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More than 500 liver functions have been identified. Many, many others have not yet been fully identified.
The liver is divided into four lobes which contain as many as 100,000 lobules which are composed of polyhedral hepatic cells. At any given time, the liver typically contains about 13% of the total volume of blood in the body and almost half of the body's blood passes through the liver every minute. Only the brain receives a greater total supply of blood.
What can go wrong? Cirrhosis...
Cirrhosis is characterized by widespread nodules in the liver combined with fibrosis. The fibrosis and nodule formation causes changes in the liver's shape and structure which eventually interfere with the flow of blood through the liver. Cirrhosis can also lead to an inability of the liver to perform its biochemical functions.
Liver Blood Flow: oxygenated blood that has returned from the lungs to the left ventricle of the heart is pumped to all of the tissues of the body. This is called the systemic circulation. After reaching the tissues, blood is returned to the right side of the heart, from where it is pumped to the lungs and then returned to the left side of the heart after taking up oxygen and giving off carbon dioxide. This is called the pulmonary circulation.
Blood from the gut and spleen flow to and through the liver before returning to the right side of the heart. This is called the portal circulation and the large vein through which blood is brought to the liver is called the portal vein. After passing through the liver, blood flows into the hepatic vein, which leads into the inferior vena cava to the right side of the heart.
The liver also receives some blood directly from the heart via the hepatic artery. In the esophagus, stomach, small intestine and rectum, the portal circulation and veins of the systemic circulation are connected.
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The liver is the site of bile formation. Bile contains bile salts, fatty acids, cholesterol, bilirubin and other compounds. The components of bile are synthesized and modified in hepatocytes (the most numerous cell type in the liver) and secreted into small bile ducts within the liver itself.
These small bile ducts form a branching network of progressively larger ducts that ultimately become the common bile duct that takes bile to the small intestine. Bilirubin is a yellow pigment that derives primarily from old red blood cells. Bilirubin is taken up by hepatocytes from the blood, modified in the hepatocytes to a water soluble form and secreted into the bile.
Biochemical Liver Functions
The liver performs many biochemical functions. Blood clotting factors are synthesized in the liver. Albumin, the major protein in the blood, is also synthesized in and secreted from the liver. The modification and/or synthesis of bile components also takes place in the liver. Many of the body's metabolic functions occur primarily in the liver including the metabolism of cholesterol and the conversion of proteins and fats into glucose. The liver is also where most drugs and toxins, including alcohol, are metabolized.
Cirrhosis results from damage to liver cells from toxins, inflammation, metabolic derangements and other causes. These can be quite numerous and surprizingly wide-spread. Common cleaning solvents, air conditioning gases (especially the new "environmentally safe" ones!), many industrial chemicals and other substances can seriously damage or totally destroy the liver.
Dead or damaged liver cells are replaced by fibrous tissue which leads to fibrosis (scarring). Liver cells continue to regenerate in an abnormal pattern primarily forming nodules that are surrounded by fibrous tissue. Grossly abnormal liver architecture eventually develops leading to decreased blood flow into and on through the liver.
Blood will back up in the portal vein and portal circulation which leads to some of the serious complications of cirrhosis. The spleen may enlarge and sequester blood cells, causing the platelet to count fall and lead to abnormal bleeding.
If the pressure in the portal circulation increases because of cirrhosis and blood back up (note: this can also sometimes occur in severe cases of acute hepatitis and liver damage), blood can flow backwards from the portal circulation to the systemic circulation where they are connected. This can lead to varicose veins in the stomach and esophagus (gastric and esophageal varices) and rectum (hemorrhoids). Gastric and esophageal varices can rupture, bleed massively and even cause death. Hypertension in the portal circulation, along with other hormonal, metabolic and kidney abnormalities in cirrhosis, can also lead to fluid accumulation the abdomen (ascites) and the peripheral tissue (peripheral edema).
Decreased bilirubin secretion from hepatocytes in cirrhosis leads to the back up of bilirubin in the blood. This leads to jaundice, the yellow discoloration of the skin and eyes. As the water-soluble form of bilirubin also backs up in the blood, bilirubin can also spill into the urine giving it a bright yellow to dark brown color.
Abnormal biochemical function of the liver in cirrhosis can lead to several complications. The serum albumin concentration falls which can lead to aggravation of ascites and edema. The metabolism of drugs can change requiring dose adjustments. In men, breast enlargement (gynecomastia) sometimes occurs because metabolism of estrogen in the liver is decreased. Decreased production of blood clotting factors can lead to bleeding complications. Derangements in the metabolism of triglycerides, cholesterol and sugar can occur. In earlier stages, cirrhosis frequently can cause insulin resistance and diabetes mellitus. In later stages or in severe liver failure, blood glucose may be low because it cannot be synthesized from fats or proteins.
Cirrhosis, especially in advanced cases, can cause profound abnormalities in the brain. In cirrhosis, some blood leaving the gut bypasses the liver as blood flow through the liver is decreased. Metabolism of components absorbed in the gut can also be decreased as liver cell function deteriorates. Both of these can lead to hepatic encephalopathy as toxic metabolites, normally removed from the blood by the liver reach the brain.
In its early stages, subtle mental changes such as poor concentration or the inability to construct simple objects occurs. In severe cases, hepatic encephalopathy can lead to stupor, coma, brain swelling and death.
Cirrhosis of the liver can also cause abnormalities in other organ systems. Cirrhosis can lead to immune system dysfunction causing an increased risk of infection. Ascites fluid in the abdomen often becomes infected with bacteria normally present in the gut (spontaneous bacterial peritonitis). Cirrhosis can also lead to kidney dysfunction and failure. In end-stage cirrhosis, a type of kidney dysfunction called hepatorenal syndrome can occur. Hepatorenal syndrome is almost always fatal unless the liver is replaced.
Clinical Symptoms and Diagnosis...
Cirrhosis is usually an easy diagnosis to make when any or all of the above abnormalities and complications are present. This is especially true when the underlying liver disease can be identified. The underlying liver disease is identified in most patients, however, sometimes it will not be discovered. Such cases are called "cryptogenic" cirrhosis. Sometimes, other conditions such as metastatic cancer, hepatic or portal vein thrombosis, severe acute hepatitis or acute bile duct obstruction can cause some of the abnormalities seen in cirrhosis. A careful history combined with special diagnostic tests will usually identify these conditions.
Some patients with cirrhosis, especially early in the course of the disease, will have no overt clinical signs or symptoms. Some may have only subtle physical changes such as red palms, red spots that blanch on pressure, on their upper body (spider angiomata), hypertrophy of the parotid glands, gynecomastia (breast enlargement) or fibrosis of tendons in the palms. Some patients may only have subtle abnormalities on blood tests, and in some cases, all blood tests may be normal. Radiological and nuclear medicine tests may give clues as to the presence of cirrhosis, but the diagnosis of cirrhosis must often be made by liver biopsy.
Although most often associated with alcohol abuse, cirrhosis of the liver can result from many causes. Almost any chronic liver disease can lead to cirrhosis.
This list gives some of the many causes:
Cirrhosis of the liver is irreversible at present. treatment of the underlying liver disease may slow or stop the progression. Some very promising work has been seen in Japan using rats and human gene therapy. Other animal studies seem to indicate induced hypothyroidism may be beneficial in slowing the progress of disease. Treatment depends upon the underlying etiology. Termination of alcohol intake will stop the progression in alcoholic cirrhosis and for this reason, it is important to make the diagnosis early in a chronic alcohol abuser. Similarly, discontinuation of a hepatotoxic drug or removal of an environmental toxin will stop progression. Treatment of metabolic diseases, such as treatment of iron overload in hemochromatosis or copper overload in Wilson disease, are also effective therapies. Chronic viral hepatitis B and C may respond to treatment with interferon and autoimmune hepatitis may improve with prednisone and azathioprine (Imuran). Drugs such as ursodiol (Actigall) may slow the progression of PBC (Primary Biliary Cirrhosis) and possibly sclerosing cholangitis.
In patients with cirrhosis of the liver, treatment must also be directed at the complications. Bleeding esophageal varices can be treated with endoscopic sclerotherapy or rubber band ligation. Ascites and edema are often responsive to a low sodium diet and such a diet must be emphasized in patients with these symptoms. More advanced ascites and edema can respond to diuretic therapy. A low protein diet and agents such as lactulose may help hepatic encephalopathy. Infections such as spontaneous bacterial peritonitis must be rapidly treated with appropriate antibiotics. Drugs metabolized in the liver must be given with caution. Coagulation disorders will sometimes respond to vitamin K.
Liver transplantation is highly effective for the treatment of end-stage cirrhosis. Transplantation is usually needed when complications such as encephalopathy, ascites or bleeding varices are uncontrollable or when biochemical function is severely depressed. In patients with primary biliary cirrhosis, a rising bilirubin indicates a poor prognosis and such patients should be considered for transplantation as the serum bilirubin concentration begins to rise. Active drug or alcohol abuse are contraindications to liver transplantation. However, alcoholics who have abstained from drinking for an extended period of time (usually more than six months), and have participated in rehabilitation programs and support groups such as Alcoholics Anonymous, can be considered as candidates and will often have a good prognosis. Liver cancer is usually a contraindication to transplantation, except in experimental protocols.
Liver transplantation is usually not performed in patients more than 70 years old.
Faced with this disease, some turn to Eastern, alternative herbal treatments; the one herb which has some characteristics which may be beneficial is GOTU KOLA.


