Clinical Enzymology

Question 1

describe CK-MM (CK-3)

Answer 1

• represents 98% of total CK in the skeletal muscle and the remaining is 1-2% CK-MB
• Chest muscle and smooth muscle contain more CK-MB but not as much as heart

Question 2

what causes elevated CK-MM

Answer 2

• Damage of skeletal muscle leads to elevated creatine kinase with mostly CK-MM in the serum
• CK-MM is elevated in diseases of rhabdomyolysis or muscular dystrophy

Question 3

24 hours after MI

Answer 3

• CK-MB level peaks
  
  • 80 KD
  • fast diffusion
  • 1/2 life 18 hours in blood

Question 4

48 hours after MI

Answer 4

• LDH (lactase dehydrogenase) levels peak
  
  • 140 KD
  • 1/2 life 5 days in blood

Question 5

describe ratio of LDH among heart/rbc/muscles/liver

Answer 5

Question 6

describe the flip

Answer 6

• Normal serum shows a low LDH1/LDH2 ratio
  
  • consistent with RBC, since they are often damaged normally resulting in their LDH leaking into blood
• After MI: the heart LDH isozymes will be released into the blood creating a high LDH1/LDH2 ratio which will now dominate the blood
• Not an early marker; shows in blood 1-2 days after MI
  
  • ​not advisable to measure several hours after MI

Question 7

what is measured as heart injury markers?

Answer 7

• Troponin is not an enzyme but rather a protein found in muscle
• Cardiac muscle specifically has cTnI and cTnT which are measured as heart injury markers
  
  • “IT guys tell you about the heart”
• Troponin C is not measure bc it does not have an isoprotein that is specific for the heart

Question 8

what is a likely marker for MI?

Answer 8

• when CK-MB >3% and there is an increase in cTnI or cTnT
• the severity of an MI is indicated by % of CK-MB of total CK

Question 9

what are the early MI markers in serum?

Answer 9

• Through an ELISA test:
  
  • CK-MB (sharp peak)
  • cTnI and cTnT
  • myoglobin (unspecific for the heart)
    
    • earliest marker
• The enzyme levels and the cardiac troponin levels peak later on

Question 10

what are MI markers in serum after days?

Answer 10

• To evaluate whether an individual suffered an MI several days ago, different serum injury markers are measured
  
  • serum CK and CK-MB are down to baseline level and the test to measure cTnI and cTnT might not be available
  • One can use serum LDH (higher 1/2 ratio) which has a 1/2 life in serum of about 5 days

Question 11

what are the enzymes measured to test liver cellular integrity

Answer 11

• Alanine aminotransferase (ALT)
• aspartate aminotransferase (AST)
• These enzymes leak out of the liver cells due to membrane damage but the hepatocyte still functions

Question 12

what does the liver function tests test for?

Answer 12

• ammonium
• albumin
• bilirubin

Question 13

describe the function of ALT

Answer 13

• Alanine aminotransferase is an enzyme which has a higher concentration in hepatocytes than in any other cell and it is found in the cytosol
• This enzyme is especially needed for eventual for gluconeogensis and the urea cycle in the liver

Question 14

describe function of AST

Answer 14

• Aspartate aminotransferase is found in high concentration in heart and liver
  
  • found both in cytosol and mitochondria

Question 15

how to test biliary excretory function?

Answer 15

• cholestatic liver enzymes are used for markers
  
  • alkaline phosphatase (ALP)
  • γ-glutamyl transferase (GGT)

Question 16

describe the function of ALP

Answer 16

• ALP cleaves phosphate groups from nucleotides and proteins
  
  • in this process, it generates an alkaline pH
• Hepatic bile canaliculi cells and biliary duct cells have a high concentration of ALP
• Bile is an alkaline fluid

Question 17

describe bile duct obstruction

Answer 17

• Extra-hepatic bile ducts are obstructed by gallstones or tumor (common pancreatic tumor, rare bile duct cancer)
• Serum markers that measure biliary excretion are:
  
  • ALP (most specific)
  • GGT
  • conjugated bilirubin

Question 18

describe the function of GGT

Answer 18

• γ-glutamyl transpeptidase uses glutathione (GSH) which is the specific tripeptide
  
  • γ-glutamyl-cysteinyl-glycine
• GGT is involved with the transport of AAs into cells and in the process GSH is cleaved and resynthesized
• GSH synthesis does not include transcription and translation

Question 19

what are the causes of acute vs chronic pancreatitis

Answer 19

• Acute due to:
  
  • heavy alcohol intake
  • gallstones
• Chronic due to:
  
  • cystic fibrosis
  • hypertriacylglycerolemia
  • years of ethanol abuse

Question 20

what is seen in pancreatitis

Answer 20

• increased levels of serum amylase
• increased levels of serum lipase (panreatic lipase)
• lipase/amylase ratio > 2 is characteristic for ethanol damage

Question 21

name the enzymes markers associated with ethanol abuse

Answer 21

• Cirrhosis or ethanol abuse have a ratio of serum AST/ALT > 2, which is the reverse of liver damage
  
  • liver damage leads to higher serum ALT levels than serum AST levels
• The development of cirrhosis can lead to increase of ALP due to the fibrosis of intrahepatic bile ducts
• Pancreatitis leads to elevated serum lipase and serum amylase
• Ethanol-induced pancreatitis leads to a specific ratio characterized by the serum ratio of lipase/amylase>2

Question 22

describe alkaline phosphatase

Answer 22

• enzyme synthesized in osteoblasts
• involved with bone formation as it creates an alkaline pH by cleavage of phosphate groups
  
  • this is needed for calcium deposits onto collagen of bones
• Increased levels of ALP in serum is a bone injury marker for bone diseases:
  
  • Padget disease
  • bone tumors
• However, high serum ALP is normal in children with growing bones or in women during pregnancy