Standard liver panel - LFTs

Question 1

Albumin?

Reference range

3.5 to 5.3 g/dL

Answer 1

• Albumin is a protein made specifically by the liver, and can be measured cheaply and easily.
• It is the main constituent of total protein (the remaining from globulins).
• Albumin levels are decreased in chronic liver disease, such as cirrhosis.
• It is also decreased in nephrotic syndrome, where it is lost through the urine.
• The consequence of low albumin can be edema since the intravascular Oncotic pressure becomes lower than the extravascular space.
• An alternative to albumin measurement is prealbumin, which is better at detecting acute changes (half-life of albumin and prealbumin is about 2 weeks and about 2 days, respectively).

Question 2

Aspartate transaminase?

Reference range

6-40 IU/L[5]

Answer 2

• AST, also called serum aspartate aminotransferase, is similar to ALT in that it is another enzyme associated with liver parenchymal cells.
• It is raised in acute liver damage, but is also present in red blood cells, and cardiac and skeletal muscle, so is not specific to the liver.
• The ratio of AST to ALT is mostly useful in differentiating between causes of liver damage.
• Elevated AST levels are not specific for liver damage, and AST has also been used as a cardiac marker.
• When the AST is higher than ALT, a muscle source of these enzymes should be considered.
• For example, muscle inflammation due to dermatomyositis may cause AST>ALT.
• This is a good reminder that AST and ALT are not good measures of liver function because they do not reliably reflect the synthetic ability of the liver and they may come from tissues other than liver (such as muscle).

Question 3

Transaminases?

Answer 3

• AST/ALT elevations instead of ALP elevations favor liver cell necrosis as a mechanism over cholestasis.
• When AST and ALT are both over 1000 IU/L, the differential can include acetaminophen toxicity, shock, or fulminant liver failure.
• When AST and ALT are greater than three times normal but not greater than 1000 IU/L, the differential can include alcohol toxicity, viral hepatitis, drug-induced level, liver cancer, sepsis,
• Wilson’s disease, post-transplant rejection of liver, autoimmune hepatitis, and steatohepatitis (nonalcoholic).
• AST/ALT levels elevated minorly may be due to rhabdomyolysis, among many possibilities.

Question 4

Alkaline phosphatase?

Reference range

30 to 120 IU/L

Answer 4

• (ALP) is an enzyme in the cells lining the biliary ducts of the liver.
• ALP levels in plasma rise with large bile duct obstruction, intrahepatic cholestasis, or infiltrative diseases of the liver.
• ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled) and elderly patients with Paget’s disease.
• In the third trimester of pregnancy, ALP is about two to three times higher.

Question 5

Alkaline phosphatase?

Reference range

30 to 120 IU/L

Answer 5

• Biliary tract disease produces relatively greater increases in ALP than increases in ALT, AST, or LD.
• ALP is associated with the plasma membrane of hepatocytes adjacent to the biliary canaliculus.
• Obstruction or inflammation of the biliary tract results in an increased concentration of the ALP in the circulation.
• Similar to ALT and AST, ALP is not specific for biliary tract disease. ALP is released by osteoblasts, the ileum, and the placenta. ALP is elevated:
  
  • 1) in children 2- to 3-fold over adults because the child’s skeleton is growing,
  • 2) with bone disease involving osteoblasts (e.g., metastatic cancer or following a fracture),
  • 3) in hyperparathyroidism where parathyroid hormone stimulates osteoblasts through a series of steps that enhances bone resorption (e.g., parathyroid adenoma, hyperplasia, or secondary hyperparathyroidism from vitamin D deficiency or renal disease),
  • 4) in cases of ileal disease, and
  • 5) during the third trimester of pregnancy because the placental isoenzyme is elevated.

Question 6

Total bilirubin?

Reference range

0.1–1.0 mg/dL

Answer 6

Measurement of total bilirubin includes both: ​

• Unconjugated and conjugated bilirubin
• Unconjugated bilirubin is a breakdown product of heme (a part of hemoglobinin red blood cells).
• It is very hydrophobic and is mainly transported bound to albumin circulating in the blood.
• Addition of high-concentration hydrophobic drugs (certain antibiotics, diuretics) and high free fatty acids can cause elevated unconjugated bilirubin.
• The liver is responsible for clearing the blood of unconjugated bilirubin, and about 30% of it is taken up by a normal liver on each pass of the blood through the liver by the following mechanism:
  
  • bilirubin is taken up into hepatocytes, ‘conjugated’ (modified to make it water-soluble) by UDP-glucuronyl-transferase, and secreted into the bile by CMOAT (MRP2), which is excreted into the intestine.
  • In the intestine, conjugated bilirubin may be metabolized by colonic bacteria, eliminated, or reabsorbed.
  • Metabolism of bilirubin into urobilinogen followed by reabsorption of urobilinogen accounts for the yellow color of urine, as urine contains a downstream product of urobilinogen.
  • Further metabolism of urobilinogen into stercobilin while in the bowels accounts for the brown color of stool.
  • Thus, having white or clay-colored stool is an indicator for a blockage in bilirubin processing and thus potential liver dysfunction or cholestasis.

Question 7

Total bilirubin?

Reference range

0.1–1.0 mg/dL

Answer 7

Increased total bilirubin (TBIL) causes jaundice, and can indicate a number of problems:

• 1. Prehepatic:
     * Increased bilirubin production can be due to a number of causes,
     * including hemolytic anemias and internal hemorrhage.
• 2. Hepatic:
     * Problems with the liver are reflected as deficiencies in bilirubin metabolism
     * (e.g., reduced hepatocyte uptake, impaired conjugation of bilirubin, and
     * reduced hepatocyte secretion of bilirubin).
     * Some examples would be cirrhosis and viral hepatitis.
• 3. Posthepatic:
     * Obstruction of the bile ducts is reflected as deficiencies in bilirubin excretion.
     * Obstruction can be located either within the liver or in the bile duct.

Question 8

Gamma glutamyl transpeptidase?

Reference range

50 to 420 IU/L

Answer 8

• Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP,
• gamma glutamyl transpeptidase (GGT) may be elevated with even minor, subclinical levels of liver dysfunction.
• It can also be helpful in identifying the cause of an isolated elevation in ALP (GGT is raised in chronic alcohol toxicity).

Question 9

Gamma glutamyl transpeptidase?

Reference range

50 to 420 IU/L

Answer 9

• The proximal convoluted tubule of the kidney, the liver, the pancreas, and the intestine are sources of GGT,
• in decreasing order of tissue concentration.
• Within the cell, GGT is located in microsomes and along the biliary tract plasma membrane,
• GGT is more commonly measured than 5’-NT because GGT testing is widely available on a variety of laboratory instruments.
• GGT is typically not elevated with bone disease. Combined elevations of ALP and GGT are compatible with biliary tract disease.
• However, if the ALP is elevated to a far greater extent than the GGT (or the GGT is normal), ALP sources other than the biliary tract, such as bone, must be investigated.
• GGT elevations occur in response to alcohol use and anticonvulsants, as GGT is induced by such agents.

Question 10

INR?

Answer 10

• Prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and
• international normalized ratio (INR) are measures of the extrinsic pathway of coagulation.
• This test is also called “ProTime INR” and “INR PT”. They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status

Question 11

Coagulation test?

Answer 11

• The liver is responsible for the production of the vast majority of coagulation factors.
• In patients with liver disease, INR can be used as a marker of liver synthetic function as it includes factor VII, which has the shortest half life (2-6 hours) of all coagulation factors measured in INR.
• An elevated INR in patients with liver disease, however, does not necessarily mean the patient has a tendency to bleed, as it only measures procoagulants and not anticoagulants.
• In liver disease the synthesis of both are decreased and some patients are even found to be hypercoagulable (increased tendency to clot) despite an elevated INR.
• In liver patients, coagulation is better determined by more modern tests such as:
  
  • thromboelastogram (TEG) or
  • thomboelastrometry (ROTEM