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The liver is one of the most versatile and complex organs in the body. The liver plays an important role in metabolising, storing or excreting the absorbed products of digestion. In this essay I am going to describe normal liver function, anatomy and I will also explain the principles of Liver Function Tests and how they can be used to diagnose liver disease.
Churchill (2009) stated that the liver weighs approximately 1.2-1.5 kg in an average adult. Moreover it lies in the upper left of the abdominal cavity. The upper part of the liver is underneath the diaphragm which is protected by ribs and the under surface faces the stomach, duodenum and the right part of the large intestine. First of all the liver has 4 lobes. According to Churchill (2009) the lobes are separated by tough ligamentous material, which acts as a support for the delicate liver tissue. The liver is anchored in position in the abdomen by ligaments constructed from folds of the peritoneum. On the posterior surface there is a cleft, the portal fissure, where the hepatic artery, hepatic portal vein, lymphatic vessels, bile ducts and nerves enter and leave. The diagram below illustrates the structure of liver.
Freeman et al. (2007) identified that the liver consists of two blood supplies, an arterial and a venous supply. The hepatic artery carries oxygenated blood to the liver. Only 20% of the blood flowing into the liver, however, is from the hepatic artery. The remainder comes from the hepatic portal vein. The hepatic portal vein performs two functions. Firstly, it carries products of digestion from the gut to the liver. These range from amino acids, lipids and carbohydrates, but also include ions, vitamins and non-electrolytes. Drugs and toxins are also picked up along this way. Secondly, blood is carried from the spleen which is involved in the breakdown of red blood cells. The liver processes breakdown products so as to make them available for re-use. All the blood leaving the liver is via the hepatic veins which take blood back to the dorsal vena cava. Moreover Elgert et al. (2009) noted that blood flow into the liver is regulated by special sphincter muscles which encircle the vessels. Secondly Jonathan et al (.2001) illustrated that there is over 500 functions of the liver. The main functions of the liver are: glucose, carbohydrate, protein, lipid and fat metabolism. It also entails ammonia conversion, drug metabolism and bile formation metabolism. In addition to that the liver is also involved in vitamin and iron storage.
Liver is vulnerable to many diseases caused by metabolic, viral, microbial, circulatory and neoplastic injuries. The damage caused usually takes a long time to manifest itself as a disease with clinical symptoms. Moreover liver diseases can be classified according to the biochemical changes that occur. They can be divided into hepatocellular and cholestatic. Hepatocellular disease causes damage to the hepatocytes due to viral infections and drugs whereas cholestasis is a blockage in the bilary duct causing an impairment to bile flow through the canaliculi into the gut(Marieb 2009).The stages involved in liver disease are as follows: fibrosis, degeneration and intracellular accumulation, necrosis and apoptosis, inflammation, regeneration(Solomon et al. 2008).At fibrosis stage a fibrous tissue is formed in response to toxic effect or irreversible damage and at the accumulation stage fat, copper and iron accumulates in the hepatocytes. In addition to that at the apoptosis stage apoptotic cell death and liquefaction necrosis occur. As the disease progresses the cells start to swell up which result in hepatitis (Ahmed et al. 2005).At regeneration stage response to tissue resection and cell death occur. Extensive disease of the liver therefore affects many vital functions and has profound effects on the body. The regenerative capacity is vital in the recovery of patients with liver damage due to viruses, drugs or trauma but if the damage is persistent it can result in loss of the normal lobar structure which is functionally inefficient. This condition is termed as liver cirrhosis.
The picture below demonstrates liver cirrhosis.
Cirrhosis of the liver
Picture adapted from: http://www.nlm.nih.gov/medlineplus/ency/imagepages/8849.htm last accessed on 15.03.10
Alcoholic cirrhosisÂ is worsened liver disease categorized by extensive fibrosis that disrupts the liver`s structure. Moreover Churchill (2009) noted that alpha-fetoprotein which is synthesised by the adult liver usually denotes the presence of a primary liver cell carcinoma.
In liver cell injury, damage to the membranes of cells and their organelles allows intracellular enzymes to leak into the blood where the elevated concentrations can be measured by carrying out liver function tests (LFTs).Freeman et al. (2007) noted that liver functions tests done individually do not provide much details but if used in combination along with medical history, imaging studies and biopsy they help in an accurate diagnosis of the specific liver disease. Chruchill (2009) described that LFTs comprise bilirubin, a compound formed by the catabolism of haemoglobin and ammonia which is a product of protein catabolism is converted into urea by the liver before being excreted by the kidneys. Proteins that are made by the liver include albumin, prothrombin, fibrinogen, cholesterol and triglycerides. The liver function tests also consist of enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH).Ahmed et al.(2005) illustrated that other LFT`s included are tests to demonstrate antibodies and DNA tests for hepatitis and otherÂ viruses, tests for smooth muscle antibodies, prealbumin, protein electrophoresis, bile acids, alpha-fetoprotein, and a constellation of other enzymes that help differentiate necrotic versus obstructive liver disease.
Elevations of these markers for liver injury indicate that something is abnormal with the liver. ALT and bilirubin are the two primary tests used largely used for this purpose. Katherine et al. (2003) emphasised that Bilirubin is measured by two tests called total and direct bilirubin. The total bilirubin measures both conjugated and unconjugated bilirubin while direct bilirubin measures only the conjugated bilirubin fraction in the blood.In Katherine et al. (2003) journal she reviewed the nature of these markersâ€™ association with alcohol use, their practical application in detecting, assessing or monitoring drinking. Katherine et al. (2003) concluded that these conventional tests are relatively inexpensive and provided valuable data on complications that may be affected by alcohol abuse and in some cases, prognosis of the liver disease. Moreover Sebastini et al. (2007) noted that performance of non-invasive markers for liver fibrosis is reduced in chronic hepatitis C with normal transaminases. Sebastini et al. (2007) further identified that in chronic hepatitis C, biopsy is the gold standard for assessment of liver fibrosis. Likewise Simonetta et al. (2009) investigated baroreceptor effectiveness and sensivity in relation to liver cirrhosis. Simonetta et al. (2009) found out that the data she obtained support the hypothesis that liver disease severity and portal hypertension have an important role in the derangement of baroreceptor function. The aetiology of cirrhosis seems to be related to baroreceptor impairment. Simonetta et al. (2009) also noticed that mortality rate is higher in people with a more damaged autonomic system which strengthens the idea of a worse prognosis.
High level of bilirubin will make the individual become jaundice. This occurs when the bile duct is blocked by a gallstone or by a tumour in the pancreas. The bilirubin can also be raised with hepatitis, liver injury or long term alcohol abuse. Furthermore albumin which is the main protein made by the liver circulates in the blood stream. Low level of blood albumin occurs due to reduced ability in production which is caused by liver disorders. Elgert et al. (2009) illustrated that other tests can also be carried out to monitor the activity of a particular liver disorder and response to treatment. The other blood tests included are blood clotting tests, gamma-glutamyl transferase and immunology tests. The blood clotting tests can be used as a marker to monitor the severity of certain liver disorders. This is caused by insufficient protein production and blood will not clot so well. High level of gamma glutamyl transferase is associated with heavy alcohol consumption. This enzyme is involved in lysis and clearing of alcohol from the body. In addition to that Elgert et al. (2009) explained that most common autoimmune disorders are cirrhosis, autoimmune hepatitis and primary sclerosing cholangitis.Primary biliary cirrhosis is associated with anti-microbial antibodies whereas autoimmune hepatitis is associated with smooth muscle antibodies. Last but not least primary sclerosing cholangitis is associated with cytoplasmic antibodies.
It is usually helpful to consider each test result in isolation to interprete the results of liver function tests. Churchill (2009) described that increased total bilirubin may indicate increased production which result in haemolysis and decreased excretion which relates to hepatitis, cholestasis and congenital disorders such as Gilberts disease. Additionally increased ALT transaminases indicate hepatocellular damage such as cirrhosis whereas increased ALP shows that there is cholestasis and infiltrations. In addition to that increased GGT signifies enzyme induction or excessive alcohol consumption whilst decreased albumin indicates severe hepatocellular dysfunction such as liver failure. The main treatments for liver disease are supportive care, specific treatment and liver transplantation. Supportive care entails alcohol withdrawal management by the use of benzodiazepines whereas in specific treatment corticosteroid (prednisolone) is used to improve outcome in patients who have severe acute alcoholic hepatitis and who do not have infection, I bleeding, renal failure or pancreatitis. Finally liver transplantation can be considered if prognosis is very severe. Differences in normal range for different laboratories can make it difficult to compare or comment on individual test results specifically.
In summary, different diseases of the liver will cause different types of damage which will affect liver function tests accordingly. Hence it can be suggested which disease may be present from a liver function test but these tests are not the conclusive way of diagnosing liver disease (Churchill, 2009).Finally it can be concluded that the liver is the most resourceful organ in the body as it has over 500 functions.