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Prof. Fang Zheng Department of Laboratory Medicine School of Medicine, Wuhan University
Content
Anatomy of Liver Functions of Liver Tests of Liver Function Liver Diseases How to use biochemical tests of liver functions?
INTRODUCTION
The liver is divided into four lobes.
The portal vein carries blood that has already passed through the capillary bed of the gastrointestinal tract. The hepatic artery carries well-oxygenated blood to the liver. Both circulations mix in a vast network of hepatic sinusoids and leave the liver via the hepatic vein. Sinusoids are lined by endothelial and Kupffers cells.
Liver Function
1. Synthesis secretion plasma proteins, bile 2. Metabolism of carbohydrate lipid, protein vitamins, hormone bile acids, bile pigment, drug and toxins 3. Detoxification (biotransformation)
Globulin: The main proteins in serum. Total serum globin: the severity of liver disease
Reference Value
Densitometric scan of a normal serum protein electrophoresis pattern showing the relative position of the albumin,1,2, and regions
alpha-fetoprotein(AFP): primary hepatocellular carcinoma Carcinoembryonic antigen(CEA): liver metastatic carcinoma or other carcinomas of the gastrointestinal system.
Bilirubin Metabolism
1) Bilirubin is the principal degradation product of heme. 2) Bilirubin transport and conjugation in the hepatocyte. 3) The generally accepted reference range for normal plasma bilirubin concentrations in healthy persons, which includes 95 per cent of all individuals values, is 1.7 to 17.1umol/L.
Bilirubin metabolism
Bilirubin
Bilirubin is derived from the tetrapyrrole prosthetic group found in haemoglobin and the cytochrome. It is normally conjugated with glucuronic acid to make it more soluble, and excreted in the bile. Both conjugated bilirubin and unconjugated bilirubin may be present in plasma. Conjugated bilirubin is water soluble, unconjugated bilirubin is not, and binds to albumin. Bilirubin is neurotoxic, and if its levels rise too high in neonates, permanent brain damage can occur.
BILIRUBIN
Bilirubin metabolites are responsible for the brown coloration of faeces. If bilirubin does not reach the gut, stools become pale in color. Bilirubin in the gut is metabolized by bacteria to produce stercobilinogen, which is partly reabsorbed and reexcreted in the urine as urobilinogen. When high levels of conjugated bilirubin are being excreted , urine may be a deep orange colour.
Jaundice
Whats Jaundice? Jaundice is a yellow discoloration of the skin or sclera. Due to the bilirubin concentration in plasma is much greater than normal (greater than about 40 mol/L)
Causes of jaundice
Jaundice indicates that there is an elevated concentration of bilirubin in serum. In neonates it is important to determine the concentration of unconjugated bilirubin in order to decide what treatment is required. In adults, the most common cause of jaundice is obstruction, and this is confirmed by the elevation of both
Jaundice/More than 34.2mol/L(2.0mg/100mL) Latent jaundice /17.2 34.2 mol/L Normal/ Less than 1.70~17.2 mol/L 80% is unconjugated bilirubin and 20% is conjugated bilirubin
Serum bilirubin
Urine Bilirubin
Because only conjugated bilirubin is excreted in urine, it is indirect test for increased concentration of conjugated bilirubin in serum. A fresh urine specimen is required since bilirubin is very unstable when exposed in light and room temperature. The chemstrip test for bilirubin in urine.
Haemolytic
Cholestatic
Hepatocellular
1.AST+ALT 2.Bilirubin later 2.No bilirubin in 2.Bilirubin in urine 3.Bilirubin in urine urine. 3.ALP Usually>3 4. ALP later 3.Reticulocytosis upper limit of reference range. 4.haemoglobin 5. haptoglobin ( 4.AST, ALT+LDH usually modestly ) 6. LDH may
Indocyanine green retention rate (ICGR): 15min<10% Chronic hepatitis: 15-20% Cirrhosis: 35%
Plasma alkaline phosphatase activity as a function of age and sex(men , women). Horizontal lines refer to multiples of the adult upper reference limit.
Unlike some disorders such as acute pancreatitis (Amylase) and myocardial infarction (Myoglobin Troponin), for which there are enzyme markers that are primarily used for one disorder and have high diagnostic efficiencies, there are no enzyme markers that are specific for any single liver disease.
When evaluating these disorders, therefore, it is appropriate to consider a panel of markers, sometimes called live function tests (LFTs). usually includes bilirubin, AST, ALT, ALP, and sometimes GGT and 5'NT although these tests can reflect various disease processes in the liver, they do not reflect hepatic reserve for synthesis and metabolic functions
Bile Acids
Bile Acids
The regulation of bile acid is a major function of the liver. Cholesterol homeostasis is in large part maintained by the conversation of cholesterol to bile acids and subsequent regulation of bile acid metabolism. Bile acid provides surface-active detergent molecules that facilitate both hepatic excretion of cholesterol to bile acids and solubilization of lipids for intestinal absorption.
Hepatitis A(HAV) is a kind of RNA virus. It is transmitted by the fecal-oral route. It is thus implicated in most instances of water-borne and food-transmitted infection and in epidemics of viral hepatitis.
IgG type
HBV is a kind of DNA virus consisted by core and surface components. HBV transmission occurs most commonly via blood and blood products, contaminated needles and intimate personal contact. HBV is present in all body fluids.
e antigen, a Transiently positive in acute hepatitis component B, reflects presence of viral replication and high infectivity Anti-HBe Antibody to e Transiently positive, may be antigen persistently present in chronic cases, reflects low infectivity Anti-HBc IgG type Positive in all acute and chronic cases, Antibody reliable marker of infection, past or to core current antigen IgM type Reflects active viral replication, not protective
Agent
markers Anti-HBs
Liver Disease
Liver disease
Acute Hepatocellular Injury Viral Hepatitis Acute Liver failure Cholestatic Liver Disease Intrahepatic Obstruction Extrahepatic Obstruction Chronic Liver Disease Chronic Hepatitis Cirrhosis Liver Cancer Alcoholic Liver Disease Fatty Liver Alcoholic Hepatitis
Cholestasis
Cholestasis represents the demonstrable accumulation in the blood stream of substances normally excreted in bile (e.g., bilirubin, cholesterol, bile acids).
Intrahepatic Obstruction Intrahepatic cholestasis often results from cirrhosis or hepatitis. Extrahepatic Obstruction Extrahepatic cholestasis is usually the result of mechanical obstruction of the common bile duct or hepatic duct.
Chronic Hepatitis chronic active hepatitis chronic persistent hepatitis Cirrhosis Liver enzyme levels in cirrhosis are variably elevated and can be normal during the terminal stages of the disease. Primary biliary cirrhosis /Elevations in ALP and aminotransferases are expected along with high titers of antimitochondrial antibody. Liver Cancer The liver enzyme results tend to be more elevated in the active form; however, differentiation is best made by performing a liver biopsy.
Cirrhosis
The most common causes of cirrhosis are chronic excess alcohol ingestion, viral hepatitis and autoimmune diseases. Cirrhosis is not reversible. There are no good biochemical indicators of cirrhosis in the early and stable period Cirrhosis can develop in children as a result of a1antitrypsin deficiency or Wilsons disease and in adult due to haemochromatosis.
Normal Liver
Fatty Liver
Cirrhotic Liver
Case history
A 49-year-old woman attend her GP with an 8-day history of anorexia, nausea and flu-like symptom. She had noticed that her urine had been dark in colour over the past 2 days. Physical examination revealed tenderness in the right upper quadrant of the abdomen. LFTS were as follows: Bilirubin AST ALT ALP -GT TP Alb mol/L U/L (g/L) 63 936 2700 410 312 68 42 Comment on these results. What is the differential diagnosis?
enzyme marker ALT and AST elevated>1000U/L ALT elevated in 3 to 4 weeks after infection ALT return to normal within 8 to 12 weeks preclinical incubation phase is longer and ALT and AST may remain normal for 2 to 6months ALT and AST return to normal within 2 to 3months ALT and AST elevated 5 to10 fold ALT and AST return to normal or subnormal
HAV HBV and HCV chronic active hepatitis end-stage liver disease
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The best markers for intrahepatic and extrahepatic cholestasis are ALP, GGT, and 5'NT AST and ALT are generally only slightly elevated in cholestasis, rarely more than 500 U/L. The largest elevations (four- to 10-fold) of ALP are typically seen in obstruction owing to gallstones or malignancy and in biliary cirrhosis. Measurement of total and direct bilirubin are also important in making the diagnosis of obstructive jaundice.
Ratio (AST/ALT)
Further differentiation of specific liver diseases is aided by calculating the ratio of AST to ALT levels. acute or chronic ? intra- or extrahepatic ?
recommended by the International Federation of Clinical Chemistry (IFCC) The ratio is normally approximately 1.15
AST/ALT
AST/ALT Disease Acute disorders of the liver <1.0 acute hepatitis Chronic disorders of the liver >1.0 alcoholic liver disease chronic active hepatitis Chronic persistent hepatitis normal Extrahepatic obstruction acute passage of a stone 1.5 intrahepatic cholestasis biliary cirrhosis and malignancy 1.5
o sel ptl u M i i
Relationship of AST and ALT to ALP and GGT in Alcoholic Live Disease
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Cholestatic Disease
Normal Albumin Decreased Albumin
Acute Hepatitis
Chronic Hepatitis
Chronic Cholestasis
Intrahepatic Cholestasis
Extrahepatic Cholestasis
Case history
A 60-years-old female with a history of breast carcinoma treated by mastectomy three years previously is now complaining of general malaise and bone pain. Biochemistry showed that fluid and electrolyte, total protein, albumin and calcium values were all normal. LFTs were as follows: Bilirubin GT mol/l 7 32 33 38 AST ALT Alkaline phosphatase U/l 890
Summary
Biochemical monitoring of liver disease is by sequential measurements of the aminotransferase, bilirubin and alkaline phosphatase. In acute liver damage there is usually intrahepatic obstruction as well as hepatocellular damage. Severe cases of acute liver damage may progress to hepatocellalur failure. Cirrhosis is the end point of both acute and chronic liver damage, as well as being caused by a number of metabolic and autoimmune diseases. Biochemical tests may be of little value in making a specific diagnosis. A liver biopsy is frequently more helpful.
The clinical significances of each liver function test? The differentiation diagnosis of jaundice. The evaluations of biochemical tests of liver functions in different liver diseases.