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The Liver and Its Functions

The liver is the largest solid organ in the body. It removes toxins from the body’s blood supply, maintains healthy blood sugar levels, regulates blood clotting, and performs hundreds of other vital functions. It is located beneath the rib cage in the right upper abdomen.

• The liver filters all of the blood in the body and breaks down poisonous substances, such as alcohol and drugs.
• The liver also produces bile, a fluid that helps digest fats and carry away waste.
• The liver consists of four lobes, which are each made up of eight sections and thousands of lobules (or small lobes).

Functions of the Liver

The liver is an essential organ of the body that performs over 500 vital functions. These include removing waste products and foreign substances from the bloodstream, regulating blood sugar levels, and creating essential nutrients. Here are some of its most important functions:

• Albumin Production : Albumin is a protein that keeps fluids in the bloodstream from leaking into surrounding tissue. It also carries hormones, vitamins, and enzymes through the body.
• Bile Production : Bile is a fluid that is critical to the digestion and absorption of fats in the small intestine.
• Filters Blood : All the blood leaving the stomach and intestines passes through the liver, which removes toxins, byproducts, and other harmful substances.
• Regulates Amino Acids : The production of proteins depend on amino acids. The liver makes sure amino acid levels in the bloodstream remain healthy.
• Regulates Blood Clotting : Blood clotting coagulants are created using vitamin K, which can only be absorbed with the help of bile, a fluid the liver produces.
• Resists Infections : As part of the filtering process, the liver also removes bacteria from the bloodstream. 
• Stores Vitamins and Minerals : The liver stores significant amounts of vitamins A, D, E, K, and B12, as well as iron and copper.
• Processes Glucose : The liver removes excess glucose (sugar) from the bloodstream and stores it as glycogen. As needed, it can convert glycogen back into glucose.

Anatomy of the Liver

The liver is reddish-brown and shaped approximately like a cone or a wedge, with the small end above the spleen and stomach and the large end above the small intestine. The entire organ is located below the lungs in the right upper abdomen. It weighs between 3 and 3.5 pounds.

The liver consists of four lobes: the larger right lobe and left lobe, and the smaller caudate lobe and quadrate lobe. The left and right lobe are divided by the falciform (“sickle-shaped” in Latin) ligament, which connects the liver to the abdominal wall. The liver’s lobes can be further divided into eight segments, which are made up of thousands of lobules (small lobes). Each of these lobules has a duct flowing toward the common hepatic duct, which drains bile from the liver.

The following are some of the most important individual parts of the liver:

• Common Hepatic Duct : A tube that carries bile out of the liver. It is formed from the intersection of the right and left hepatic ducts.
• Falciform Ligament : A thin, fibrous ligament that separates the two lobes of the liver and connects it to the abdominal wall.
• Glisson’s Capsule : A layer of loose connective tissue that surrounds the liver and its related arteries and ducts.
• Hepatic Artery : The main blood vessel that supplies the liver with oxygenated blood.
• Hepatic Portal Vein : The blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas, and spleen to the liver. 
• Lobes : The anatomical sections of the liver.
• Lobules : Microscopic building blocks of the liver.
• Peritoneum : A membrane covering the liver that forms the exterior.

Maintaining a Healthy Liver

The best way to avoid liver disease is to take active steps toward a healthy life. The following are some recommendations that will help keep the liver functioning as it should:

• Avoid Illicit Drugs : Illicit drugs are toxins that the liver must filter out. Taking these drugs can cause long-term damage.
• Drink Alcohol Moderately : Alcohol must be broken down by the liver. While the liver can moderate amounts, excessive alcohol use can cause damage.
• Exercise Regularly : A regular exercise routine will help promote general health for every organ, including the liver.
• Eat Healthy Foods : Eating excessive fats can make it difficult for the liver to function and lead to fatty liver disease .
• Practice Safe Sex : Use protection to avoid sexually transmitted diseases such as hepatitis C .
• Vaccinate : Especially when traveling, get appropriate vaccinations against hepatitis A and B , as well as diseases such as malaria and yellow fever, which grow in the liver.

If you need help for a liver condition, give us a call at (877) LIVER MD/ (877) 548-3763 or get in touch using our online request form .

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The Many Vital Functions of the Liver

The liver is the heaviest organ in the body and one of the largest. It's located in the upper right portion of your belly under the ribs and is responsible for functions vital to life.

The liver primarily processes nutrients from food, makes bile, removes toxins from the body, and builds proteins. It metabolizes many drugs. It breaks down fat and produces cholesterol. It converts glycogen into glucose. It creates immune factors necessary to fight infection.

It's easy to see how inflammation of the liver , or hepatitis , interferes with these important functions and can lead to poor health. Fortunately, the liver is extremely resilient and most cases of liver inflammation don't even come to medical attention, but in cases of severe liver disease , there can be a serious interruption of these essential liver functions. Let's look at each of these functions a little closer.

Processing Nutrients from Food

The digestive system immediately begins to break down the food that we eat into smaller and smaller pieces. Eventually, these nutrients will enter the blood and travel to the liver through the hepatic portal system , the major pathway that blood takes from the ​ digestive system to the liver.

The liver will then process these nutrients in different ways, depending on the body's needs. It usually stores some of the nutrients in a form that the body can use for quick energy. The rest will be used to make other important chemicals the body needs.

When the liver is severely damaged, such as in liver failure , it can't continue to process nutrients from the blood that the body must have. Without aggressive medical care, the absence of these essential liver functions can result in signs of serious illness like brain damage and coma .

Making Bile

Bile is a thick, green-yellow fluid that the liver produces to help digest food, especially fat, as it passes from the stomach to the intestines. This fluid is made in the liver but is stored in a nearby sac called the gallbladder. When a person eats a meal heavy in fat, like a juicy steak, the body will use its store of bile to help break down the fats in the steak for digestion.

Removing Toxins From the Blood

All of the blood in the body will eventually pass through the liver. This is important because the liver needs to pull out any bad things in the blood, such as toxins, and remove them from the body. It metabolizes many drugs and alcohol and helps remove other toxins such as damaged cells, proteins, and old hormones.

The liver prepares all of these types of toxins to be removed from the body. However, when the liver is damaged, these toxins can't be removed and they start to accumulate creating problems.

Building Proteins

A protein is a complex chemical that is essential to living things, like plants, animals, and people. Proteins are everywhere in the body and need to be constantly produced to sustain life. The liver is in charge of building many kinds of proteins that the body uses every day.

For instance, there are many proteins produced by the liver that are responsible for blood clotting. When the liver is damaged , sometimes the body isn't able to clot blood effectively. In mild cases, it just takes a long time for bleeding to stop. However, in severe cases, the blood wouldn't be able to clot. A simple cut on the skin would lead to continued bleeding (though not necessarily a dangerous amount), and possibly bruises.

Gastrointestinal Society: Canadian Society of Intestinal Research. The liver - An amazing organ .

Centers for Disease Control and Prevention. What is viral hepatitis ?

Johns Hopkins Medicine. Liver: Anatomy and functions .

National Institute of Diabetes and Digestive and Kidney Diseases. Your digestive system and how it works .

American Liver Foundation. The progression of liver disease .

Johns Hopkins Medicine. Biliary system anatomy and functions .

Center for Liver Disease and Transplantation. The liver and its functions .

MedlinePlus. Loss of brain function - liver disease .

By Charles Daniel  Charles Daniel, MPH, CHES is an infectious disease epidemiologist, specializing in hepatitis.

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The Liver: A ‘Blob’ That Runs the Body

By Natalie Angier

• June 12, 2017

To the Mesopotamians, the liver was the body’s premier organ, the seat of the human soul and emotions. The ancient Greeks linked the liver to pleasure: The words hepatic and hedonic are thought to share the same root .

The Elizabethans referred to their monarch not as the head of state but as its liver, and woe to any people saddled with a lily-livered leader, whose bloodless cowardice would surely prove their undoing.

Yet even the most ardent liverati of history may have underestimated the scope and complexity of the organ. Its powers are so profound that the old toss-away line, “What am I, chopped liver?” can be seen as a kind of humblebrag.

After all, a healthy liver is the one organ in the adult body that, if chopped down to a fraction of its initial size, will rapidly regenerate and perform as if brand-new. Which is a lucky thing, for the liver’s to-do list is second only to that of the brain and numbers well over 300 items, including systematically reworking the food we eat into usable building blocks for our cells; neutralizing the many potentially harmful substances that we incidentally or deliberately ingest; generating a vast pharmacopoeia of hormones, enzymes, clotting factors and immune molecules; controlling blood chemistry; and really, we’re just getting started.

“We have mechanical ventilators to breathe for you if your lungs fail, dialysis machines if your kidneys fail, and the heart is mostly just a pump, so we have an artificial heart,” said Dr. Anna Lok, president of the American Association for the Study of Liver Diseases and director of clinical hepatology at the University of Michigan.

“But if your liver fails, there’s no machine to replace all its different functions, and the best you can hope for is a transplant.”

And while scientists admit it hardly seems possible, the closer they look, the longer the liver’s inventory of talents and tasks becomes.

In one recent study , researchers were astonished to discover that the liver grows and shrinks by up to 40 percent every 24 hours, while the organs around it barely budge.

Others have found that signals from the liver may help dictate our dietary choices, particularly our cravings for sweets, like a ripe peach or a tall glass of Newman’s Own Virgin Limeade — which our local supermarket chain has, to our personal devastation, suddenly stopped selling, so please, liver, get a grip.

Scientists have also discovered that hepatocytes, the metabolically active cells that constitute 80 percent of the liver, possess traits not seen in any other normal cells of the body. For example, whereas most cells have two sets of chromosomes — two sets of genetic instructions on how a cell should behave — hepatocytes can enfold and deftly manipulate up to eight sets of chromosomes, and all without falling apart or turning cancerous.

That sort of composed chromosomal excess, said Dr. Markus Grompe, who studies the phenomenon at Oregon Health and Science University, is “superunique,” and most likely helps account for the liver’s regenerative prowess.

Scientists hope that the new insights into liver development and performance will yield novel therapies for the more than 100 disorders that afflict the organ, many of which are on the rise worldwide, in concert with soaring rates of obesity and diabetes.

“It’s a funny thing,” said Valerie Gouon-Evans, a liver specialist at the Mount Sinai School of Medicine. “The liver is not a very sexy organ. It doesn’t look important. It just looks like a big blob.

“But it is quietly vital, the control tower of the body,” and the hepatocytes that it is composed of “are astonishing.”

The liver is our largest internal organ, weighing three and a half-pounds and measuring six inches long. The reddish-brown mass of four unevenly sized lobes sprawls like a beached sea lion across the upper right side of the abdominal cavity, beneath the diaphragm and atop the stomach.

The organ is always flush with blood, holding about 13 percent of the body’s supply at any given time. Many of the liver’s unusual features are linked to its intimate association with blood.

During fetal development, blood cells are born in the liver, and though that task later migrates to the bone marrow, the liver never loses its taste for the bodywide biochemical gossip that only the circulatory system can bring.

Most organs have a single source of blood. The liver alone has two blood supplies, the hepatic artery conveying oxygen-rich blood from the heart, the hepatic portal vein dropping off blood drained from the intestines and spleen. That portal blood delivers semi-processed foodstuffs in need of hepatic massaging, conversion, detoxification, storage, secretion, elimination.

“Everything you put in your mouth must go through the liver before it does anything useful elsewhere in the body,” Dr. Lok said.

The liver likes its bloodlines leaky. In contrast to the well-sealed vessels that prevent direct contact between blood and most tissues of the body, the arteries and veins that snake through the liver are stippled with holes, which means they drizzle blood right onto the hepatocytes.

The liver cells in turn are covered with microvilli — fingerlike protrusions that “massively enlarge” the cell surface area in contact with blood, said Dr. Markus Heim, a liver researcher at the University of Basel.

“Hepatocytes are swimming in blood,” he said. “That’s what makes them so incredibly efficient at taking up substances from the blood.”

As the master sampler of circulating blood, the liver keeps track of the body’s moment-to-moment energy demands, releasing glucose as needed from its stash of stored glycogen, along with any vitamins, minerals, lipids, amino acids or other micronutrients that might be required.

New research suggests the liver may take a proactive, as well as a reactive, role in the control of appetite and food choice.

Humans are famously fond of sweets, for example, presumably a legacy of our fruit-eating primate ancestors. But to gorge on sugar-rich foods, even in the relatively healthy format of a bucketful of Rainier cherries, could mean neglecting other worthy menu items.

Reporting in the journal Cell Metabolism , Matthew Gillum of the University of Copenhagen and his colleagues showed that after exposure to a high-sugar drink, the liver seeks to dampen further sugar indulgence by releasing a signaling hormone called fibroblast growth factor 21, or FGF21.

The effort is not always successful. For reasons that remain unclear, the hormone comes in active and feeble varieties, and the researchers found that people with a mutant version of FGF21 confessed to a lifelong passion for sweets.

The scientists are searching for other liver-borne hormones that might influence the hunger for protein or fat.

“It makes sense that the liver could be a nexus of metabolic control,” Dr. Gillum said. “At some level it knows more than the brain does about energy availability, and whether you’re eating too many pears.”

The liver also keeps track of time. In a recent issue of the journal Cell , Ulrich Schibler of the University of Geneva and his colleagues described their studies of the oscillating liver, and how it swells and shrinks each day, depending on an animal’s normal circadian rhythms and feeding schedule.

The researchers found that in mice, which normally eat at night and sleep during the day, the size of the liver expands by nearly half after dark and then retrenches come daylight. The scientists also determined the cause of the changing dimensions.

“We wanted to know, is it just extra water or glycogen?” Dr. Schibler said. “Because that would be boring.”

It wasn’t boring. “The total gemish, the total soup of the liver turns out to be different,” he said. Protein production in mouse hepatocytes rises sharply at night, followed by equivalent protein destruction during the day.

Evidence suggests that a similar extravaganza of protein creation and destruction occurs in the human liver, too, but the timing is flipped to match our largely diurnal pattern.

The researchers do not yet know why the liver oscillates, but Dr. Schibler suggested it’s part of the organ’s fastidious maintenance program.

“The liver gets a lot of bad stuff coming through,” he said. “If you damage some of its components, you need to replace them.” By having a rhythm to that replacement, he said, “you keep the liver in a good state.”

Adding to the liver’s repair protocol, Dr. Grompe of Oregon Health and Science University said, is the extreme plasticity of hepatocytes.

He and others have shown that, through their extraordinary ability to handle multiple sets of chromosomes and still perform and divide normally, liver cells become almost like immune cells — genetically diverse enough to handle nearly any poison thrown at them.

“Our ancestors didn’t have healthy refrigerated food,” he said. “They ate a lot of crap, probably literally, and the liver in prehistoric times was continuously bombarded with toxins. You need every mechanism there is to adapt to that.”

The liver rose to the evolutionary challenge. So yes, I’m chopped liver — and proud.

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A Guide to Better Nutrition

A viral TikTok trend touts “Oatzempic,” a half cup of rolled oats with a cup of water and the juice of half a lime, as a weight-loss hack. We asked the experts if there’s anything to it .

How much salt is too much? Should I cut back? We asked experts these and other questions about sodium .

Patients were told for years that cutting calories would ease the symptoms of polycystic ovary syndrome. But research suggests dieting may not help at all .

We asked a nutrition expert how she keeps up healthy habits without stressing about food. Here are seven tips  she shared for maintaining that balance.

There are many people who want to lose a few pounds for whom weight loss drugs are not the right choice. Is old-fashioned dieting a good option ?

Read these books to shift into a healthier way of thinking about food .

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David H. Wasserman

The liver is a critical hub for numerous physiological processes. These include macronutrient metabolism, blood volume regulation, immune system support, endocrine control of growth signaling pathways, lipid and cholesterol homeostasis, and the breakdown of xenobiotic compounds, including many current drugs. Processing, partitioning, and metabolism of macronutrients provide the energy needed to drive the aforementioned processes and are therefore among the liver's most critical functions. Moreover, the liver's capacities to store glucose in the form of glycogen, with feeding, and assemble glucose via the gluconeogenic pathway, in response to fasting, are critical. The liver oxidizes lipids, but can also package excess lipid for secretion to and storage in other tissues, such as adipose. Finally, the liver is a major handler of protein and amino acid metabolism as it is responsible for the majority of proteins secreted in the blood (whether based on mass or range of unique proteins), the processing of amino acids for energy, and disposal of nitrogenous waste from protein degradation in the form of urea metabolism. Over the course of evolution this array of hepatic functions has been consolidated in a single organ, the liver, which is conserved in all vertebrates. Developmentally, this organ arises as a result of a complex differentiation program that is initiated by exogenous signal gradients, cellular localization cues, and an intricate hierarchy of transcription factors. These processes that are fully developed in the mature liver are imperative for life. Liver failure from any number of sources (e.g. viral infection, overnutrition, or oncologic burden) is a global health problem. The goal of this primer is to concisely summarize hepatic functions with respect to macronutrient metabolism. Introducing concepts critical to liver development, organization, and physiology sets the stage for these functions and serves to orient the reader. It is important to emphasize that insight into hepatic pathologies and potential therapeutic avenues to treat these conditions requires an understanding of the development and physiology of specialized hepatic functions.

Liver cellular anatomy

The liver is composed of several cell types of different embryological origin including hepatocytes, biliary epithelial cells (cholangiocytes), stellate cells, Kupffer cells, and liver sinusoidal endothelial cells. Each of these cell types possesses unique functions that cooperatively regulate hepatic function at multiple levels. Hepatocytes are the primary epithelial cell population of the liver. They make up the majority of the liver volume and perform many of the functions ascribed to the liver. Cholangiocytes are the second most abundant epithelial population of the liver and have a more traditional epithelial function as the cells lining the lumen of the bile ducts. Stellate cells represent a dynamic cell population that can exist in a quiescent or activated state. In the quiescent state stellate cells store vitamin A in lipid droplets; however, other functions in this quiescent state remain unclear. Damage to the liver leads to activation of stellate cells. Upon activation, stellate cells proliferate and progressively lose vitamin A stores. Stellate cells are also responsible for deposition and organization of collagen in the injured liver. This process contributes to scarring of the liver, which can progress to cirrhosis, a critical pathology contributing to end stage liver disease. Kupffer cells are the resident macrophage population of the liver. These cells recognize the many pathogenic stimuli introduced through the portal circulation and can attain pro- or anti-inflammatory roles in liver wound healing depending on a number of contributing factors. Finally, liver sinusoidal endothelial cells are a specialized endothelial population with unique characteristics. These cells form fenestrated sieve plates at the sinusoidal lumen. This structure creates pores ranging in size from 50–180 nm in humans or 50–280 nm in mice and rats. This organization is critical for exchange of proteins and particles within these size limits between plasma and the cell types of the liver, while maintaining certain barrier functions.

The cells of the liver are organized around the functional structural unit of the liver — the lobule ( Figure 1A ). This consists of chords of hepatocytes organized in a typically hexagonal shape around the central vein ( Figure 1A ). At the vertices of this hexagon are the portal triads consisting of closely grouped branches of the hepatic artery, portal vein, and bile ducts ( Figure 1A ). Circulatory units within the hepatocyte chords differ from a typical capillary bed in that the endothelial cells of the liver do not form tight junctions ( Figure 1B ). This creates a sinusoidal network that minimizes barriers between hepatocytes and the blood traversing the sinusoid. Oxygen-rich blood from the hepatic artery mixes with nutrient-rich blood from the portal circulation in the sinusoid before flowing over the cells of the lobule and draining into the central vein ( Figure 1A, B ). This organization causes the blood composition exiting the lobule to have different characteristics than the blood entering the lobule. As blood progresses across the lobule, cells utilize oxygen and process nutrients, while generating metabolites and waste products. Blood becomes deoxygenated and metabolic byproducts are secreted from cells along the length of the sinusoid. This creates gradients of oxygen, nutrients, and waste presented to cells of the liver based on their lobular location. These and other gradients formed across the sinusoids of the lobule result in a partitioning of functions based on localization, such as increased oxidative metabolism in areas with higher blood oxygen content. This partitioning of functions has been termed ‘metabolic zonation’ and typically breaks the lobule into three distinct ‘zones’. Each zone possesses hepatocytes with differential metabolic gene expression and functionality. These metabolic zones are typically depicted as discrete regions ( Figure 1A ), but hepatic zonation actually exists on a flexible spectrum. For example, hepatocytes from Zone 2 can assume the functional attributes of Zone 1 hepatocytes in the face of damage or loss of function. This may occur in response to various liver-damaging pathologies such as viral hepatitis. A hallmark of the liver is that its diverse cell populations couple with its anatomical organization to maintain hepatic functionality.

(A) Geometric representation of a hepatic lobule. Appearing roughly hexagonal in shape, the vertices represent the portal triad area. Each triad contains branches of the hepatic artery, portal vein, and bile duct. Oxygenated blood from the hepatic artery mixes with nutrient-rich blood from the portal circulation drained from the gut. Upon mixing, this blood equilibrates and fl ows across the lobule through a sinusoidal network before draining in to branches of the central vein. This organization leads to formation of a number of gradients including oxygen, hormones, nutrients, and waste products. This gradient formation and the consequential organization of relevant metabolic processes has been dubbed ‘metabolic zonation’. These zones are depicted as roughly equal, but can shift in size and location based on a number of factors (e.g. hepatocellular damage or altered blood flow). (B) A schematic representation of a sinusoid within the liver and the corresponding zonation of several metabolic processes across the sinusoid. A number of cell types exist within the sinusoid including hepatocytes, biliary epithelial cells (cholangiocytes), endothelial cells, Kupffer cells, and stellate cells. As previously mentioned blood flows through the sinusoid leading to a number of gradients along the length of this vessel. Liver endothelial cells do not form tight junctions, but instead have sieve plate networks between them. This creates a minimal barrier between the circulating blood and hepatocytes. Hepatocytes perform a majority of the hepatic metabolic functions. The gradients depicted below the scheme pertain to both essential molecules (oxygen) and metabolic processes along the sinusoid. These processes are critical to both liver and whole body metabolic homeostasis. Therefore, it is important to note the flexibility of these gradients as they are often modified during times of variable nutrient availability, such as the fasting or fed states.

Initiation of liver development

As the function and organization of the liver are critical to so many processes it is important to understand how these aspects of the liver arise developmentally. Described here is the general organization of hepatic development that occurs in many animals including zebra fish, mice, rats, and humans. The duration and identity of signals involved in each of these developmental aspects may vary between species. The goal of this section is to give a general overview of hepatic development in common model organisms and humans. For simplicity, specific proteins and transcription factors referenced have been derived from studies in mice and rats except where specifically noted.

The definitive endoderm, ectoderm, and mesoderm make up the three major cell layers established during embryonic gastrulation. Cells from the definitive endoderm proceed to form the epithelium of the respiratory and digestive tracts as well as associated organs such as liver and pancreas. The primary metabolic cell population of the liver, hepatocytes, and the bile duct lining epithelial cells, cholangiocytes, arise from the posterior foregut region within the definitive endoderm. Definitive endoderm specification and segregation require a complex array of extracellular growth factor signals in a proper temporal order. Some of the earliest signals for initiation of hepatic bud outgrowth from the posterior foregut endoderm include fibroblast growth factor (FGF), and bone morphogenic proteins (BMPs), which are derived from the overlying mesodermally derived cardiac mesoderm and septum transversum. Other signals include transforming growth factor β (TGF-β), Wnt, and NOTCH. These signals are supported by expression and activity of transcription factors in the FoxA and GATA families within the endodermally derived epithelium. Specific members of these families, notably FoxA1 and GATA4, act as pioneer factors, interacting with their DNA-binding motifs within compact chromatin to modify nucleosome localization. This alteration of chromatin conformation creates an environment of transcriptional competence for these and other downstream transcription factors. The sum of these modifications results in a ‘footprint’ of transcriptional access, leading to the establishment and maintenance of a gene expression program, critical for differentiation and mature function.

Cell patterning and maturation during liver development

Cells of the hepatic bud give rise to bipotential progenitor cells known as hepatoblasts, which further differentiate into the liver parenchymal cells: hepatocytes and cholangiocytes. Importantly, prior to the formation of the bone marrow, the developing liver bud serves as the center of fetal hematopoiesis. Signals from hematopoietic cells, such as oncostatin M, can also govern hepatoblast proliferation and E-cadherin-mediated cell junction formation in hepatoblasts. While there are several other contributors to hepatoblast differentiation, the gradient of TGF-β secreted from the portal vein mesenchyme is integral to cholangiocyte and hepatocyte differentiation. This contributes to the hepatoblast fates that are dependent on portal vein proximity. Mechanistically, higher TGF-β signaling in portal vein proximal hepatoblasts drives cholangiocyte fate by decreasing expression of CCAAT/ enhancer binding protein (C/EBP) α and promoting expression of Hnf6 (aka Oc1) and Hnf1β. This transcription factor profile promotes cholangiocyte-specific gene transcription through HNF6 and HNF1β, while suppressing hepatocyte specific genes by decreasing C/EBPα levels. Hepatoblasts located further from the portal vein develop into hepatocytes, forming chords across the developing hepatic lobules. These cells receive lower levels of TGF-β, which leads to a higher level of C/EBPα. In turn, C/EBPα inhibits the expression of TGF-β receptor II, creating a positive feedback loop of TGF-β signal inhibition. C/EBPα also regulates expression of HNF1α and HNF4α, which in turn act as feed forward co-activators of a number of hepatocyte-specific genes. Finalization of hepatocyte differentiation is linked to oncostatin M, glucocorticoids, hepatocyte growth factor (HGF), Wnt, and yes-associated protein signaling (YAP). Interestingly, Wnt/β-catenin signaling has been implicated in establishment of metabolic zonation. In fact, a balance of stimulation and suppression of genes by HNF4α is influenced by the β-catenin activated transcription factor LEF1 to establish zonal specific expression of various enzymes (e.g. glutamine synthetase).

Perinatal metabolic programming

In the final term of gestation (week 34–37 in humans; day 18–21 in rats and mice), the liver prepares for a metabolic switch from an organ of glucose consumption to one in which glucose is both stored and produced. This is evidenced by a decrease in glycolytic enzyme expression coupled with increases in enzymes critical to gluconeogenic and glycogenic processes. The rate of enzyme activities such as the gluconeogenic enzymes phosphenolpyruvate carboxykinase and glucose-6-phosphatase, and the glycogenic enzyme glycogen synthase, are dependent on the metabolic zones of the hepatic lobule.

The switch from placental to maternal-independent endogenous and exogenous nutrient provision leads to a drop in blood glucose, which is accompanied by a stark rise in the hepatic sinusoidal glucagon to insulin ratio ( Figure 2A ). These hormones have opposing actions with regards to several hepatic metabolic processes and are the primary physiologic regulators of glucose homeostasis in the adult organism. In the fed state, when insulin is high and glucagon is low, the liver is a site of glucose uptake and anabolic processes are accelerated. Insulin inhibits gluconeogenesis while promoting glycogen and lipid synthesis in hepatocytes, amongst other metabolic effects. As an organism transitions away from placental nutrition, glucagon levels rise and insulin levels fall. Glucagon promotes glycogenosis, gluconeogenesis, fat oxidation and metabolism of other macronutrients by hepatocytes. These effects of the increased glucagon to insulin ratio are required for maintenance of blood glucose concentrations ( Figure 2A ). The switch in perinatal metabolic programming of the liver can be stimulated by hormone-mediated increases in cyclic adenosine monophosphate (cAMP) and is relatively insensitive to insulin. These processes are also regulated by glucocorticoid signaling, which appears necessary for functional differentiation of glycogen storage and gluconeogenesis. During the perinatal period, a number of transcription factors are induced, which regulate expression of key enzymes in these processes. Among these are FoxO1, glucocorticoid receptor, cAMP response element-binding protein (CREB), peroxisome proliferator activated receptor (PPAR) γ coactivator 1α, HNF6, and HNF4α. Transcription factors such as HNF6, HNF4α, and the glucocorticoid receptor intertwine differentiation and metabolic control in hepatocytes, indicating a potentially important connection in the two processes.

(A) In the fasting state the liver is in a net hepatic glucose output mode due to the low insulin to glucagon ratio. Glucose is derived from both glycogen and gluconeogenesis. Gluconeogenic substrates are provided in the form of amino acids (gut and muscle), lactate (muscle), pyruvate (muscle), and glycerol (adipose tissue). Fatty acids from adipose tissue lipolysis are also directed to several pathways, such as beta-oxidation and the TCA cycle. These processes support gluconeogenesis through production of ATP and reducing equivalents. Ketone bodies may also be produced from lipid oxidation and act as an additional energy shuttle between the liver and other organs. Amino acids can also enter the TCA cycle as anaplerotic substrates and be utilized for synthesis of proteins. Nitrogen released as a result of deamination during amino acid metabolism are disposed of during ureagenesis. Urea is released from the liver and excreted by the kidneys. (B) During feeding, water soluble nutrients enter the portal venous circulation from the intestine. At the liver, the insulin to glucagon ratio is elevated leading to net hepatic glucose uptake. Glucose may undergo glycolysis, as a means of ATP production, or may be stored as glycogen. Amino acids may be oxidized for energy production or utilized as anaplerotic substrates for the TCA cycle. Once again, these amino acids, as in the fasted state, may be used for synthesis of local or secreted proteins. Ingested fats are assembled to form triglycerides from fatty acids and glycerol. These triglycerides are packaged into chylomicrons, which then enter the lymphatic system. Chylomicrons drain from the lymphatics to the circulation and, upon reaching the liver, are unloaded of remaining fatty acids and glycerol. Fatty acids can be used for restoration of energy state, repletion of TCA cycle intermediates, or re-esterified to triglycerides. Triglycerides can be loaded on to very low density lipoproteins, which shuttle lipid to other tissues including muscle and adipose depots.

Glucose metabolism

As discussed at the outset, the ability of the liver to store, synthesize, metabolize, and release glucose is necessary for the postnatal metabolic transition and is maintained throughout the life of an organism. Upon feeding, the liver shifts from a mode of net output to net uptake ( Figure 2B ). This requires a decline in glucagon and an increase in insulin and results in decreased liver glucose output from glycogen stores and gluconeogenesis ( Figure 2B ). Glycolysis and glycogen deposition increase in hepatocytes, leading to net hepatic glucose uptake ( Figure 2B ). The glycogenic response restores glycogen reserves. As an organism transitions from an absorptive state to a fasting state insulin decreases and glucagon increases ( Figure 2A ). This shifts the liver from glucose storage to net glucose output, which involves glycogen breakdown and gluconeogenesis ( Figure 2A ). Glucose output is dynamic and responsive to the energy needs throughout the body (e.g. brain, skeletal muscle, and immune system).

One of the growing pathologic concerns in developed countries is the hepatic response to over-nutrition. A key component of this pathologic response is insulin resistance at the liver, which is closely associated with type II diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. Given the immense public health implications of these disease states it is important to understand the functional consequences of this condition. Hepatic insulin resistance is characterized by an impaired ability of insulin to decrease net glucose output from the liver. This contributes to increased blood glucose. While the inhibitory effect of insulin on hepatic glucose output is lost, the stimulatory effect of insulin on lipogenesis is maintained. This dissociation of insulin's effects on carbohydrate and lipid metabolism creates a ‘selective insulin resistance’ and is thought to contribute to a number of pathological conditions (e.g. metabolic syndrome, non-alcoholic fatty liver disease, and cardiovascular disease). There are a number of underlying factors implicated in the development of hepatic insulin resistance. These involve altered coupling of insulin receptor to intracellular signaling proteins, protein levels, kinase activities, nuclear localization of transcription factors, and a number of other molecular mechanisms. Additionally, insulin resistance is associated with an increased flux of gluconeogenic substrates and fatty acids to the liver during over-nutrition. This creates a paradigm where increased substrate fluxes are coupled with a deficit in appropriate molecular control resulting in many of the pathologic consequences of insulin resistance.

Lipid and cholesterol metabolism

The liver is critical for digestive absorption and performs uptake, synthesis, packaging, and secretion of lipids and lipoproteins. The liver's biliary synthesis and secretion system enables efficient absorption of lipid from digestion. Chylomicrons are assembled from lipoproteins and digested lipids in the gut before progressing through the lymphatic system to the circulation. Fatty acids are then extracted from chylomicron remnants by lipoprotein lipase at the liver. These fatty acids are then transported into hepatocytes via a number of transport proteins (e.g. fatty acid transport proteins 2, 4 and 5 and CD36). The liver is able to utilize fatty acids as an internal energy source through oxidative pathways, but can also provide energy to other organs from the ketogenic products (acetoacetate and beta hydroxybutyrate) ( Figure 2A,B ). This ability to provide ketones as an energetic substrate is necessary for organisms undergoing extreme fasting or consuming extremely low levels of dietary carbohydrates. The release of ketones from the liver prevents excess formation of tricarboxylic acid cycle intermediates and could thereby protect oxidative status. During times of feeding, the liver is also important for providing lipid substrates for the body. The liver can assemble fatty acids and glycerol into triglycerides, which are packaged with very low density lipoprotein particles for secretion from hepatocytes into the bloodstream ( Figure 2B ). These can then reach other organs such as the adipose tissue for storage or the skeletal muscle for use as an energy source. This lipid handling ability of the liver is also critical for absorption of a number of lipid-soluble vitamins. Without proper hepatic lipid uptake and secretion, vitamin deficiencies at the whole body or organ-specific level can occur. In addition to its function with regards to classical fat molecules, the liver is also critical for cholesterol homeostasis within the body. Cholesterol can be absorbed from the intestine or synthesized de novo in the liver. Cholesterol is a required molecule for assembly of cellular membranes as well as maintenance of membrane fluidity. While a lack of cholesterol can be damaging, an excess is also detrimental to health. Excess cholesterol from the diet and de novo synthesis can result in inappropriate cell membrane dynamics, and may also stimulate pathologic processes contributing to atherosclerosis or cardiovascular disease. Statins are a drug class that inhibits HMG-CoA reductase, the rate limiting enzyme in cholesterol production. This results in a cholesterol-lowering effect that is necessary for statin-mediated improvement of outcomes for cardiovascular events and atherosclerosis. Statins also possess pleiotropic actions which are thought to be significant at higher statin dosages. Therefore, cholesterol-lowering is considered the primary benefit of statins to disease processes with pleiotropic statin effects becoming relevant at higher doses.

Protein and amino acid metabolism

Synthesis and breakdown of proteins are critical to all cellular and organ-level functions. However, these metabolic processes within the liver have broader implications. As a protein synthetic organ, the liver is responsible for 85–90% of circulating protein volume. Albumin is the most abundant of these secreted proteins, contributing 55% of the total plasma protein on average. This protein is essential for maintenance of blood volume and possesses carrier functions in transporting a number of critical molecules such as lipids and hormones. The liver also secretes acute-phase proteins, growth factors, and numerous other peptides that are involved in systemic regulation. Additionally, the liver has a high capacity to break down proteins and metabolize the amino acids that comprise them ( Figure 2A,B ). Amino acid metabolism can provide energy for the hepatocyte, but requires disposal of nitrogenous wastes ( Figure 2A,B ). The liver urea cycle is one mechanism for this, disposing of otherwise damaging reactive nitrogenous molecules. The carbon skeleton of specifi c amino acids may also be incorporated into the tricarboxylic acid cycle to serve as gluconeogenic substrates ( Figure 2A,B ). This allows conversion of amino acids from tissues such as skeletal muscle and intestine to glucose. This conversion of gluconeogenic amino acids to glucose is pertinent to glucose homeostasis and the provision of energy to glucose-dependent organs in times of extended fasting.

Concluding remarks

The liver is a dynamic, heterogeneous organ that is under highly regulated physiological control. Development and control of these functions is established through appropriate timing, localization, and intensity of signals. Despite progress in our understanding of hepatic development, metabolism, and repair, hepatic pathologies continue to have significant global morbidity and mortality burdens. This drives the need to understand these diseases and how to best treat them. This can be accomplished through therapeutic and public health initiatives reinforced by knowledge of hepatic physiology and emerging disease treatment paradigms.

Further Reading

• Bechmann LP, Hannivoort RA, Gerken G, Hotamisligil GS, Trauner M, Canbay A. The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol. 2012; 56 :952–964. [ PubMed ] [ Google Scholar ]
• Gordillo M, Evans T, Gouon-Evans V. Orchestrating liver development. Development. 2015; 142 :2094–2108. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Gruppuso PA, Sanders JA. Regulation of liver development: implications for liver biology across the lifespan. J Mol Endocrinol. 2016; 56 :115–125. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hijmans BS, Grefhorst A, Oosterveer MH, Groen AK. Zonation of glucose and fatty acid metabolism in the liver: mechanism and metabolic consequences. Biochimie. 2014; 96 :121–129. [ PubMed ] [ Google Scholar ]
• Rui L. Energy metabolism in the liver. Compr Physiol. 2014; 4 :177–197. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev Cell. 2010; 18 :175–189. [ PubMed ] [ Google Scholar ]
• Trefts E, Williams AS, Wasserman DH. Progress in Molecular Biology and Translational Science. 1st. Vol. 135. Amsterdam: Elsevier; 2015. Exercise and the regulation of hepatic metabolism; pp. 203–225. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Wasserman DH. Four grams of glucose. 2009; 37232 :11–21. [ PMC free article ] [ PubMed ] [ Google Scholar ]

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22.7A: The Liver

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The liver makes bile, which is essential for the digestion of fats.

Learning Objectives

• Summarize the roles of the liver in digestion
• The liver is a vital organ with a wide range of functions, including detoxification, protein synthesis, and the production of bile, which is necessary for digestion.
• The bile produced by the liver is essential for the digestion of fats. Bile is formed in the liver and either stored in the gallbladder or released directly into the small intestine.
• liver : A large organ in the body that stores and metabolizes nutrients, destroys toxins, and produces bile. It is responsible for thousands of biochemical reactions.
• bile : A bitter, brownish-yellow or greenish-yellow secretion produced by the liver, stored in the gallbladder, and discharged into the duodenum, where it aids the process of digestion.

The Role of the Liver

The liver normally weighs between 1.3—3.0 kilograms and is a soft, pinkish-brown organ. It is the second-largest organ in the body, and is located on the right side of the abdomen.

Human liver : Photo of recently removed human liver.

The liver plays a major role in metabolism and has a number of functions in the body, including glycogen storage, plasma protein synthesis, and drug detoxification. It also produces bile, which is important for digestion.

The liver is supplied by two main blood vessels on its right lobe: the hepatic artery and the portal vein. The portal vein brings venous blood from the spleen, pancreas, and small intestine so that the liver can process the nutrients and byproducts of food digestion.

The bile produced in the liver is essential for the digestion of fats. Bile is formed in the liver, and it is stored in the gallbladder or released directly into the small intestine. After being stored in the gallbladder, the bile becomes more concentrated than when it left the liver; this increases its potency and intensifies its effect in digesting fats.

The Multifaceted Role of the Liver in Human Body

This essay about the liver’s essential functions within the human body outlines its critical roles in metabolism, detoxification, synthesis, regulation, and immunity. It describes how the liver processes nutrients, manages energy reserves, detoxifies harmful substances, and produces vital compounds like bile and various proteins. Furthermore, the essay touches on the liver’s involvement in the immune system, highlighting its capability to fend off infections. The importance of maintaining liver health through responsible lifestyle choices is underscored, given the liver’s susceptibility to damage from factors like alcohol abuse and environmental toxins. The essay concludes by emphasizing the liver’s indispensable role in sustaining life and overall health, advocating for awareness and actions conducive to its well-being.

How it works

The hepatic organ, often likened to the corporeal chemical processing center, emerges as one of the utmost vital entities, wielding a pivotal stance in fostering overall well-being. Its functionalities exhibit such intricate and indispensable nature that sans its presence, survival stands as an insurmountable feat. This exposition plunges into the manifold roles of the liver, accentuating its significance transcending the well-established purview of detoxification.

Primarily, the liver assumes a pivotal stance in metabolic orchestrations, acting as a nexus for nutrient digestion, synthesis, and reservoir.

Upon nutrient ingestion, carbohydrates undergo conversion into glucose, which then finds refuge within the liver in the form of glycogen. When the corporeal mechanism clamors for energy, the liver undertakes the conversion of glycogen back into glucose, thereby ensuring a perpetually steadfast energy provision. Analogously, the liver spearheads the metabolization of proteins and lipids, transmuting them into imperative substances conducive to energy generation and the fabrication of vital bodily constituents.

Detoxification, arguably the liver’s most acclaimed forte, entails the sieving of the bloodstream to expunge deleterious substances, encompassing pharmaceuticals, ethanol, and environmental contaminants. This indispensable course stands as a barricade against the accumulation of pernicious agents poised to precipitate formidable health adversities. The liver’s adeptness in detoxification attests to its mantle as the custodian of the corporeal internal milieu.

Furthermore, the liver assumes a momentous role in the synthesis and governance of myriad substances indispensable to health. Notably, it engenders bile, a requisite compound pivotal for the digestion and assimilation of lipids and lipid-soluble vitamins within the intestine. Moreover, the liver exerts meticulous control over the levels of sundry hormones and plasma proteins, encompassing albumin, which upholds the blood’s osmotic equilibrium, and coagulation factors, pivotal for hemostasis.

The liver’s contribution to immunological fortification warrants profound acknowledgment. It constitutes a pivotal constituent of the reticuloendothelial system, housing myriad immune cells poised to discern and obliterate pathogens infiltrating from the intestinal domain. This immunological stewardship assumes paramount significance in thwarting the dissemination of infections and perpetuating overall vitality.

Despite its inherent resilience, the liver remains susceptible to onslaught. Lifestyle predilections such as intemperate ethanol consumption, suboptimal dietary habits, and exposure to environmental toxins can undermine its functionalities. Maladies such as hepatitis, hepatic steatosis, and cirrhosis can engender formidable health ramifications, accentuating the imperative of hepatic preservation within the broader spectrum of well-being.

In summation, the liver’s functional repertoire stands as multifaceted and indispensable, encompassing metabolism, detoxification, synthesis, governance, and immunological fortification. Its adeptness in discharging a gamut of tasks renders it indispensible to human vitality. Comprehending the liver’s manifold roles not only underscores the import of this organ but also accentuates the necessity for lifestyle choices conducive to its optimal operation. The liver’s inherent resilience and regenerative potential proffer optimism for convalescence from harm, provided it remains within manageable bounds. Thus, the liver merits acclaim not solely for its intricacy and adaptability but also for its momentous contributions to life and vitality.

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Essay about The Liver and Its Functions

The Liver is the body's largest gland, weighing about three to four pounds. It is located beneath the diaphragm in the right upper quadrant (RUQ) of the abdominal cavity. Without the liver, our bodies would be poisoned and unfit for us to do anything at all. It is a metabolically active organ responsible for many vital life functions. The primary functions of the liver are: Bile productions and excretion. Excretion of bilirubin, cholesterol, hormones, and drugs. Metabolism of fats, proteins, and carbohydrates. Enzyme activation. Storage of glycogen, vitamins, and minerals. Synthesis of plasma proteins, such as albumin, and clotting factors. And blood detoxification and purification. The liver is the body's energy factory. …show more content…

The bile moves into the gallbladder via tiny tubes. The bile is stored in the gallbladder and waits, becoming concentrated, for the signal to be released into the duodenum aiding in digestion. Without bile, the body could not digest fats, as fats do not absorb into water. The bile acts as a detergent and allows the two to mix. The liver is an unusual organ because nearly every one of its cells is exactly alike. The working cells of the liver are known as hepatocytes. Hepatocytes have a unique capacity to reproduce in response to liver injury. Liver regeneration can occur after surgical removal of a portion of the liver (hepatectomy) or after injuries that destroy parts of the liver. And this regeneration can adjust its size to match its host. Within a week after partial hepatectomy, hepatic mass is back essentially to what it was prior to surgery. Even though the liver has the ability to react to damage and can repair itself, repetitive insults can produce liver failure or deadly diseases, infections, and disorders. A few such diseases are viral hepatitis, yellow fever, and rubella. Some of the disease caused by bacteria are amebic dysentery, leptospirosis, and streptococcal infections. These diseases can fatally damage the liver. Liver failure is the acute failure of the liver to perform its body function. Proteins that allow the blood to clot are not produced so the patient bruises and bleeds easily. A viscous fluid will sometimes collect

Essay about Cirrhosis

Metabolism and genetics also participate in cirrhosis for example abnormal collection of iron (hemochromatosis) or copper (Wilson's disease) in the liver causing injury, scarring and cirrhosis. Further cause of cirrhosis is the Autoimmune chronic active hepatitis that happens when the immune system attacks the liver and causes inflammation, damage, and cirrhosis. Drugs and chemicals also cause injury of the liver.

Portal Hypertension Paper

The liver’s job is to produce bile, and in return the job of the bile is to emulsify or break down the large amounts of fat, which will assist the body in digesting the remaining food easier (Guyton & Hall, 2011). The next stage is metabolism. The digestive systems job is to metabolize and break down the needed energy for the body and to send the excess wastes to go through detoxification (Guyton & Hall, 2011). As the blood circulates through the portal vein, toxins are removed, to prevent a rise in ammonia levels (Guyton & Hall, 2011). Once all wastes have been removed, the needed vitamins and nutritional needs are stored in the tissues in the body (Guyton & Hall, 2011). The next stage is the production of prothrombin and fibrinogen for coagulation and finally the immunity is for the Kupffer cells to attack and

Gallbladder Research Paper

The gallbladder is a hollow structure which is located right below the liver, and to the right side of the abdomen. Its main function is to store bile, which is made in the liver. The gallbladder is part of the biliary tract. The gallbladder holds the bile when it is not being used for digestion. The bile helps to break down fats during digestion. It also moves waste products from the liver into the duodenum. The bile duct is a long tube that carries the bile. It connects the liver and the gallbladder. Bile is an alkaline fluid. When it is discharged into the duodenum, it neutralises the acidity of the food coming from the stomach.

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Chemical Digestion Research Paper

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Major Body Cavities

The abdominal cavity which contains the stomach, most of the large intestine, the small intestine, the gallbladder, spleen, kidney and liver. The small intestine is very important and its job is to digest food and also take nutrients from food to help give back to the body. The gallbladder is a small storage organ also needed in digestion and holds bile products produced by the liver until needed for digesting fatty foods. The kidney is also vital because it helps aid in essential processes such as regulating blood pressure. The liver is very vital and performs multiple critical functions to keep the body pure of toxins and harmful substances. Without a healthy liver, a person cannot survive. Then the pelvic cavity which will contain also portions of the large intestine, reproductive organs, and the urinary bladder. The large intestine is also known for helping during digestion by taking undigested food and absorbing as much water as it can and expels the waste. The reproductive organs play a vital role in the survival of our species. Lastly, the urinary bladder functions as a storage vessel. It is one of the most elastic organs and is able to increase its volume

What Causes Acute Liver Failure

An acute liver failure happens when the normal function of the liver stops. This happens to people that never before had liver problems. And it happens in a short time of period like a couple of weeks and even days. So it can happen fast and it also causes complications that can be very bad. It causes strong pain on the brain and intense bleeding.

Hepatitis Research Paper

There is no doubt that hepatitis is one of the most dangerous disease and has its bad and negative effects. At the beginning hepatitis is a medical condition that means injury to the liver with inflammation of the liver cells. Simply hepatitis is a disease that includes any type of inflammation of the liver. It may present in acute or chronic forms. Doctors call the inflammation that lasts less than six months acute hepatitis and inflammation that lasts longer than six months chronic hepatitis.

Muscular System Vs Digestive System

The pancreas is important because it breaks down the fat, carbohydrates and protein from the food we eat. The liver is important because it has many different functions within the digestive system. But liver makes up secrete bile and it cleanses it and purifies the blood coming from the small

First Pass Metabolism

Liver is the main organ for the metabolism of exogenous material. As first pass metabolism is the major elimination route of many drugs the drug exposure in the liver can be very high and hence there is a significant incidence of Drug Induced Liver Injury (DILI) associated with this.

Liver Cell Inflammation

Inflammation is a kind of protective immune response of body towards the hazardous stimulants like pathogens, irritants or even dead cells. The components of this protective immune response include blood vessels, mast cells , tumor necrosis factor (TNF-α), tryptase, chemokines, reactive oxygen species (ROS), histamine, bradykinin, prostaglandin and leukotrines, interleukin-1. The inflammatory process is associated with stoppage of harmful stimuli, clearance of damaged tissues and repairing of injury. Inflammation is strictly regulated by the body. The extent of this response determines its positive or negative effect on body. Extremely low level of inflammation can’t stop tissue damage where as chronic inflammation frequently becomes the cause of disease itself.

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The most significant agent determining postoperative morbidity and mortality is the capacity of the remnant liver to regenerate [3]. Clinical inquiries found that, following removal of up to 50% of functional liver, there was usually only a gentle and short-lived rise in serum bilirubin and depression of serum proteins indicating sustained briefness of hepatocellular function [4] [5] [6] [7] [8] [9]. While

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Damage or injury to the liver caused by a drug, chemical or other agent. Symptoms vary depending on the degree of exposure and hence extent of the liver damage or injury. Mild liver damage may cause few of any symptoms whereas severe damage can ultimately result in liver failure.

Explain Why The Liver Is The Body's Largest Intestinal Organs

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What is the relationship between the liver and pancreas?

The liver and pancreas are organs in the upper abdomen. The liver is vital for metabolism, detoxification, digestion, and more. The pancreas produces essential enzymes and hormones. Together, they help maintain healthy blood glucose levels and other functions.

The liver is the largest solid organ and gland in the body. It carries out many vital tasks, including roles in metabolism, digestion, immunity, and detoxification. The pancreas is another gland organ that produces insulin and other important hormones and enzymes. These organs work together to keep blood sugars within a healthy range .

In this article, we will explore the functions and location of the liver and pancreas and discuss how to keep both organs healthy.

Liver location and function

The liver sits in the right hypochondriac and epigastric regions, which are in the upper right quadrant of the abdomen. It sits below the diaphragm but above the stomach, intestines, and right kidney.

The liver performs over 500 vital functions , including:

• Producing albumin: This protein helps transport important substances.
• Producing bile: This fluid helps with digestion.
• Filtering blood: The liver removes toxins and other harmful substances.
• Regulating amino acids: This helps with protein production.
• Supporting blood clotting: Bile helps with this process.
• Supporting the immune system: The liver destroys pathogens during blood filtration.
• Storing vitamins and minerals: It can release these when the body requires them.
• Regulating glucose levels: It does this by storing and releasing sugar.

Pancreas location and function

The pancreas is a long, soft organ present in the upper left abdominal region. It sits below the liver, behind the stomach, and extends from the upper part of the small intestine to the spleen .

The main function of the pancreas is to produce chemicals in the correct quantities to help people digest and process the foods they consume. It has both exocrine and endocrine functions:

This term refers to when a gland creates and releases substances through a duct or opening.

The pancreas produces enzymes , such as trypsin, chymotrypsin, amylase, and lipase, which help break down food. These pancreatic juices release into the pancreatic duct and join the common bile duct, which originates in the liver. The juices then enter the first part of the small intestine, where they begin digesting food.

This term refers to when a gland produces hormones that release directly into the blood and travel to tissues and organs throughout the body.

The endocrine function of the pancreas involves a group of cells known as the islets of Langerhans , or islet cells . These cells create and release important hormones , such as insulin and glucagon , which maintain the balance of blood sugars.

Relationship

The main relationship between these two organs is the regulation of blood sugars. They also have a structural link and work together to help with digestion.

Blood sugar

The pancreas produces and secretes the hormones insulin and glucagon .

Beta cells in the pancreas produce insulin, which stimulates the uptake of glucose from the blood into cells, lowering a person’s blood sugar. The liver and muscles can either use the glucose for immediate energy or store it as a molecule called glycogen.

Alpha cells in the pancreas produce glucagon, which stimulates cells in the liver and muscles to release glucose, raising a person’s blood sugar.

The liver can both store and produce sugar, depending on the body’s requirements. Insulin and glucagon signal whether the liver needs to store or manufacture glucose. For example, during a meal, the pancreas will secrete insulin and suppress glucagon, causing the liver to store glucose as glycogen.

Alternatively, when blood sugars are low, the liver can convert glycogen into glucose through a process known as glycogenolysis . The liver can also use other substances such as amino acids, waste products, and fat byproducts to produce sugar through a process known as gluconeogenesis .

In situations where blood sugar supplies are low, the body will conserve glucose for the brain, red blood cells, and kidneys. When this occurs, the liver can produce an alternative fuel source from fats, known as ketones , through a process called ketogenesis .

The liver and pancreas have a structural connection through ducts. The bile duct and pancreatic duct join at the duodenum, which is the first section of the small intestine.

The bile duct is a tube that passes bile in and out of the liver and forms part of the biliary system . The liver secretes bile, which travels through hepatic ducts and eventually joins the bile duct. The body also stores some bile in the gallbladder. Bile helps with digestion.

The pancreas secretes pancreatic enzymes , which flow through the pancreatic ducts to the duodenum. These pancreatic juices also help aid digestion by breaking down fats, proteins, and carbohydrates.

How to keep the organs healthy

As both the liver and pancreas play important roles in the human body, it is vital that people attempt to keep these organs healthy.

Some suggestions for maintaining liver health may include :

• maintaining a moderate weight
• consuming a healthy, varied diet
• exercising regularly
• avoiding alcohol or drinking only in moderation
• avoiding illegal drugs and toxins
• receiving vaccinations for conditions such as hepatitis

Tips for a healthy pancreas are largely similar. If a person is experiencing inflammation of the pancreas, known as pancreatitis , a doctor may advise them to try a pancreatitis diet .

This nutritional plan emphasizes:

• consuming fruits, vegetables, beans, lentils, and whole grains
• eating lean meats
• including medium-chain triglycerides , a type of fat
• avoiding alcohol, fried foods, high fat foods, and refined carbohydrates

Click here to learn more about the pancreatitis diet .

The liver and pancreas are two important organs present in the abdominal area. They perform several vital bodily functions and work closely together to help regulate blood sugar.

They also play an important role in digestion. It is advisable to maintain a moderate weight, exercise regularly, and consume a healthy and varied diet to keep both organs healthy.

Last medically reviewed on August 5, 2022

• Pancreatic Cancer
• Liver Disease / Hepatitis

How we reviewed this article:

• 13 ways to a healthy liver. (2021). https://liverfoundation.org/13-ways-to-a-healthy-liver/
• Anatomy & physiology. (n.d.). https://training.seer.cancer.gov/anatomy/
• Bile. (n.d.). https://www.cancer.gov/publications/dictionaries/cancer-terms/def/bile
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• Review Article
• Published: 06 August 2020

Liver regeneration: biological and pathological mechanisms and implications

• George K. Michalopoulos   ORCID: orcid.org/0000-0001-9922-6920 1 &
• Bharat Bhushan   ORCID: orcid.org/0000-0002-1716-9764 1  

Nature Reviews Gastroenterology & Hepatology volume  18 ,  pages 40–55 ( 2021 ) Cite this article

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• Hepatocytes
• Liver diseases

The liver is the only solid organ that uses regenerative mechanisms to ensure that the liver-to-bodyweight ratio is always at 100% of what is required for body homeostasis. Other solid organs (such as the lungs, kidneys and pancreas) adjust to tissue loss but do not return to 100% of normal. The current state of knowledge of the regenerative pathways that underlie this ‘hepatostat’ will be presented in this Review. Liver regeneration from acute injury is always beneficial and has been extensively studied. Experimental models that involve partial hepatectomy or chemical injury have revealed extracellular and intracellular signalling pathways that are used to return the liver to equivalent size and weight to those prior to injury. On the other hand, chronic loss of hepatocytes, which can occur in chronic liver disease of any aetiology, often has adverse consequences, including fibrosis, cirrhosis and liver neoplasia. The regenerative activities of hepatocytes and cholangiocytes are typically characterized by phenotypic fidelity. However, when regeneration of one of the two cell types fails, hepatocytes and cholangiocytes function as facultative stem cells and transdifferentiate into each other to restore normal liver structure. Liver recolonization models have demonstrated that hepatocytes have an unlimited regenerative capacity. However, in normal liver, cell turnover is very slow. All zones of the resting liver lobules have been equally implicated in the maintenance of hepatocyte and cholangiocyte populations in normal liver.

Hepatocyte proliferation during liver regeneration is controlled by multiple extracellular signals, two of which (MET and EGFR) are directly mitogenic and others only delay liver regeneration if they are bypassed.

Intracellular signalling pathways in hepatocytes are very rapidly (within minutes) activated after partial hepatectomy. The mechanisms triggering these pathways are not clear.

All hepatic cell types participate in cell proliferation during liver regeneration. No ‘stem cells’ are involved.

If hepatocyte or cholangiocyte proliferation is seriously impaired, then each of the two cell types can transdifferentiate into the other and function as a facultative stem cell.

Loss of hepatocytes occurring in chronic liver diseases triggers compensatory proliferation of the surviving hepatocytes and exposes them to potentially genotoxic injury that might lead to neoplasia.

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Michalopoulos, G.K., Bhushan, B. Liver regeneration: biological and pathological mechanisms and implications. Nat Rev Gastroenterol Hepatol 18 , 40–55 (2021). https://doi.org/10.1038/s41575-020-0342-4

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The liver, a functionalized vascular structure

Affiliations.

• 1 Department of Mechanical Engineering, Villanova University, Villanova, PA, 19085, USA. [email protected].
• 2 Departamento de Física, Facultad de Ciencias, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, CP04510, Coyoacán, Ciudad de México, Mexico.
• 3 Centro Médico 20 de Noviembre, ISSSTE,, Félix Cuevas 540, Del Valle Sur, Benito Juárez, CP03100, Ciudad de México, Mexico.
• PMID: 33004881
• PMCID: PMC7531010
• DOI: 10.1038/s41598-020-73208-8

The liver is not only the largest organ in the body but also the one playing one of the most important role in the human metabolism as it is in charge of transforming toxic substances in the body. Understanding the way its blood vasculature works is key. In this work we show that the challenge of predicting the hepatic multi-scale vascular network can be met thanks to the constructal law of design evolution. The work unveils the structure of the liver blood flow architecture as a combination of superimposed tree-shaped networks and porous system. We demonstrate that the dendritic nature of the hepatic artery, portal vein and hepatic vein can be predicted, together with their geometrical features (diameter ratio, duct length ratio) as the entire blood flow architectures follow the principle of equipartition of imperfections. At the smallest scale, the shape of the liver elemental systems-the lobules-is discovered, while their permeability is also predicted. The theory is compared with good agreement to anatomical data from the literature.

• Dendritic Cells / physiology*
• Hepatic Artery / physiology*
• Hepatic Veins / physiology*
• Liver / blood supply*
• Liver Circulation*
• Models, Theoretical*