{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

Liver F.T - INTRODUCTION INTRODUCTION The liver plays a...

Info icon This preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: INTRODUCTION INTRODUCTION The liver plays a major role in protein, carbohydrate and lipid homeostasis. The liver contains an extensive reticuloendothelial system of the synthesis and breakdown of blood cells. and Liver cells metabolize, detoxify and excrete both endogenous and exogenous compounds. compounds. LIVER FUNCTION TESTS (LFTS) (LFTS) Are measurements of blood components Are which simply provide a lead to the existence, the extent and the type of liver damage. damage. Usually, a request for LFTs will provide results for bilirubin, the amino-transferases and alkaline phosphatase in a serum specimen. Knowledge of the serum albumin concentration may also be of some value in the investigation of liver disease. the These biochemical investigations can assist These in differentiating the following:in – Obstruction to the biliary tract. – Acute hepatocellular damage. – Chronic liver disease. Chronic Serum total bilirubin concentration and serum alkaline phosphatase activity are indices of cholestasis, a blockage of bile flow. flow. The serum aminotransferase activities are a The measure of the integrity of liver cells. The serum albumin concentration is a measure of the liver’s synthetic capacity. measure The most commonly performed blood tests blood 1-Serum bilirubin 2-Prothrombin time (PTT) 3-Serum albumin 4-Serum alkaline phosphatase 5-Serum aminotransferases (ALT, AST) 6-Gamma-glutamyl transpeptidase 7-Lactate dehydrogenase 8-Alpha-fetoprotein 8-Alpha-fetoprotein 1. Bilirubin: Bilirubin: Is derived from haem, An adult normally produces about 450 µmol of bilirubin daily. produces It is insoluble in water and is transported in It plasma almost totally bound to albumin. plasma It is taken up by the liver cells and It conjugated to form mono-and diconjugated glucuronides which are much more soluble glucuronides in water than unconjugated bilirubin (indirect). The conjugated bilirubin (direct) is excreted into the bile. Normal bile contains bilirubin monoglucuronide as 25% and diglucuronide as 75% of the total. Then through the bile duct it passes to the intestine, where it reduced by bacterial action to a group of compounds (stercobilinogen), most of which are excreted in faeces. Some are absorbed and eventually re-excreted from the body by way of bile. Small amounts of these tetrapyorroles are found in urine in which they are known as urobilinogen. When the biliary tract becomes blocked, blirubin is not excreted and serum concentrations rise. The patient becomes jaundiced. Disordered bilirubin metabolism: Disordered Disordered bilirubin metabolism can be Disordered considered under four headings: considered 1. Increased formation of bilirubin. 2. Abnormal uptake of bilirubin in the 2. liver cells. 3. Defective conjugation. 4. Failure of normal amounts of bile to reach the deudenum. reach Disorders 1, 2 and 3 result in accumulation of unconjugated bilirubin and the condition is referred to as “retention jaundice”. is Type 4 is accompanied by passage of Type conjugated bilirubin from bile capillaries and then resulting into “regurgitation jaundice”. It may be due to intracellular obstruction of bile circulation or extracellular obstruction to the passage of bile into deudenum. 2- The aminotransferases (AST & ALT): 2Are both present in liver cells. ALT is cytosolic enzyme, whereas AST is ALT predominately mitochondrial. predominately These are released into serum upon cell These damage or destruction. ALT is the most sensitive marker for liver cell damage sensitive 3- Serum alkaline phosphatase (ALP): 3ALP is excreted through biliary system in ALP the same manner as bilirubin is excreted via the bile ducts. It is also found in bone and the placenta. Renal or intestinal damage can also cause the alkaline phosphatase to rise. the 4- Determination of γ - glutamyl transferase: 4Is a microsomal enzyme which is widely Is distributed in tissues including liver and renal tubular. The activity of γ-GT in plasma is raised whenever there is cholestasis, and it is a very sensitive index of liver pathology. It is also affected by ingestion of alcohol, even in the absence of recognizable liver disease. 5-Lactic dehydrogenase test: 5-Lactic This test can detect tissue damage and aides in the diagnosis of liver disease. aides 6- Plasma proteins: 6A) Albumin Hypoalbuminaemia is a feature of Hypoalbuminaemia advanced chronic liver disease. It can also occur in severe acute liver damage. The production time, which is a measure of the activities certain coagulation factors made by the liver, is sometimes used as an indicator of hepatic synthetic function. B) Prothrombin has a very short half life, and an increased prothrombin time may be the earliest indicator of hepatocellular damage. C) The total serum globulin concentration is sometimes used as a crude measure of the severity of liver disease. D) Alpha-fetoprotein (AFP): Is synthesized by the fetal liver. In normal adults it is present in plasma at low concentrations (<20µg/L). Measurement of AFP is of value in the investigation of hepatocellular carcinoma in which serum concentrations are increased in 80-90% of cases. in AFP is also used as a marker for germ cells AFP tumors. tumors. E) Other proteins such as α1-antitrypsin are -antitrypsin measured in the diagnosis of specific diseases affecting the liver. diseases JAUNDICE OR ICTERUS JAUNDICE Refers to the yellow pigmentation of the Refers skin, conjunctive, and mucous membranes by bilirubin. by Clinically it becomes apparent when the Clinically serum bilirubin concentration exceeds 2 mg/dL. There are three types of jaundice: There A- Pre-hepatic. B- Hepatic. BC- Post-hepatic. C- A: Pre-hepatic (haemolytic) Jaundice: It occurs due to excessive destruction of red blood cells, resulting in increased bilirubin formation.( hyperbilirubinaemia) bilirubin This is commonly encountered in babies. The enzymes responsible for conjugation The are not fully active at birth, so the new born liver barely has the capacity to excrete its normal bilirubin load. Jaundice before 24 hrs of age is abnormal but moderate hyperbilirubinaemia (< 5 mg/dL) within the first week may not be pathological. A rapidly rising unconjugated bilirubin in a neonate should be carefully monitored. May exceed the protein biding capacity and deposited in the brain, causing kernicterus. deposited If the concentration approaches 200 µmol/L. Phototherapy should be used to break down the molecule and reduce the level. If the concentration rise above 300 µmol/L. exchange transfusion may be necessary. B. Hepatic (hepatocellular) Jaundice: B. Obstruction may be secondary to damage to the hepatocytes by infection or toxins, rather than damage to the biliary tract. The most common causes of acute jaundice seen in adults are viral hepatitis and paracetamol poisoning. In these cases, not only are the bilirubin and alkaline phosphatase levels raised, but AST and ALT are elevated indicating hepatocellular damage. Gilbert's disease: may be caused by an inability of the may hepatocytes to take up bilirubin from the blood. As a result, unconjugated bilirubin accumulates. Crigler-Najjar syndrome: A conditions in which conjugation is impaired. Dubin-Johnson syndrome: is associated with inability of the hepatocytes to secrete conjugated bilirubin after it has been formed. Conjugated bilirubin returns to the blood. Conjugated C. Post-hepatic (obstructive) Jaundice: C. Gallstones can partially or fully block the bile duct. Such a blockage is known as extra hepatic obstruction. If the blockage is complete, both bilirubin and alkaline phosphatase are raised. phosphatase There is little or no uroblinogen in urine. There Stools will be pale in color. When the obstruction is removed, the stools regain their color and urine again becomes positive for urobilinogen. The levels of alkaline phosphatase released into serum will mirror the degree of obstruction. Intra hepatic biliary obstruction is much more difficult to diagnose than extra hepatic obstruction. The bile canaliculi become blocked due to cirrhosis, liver cancer or infection. This leads to an increased concentration of conjugated blirubin in serum. Application of clinical laboratory tests to differentiate the type of jaundice: jaundice: Group (1) tests: Group Specimen 1: serum serum Tests: total bilirubin, direct bilirubin, and indirect bilirubin. Specimen 2: Urine: Tests: bile pigments, bile salts and urobilinogen. Group 2 tests: Group Liver enzyme panel: Serum Liver 1. ALT 2. AST 1. 3. ALP and 4.Gamma-G.T. Group 3 tests: Serum total proteins, albumin, Serum globulins, A/G ratio. Thymol turbidity test. LIVER DISEASES LIVER Acute liver disease: Acute liver damage is caused by poisoning, Acute infection and inadequate perfusion. Investigation: Biochemical markers of liver disease such as AST and ALT will indicate hepatocyte damage. Elevated serum bilirubin and alkaline phosphatase levels show the presence of cholestasis. cholestasis. Liver poisoning: The most well-documented poisons which affect the liver are paracetamol and carbon tetrachloride. Some plant and fungal toxins can also cause fatal liver damage within 48 hrs. cause Liver infection: Liver Both bacteria and viruses can give rise to infective hepatitis which causes many death worldwide. death Hepatitis A, hepatitis B and hepatitis C are the most common. the In acute liver damage there is usually intra In hepatic obstruction as well as hepatocellular damage. hepatocellular Severe causes of acute liver damage may Severe progress to hepatocellular failure. Hepatic failure may give rise to renal failure due to exposure of the glomeruli to toxins usually metabolized by the liver. usually Chronic liver disease: Chronic Three forms of chronic liver damage are: – Alcoholic fatty liver. – Chronic active hepatitis Chronic – Primary biliary cirrhosis Primary All of these conditions may progress to cirrhosis, a disease characterized by shrinking of the liver with disorganization of its architecture and the development of fibrosis in the remaining hepatocellular tissue. tissue. The most common causes of cirrhosis are: The – Chronic excess alcohol ingestion. – Viral hepatitis. – Auto immune disease. Clinical Features: There are no good biochemical indicators There of cirrhosis in the early and stable period which may last for many years. In the terminal stage the feature include: In – Developing jaundice. – Encephalopathy, which may be related to Encephalopathy, toxins. – Ascites (fluid build-up in the abdominal Ascites cavity) due to reduced albumin synthesis. cavity) – Bleeding tendencies. – Terminal liver failure. Unusual causes of cirrhosis: Unusual Cirrhosis can develop in children as a result Cirrhosis of α1-antitrypsin deficiency or Wilson’s of -antitrypsin disease, and in adults due to haemochromatosis. Other liver problems: Primary hepatoma, is associated with a number of conditions such as cirrhosis or hepatitis, although a number of causative carcinogens, such as aflatoxins. Alpha-fetoprotein is a useful marker of primary hepatic tumors. NORMAL RANGES NORMAL Total bilirubin: up to 1.0 mg/dL. Direct bilirubin: up to 0.5 mg/dL. Indirect bilirubin: up to 0.5 mg/dL Indirect ALT : 25°C Up to 22 IU Up to 17 IU 30°C 37°C Up to 29 IU Up to 29 IU Up to 22 IU Up to 31 IU • Temperature Men Women AST: AST: ALP: Adults: 20 – 81 I.U. Adults: Children: 93 – 221 I.U. Children: Gamma-G.T. Male: 4 – 23 I.U Male: Female 3.5 – 13 I.U Female References References AGA Clinical Practice Committee. AGA medical AGA position statement: evaluation of liver chemistry tests. Gastroenterology 2002;123:1364-66. tests. Gaw, A., murphy,J., Cowan, A., O Reilly,J., Gaw, Stewart, J., Shepherd, J (2004). Clinical Biochemistry,3th edition. Churchill Livingstone. Page (12-22). Beckett, G., Walker, S., Rae, P., Ashby, P (2005). Lecture notes: Clinical Biochemistry. 7th ed. Blackwell. P (20-49). ...
View Full Document

{[ snackBarMessage ]}