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MLT Enzymes and Bili

MLT Enzymes and Bilirubin Testing

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)
Created by: Nsikanete