Physiology, Cholesterol


Article Author:
Trevor Huff


Article Editor:
Ishwarlal Jialal


Editors In Chief:
Jasleen Jhajj
Cliff Caudill
Evan Kaufman


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
3/13/2019 6:29:21 PM

Introduction

Cholesterol is a lipophilic molecule that is essential for human life. It has many roles that contribute to normally functioning cells. For example, cholesterol is an important component of the cell membrane. It contributes to the structural makeup of the membrane as well as modulates its fluidity. Cholesterol functions as a precursor molecule in the synthesis of vitamin D, steroid hormones (e.g., cortisol and aldosterone and adrenal androgens), and sex hormones (e.g., testosterone, estrogens, and progesterone). Cholesterol is also a constituent of bile salt, which is used in digestion to facilitate absorption of fat-soluble vitamins A, D, E, and K [1].

Since cholesterol is mostly lipophilic, it is transported through the blood, along with triglycerides, inside lipoprotein particles (HDL, IDL, LDL, VLDL, and chylomicrons). These lipoproteins can be detected in the clinical setting to estimate the amount of cholesterol in the blood. Chylomicrons are not present in non-fasting plasma.

Issues of Concern

While cholesterol is central to many healthy cell functions, it also can have a harmful effect on the body if it is allowed to reach abnormal blood concentrations. Interestingly, when LDL-cholesterol levels are too high, the condition referred to as hypercholesterolemia, the risk for premature atherosclerotic cardiovascular diseases (ASCVD) increases [2]. Particular care should be taken to educate patients about the harmful effects of high cholesterol and how to reduce their serum cholesterol levels. Patient lifestyle changes like diet (reduction in saturated fat and trans fat with an increase in fiber and total calories if obese and supplementation with plant stanols), smoking cessation, and exercise are often a favorable approach to cholesterol reduction. However, in cases that are refractory to these behavioral modifications, cholesterol-lowering drugs, such as statins, should be used.

Cellular

Cholesterol can be introduced into the blood through the digestion of dietary fat via chylomicrons. However, since cholesterol has an important role in cellular function, it can also be directly synthesized by each cell in the body. The synthesis of cholesterol begins from Acetyl-CoA and follows a series of complex reactions that will not be covered in this article. A primary location for this process is the liver, which accounts for most de-novo cholesterol synthesis.

Since cholesterol is mostly a lipophilic molecule, it does not dissolve well in blood. For this reason, it is packaged in lipoproteins which have phospholipid, and apolipoprotein [3]. Lipoproteins are made up of a lipid core (which can contain cholesterol esters and triglycerides) and a hydrophilic outer membrane comprising phospholipid, apolipoprotein, and free cholesterol. This allows the lipid molecules to move around the body through the blood and be transported to cells that need them. There are several types of lipoproteins that travel through the blood, and they each have different purposes. There are high-density lipoproteins (HDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and very low-density lipoproteins (VLDL). Notably, LDL particles are thought to act as a major transporter of cholesterol, at least two-thirds of circulating cholesterol resides in LDL, to the peripheral tissues. Conversely, HDL molecules are thought to do the opposite. They take excess cholesterol and return it to the liver for excretion. Clinically, these two lipoproteins are significant since high LDL, and low HDL increase a patient’s risk of atherosclerotic vascular diseases [4][5].

Within the cell, cholesterol has several vital functions. Some of the primary uses for cholesterol are related to the cell membrane . It is required for the normal structure of the membrane; it contributes to its fluidity [6]. This fluidity can influence the ability of some small molecules to diffuse through the membrane which ultimately changes the internal environment of the cell [7]. Also within the membrane, cholesterol plays a role in intracellular transportation. Beyond its place in the cell membrane, cholesterol has several other biological functions. Of note, cholesterol is known to be an important precursor molecule for the synthesis of vitamin D, cortisol, aldosterone, progesterone, estrogen, testosterone, bile salts, among others [8].

Related Testing

Physicians can order a lipid panel (lipid profile) to determine the cholesterol concentrations in a patient’s blood. A typical test result will include the concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, and total cholesterol. These values are used to screen patients for abnormalities in cholesterol and triglyceride blood levels. With this information, physicians can estimate a patient's risk for certain health problems such as coronary artery disease, peripheral arterial disease (PAD), and stroke. Most laboratories report both the LDL-cholesterol and the non-HDL cholesterol which is a secondary target for treatment.

Pathophysiology

Hypercholesterolemia (high LDL-cholesterol) is one of the major risk factors that contribute to the formation of atherosclerotic plaques. These plaques lead to an increased possibility of a variety of negative clinical outcomes including, but not limited to coronary artery disease. PAD, aortic aneurysms,  and stroke. A major contributor to the increased risk of atherosclerotic lesion formation is high levels of low-density lipoprotein (LDL) in the blood. Also, it has also been shown that an elevated high-density lipoprotein (HDL) blood concentration is correlated with decreased risk in epidemiological studies, but clinical trials with therapies that elevate HDL-cholesterol have yielded null results. For this reason, a major focus of patient care is primarily to decrease LDL levels.

The process through which atherosclerotic plaques develop begins with endothelial damage. Endothelial damage leads to the dysfunction of endothelial cells, and therefore, increases the number of LDL particles that can permeate through the vascular wall. Lipoproteins, especially LDL, can then accumulate within the vessel wall trapped by a cellular matrix in the intima. LDL is then modified and taken up via scavenger receptors on macrophages resulting in foam-cell formation. As more lipid accumulates within the wall of the vessel, smooth muscle cells begin to migrate into the lesion. Ultimately, these smooth muscle cells encapsulate the newly formed plaque forming the fibrous plaque, the protector of the lesion, preventing the lipid core from being exposed to the lumen of the vessel. Atherosclerotic plaques can lead to occlusion of the vessel (decreasing blood flow distally and causing ischemia)  or more commonly because of abundant lipid and macrophages (vulnerable plaque) rupture, inducing the formation of a thrombus which can completely block the flow of blood (as occurs in acute myocardial infarctions, unstable angina).

Clinical Significance

Hypercholesterolemia refers to the condition in which a patient has elevated blood concentrations of LDL-cholesterol. High LDL is of particular clinical importance, but it should be noted that hypercholesterolemia can also include very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), i.e., non-HDL-cholesterol. High levels of LDL have been associated with an increased risk of atherosclerosis which can lead to several other conditions such as coronary artery disease, stroke, and peripheral arterial disease. Several factors can lead to increased LDL levels. Some of these factors include genetics, diet, stress, sedentary lifestyle, and medications and other disorders such as nephrotic syndrome and hypothyroidism.

On clinical examination looking for absent pulses, bruits, arcus senilis (younger than 50 years of age) tendon xanthoma, xanthelasma and aortic stenosis are all stigmata of very high cholesterol levels as in familial hypercholesterolemia.

Genetic defects that lead to increased LDL levels in the blood include genes that regulate LDL receptors in the liver. LDL receptors mediate the uptake of LDL into the liver. Endocytosis of LDL is a primary way that the body decreases cholesterol levels so it follows that a decrease in LDL receptor function would also increase LDL concentrations in the blood. Patients with a genetic disposition for high cholesterol can be placed on cholesterol-lowering medications like statins to decrease their risk.

Diet has a variable effect on cholesterol levels among individuals [9]. However, it has been shown that diets high in saturated fats and trans fats can increase cholesterol in the blood [10]. Dietary cholesterol has not been shown to contribute significantly to LDL concentrations, but its role is still in question [11][12][13]. Lifestyle changes such as regular aerobic exercise can also be used to help control cholesterol levels. Saturated fats should not comprise any more than 7% to 10% of the diet .

Hypercholesterolemia is often treated medically with lifestyle modification and medications. The goal of lifestyle changes is typically for the patient to increase physical activity, lose weight, and to follow a heart-healthy diet. For patients with higher risk, a lipid-lowering drug (often a statin) will be used in conjunction with these behavioral changes. Statins have been shown to reduce ASCVD in patients and are the favored drugs because there are now generic formulations which make them cost-effective [14][15][16][17].


  • Image 5829 Not availableImage 5829 Not available
    Contributed by Boris T.M. (Public Domain, https://commons.wikimedia.org/w/index.php?curid=645994)
Attributed To: Contributed by Boris T.M. (Public Domain, https://commons.wikimedia.org/w/index.php?curid=645994)

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Physiology, Cholesterol - Questions

Take a quiz of the questions on this article.

Take Quiz
Cholesterol travels to the peripheral tissues primarily in which lipoprotein?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Cholesterol is the precursor for which of the following molecules?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
From the following choices, what is a major function of cholesterol within the cell?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 67-year-old man presents to the emergency department with an acute onset of chest pain that radiates to his left arm. He is subsequently diagnosed with a myocardial infarction and is treated. Which of the following is a major risk factor for the development of his underlying disease?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following organs is the primary site for cholesterol synthesis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Physiology, Cholesterol - References

References

Hypercholesterolemia, Ibrahim MA,Jialal K,,, 2017 Jun     [PubMed]
Cholesterol and Lipoprotein Metabolism and Atherosclerosis: Recent Advances In reverse Cholesterol Transport., Wang HH,Garruti G,Liu M,Portincasa P,Wang DQ,, Annals of hepatology, 2017 Oct 28     [PubMed]
Bile Acid Physiology., Di Ciaula A,Garruti G,Baccetto RL,Molina-Molina E,Bonfrate L,Wang DQ,Portincasa P,, Annals of hepatology, 2017 Oct 28     [PubMed]
[Risk factors for atherosclerosis in obese children aged 6-12 years]., Karney A,Brągoszewska H,Soluch L,Ołtarzewski M,, Developmental period medicine, 2017     [PubMed]
Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association., Sacks FM,Lichtenstein AH,Wu JHY,Appel LJ,Creager MA,Kris-Etherton PM,Miller M,Rimm EB,Rudel LL,Robinson JG,Stone NJ,Van Horn LV,, Circulation, 2017 Jul 18     [PubMed]
Dyslipidemia management in primary prevention of cardiovascular disease: Current guidelines and strategies., Hendrani AD,Adesiyun T,Quispe R,Jones SR,Stone NJ,Blumenthal RS,Martin SS,, World journal of cardiology, 2016 Feb 26     [PubMed]
New Strategies to Treat High Cholesterol., Blum CB,Stone NJ,, JAMA, 2016 Mar 15     [PubMed]
Treatment of Blood Cholesterol to Reduce Risk for Atherosclerotic Cardiovascular Disease., Lloyd-Jones DM,Goff DC,Stone NJ,, Annals of internal medicine, 2016 Jan 19     [PubMed]
Lowering LDL cholesterol is good, but how and in whom?, Stone NJ,Lloyd-Jones DM,, The New England journal of medicine, 2015 Apr 16     [PubMed]
The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials., Mihaylova B,Emberson J,Blackwell L,Keech A,Simes J,Barnes EH,Voysey M,Gray A,Collins R,Baigent C,, Lancet (London, England), 2012 Aug 11     [PubMed]
Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol., Stefanick ML,Mackey S,Sheehan M,Ellsworth N,Haskell WL,Wood PD,, The New England journal of medicine, 1998 Jul 2     [PubMed]
Individual cholesterol variation in response to a margarine- or butter-based diet: A study in families., Denke MA,Adams-Huet B,Nguyen AT,, JAMA, 2000 Dec 6     [PubMed]
Dietary cholesterol: from physiology to cardiovascular risk., Lecerf JM,de Lorgeril M,, The British journal of nutrition, 2011 Jul     [PubMed]
Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects., Dubois C,Armand M,Mekki N,Portugal H,Pauli AM,Bernard PM,Lafont H,Lairon D,, Journal of lipid research, 1994 Nov     [PubMed]
Influence of Cholesterol on the Oxygen Permeability of Membranes: Insight from Atomistic Simulations., Dotson RJ,Smith CR,Bueche K,Angles G,Pias SC,, Biophysical journal, 2017 Jun 6     [PubMed]
Modulation of membrane function by cholesterol., Yeagle PL,, Biochimie, 1991 Oct     [PubMed]
Bile acid synthesis from cholesterol: regulatory and auxiliary pathways., Javitt NB,, FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1994 Dec     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Optometry-Basic Science. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Optometry-Basic Science, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Optometry-Basic Science, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Optometry-Basic Science. When it is time for the Optometry-Basic Science board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Optometry-Basic Science.