Hickey 1

Stephanie Hickey

Nutrition 445

Shearer

14 April 2013

Case Study 3

Hypercholesterolemia:Elevated levels of blood cholsterol

A 36-year old man was found to have hypercholesterolemia. A dietary evaluation indicated that he was consuming about 600 mg/day of cholesterol. His plasma cholesterol concentration on two separate occasions was approximately 330 mg/dL (8.5 mmol/L). Ultracentrifugal analysis revealed that the cholesterol elevation was due to an increase in plasma LDL. He was treated with a cholesterol-free vegetarian diet for 3 months, but his plasma cholesterol level decreased to only 300 mg/dL (7.7 mmol/L). Subsequently he was treated with colestipol hydrochloride, a bile acid-binding resin that is not absorbed. The resin binds bile acids, causing increased amount to be excreted in the feces. This treatment lowered the fasting plasma cholesterol concentration to 250 mg/dL (6.4 mmol/L).

LDL lipoprotein most associated with CVD

Plants don’t make cholesterol (vegetarian diet)

People on a true vegetarian diet are getting no dietary cholesterol

LDL-forward transporting cholesterol to non-hepatic tissues-when you are delivering less cholesterol to the dietary tissues there will be a reduction in total cholesterol

Bile-binding acid resin: made from cholesterol, only major way we lost cholesterol from the body: combine cholesterol to bile acids to be excreted

Bile acids are derivatives of cholesterol

Questions:

  1. How is dietary cholesterol absorbed?

Within the intestinal lumen, dietary cholesterol is introduced to the brush border of the enterocyte MPC1L1 as a micelle created by activity of bile salts, cholesterol and fatty acids. The role of bile salts is important in the absorption of dietary cholesterol through the formation of emulsions. Availability of enough bile acid is a crucial factor because of the incorporation of cholesterol into micelles is needed for absorption due to it being a hydrophobic molecule. The intestine regulates the amount of dietary cholesterol and is selective in the sterols that enter the body. Cholesterol is absorbed in the duodenum and jejunum of the small intestine while the bile acids is absorbed by bile acid transporters located in the ileum of the small intestine sending them back to the liver, completing the enterohepatic circulation (Lu, Lee, & Patel, 2001). The role of pancreatic lipase is to digest cholesterol by breaking the bonds between the glycerol backbones and the fatty acids, cleaving the fatty acids at positions of SN-1 and SN-3 on the glycerol. This function of pancreatic lipase results in a mixture of diacylglycerols, monoacylglycerols and free fatty acids. After the absorption of cholesterol, the free cholesterol (formed by pancreatic lipase acting on cholesterol) and fatty acids are re-esterified in the enterocytes by acetyl-CoA cholesterol acyl-transferase (ACAT) bundled along with triglyceride, phospholipids and apoB-48 into chylomicrons following being secreted from the basolateral side of the enterocyte.

(Lu, Lee, & Patel, 2001)

  1. How is it possible for a patient to continue to have high plasma cholesterol after being on a cholesterol-free diet for 3 months?

The cholesterol we ingest derives from animals, which is also the primary source of saturated fat and our body synthesizes cholesterol from a variety of precursors (Gropper & Smith, 2013). The cholesterol that comes from our diet is 25% of our daily intake and is called exogenous cholesterol, meaning that the other 75% of cholesterol is made from the body and is called endogenous production (Scirica & Cannon, 2005). When intake of cholesterol is decreased, the body will synthesize more cholesterol and absorb more cholesterol from the small intestine. HDL is involved in one of the major routes on how cholesterol may be excreted from the body. Individuals respond differently to dietary cholesterol, those who are sensitive to dietary cholesterol are hyperresponders whereas those who are not are hyporesponders (Djousse & Gaziano, 2009). But, this individual seems to have poor endogenous cholesterol synthesis regulation. Free cholesterol, following LDL degradation, can modulate the activity of HMG-CoA reductase and ACAT; also suppress the synthesis of LDL receptors which prevents more LDL to enter. As the total body cholesterol increases, the rate of synthesis decreases which is caused by a negative feedback regulation of the HMG-CoA reductase reaction.

  1. What connection is there between bile acids and cholesterol?

Bile acids regulate cholesterol homeostasis (Staels & Fonseca, 2009). Cells get cholesterol from the circulation in the form of plasma lipoproteins and through cholesterol synthesis from acetyl coenzyme A (acetyl-CoA). Cholesterol is also known not only as a precursor for steroid hormones, but also bile acids (Goedeke & Fernandez-Hernando, 2012). Bile acids express the primary pathway for cholesterol catabolism and accounts for about 50% of the daily turnover of cholesterol (Staels & Fonseca, 2009). Individuals with hypercholesterolemia may be given medication that will bind bile in the GI tract which will enhance the fecal excretion from the body. The increase of fecal excretion of the bile will decrease recirculation of bile. This will decrease the absorption of cholesterol, which will require the body to use cholesterol to synthesize new bile acids. The increased use of cholesterol to make more bile decreases the body’s cholesterol concentrations (Gropper & Smith, 2013). Other connections that bile acids have to cholesterol are that the synthesis of bile acids occurs in the liver in multiple enzymatic reactions in the hepatocyte that transforms hydrophobic cholesterol into more water-soluble amphipathic compounds.

  1. How does a bile acid-binding resin lower the plasma cholesterol concentration?

Bile acids assist in the digestion and absorption of dietary fats. They are usually secreted into the GI tract through the bile duct followed by being reabsorbed and transported back to the liver for the cycle to be repeated (Bardal, Waechter, & Martin, 2011). Bile-acid resins have effects on lowering LDL cholesterol. Examples of bile-acid resins are cholestyramine, colestipol, and colesevelam, which are anion exchange resins that bind negatively, charged bile acids and bile salts within the small intestine (Clark, Finkel, Rey, & Whalen, 2008). Before the bile acids leave the liver, they are conjugated to glycine or taurine, which create two major bile acids, glycocholic acid and taurocholic acid, which increases their fecal excretion. This then decreases the concentrations of these compounds that are sent back to the liver. As a result, this removes the feedback inhibition of 7α-hydroxylase and increases the hepatic conversion of cholesterol to bile acids (Lemke, Williams, Roche, & Zito, 2013).

(Clark, Finkel, Rey, & Whalen, 2008)

  1. What additional treatment would you suggest for a patient with this disease?

I would suggest first with lifestyle changes before prescribing medications. I would recommend for the patient to continue watching their diet by reducing the total and saturated fat in the diet by limiting on hydrogenated oils or animal fats and increasing their intake of fruits and vegetables. In addition, to participate more frequently in aerobic exercise to lose weight. Some advantages of aerobic exercise consist of reducing the risk of mortality from coronary artery disease, an increase in HDL cholesterol, weight loss, and positive mental health benefits such as, reducing stress or anxiety. If don’t see the changes that would like to see, this is when I would recommend combining lifestyle changes with medications. I would suggest taking statins because they are known to lower LDL cholesterol by decreasing the body’s synthesis of cholesterol. Another possible medication would be bile acid resins, which bind with bile acids in the small intestine resulting in a decreased amount of cholesterol absorbed from the diet.

Statin acts on HMG-CoA reductase (inhibits)

Works Cited

Djousse, Luc, and J. Michael Gaziano. "Dietary Cholesterol and Coronary Artery Disease: A Systematic Review." PubMed, 2009. Web. 9 Nov. 2013.

Finkel, Richard, Jose A. Rey, and Karen Whalen. "III. Drugs That Lower the Serum Lipoprotein Concentration." Lippincott's Illustrated Reviews: Pharmacology. By Michelle A. Clark. 5th ed. Baltimore: Lippincott Williams & Wilkins, 2008. 273. Print.

Goedeke, Leigh, and Carlos Fernandez-Hernando. "Regulation of Cholesterol Homeostasis." PubMed, 19 Oct. 2011. Web. 9 Nov. 2013.

Gropper, Sareen S., and Jack L. Smith. Advanced Nutrition and Human Metabolism. 6th ed. Belmont: Wadsworth Cengage Learning, 2013. Print.

Lu, Kangmo, Mi-Hye Lee, and Shailendra B. Patel. "Dietary Cholesterol Absorption; More than Just Bile." PubMed, 2001. Web. 9 Nov. 2013.

Scirica, Benjamin M., and Christopher P. Cannon. "Treatment of Elevated Cholesterol." PubMed, 2005. Web. 9 Nov. 2013.

Waechter, Jason E., and Douglas S. Martin. "Bile Acid Sequestrants." Applied Pharmacology. By Stan K. Bardal. 1st ed. St. Louis: Elsevier Saunders, 2011. 115-18. Print.