1. The Liver: A Vital Organ
According to McCuskey (2012), one of the largest abdominal organs and the most complex in the body is the liver as it has many essential metabolic functions. The nutrients are converted into substances stored in the body to be supplied for cells when needed. Moreover, the toxic substances are converted into harmless substances to be released from the body. Scheuerlein and Köckerling (2000) stated that the human adult liver weighs about 1.4 kg (3.1 pounds) and located in the right upper abdomen, below the diaphragm. The principal cell type in the liver is hepatocytes and biliary epithelial cells both are derived from the embryonic endoderm. It takes up most of the space under the ribs and some space in the left upper abdomen, too. It is distinguished from outside as the larger right lobe and smaller left lobe. The two lobes are separated by a band of connective tissue that anchors the liver to the abdominal cavity. The gallbladder, wherein bile is stored, is located in a small hollow on the underside of the liver (Ellis, 2011).
2. Anatomy of the liver:
Liver consists of a myriad of individual microscopic functional units call lobules. It performs several functions which include the removal of endogenous and exogenous materials from the blood, complex metabolic processes including bile production, carbohydrate homeostasis, lipid metabolism, urea formation, and immune functions. The liver also consists of distinct lobes: the left, right, caudate, and quadrate lobes (McCuskey, 2012).
Ellis (2011) stated that the liver originated from the ventral mesogastrium and only the upper posterior surface is outside of that structure. The liver is connected to the anterior body wall through the ligamentumteres and falciform ligament. The lesser omentumconnects it to the stomach and the coronary and triangular ligaments to the diaphragm. The liver is smooth and featureless on the diaphragmatic surface and presents with a series of indentations on the visceral surface where it meets the right kidney, adrenal gland, inferior vena cava, hepatoduodenal ligament and stomach (Scheuerlein and Köckerling, 2000).
The liver can be considered in terms of blood supply hepatocytes, Kupffer cells and biliary passages. The portal vein and hepatic artery are the main suppliers of blood to the liver, the former providing about 75% of the total 1500 ml/min flow. Small branches from each vessel the terminal portal venule and the terminal hepatic arteriole enter each acinus at the portal triad. In order to exchange nutrients the gathered blood goes through sinusoids between plates and hepatocytes. The hepatic vein carries efferent blood into the inferior vena cava and a supply of lymphatic vessels drains the liver (Abdel-Misih&Bloomston, 2010).
According to Fausto& Campbell (2003), parenchymal cells or hepatocytes comprise the majority of the organ and perform complex metabolic processes. Hepatocytes are responsible for the liver’s central role in metabolism and they are also in charge for the formation and excretion of bile; regulation of carbohydrate homeostasis; lipid synthesis and secretion of plasma lipoproteins; control of cholesterol metabolism; and formation of urea, serum albumin, clotting factors, enzymes, and numerous proteins. The liver also has a role in the metabolism and detoxification of drugs and other foreign substances.
Gissen; Arias (2015) stated that kupffer cells line the hepatic sinusoids. They are part of the reticuloendothelial system and it filters out foreign particles, bacteria and gut-derived toxins. Also, they have a role in liver immune processes. Moreover, Biliary passages begin as tiny bile canaliculi formed by hepatocytes. These microvilli -lined structures progress into ductules, interlobular bile ducts, and larger hepatic ducts. The main hepatic duct joins the cystic duct from the gallbladder to form the common bile duct, which drains into the duodenum.
2.1 Bile ducts
Bile ducts are known as the tube that carries out the bile through the liver and gallbladder and form a branched structure known as the biliary tree. Bile canaliculi are known as the microscopic canals which receives bile produced from the liver cells (Boyer, 2013). These bile ducts are then joined together to form the larger left and right hepatic ducts, that carries bile from the left and right lobes of the liver. Those two hepatic ducts combined together to form the common hepatic duct that drains all bile away from the liver. The common hepatic duct ultimately joins with the cystic duct from the gallbladder to form the common bile duct, carrying bile to the duodenum of the small intestine. The bile produced by the liver is pushed back up the cystic duct by peristalsis to arrive in the gallbladder for storage, until it is needed for digestion(Strazzabosco;Fabris, 2008).
2.2 Blood Vessels
The blood supply of the liver is one of a kind among all organs of the body due to the hepatic portal vein system. Blood passes through capillaries into distinct organs which are spleen, stomach, pancreas, gallbladder and intestines and then it is collected into the hepatic portal vein. The hepatic portal vein then delivers this blood to the tissues of the liver where the contents of the blood are divided up into smaller vessels to the rest of the body. The liver collects the blood coming from the tissues to hepatic veins that lead to the vena cava and return to the heart. The liver additionally has its own arrangement of arteries and arterioles that give oxygenated blood to its tissues simply like any other organ (Lautt, 2009).
The liver, internal structure is made up of around 100,000 small hexagonal functional units known as lobules. Each lobule comprised of a central vein encompassed by 6 hepatic portal veins and 6 hepatic arteries. These blood vessels are connected by many capillary-like tubes called sinusoids, which reach out from the portal veins and arteries to meet the central vein. Each sinusoid passes through liver tissue containing 2 main cell types (McCuskey, 2012). First, the kupffer cells are a type of macrophage that capture and worn out red blood cells passing through the sinusoids. Second, the hepatocytes are cuboidal epithelial cells that line the sinusoids and make up the majority of cells in the liver.
1. Physiology of the Liver:
The liver has different major functions in the body. First, the liver is in charge of producing enzymes and solutions necessary for digestion and this incorporate the production of bile. Additionally, the liver is responsible for the storage of sugars for energy use such as glucose, a basic sugar stored as glycogen in the liver until needed. Another major functions of the liver are to detoxify and expel harmful substances in the bloodstream, the production of cholesterol, which is a lipid necessary for hormone production, digestion and recycling of red blood cells and vitamin storage such as vitamin A and K. Finally, the liver will also break down and process other drugs that enter system, including medications and recreational drugs (Shier, Butler ; Lewis, 2001).
The process of digestion is done through the production of bile which is a mixture of water, bile salts, cholesterol, and the pigment bilirubin. Hepatocytes in the liver produce bile, which is then passes by the bile ducts to be stored in the gallbladder. When food containing fats achieves the duodenum, the cells of the duodenum discharge the hormone cholecystokinin to stimulate the gallbladder to discharge bile.Finally, Bile travels through the bile ducts and is released into the duodenum where it emulsifies large masses of fat into smaller pieces that are easier for the body to digest (Cheng et al., 2010).
Boland (2016) stated that the hemoglobin is metabolized by hepatocytes into heme and globin. Globin protein is broken down and it is used as a source of energy for the body. The iron-containing heme group is converted into the pigment bilirubin which is added to the bile to be released from the body. Additionally, bilirubin gives bile its unique greenish color and later the intestinal bacteria convert the bilirubin into the brown pigment stercobilin that gives the feces their brown color.
Karasov; Douglas (2013) stated that many metabolic functions are carried by the liver such as providing the body with the energy needed and also it regulates the production, storage, and release of sugar, fats, and cholesterol. Glucose is converted into glycogen by the liver and it is stored as soon as it is needed glycogen is converted back into glucose in a process called gluconeogenesis. Also, the liver converts fatty acids into ketones, which can be used as fuel. Additionally, the liver controls the metabolism, production, and excretion of cholesterol, which is an important component of cell membranes and certain hormones.
Ellis (2011) stated that the liver plays an important role in detoxification of substances that are harmful to the body such as alcohol, drugs, solvents, pesticides, and heavy metals. The liver hepatocytes screen the blood contents and evacuate many toxic substances from the body. Also, to keep hormone levels within homeostatic limits, the liver also metabolizes and removes from circulation the hormones produced by the body’s own glands.
The liver provides storage for many essential nutrients, vitamins, and minerals obtained from blood that passes by the hepatic portal system. Glucose is transported into hepatocytes by the aid of insulin hormone and it is stored as the polysaccharide glycogen. Also, hepatocytes absorb and store fatty acids from digested triglycerides. The liver maintains its homeostasis of blood glucose through the liver storage of nutrients. Additionally, the liver stores vitamins and minerals – such as vitamins A, D, E, K, and B12, and the minerals iron and copper in order to keep constant supply of these essential substances to body tissues (Scheuerlein and Köckerling, 2000).
The liver produces different vital protein components of blood such as prothrombin, fibrinogen, and albumins. Prothrombin and fibrinogen proteins are coagulation factors engaged with the arrangement of blood clots. Albumins are proteins that keep up the isotonic condition of the blood with the goal that cells of the body don’t gain or lose water within the existence of body fluids (Cheng et al., 2010).
2. Liver function tests
Liver function tests are blood tests used to help diagnose and monitor liver disease or damage. The tests measure the levels of certain enzymes and proteins in your blood. Levels that are higher or lower than normal can indicate liver problems (Marrero, 2005). Some common liver function tests include:
2.1 Alanine transaminase ALT
It is liver enzyme which participates in protein metabolism. It is an intracellular enzyme so when hepatic damage occurs, ALT is on the loose in the blood leading to elevation of ALT (Roderick, 2004).
2.2 Aspartate transaminase AST
It is a hepatic enzyme help in the metabolism of amino acids including alanine. AST like ALT, it has low level in the blood as it is an intracellular enzyme so any damage in liver cells leading to releasing and level is increasing in blood (Hall ; Cash, 2012).
2.3 Alkaline phosphatase ALP
It is multi-placed enzyme that is present in bones, bile duct and liver so it is not accurate enzyme. Although, the excess elevation of ALP is an indication of liver damage and also for bile acid obstruction and bone fruction (Gowda et al., 2009).
2.4 Albumin and total protein
Albumin is a blood protein that is synthesized inside the liver, any damage or failure in liver lead to the decrease in protein levels (Kang, 2013).
Bilirubin is a material created throughout the usual break of RBCs. Bilirubin transfer to the liver and then it is eliminated in stool. High levels of bilirubin may designate liver damage and other types of anemia diseases (Giannini, Testa ; Savarino, 2005).
2.6 Gamma-glutamyltransferase (GGT)
According to Koenig ; Seneff (2015), GGT is a multi-placed enzyme which present in organs throughout the body, but it is in high levels inside the liver. GGT is high in the blood in most diseases that affect injures to the bile ducts or liver. This test procedure the level of GGT in a blood sample.in general, GGT is current in fewer levels, but when the liver is wounded, the GGT level may increase. GGT is frequently the first liver enzyme to increase in the blood when any of the bile ducts that transmit bile from the liver to the bowels develop into blocked, for example, by tumors or stones.
2.7 L-lactate dehydrogenase (LD)
LD is an enzyme establish in the liver. High levels may designate liver injure but it is capable to be high in many other disorder (Zhang, 2015).
2.8 Alpha-fetoprotein (AFP)
According to Cartier ; Aubé (2014), AFP is a protein formed mainly by the liver in an increasing fetus and the part of an embryo rise. AFP levels are typically elevated when a baby is born and then turn down quickly. Liver injure and assured cancers can raise AFP concentration considerably. This test measures the level of AFP in the blood. AFP is created when liver cells are stimulated. In chronic liver diseases AFP may be chronically high. Very high concentrations of AFP can be formed by definite tumors. This distinctive makes the AFP test useful as a tumor marker. Enlarged amounts of AFP are established in many people with a type of liver cancer called hepatocellular carcinoma and in a liver cancer happening in infants call hepatoblastoma (Carr et al., 2018).
2.9 Prothrombin time (PT)
PT is the time taken for the blood to clot. Increased PT may indicate liver damage however; it can also increase while taking certain blood-thinning drugs, such as warfarin (Thachil, 2008).
According to Carr et al., (2014) stated that the blood is made up of different types of cells that float in liquid called plasma and those types of blood cells are: red blood cells, white blood cells and platelets, or thrombocytes. Platelets are tiny blood cells that help body form clots to stop bleeding. If one of the blood vessels gets damaged it releases out signals to platelets and then it goes to the site of damage and form a clot to repair the damage in a process called adhesion. Also, chemical signals are sent to attract more platelets to pile onto the clot in a process called aggregation. A normal platelet count is 150,000 to 450,000 platelets per microliter of blood. Platelets are made in bone marrow along with white and red blood cells and once they are circulated into bloodstream they live for 8 to 10 days. Additionally, there are medical conditions involved with abnormal platelet counts such as thrombocytopenia, thrombocythemia, thrombocytosis and platelet dysfunction (Pang, 2015).
4. Classification of Liver Function Tests:
According to Thapa ; Walia (2007), liver function tests are classified into:
1. Tests for ability of the liver to move organic anions or drug metabolism from serum bilirubin, urine bilirubin, urobilinogen etc.
2. Tests for liver cell damage like serum enzyme tests Aminotransferases, alkaline phosphatase, ã glutamyltranspeptidase, 5nucleotidase or leucineaminopeptidase.
3. Tests of the Liveer capacity to create Serum proteins, albumin, prealbumin, serum ceruloplasmin, procollagen III peptide, alpha 1 antitrypsin, alphafeto protein or prothrombin time.
• Serum Bilirubin:
Bilirubin is an endogenous anion resulting from hemoglobin deprivation from the RBC. When the liver function tests are uncharacteristic and the serum bilirubin levels more than 17µmol/L proposeprimary liver disease (Kalakonda ; John, 2017).
Types of bilirubin:
According to Wang, Chowdhury ; Chowdhury (2006), the types of bilirubin are:
o Total bilirubin: normally 0.2-0.9 mg/dl (2-15µmol/L). It is slightly higher by 3-4 µmol/L in males as compared to females.
o Direct Bilirubin: in case acute viral hepatitis of increasing bilirubin level is directly proportional with both degree of damage and the course of the disease normal range is 0.3mg/dl (5.1µmol/ L)
o Indirect bilirubin: is calculated by the difference of the total and direct bilirubin and is a measure of unconjugated fraction of bilirubin.
Improved unconjugated bilirubin: This results from over-production or impair uptake, conjugation.
Elevated conjugated bilirubin: Impaired hepatocelullar excretion of bile ducts of conjugated bilirubin from hepatocytes.
• Urine Bilirubin
Bilirubin should not present in urine and its appearance in urine is an indication of hepatobiliary disease. Assessable amount of conjugated bilirubin are create just in hepatobiliary disease due to decreasing in the renal threshold for conjugated bilirubin (Ramakrishnan ; Jialal, 2018).
Elevation of urobilinogen is a serious indication for hepatocellular disorder especially in alcoholic liver damage, cirrhosis or malignant cancer of the liver. It is noticeably improved in hemolysis in viral hepatitis (Kupka, 1987).
b. Enzymes that detect cholestasis
1. Alkaline Phosphatase (ALP)
In acute viral hepatitis, alkaline phosphatase is frequently furthermore usual or reasonably improved. Hepatitis A can in attendance a cholestatic portrait with noticeable and protracted burning and increase of alkaline phosphatase (Gowda et al., 2009).
3. ? Glutamyl transpeptidase (GGT)
? Glutamyl transpeptidase (GGT) is a membrane bound glycoprotein which catalyses the transfer of g glutamyl group to other peptides, amino acids and water. Large amounts are found in the kidneys, pancreas, liver, intestine and prostate (Koenig ; Seneff, 2015).
C. Tests of the Liver’s biosynthetic capacity
1. Serum Proteins
The liver is the main basis of most the serum proteins. The parenchymal cells are accountable for mixture of albumin, fibrinogen and other coagulation factors (Limdi & Hyde, 2003).
Albumin is quantitatively the most significant protein in plasma synthesize by the liver and is a helpful indicator of hepatic occupation. Since the half-life of albumin in serum is as long as 20 days, the serum albumin altitude is not a dependable marker of hepatic protein combination in sensitive liver disease. Standard serum values range from 3.5g/dl to 4.5 g/dl. The usual adult has just about 300 to 500 g of albumin (Moman & Bhimji, 2017).
The serum prealbumin level is 0.2- 0.3 g/L. these levels fall in liver disease presumably due to reduced synthesis. Because of its short half-life, changes may precede alteration in serum albumin (Mann, Sheard & Bollman, 1925).
• Serum Ceruloplasmin
Normal plasma levels are 0.2-0.4g/L. It is synthesized in the liver and is an acute phase protein (Meng et al., 2013).
• Procoliagen III Peptide
The serum concentration of this peptide appears to increase not only with hepatic fibrosis but also with inflammation and necrosis (Takahashi et al., 1984).
• Alpha Feto Protein (AFP)
The AFP principal one in fetal plasma in early gestation is subsequently present at very low levels (