Enzymes Liver Pancreas

Cell destruction Cell Proliferation Increases synthesis oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases       Substrate concentration Enzyme concentration pH Temperature Cofactors inhibitors

Elevation of enzyme levels caused by:

Enzyme Classification: 6 classes:

Factors that influence enzymatic reactions 6

Enzyme reactions requires: 4 Zero Order difference in rate? Why?

1.Enzyme 2.Substrate 3.E-S complex 4.End Product the at nearby concentrations of substrate is almost negligible At these concentrations almost all of the enzyme molecules are bound to substrate and the rate is independent of substrate, zero order. At substrate concentrations near point A the rate appears to be directly proportional to substrate concentration At the substrate concentration exactly half the enzyme molecules are in an ES complex at any instant and the rate is exactly one half of Vmax concentration of substrate that gives "halfmaximal activity". if enzyme is elevated that all substrate is consumed early in reaction. Then the rate change is minimal = Errors sudden decrease in reaction rate, may indicate that the patient sample containing a enzyme level requires a dilution or decreased amount. Lipase: Triglyceride substrate Omylase: Starch substrate Elevated in liver and bone disorders Normal elevations in children and during pregnancy. 1

reaction rate - first order

½ Vmax = Point B

Constant Km =

Fixed Time problem

Kinetic problem Acute pancreatitis enzymes

Alkaline Phosphatase

vitamins. Because of its covalent bond during the recovery phase of hepatocellular jaundice it may persist in the blood for a week or more after urine clears.aspartate transaminase GGT . in conventional methods it is measured as part of conjugated bilirubin. AST. toxic agents etc. drugs. 1.Which is sensitive indicator of alcoholism? first organ to encounter nutrients.gamma-glutamyltranspeptidase Alkaline phosphatase Aldolase 1.CK. Excretory 3.GGT Liver viruses (hepatitis). alkaline PO4 4.Which enzymes are helpful in diagnosis of muscle disorders? 3.Alk PO4 delta bilirubin Liver function evaluated with enzyme testing 1.ALT. ALT. Detoxification and protective 4. LD. aldolase 3.AST.GGT 5. Synthetic and Metabolic 2. Hematology/Coagulation FUNCTIONS OF LIVER CATEGORIES of LIVER DISEASE (amyloid.Which enzymes tests for hepatic function? 4. neoplasm) 2 .Is AST or ALT more specific for liver disease? 6.Which is helpful in diagnosing bone disease? 2.Which one enzyme is most sensitive for all types of liver disease? 5.alanine transaminase AST . Most common liver injury is due to 2.Enzymes Liver Pancreas Acid Phosphatase Elevated in prostatic cancer Tested for as confirmation in rape cases if found in vaginal fluid fraction of bilirubin covalently bound to albumin.ALT is primarily found in liver & RBCs 6.

viral. Drug Induced: Most common fatty liver (vacuoles of fat) drugs LIVER DISEASES 4 categories Most Common? Steatosis HEPATOTOXIC AGENTS many Halothane Necrosis means neoplasia BILIRUBIN Conjugated (water soluble) bilirubin is excreted from liver into the removes the glucuronide from bilirubin and reduces bilirubin to premature death of cells in living tissue The formation or presence of a new. abnormal growth of tissue. excreted in 2 ways how? urine or oxidized to form urobilin and excreted in feces. urobilinogen. drugs Tumors: uncommon in US but common in other cultures for unknown reasons.Enzymes Liver Pancreas Cirrhosis: Inflammation of the liver: scaring and abnormal architecture of the liver Alcohol is common cause Autoimmune. but measures as conjugated 3 Delta bilirubin . Reye’s Syndrome: death from liver destruction following viral infection. bile. turns color which gives feces and urine its color. BILIRUBIN METABOLISM Excreted as: 2 chemicals? Where? stays attached until the albumin molecule is turned over. associated with aspirin use.

Overproduction 2. 1.transferase Acquired: drug inhibits the enzyme Neonatal jaundice: the enzyme is not fully developed yet 4 JAUNDICE 2 kinds total bilirubin = normal Classification of Jaundice Prehepatic Hepatic Jaundice Posthepatic Jaundice BILIRUBIN IN BLOOD 2 causes Defective Conjugation Gilbert’s syndrome Crigler-Najjar syndrome Defective Conjugation Non-inherited . Defects in the conjugation reaction 4. decrease of bilirubin transport into hepatocytes deficiency of UDPG. (3) Defective Conjugation (4) Reduced Excretion: Damage to liver cells. rate of hemolysis exceeds liver’s ability to clear bilirubin. obstruction of common bile duct by gall stones. neoplasms.0 mg/dL). hepatitis.5 . (5) Obstruction: Mechanical obstruction of bile flow. (2) Impaired Uptake by Liver Cells: drugs block bilirubin uptake into liver hepatocytes. no bilirubin in urine defective conjugation. Conjugated bilirubin rises.Enzymes Liver Pancreas Clinical manifestation of hyperbilirubinemia Icterus and mucous membranes Kernicterus: blood brain barrier < 1 mg/dL (hemolytic) unconjugated hyperbilirubinemia. hepatocellular damage or necrosis inability to transport conjugated bilirubin out of liver. sickle cell disease). transport failure. (hemolytic anemia. HYPERBILIRUBINEMIA jaundice with yellow skin and sclera (2. gallstones in bile duct Mostly conjugated bilirubin rises. drug induced.5. Impaired uptake by liver cells 3. cirrhosis. spasms or stricture. Obstruction to the flow of bile (1) Overproduction: due to excess RBC destruction. Reduced excretion into the bile 5. Almost all unconjugated.

hemolytic disease and defective liver-cell function (hepatitis) Direct Bilirubin = Indirect Bilirubin = BILIRUBIN REFERENCE INTERVALS -2 days) -5 days) Direct Elevated conjugated implies Conjugated Elevated (cholestasis) In the liver 2 categories of reasons Unconjugated Elevated In the liver 3 categories of reasons 5 .0 Direct 0 .2 mg/dL liver disease or bile ducts Decreased secretion into canaliculi hepatitis and/or drugs Decreased drainage stones in gall bladder carcinoma drugs tumors cirrhosis  RBC hemolysis  Inhibition of transport into hepatocyte by drugs  Decreased conjugation Neonatal jaundice Inhibition of enzyme by drugs Gilbert Syndrome UROBILINOGEN metabolism.Enzymes Liver Pancreas BILIRUBIN TERMINOLOGY Total Bilirubin = All forms of Bilirubin= Direct + Indirect+ Delta water soluble conjugated Bilirubin – diglucuronide and delta Bilirubin (albumin bound) not water soluble alcohol soluble requires accelerator unconjugated Bilirubin toxic .5 -5 days) 1.5 – 12.4 – 11.1.0 mg/dL -2 days) 3.0. a brown pigment. Bacteria in intestines converts urobilinogen into urobilin.

aid absorption of cholesterol and triglycerides Liver Proteins Transthyretin Ceruloplasmin Alpha1 antitrypsin Haptoglobin Beta2 microglobulin Transferrin Alpha fetoprotein (Transports/ binds iron) (Copper carrier) (Acute phase protein) (Transports/ binds free Hb) Bile Acids (Prealbumin:nutritional indicator) (early liver cancer marker) ALBUMIN Chronic Hepatitis Acute Hepatitis hepatocytes as a marker of general liver function. purple color formation with Ehrlich’s reagent (pdimethylaminobenzaldehyde).5 – 5.22 mg/dL 6 .Enzymes Liver Pancreas biliary obstruction. -21 days INCREASED ALBUMIN In 4? Albumin – Normal Range Transthyretin (prealbumin) RI 3.5 g/dL 18 .

fungus. cancer Bile Duct Disease primary biliary cirrhosis Drug-Induced cholestasis Liver Infiltration cancer. ALT seldom more than 5x.no effect ALKALINE PHOSPHATASE REFERENCE INTERVALS 44 to 147 IU/L Bile Duct Obstruction gall stones. maybe normal) AST:ALT ratio  ALT Male: 10-40 U/L Female: 7-35 U/L ALKALINE PHOSPHATASE Factors effecting ALP inhibits enzyme activity -3 X .Enzymes Liver Pancreas AST & ALT: OTHER FACTORS Hemolysis Age/ Gender Diurnal Variation Race Exercise Body weight Muscle injury AST Reference Range ALT Reference Range 5-30 U/L -50 then decreases > ALT 6-37 U/L  Less than 1:1 viral hepatitis nonalcoholic steatohepatitis Greater than 1:1 (2:1. surgery. 3:1) chronic alcohol-induced liver damage (AST rarely more than 8x normal. sarcoidosis may give highest values 7 MARKEDLY ELEVATED ALP (Normal or slightly elevated AST ALT) .

gastric hypersecretion.37 U/L female . disease Reference Ranges ALT AST ALP GTT . may be consequence of high ammonia (up to 5x) GASTRIN hormones.90 U/L age important .45 U/L male 5 – 30 U/L Female AMMONIA (NH3) Elevated in blood when liver failure levels low in Serum Encephalopathy. elevated gastrin Acute Pancreatitis Blockage of pancreatic duct with gallstones Alcohol excess Physical Trauma Chronic Pancreatitis Gall Bladder disease Alcoholism Pancreatic Cancer 4th most frequent form of fatal cancer 5 year survival <5% Pancreatic Insufficiency Cystic Fibrosis Chronic Pancreatitis Pancreatic diseases 8 . and enzymes Zollinger-Ellison syndrome : Gastric-producing tumor leading to peptic ulcers.Enzymes Liver Pancreas high concentrations of kidney and liver but also pancreas and intestine GGT -Transferase from liver.30 U/L . or damage to nerves in the brain.

pulmonary infections. Mucus obstructs pancreatic secretions from reaching duodenum Manifestations: intestinal obstruction. titrate fatty acids using pH indicator Turbidimetric: measure decrease in turbidity due to hydrolysis of substrate coupled with enzymatic reaction LIPASE: Testing METHODS Fecal Fat analysis Other pancrease test mutations in a gene located on chromosome 7.Enzymes Liver Pancreas AMYLASE particularly acute pancreatitis AMYLASE: Testing METHODS formed Amyloclastic: measure decrease in starch substrate from dye-labeled substrate Hydrolyzes triglycerides LIPASE earlier and persist longer Titrimetric: olive oil substrate. malabsorption CYSTIC FIBROSIS 9 . Causes production of thick mucus due to faulty transport of Na and Cl within cells lining lungs and pancreas.

nutritional supplementation. Gene Therapy CYSTIC FIBROSIS Symptoms Treatment: CYSTIC FIBROSIS DIAGNOSIS SWEAT CHLORIDE ANALYSIS CONSIDERED MOST RELIABLE SINGLE TEST FOR DIAGNOSIS OF CYSTIC FIBROSIS Elevated sweat sodium and chloride (>60 mmol/L) in cystic fibrosis Iontophoresis.Enzymes Liver Pancreas Symptoms: salty-tasting sweat. using drug pilocarpine to induce sweat Sweat is collected on preweighed gauze Chloride/ Na is measured d-Xylose: pentose sugar not normally in blood Ability to absorb D-xylose helps in diagnosing malabsorption problems in intestine vs pancreatic insufficiency Test Fast. wheezing or pneumonia. antibiotics. poor weight gain. void in AM. bulky stools Treatment: vigorous percussion on back and chest. drink d-Xylose and water Collect blood at 2 hours. persistent coughing. and Urine collected after 5 hours SWEAT CHLORIDE ANALYSIS Tests of Intestinal Function D-Xylose Absorption Test 10 . using drug pilocarpine to induce sweat Sweat is collected on preweighed gauze Elevated sweat sodium and chloride (>60 mmol/L) in cystic fibrosis Iontophoresis.