Liver Function test

LIVER

The liver is the largest gland in the body, weighing between 1 and 2.3 kilograms. It occupies the majority of the right hypochondriac region, a portion of the epigastric region, and extends into the left hypochondriac region in the upper part of the abdominal cavity. The top and fore surfaces are flat and angled to align the underside of the diaphragm; the posterior surface is uneven.

Human Liver; Inferior view (Source: Ross Wilson Anatomy & Physiology)

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

A variety of excretory, synthetic, and biochemical activities are performed by the liver. A variety of tests are performed in clinical laboratories to aid in the biochemical evaluation of these functions. Alkaline phosphatase, ALT, AST, and GGT enzymes are useful in determining the liver’s proper functioning and inflammatory status. The liver is the site for metabolism of carbohydrate, protein and lipids. The liver may be assessed by measurement of total and direct bilirubin, total protein and albumin, cholesterol and triglycerides, urea and ammonia.

LIVER FUNCTION TESTS

Liver function tests are most often used to

  1. Tests of excretion by the liver
  2. Evaluation of synthesis in liver
  3. Evaluation of enzyme activity.

TEST OF EXCRETION BY THE LIVER

BILIRUBIN

The rate at which bilirubin is released through hemoglobin degradation determines the amount of bilirubin in the blood. The heme part of hemoglobin degrades into bilirubin. Heme is destroyed in reticuloendothelial system cells, mostly in the spleen. The heme’s protoporphyrin ring is opened, allowing iron to escape into the biliverdin type. Biliverdin is converted to bilirubin, a yellow-pigmented molecule. The tetrapyrole molecule bilirubin has a poor solubility in water and plasma. It is bound to albumin for transport as it is released into the blood. Delta bilirubin is bilirubin that is covalently bound.

When bilirubin-albumin enters the liver, albumin is lost and the enters the hepatocyte. The liver enzyme uridyl diphosphate glucuronyltransferase (UDPG-transferase) converts glucuronate, a sugar, to the bilirubin molecule inside the hepatocyte. To form diglucuronate-bilirubin, 85 percent of bilirubin is conjugated with two molecules of glucuronate. To form monoglucuronate-bilirubin, much of the remaining bilirubin is conjugated with one sugar molecule. The incorporation of the sugar group improves the molecule’s solubility.

Heme Degradation Pathway (Source: Arneson Clinical Chemistry)

The bile duct transports conjugated bilirubin into the intestine, where intestinal bacteria convert it to urobilinogen. Any urobilinogen may be reabsorbed and returned to the portal circulation and liver via the intestinal mucosa. The residual urobilinogen is excreted in the urine or oxidized to urobilin, which is then excreted in the feces. Urobilin is one of the components in feces that gives it its distinctive 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 characteristic condition of yellow discoloration of the scalp, sclera, and mucous membranes. Increased bilirubin is the most frequent cause, and isn’t clinically noticeable when bilirubin levels reach 3 to 5 mg/dL.

Jaundice may be divided into three categories:

Prehepatic

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

Posthepatic

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

When the biliary duct is fully blocked, no bilirubin enters the gut, no urobilinogen is produced, and no bilirubin is detected in the urine or feces.

EVALUATION OF SYNTHESIS IN LIVER

Serum Proteins

Since serum albumin and a limited fraction of globulin are synthesized in the liver, liver disease affects serum proteins both quantitatively and qualitatively. The concentration of serum albumin decreases in any disease that causes hepatocellular damage. Also when there is extreme albumin deficiency, serum globulins may rise to a level that allows them to sustain a normal or elevated total protein concentration in many liver disorders.

Serum albumin levels fluctuate over time, providing useful indicators of hepatic disease incidence, progression, and prognosis. Hepatocellular cause of jaundice or liver disease is shown by low albumin and high globulins in the blood. Since secondary hepatocellular disruption has resulted, serum protein variations result in obstructive jaundice. Cholangitis and biliary cirrhosis, on the other hand, may cause liver damage without causing protein changes. Additionally, before full recovery from hepatitis, serum protein changes can return to normal. Serum protein changes are caused by a variety of factors, including liver disease.

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.

The presence of a normal prothrombin concentration would not rule out the possibility of impaired liver activity. When a jaundice patient has a low prothrombin level (i.e. extended PT), prothrombin should be measured after 2-4 mg vitamin K is given. A low prothrombin level in the absence of jaundice normally means severe liver injury.


EVALUATION OF ENZYME ACTIVITY

Cholesterol and Esters

A persistently low Cholesterol Ester/Total Cholesterol ratio suggests ongoing hepatocellular damage; nevertheless, an increase in cholesterol ester is regarded as a positive sign and signifies progress. A increase in total cholesterol is commonly associated with biliary obstruction, but the cholesterol ester concentration is also unchanged.

Serum Transaminases

Kreb’s cycle enzymes abound in the liver and tissues. A group of enzymes responsible for transferring NH2 groups from amino acids to keto acids, allowing for amino acid metabolism, is one of these enzymes. The enzymes are released as muscle or liver cells are destroyed, and their levels in plasma increase as a result. The serum levels of SGOT and SGPT, as well as LDH concentration, increase to very high levels in obstructive jaundice and, more so, acute hepatitis (300-1500 units, natural is 5-40 units) (normal concentration, 200-450 units). Serum transaminases can be elevated to a mild degree in chronic hepatitis.

As a result of a neoplastic disorder, liver cells are destroyed. The accumulation of transaminases in the serum is moderately elevated as cancer spreads to the liver. While both AST and ALT serum activities rise as disease processes compromise liver cell integrity, ALT is a more liver-specific enzyme. Serum ALT function elevations are uncommon in cases other than parenchymal liver disease. Furthermore, increases in ALT activity last longer than increases in AST activity.

Serum Alkaline Phosphatase

Serum level elevations from The liver and bone are the most important sources of ALP activity. Hepatocytes produce ALP in response to any biliary tree obstruction. Some of the recently produced enzymes circulate in the bloodstream, boosting serum enzyme production. Since the ALP is encoded at several genetic loci, some of which are genuine isoenzymes. The ALP types found in the bones, liver, and kidney both have the same primary structure and code for the same genetic loci, but the carbohydrate content varies. Serum alkaline phosphatase is elevated in acute and chronic hepatocellular disease, though not to the level seen in obstructive jaundice.

Serum alkaline phosphatase can increase in the absence of jaundice in some cases of metastatic liver carcinoma. It’s important to remember that phosphatase levels can be normal early on in obstructive disease and after obstruction is relieved. Pregnancy, as well as diseases including Paget’s disease of the bone, hyperparathyroidism, and rickets/osteomalacia, are linked to elevated serum alkaline phosphatase levels, which must be ruled out.

Gamma-Glutamyl Transferase

Peptidase enzymes catalyze the hydrolysis of peptides to produce amino acids or smaller peptides. They are a diverse group of enzymes of varying specificities, and some of them act as amino acid transferases, catalyzing the transfer of amino acids from one peptide to another.

Despite the fact that GGT is found at the greatest concentration in renal tissue, the enzyme found in serum tends to derive mainly from hepatobiliary disorder, since it is elevated in most subjects with liver disease regardless of source, however its application is restricted due to its lack of precision. The majority of sera from heavy drinkers and patients with alcoholic hepatitis have elevated GGT activities.

Cholinesterase

Patients with atypical forms of the enzyme are at risk of prolonged responses to certain muscle relaxants used in surgical procedures, and measurements of CHE production in serum are used as a monitor of liver function, as an indication of potential insecticide toxicity, and for the diagnosis of patients with atypical forms of the enzyme that are at risk of prolonged responses to certain muscle relaxants used in surgical procedures. Many insecticides, such as parathion, sarin, and tetraethyl pyrophosphate, are organic phosphorous insecticides that inhibit cholinesterase activity.

References:

  1. Concise Book of Medical Laboratory Technology-Methods and Interpretation by Ramnik Sood
  2. Textbook of Clinical Chemistry and Molecular Diagnosis by Tietz
  3. Arneson Clinical Chemistry-A Laboratory Perspective by Arneson W and Brickell J
  4. Ross Wilson Anatomy and Physiology in Health and Illness
  5. The Medical Laboratory Science Examination Review by Elseviers Pub
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