7 and 10 Lipid Disorders and Case review Flashcards
2 yo with severe abdominal pain and rash, draw blood and and overnight in fridge seperates out to blood and fat. Why
Hyperchylomicronemia
Rare disease of childhood or seen in Type V adults
Genetically absent or redueced LPL or apoC2 or apoC3
Hyperchylomicronemia
What do we expect to see for TG in hyperchylomicronemia
TG from 2000 to 25000
Function of chylomicrons
carry mostly TG from gut to liver
Long term tx for hyperchylomicronemia
near total fat restriction and use of medium chain fatty acids to bypass more common long chain FAs
What happens microscopically during atherosclerosis
LDL crosses into endothelium into the intima
Monocytes phagocytize cholesterol
Cholesterol gets oxidixed
Vascular adhesion and metalloporoteinases activated to remodel the artrial wall
SMS migraiton
foam cell formation
Pt history: nonsmoking, asymptomatc female athlete, had high cholesterol since college, father had heart stents placed in mid 50s but didn't have a heart attack BP: 118/72 and BMI of 23 TC; 305 TG:55 HDL:85 LDL:209 Whats her risk for ASCVD?
Increased and we need to start tx today
Pt history: nonsmoking, asymptomatc female athlete, had high cholesterol since college, father had heart stents placed in mid 50s but didn't have a heart attack BP: 118/72 and BMI of 23 TC; 305 TG:55 HDL:85 LDL:209 DX?
Type IIA Familial Hypercholesterimia
Whats the metabolic issue with Type IIA Familial HYpercholesterimia?
LDL-R is defective, won’t remove cholesterol form circulation
–mutation in LDL-R, ApoB or PSCK9 GOF mutation
Tx recommendation for Type IIA Hypercholesterimia
High dose high intensity statins to decrease intracellular cholesterol, activate nuclear receptors and upregulate production of LDL-R
Pt goes undiagnosed with Type IIA Familial Hypercholesterimia until age 42. Comes in with chest pain, dyspnea on exertion: Dx?
Myocardial infarction (heart issues) see on EKG and enZ that pt had an infarct...recommend emergency angiogram and place stents
What tx do you recommend to a pt that has children and is diagnosed with Type IIA familial hypercholesterimia
Have kids on heart healthy diet and exercise as well as have lipids checked and tx if elevated (if over 12 years)
Pt Hx
45yo male smokes 1ppd
BP: 135/85 BMI:32 Waist:39 FBS:94
Exercise; none and has 2-4 beers a day
TC is 210 TG:165 HDL:40 LDL:137 nonHDL:170
What is he most at risk for?
Atherosclerotic heart disease
smoking causes more heart disease then cancer
What is the leading cause of disease and death
ASCVD
ASCVD stands for what diseases?
Aterosclerotic CV Disease
Heart attacks + STrokes + Peripheral Arthery Disease
CAD stands for
Coronary Atheroscloerotic Disease
Whats the biggest RISK of MI
LDL:HLD (then diabetes, smoking, HTN..)
Lifestyle can make a ____ differenct from lowest to highestl quintile in lifetime ASCD risk
10 fold
What are Heart healthful meausures for
BMI
BP
FBS
BMI <100
LDL-C >100
HDL <40
risk for ASCVD
TRIG 200-499 risk for
>1000 at risk for
CAD
risk for pancreatitis
Normal vs Optimal for: HDL LDL TC TG
Normal HDL: M>40 and F>50~ same for optimal
Normal LDL: <75
Which types of lipid disorders are predominantely genetic with minimal lifestyle influence?
Type I and IIA
Which lipid disorders are dormand until lifestyle (diabesity) or other disease (diabetes) unmask them
Type IIB, III, IV, and V
What lipoprotein is in excess in Type I severe hypertriglylceridemia?
Excess chylomicron bc we can’t off load TG they pick up in enterocyte d/t LPL or apoC2/C3 defect
What defect do we see in Type I hyperTG?
LPL or apoC2/C3
In a lipid panel, you see TG in chilld >2000, what do you suspect?
Type I hyperTG d/t LPL or apoC2/3 defect
Common presentation of IIa Familial Hypercholesterimia
see CAD < age of 60
In IIa familial hypercholesterolemia, what is the primary defect… what does this result in?
Defect of LDL-R–> end up with excess LDL
What lipid panel would we see in someone with IIa?
TC>275 and LDL-C >190 d/t LDL-R defect
Do we see TG abnormalities in IIa?
NOPE. just elevated LDL and TC
What risk are you at with CAD if you have IIb familial combined hyperlipidemia or with Metabolic syndrome?
CAD is 2x normal risk despite borderline lipid numbers
What lipoproteins are in excess in IIb familial combined hyperlipidemia or with metabolic syndrome
Excess LDL and VLDL
also more LDL-P
lipid panel: LDL 100 TG: 200-500 HDL <40 pt at 2x risk for CAD
This is IIb familial combined hyperlipidemia or with metabolic syndrome
What is the primary defect in IIb?
overproduciton of apoB100
What is the role of Hepatic lipase in IIb familial combined?
Pt has High TGS that drive CETP
CETP moves TG to LDL and HDL
When you have LDL with lots of TG, Hepatic lipase is all like, wow, too much and then makes sdHDL and sdLDL
What is the funciton of CETP?
Takes VLDL to HDL or LDL
see increased VLDL in high central adiposity or insulin resistance
Type III Dysbetalipoproteinemia causes premature CAD and is d/t :
overproduction of ApoE2/E2 + envirornment
What is the role of ApoE2 in Type III Dybetalipoproteinimeia?
ApoE2/E2 is poorly recognized on IDL by the LDL-R so doesn’t get taken up
What abnormal lipids do we expect to see in Type III Dybetalipoproteiniemia
TC and TG bonth 200 to 500
pts comes in with TC andn TG both 200 to 500 and excess VLDL and IDL with nodules on knees and orange creases on hands. Dx
Type III
What lipoproteins are in excess in pt with type III dybetaliporoteinmia
excess VLDL and IDL
Type IV hypertriglyceridemia can lead to
pancreatitis (not diabetic releated)
What lipoprotein is in excess in pt with Type IV hyperTG?
excess VLDL
What is our primray defect in type IV hyperTG?
defect of LPL or ApoC3 (means VLDL will accumulate)
What lpids are abnormal in pt with type IV hyperTG
TGS between 500-1000
Pt comes in with TG between 500-1000 and and exces VLDL, what is the primary defect
Type IV hyperTG:
defect is ApoC2 or LPL thus can’t break down VLDL
Pt comes to clinic with TC>275 and LDL-C >190 with an excess LDL level. What is the primary defect
LDL-R; patient has IIa familial hypercholesterolemia
YOung pt comes in with TG over 2000, what lipoprotein would you expect to be in excess?
has Type I severe hypterTG
mutation in LPL or apoC2/C3 thus very high chylomicrons bc they can’t offload
Pt comes in with excess LDL and VLDL.
His LDL is around 100 but had TG 200-500 with low HDL, what is the defect
Overproduction of apoB100:
Type IIB famililal hyperlipidemia or with metabolic syndrome
Pt comes in with elevated TC and TG both between 200-500. Here VLDL and IDL are elevated. DX?
Type III Dysbetalipoproteinemia,
Dt ApoE2 overproduction
Type V Familial hyperTG is dt defect where?
On the ApoC2 or C3 on BOTH VLDL and chylomicron
What Lipoproteins are elevated in Type V familial hyperTG?
VLDL and chylomicron
What does a lipid panel for pts with Type V familial hyperTG look like
TGs >1000
also have elevated chyomicrons and VLDL
Pt comes in with TG>1000 and elevated chylomicrons and VLDL, what do you expect primary defect is?
ApoC2 or C3 on both chylomicron and VLDL isn’t fnx properly
VLDL, chylomicrons and IDL are primary filled with:
TGs
elevated LDL, smoking, high BP and Family Hx all CV risk factors that cause:
LDL infiltrate into intima
90% of circulating cholesterol is
LDL
What lipoproteins are risk factors for atherosclerosis
IDL (VLDL remnants) and LDL
IDL and VLDL remntants as well
pt had apoA1 mutation means they cannot make
HDL = increased risk for disease
most potentially lethal inherited disease in world; see heterozygotes 1/500 and is autosomal dominant most often
famililal hypercholesterolemia
–> 50% males have MI or die from MI by 55, females by 65
LDL is 2X to 5X normal since birth
tx with statins to lower LDL by 12 yo to decrease risk
What catabolized LDL-R
PCSK9
Metabolic syndrome_____ risk of CAD even in absence of diabetes
doubles risk
increases LDL-P
increases VLDL remnants
can cause atherogenic dyslidemia
AHA criteria for Metabolic syndrome waist for men and women TG for men and women HDL for men and women BP FBG
waist men: >40 in and women >35
TBS for both >150
HDL for men 135/85 and women 135/85
FBG for both >100
Visceral adiposity and insulin resistance drive FFA to liver where TG-rich_____ are pushed into circulation
VLDL
What enZ acts on VLDL to make HDL and LDL
CETP
what enZ acts on LDL and HDL to make them sdHDL and sdLDL?
hepatic lipase
