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
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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)
2. 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
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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.
3. 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.
4. 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
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the hepatic conversion of cholesterol to bile acids (Lemke, Williams, Roche, & Zito, 2013).
(Clark, Finkel, Rey, & Whalen, 2008)
5. 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)
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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.