Hypertriglyceridemia

Definitions & Key takeaways

Hypertriglyceridemia is a condition characterized by high levels of triglycerides in the blood. If individuals' serum triglyceride concentrations are above 150 mg/dL, they are considered hypertriglyceridemia. High levels of triglycerides in the blood are associated with a high risk of developing heart disease, stroke, and other health problems. There are many different causes of hypertriglyceridemia, including genetics, obesity, eating too much processed or unhealthy foods, not getting enough exercise, smoking cigarettes, and drinking alcohol.

Chapters:

Watch video only

Introduction0:00–0:28

With hypertriglyceridemia. Hyper means high emia refers to blood levels and triglycerides are the most abundant fatty molecules in an organism.
So, hypertriglyceridemia is when there's excess triglycerides in the blood. Specifically, hypertriglyceridemia is when there are more than 100 and 50 mgs of triglycerides per deciliter of blood triglycerides can be deposited in subcutaneous tissue and around organs and function as energy storage in the body.

Physiology0:28–3:56

We can either get triglycerides from our diet which are called exogenous triglycerides or our liver can synthesize them from other molecules.
In which case, they're called endogenous triglycerides. Now, exogenous triglycerides are first absorbed in the small intestine and then they undergo a series of changes in order to be transported and deposited in the body.
So, after triglycerides are absorbed, they enter the intestinal mucosal cells inside of which they're coupled with various apolipoproteins and phospholipids to create kylo microns, which are one type of lipoprotein.
Lipoproteins are made up of lipids like triglycerides or cholesterol or phospholipids and proteins like apolipoproteins, C two c three or e the main job of lipoproteins is to carry insoluble molecules like triglycerides from the intestines to the circulation.
That's because normally triglycerides are insoluble in liquid environments like blood. Now, the newly created chylomicrons enter the bloodstream and bind to the wall of capillaries.
In adipose and skeletal muscle tissue at the binding site. They interact with the lipoprotein lipase enzyme leading to the breakdown of the triglyceride core and liberation of free fatty acids directly into the adipocytes or skeletal muscle cell where they're either stored or used for energy.
After triglycerides leave the chylomicron, what's left is called the remnant Chylomicron. Remnant chylomicrons are high in cholesterol esters and they're cleared from circulation by the liver.
When the apolipoprotein E binds to apolipoprotein B1 100 E receptor on the hepatic cell membrane. The remnant chylomicrons are then degraded by acid hydrolases to a mixture of amino acids, free fatty acids and cholesterol.
Now let's switch gears and look at how endogenous triglycerides are synthesized. First, the liver makes another type of lipoproteins called very low density lipoproteins or VLDL.
The fatty acids are either synthesized from scratch from carbohydrates or released from adipose tissue. Then the liver exports the triglyceride rich, very low density lipoprotein molecules into the bloodstream which carries them to muscle and adipose cells here, very low density lipoproteins are cleaved by lipoprotein lipase to intermediate density lipoproteins.
IDL also called VLDL remnants. The intermediate density lipoproteins are further metabolized to low density lipoproteins.
LDL and are released into the bloodstream which are taken up by the low density lipoprotein receptor in numerous tissues including the liver So, hypertriglyceridemia can result from anomalies in either the exogenous or the endogenous pathways.

Pathology3:56–5:08

But in either case, excessive triglyceride levels accumulate in the body depending on where they accumulate. They may cause complications like atherosclerosis and acute pancreatitis.
Now, atherosclerosis can occur via a pathway that involves an endothelial dysfunction. This dysfunction allows small triglyceride remnants to reach the intimal layer where they get taken out by the macrophages.
Leading to the formation of foam cells. Foam cells promote fatty streak formation.
The precursor of atherosclerotic plaque, acute pancreatitis. On the other hand occurs due to high concentrations of large chylomicrons in the blood which can obstruct the capillaries leading to ischemia of the pancreas.
Now, hypertriglyceridemia is commonly classified as either primary or familial hypertriglyceridemia and secondary or acquired hypertriglyceridemia.

Secondary triglyceridemia5:08–7:16

Secondary causes are more common and they may be associated with obesity, diabetes, mellitus, high carbohydrate diets, hypothyroidism or increased alcohol intake, all of which impact lipid metabolism.
So, three of the most common secondary forms of hypertriglyceridemia are obesity, diabetes, mellitus type one and two and high carbohydrate diets with obesity associated hypertriglyceridemia.
There is a hepatic overproduction of very low density lipoproteins and decrease circulating triglycerides breakdown. On the other hand, in uncontrolled diabetes, both type one and two hypertriglyceridemia is associated with a lipoprotein lipase that is either ineffective or less effective than normal.
Finally, high carbohydrate diets where carbohydrates make up more than 60% of the total caloric intake lead to increased carbohydrate breakdown and increased production of free fatty acids.
As a consequence, the excess free fatty acids can be used to synthesize more triglycerides, therefore, causing hypertriglyceridemia.
Other conditions cause hypertriglyceridemia through different mechanisms. For example, in hypothyroidism, triglycerides are elevated due to reduced hepatic lipase activity which slows very low density lipoprotein remnant catabolism.
Next, excessive alcohol intake causes hypertriglyceridemia mainly because alcohol impairs lipid breakdown, causing increased plasma VLDL with or without hyperchylomicronemia.
Finally, several drugs like glucocorticoids, beta blockers, thiazide diuretics, HIV, antiretroviral agents, retinoids and oral estrogen replacement can also cause hypertriglyceridemia.
Although the mechanisms are not well understood. On the other hand, primary or familial hypertriglyceridemia usually occurs due to genetic causes such as mutations of the genes encoding a type of apolipoprotein.

Primary triglyceridemia7:16–9:34

Primary hypertriglyceridemia is included in what is known as familial dyslipidemias. There are four hyperlipidemias of which only three cause hypertriglyceridemia type.
One is called familial hyperchylomicronemia and is defined as high levels of chylomicrons in the blood. It occurs due to autosomal recessive mutations.
Now, mutations in at least five different genes cause hyperchylomicronemia but the ones encoding for lipoprotein lipase and its cofactor apo lipoprotein C two are most common.
Basically, these mutations lead to a severely reduced or absent lipoprotein lipase enzyme activity and to an absent or nonfunctional apolipoprotein C two with lipoprotein lipase being the primary enzyme for triglycerides breakdown and release of fatty acids in the circulation.
Its absence or reduction will lead to high levels of these lipids, type three or familial dy beta lipoproteinemia occurs when the kylo micro remnants cannot be removed by the liver.
The mechanisms through which it is produced are not fully revealed yet. But it is suspected that the clearance of chylomicron remnants from the circulation is done with the help of apolipoprotein.
E any defects related to apolipoprotein E or its receptor will affect this process leading to hypertriglyceridemia. Finally type four or familial hypertriglyceridemia involves autosomal dominant mutations of the lipoprotein lipase gene.
In this case, there's an increase in hepatic synthesis of VLDL and a decreased removal of VLDL resulting in hypertriglyceridemia.

Symptoms9:34–10:32

Now, regarding symptoms, hypertriglyceridemia usually doesn't cause symptoms until triglyceride levels are greater than 1000 to 2000 mgs per deciliter, which is why most people have asymptomatic hypertriglyceridemia above that level due to excessive accumulation of triglycerides in the body.
Signs and symptoms may include hepatosplenomegaly and lipemia retinalis, which can be observed as a creamy appearance within retinal blood vessels.
Hypertriglyceridemia can also manifest as small papules on the skin known as xanthomas with atherosclerosis symptoms can include chest pain and shortness of breath.
While with acute pancreatitis, symptoms like epigastric pain, nausea and vomiting can occur. The initial diagnosis of hypertriglyceridemia is made with blood tests usually as the lipid profile part of a cardiovascular risk assessment.

Diagnosis10:32–11:25

Then hypertriglyceridemia can be classified as mild when triglycerides. Blood level is from 100 and 50 to 499 mg per deciliter, moderate from 500 to 886 mg per deciliter and severe when the triglycerides blood level is higher than 886 mg per deciliter.
Then other tests can be done to distinguish between primary and secondary hypertriglyceridemia. These may include lipid analysis, liver function tests, urinalysis, fasting blood glucose level or genetic testing.

Treatment11:25–12:08

So, when it comes to treatment, hypertriglyceridemia may be improved with the help of diet exercise and alcohol reduction medication is required when triglyceride levels are above 886 mgs per deciliter fibrates such as fenofibrate are the best initial medical treatment for hypertriglyceridemia.
Niacin and omega three fatty acids may also be used. HMG coa reductase inhibitors also known as statins such as atorvastatin or simvastatin are the first choice drugs for moderate hypertriglyceridemia.
Ok, quick recap hypertriglyceridemia is characterized by high blood levels of triglycerides. Hypertriglyceridemia can be primary or secondary, primary is mainly caused by genetic defects.

Review12:08–12:53

While secondary hypertriglyceridemia occurs due to several conditions among which obesity or diabetes are most common. The diagnosis is made based on blood tests but other tests are required to differentiate between primary and secondary hypertriglyceridemia.
Treatment includes diet and exercising to help improve the level of triglycerides. But when those are not enough medication such as fibrates or statins are required