10. Interpretation of Liver Biochemisty Flashcards
What does GGT stand for?
Gamma glutamyl transpeptidase
Where are AST and ALT located?
Heptocytes
AST: cytoplasm and mitochondria
Which is more specific to the liver, ALT or AST?
ALT more specific to the liver
**skeletal and myocardial muscle injury cause increased AST, increased ALT to a lesser extent
Where is alkaline phosphatase localized in the liver?
Surface of liver cells that are adjacent to the bile canaliculi
Where are the four places that alkaline phosphotase is located?
Liver
Bone
Intestine
Placenta
If not sure that ALP elevation is attributed to the intestine, what should be checked?
- GGT
- Isoenzymes
- 5’ nucleotidase
Liver cells conjugate indirect bilirubin through the action of:
UDP-glucuronyltransferase
What type of bilirubin will be increased in Hemolysis and Gilbert’s?
Indirect/unconjugated
What are two good indicators of liver synthetic function?
Albumin
INR
Replacement of ____ corrects INR due to nutritional deficiency but not due to hepatic dysfunction
Vitamin K
What type of bilirubin is increased in liver injury, bile duct problems, and rare metabolic problems?
Direct/conjugated
Normal ranges for AST/ALT
AST: 10-45 U/L
ALT: 8-40 U/L
Normal ranges of alkaline phosphatase
40-129 U/L
Normal ranges of total and direct bilirubin
Total: 0.2-1 mg/dL
Direct: 0-0.2 mg/dL
Normal range for INR
0.9-1.3
Normal range for albumin
3.5-5 g/dL
Normal range for GGT
0-50 U/L
What are hepatocellular injuries that will raise ALT and AST?
Alcohol Viral hepatitis AI hepatitis Hemochromatosis Wilson's disease Fatty liver Alpha-1 antitrypsin deficiency Medications
What are cholestatic/obstructive issues that lead to increase in ALP?
Stones
Primary biliary cirrhosis
Primary sclerosing cholangitis
Medications
What lab changes will be seen with infiltrative liver disease?
ALP elevation
Occasional bilirubin elevation
What are three exs of infiltrative liver disease?
Amyloid
Sarcoid
Tumors
When is GGT most useful?
Determining the source of alkaline phosphate elevation (bone vs liver)
What are the problems that lead to an ALT over 500?
Hepatitis A Hepatitis B Autoimmune hepatitis Medications Ischemia **Sometimes stone passage
Alcoholic liver disease rarely results in transaminases over
300
AST:ALT over ____ is suggestive of alcoholic liver disease
2:1
What is the best way to determine if the liver problem is acute or chronic?
INR
Serum enzyme tests can be grouped into two categories based on the cause of elevated activity:
- Hepatocellular damage
2. Cholestasis
What is cholestasis?
Any condition in which the flow of bile to the liver is inhibited or blocked
What is the role of ALT and AST?
Catabolize glucogenic amino acids
If you are in starvation mode, you can breaking down protein to feed into the TCA cycle
What are the two isoforms of AST?
GOT1: cytoplasmic
GOT2: mitochondrial
What do both GOT1 and GOT2 require as a cofactor?
Pyridoxal phosphate (PLP) **this is AST/SGOT
What is the tissue distribution of AST/SGOT?
BROAD: liver, cardiac muscle, skeletal muscle, kidney, brain, pancreas, lung. leukocytes
What isoform of AST is resposible for 80% of the activity in human liver?
GOT2 (mitochondrial form)
What is the other name for ALT?
SGPT (serum glutamic pyruvic transaminase)
WHat is the cofactor for ALT/SGPT?
Pyridoxyl phosphate (PLP)
What is the tissue distribution of ALT/SGPT?
Mostly found in the liver
ALT converts alanine and alpha ketoglutaric acid to:
L-glutamic acid
Pyruvate
Elevated AST and ALT are NOT specific for hepatobiliary disorders, also found in patients with:
Severe cardiac and skeletal muscle damage
Which transaminase is more often increased in patients with MI?
AST
Why is ALT lower than AST in alcoholic hepatitis?
Liver ALT is more sensitive to PLP deficiency than the liver
What is a membrane-bound metaloenzyme that catalyzes the hydrolysis of phosphomonoesters at an alkaline pH?
Alkaline phosphatase
Where are the four isozymes of ALP found?
Non-specific liver/bone/kidney
Intestinal
Placental
Germ-cell
ELevated serum ___ is seen in disorders of bone with increased osteoblastic activity, and with normal growth and pregnancy
ALP
What is 4’ nucleotidase involved in?
Purin catabolism
Hydrolysis of nucleotides like adenosine 5’ phosphate in which the phosphate is attached to the 5’ position of the pentose ring
What is the tissue distribution of 5’ nucleotidase?
Liver, intestines, brain, heart, blood vessels, pancrease
**in the liver, the enzyme is associated primarily with canalicular and sinusoidal plasma membranes
In contrast to alkaline phosphatase, 5’ nucleotidase is not elevated in:
Bone disease or pregnancy
What is the role of GGT (gamma glutamyl transpeptidase)?
Catalyzes the transfer of the gamma glutamyl group for the gamma glutamyl containing peptides such as glutathione to other peptides, amino acids, and water
**amino acid transport across membranes, hydrolysis of glutathione/glutathione homeostasis
What is the tissue distribution of GGT?
Broad: liver, kidney, brain, heart, spleen, and pancreas
Unlike alkaline phosphatase, GGT is NOT elevated in:
Bone disease
Certain meds like ___ and ___ along with ___ abuse can elevate levels of GGT?
Barbituates and anti-convulsants
Alcohol abuse: increases hepatic microsomal GGT
