USMLE® Step 1 style questions USMLE
A 26-year-old man is evaluated in the emergency department for epigastric pain that began an hour ago. He reports that the pain radiates to the back and is 9 out of 10 in severity. The patient consumes a diet rich in fresh fruits and vegetables. He drinks 2-3 glasses of wine per week on social occasions. Family history is notable for recurrent episodes of pancreatitis in his father and paternal uncle. His temperature is 37.7°C (99.9°F), blood pressure is 125/83 mmHg, and pulse is 96/min. Physical examination is notable for tenderness on light palpation of the epigastric region. Abdominal exam also reveals hepatosplenomegaly and the following finding:
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Xanthomas are found on the patient’s bilateral elbows. Which of the following set of laboratory findings would be most likely expected in this patient?
Hypertriglyceridemia exam links
Content Reviewers:Viviana Popa, MD
Contributors:Zachary Kevorkian, MSMI, David G. Walker, Alex Aranda
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 150 mg of triglycerides per deciliter of blood.
Triglycerides can be deposited in subcutaneous tissue and around organs and function as energy storage in the body.
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 chylomicrons, which are one type of lipoprotein.
Lipoproteins are made up of lipids (like triglycerides or cholesterol) or phospholipids and proteins (like apolipoproteins CII, CIII, 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 a remnant chylomicron.
Remnant chylomicrons are high in cholesterol esters and they’re cleared from circulation by the liver when the apolipoprotein E binds to Apo-B100/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 VLDL molecules into the bloodstream, which carries them to muscle and adipose cells.
Here, VLDL are cleaved by lipoprotein lipase to intermediate-density lipoproteins(IDL), also called VLDL remnants.
The IDL are further metabolized to low-density lipoproteins, LDL, and are released into the bloodstream, which are taken up by the LDL receptor in numerous tissues including the liver.
Ok, so hypertriglyceridemia can result from anomalies in either the exogenous or the endogenous pathways, 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 triglycerides remnants to reach the intimal layer where they get taken up 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 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.
Alright, so three of the most common secondary forms of hypertriglyceridemia are obesity, diabetes mellitus type 1 and 2, and high carbohydrate diets.
With obesity-associated hypertriglyceridemia, there is a hepatic overproduction of VLDL and decreased circulating triglycerides breakdown.
On the other hand, in uncontrolled diabetes mellitus, both type 1 and type 2, 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
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.
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