Lipids 1

What are the two main lipids in the blood?

Cholesterol and triglycerides.

Cholesterol is an essential component of what body structure?

All animal cell membranes.

What two substances does cholesterol form?

Steroid hormones and bile acids.

Cholesterol is a precursor for which vitamin?

Vitamin D.

What is the function of triglycerides?

They aid in the transfer of energy from food into the cells.

What are lipoproteins?

Globular particles that carry cholesterol and triglycerides and contain apoproteins (apolipoproteins).

What is the main job of lipoproteins?

To carry insoluble molecules.

How are lipoproteins classified?

By density.

Which lipoprotein is the least dense?

Chylomicrons.

When are chylomicrons normally found in the blood?

Only after eating fat-containing foods.

Where are chylomicrons assembled, and where do they travel?

Assembled in the gut and travel via the portal vein to the liver.

What is the function of chylomicrons?

To transfer energy from food to muscle and fat cells (they are normally completely metabolized).

What does the liver use to manufacture VLDL?

Its own stores of fat and carbohydrates (making apolipoprotein B-containing VLDL particles).

As VLDL loses triglycerides, what does it sequentially become?

VLDL becomes IDL, then becomes LDL.

What takes up excess LDL particles?

The liver's LDL receptors.

After LDL is taken up by the liver, where does its cholesterol go?

It is excreted into the bile.

Where is HDL made?

In the liver and intestine.

What are the functions of HDL?

It facilitates the transfer of apoproteins among lipoproteins and participates in cholesterol transport (to other lipoproteins or into the liver).

For which lipoproteins is apolipoprotein B-100 the structural protein?

VLDL, IDL, LDL, and lipoprotein(a).

ApoB-100 is the ligand for which receptor?

The LDL receptor.

ApoB-100 is required for the assembly and secretion of which lipoprotein?

VLDL.

Apolipoprotein B-48 is a truncated form of what?

B-100.

Does apolipoprotein B-48 bind the LDL receptor?

No.

ApoB-48 is required for the assembly and secretion of which lipoprotein?

Chylomicrons.

What is lipoprotein(a) [Lp(a)]?

An LDL-like particle carrying a single apoprotein(a) strand bound to the apoB-100 component.

What determines Lp(a) levels?

Almost entirely genetics; it is largely unaffected by diet or exercise.

How does Lp(a) relate to ASCVD risk?

ASCVD risk increases with higher Lp(a) concentrations.

What is the target total cholesterol for most patients?

<200 mg/dL.

What is the target triglyceride level for most patients?

<150 mg/dL.

What is the target LDL for most patients?

<100 mg/dL.

What is the target HDL for most patients?

>50 mg/dL.

What is the target Lp(a) for most patients?

<30 mg/dL.

In the exogenous pathway, what happens to cholesterol and fat that enter intestinal cells?

Fatty acids are assembled into triglycerides and packaged with a small amount of cholesterol and lipoproteins to form chylomicrons.

In the exogenous pathway, how do chylomicrons reach the bloodstream?

They move into lymphatic vessels, then enter the bloodstream.

What does lipoprotein lipase (LPL) do to chylomicrons?

Breaks them down, freeing triglycerides into fatty acids.

In the exogenous pathway, what happens to the freed fatty acids?

They serve as energy in muscle cells or are stored in adipocytes.

Where do chylomicron remnants go?

To the liver, where they deposit leftover lipid molecules.

In the endogenous pathway, what does the liver package into VLDL?

Synthesized fatty acids and cholesterol combined with chylomicron remnants.

In the endogenous pathway, what does LPL do to VLDL?

Releases triglycerides for use in nearby tissues.

In the endogenous pathway, as VLDL loses triglycerides, what does it become?

First an IDL, then eventually an LDL.

How are LDLs taken into cells?

Endocytosed by cells with LDL receptors in the liver and/or peripheral tissues requiring cholesterol.

Which enzyme breaks down both chylomicrons and VLDL to release triglycerides?

Lipoprotein lipase (LPL).

What is hypolipidemia?

Characterized by low levels of lipids (triglycerides and/or cholesterol).

What is the typical total cholesterol level in hypolipidemia?

<120 mg/dL.

What is the most common cause of hypolipidemia?

Abetalipoproteinemia.

What is the inheritance pattern of abetalipoproteinemia?

Autosomal recessive.

Which protein is affected in abetalipoproteinemia, and what is its role?

The microsomal triglyceride transfer protein (MTP), which packages triglycerides into lipoproteins for blood transport.

When does abetalipoproteinemia present?

In early infancy.

How does abetalipoproteinemia lead to failure to thrive?

Low levels of chylomicrons cause malabsorption, leading to failure to thrive.

What GI finding is seen in abetalipoproteinemia?

Malodorous steatorrhea.

What vitamin-deficiency findings occur in abetalipoproteinemia?

Osteomalacia and spinocerebellar degeneration.

How is abetalipoproteinemia diagnosed?

Intestinal biopsy showing cells with large amounts of fat.

What is the general treatment of abetalipoproteinemia?

Reduce dietary fats and give vitamin supplements.

Why is vitamin A given in abetalipoproteinemia?

To prevent retinal damage.

Why is vitamin E given in abetalipoproteinemia?

To prevent neuro issues.

What total cholesterol level defines hyperlipidemia?

>200 mg/dL.

What triglyceride level defines hyperlipidemia?

>150 mg/dL.

What LDL level defines hyperlipidemia?

>100 mg/dL.

What are the two broad classifications of hyperlipidemia?

Primary (familial, inherited) and secondary (acquired).

What is the inheritance of primary hyperlipidemia?

Familial/inherited - autosomal dominant or recessive (many variations).

What is the most common cause of secondary hyperlipidemia?

Diabetes mellitus.

How does diabetes cause secondary hyperlipidemia?

Low insulin decreases LPL activity, so VLDL sits in the blood and is eventually converted to LDL (normally insulin increases LPL activity and lipid uptake).

How does hypothyroidism cause secondary hyperlipidemia?

Slow metabolism reduces synthesis of LDL receptors, so LDL can't return to the liver and blood levels rise.

How does nephrotic syndrome cause secondary hyperlipidemia?

Plasma proteins are lost in the urine, and to compensate the liver makes more VLDL.

Which medications can cause secondary hyperlipidemia?

OCPs, beta blockers, and thiazide diuretics.

Are patients with hyperlipidemia usually symptomatic?

No - usually asymptomatic; most abnormalities are detected on lab screening.

What skin manifestations occur in hyperlipidemia?

Xanthomas, xanthelasma, and corneal arcus.

What liver complication results from hyperlipidemia?

Hepatic steatosis (fatty liver disease).

What vascular complications result from hyperlipidemia?

ASCVD, stroke, peripheral vascular disease, and carotid artery stenosis.

How is hypertriglyceridemia defined?

Excess triglycerides in the blood, >150 mg/dL.

What are the two broad classifications of hypertriglyceridemia?

Primary (familial, inherited) and secondary (acquired, more common).

How does obesity cause secondary hypertriglyceridemia?

Hepatic overproduction of VLDL and decreased breakdown of circulating triglycerides.

How does uncontrolled diabetes cause secondary hypertriglyceridemia?

Ineffective LPL.

How does a high carb diet cause secondary hypertriglyceridemia?

Increased production of free fatty acids from carbohydrate metabolism, producing more triglycerides.

How does hypothyroidism cause secondary hypertriglyceridemia?

Reduced hepatic lipase activity slows VLDL remnant catabolism.

How does excessive alcohol cause secondary hypertriglyceridemia?

Alcohol impairs lipid breakdown, increasing plasma VLDL.

Which medications cause secondary hypertriglyceridemia?

Glucocorticoids, thiazide diuretics, beta blockers, HIV antiretrovirals, retinoids, and oral estrogen replacement therapies.

Are most patients with hypertriglyceridemia symptomatic?

No - most are asymptomatic, usually with no symptoms until triglycerides exceed 1000-2000 mg/dL.

What physical findings appear in severe hypertriglyceridemia?

Hepatosplenomegaly, lipemia retinalis, and xanthomas.

What triglyceride range is classified as moderate hypertriglyceridemia?

150-499 mg/dL.

What triglyceride range is classified as moderate-to-severe hypertriglyceridemia?

500-999 mg/dL.

What triglyceride level is classified as severe hypertriglyceridemia?

>1000 mg/dL.

What is the primary therapy for hypertriglyceridemia?

Lifestyle and dietary changes.

What should be avoided in the hypertriglyceridemia diet?

Alcohol, simple and refined sugars, and fatty processed food; also restrict total calories.

What is the first-choice medication for hypertriglyceridemia with elevated LDL?

Statins.

What is added if fasting triglycerides stay elevated despite diet and optimal LDL-lowering therapy?

Triglyceride-lowering medications.

What triglyceride level puts a patient at risk for pancreatitis?

>1000 mg/dL.

At what triglyceride level does CV risk (atherosclerosis) increase significantly?

>150 mg/dL.

What is metabolic syndrome?

The co-occurrence of metabolic risk factors for T2DM and CVD.

What four components are included in metabolic syndrome?

Abdominal obesity, hyperglycemia, dyslipidemia, and hypertension.

What are the risk factors for metabolic syndrome?

Excessive weight gain, poor diet, sedentary lifestyle, and genetic factors.

Describe the pathophysiology of metabolic syndrome.

Adipose tissue secretes adipokines causing widespread systemic inflammation and insulin resistance, which may lead to endothelial dysfunction, vascular inflammation, and eventual ASCVD.

What skin findings suggest metabolic syndrome?

Acanthosis nigricans, xanthomas, and abdominal striae.

What sleep, respiratory, and mood findings occur in metabolic syndrome?

Snoring, fatigue, dyspnea, and depression.

What neurologic and extremity findings occur in metabolic syndrome?

Peripheral neuropathy and lower extremity edema.

How many criteria are required to diagnose metabolic syndrome?

3 or more of the 5 criteria.

Metabolic syndrome criterion - central obesity waist thresholds?

>40 inches in a biological male, >35 inches in a biological female.

Metabolic syndrome criterion - blood pressure?

>130/85 mmHg or on antihypertensives.

Metabolic syndrome criterion - triglycerides?

>150 mg/dL or on triglyceride-lowering medications.

Metabolic syndrome criterion - HDL?

<40 mg/dL in males or <50 mg/dL in females, or on HDL-raising medications.