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145-517: Lipoproteins are divided into five subgroups, by density/size (an inverse relationship), which also correlates with function and incidence of cardiovascular events. Unlike the larger lipoprotein particles, which deliver fat molecules to cells, HDL particles remove fat molecules from cells. The lipids carried include cholesterol , phospholipids , and triglycerides , amounts of each are variable. Increasing concentrations of HDL particles are associated with decreasing accumulation of atherosclerosis within

290-426: A benign tumour the most common type of liver tumour, thought to be congenital. A genetic disorder causing multiple cysts to form in the liver tissue, usually in later life, and usually asymptomatic, is polycystic liver disease . Diseases that interfere with liver function will lead to derangement of these processes. However, the liver has a great capacity to regenerate and has a large reserve capacity. In most cases,

435-437: A myelin sheath, rich in cholesterol since it is derived from compacted layers of Schwann cell or oligodendrocyte membranes, provides insulation for more efficient conduction of impulses. Demyelination (loss of myelin) is believed to be part of the basis for multiple sclerosis . Cholesterol binds to and affects the gating of a number of ion channels such as the nicotinic acetylcholine receptor , GABA A receptor , and

580-428: A cell via endocytosis . These vesicles then fuse with a lysosome , where the lysosomal acid lipase enzyme hydrolyzes the cholesterol esters. The cholesterol can then be used for membrane biosynthesis or esterified and stored within the cell, so as to not interfere with the cell membranes. LDL receptors are used up during cholesterol absorption, and its synthesis is regulated by SREBP , the same protein that controls

725-412: A change in this domain's oligomerization state, which makes it more susceptible to destruction by the proteasome . This enzyme's activity can also be reduced by phosphorylation by an AMP-activated protein kinase . Because this kinase is activated by AMP, which is produced when ATP is hydrolyzed, it follows that cholesterol synthesis is halted when ATP levels are low. As an isolated molecule, cholesterol

870-410: A dual blood supply from the hepatic portal vein and hepatic arteries. The hepatic portal vein delivers around 75% of the liver's blood supply and carries venous blood drained from the spleen, gastrointestinal tract, and its associated organs. The hepatic arteries supply arterial blood to the liver, accounting for the remaining quarter of its blood flow. Oxygen is provided from both sources; about half of

1015-911: A form of vitamin B3 ) increases HDL by selectively inhibiting hepatic diacylglycerol acyltransferase 2, reducing triglyceride synthesis and VLDL secretion through a receptor HM74 otherwise known as niacin receptor 2 and HM74A / GPR109A, niacin receptor 1 . Pharmacologic (1- to 3-gram/day) niacin doses increase HDL levels by 10–30%, making it the most powerful agent to increase HDL-cholesterol. A randomized clinical trial demonstrated that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular events. Niacin products sold as "no-flush", i.e. not having side-effects such as "niacin flush ", do not, however, contain free nicotinic acid and are therefore ineffective at raising HDL, while products sold as "sustained-release" may contain free nicotinic acid, but "some brands are hepatotoxic"; therefore

1160-722: A greater incidence of atherosclerotic heart disease. Studies confirm the fact that HDL has a buffering role in balancing the effects of the hypercoagulable state in type 2 diabetics and decreases the high risk of cardiovascular complications in these patients. Also, the results obtained in this study revealed that there was a significant negative correlation between HDL and activated partial thromboplastin time (APTT). Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against cardiovascular diseases such as ischemic stroke and myocardial infarction . Low concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) increase

1305-408: A key role in this phenomenon. At birth, the liver comprises roughly 4% of body weight and weighs on average about 120 g (4 oz). Over the course of further development, it will increase to 1.4–1.6 kg (3.1–3.5 lb) but will only take up 2.5–3.5% of body weight. Hepatosomatic index (HSI) is the ratio of liver weight to body weight. In the growing fetus, a major source of blood to

1450-466: A lower intake of food has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (sterol regulatory element-binding protein 1 and 2). In the presence of cholesterol, SREBP is bound to two other proteins: SCAP (SREBP cleavage-activating protein) and INSIG-1 . When cholesterol levels fall, INSIG-1 dissociates from

1595-410: A population of the bipotential hepatoblasts. Hepatic stellate cells are derived from mesenchyme. After migration of hepatoblasts into the septum transversum mesenchyme, the hepatic architecture begins to be established, with liver sinusoids and bile canaliculi appearing. The liver bud separates into the lobes. The left umbilical vein becomes the ductus venosus and the right vitelline vein becomes

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1740-416: A positive impact on raising HDL levels: Most saturated fats increase HDL cholesterol to varying degrees but also raise total and LDL cholesterol. HDL levels can be increased by smoking cessation , or mild to moderate alcohol intake. Cannabis in unadjusted analyses, past and current cannabis use was not associated with higher HDL-C levels. A study performed in 4635 patients demonstrated no effect on

1885-412: A precursor for other compounds, such as phytosterols and steroidal glycoalkaloids , with cholesterol remaining in plant foods only in minor amounts or absent. Some plant foods, such as avocado , flax seeds and peanuts , contain phytosterols, which compete with cholesterol for absorption in the intestines and reduce the absorption of both dietary and bile cholesterol. A typical diet contributes on

2030-409: A role in the production of clotting factors, as well as red blood cell production. Some of the proteins synthesized by the liver include coagulation factors I (fibrinogen), II (prothrombin), V , VII , VIII , IX , X , XI , XII , XIII , as well as protein C , protein S and antithrombin . The liver is a major site of production for thrombopoietin , a glycoprotein hormone that regulates

2175-420: A superficial division of the liver into a left and right lobe. From below, the two additional lobes are located between the right and left lobes, one in front of the other. A line can be imagined running from the left of the vena cava and all the way forward to divide the liver and gallbladder into two halves. This line is called Cantlie's line . Other anatomical landmarks include the ligamentum venosum and

2320-639: A way as to bind large steroid substrates like cholesterol. Animal fats are complex mixtures of triglycerides , with lesser amounts of both the phospholipids and cholesterol molecules from which all animal (and human) cell membranes are constructed. Since all animal cells manufacture cholesterol, all animal-based foods contain cholesterol in varying amounts. Major dietary sources of cholesterol include red meat , egg yolks and whole eggs , liver , kidney , giblets , fish oil , shellfish, and butter . Human breast milk also contains significant quantities of cholesterol. Plant cells synthesize cholesterol as

2465-401: Is a "satellite" of hepatitis B virus (it can only infect in the presence of hepatitis B), and co-infects nearly 20 million people with hepatitis B, globally. Hepatic encephalopathy is caused by an accumulation of toxins in the bloodstream that are normally removed by the liver. This condition can result in coma and can prove fatal. Budd–Chiari syndrome is a condition caused by blockage of

2610-415: Is a dark reddish brown, wedge-shaped organ with two lobes of unequal size and shape. A human liver normally weighs approximately 1.5 kilograms (3.3 pounds) and has a width of about 15 centimetres (6 inches). There is considerable size variation between individuals, with the standard reference range for men being 970–1,860 grams (2.14–4.10 lb) and for women 600–1,770 g (1.32–3.90 lb). It

2755-429: Is absent among prokaryotes ( bacteria and archaea ), although there are some exceptions, such as Mycoplasma , which require cholesterol for growth. Cholesterol also serves as a precursor for the biosynthesis of steroid hormones , bile acid and vitamin D . Elevated levels of cholesterol in the blood, especially when bound to low-density lipoprotein (LDL, often referred to as "bad cholesterol"), may increase

2900-407: Is also implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane , which brings receptor proteins in close proximity with high concentrations of second messenger molecules. In multiple layers, cholesterol and phospholipids, both electrical insulators, can facilitate speed of transmission of electrical impulses along nerve tissue. For many neuron fibers,

3045-466: Is associated with atheromatous disease progression in the arteries. Cholesterol is susceptible to oxidation and easily forms oxygenated derivatives called oxysterols . Three different mechanisms can form these: autoxidation, secondary oxidation to lipid peroxidation, and cholesterol-metabolizing enzyme oxidation. A great interest in oxysterols arose when they were shown to exert inhibitory actions on cholesterol biosynthesis. This finding became known as

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3190-407: Is both the heaviest internal organ and the largest gland in the human body. It is located in the right upper quadrant of the abdominal cavity , resting just below the diaphragm, to the right of the stomach, and overlying the gallbladder . The liver is connected to two large blood vessels : the hepatic artery and the portal vein . The hepatic artery carries oxygen-rich blood from the aorta via

3335-666: Is identical, although some is carried as its native "free" alcohol form (the cholesterol-OH group facing the water surrounding the particles), while others as fatty acyl esters, known also as cholesterol esters, within the particles. Lipoprotein particles are organized by complex apolipoproteins , typically 80–100 different proteins per particle, which can be recognized and bound by specific receptors on cell membranes, directing their lipid payload into specific cells and tissues currently ingesting these fat transport particles. These surface receptors serve as unique molecular signatures, which then help determine fat distribution delivery throughout

3480-660: Is important for the synthesis of steroid hormones . Several steps in the metabolism of HDL can participate in the transport of cholesterol from lipid-laden macrophages of atherosclerotic arteries , termed foam cells , to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL toward atherosclerosis. HDL carries many lipid and protein species, several of which have very low concentrations but are biologically very active. For example, HDL and its protein and lipid constituents help to inhibit oxidation , inflammation , activation of

3625-450: Is known as the duodenal impression. The inferior surface of the left lobe of the liver presents behind and to the left of the gastric impression. This is moulded over the upper front surface of the stomach, and to the right of this is a rounded eminence, the tuber omentale , which fits into the concavity of the lesser curvature of the stomach and lies in front of the anterior layer of the lesser omentum . Microscopically, each liver lobe

3770-437: Is of low abundance in lipid rafts. PC localizes to the disordered region of the cell along with the polyunsaturated lipid phosphatidylinositol 4,5-bisphosphate (PIP2). PLD2 has a PIP2 binding domain . When PIP2 concentration in the membrane increases, PLD2 leaves the cholesterol-dependent domains and binds to PIP2 where it then gains access to its substrate PC and commences catalysis based on substrate presentation. Cholesterol

3915-423: Is only minimally soluble in water , or hydrophilic . Because of this, it dissolves in blood at exceedingly small concentrations. To be transported effectively, cholesterol is instead packaged within lipoproteins , complex discoidal particles with exterior amphiphilic proteins and lipids, whose outward-facing surfaces are water-soluble and inward-facing surfaces are lipid-soluble. This allows it to travel through

4060-446: Is oxidized by the liver into a variety of bile acids . These, in turn, are conjugated with glycine , taurine , glucuronic acid , or sulfate . A mixture of conjugated and nonconjugated bile acids, along with cholesterol itself, is excreted from the liver into the bile . Approximately 95% of the bile acids are reabsorbed from the intestines, and the remainder are lost in the feces. The excretion and reabsorption of bile acids forms

4205-411: Is removed by HDL receptors such as scavenger receptor BI (SR-BI), which mediate the selective uptake of cholesterol from HDL. In humans, probably the most relevant pathway is the indirect one, which is mediated by cholesteryl ester transfer protein (CETP) . This protein exchanges triglycerides of VLDL against cholesteryl esters of HDL. As the result, VLDLs are processed to LDL , which are removed from

4350-403: Is required to build and maintain membranes and modulates membrane fluidity over the range of physiological temperatures. The hydroxyl group of each cholesterol molecule interacts with water molecules surrounding the membrane, as do the polar heads of the membrane phospholipids and sphingolipids , while the bulky steroid and the hydrocarbon chain are embedded in the membrane, alongside

4495-449: Is responsible for the breakdown and excretion of many waste products. It plays a key role in breaking down or modifying toxic substances (e.g., methylation ) and most medicinal products in a process called drug metabolism . This sometimes results in toxication , when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine. The liver converts ammonia into urea as part of

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4640-405: Is seen to be made up of hepatic lobules . The lobules are roughly hexagonal, and consist of plates of hepatocytes , and sinusoids radiating from a central vein towards an imaginary perimeter of interlobular portal triads. The central vein joins to the hepatic vein to carry blood out from the liver. A distinctive component of a lobule is the portal triad , which can be found running along each of

4785-477: Is some evidence that the HDL reduction is caused by increased reverse cholesterol transport , it is unknown if AR agonists' HDL-lowering effect is pro- or anti-atherogenic. Pharmacological therapy to increase the level of HDL cholesterol includes use of fibrates and niacin . Fibrates have not been proven to have an effect on overall deaths from all causes, despite their effects on lipids. Niacin (nicotinic acid,

4930-476: Is taken up from here to the bloodstream by the liver. VLDL particles are produced by the liver from triacylglycerol and cholesterol which was not used in the synthesis of bile acids. These particles contain apolipoprotein B100 and apolipoprotein E in their shells and can be degraded by lipoprotein lipase on the artery wall to IDL. This arterial wall cleavage allows absorption of triacylglycerol and increases

5075-502: Is the densest because it contains the highest proportion of protein to lipids . Its most abundant apolipoproteins are apo A-I and apo A-II . A rare genetic variant, ApoA-1 Milano , has been documented to be far more effective in both protecting against and regressing arterial disease, atherosclerosis . The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles, whose NMR structure

5220-456: Is the principal sterol of all higher animals , distributed in body tissues , especially the brain and spinal cord , and in animal fats and oils . Cholesterol is biosynthesized by all animal cells and is an essential structural and signaling component of animal cell membranes . In vertebrates , hepatic cells typically produce the greatest amounts. In the brain, astrocytes produce cholesterol and transport it to neurons . It

5365-405: Is the tube of endoderm that extends out from the foregut into the surrounding mesenchyme. The mesenchyme of septum transversum induces this endoderm to proliferate, to branch, and to form the glandular epithelium of the liver. A portion of the hepatic diverticulum (that region closest to the digestive tube) continues to function as the drainage duct of the liver, and a branch from this duct produces

5510-494: Is then reduced to mevalonate by the enzyme HMG-CoA reductase . Production of mevalonate is the rate-limiting and irreversible step in cholesterol synthesis and is the site of action for statins (a class of cholesterol-lowering drugs). Mevalonate is finally converted to isopentenyl pyrophosphate (IPP) through two phosphorylation steps and one decarboxylation step that requires ATP . Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through

5655-629: Is thought to be less accurate. The American Heart Association , NIH and NCEP provide a set of guidelines for fasting HDL levels and risk for heart disease . High LDL with low HDL level is an additional risk factor for cardiovascular disease. As technology has reduced costs and clinical trials have continued to demonstrate the importance of HDL, methods for directly measuring HDL concentrations and size (which indicates function) at lower costs have become more widely available and increasingly regarded as important for assessing individual risk for progressive arterial disease and treatment methods. Since

5800-413: Is uneven and concave. It is covered in peritoneum apart from where it attaches the gallbladder and the porta hepatis. The fossa of gallbladder lies to the right of the quadrate lobe, occupied by the gallbladder with its cystic duct close to the right end of porta hepatis. Several impressions on the surface of the liver accommodate the various adjacent structures and organs. Underneath the right lobe and to

5945-473: The GI tract , an important protective mechanism. The intake of naturally occurring phytosterols, which encompass plant sterols and stanols , ranges between ≈200–300 mg/day depending on eating habits. Specially designed vegetarian experimental diets have been produced yielding upwards of 700 mg/day. Cholesterol is present in varying degrees in all animal cell membranes , but is absent in prokaryotes. It

High-density lipoprotein - Misplaced Pages Continue

6090-538: The Nobel Prize in Physiology or Medicine in 1964 for their discoveries concerning some of the mechanisms and methods of regulation of cholesterol and fatty acid metabolism . Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the homeostatic mechanisms involved are only partly understood. A higher intake of food leads to a net decrease in endogenous production, whereas

6235-441: The ampulla of Vater . The liver plays a major role in carbohydrate, protein, amino acid, and lipid metabolism. The liver performs several roles in carbohydrate metabolism. The liver is responsible for the mainstay of protein metabolism , synthesis as well as degradation. All plasma proteins except Gamma-globulins are synthesised in the liver. It is also responsible for a large part of amino acid synthesis . The liver plays

6380-490: The calcium metabolism and all steroid hormones , including the adrenal gland hormones cortisol and aldosterone , as well as the sex hormones progesterone , estrogens , and testosterone , and their derivatives. The stratum corneum is the outermost layer of the epidermis. It is composed of terminally differentiated and enucleated corneocytes that reside within a lipid matrix, like "bricks and mortar." Together with ceramides and free fatty acids, cholesterol forms

6525-425: The celiac trunk , whereas the portal vein carries blood rich in digested nutrients from the entire gastrointestinal tract and also from the spleen and pancreas . These blood vessels subdivide into small capillaries known as liver sinusoids , which then lead to hepatic lobules . Hepatic lobules are the functional units of the liver. Each lobule is made up of millions of hepatic cells (hepatocytes), which are

6670-442: The duodenum to help with digestion . The liver's highly specialized tissue , consisting mostly of hepatocytes , regulates a wide variety of high-volume biochemical reactions, including the synthesis and breakdown of small and complex organic molecules, many of which are necessary for normal vital functions. Estimates regarding the organ's total number of functions vary, but is generally cited as being around 500. For this reason,

6815-421: The fibrinogen beta chain protein. Organogenesis , the development of the organs, takes place from the third to the eighth week during embryogenesis . The origins of the liver lie in both the ventral portion of the foregut endoderm (endoderm being one of the three embryonic germ layers ) and the constituents of the adjacent septum transversum mesenchyme . In the human embryo , the hepatic diverticulum

6960-552: The gallbladder , which then excretes them in a non- esterified form (via bile) into the digestive tract. Typically, about 50% of the excreted cholesterol is reabsorbed by the small intestine back into the bloodstream. Almost all animal tissues synthesize cholesterol from acetyl-CoA . All animal cells (exceptions exist within the invertebrates) manufacture cholesterol, for both membrane structure and other uses, with relative production rates varying by cell type and organ function. About 80% of total daily cholesterol production occurs in

7105-399: The hepatic veins (including thrombosis ) that drain the liver. It presents with the classical triad of abdominal pain, ascites and liver enlargement . Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from

7250-406: The inward-rectifier potassium channel . Cholesterol also activates the estrogen-related receptor alpha (ERRα), and may be the endogenous ligand for the receptor . The constitutively active nature of the receptor may be explained by the fact that cholesterol is ubiquitous in the body. Inhibition of ERRα signaling by reduction of cholesterol production has been identified as a key mediator of

7395-441: The liver and the intestines ; other sites of higher synthesis rates include the brain , the adrenal glands , and the reproductive organs . Synthesis within the body starts with the mevalonate pathway where two molecules of acetyl CoA condense to form acetoacetyl-CoA . This is followed by a second condensation between acetyl CoA and acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl CoA ( HMG-CoA ). This molecule

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7540-454: The nonpolar fatty-acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases membrane packing, which both alters membrane fluidity and maintains membrane integrity so that animal cells do not need to build cell walls (like plants and most bacteria). The membrane remains stable and durable without being rigid, allowing animal cells to change shape and animals to move. The structure of

7685-428: The ornithine cycle or the urea cycle, and the urea is excreted in the urine. Because the liver is an expandable organ, large quantities of blood can be stored in its blood vessels. Its normal blood volume, including both that in the hepatic veins and that in the hepatic sinuses, is about 450 milliliters, or almost 10 percent of the body's total blood volume. When high pressure in the right atrium causes backpressure in

7830-403: The right and left triangular ligaments . These peritoneal ligaments are not related to the anatomic ligaments in joints, and the right and left triangular ligaments have no known functional importance, though they serve as surface landmarks. The falciform ligament functions to attach the liver to the posterior portion of the anterior body wall. The visceral surface or inferior surface

7975-410: The round ligament of the liver , which further divide the left side of the liver in two sections. An important anatomical landmark, the porta hepatis , divides this left portion into four segments, which can be numbered starting at the caudate lobe as I in an anticlockwise manner. From this parietal view, seven segments can be seen, because the eighth segment is only visible in the visceral view. On

8120-423: The tetracyclic ring of cholesterol contributes to the fluidity of the cell membrane, as the molecule is in a trans conformation making all but the side chain of cholesterol rigid and planar. In this structural role, cholesterol also reduces the permeability of the plasma membrane to neutral solutes, hydrogen ions, and sodium ions. Cholesterol regulates the biological process of substrate presentation and

8265-511: The "oxysterol hypothesis". Additional roles for oxysterols in human physiology include their participation in bile acid biosynthesis, function as transport forms of cholesterol, and regulation of gene transcription. In biochemical experiments, radiolabelled forms of cholesterol, such as tritiated-cholesterol, are used. These derivatives undergo degradation upon storage, and it is essential to purify cholesterol prior to use. Cholesterol can be purified using small Sephadex LH-20 columns. Cholesterol

8410-658: The 1.6–3.0 grams per day range (Health Canada, EFSA, ATP III, FDA). A meta-analysis demonstrated a 12% reduction in LDL-cholesterol at a mean dose of 2.1 grams per day. The benefits of a diet supplemented with phytosterols have also been questioned. According to the lipid hypothesis , elevated levels of cholesterol in the blood lead to atherosclerosis which may increase the risk of heart attack , stroke , and peripheral artery disease . Since higher blood LDL – especially higher LDL concentrations and smaller LDL particle size – contributes to this process more than

8555-441: The 1970s) or newer NMR spectroscopy methods (See also nuclear magnetic resonance and spectroscopy ), developed in the 1990s. Five subfractions of HDL have been identified. From largest (and most effective in cholesterol removal) to smallest (and least effective), the types are 2a, 2b, 3a, 3b, and 3c. Men tend to have noticeably lower HDL concentrations, with smaller size and lower cholesterol content, than women. Men also have

8700-557: The 2015 iteration of the Dietary Guidelines for Americans dropped the previously recommended limit of consumption of dietary cholesterol to 300 mg per day with a new recommendation to "eat as little dietary cholesterol as possible", thereby acknowledging an association between a diet low in cholesterol and reduced risk of cardiovascular disease. A 2013 report by the American Heart Association and

8845-693: The American College of Cardiology recommended focusing on healthy dietary patterns rather than specific cholesterol limits, as they are hard for clinicians and consumers to implement. They recommend the DASH and Mediterranean diet , which are low in cholesterol. A 2017 review by the American Heart Association recommends switching saturated fats for polyunsaturated fats to reduce cardiovascular disease risk. Some supplemental guidelines have recommended doses of phytosterols in

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8990-541: The HDL particles have a net negative charge and vary by density & size, ultracentrifugation combined with electrophoresis have been utilized since before 1950 to enumerate the concentration of HDL particles and sort them by size with a specific volume of blood plasma. Larger HDL particles are carrying more cholesterol. Concentration and sizes of lipoprotein particles can be estimated using nuclear magnetic resonance fingerprinting. The HDL particle concentrations are typically categorized by event rate percentiles based on

9135-521: The HDL-C levels (P=0.78) [the mean (standard error) HDL-C values in control subjects (never used), past users and current users were 53.4 (0.4), 53.9 (0.6) and 53.9 (0.7) mg/dL, respectively]. Exogenous anabolic androgenic steroids , particularly 17α-alkylated anabolic steroids and others administered orally, can reduce HDL-C by 50 percent or more. Other androgen receptor agonists such as selective androgen receptor modulators can also lower HDL. As there

9280-656: The IDEAL and the EPIC prospective studies found an association between high levels of HDL cholesterol (adjusted for apolipoprotein A-I and apolipoprotein B) and increased risk of cardiovascular disease, casting doubt on the cardioprotective role of "good cholesterol". Liver The liver is a major metabolic organ exclusively found in vertebrate animals , which performs many essential biological functions such as detoxification of

9425-497: The SREBP pathway regulates the expression of many genes that control lipid formation and metabolism and body fuel allocation. Cholesterol synthesis can also be turned off when cholesterol levels are high. HMG-CoA reductase contains both a cytosolic domain (responsible for its catalytic function) and a membrane domain. The membrane domain senses signals for its degradation. Increasing concentrations of cholesterol (and other sterols) cause

9570-545: The SREBP-SCAP complex, which allows the complex to migrate to the Golgi apparatus . Here SREBP is cleaved by S1P and S2P (site-1 protease and site-2 protease), two enzymes that are activated by SCAP when cholesterol levels are low. The cleaved SREBP then migrates to the nucleus and acts as a transcription factor to bind to the sterol regulatory element (SRE), which stimulates the transcription of many genes. Among these are

9715-478: The TLF molecule. In the stress response , serum amyloid A , which is one of the acute-phase proteins and an apolipoprotein, is under the stimulation of cytokines ( interleukin 1 , interleukin 6 ), and cortisol produced in the adrenal cortex and carried to the damaged tissue incorporated into HDL particles. At the inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in

9860-504: The absorption of vitamin K from the diet. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder. The liver produces insulin-like growth factor 1 , a polypeptide protein hormone that plays an important role in childhood growth and continues to have anabolic effects in adults. The liver is responsible for the breakdown of insulin and other hormones . The liver breaks down bilirubin via glucuronidation , facilitating its excretion into bile. The liver

10005-791: The action of geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum . Oxidosqualene cyclase then cyclizes squalene to form lanosterol . Finally, lanosterol is converted to cholesterol via either of two pathways, the Bloch pathway, or the Kandutsch-Russell pathway. The final 19 steps to cholesterol contain NADPH and oxygen to help oxidize methyl groups for removal of carbons, mutases to move alkene groups, and NADH to help reduce ketones . Konrad Bloch and Feodor Lynen shared

10150-572: The association more pronounced in younger subjects. Because cardiovascular disease is relatively rare in the younger population, the impact of high cholesterol on health is larger in older people. Elevated levels of the lipoprotein fractions, LDL, IDL and VLDL, rather than the total cholesterol level, correlate with the extent and progress of atherosclerosis. Conversely, the total cholesterol can be within normal limits, yet be made up primarily of small LDL and small HDL particles, under which conditions atheroma growth rates are high. A post hoc analysis of

10295-407: The association of so-called LDL cholesterol (actually a lipoprotein ) with "bad" cholesterol. HDL particles are thought to transport cholesterol back to the liver, either for excretion or for other tissues that synthesize hormones, in a process known as reverse cholesterol transport (RCT). Large numbers of HDL particles correlates with better health outcomes, whereas low numbers of HDL particles

10440-403: The basic metabolic cells. The lobules are held together by a fine, dense, irregular, fibroelastic connective tissue layer extending from the fibrous capsule covering the entire liver known as Glisson's capsule after British doctor Francis Glisson . This tissue extends into the structure of the liver by accompanying the blood vessels, ducts, and nerves at the hepatic hilum. The whole surface of

10585-428: The basis of the enterohepatic circulation , which is essential for the digestion and absorption of dietary fats. Under certain circumstances, when more concentrated, as in the gallbladder , cholesterol crystallises and is the major constituent of most gallstones ( lecithin and bilirubin gallstones also occur, but less frequently). Every day, up to 1 g of cholesterol enters the colon. This cholesterol originates from

10730-409: The best evidence to date suggests it has no benefit for primary or secondary prevention of cardiovascular disease. The PPAR modulator GW501516 has shown a positive effect on HDL-C and an antiatherogenic where LDL is an issue. However, research on the drug has been discontinued after it was discovered to cause rapid cancer development in several organs in rats. Cholesterol Cholesterol

10875-455: The blood and constitute plasma proteins and hepatokines . Other liver-specific proteins are certain liver enzymes such as HAO1 and RDH16 , proteins involved in bile synthesis such as BAAT and SLC27A5 , and transporter proteins involved in the metabolism of drugs, such as ABCB11 and SLC2A2 . Examples of highly liver-specific proteins include apolipoprotein A II , coagulation factors F2 and F9 , complement factor related proteins , and

11020-520: The blood and excretes it through bile. Other disorders caused by excessive alcohol consumption are grouped under alcoholic liver diseases and these include alcoholic hepatitis , fatty liver , and cirrhosis . Factors contributing to the development of alcoholic liver diseases are not only the quantity and frequency of alcohol consumption, but can also include gender, genetics, and liver insult. Liver damage can also be caused by drugs , particularly paracetamol and drugs used to treat cancer. A rupture of

11165-701: The blood via emulsification . Unbound cholesterol, being amphipathic, is transported in the monolayer surface of the lipoprotein particle along with phospholipids and proteins. Cholesterol esters bound to fatty acid, on the other hand, are transported within the fatty hydrophobic core of the lipoprotein, along with triglyceride. There are several types of lipoproteins in the blood. In order of increasing density, they are chylomicrons , very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Lower protein/lipid ratios make for less dense lipoproteins. Cholesterol within different lipoproteins

11310-399: The blood. Surprisingly, in rats, blood cholesterol is inversely correlated with cholesterol consumption. The more cholesterol a rat eats the lower the blood cholesterol. During the first seven hours after ingestion of cholesterol, as absorbed fats are being distributed around the body within extracellular water by the various lipoproteins (which transport all fats in the water outside cells),

11455-469: The blood. These LDL particles are oxidized and taken up by macrophages , which become engorged and form foam cells. These foam cells often become trapped in the walls of blood vessels and contribute to atherosclerotic plaque formation. Differences in cholesterol homeostasis affect the development of early atherosclerosis (carotid intima-media thickness). These plaques are the main causes of heart attacks, strokes, and other serious medical problems, leading to

11600-468: The body. Chylomicrons, the least dense cholesterol transport particles, contain apolipoprotein B-48 , apolipoprotein C , and apolipoprotein E (the principal cholesterol carrier in the brain ) in their shells. Chylomicrons carry fats from the intestine to muscle and other tissues in need of fatty acids for energy or fat production. Unused cholesterol remains in more cholesterol-rich chylomicron remnants and

11745-515: The brain. De novo synthesis, both in astrocytes and hepatocytes, occurs by a complex 37-step process. This begins with the mevalonate or HMG-CoA reductase pathway , the target of statin drugs, which encompasses the first 18 steps. This is followed by 19 additional steps to convert the resulting lanosterol into cholesterol. A human male weighing 68 kg (150 lb) normally synthesizes about 1 gram (1,000 mg) of cholesterol per day, and his body contains about 35 g, mostly contained within

11890-513: The cell membranes. Typical daily cholesterol dietary intake for a man in the United States is 307 mg. Most ingested cholesterol is esterified , which causes it to be poorly absorbed by the gut. The body also compensates for absorption of ingested cholesterol by reducing its own cholesterol synthesis. For these reasons, cholesterol in food, seven to ten hours after ingestion, has little, if any effect on concentrations of cholesterol in

12035-467: The centre of each segment are branches of the portal vein, hepatic artery, and bile duct. In the periphery of each segment is vascular outflow through the hepatic veins. The classification system uses the vascular supply in the liver to separate the functional units (numbered I to VIII) with unit 1, the caudate lobe, receiving its supply from both the right and the left branches of the portal vein. It contains one or more hepatic veins which drain directly into

12180-524: The cholesterol content of the HDL particles, LDL particles are often termed "bad cholesterol". High concentrations of functional HDL, which can remove cholesterol from cells and atheromas, offer protection and are commonly referred to as "good cholesterol". These balances are mostly genetically determined, but can be changed by body composition, medications , diet, and other factors. A 2007 study demonstrated that blood total cholesterol levels have an exponential effect on cardiovascular and total mortality, with

12325-492: The circulation by the LDL receptor pathway. The triglycerides are not stable in HDL, but are degraded by hepatic lipase so that, finally, small HDL particles are left, which restart the uptake of cholesterol from cells. The cholesterol delivered to the liver is excreted into the bile and, hence, intestine either directly or indirectly after conversion into bile acids . Delivery of HDL cholesterol to adrenals, ovaries, and testes

12470-414: The common hepatic duct to form the common bile duct. The biliary system and connective tissue is supplied by the hepatic artery alone. Bile either drains directly into the duodenum via the common bile duct, or is temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the second part of the duodenum together at the hepatopancreatic ampulla, also known as

12615-759: The concentration of circulating cholesterol. IDL particles are then consumed in two processes: half is metabolized by HTGL and taken up by the LDL receptor on the liver cell surfaces, while the other half continues to lose triacylglycerols in the bloodstream until they become cholesterol-laden LDL particles. LDL particles are the major blood cholesterol carriers. Each one contains approximately 1,500 molecules of cholesterol ester. LDL particle shells contain just one molecule of apolipoprotein B100 , recognized by LDL receptors in peripheral tissues. Upon binding of apolipoprotein B100 , many LDL receptors concentrate in clathrin -coated pits. Both LDL and its receptor form vesicles within

12760-421: The concentrations increase. Plants make cholesterol in very small amounts. In larger quantities they produce phytosterols , chemically similar substances which can compete with cholesterol for reabsorption in the intestinal tract, thus potentially reducing cholesterol reabsorption. When intestinal lining cells absorb phytosterols, in place of cholesterol, they usually excrete the phytosterol molecules back into

12905-406: The decomposition of red blood cells . The liver is also an accessory digestive organ that produces bile , an alkaline fluid containing cholesterol and bile acids , which emulsifies and aids the breakdown of dietary fat . The gallbladder , a small hollow pouch that sits just under the right lobe of liver, stores and concentrates the bile produced by the liver, which is later excreted to

13050-401: The diaphragmatic surface, apart from a triangular bare area where it connects to the diaphragm, the liver is covered by a thin, double-layered membrane, the peritoneum , that helps to reduce friction against other organs. This surface covers the convex shape of the two lobes where it accommodates the shape of the diaphragm. The peritoneum folds back on itself to form the falciform ligament and

13195-567: The diet, bile, and desquamated intestinal cells, and it can be metabolized by the colonic bacteria. Cholesterol is converted mainly into coprostanol , a nonabsorbable sterol that is excreted in the feces. Although cholesterol is a steroid generally associated with mammals, the human pathogen Mycobacterium tuberculosis is able to completely degrade this molecule and contains a large number of genes that are regulated by its presence. Many of these cholesterol-regulated genes are homologues of fatty acid β-oxidation genes, but have evolved in such

13340-418: The edge of the liver lobule, where they merge to form bile ducts. Within the liver, these ducts are termed intrahepatic bile ducts, and once they exit the liver, they are considered extrahepatic. The intrahepatic ducts eventually drain into the right and left hepatic ducts, which exit the liver at the transverse fissure , and merge to form the common hepatic duct. The cystic duct from the gallbladder joins with

13485-448: The effects of statins and bisphosphonates on bone , muscle , and macrophages . On the basis of these findings, it has been suggested that the ERRα should be de-orphanized and classified as a receptor for cholesterol. Within cells, cholesterol is also a precursor molecule for several biochemical pathways . For example, it is the precursor molecule for the synthesis of vitamin D in

13630-454: The endothelium , coagulation , and platelet aggregation . All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet known which are the most important. In addition, a small subfraction of HDL lends protection against the protozoan parasite Trypanosoma brucei brucei . This HDL subfraction, termed trypanosome lytic factor (TLF), contains specialized proteins that, while very active, are unique to

13775-405: The enzymes that use substrate presentation as a mechanism of their activation. Phospholipase D2 ( PLD2 ) is a well-defined example of an enzyme activated by substrate presentation. The enzyme is palmitoylated causing the enzyme to traffic to cholesterol dependent lipid domains sometimes called " lipid rafts ". The substrate of phospholipase D is phosphatidylcholine (PC) which is unsaturated and

13920-414: The epidermis. Steroid sulfate sulfatase then decreases its concentration in the stratum corneum, the outermost layer of the epidermis. The relative abundance of cholesterol sulfate in the epidermis varies across different body sites with the heel of the foot having the lowest concentration. Cholesterol is recycled in the body. The liver excretes cholesterol into biliary fluids, which are then stored in

14065-564: The family Herpesviridae such as the herpes simplex virus . Chronic (rather than acute) infection with hepatitis B virus or hepatitis C virus is the main cause of liver cancer . Globally, about 248 million individuals are chronically infected with hepatitis B (with 843,724 in the U.S.), and 142 million are chronically infected with hepatitis C (with 2.7 million in the U.S.). Globally there are about 114 million and 20 million cases of hepatitis A and hepatitis E respectively, but these generally resolve and do not become chronic. Hepatitis D virus

14210-448: The functional lobes are further divided into a total of eight subsegments based on a transverse plane through the bifurcation of the main portal vein. The caudate lobe is a separate structure that receives blood flow from both the right- and left-sided vascular branches. The Couinaud classification divides the liver into eight functionally independent liver segments. Each segment has its own vascular inflow, outflow and biliary drainage. In

14355-485: The functions of a mature hepatocyte, and eventually mature hepatocytes appear as highly polarized epithelial cells with abundant glycogen accumulation. In the adult liver, hepatocytes are not equivalent, with position along the portocentrovenular axis within a liver lobule dictating expression of metabolic genes involved in drug metabolism, carbohydrate metabolism , ammonia detoxification, and bile production and secretion. WNT/β-catenin has now been identified to be playing

14500-412: The gallbladder. Besides signals from the septum transversum mesenchyme, fibroblast growth factor from the developing heart also contributes to hepatic competence, along with retinoic acid emanating from the lateral plate mesoderm . The hepatic endodermal cells undergo a morphological transition from columnar to pseudostratified resulting in thickening into the early liver bud . Their expansion forms

14645-591: The high cost of directly measuring HDL and LDL ( low-density lipoprotein ) protein particles, blood tests are commonly performed for the surrogate value, HDL-C, i.e. the cholesterol associated with ApoA-1 /HDL particles. In healthy individuals, about 30% of blood cholesterol, along with other fats, is carried by HDL. This is often contrasted with the amount of cholesterol estimated to be carried within low-density lipoprotein particles, LDL , and called LDL-C. HDL particles remove fats and cholesterol from cells, including within artery wall atheroma , and transport it back to

14790-405: The imaginary plane, Cantlie's line, joining the gallbladder fossa to the inferior vena cava . The plane separates the liver into the true right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The right lobe is further divided into an anterior and posterior segment by the right hepatic vein. The left lobe is divided into the medial and lateral segments by

14935-437: The inferior vena cava, allowing placental blood to bypass the liver. In the fetus, the liver does not perform the normal digestive processes and filtration of the infant liver because nutrients are received directly from the mother via the placenta . The fetal liver releases some blood stem cells that migrate to the fetal thymus , creating the T cells (or T lymphocytes). After birth, the formation of blood stem cells shifts to

15080-463: The inferior vena cava. The remainder of the units (II to VIII) are numbered in a clockwise fashion: About 20,000 protein coding genes are expressed in human cells and 60% of these genes are expressed in a normal, adult liver. Over 400 genes are more specifically expressed in the liver, with some 150 genes highly specific for liver tissue. A large fraction of the corresponding liver-specific proteins are mainly expressed in hepatocytes and secreted into

15225-423: The left hepatic vein. The hilum of the liver is described in terms of three plates that contain the bile ducts and blood vessels. The contents of the whole plate system are surrounded by a sheath. The three plates are the hilar plate , the cystic plate and the umbilical plate and the plate system is the site of the many anatomical variations to be found in the liver. In the widely used Couinaud system,

15370-407: The lipid mortar, a water-impermeable barrier that prevents evaporative water loss. As a rule of thumb, the epidermal lipid matrix is composed of an equimolar mixture of ceramides (≈50% by weight), cholesterol (≈25% by weight), and free fatty acids (≈15% by weight), with smaller quantities of other lipids also being present. Cholesterol sulfate reaches its highest concentration in the granular layer of

15515-445: The liver and drain into the inferior vena cava. The biliary tract is derived from the branches of the bile ducts. The biliary tract, also known as the biliary tree, is the path by which bile is secreted by the liver then transported to the first part of the small intestine, the duodenum . The bile produced in the liver is collected in bile canaliculi , small grooves between the faces of adjacent hepatocytes. The canaliculi radiate to

15660-492: The liver are carried out by the liver cells or hepatocytes. The liver is thought to be responsible for up to 500 separate functions, usually in combination with other systems and organs. Currently, no artificial organ or device is capable of reproducing all the functions of the liver. Some functions can be carried out by liver dialysis , an experimental treatment for liver failure . The liver also accounts for about 20% of resting total body oxygen consumption. The liver receives

15805-417: The liver can be caused by a liver shot used in combat sports. Primary biliary cholangitis is an autoimmune disease of the liver. It is marked by slow progressive destruction of the small bile ducts of the liver, with the intralobular ducts ( Canals of Hering ) affected early in the disease. When these ducts are damaged, bile and other toxins build up in the liver ( cholestasis ) and over time damages

15950-559: The liver for excretion or re-utilization; thus the cholesterol carried within HDL particles (HDL-C) is sometimes called "good cholesterol" (despite being the same as cholesterol in LDL particles). Those with higher levels of HDL-C tend to have fewer problems with cardiovascular diseases , while those with low HDL-C cholesterol levels (especially less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease. Higher native HDL levels are correlated with lowered risk of cardiovascular disease in healthy people. The remainder of

16095-435: The liver has sometimes been described as the body's chemical factory . It is not known how to compensate for the absence of liver function in the long term, although liver dialysis techniques can be used in the short term. Artificial livers have not been developed to promote long-term replacement in the absence of the liver. As of 2018 , liver transplantation is the only option for complete liver failure . The liver

16240-490: The liver in response to injury or inflammation. The most common chronic liver disease is nonalcoholic fatty liver disease , which affects an estimated one-third of the world population. Hepatitis is a common condition of inflammation of the liver. The most usual cause of this is viral , and the most common of these infections are hepatitis A , B , C , D , and E . Some of these infections are sexually transmitted . Inflammation can also be caused by other viruses in

16385-404: The liver is the umbilical vein, which supplies nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus and passes upward along the free margin of the falciform ligament of the liver to the inferior surface of the liver. There, it joins with the left branch of the portal vein. The ductus venosus carries blood from the left portal vein to the left hepatic vein and then to

16530-419: The liver only produces symptoms after extensive damage. Hepatomegaly refers to an enlarged liver and can be due to many causes. It can be palpated in a liver span measurement. Consuming caffeine regularly may help safeguard individuals from liver cirrhosis . Additionally, it has been shown to slow the advancement of liver disease in those already affected, lower the risk of liver fibrosis, and provide

16675-584: The liver tissue in combination with ongoing immune related damage. This can lead to scarring ( fibrosis ) and cirrhosis . Cirrhosis increases the resistance to blood flow in the liver, and can result in portal hypertension . Congested anastomoses between the portal venous system and the systemic circulation, can be a subsequent condition. There are also many pediatric liver diseases, including biliary atresia , alpha-1 antitrypsin deficiency , alagille syndrome , progressive familial intrahepatic cholestasis , Langerhans cell histiocytosis and hepatic hemangioma

16820-467: The liver volume is occupied by parenchymal hepatocytes. Nonparenchymal cells constitute 40% of the total number of liver cells but only 6.5% of its volume. The liver sinusoids are lined with two types of cell, sinusoidal endothelial cells , and phagocytic Kupffer cells . Hepatic stellate cells are nonparenchymal cells found in the perisinusoidal space , between a sinusoid and a hepatocyte. Additionally, intrahepatic lymphocytes are often present in

16965-444: The liver's oxygen demand is met by the hepatic portal vein, and half is met by the hepatic arteries. The hepatic artery also has both alpha- and beta-adrenergic receptors; therefore, flow through the artery is controlled, in part, by the splanchnic nerves of the autonomic nervous system. Blood flows through the liver sinusoids and empties into the central vein of each lobule. The central veins coalesce into hepatic veins, which leave

17110-534: The liver, except for the bare area , is covered in a serous coat derived from the peritoneum , and this firmly adheres to the inner Glisson's capsule. Terminology related to the liver often starts in hepat- from ἡπατο-, from the Greek word for liver. The liver is grossly divided into two parts when viewed from above – a right and a left lobe – and four parts when viewed from below (left, right, caudate , and quadrate lobes ). The falciform ligament makes

17255-421: The liver, the liver expands, and 0.5 to 1 liter of extra blood is occasionally stored in the hepatic veins and sinuses. This occurs especially in cardiac failure with peripheral congestion. Thus, in effect, the liver is a large, expandable, venous organ capable of acting as a valuable blood reservoir in times of excess blood volume and capable of supplying extra blood in times of diminished blood volume. Because

17400-429: The lobule's corners. The portal triad consists of the hepatic artery, the portal vein, and the common bile duct. The triad may be seen on a liver ultrasound, as a Mickey Mouse sign with the portal vein as the head, and the hepatic artery, and the common bile duct as the ears. Histology , the study of microscopic anatomy, shows two major types of liver cell: parenchymal cells and nonparenchymal cells. About 70–85% of

17545-461: The low-density lipoprotein ( LDL ) receptor and HMG-CoA reductase . The LDL receptor scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to an increase in endogenous production of cholesterol. A large part of this signaling pathway was clarified by Dr. Michael S. Brown and Dr. Joseph L. Goldstein in the 1970s. In 1985, they received the Nobel Prize in Physiology or Medicine for their work. Their subsequent work shows how

17690-552: The lymph formed in the body under resting conditions arises in the liver. The liver is a vital organ and supports almost every other organ in the body. Because of its strategic location and multidimensional functions, the liver is prone to many diseases. The bare area of the liver is a site that is vulnerable to the passing of infection from the abdominal cavity to the thoracic cavity . Liver diseases may be diagnosed by liver function tests –blood tests that can identify various markers. For example, acute-phase reactants are produced by

17835-440: The majority of cholesterol is ingested or synthesized by hepatocytes and transported in the blood to peripheral cells. The levels of cholesterol in peripheral tissues is dictated by a balance of uptake and export. Under normal conditions, brain cholesterol is separate from peripheral cholesterol, i.e., the dietary and hepatic cholesterol do not cross the blood brain barrier. Rather, astrocytes produce and distribute cholesterol in

17980-529: The newly synthesized HDL to assume a spherical shape. HDL particles increase in size as they circulate through the blood and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, such as by interaction with the ABCG1 transporter and the phospholipid transport protein (PLTP) . HDL transports cholesterol mostly to the liver or steroidogenic organs such as adrenals , ovary , and testes by both direct and indirect pathways. HDL

18125-461: The order of 0.2 gram of phytosterols, which is not enough to have a significant impact on blocking cholesterol absorption. Phytosterols intake can be supplemented through the use of phytosterol-containing functional foods or dietary supplements that are recognized as having potential to reduce levels of LDL -cholesterol. In 2015, the scientific advisory panel of U.S. Department of Health and Human Services and U.S. Department of Agriculture for

18270-432: The organism, and the synthesis of proteins and various other biochemicals necessary for digestion and growth. In humans , it is located in the right upper quadrant of the abdomen , below the diaphragm and mostly shielded by the lower right rib cage . Its other metabolic roles include carbohydrate metabolism , the production of hormones , conversion and storage of nutrients such as glucose and glycogen , and

18415-739: The people participating and being tracked in the MESA trial, a medical research study sponsored by the United States National Heart, Lung, and Blood Institute. The lowest incidence of atherosclerotic events over time occurs within those with both the highest concentrations of total HDL particles (the top quarter, >75%) and the highest concentrations of large HDL particles. Multiple additional measures, including LDL particle concentrations, small LDL particle concentrations, VLDL concentrations, estimations of insulin resistance and standard cholesterol lipid measurements (for comparison of

18560-592: The plasma data with the estimation methods discussed above) are routinely provided in clinical testing. While higher HDL levels are correlated with lower risk of cardiovascular diseases, no medication used to increase HDL has been proven to improve health. As of 2017, numerous lifestyle changes and drugs to increase HDL levels were under study. HDL lipoprotein particles that bear apolipoprotein C3 are associated with increased, rather than decreased, risk for coronary heart disease . Certain changes in diet and exercise may have

18705-429: The pores in the hepatic sinusoids are very permeable and allow ready passage of both fluid and proteins into the perisinusoidal space , the lymph draining from the liver usually has a protein concentration of about 6 g/dl, which is only slightly less than the protein concentration of plasma. Also, the high permeability of the liver sinusoid epithelium allows large quantities of lymph to form. Therefore, about half of all

18850-753: The portal vein. The expanding liver bud is colonized by hematopoietic cells . The bipotential hepatoblasts begin differentiating into biliary epithelial cells and hepatocytes. The biliary epithelial cells differentiate from hepatoblasts around portal veins, first producing a monolayer, and then a bilayer of cuboidal cells. In ductal plate, focal dilations emerge at points in the bilayer, become surrounded by portal mesenchyme, and undergo tubulogenesis into intrahepatic bile ducts. Hepatoblasts not adjacent to portal veins instead differentiate into hepatocytes and arrange into cords lined by sinusoidal epithelial cells and bile canaliculi. Once hepatoblasts are specified into hepatocytes and undergo further expansion, they begin acquiring

18995-400: The production of platelets by the bone marrow. The liver plays several roles in lipid metabolism: it performs cholesterol synthesis, lipogenesis , and the production of triglycerides , and a bulk of the body's lipoproteins are synthesized in the liver. The liver plays a key role in digestion, as it produces and excretes bile (a yellowish liquid) required for emulsifying fats and help

19140-611: The products of a cholesterol oxidase reaction to an indicator reaction. The reference method still uses a combination of these techniques. Most laboratories now use automated homogeneous analytical methods in which lipoproteins containing apo B are blocked using antibodies to apo B, then a colorimetric enzyme reaction measures cholesterol in the non-blocked HDL particles. HPLC can also be used. Subfractions (HDL-2C, HDL-3C) can be measured, but clinical significance of these subfractions has not been determined. The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but

19285-602: The recommended form of niacin for raising HDL is the cheapest, immediate-release preparation. Both fibrates and niacin increase artery toxic homocysteine , an effect that can be counteracted by also consuming a multivitamin with relatively high amounts of the B-vitamins, but multiple European trials of the most popular B-vitamin cocktails, trial showing 30% average reduction in homocysteine, while not showing problems have also not shown any benefit in reducing cardiovascular event rates. A 2011 extended-release niacin (Niaspan) study

19430-412: The red bone marrow . After 2–5 days, the umbilical vein and ductus venosus are obliterated; the former becomes the round ligament of liver and the latter becomes the ligamentum venosum. In the disorders of cirrhosis and portal hypertension , the umbilical vein can open up again. Unlike eutherian mammals, in marsupials the liver remains haematopoietic well after birth. The various functions of

19575-415: The right of the fossa , between the bare area and the caudate lobe, and immediately above the renal impression. The greater part of the suprarenal impression is devoid of peritoneum and it lodges the right suprarenal gland. Medial to the renal impression is a third and slightly marked impression, lying between it and the neck of the gall bladder. This is caused by the descending portion of the duodenum, and

19720-410: The right of the gallbladder fossa are two impressions, one behind the other and separated by a ridge. The one in front is a shallow colic impression, formed by the hepatic flexure and the one behind is a deeper renal impression accommodating part of the right kidney and part of the suprarenal gland . The suprarenal impression is a small, triangular, depressed area on the liver. It is located close to

19865-666: The risk for atherosclerotic diseases. Data from the landmark Framingham Heart Study showed that, for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low. On the converse, however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high. Even people with very low LDL levels achieved by statin treatment are exposed to increased risk if their HDL levels are not high enough. Clinical laboratories formerly measured HDL cholesterol by separating other lipoprotein fractions using either ultracentrifugation or chemical precipitation with divalent ions such as Mg, then coupling

20010-471: The risk of cardiovascular disease . François Poulletier de la Salle first identified cholesterol in solid form in gallstones in 1769. In 1815, chemist Michel Eugène Chevreul named the compound "cholesterine". The word cholesterol comes from Ancient Greek chole- ' bile ' and stereos 'solid', followed by the chemical suffix -ol for an alcohol . Cholesterol is essential for all animal life. While most cells are capable of synthesizing it,

20155-411: The serum cholesterol after subtracting the HDL is the non-HDL cholesterol . The concentration of these other components, which may cause atheroma , is known as the non-HDL-C . This is now preferred to LDL-C as a secondary marker as it has been shown to be a better predictor and it is more easily calculated. With a size ranging from 5 to 17 nm, HDL is the smallest of the lipoprotein particles. It

20300-416: The sinusoidal lumen. The central area or hepatic hilum , includes the opening known as the porta hepatis which carries the common bile duct and common hepatic artery , and the opening for the portal vein. The duct, vein, and artery divide into left and right branches, and the areas of the liver supplied by these branches constitute the functional left and right lobes. The functional lobes are separated by

20445-404: The synthesis of cholesterol de novo , according to its presence inside the cell. A cell with abundant cholesterol will have its LDL receptor synthesis blocked, to prevent new cholesterol in LDL particles from being taken up. Conversely, LDL receptor synthesis proceeds when a cell is deficient in cholesterol. When this process becomes unregulated, LDL particles without receptors begin to appear in

20590-405: The tissues manifests itself as amyloidosis . It has been postulated that the concentration of large HDL particles more accurately reflects protective action, as opposed to the concentration of total HDL particles. This ratio of large HDL to total HDL particles varies widely and is measured only by more sophisticated lipoprotein assays using either electrophoresis (the original method developed in

20735-565: The walls of arteries, reducing the risk of sudden plaque ruptures , cardiovascular disease , stroke and other vascular diseases . HDL particles are commonly referred to as "good cholesterol", because they transport fat molecules out of artery walls, reduce macrophage accumulation, and thus help prevent or even regress atherosclerosis. Higher HDL-C may not necessarily be protective against cardiovascular disease and may even be harmful in extremely high quantities, with an increased cardiovascular risk, especially in hypertensive patients. Because of

20880-472: Was halted early because patients adding niacin to their statin treatment showed no increase in heart health, but did experience an increase in the risk of stroke. In contrast, while the use of statins is effective against high levels of LDL cholesterol, most have little or no effect in raising HDL cholesterol. Rosuvastatin and pitavastatin , however, have been demonstrated to significantly raise HDL levels. Lovaza has been shown to increase HDL-C. However,

21025-482: Was published; the complexes are capable of picking up cholesterol, carried internally, from cells by interaction with the ATP-binding cassette transporter A1 (ABCA1) . A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of the lipoprotein particle, eventually causing

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