Liver Functions

The Liver The characteristic structure and organization of the liver enables it to perform vital roles in regulating, synthesizing, storing, secreting, transforming, and breaking down many different substances in the body. In addition, the liver's ability to regenerate lost tissue helps maintain these functions, even in the face of moderate damage. This section of the module focuses on the structural aspects of the liver and its ability to regenerate. 

Liver Functions 

The body depends on the liver to perform a number of vital functions , and although there is substantial overlap, they can be divided into three basic categories: 

regulation, synthesis, and secretion of many substances important in maintaining the body's normal state 

storage of important nutrients such as glycogen (glucose), vitamins, and minerals,  purification, transformation, and clearance of waste products, drugs, and toxins 

Disease or traumatic injury can greatly reduce the liver's ability to carry out these normal activities. Thus, most of the clinical manifestations of liver dysfunction (discussed later in this module) stem from cell damage and impairment of the normal liver capacities. For example, viral hepatitis causes damage and death of hepatocytes. In this case, manifestations may include increased bleeding (due to decreased synthesis of clotting factors), jaundice (yellow pigmentation due to decreased clearance of bilirubin ), and increased levels of circulating hepatocyte enzymes (released from dead liver cells). 

1. Regulations, Synthesis, and Secretion. Hepatocytes are metabolically active cells that serve many functions. For example, they take up glucose, minerals, and vitamins from portal and systemic blood and store them. In addition, hepatocytes can produce many important substances needed by the body, such as blood clotting factors, transporter proteins, cholesterol, and bile components. Finally, by regulating blood levels of substances such as cholesterol and glucose, the liver helps maintain body homeostasis. 

a. Glucose. The liver plays a major role in maintaining blood concentrations of glucose, by storing or releasing glucose as needed. 

b. Proteins. Most blood proteins (except for antibodies) are synthesized and secreted by the liver. One of the most abundant serum proteins is albumin. Impaired liver function that results in decreased amounts of serum albumin may lead to edema, swelling due to fluid accumulation in the tissues. 

The liver also produces most of the proteins responsible for blood clotting, called coagulation or clotting factors. If the blood cannot clot normally due to a decrease in the production of these factors, excessive bleeding may result. 

c. Bile. Bile is a greenish fluid synthesized by hepatocytes and secreted into biliary ducts. It then leaves the liver to be temporarily stored in the gallbladder before emptying into the small intestine. The major components of bile include cholesterol, phospholipids, bilirubin (a metabolite of red blood cell hemoglobin), and bile salts. Importantly, bile salts act as "detergents" that aid in the digestion and absorption of dietary fats. Liver damage or obstruction of a bile duct (e.g., gallstone) can lead to cholestasis, (the blockage of bile flow, which causes the malabsorption of dietary fats), steatorrhea (foul-smelling diarrhea caused by non-absorbed fats), and jaundice. 

d. Lipids. Cholesterol, a type of lipid, is a substance found in cell membranes that helps maintain the physical integrity of cells. The liver synthesizes cholesterol, which is then packaged and distributed to the body to be sued or excreted into bile for removal from the body. Increased cholesterol concentrations in bile may predispose to gallstone formation. 

The liver also synthesizes lipoproteins, which are made up of cholesterol, triglycerides (containing fatty acids), phospholipids, and proteins. Lipoproteins circulate in the blood and shuttle cholesterol and fatty acids (an energy source) between the liver and body tissues. Most liver diseases do not significantly affect serum lipid levels, with the exception of cholestatic diseases, which may be associated with increased levels. 

2. Storage. As mentioned above, the liver is designed to store important substances such as glucose (in the form of glycogen). The liver also stores fat-soluble vitamins (vitamins A, D, E and K), folate, vitamin B 12 , and minerals such as copper and iron. However, excessive accumulation of certain substances can be harmful. For example, patients with an inherited condition known as Wilson's disease cannot secrete copper into bile normally and usually have a low blood level of the copper-binding protein ceruloplasmin. Retained copper accumulates in the liver (leading to cirrhosis and in the central nervous system (resulting in neuropsychiatric symptoms). 

3. Purification, Transformation, and Clearance. The liver removes harmful substances (such as ammonia and toxins) from the blood and then breaks them down or transforms them into less harmful compounds. In addition, the liver metabolizes most hormones and ingested drugs to either more or less active products. 

Here's how:

Most of what you put into your mouth isn't exactly pure. 

Plants are sprayed with chemicals, animals are injected with potent hormones, and lots of foods are genetically engineered with so much stuff that they make Frankenstein look as natural as a puppy. .

What's that mean to us?

For one, it means that these toxins enter our body

While we commonly think of de-tox as some 30-day program for troubled celebs, the natural de-tox program happens inside your liver all the time.

Here's how:

Most of what you put into your mouth isn't exactly pure. Plants are sprayed with chemicals, animals are injected with potent hormones, and lots of foods are genetically engineered with so much stuff that they make Frankenstein look as natural as a puppy. .

What's that mean to us?

 For one, it means that these toxins enter our body and can potentially destroy your tissues or create damage to your cells. So it's the liver's job to cope with these toxic chemicals as they travel from our environment via food into our bodies, almost like a drug smuggling border crosser that tries to make it past customs.

How does the liver do this?

Rows of liver cells are separated by space, and those spaces act like a sieve, which is where the blood flows. This sieve-like the customs agent finding out what illegal goods you're bringing across the border-removes toxic substances from the bloodstream.

Those toxins can come in the form of everything from drugs and alcohol to chemicals and microorganisms. The way it does this isn't with drug-sniffing dogs, but with special cells called Kupffer cells that eat up and break down the toxins.

In short, these cells de-arm the toxins by converting a dangerous chemical to a less harmful one or by packaging them for easier disposal through our bile or urine. The latter approach reveals how the sly liver doesn't always have to fight its enemies head-on. Instead it often uses a martial arts approach, and paralyzes toxins by wrapping them in a water-soluble chemical so they land in your toilet rather than a vital organ.

a. Ammonia. The liver converts ammonia to urea, which is excreted into the urine by the kidneys. In the presence of severe liver disease, ammonia accumulates in the blood because of both decreased blood clearance and decreased ability to form urea. Elevated ammonia levels can be toxic, especially to the brain, and may play a role in the development of hepatic encephalopathy. 

b. Bilirubin. Bilirubin is a yellow pigment formed as a breakdown product of red blood cell hemoglobin. The spleen, which destroys old red cells, releases "unconjugated" bilirubin into the blood, where it circulates in the blood bound to albumin . The liver efficiently takes up bilirubin and chemically modifies it to "conjugated," or water-solube, bilirubin that can be excreted into bile. Increased production or decreased clearance of bilirubin results in jaundice, a yellow pigmentation of the skin and eyes from bilirubin accumulation. 

c. Hormones. Since the liver plays important roles in hormonal modification and inactivation, chronic liver disease may cause hormonal imbalances. For example, the masculinizing hormone testosterone and the feminizing hormone estrogen are metabolized and inactivated by the liver. Men with cirrhosis, especially those who abuse alcohol, have increased circulating estrogens relative to testosterone derivatives, which may lead to body feminization. 

d. Drugs. Nearly all drugs are modified or degraded in the liver. In particular, oral drugs are absorbed by the gut and transported via the portal circulation to the liver. In the liver, drugs may undergo first-pass metabolism, a process in which they are modified, activated, or inactivated before they enter the systemic circulation, or they may be left unchanged. 

Alcohol is primarily metabolized by the liver, and accumulation of its products can lead to cell injury and death. 

In patients with liver disease, drug detoxification and excretion may be dangerously altered, resulting in drug concentrations that are too low or too high or the production of toxic drug metabolites. Therefore, medications that are metabolized by the liver must be used with caution in patients with hepatic disease; these patients may need lower doses of the drug. 

e. Toxins. The liver is generally responsible for detoxifying chemical agents and poisons, whether ingested or inhaled. Pre-existing liver disease may inhibit or alter detoxification processes and thus increase the toxic effects of these agents. Additionally, exposure to chemicals or toxins may directly affect the liver, ranging from mild dysfunction to severe and life-threatening damage. 

Summary 

From its sheltered position in the abdominal cavity, the liver filters blood from both the portal and systemic circulations. The body depends on the liver to regulate, synthesize, store, and secrete many important proteins and nutrients and to purify, transform, and clear toxic or unneeded substances. To carry out these functions, hepatocytes are organized for optimal contact with sinusoids (leading to and from blood vessels) and bile ducts. A special feature of the liver is its ability to regenerate, but this capacity can be exceeded by repeated or extensive damage. 

 The liver is the largest gland in the body (approximately 1500 grams) and is located in the right upper quadrant of the  adodomen.It is glossy in appearance and dark red in color from the rich supply of blood flowing through it. 

Approximately 25% of the cardiac output flows to the liver. It performs many important functions: 

1) the uptake, storage, and disposal of nutrients (protein, glucose and fat), drugs and toxins and 2) the production of synthesis proteins critical for blood clotting) and metabolism of substances produced by the body (Vitamins A, B, D, B-12