Liver function tests

Liver function tests

Liver function tests
Intervention ICD-10-PCS K-70 to K-77 ICD-9-CM MeSH 570573 D008111 [1]

MedlinePlus 003436 [2]

Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver.[] The parameters measured include Prothrombin time (PT/INR), aPTT, albumin, bilirubin (direct and indirect) and others. According to someWikipedia:Avoid weasel words, liver transaminases (AST/ALT (SGOT/SGPT) are not liver function tests but liver damage testbiomarkers of liver injury in a patient with some degree of intact liver function.[citation needed] Other sources include transaminases.[][] Most liver diseases cause only mild symptoms initially, but it is vital that these diseases be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance. This testing is performed by a medical technologist on a patient's serum or plasma sample obtained by phlebotomy. Some tests are associated with functionality (e.g., albumin); some with cellular integrity (e.g., transaminase) and some with conditions linked to the biliary tract (gamma-glutamyl transferase and alkaline phosphatase). Several biochemical tests are useful in the evaluation and management of patients with hepatic dysfunction. These tests can be used to (1) detect the presence of liver disease, (2) distinguish among different types of liver disorders, (3) gauge the extent of known liver damage, and (4) follow the response to treatment. Some or all of these measurements are also carried out (usually about twice a year for routine cases) on those individuals taking certain medications anticonvulsants are a notable example in order to ensure that the medications are not damaging the person's liver.

Standard liver panel

Albumin
Reference range 3.5 to 5.3 g/dL

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 intra-vascular oncotic pressure is lower than the extravascular space. An alternative to albumin measurements is pre-albumin, which is better at detecting acute changes (half-life of albumin and pre-albumin is ~2 weeks and ~2 days respectively.

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Aspartate transaminase
Reference range 6-40 IU/L [3]

Aspartate transaminase (AST) also called serum glutamic oxaloacetic transaminase (SGOT) or aspartate aminotransferase (ASAT) 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 and is therefore not specific to the liver. The ratio of AST to ALT is sometimes 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.

Transaminitis
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 >3X of normal but not > 1000 IU/L, the differential can include alcohol toxicity, viral hepatitis, drug induced, liver cancer, sepsis, Wilson disease, post-transplant rejection of liver, autoimmune hepatitis, and steatohepatitis (non-alcoholic). When AST/ALT elevated are minor it may be due to rhabdomyolysis among many possibilities.

Alkaline phosphatase
Reference range 30 to 120 IU/L []

Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma will 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 3rd trimester of pregnancy, ALP is ~2-3X higher.

Total bilirubin
Reference range 0.11.0mg/dL

Unconjugated Bilirubin is a breakdown product of heme (a part of hemoglobin in red blood cells). Unconjugated bilirubin is very hydrophobic and relies on transportation on albumin that is circulating in the blood. This is why addition of high concentration hydrophobic drugs (certain antibiotics, diuretics) and high free fatty acids can cause elevated unconjugated bilirubin. Heme can also come from myoglobin, found mostly in muscle, cytochromes, found mostly in mitochondria, catalase, peroxidase, and nitric oxide synthase. The liver is responsible for clearing the blood of unconjugated bilirubin and about 30% of bilirubin is taken up by a normal liver each pass through the liver. It does this 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 (1) metabolized by colonic bacteria, (2) eliminated, (3) reabsorbed. Metabolism of bilirubin into urobilinogen followed by reabsorption of urobilinogen accounts for the yellow color of urine as we urinate 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 cholestatis.

Liver function tests Increased total bilirubin (TBIL) causes jaundice, and can indicate a number of problems: 1. Prehepatic: Increased bilirubin production. This can be due to a number of causes, including hemolytic anemias and internal hemorrhage. 2. Hepatic: Problems with the liver, which 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, reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver or in the bile duct).

Direct bilirubin (conjugated bilirubin)

Reference range 0.10.4mg/dL

The diagnosis is narrowed down further by looking at the levels of direct bilirubin. If direct (i.e. conjugated) bilirubin is normal, then the problem is an excess of unconjugated bilirubin (indirect bilirubin), and the location of the problem is upstream of bilirubin conjugation in the liver. Hemolysis, viral hepatitis, or cirrhosis can be suspected. If direct bilirubin is elevated, then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction by gallstones or cancer should be suspected.

Congenital Bilirubin Disorders

About 5% of the population have Gilbert's syndrome, a mutation (or variation) in the UDP-glucuronyl-transferase promotor that manifests itself as jaundice when the individual is stressed (i.e. starves). Autosomal recessive knockouts of UDP-glucuronyl-transferase itself can lead to Crigler-Najjar Syndrome and elevations of unconjugated bilirubin. Defects in CMOAT (MRP2) results in Dubin-Johnson Syndrome and elevations of conjugated bilirubin.

High Bilirubin in neonates

Neonates are especially vulnerable to bilirubin levels due to an immature blood-brain barrier that predisposed them to kernicterus / bilirubin encephalopathy which can result in permanent neurological damage. Neonates also have a low amount of functional UDP-glucuronyl-transferase and can have elevated unconjugated bilirubin since conjugated is limited. For this reason, newborns are often treated with UV light to turn the hydrophobic, albumin-binding unconjugated bilirubin into a form that is more hydrophilic and able to be secreted out via urine, sparing the neonate's brain.

Gamma glutamyl transpeptidase

Reference range 0 to 42 IU/L []

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, sub-clinical 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).

Liver function tests

INR
The 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.

Other tests commonly requested alongside LFTs

Pathophysiology sample values BMP/ELECTROLYTES: Na+ = 140 Cl = 100 BUN = 20 / Glu = 150 K+ = 4 CO2 = 22 PCr = 1.0 \

ARTERIAL BLOOD GAS: HCO3- = 24 paCO2 = 40 paO2 = 95 pH = 7.40

ALVEOLAR GAS: pACO2 = 36 pAO2 = 105 OTHER: Ca = 9.5 CK = 55 Mg2+ = 2.0 BE = 0.36 PO4 = 1 AG = 16 A-a g = 10

SERUM OSMOLARITY/RENAL: PMO = 300 PCO = 295 POG = 5 BUN:Cr = 20

URINALYSIS: UNa+ = 80 UK+ = 25 UCl = 100 USG = 1.01 UAG = 5 UCr = 60 FENa = 0.95 UO = 800

PROTEIN/GI/LIVER FUNCTION TESTS: LDH = 100 ALP = 71 TP = 7.6 Alb = 4.0 AST = 25 ALT = 40 TBIL = 0.7 BC = 0.5

AST/ALT = 0.6 BU = 0.2 AF alb = 3.0 SAAG = 1.0 CSF: CSF alb = 30 CSF glu = 60 CSF/S alb = 7.5 CSF/S glu = 0.4 SOG = 60

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5' Nucleotidase
5' Nucleotidase (5'NTD) is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT for ascertaining whether an elevated ALP is of biliary or extra-biliary origin.

Coagulation test
The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. Increased levels of INR means that blood is taking more time than usual to coagulate or clot. The INR will be increased only if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired; it is not a sensitive measure of liver function. It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors) as they could bleed excessively.

Serum glucose
The serum glucose test may be abbreviated as "BG" or "Glu". The liver's ability to produce glucose (gluconeogenesis) is usually the last function to be lost in the setting of fulminant liver failure.

Lactate dehydrogenase
Lactate dehydrogenase (LDH) is an enzyme found in many body tissues, including the liver. Elevated levels of LDH may indicate liver damage (need citation). LDH isotype-3 (or cardiac) is used for estimating damage to cardiac tissue, although Troponin and Creatine Kinase tests are more preferred nowadays.[4]

References
[1] [2] [3] [4] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D008111 http:/ / www. nlm. nih. gov/ medlineplus/ ency/ article/ 003436. htm "http:/ / www. gpnotebook. co. uk/ simplepage. cfm?ID=322240579" http:/ / www. ncbi. nlm. nih. gov/ pubmed/ 14659867

External links
Liver function tests (http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Liver+function+ tests) at the US National Library of Medicine Medical Subject Headings (MeSH) Overview (http://www.mayoclinic.com/health/liver-function-tests/MY00093) at Mayo Clinic Abnormal Liver Function Tests (http://www.patient.co.uk/showdoc/40024562) Overview of liver enzymes (http://liverenzymes.net)

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