Liver Function Test PDF

University of Babylon Faculty of Pharmacy By Dr.Lec.Aamer Mousa Ali Objectives  Blood leaves the stomach and intestines, passing through the liver (hepatic portal vein(  While oxygenated blood is supplied through the hepatic artery.  Two...

University of Babylon Faculty of Pharmacy By Dr.Lec.Aamer Mousa Ali Objectives  Blood leaves the stomach and intestines, passing through the liver (hepatic portal vein(  While oxygenated blood is supplied through the hepatic artery.  Two main liver lobes are each made up of thousands of lobules; lobules connect to small ducts that connect to larger ducts, forming the hepatic duct.  The hepatic duct transports bile, produced by the hepatocytes, to the gallbladder and duodenum. Anatomy of liver  Figure 1-2 :Schematic illustrating section through the liver showing organization of hepatocytes in relation to bile canaliculi, bile duct, hepatic artery, and portal vein Parenchymal cells, or hepatocytes, comprise around 80% of the cells in the liver and perform the main metabolic functions associated with metabolism and detoxification. However,other important functions are performed by the non-parenchymal cells: endothelial lining cells, It cells, which store fat, Kupffer cells, which are modified macrophages, and pit cells,which are related to natural killer cells and are thought to play a role in defense against infection. Figure 1.2 shows the hepatocytes in the liver, bile canaliculi, and their association with the bile duct, branches of the hepatic artery and portal vein. General liver metabolism More than 500 vital functions are associated with the liver; some of the better characterised are listed below: production and excretion of bile cholesterol metabolism drug metabolism and detoxification haemoglobin degradation protein metabolism; production of albumin nitrogen metabolism, ammonia detoxification synthesis of coagulation factors storage, including glucose (in the form of glycogen), vitamin B12, iron and copper carbohydrate metabolism lipid metabolism The Function of Liver  Liver is largest and most complex internal organ  Liver is a multifunctional organ that is involved in diverse body functions. 1. Metabolic Functions Liver actively participates in carbohydrate metabolism, lipid, protein, mineral and vitamin metabolisms. 2. Excretory Functions Bile pigments, bile salts and cholesterol are excreted in bile into intestine. 3. Protective functions & detoxification Kupffer cells of liver perform phagocytosis to eliminate foreign compounds. For example ammonia is detoxified to urea and metabolism of xenobiotics (detoxification.) Clearance of hormones such as insulin, parathyroid hormone, oestrogen, cortisol 4. Hematological and synthetic functions Liver participates in formation of blood (particularly in embryo)  Synthesis of plasma proteins (albumin and prothrombin), hormones e.g angiotensinogen, insulin- like growth factor and triiodothyronine.  Destruction of erythrocytes (Bilirubin).5 Storage functions  glucose (as glycogen), fat-soluble vitamins (vitamins A, D, E and K), folate,vitamin B12 and minerals such as copper and iron.  excessive accumulation of certain substances can be harmful  In the inherited condition of Wilson’s disease, the secretion of copper into bile is abnormal, resulting in a low blood level of the copper-binding protein ceruloplasmin. Copper accumulates in the liver (leading to cirrhosis) and in the CNS, resulting in neuropsychiatric symptoms. .6Serum enzymes Acting as markers of liver damage SOME EXAMPLES OF LIVER DYSFUNCTION  Hepatocellular disease  Cholestasis (obstruction of bile flow)  Cirrhosis (chronic scarring)  Hepatitis (causing inflammation)  Jaundice (yellow discoloration of sclera and skin)  Liver cancer  Steatosis (fatty liver)  Genetic Disorders  Primary type Hemochromatosis (high iron storage due to increased absorption)  Secondary hemochromatosis is acquired, result of blood- related disorders such as certain anemias and thalassemia that increase RBC hemolysis Test to assess liver function Liver function tests(LFT) are helpful to detect the abnormalities and extent of liver damage. LFT assays are frequently more sensitive than clinical signs and symptoms. Typically the LFT comprises of: - Total protein  Albumin and globulin  (Prothrombin Time)  Transaminases – AST & ALT  Alkaline phosphatase  Bilirubin, usually fractionated  Gamma Glutamyl Transpeptidase (GGT) Total protein Not a very useful measure, non-specific; only provides information on:  General nutritional status  Severe organ disease (protein losing disease)  Fractionated values of greater use  Total protein Note! Measures of protein are in serum – avoid dilution of proteins from anticoagulant Precipitation is used to fractionate proteins into albumin and globulin  A/G ratio is a frequently used value in determining serum protein abnormalitiesNormal A/G ratio: 1.2/1 – 1.5/1  Albumin changes  Globulin changes:  in disease from increased synthesis  Refractive index (useful if level > 2.5g/dL) Albumin and globulin Albumin  Usu most abundant protein in serum [3.5 to 5g/dL ]  ↓albumin  Impaired synthesis (malnutrition, malabsorption, hepatic dysfunction, cirrhosis)  Loss (ascites, protein losing-nephropathy, enteropathy)  May result in peripheral oedema  Up to 25% of albumin in hyperglycaemia becomes glycosylated with HbA1c – aka fructosamine useful in monitoring DM Albumin and globulin Albumin  albumin  Unusual – can occur in dehydration or as artifactfm tourniquet use Types of globulin of clinical significance:  1-antitrypsin (AAT)  2-macroglobulin  Haptoglobin  Transferrin  Ceruloplasmin  Ceruloplasmin  Cu containing enzyme (ferroxidase) in serum  ↓ in Wilson’s disease  Associated with chronic hepatitis (acute) and may have neurologic/ psychiatric sequelae -Fetoprotein  One of the major plasma proteins in foetal life  Function not known, similar structure to albumin  Falls thru-out gestation (~10,000 ng/mL at birth) and by age one yr ( 10 - 30 IU/l) are observed in : chronic alcoholism, pancreatic disease, myocardial infarction, renal failure, chronic obstructive pulmonary disease and in diabetes mellitus  In liver diseases, GGT elevation parallels that of ALP  In alcoholic liver disease GGT levels may be parallel to alcohol intake Bilirubin  It is the yellowish pigment observed in jaundice  Is the end product of RBC breakdown (RBCs lifespan: 120 days) 1. Hemoglobin from the RBCs break down into a heme and a globulin 2. The heme group is taken up by macrophages of the reticuloendothelial system (including tissue macrophages and that of the liver and spleen) into bilrubin 3. Birubin is insoluble in the blood so it attaches and is carried to the liver by albumin 4. Bilrubin is derived from the albumin, enters the hepatocytes and conjugates with glucoronic acid by the enzyme UDP-glucourinile transferase 5. This soluble conjugated form is excreted via the bile duct into the intestine where the bacteria removes the glucoronic acid and converts bilrubin into urobilinogen 6. some of the urobilinogen is reabsorbed from the gut and enters the portal circulation  some is recycled in the enterohepatic cells  the remainder is transported along with the blood to the kidneys where it is converted into UROBILIN that is excreted in the urine, giving it it’s characteristic YELLOW color  mainly urobilinogen in the gut is oxidized by the bacteria into strecobilin which is excreted in the feces giving it its BROWN appearance SERUM BILIRUBIN LEVELS  Normal: 0.2 to 0.8 mg/dl  Unconjugated/free/indirect (bilirubin-albumin complex): 0.2 to 0.7 mg/dL  Conjugated/direct: 0.1 to 0.4 mg/dL  Latent jaundice: Above 1 mg/dL  patient does NOT presents with jaundice (subclinical jaundice)  Jaundice: Above 2 mg/dL  High bilirubin levels are observed in gallstones, acute and chronic hepatitis