Liver Diseases & Liver Function Tests PDF

LIVER DISEASES & LIVER FUNCTION TESTS Prof. Dr. Halil RESMİ 08/10/2024 (Tuesday Groups) 09/10/2024 (Wednesday Groups)  METABOLISM OF THE LIVER Metabolism of the liver includes; Carbohydrate metabolism Nitrogen metabolism Bile acid formation Bilirubin metabolism...

LIVER DISEASES & LIVER FUNCTION TESTS Prof. Dr. Halil RESMİ 08/10/2024 (Tuesday Groups) 09/10/2024 (Wednesday Groups)  METABOLISM OF THE LIVER Metabolism of the liver includes; Carbohydrate metabolism Nitrogen metabolism Bile acid formation Bilirubin metabolism Lipid metabolism Blood protein synthesis Detoxification Metabolic end-product excretion Storage function  ANATOMY OF THE LIVER Largest organ in the body (1.2 to 1.5 kg), It is divided into two lobes, Located in the abdominal cavity, just below the diaphragma. LIVER TOPOGRAPHY BILIARY C ANALICULI  LIVER CELLS Two primary cells of the liver are hepatocytes and Kuppfer cells. Hepatocytes are responsible for the metabolic functions of the liver.  PROTEIN METABOLISM IN THE LIVER Most of the serum proteins are synthesized in the liver (with two exception in adults; gamma globulins and hemoglobin). Many proteins syntesized by the liver are exceted into blood circulation. MAJOR PLASMA PROTEINS  ALBUMIN One of the most important proteins produced by the liver, Present in concentrations of 4.0-5.0 g/dL, Albumin represents 50-60% (by weight) of all plasma proteins, Albumin a role in maintenance of oncotic pressure, Transport; calcium, unconjugated bilirubin, free fatty acids, drugs, steroid hormons.  PREALBUMIN (TRANSTHYRETIN) A minor protein of plasma produced by the liver, It is a sensitive indicator of protein- nutritional status, Measurement of prelbumin and albumin is useful for diagnosis and monitoring of malnutrition.  NONPROTEIN NITROGENS Urea, creatinine, ammonia and uric acid account for 70-75 % of serum nonprotein nitrogen, Most of the metabolisms of nonprotein nitrogen occurs in liver, Urea is produced by liver.  BILE PIGMENT FORMATION Senescent erythrocytes are phagocytized (by reticuloendothelial system/RES) and hemoglobin is released from the cell, Globin protein chains and heme are separated each other, The heme portion of Hb is converted to bilirubin, The released iron is bound by transferrin (iron transfer protein) and returned to liver and bone marrow.  Globin chains are degraded to amino acids by protein degrading enzyme systems, Bilirubin (known as unconjugated bilirubin) is bound to albumin and transpoted from RES tissues to hepatocytes (liver), In hepatocytes, bilirubin is converted to bilirubin glucronate by adding glucronate. Bilirubin glucronate is known as conjugated bilirubin.  Approx. 0.2-0.8 mg/dL of unconjugated bilirubin presents in the blood. The bilirubin-diglucronide is excreted by hepatocytes to the biliary canaliculi, Normal adult serum contains only small amount of conjugated bilirubin (0.0-0.3 mg/dL ).  LIVER FUNCTION ALTERATIONS DURING DISEASE-JAUNDICE Jaundice (icterus) is a general term that defines abnormal metabolism or retention of bilirubin, Jaundice causes a yellow discoloration of the skin, mucous membranes and sklera.  TYPES OF JAUNDICE It is typically seen at the serum levels approx. 5 mg/dL. The primary types of jaundice are; Prehepatic Hepatic Posthepatic  Prehepatic jaundice; acute or chronic hemolytic anemia. Hepatic jaundice includes disorders of; 1. Metabolism and transport defects Gilbert’s disease Dubin-Johnson syndrome Craig-Najjar disease 2. Neonatal physiological jaudince 3. Disease resulting in hepatocellular injury or destruction. Posthepatic jaudince is generally caused by obstruction (occlusion by stones, compression by tumors).  MECHANISMS OF HYPERBILIRUBINEMIA (EXPLANATIONS FOR SL IDE 23) Mechanisms of hyperbilirubinemia. A) Normal bilirubin metabolism. B) Gilbert disease and certain drugs (e.g. irinotecan): defective bilirubin uptake from the blood, resulting in unconjugated hyperbilirubinemia. C) Physiologic jaundice of the newborn and Crigler–Najjar syndrome, inability to conjugate bilirubin. D) Hemolytic anemia, the capacity of the hepatocytes is overwhelmed, resulting in unconjugated hyperbilirubinemia. E) Dubin–Johnson syndrome: Hepatocytes are unable to secrete conjugated bilirubin into the biliary system. F) Obstruction in the biliary outflow tract (e.g., gallstones, tumor, mass) results in backup and reabsorption of conjugated bilirubin.  LIVER FUNCTION TESTS Enzymes (Liver enzymes) Bilirubin Serum proteins Protrombine time Urea and ammonia  LIVER ENZYMES Liver function tests are frequently used to identify the liver disease. Liver enzymes: ❖Alkaline phosphatase (ALP) ❖Gamma-glutamyltransferase (GGT/γGT) ❖Aspartate aminotransferase (ALT)/Alanine aminotransferase (AST)  ALKALINE PHOSPHATASE (ALP) ALP is a group of enzymes that catalyze monophosphate esters of an alkaline pH, Enzymes present almost all tissues, ALP activity is highest in liver, bone, intestine, kidney and placenta.  ALKALINE PHOSPHATASE (ALP) ALP activity increases greatly (10 fold) after a extrahepatobiliary obstruction (such as cholelithiasis or gallstone), Intrahepatic biliary obstruction has a mild increase (2-3 fold), Hepatocyte necrosis does not elevate ALP activity unless an associated biliary disease.  ALKALINE PHOSPHATASE (ALP) The most common bone disease causing elevation of ALP are Paget’s disease, Rickets and osteomalacia.  GAMMA-GLUTAMYLTRANSFERASE (GGT) GGT is a membrane-located enzyme that plays roles in glutathione metabolism and amino acid resorption from glomerular filtrate. GGT activity is highest in the renal tissue, but serum GGT is elevated as a result of liver disease.  GAMMA-GLUTAMYLTRANSFERASE (GGT) Serum GGT is elevated earlier than other liver enzymes in the disease such as, Acute cholecytitis Acute pancreatitis Acute and subacute liver necrosis Liver metastasis of neoplasms.  GAMMA-GLUTAMYLTRANSFERASE (GGT) GGT gives the opportunity to distinguish of liver diseases from other disease in which ALP is high. GGT is normal in bone disease.  AST & ALT AST and ALT catalyse the conversion of aspartate and alanine to oxaloactate and pyruvic acid respectively, The highest ALT levels found in liver, AST is present in heart, skeletal muscle and liver nearly the same extent, At the onset of viral jaundice both enzyme increase rapidly, Remains elevated 1-2 weeks.  AST & ALT In a acute liver necrosis; both ALT and AST increase significantly, incerase in ALT higher than AST, In cirrhotic liver necrosis; ALT/AST elevated but generally not above 300 U/L, Neoplastic disease also elevates serum transaminases.  LACTATE DEHYDROGENASE (LDH/LH) LDH activity is highest in the kidney and heart, When only liver is known to be involved measurement of LDH can be useful, Erythrocytes have high level of LDH, hemolyzed serum samples should not be analyzed.  SERUM PROTEINS IN EVALUATION LIVER FUNCTION Serum albumin is low in chronic liver disease. In chronic active hepatitis; albumin/globin (IgM and IgG) decreases.  SERUM PROTEINS IN EVALUATION LIVER FUNCTION A decrease in serum albumin is not specific for liver disease because it is also seen in malabsorption, malnutrition and renal disease. Coagulation factors also produced by the liver and significantly decrease in presence of a liver disease.  PROTHROMBIN TIME Prothrombin is one of the key proteins in the blood coagulation system. Prothrombin is converted to the active form, thrombin, catalyses the conversion of fibrinogen to fibrin, thus ensuring clot formation. Prothrombin is produced by the liver. Because of its short half-life, PT is represents a very sensitive test for liver protein synthesis function.  PROTHROMBIN TIME The “Prothrombin Time" (PT) is one way of measuring how long it takes blood to form a clot, and it is measured in seconds (12-15 sec). A normal PT indicates that a normal amount of blood-clotting protein is available. A longer PT usually means that there is serious liver damage or cirrhosis.  UREA & AMMONIA IN EVALUATION OF LIVER FUNCTION Ammonia (a toxic end product of amino acid metabolism) is transported to liver and converted to urea (a water-soluble, nontoxic product). Urea passes to blood and then to urine. UREA AND AMMONIA IN EVALUATION OF LIVER FUNCTION Adult patients exhibit elevated blood ammonia in the terminal stage of liver cirrhosis, acute and subacute liver necrosis. Liver disease (without a renal impairment) causes low serum urea levels.  VIRAL HEPATITIS Hepatitis A, B, C, D, and E are the main viral causes of hepatitis in humans. Their primary infection site is the liver. They are further grouped by therir primary route of transmission: the fecal-oral route or the blood-fluid route. Hepatitis A (HAV) and hepatitis E (HEV), and hepatitis B, C, and D (HBV, HCV, and HDV) are transmitted through the blood-fluid route.  VIRAL HEPATITIS All 5 types can cause acute viral hepatitis, which is marked by necrosis and inflammation of the liver. Although hepatitis A and E cause only acute hepatitis infection, hepatitis B, C, and D can cause both acute and chronic forms of infection.  HEPATITIS A Approx. 25% of the worldwide cases of acute hepatitis are caused by HAV. There are 8 genotypes of HAV, four of which can infect humans, They are so closely related to each other antigenically that there is only one serotype. HAV replicates only in the liver and virus is excreted into bile and then into the intestine, High concentration of HAV can be found in the stool.  DIAGNOSIS OF HAV INFECTION The earliest marker of HAV infestion is the presence of anti-HAV (aHAV) IgM, Past infection is detected when the combination of the absence of anti-HAV IgM and the presence of a aHAV IgG (indicated by total HAV) is evident. Nucleic acid test, such as PCR can be used to detect enviromental contamination by HAV.  MONITORING HAV INFECTION Serum ALT and bilirubin levels or aHAV IgM can be used to monitor the infection. Usually, ALT levels will return to within the reference interval 5 to 7 weeks after the initial elevation, aHAV IgM becomes undetectable several months following normalization of the serum ALT level.  CLINIC AL VIROLOGIC AL AND SEROLOGIC AL EVENTS ASSOCIATED WITH HEPATITIS A VIRUS INFECTION  HEPATITIS B The fatality rate following HAB infection is 0,5- 1,5%, and most patients infected with HBV will recover completely. More than 10% of HBV-infected patients will become chronic carriers. Approx. 25% of chronic HBV carriers infected perinatally will die from cirrhosis or liver cancer. Immunization with hepatitis B surface antigen vaccine very efficient at preventing HBV infections.  LAB TEST FOR HBV Lab. findings in the acute phase ot the infection include; HBV serological markers, Elevations in ALT and AST, Serum bilirubin, A prolonged prothrombin time indicates fulminant liver failure (occurs in 0,1% to 0,5% of the acute HBV infections). SEROLOGICAL MARKERS  DIAGNOSTIC TEST FOR HBV The detection of serum HBsAg is used as the diagnostic marker for current infection of hepatitis B. Its appearance in blood is the earliest serological markers. It is usually seen less than 4 weeks post infection. Serum levels of HBsAg has a peak around 8-12 weeks, Fall during the recovery phase, and generally become undetectable within 6 months of the onset of acute infection. SEROLOGIC AL EVENTS ASSOCIATED WITH HEPATITIS A VIRUS INFECTION