Liver

The liver plays a major role in metabolism and has a number of functions in the body including detoxification, glycogen storage and plasma protein synthesis. It also produces bile which is important for digestion. It´s main function may be in accommodation of our organism to our surroundings. Therefore also the feelings are so important to the liver. In traditional chinese medicine the liver is our temper, or our heat.

Medical terms related to the liver often start in hepato- or hepatic from the Greek word hepar. The adult human liver normally weighs between 1.0 - 2.5 kilograms. It is unique and the only human organ capable of natural regeneration of lost tissue. The liver thus has a very big flexibility. But this regeneration is not complete, thus the need for transplantings sometimes. When the liver has lost about 70% of its functional capacity this can be seen in liver lab tests, and its renewal is also then disturbed. When liver cells are sclerified they no longer can renew themself, because sclerosis means scar tissue. Earlier stages can be renewed, but the process may be long. Often some kind of lifequality change is required first.

Living donor liver transplantation is a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20% of an adult's liver (Couinaud segments 2 and 3) is needed to serve as a liver allograft for an infant or small child. More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic lobe which amounts to 60% of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. But there have been at least two donor deaths out of the first several hundred cases.

Surface anatomy
Apart from a patch where it connects to the diaphragm, the liver is covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction against other organs. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments. The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe.

If the liver is flipped over, to look at it from behind (the visceral surface), there are two additional lobes between the right and left. These are the caudate lobe (the more superior), and below this the quadrate lobe.

From behind, the lobes are divided up by the ligamentum venosum and ligamentum teres (anything left of these is the left lobe), the transverse fissure (or porta hepatis) divides the caudate from the quadrate lobe, and the right sagittal fossa, which the inferior vena cava runs over, separates these two lobes from the right lobe.

Functional anatomy
It is crucial to understand the organization of liver based on blood supply and biliary drainage, and its fysical support. In the widely used Couinaud or "French" system, the functional lobes are further divided into a total of eight segments based on secondary and tertiary branching of the blood supply.In the growing fetus, a major source of blood to the liver is the umbilical vein which supplies nutrients to the growing fetus. After birth, the umbilical vein and ductus venosus are completely obliterated two to five days postpartum; the former becomes the ligamentum teres and the latter becomes the ligamentum venosum . In the disease state of cirrhosis and portal hypertension, the umbilical vein can open up again.

Physiology
The liver has about 200 different "tasks", and is therefore a very busy organ. It gives warmth to the body. In traditional chinese medicine it gives us the heat, together with the hormonal metabolism.

* The liver produces and excretes bile required for food digestion. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
* The liver performs several roles in carbohydrate metabolism:
o Gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol)
o Glycogenolysis (the formation of glucose from glycogen)
o Glycogenesis (the formation of glycogen from glucose)
o The breakdown of insulin and other hormones
* The liver also performs several roles in lipid metabolism:
o Cholesterol synthesis
o The production of triglycerides (fats).
* The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, and XI, as well as protein C, protein S and antithrombin.
* The liver neutralizes toxins, most medicinal products, and hemoglobin.
* The liver converts ammonia to urea.
* The liver stores of a multitude of substances, including glucose in the form of glycogen, vitamin B12, iron, and copper.
* In the first trimester fetus, the liver is the main site of red blood cell production. By the 42nd week of gestation, the bone marrow has almost completely taken over that task.

Diseases of the liver
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 the blood and excretes it through bile.

* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
* Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by alcoholism or other toxins, or hepatitis
* Hemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage
* Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract)
* Wilson's disease, a hereditary disease which causes the body to retain copper
* Primary sclerosing cholangitis, an inflammatory disease of the bile duct, autoimmune in nature.
* Primary biliary cirrhosis, autoimmune disease of small bile ducts
* Budd-Chiari syndrome, obstruction of the hepatic vein.
* Steatosis, fatty liver syndrome.

Most liver diseases cause only mild symptoms initially, while it is vital that these diseases are detected early. Hepatic involvement in some diseases can be of crucial importance.

Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays to test the proper function of the liver. These are enzymes that are most abundant in liver tissue, metabolites or products.

Regular liver panel
*Total Protein (TP). The liver produces most of the plasma proteins in the body. So it makes sense to measure the amount of protein in the blood. Reference range (60-80 g/L).
*Albumin (Alb). Albumin is a protein made specifically by the liver. It is the main constituent of total protein; the remaining fraction is called globulin (including e.g. the immunoglobulins). Albumin levels are decreased in chronic liver disease, such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. Poor nutrition or states of protein catabolism may also lead to hypoalbuminaemia. The half-life of albumin is approximately 20 days. Albumin is not considered to be an especially useful marker of liver synthetic function, coagulation factors (see below) are much more sensitive. The reference range is 30-50 g/L.
*Alanine transaminase (ALT), also called Serum Glutamic Pyruvic Transaminase (SGPT) or Alanine aminotransferrase (ALAT) is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or paracetamol overdose. Elevations are often measured in multiples of the upper limit of normal (ULN). The reference range is 15-45 U/L in most laboratories. When liver cell death increases, ALT levels rise above the normal range. The spillover of this enzyme into blood is routinely measured as a marker of abnormal liver-cell damage. For example, alcoholic or viral hepatitis will increase ALT levels, as will severe congestive heart failure. An elevated ALT in the presence of normal levels of plasma alkaline phosphatase helps distinguish liver disease caused by liver-cell damage from diseases caused by problems in biliary ducts.
*Alkaline phosphatase (ALP), is an enzyme in the cells lining the biliary ducts of the liver. If there is an obstruction in the bile duct, e.g. gallstones, ALP levels in plasma will rise. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled). The reference range is usually 30-120 U/L.
*Total bilirubin (TBIL). Bilirubin is a breakdown product of heme (a part of hemoglobin in red blood cells). The liver is responsible for clearing this, excreting it out through bile into the instestine. Problems with the liver or blockage of the drainage of bile will cause increased levels of bilirubin, as will increased haemolysis of red cells.
Direct bilirubin, or unconjugated bilirubin is often measured in tandem, especially if the total bilirubin level is elevated. Bilirubin is unconjugated before the liver modifies it for excretion. It is dangerous in babies, as it can pass the blood-brain barrier causing kernicterus.

Other tests commonly requested alongside LFTs:
*Aspartate transaminase (AST), also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage. It is also present in red cells and cardiac muscle.
*Gamma glutamyl transpeptidase (GGT). Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, Gamma glutamyl transpeptidase (GGT) may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. GGT is raised in alcohol toxicity (acute and chronic).
*Coagulation tests (e.g. INR). The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. If the INR is increased, it means it is taking longer than usual for blood to clot. The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired: it is not a sensitive measure of liver function.
*Hyaluronic Acid Test. Hyaluronic Acid (HA), also called hyaluronate or hyaluronan, is a mucopolysaccharide widely distributed throughout the body. HA is produced mainly by fibroblasts and other specialized connective tissue cells. As a free molecule, HA can be found in the plasma and synovial fluid. HA is quickly removed from circulation by specific receptors present in sinusoidal cells (SEC) of the liver; the estimated half-life in plasma is 5-6 minutes. Increased plasma HA levels may result from one or more of the following:

* Decreased removal of HA from plasma, as a result of liver damage
* Increased production of HA by synovial cells or fibroblasts
Serum HA is elevated in patients with alcoholic liver disease and can be used to detect the progression from alcoholic fatty liver to cirrhosis. Until now, the diagnosis of liver fibrosis and cirrhosis has been established mainly by histologic examination of liver biopsy samples. However, since the fibrotic changes are often distributed unevenly throughout the liver, liver biopsy has been associated with a sampling error of up to 24%. The risk of complications including bleeding and infection, the discomfort to patients and the high cost of hospitalization associated with this invasive procedure limit the use of liver biopsy as a routine screening procedure for cirrhosis. Serum HA levels have been correlated with the degree of fibrosis and cirrhosis in chronic liver disease and may be a non-invasive, less costly method to assess disease status in these patients. Unlike conventional liver function tests, HA levels reflect the function of sinusoidal endothelial cells (SEC) and may be an early marker of toxic liver damage.

Liver failure.
Liver failure can be considered more of a functional syndrome than an anatomical one. Treatment of liver failure includes two components – treating the cause of liver failure and prevention of the development of neurological damage. The second component is more important. Some of the signs of liver failure are:

*General failure of health like weakness, loss of appetite, wasting etc.
*Jaundice
*Bluish discoloration of the nails
*Fever
*Fetor hepaticus – It is a sweetish slightly fecal smell of breath
*Ascites – collection of fluid in the abdominal cavity
*Changes in the protein metabolism
*Skin changes like spider nevi, redness of the palms, white nails etc
*Endocrine changes – In the male, the changes are towards feminization. The changes include small, soft testes, loss of secondary sexual hair, enlargement of breast, diminished sexual desire and potency. In the females, the changes are less and towards gonadal atrophy
*Defective blood clotting

Steatosis.
As the liver becomes more fatty, liver enzymes start to increase and the liver can become inflamed. This inflammation can result in scarring and cirrhosis, or hardening of the liver. Liver function can become compromised. It's estimated that about 10-20 percent of the population of the United States is afflicted with fatty liver syndrome. While fatty liver DOES affect liver function, it's believed that someone who has fatty liver syndrome is not likely to suffer permanent liver damage.
Fatty liver or steatosis hepatis is a reversible condition seen in chronic alcoholism and many other conditions, where large vacuoles of lipid accumulate in hepatocytes (the cells of the liver). The lipid within the vacuoles is a particular type of lipid known as triglyceride. Many chemicals, such as alcohol and drugs can cause fatty liver. Also hormones as thyroxine. TSH is warranted, as hypothyroidism is more prevalent in steatose/NASH patients.
Fatty liver can occur in diabetes mellitus and in pregnancy. It can also be seen in starvation and obesity. In addition, it is also a minor symptom of hepatitis. The treatment of fatty liver depends on what is causing it, and generally, treating the underlying cause will remove the problem.

A fatty liver symptom isn't typically easy to diagnose, because fatty liver disease usually doesn't present many symptoms in the early stages. As a result, many people with fatty liver don't realize they're developing a liver problem. When a fatty liver symptom does appear, it might be

* Abdominal swelling
* Fever
* Jaundice, or yellowing of the skin
* Overall itchiness
* Right-side abdominal pain
* Small yellow skin nodules

Any of these should be considered a possible fatty liver symptom. If any of these symptoms should appear, the patient is advised to have liver function tests done. If fatty liver is present, the test results will show an enlarged liver or minor elevation of liver enzymes.

Non-alcoholic steatohepatitis (NASH)is fatty inflammation of the liver when this is not due to excessive alcohol use. It is a major cause of cryptogenic cirrhosis of the liver. In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications.
It differs from the simple accumulation of fat in the liver (fatty liver, or hepatic steatosis) in that the inflammation of NASH causes damage to the liver cells. Sometimes dull right upper quadrant pain is felt, occasionally radiating to the right shoulder. Mild icterus (jaundice) can sometimes be noticed.

NASH is associated with metabolic syndrome X, diabetes mellitus (type II) and insulin resistance. Disturbed liver enzymes are common. The main cause is insulin resistance, which explains co-occurrence of NASH and syndrome X. NASH was described in 1980 (the Mayo Clinic).

NASH can also be caused by the following medications:

* Amiodarone, a class III antiarrhythmic agent used in the treatment of ventricular arrhythmias and the suppression of atrial and ventricular arrhythmias.
* Antiviral drugs (nucleoside analogues ), Most of the antivirals now available are designed to help deal with HIV; herpesvirus, which are best known for causing cold sores but actually cover a wide range of diseases; and the hepatitis B and C viruses, which can cause liver cancer.
* Aspirin / NSAIDS. Aspirin was the first discovered member of the class of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs), not all of which are salicylates, though they all have similar effects and a similar action mechanism. Aspirin suppresses the production of prostaglandins and thromboxanes. This happens because cyclooxygenase (COX-1), an enzyme which participates in the production of prostaglandins and thromboxanes, is irreversibly inhibited when aspirin acetylates it. Prostaglandins are local hormones (paracrine) produced in the body and have diverse effects in the body, including but not limited to transmission of pain information to the brain, modulation of the hypothalamic thermostat and inflammation. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are primarily caused by blood clots, and their reduction with the introduction of small amounts of aspirin has been seen to be an effective medical intervention. The side effect of this is that the ability of the blood in general to clot is reduced, and excessive bleeding may result from the use of aspirin. More recent work has shown that there are at least two different types of cyclooxygenase: COX-1 and COX-2. Aspirin inhibits both of them.

Newer NSAID drugs called COX-2 selective inhibitors have been developed that only inhibit COX-2, with the hope that this would reduce the gastrointestinal side effects.

However, several of the new COX-2 selective inhibitors have been recently withdrawn, after evidence emerged that COX-2 inhibitors increase the risk of heart attack. It is proposed that endothelial cells lining the arteries in the body express COX-2, and by selectively inhibiting COX-2, prostaglandins (specifically PGF2) are downregulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anti-coagulative effect of PGF2 is decreased, increasing the risk of thrombus and associated heart attacks and other circulatory problems.
* Corticosteroids. are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. They work through the same eikosanoid-circles as above.
* Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.
* Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney.
* Methotrexate, to treat many kinds of cancers.
* Nifedipine, is a dihydropyridine calcium channel blocker. Its main uses are in angina pectoris and hypertension, although a large number of other uses have recently been found for this agent, such as Raynaud's phenomenon, and esophagus-spasms.
* Perhexiline maleate
* Tamoxifen, is an oral selective estrogen receptor modulator which is used in breast cancer.
* Tetracycline is an antibiotic produced by the streptomyces bacterium.
* Valproic acid is a sodium salt of valproic acid. is a anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder; but also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal ), complex partial seizures , and the seizures associated with Lennox-Gastaut syndrome .

Valproate is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain.

Cirrhosis.
Cirrhosis is a chronic disease of the liver in which liver tissue is replaced by connective tissue, resulting in the loss of liver function. Cirrhosis is caused by damage from toxins (including alcohol), metabolic problems, chronic viral hepatitis or other causes. Cirrhosis is sometimes referred to by its obsolete eponym Laennec's cirrhosis after René Laënnec. Cirrhosis is irreversible but treatment of the causative disease will slow or even halt the damage.

Cirrhosis has many possible causes; sometimes more than one cause are present in the same patient. Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates. The hepatitis B virus is probably the most common cause of cirrhosis worldwide, especially South-East Asia. Inherited diseases. These interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.

* Alpha 1-antitrypsin deficiency
* Hemochromatosis (iron accumulation)
* Wilson's disease (copper accumulation)
* Galactosemia
* Glycogen storage diseases
* Cystic fibrosis

Early symptoms include red palms , spider angioma (red spots on the upper body), hypertrophy of the parotid glands, and fibrosis of tendons in the hands. Clubbing may develop.

Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces healthy cells, liver function starts to fail and a person may experience the following symptoms:

* exhaustion
* fatigue
* loss of appetite
* nausea
* weakness
* weight loss
* abdominal pain

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.

* Bruising and bleeding due to decreased production of coagulation factors.
* Jaundice due to decreased processing of bilirubin.
* Itching due to bile products deposited in the skin.
* Hepatic encephalopathy - the liver does not clear ammonia and related nitrogenous substances from the blood, which affect cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
* Sensitivity to medication due to decreased metabolism of the active compounds.
* Insulin resistance and type 2 diabetes.
* Hepatocellular carcinoma is primary liver cancer, commonly caused by cirrhosis. It has a high mortality rate.
* Portal hypertension - blood normally carried from the intestines and spleen through the portal vein flows more slowly and the pressure increases; this leads to the following complications:
o Ascites - fluid leaks through the vasculature into the abdominal cavity.
o Esophageal varices - collateral portal blood flow through vessels in the stomach and esophagus. These blood vessels may become enlarged and are more likely to burst.
* Problems in other organs. Cirrhosis can cause immune system dysfunction, leading to infection. Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines (spontaneous bacterial peritonitis). Cirrhosis can also lead to impotence, kidney dysfunction and renal failure (hepatorenal syndrome ) and osteoporosis.
# Drugs or toxins.
# Repeated bouts of heart failure with liver congestion.
# Certain parasitic infections (like schistosomiasis).

Vitamins and nutrient supplies.
Doctors often claim that excess vitamins and nutrients may be dangerous. And of course it may be so. But I have tried to look for such natural remedy issues without success. I have found simply nothing.

The main reason for such interferens is
* excess fat-soluble vitamins as vit A.
* excess betacaroten as an antioxidant. Observe that antioxidants in a way neutralize the workings of free radicals, that our body itself manufacture, and which is needed by our immune system. Excess of antioxidants means eventually that cancercells avoid destruction.
* webshop remedies are not always safe. In the best they can continue absolutely no essential essence, but at worst they can continue heavily toxins or parasites. Remedies bought from webshops abroad is done at own risk.
* Individual differences, partly heredical. For example differences in detoxification system due to cytocrom differences. Also deseaces may change the tolerance to high doses of vitamins/nutrients. In the same way some sick people or older people may have an increased demand for vitamins/nutrient supply.

Used in the way terapeuts or doctors ordinate vitamins are usually safe to use.

References:
Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434-438. PMID 7382552.

http://www.biologydaily.com/biology/Liver

WikiLiver: A Wiki dedicated to the liver

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