INNOVLITE(INDIA) PVT Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory bloodassays designed to give information about the state of a patients liver 1 The parameters.INNOVLITE(INDIA) PVT Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory bloodassays designed to give information about the state of a patients liver 1 The parameters.
Liver function tests : (LFTs or LFs), are groups of clinical biochemistry laboratory bloodassays designed to give information about the state of a patient's liver.[1] The parameters measured include PT/INR, aPTT, albumin, bilirubin (direct and indirect) and others According to some [who?], liver transaminases (AST/ALT (SGOT/SGPT) are notliver function tests, but are biomarkers of liver injury in a patient with some degree of intact liver function [citation needed] Other sources include transaminases.[2][3] 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 What are normal levels of AST and ALT? • The normal range of values for AST (SGOT) is from to 40 units per liter of serum (the liquid part of the blood) • The normal range of values for ALT (SGPT) is from to 56 units per liter of serum The ranges of AST and ALT numbers may differ slightly depending on the technique and protocols used by different laboratories However, normal reference ranges are routinely provided by each laboratory and printed in the report What elevated liver tests (AST and ALT) mean? AST (SGOT) and ALT (SGPT) are sensitive indicators of liver damage or injury from different types of diseases But it must be emphasized that higher-than-normal levels of these liver enzymes should not be automatically equated with liver disease They may mean liver problems or they may not For example, elevations of these enzymes can occur with muscle damage The interpretation of elevated AST and ALT levels depends upon the entire clinical evaluation of an individual, and so it is best done by physicians experienced in evaluating liver disease and muscle disease Moreover, the precise levels of these enzymes not correlate well with the extent of liver damage or the prognosis (outlook) Thus, the exact levels of AST (SGOT) and ALT (SGPT) cannot be used to determine the degree of liver disease or predict the future For example, individuals with acute viral hepatitis A may develop very high AST and ALT levels (sometimes in the thousands of units/liter range) But most people with acute viral hepatitis A recover fully without residual liver disease Conversely, people with chronic hepatitis C infection typically have only a little elevation in their AST and ALT levels while having substantial liver injury and even advanced scarring of the liver (cirrhosis) 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 higher 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 Alanine transaminase Reference range to 56 IU/L[4] Alanine transaminase (ALT), also called serum glutamic pyruvate transaminase (SGPT) or alanine aminotransferase (ALAT) is an enzyme present in hepatocytes (liver cells) Aspartate transaminase Reference range 6-40 IU/L[5] 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 [6][7] 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 cholestatis When AST and ALT are both over 1000 the normal amount, the differential can include acetaminaphen toxicity, shock, or fulminant liver failure When AST and ALT are >3X of normal but not 1000X, the differntial can include alcohol toxicity, viral hepatitis, drug induced, liver cancer, sepsis, Wilson disease, post-transport rejection of liver, autoimmune hepatitis, and steatohepatitis (non-alcoholic) When AST/ALT elevated are minor it may be due to rhabdomyolysis amoug many possibilities Alkaline phosphatase Reference range 30 to 120 IU/L[4] 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 0.1–1.0 mg/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 Increased total bilirubin (TBIL) causes jaundice, and can indicate a number of problems: Prehepatic: Increased bilirubin production This can be due to a number of causes, including hemolytic anemias and internal hemorrhage 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 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 0.1–0.4 mg/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 disease, a mutation (or variation) in the UDPglucuronyl-transferase promotor that manifests itself as jaundice when the individual is stressed (ie 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 inDubin-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-glucuronyltransferase 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 to 42 IU/L[4] 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) INR Other tests commonly requested alongside LFTs Pathophysiology sample values BMP/ELECTROLYTES: Na+ = 140 Cl− = 100 BUN = 20 / Glu = 150 K+ = CO2 = 22 PCr = 1.0 \ ARTERIAL BLOOD GAS: HCO3- = 24 paCO2 = 40 paO2 = 95 ALVEOLAR GAS: pH = 7.40 pACO2 = 36 pAO2 = 105 A-a g = 10 OTHER: Ca = 9.5 Mg2+ = 2.0 PO4 = CK = 55 BE = −0.36 AG = 16 SERUM OSMOLARITY/RENAL: PMO = 300 PCO = 295 POG = BUN:Cr = 20 URINALYSIS: UNa+ = 80 UCl− = 100 UAG = FENa = 0.95 UK+ = 25 USG = 1.01 UCr = 60 UO = 800 PROTEIN/GI/LIVER FUNCTION TESTS: LDH = 100 TP = 7.6 AST = 25 TBIL = 0.7 ALP = 71 Alb = 4.0 ALT = 40 BC = 0.5 AST/ALT = 0.6 BU = 0.2 AF alb = 3.0 SAAG = 1.0 SOG = 60 CSF: CSF alb = 30 CSF glu = 60 CSF/S alb = 7.5 CSF/S glu = 0.4 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 C-reactive Protein test is more preferred nowadays ... 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 liver damage [6][7] 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. .. 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