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MLT Enzymes and Bili
MLT Enzymes and Bilirubin Testing
Question | Answer |
---|---|
What is the largest gland and most versatile organ in the body, and how much does it weight? | Liver; 1400-1600 grams |
What does total loss of liver function result in? | It results in death from hypoglycemia within 24 hours |
What are the 2 major vessles that supply the liver with blood? | Hepatic Artery and Portal Vein; 15ml blood/min |
What supplies 20% of hte overall blood and mojority of the O2 to the liver? | Hepatic Artery |
What drains the GI tract and transports most recently absorbed material from the intestines? | Portal Vein |
What is the functional unit of the liver? | Hepatic Lobule |
What is the Hepatic Lobule composed of? | "Cords" of hepatocytes (liver cells) |
What are Sinusoids? | Thin walled vessles between the cords; Lined by Endothelial and Kupffer's (phagocytic in nature) cells |
What is the most important function of the hliver? | Excretion of bile |
What is BIle? | The main digestive chemical synthesized by the liver |
How much bile is produced in one day? | 3 liters |
What is formed in the liver from cholesterol? | Primary bile acids, cholic acid, and chenodeoxycholic acid |
What are bile acids conjugated with to form bile salts? | Glycine or Taurine |
Where is Bile stored during fasting or between meals? | Gallbladder |
How many times does bile circulate daily? | 2-5 times |
All plasma protein and all blood clotting factors are produced in the liver except which one? | Clotting factor 8 |
What enzymes are produced in the liver? | AST, ALT, SGOT, ALP, 5NT, and GGT |
What is glycogenesis? | formation of glucose by the breakdown of glycogen |
What is the breakdown of glycogen due to hydrolysis? | Glycogenolysis |
What is the formation of glucose from noncarbohydrate sources? | Glyconeogenesis |
Where is the major site of chylomicron remnants removal? | Liver |
What are the fat soluble vitamins? | A, D, E, K |
What is Somatomedin? | Group of peptides formed in the liver that mediates growth |
What is the most important mechanism of detox and drug metabolism in the liver? | What is the Microsomal Drug Metabolism System |
What is the waste product of RBC breakdown and is the principal pigment in bile? | Bilirubin |
When Hgb is destroyed, what happens to its components (protein, iron and porphyrin)? | Both iron and protein are reused and porphyrin is broken down as waste |
How is bilirubin transported to the liver? | It is attached to albumin |
What enzyme is used to catalyze the cinjugation of bilirubin? | Uridyldiphosphate glucuronyul transferase (UDPGT) |
ctWhat is another name for conjugated bilirubin? | Bilirubin Diglucuronide or Direct bilirubin |
How is urobilinogen excreted in the stool? | It is oxidized to Urobilin (producing red-brown color), and excreted in teh stool |
What product of bilirubin metabolism is excreted in the urine? | Urobilinogen |
What is Jaundice? | Yellowish pigment inteh sclera of the eyes, skin, and mucus membrane due to the rise of bilirubin concentration in the blood |
What are the causes of Prehepatic /Hemolytic Jaundice? | Increased RBC destruction, larger load than liver can handle |
What type of bilirubin is elevated when a patient has Prehepatic/Hemolytic Jaundice? | Unconjugated Bilirubin |
What conditions are associated with Prehepatic/Hemolytic Jaundice? | Autohemolytic anemia, HDN, and Incompatible transfusion |
What are the causes of Hepatic Jaundice? | Inpaired cellular uptake of bilirubin, Defective conjugation, and abnormal secretion of bilirubin by the liver cells |
What disease is associated with Hepatic Jaundice? | Hepatitis A |
What is the cause of Post Hepatic Jaundice? | Impaired excretion of bilirubin caused by mechanical obstruction of the bile into the intestines |
What type of bilirubin is elevated when there is an obstruction of the common bile duct? | Conjugated bilirubin |
What are enzymes? | Specific biologic proteins that catalyze biochemical reactions |
How do enzymes operate? | They operate by lowering the energy of activation |
What are the structures of enzymes? | enzymes are proteins in nature, structures are primary, secondary, tertiary and quarternary |
What does the lock and key model assume? | Assumes that an enzyme active site will only accept a specific substrate |
What does the induced fit model recognize? | it recognizes that there is much flexibility in an enzyme's structure and that an enzyme is able to conform to a substrate |
What are reactants in an enzymatic reastion called? | Reactants |
What are the factors influencing enzymatic reactions? | Ph ( 7-8), Temp (optimal temp is 37 C), Substrate concentration , and enzyme concentration |
What is first order Kinetics? | Reaction rate is directly proportional to substrate concentration |
What is zero order kinetice? | Reaction rate is directly proportional to enzyme concentration |
What happens to the enzyme reaction rate when the normal pH and temperature ranges are exceeded? | Reaction rates are reduced |
Once optimum temp is reached, what happens to the enzyme if temp is increased further? | Denaturation of the enzyme |
What are cofactors? | nonprotein entities that must bind to a particular entities before a reaction occurs; the prosthetic group needed to activate the apoenzyme |
What is a apoenzyme? | Protein portion of enzyme that's almost ready to work.; needs cofactor |
what acts as a second substrate, is consumed during reaction and must be in excess quantity of the substrate? | Coenzyme |
What is a second unit that temporarily binds to an apoenzyme in order for it to work? | Coenzyme |
What is an inhibitor? | Any chemical substance interferring with enzyme reactions |
When does enzyme inhibition occur? | Occurs when a substance known as an inhibitor binds to an enzyme and decreases its activity |
Which inhibitor physicall binds to the active site, and can be reversed by increased substrate concentration to saturated point? | competitive Inhibitor |
Which inhibitor binds to an allosteric site (point other than active site), and can't be overcome by adding more substrate? | Non-competitive Inhibitor |
Which inhibitor binds to enzyme-substrate complex preventing product formation? | Uncompetitive inhibitor |
What is the measurement of catalytic activity? | Quantitation |
What is it when the reaction is measured after a predetermined time | End-point (colorimetric or direct) |
What is it when the reaction is measured at specific time intervals, usually 30 or 60 seconds? | Multipoint (rate or kinetic) |
How are enzyme concentrations expressed? | IU/L (international units/Liter) |
What is an international Unit? | the amount of enzyme that will catalyze reaction of 1 micromole of substrate per minute, at optimal conditions |
What is the function of Creatine kinase (CK)? | catalyzes the reversible phosphorylation of creatine, utilizing ATP |
What are the tissue sources when testing for CK? | Skeletal Muscle, Heart , and Brain |
What are elevated levels of CK used to detect? | Disorders of muscle and cardiac tissue; bis e4-8 hrs, peaks 12-24 hrs, and normal in 48-72 hrs |
What is CK-BB (brain type0? | An isoenzyme that migrates fastes in an electric field |
What is CK-MB (hybrid type)? | An isoenzyme that migrates second furthest, and is elevated in AMI and serious muscle disorders |
Which isoenzyme doesn't migrate and is elevated in AMI, muscle disorders and muscle trauma? | CK-MM (Muscle type) |
What is the purpose of Lactose Dehydrogenase (LD)? | Catalyzes the conversion of lactic acid and pyruvic acid |
What are the tissue sources for LD? | S.H.E.L.K.- Sleletal muscles, Heart, erythrocytes, Liver, Kidney |
In cardiac disorders, when does LD levels Rise, peak and return to normal? | rise 12-24 hrs, Peaks 48-72 hrs, normal in 7-10 days |
When LD rises for Hematologic/Neoplastic disorders, when are highest levels seen? | In Pernicious Anemia |
When are the isoenzyems for LD elevated? | LD1/ LD2 - elevates in AMI and anemias; LD3- elevates in pulmonary disorders; LD4/LD5 - elevates in hepatic damage and muscle trauma |
Where are the highest concentrations of Aspartate Aminotransferase (AST) found | Cardiac Tissue, Liver, and Skeletal Muscles |
What are the elevations of AST limited to? | Hepatocellular disorders( acute disorders, Viral hepatitis and Cirrhosis) and Skeletal muscle involvement (Muscular dystrophies and inflammatory conditions) |
Where are the highest concentrations of Alanine Aminotransferase (ALT) found , and where are higher elevations seen? | Highest concentration in teh liver; higher elevations seen in hepatocellular disorders |
Where are the highest concentrations of Alkaline Phosphatase (ALP) found? | Intestine, liver, bone, spleen, placenta, and kidney |
Elevations of ALP are significant in the evaluations of what disorders? | Hepatobiliary and bone disorders; In the bone elevations observed when there is involvement in Osteoblast |
Why is ALP elevated during pregnancy? | Due to the production of ALP in the placenta; can be detected between 16 and 20 weeks |
What is the richest source of Acid Phosphatase (ACP)? | prostate; aids is diagnosing prostatic carcinoma, and in the investigation of rape |
Which enzymeis an excellent indicator fo chronic alcoholism and is useful in monitoring the effects of abstention from alcohol? | Gamma Glutamyltranspeptidase (GGT) |
Which enzyme is used for the breakdown of starch and glycogen and is helpful in the diagnosis of acute pancreatitis? | Amylase; also elevated in mumps |
which enzyme is used to hydrolyze the esterfication of fats to produce alcohols and fatty acids, and is also helpful in the diagnosis in acute pancreatitis? | Lipase |
Which enzyme catalyzes the oxidation of glucose-6-Phosphate to 6-Phosphogluconate? | Glucose-6-Phosphate Dehydrogenase (G6PD) |
what are the tissue sources for testing G6PD? | Erythrocytes, Spleen, Adrenal Cortex, Thymus, Lymph Nodes, and Lactating mammary glands |
What is the function of G6PD in RBC's and what cal it lead to? | protects RBC's from oxidants and can lead to drug-induced hemolytic anemia (antimalarial drugs) |
What catalyst is used in the Evelyn-Malloy's method of bilirubin testing? | 50% methanol |
What catalyst is used in Jendrassic-Grof's method of bilirubin testing? | Caffein |
What are the specimen requirements for bilirubin testing? | Serum or plasma; sample must be protected from light |
What are the adult reference ranges for bilirubin? | conjugated (direct) 0 - .2 mg/dl; Unconjugated (indirect) .2 - .8 mg/dl; Total bili .2 - 1.0 mg/dl |
What is the total bilirubin referance ranges for premature infants? | (24 hr 1- 6 mg/dl); (48 hr 6- 8 mg/dl); (3 - 5 days 10- 12 mg/dl) |
What is the reference ranges for bilirubin in a full term infant? | (24 hr 2 -6 mg/dl); (48 hrs 6-7 mg/dl); (3 - 5 days 4 - 6 mg/dl) |
What are the reference rangen for total CK? | Male 15 - 160 U/L; female 15 - 130 U/L |
What is the reference range for CK-MB? | , 6% of total CK |
What is the refereence range for total LD? | Serum 100 - 225 U/L |
What are the normal fractions for LD isoenzymes? | (LD1 14- 26% of total); (LD2 29 - 39% of total); (LD3 20 - 26% of total); (LD4 8 - 16% of total); (LD5 6 - 16% of total) |
What is the normal reference range for AST? | serum 5 - 30 U/L |
What is the reference range for ALT? | serum 6 - 37 U/L |
What is the reference range for ACP? | prostatic 0 - 3.5 ng/ml |
What is the reference range for GGT? | males 25 - 130 U/L; Females 5 - 30 U/L |
What is the reference range for AMS? | serum 25 - 130 U/L; Urine 1 -15 units/hr |
What is the reference range for Lipase? | serum 0 - 1 U/ml |
What is the reference range for G6PD? | serum 0 - 0.18 U/L |
What is the purpose of enzyme testing? | To determine the level of specific enzymes in the blood |
What are the methodologies of enzyme testing? | All are either Colorimetric (direct0 or Kinetic (indirect/rate) |
What is the methodology for amylase testing? | Colorimetric; Use of a starch-iodine reaction, measured in Somogyi units |
What are Somogyi Units? | Expression of the number of milligrams of glucose released in 30 minutes at 37 C |
What is the methodology used to test for lipase? | Cherry-Crandall Method; uses olive oil as a substrate and measures the liberated fats by titration after a 24 hour period |
What are the specimen requirements for enzyme testing? | Serum; hemolysis affect most enzymes |
Which enzyme requires an EDTA sample? | G6PD |
What enzymes are used in LFT assessment? | ALP , Aminotransferases (AST & ALT), and 5NT (5 Nucleotidase) |
What is the use of 5NT? | Used in conjunction with ALP to differentiate liver from bone involvement when phosphatase elevations are seen; elevations indicate liver involvement |
What is the first enzyme seen in the serum of heavy drinkers? | GGT |
What are the most frequently used enzymes for diagnosing/monitoring AMI? | CK, AST, and LD |
Which pattern is the most relaible diagnostic criteria for detecting AMI? | Pattern 1; CK-MB >= 6% total CK, LD1 > LD2 |
Which pattern indicates some degree of MI but not necessarily AMI? | Pattern 2; CK >= 6% total CK-MB, LD2> LD1 |
Which pattern indicates no AMI occured, regardless of LD isoenzyme data? | Pattern 3; CK-MB < 6% total CK |
Which pattern usually indicates noncardiac disorder such as, intravascular homolysis, renal cortex infarction, and megaloblastic anemia? | Pattern 4; CK-MB < 6% total CK, LD1 > LD2 |
What are the most frequent enzymes used in evaluating Hepatocellular disorders? | AST, ALT, LD, and LD-5 |
What are the most frequent enzymes used in evaluating biliary tract obstructions? | ALP, GGT, 5NT, and LAP |
What is the most sensitive enzyme for liver disorders? | GGT |
What enzymes are most frequently ised in evaluating sleletal muscle disorders> | CK, AST, LD, and Aldolase |
What are some conditions where enzyme elevations are seen? | Myopathies, Muscle trauma, Physical exertion, and intramuscular injections |
What are some conditions where enzyme levels stay normal to only slight elevated? | Multiple Sclerosis, Masthenia Gravis, and poliomyelitis |
Where is the highest level of CK seen? | Muscular Dystrophy |
What is the major enzyme associated with bone disorders? | ALP, specifically ALP-bone fraction |
Which enzyme is increased in bone cancers? | Increased fraction of ACP & ALP |
Which enzyme is increased in liver metastases? | Increase in ALP |
Which enzyme is increased in Cellular Metastases? | LD elevations can be seen in AML, ALL, and CLL; markedly evevated level of LD indicative of ALL |
Which 2 enzymes are helpful in the diagnosis of acute pancretitis? | Amylase (rise 2 - 12 hrs, peak 24hrs, normal in 3 days), and Lipase (elevation follow AMS, takes up to 14 days) |