23. Clinical Enzymology Flashcards
Increased levels of intracellular enzymes in the serum caused by…
Cellular injury
Ranges of Injury (increased enzyme levels)
2-3 times upper limits of normal
Mild
Ranges of Injury (increased enzyme levels)
2-20 times upper limits of normal
Moderate
Ranges of Injury (increased enzyme levels)
Greater than 20 times upper limits of normal
Marked
Multiple forms of the same enzyme.
Catalyze the same biochemical reaction.
Have different biochemical and immunological properties.
Often have a different amino acid sequence or different amino acid composition and can be separated by electrophoresis.
Isoenzymes
Different tissues frequently contain isoenzymes with different proportions of subunits. So what can you do in case of cell damage?
In case of cell damage, the resulting particular serum pattern can indicate the affected organ.
Catalyzes a reversible reaction.
At high ATP levels, Creatine Phosphate (CrP) is formed.
At high CrP levels, ATP is formed using the energy-rich CrP.
Creatine Kinase (CK)
Kinase adds atp to something.
These three Creatine Kinase (CK) isozymes in serum are used as injury markers.
CK containers the two subunits B and M, leading to the three isozymes:
CK-BB (CK-1)
CK-MB (CK-2)
CK-MM (CK-3)
Mainly has CK-BB.
sCK-BB is elevated after CNS damage.
Brain
Has the highest percentage of CK-MB:
30% CK-MB (most CK-MB found in this organ) and 70% CK-MM.
SCK-MB and sCK-MM are elevated after myocardial infarction.
Heart muscle
Has 98% CK-MM and 2% CK-MB
SCK-MM is elevated in rhabdomyolysis or muscular dystrophy
Skeletal muscle
Tetramer of H and M subunits
Lactate dehydrogenase (LDH)
H4 in heart, RBC
LDH-1
H3,M1 in Heart and RBC
LDH-2
M4 in Muscle Liver
LDH-5
Severity is measured by the increase of LDH in serum following RBC destruction
Hemolytic Anemia
Leads to increase of heart LDH isozymes in serum which show a high LDH-1/LDH-2 ratio.
Myocardial infarction.
Since hemolytic anemia is a pathological state more erythrocytes become lyses. Since […] is the main isozyme present in erythrocytes, we will see an exaggerated increase in serum LDH.
Furthermore, we will also see an increase in serum: […], […], […]
LDH-2
Increase in serum: Hemoglobin, Indirect bilirubin, Reticulocytes
Timeframe in serum for MI markers
These levels peak after 24 hours
CK-MB
Timeframe in serum for MI markers
These levels peak after 48 hours
LDH
Total CK found in serum after an MI contains mainly [this] kind of CK but also the heart characteristic [this] kind of CK
After an MI contains mainly CK-MM but also the heart characteristic CK-MB.
A large […/…] ratio indicates a large area of damaged heart muscle.
CK-MB/total CK
One of two criteria for indication of an MI:
The CK-MB/total CK ration is > [..]% (Is larger than)
6%
One of two criteria for indication of an MI:
The CK-MB/total CK ration is > [..]% and troponins are increased.
3%
Proteins involved in muscle contraction
Troponins
Specific troponins isoforms are measured as heart injury markers
Inhibition of actomyosin ATPase
Cardiac troponin I (cTnI)
Specific troponins isoforms are measured as heart injury markers
Tropomyosin binding
Cardiac troponin T (cTnT)
Myocardial infarction leads to myocardial cell death.
And […….] these two biochemical markers accumulate in blood and can be used for the diagnosis of an acute MI:
- Increase in cardiac troponins (cTnI or cTnT)
- Increase in CK-MB
New method used to determine MI injury markers.
Used to measure CK-MB, cTnI, cTnT, and myoglobin
Elisa: Enzyme-linked Immunosorbent Assays
Not all pts suffering from chest pain have MIs.
Chest pain also occurs in Severe exercise, acid reflux, intestinal gas
Cardiac troponins and CK-MB are measured.
An increase can indicate MI.
No increase can rule out an MI in patients with current chest pain and inconclusive ECG.
Myoglobin and CK isoforms
Problem is its non specific. When absent, can rule out MI.
1-2 hours, peaks at 6 hours, back to normal in 2 days.
CK-MB
2-6 hours rises
Peaks at 20 hours
Normal after 2-3 days.
“Early increase, sharp peak after 1 day and back to baseline at 2 days.”
Troponin
Most specific
Peaks in 12-24 hours
Stays up for 7-10 days.
Most sensitive
“Early increase but the stay elevated longer than CK-MB.
cTnT stays longer elevated than cTnI.
Liver injury leads to loss of function and to leakage of membrane
Liver function test examples
Ammonium
High
“Smoke some ammonium and you’ll get high”
Liver injury leads to loss of function and to leakage of membrane
Liver function test examples
Albumin
Reduced
Al is a bum who is reduced to lowest levels
Liver injury leads to loss of function and to leakage of membrane
Liver function test examples
Bilirubin
High
“Let’s get high with Billy and Rubin”
Liver membrane integrity test
Alanine aminotransferase (ALT) - only found in cytoplasm. That’s where “Alan hangs out.”
Aspartate aminotransferase (AST) - In cytoplasm AND Mitochondria. Aspirating due to all the hard work in the mitochondria.
Ratio of ALT/AST can indicate source of liver damage
High ALT/AST ratio is characteristic of…
Hepatic viral infection. (Hepatitis A, B, C, D, E)
Ratio of ALT/AST can indicate source of liver damage
High AST/ALT ratio is characteristic of…
Hepatic alcohol damage.
The alcohol goes to damage mitochondria, so AST released.
Bile duct obstruction
Extra-hepatic bile ducts are obstructed by
-Gallstones (cholesterol gallstones)
-Tumors (tumor in head of pancreas)
Gallstones and tumors are so “Extra”. But really a lot of both of them can happen and is not good.
Bile duct obstruction
Inter-hepatic bile ducts can be irritated in…
Liver cirrhosis.
Injury markers for obstructed bile ducts
Any obstruction in biliary.
- Alkaline Phosphatase (ALP)
- Gamma-glutamyl transferase (GGT)
AL Pacino is Getting GeriaTric. So his bile is obstructed.
[…] is found in high concentration in cells of the bile canaliculi and biliary ducts. […] cleaves phosphatase from nucleotides and proteins which leads to the alkaline pH of bile.
Alkaline phosphatase (ALP)
AL Pacino starts to make alkaline pH of bile.
[…] is bound to the plasma membrane of hepatocytes (liver cells) and is part of the hepatic […] cycle for glutathione (GSH) synthesis.
[…] increase in serum indicated injury in bile ducts and of the liver. It can result from gallstones, ethanol, or medical drugs.
Gamma-glutamyl Transferase (GGT)
Grandma is Getting geriaTric. So lots of gallstones and medical drugs. Can’t explain the alcohol though.
Acute injury of this due to: Heavy alcohol intake (40%)
Gallstone blockage (40%)
Chronic due to: Cystic Fibrosis (CF), Hyperlipidemia, Years of ethanol abuse (alcohol)
Pancreatitis
Acute pancreatitis indicated by increased serum levels of…
Alpha-amylase and pancreatic lipase
Ethanol as pancreatitis
Serum lipase/amylase ratio greater than 2
Gallstones as marker for pancreatitis
Blockage: increase of serum amylase, lipase, ALP and GGT
Chronic pancreatitis
Can show less enzyme increase in serum due to less synthesis inside the pancreas.
Alcohol related damage of liver
Serum: AST/ALT ratio larger than 2
GGT and ALP (cirrhosis)
Alcohol related damage of pancreas
Serum: Lipase/amylase ratio larger than 2
GGT
[…] Found in bone, bile ducts, placenta, and intestine
Alkaline phosphatase
ALP in bones creases an alkaline pH for calcium deposition onto collagen.
Natural rise of ALP (alkaline phosphatase occurs in serum during bone growth and healing of fractures and during pregnancy.
Abnormal increase of Alkaline phosphatase (ALP) in serum happens in […] this disease or […] this.
Happens in Paget disease or bone tumors.
AL Pacino has PAGET
Note: high serum ALP is also found in bile duct obstruction but is then combined with high GGT.
Prostate cancer
Prostate specific antigen test
(Instead of test for acid phosphatase)
Liver cancer
Alpha-fetoprotein (AFP):
This protein is normally synthesized in the fetal liver (instead of albumin).
In adults it can indicate liver cancer.
