Liver Function Tests (LFTs) are blood tests that provide critical insights into your liver’s health. These tests measure specific enzymes, proteins, and substances that indicate liver functionality and help detect liver diseases or damage early. In this article, we’ll explore the liver’s role in your body, the importance of LFTs, and how these tests can guide your healthcare decisions.
The Liver: Your Body’s Vital Organ
The liver is the largest gland in the body, weighing between 1 and 2.3 kilos. It takes up a large portion of the right hypochondriac area, a segment of the epigastric region, and expands into the left hypochondriac area in the upper portion of the abdominal cavity. The top and fore surfaces are flat and inclined to fit with the bottom of the diaphragm; the posterior surface is irregular.
Organs associated with the liver
- Superiorly and anteriorly – diaphragm and anterior abdominal wall
- Inferiorly – stomach, bile ducts, duodenum, hepatic flexure of the colon, right kidney and adrenal gland
- Posteriorly – esophagus, inferior vena cava, aorta, gall bladder, vertebral column and diaphragm
- Laterally – lower ribs and diaphragm.
BIOCHEMICAL FUNCTIONS OF THE LIVER
The liver is responsible for a range of excretory, synthesis, and biochemical functions. In clinical laboratories, a number of assays are done to help in the biochemical assessment of these activities. The enzymes alkaline phosphatase, ALT, AST, and GGT are important in detecting the correct functioning and inflammatory condition of the liver. The liver is the site of glucose, protein, and lipid metabolism. Total and direct bilirubin, total protein and albumin, cholesterol and triglycerides, urea and ammonia may all be tested to evaluate the liver.
LIVER FUNCTION TEST
Liver function tests are most often used to
- Tests of excretion by the liver
- Evaluation of synthesis in liver
- Evaluation of enzyme activity.
TEST OF EXCRETION BY THE LIVER
Bilirubin
The level of bilirubin in the blood is determined by the rate at which it is released through hemoglobin degradation. Bilirubin is formed when the heme component of hemoglobin degrades. Heme is metabolized in cells of the reticuloendothelial system, primarily in the spleen. The protoporphyrin ring of the heme is broken, enabling iron to escape into the biliverdin form. Bilirubin, a yellow-pigmented molecule, is formed from biliverdin. Bilirubin, a tetrapyrole molecule, is poorly soluble in water and plasma. It is linked to albumin for transportation into the bloodstream. Delta bilirubin is covalently bonded to bilirubin.
When bilirubin-albumin reaches the liver, albumin is released and enters the hepatocyte. Inside the hepatocyte, the liver enzyme uridyl diphosphate glucuronyltransferase (UDPG-transferase) incorporates glucuronate, into the bilirubin molecule. Approximately 85% of bilirubin is conjugated using two molecules of glucuronate to generate diglucuronate-bilirubin. The remaining bilirubin is conjugated with one sugar molecule to generate monoglucuronate-bilirubin. The addition of the sugar group increases the molecule’s solubility.
The bile duct delivers conjugated bilirubin into the colon, where it is converted to urobilinogen by intestinal microorganisms. Through the intestinal mucosa, any urobilinogen can be reabsorbed and returned to the portal circulation and liver. The urobilinogen residue is eliminated in the urine or oxidized to urobilin, which is ultimately expelled in the feces. Urobilin is a component in feces that contributes to its characteristic brown color.
Total bilirubin is composed of three fractions
- Conjugated bilirubin (soluble and excretable)
- Unconjugated (water-insoluble and nonexcretable)
- Delta Bilirubin (bilirubin covalently bound to albumin)
Increased levels of unconjugated bilirubin, particularly in infants, increase the risk of kernicterus.
Jaundice:
Jaundice is a disorder characterized by yellowing of the scalp, sclera, and mucous membranes. The most common reason is elevated bilirubin, which is not clinically detectable until bilirubin levels approach 3 to 5 mg/dL.
Jaundice may be divided into three categories:
Pre-Hepatic
Increased bilirubin levels in the liver cell cause this condition, which is most often due to increased RBC destruction.
Causes
- Hemolytic anemia
- Exposure to chemicals
- Some cancers
- Autoimmune hemolytic anemia
- Transfusion reaction
- Hemolytic disease of the newborn
- Congestive heart failure
Laboratory Findings
- Total Bilirubin: Normal or increased
- Conjugated bilirubin: Normal to increased
- Unconjugated bilirubin: Increased
- Urine urobilinogen: Increased
Hepatic
Direct injury to the liver cell causes this condition.
Causes
- Gilbert’s disease
- Crigler-Najjar syndrome
- Dubin-Johnson syndrome
- Rotor’s syndrome
- Cirrhosis
- Viral hepatitis
- Alcoholic liver disease
- Hepatocellular carcinoma
- Neonatal physiologic jaundice
Laboratory Findings
- Total bilirubin: Increased
- Conjugated bilirubin: Increased
- Unconjugated bilirubin: Normal or increased
- Urine urobilinogen: Normal or increased
Post-Hepatic
It’s caused by a blockage of the liver’s bile supply.
Causes
- Bile duct stones
- Gallbladder stones
- Cancer of the bile ducts
- Bile duct stenosis
Laboratory findings
- Total bilirubin: Increased
- Conjugated bilirubin: Increased
- Unconjugated bilirubin: Increased
- Urine urobilinogen: Decreased
Urobilinogen
No bilirubin reaches the stomach, no urobilinogen is formed, and no bilirubin is identified in the urine or feces when the biliary duct is completely closed.
EVALUATION OF SYNTHESIS IN LIVER
Serum Proteins
Because serum albumin and a small percentage of globulin are generated in the liver, liver disease influences serum proteins quantitatively as well as qualitatively. Serum albumin concentrations fall in any condition that induces hepatocellular injury. Serum globulins may also increase to a level that enables them to maintain a normal or higher total protein content in many liver disorders when there is severe albumin deficit.
Serum albumin levels change throughout time and can be used to predict the occurrence, progression, and prognosis of hepatic disorders. Low albumin and high globulins in the blood indicate a hepatocellular etiology of jaundice or liver disease. Because of subsequent hepatocellular disruption, serum protein fluctuations cause obstructive jaundice. Cholangitis and biliary cirrhosis, on the other hand, can harm the liver without generating protein alterations. Furthermore, serum protein alterations might return to normal before full recovery from hepatitis. A range of conditions, including liver diseases, can trigger fluctuations in serum protein levels.
Prothrombin Concentration
Prothrombin deficiency can occur as a result of:
- Inadequate bile absorption from the gastrointestinal tract,
or
- A impaired liver’s inability to translate vitamin K into prothrombin.
Normal prothrombin levels do not rule out the potential for impaired liver function. When a jaundice patient has a low prothrombin level (prolonged PT), prothrombin should be tested after 2-4 mg of vitamin K is given. A low prothrombin level in the absence of jaundice usually indicates significant liver damage.
EVALUATION OF ENZYME ACTIVITY
Cholesterol and Esters
A chronically low cholesterol ester/total cholesterol ratio indicates persistent hepatocellular damage; however, a rise in cholesterol ester is considered a positive marker and suggests improvement. Although a rise in total cholesterol is usually linked with biliary obstruction, the concentration of cholesterol ester remains constant.
Serum Transaminases
Kreb’s cycle enzymes are abundant in the liver and tissues. One of these enzymes is a family of enzymes responsible for converting NH2 groups from amino acids to keto acids, allowing for amino acid metabolism. The enzymes are produced when muscle or liver cells are damaged, and their levels in plasma rise as a result. Serum levels of SGOT and SGPT, as well as LDH concentration, rise to extremely high levels in obstructive jaundice and, more specifically, acute hepatitis. Serum transaminases can be slightly increased in chronic hepatitis.
Liver cells are damaged as a result of a neoplastic disorder. As cancer progresses to the liver, transaminase levels in the blood rise moderately. While both AST and ALT serum activity increase when disease processes damage the integrity of liver cells, ALT is a more liver-specific enzyme. Elevations in serum ALT function are unusual in conditions other than parenchymal liver disease. Furthermore, ALT activity increases last longer than AST activity increases.
Serum Alkaline Phosphatase
Serum levels increase from The liver and bone are the primary sources of ALP activity. In response to any biliary system blockage, hepatocytes generate ALP. Some of the newly synthesized enzymes circulate in the circulation, increasing serum enzyme synthesis. Because ALP is encoded at several chromosomal loci, some of which are true isoenzymes. The ALP types found in the bones, liver, and kidney share the same core structure and code for the same genetic loci, but their carbohydrate content differs. Serum alkaline phosphatase levels are raised in acute and chronic hepatic illness, although not to the degree found in obstructive jaundice.
In some cases of metastatic liver cancer, serum alkaline phosphatase levels might rise in the absence of jaundice. Phosphatase levels can be normal early in obstructive disease and after blockage is removed. Elevated blood alkaline phosphatase levels have been associated with pregnancy, as well as disorders such as Paget’s disease of the bone, hyperparathyroidism, and rickets/osteomalacia, which must be screened.
Gamma-Glutamyl Transferase
Peptidase enzymes accelerate peptide breakdown, resulting in amino acids or smaller peptides. They are a varied set of enzymes with various specificities, and some of them operate as amino acid transferases, catalyzing amino acid transfer from one peptide to another.
Despite the fact that GGT is produced in a higher concentration in renal tissue, the enzyme found in the blood is mostly related to hepatobiliary disorders since it is higher in most people with liver disease regardless of source, but its usefulness is limited because of its lack of precision. GGT activities are higher in the majority of serum from heavy drinkers and patients with alcoholic hepatitis.
Cholinesterase
Measurements of cholinesterase (CHE) production in serum are used as a monitor of liver function, an indication of potential insecticide toxicity, and for the diagnosis of patients with atypical forms of the enzyme who are at risk of prolonged responses to certain muscle relaxants used in surgical procedures. Many organic phosphorous insecticides, including parathion, sarin, and tetraethyl pyrophosphate, block cholinesterase action.
References:
- Concise Book of Medical Laboratory Technology-Methods and Interpretation by Ramnik Sood
- Textbook of Clinical Chemistry and Molecular Diagnosis by Tietz
- Arneson Clinical Chemistry-A Laboratory Perspective by Arneson W and Brickell J
- Ross Wilson Anatomy and Physiology in Health and Illness
- The Medical Laboratory Science Examination Review by Elseviers Pub