18

pm: ACAT (acylcholesterol acyl transferase)
outer mito: CPT I (carnitine palmitoyltransferase)
inner mito: CPT II

Question 19

systemic primary carnitine deficiency

Answer 19

impaired transport of FAs > mito > toxic accumulation

weakness, hypoketoic hypoglycemia

Question 20

hypertriglyceridemia

Answer 20

high VLDL, TG
can be genetic: auto dominant (hyperproduction of VLDL)
can cause pancreatitis (TG > 1000mg/dl)

Question 21

familial lipoprotein lipase deficiency

Answer 21

pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas
severe hypertriglyceridemia
chylomicron clearance impaired > milky blood

Question 22

MCAD (medium chain acyl coa dehydrogenase) deficiency

Answer 22

accumulation of 8-10C chain FAs in blood

hypoketotic hypoglycemia, liver dysfxn

Question 23

LCAD (long chain acyl coa dehydrogenase) deficiency

Answer 23

presents earlier than MCAD deficiency, worse s/s

mother can get fatty liver of pregnancy

Question 24

diabetic ketoacidosis mech

Answer 24

glucose uptake decr > fat metab incr > ketone body prod incr > diabetic ketoacidosis

primarily type I diabetes

Question 25

zellweger syndrome (relation to lipids)

Answer 25

deficiency/absense of peroxisomes very long chain/branched FAs normally broken down/modified here > impaired, multiple organ systems affected usually only live 6 mo> 1 yr old

Question 26

regulation of HMG-CoA Reductase inhibition (2) activation (2)

Answer 26

inhibition: (1) high glucagon, (2)statins activation: (1) high insulin, (2) SREBPs (sterol regulatory element binding prots) -monitor low cholesterol, upreg HMG CoA reductase synthesis

Question 27

Niemann-Pick Disease

Answer 27

deficiency of Niemann-pick c1 like 1 transporter (normally transports dietary cholesterol > body) diease: hypocholesterolemia ezetimide drug acts here!

Question 28

tangier's disease (ABC1 transporter protein deficiency)

Answer 28

ABC1: moves excess cholesterol to outer leaflet for easy access for HDL tangiers: ABC1 defect > HDL can't reverse transport > 'defective' HDL removed from circulation (HDL levels in these pts: 1-5% of normal) s/s: orange tonsils, hepatosplenomegaly, lipid deposits in schwann cells (peripheral neuropathy)

Question 29

ApoA1 Milano mutation

Answer 29

ApoA1 pt mutation better at reverse chol transport than normal, decreased atherosclerosis ApoA1 stimulates LCAT: better at 'trapping' chol in HDL low HDL levels, hypertriglyceridemia, but NO atherosclerosis (incr longevity, low CV disease)

Question 30

gallstones (assoc w bile acids) primary vs secondary bile acids

Answer 30

high [lithocholic acid] = incr likelihood of gallstones (lith = stone) lithocholic = secondary bile acid (has modifications by gut bac) primary acids = synth by liver

Question 31

lipemia retinalis

Answer 31

s/s of high lipids: | bv of eye look milky

Question 32

``` normal serum levels: cholesterol LDL HDL TG ```

Answer 32

chol: 180-200mg/dl LDL:

Question 33

cholesterol as a biosynthetic mol:

Answer 33

used for: bile acids synth steroid H synth vitamin D synth

Question 34

statin mech of action, main effect

Answer 34

moa: inhibits HMG-CoA reductase, incr in LDL Rs | large decr LDL, modest decr TG/incr HDL

Question 35

fibrates mech of action, main effect

Answer 35

moa: incr LPL activity (incr VLDL catabolism), incr ApoA1 (incr HDL) large decr TGs, modest incr HDL/decr LDL/chol

Question 36

niacin mech of action, effect, side effect

Answer 36

niacin = vit b3 decr hepatic synth of TGs large decr TG, slight incr HDL/decr chol/LDL flushing side effect! can give aspirin

Question 37

ezetimibe: moa, effect

Answer 37

niemann-pick c1 like 1 transporter inhibitor (inhibits dietary cholesterol abs) decr total chol/LDL

Question 38

bile acid resins/sequestrants cholestyramine moa, effect, side effect

Answer 38

inhibs bile acid reuptake > liver uses more chol to synth new bile acids decr chol/LDL, slight incr HDL/TG contraindicated in hypertg gi side effects