140 - Practical Use of Liver Enzymes in Diagnosing Liver Disease Flashcards
Examples of liver-secreted blood proteins
Clotting factors
Breakdown of what marks cell death?
Cytoskeleton
Mild appearance of damaged cells
Cytoskeleton is damaged.
Blebs form from surface of cell, released into the blood
Features of apoptosis 1 2 3 4
- Nuclear degeneration
- Cytoskeletal degeneration
- Membrane Blebbing
- Shrinking
Things to consider with enzymes detected in the blood
1
2
3
1) Which cell did they escape from?
2) How did they get into the blood?
3) How will they be removed from the blood?
Cytoplasmic liver enzymes
ALT, AST, LD
Membrane liver enzymes
ALP, GGT
Organelle liver enzymes
Mitochondrial AST, lysosomal Superoxide dismutase
Things released from necrotic liver cells
ASL, AST, LD
Things released in biliary disease
AST, GGT
Things released with inducing drugs
GGT, ALP
ALT
Converts pyruvate to lactate (Cori cycle, anaerobic use of glucose)
Cori cycle
Occurs mainly in liver and muscle.
Anaerobic use of glucose
AST
Converts oxo-glutarate and aspartate to oxaloacetic acid and glutamate in the malate shuffle.
Where is ALT found?
Mostly in liver.
Slightly less in muscle and kidney.
More specific to liver than AST is.
Where is AST found?
In cytosol and in mitochondria.
Liver, muscle, blood cells.
Less specific to the liver than ALT is.
ALT half life
36 hours
AST half life
18 hours
GGT half life
5-7 days
AST>ALT
Acute, affecting mitochondria.
EG: an acute virus, ethanol damage.
ALT>AST
Chronic/resolving disease (because AST has a shorter half life than ALT).
EG: In hep B, C. With drugs, chronic viruses, metabolic problems.
Examples of viral diseases that can damage liver cells
Hep A, B, C, D, E.
EBV, CMV, Q fever, rubells
Normal ALT concentration in the blood
7 - 56 units/L
ALT level at which a patient will start feeling sick
1000 units/L
Maximum ALT possible in the blood
10, 000 units/L.
If patient has this, is in acute liver failure.
Severe hep A ALT level
5000 units/L.
Significant, as indicates that about half the liver has been lost.
Relationship between ALT levels and hep B core IgM and surface IgG levels
High ALT coincide with high core IgM, low surface IgG
ALT levels of chronic hep B, C
Fairly low ALT (~100 units/L)
Examples of hepatotoxic drugs
ANTIBIOTICS – Flucloxacillin, amoxil • STATINS – Atorvastatin, Simvistatin, Pravastatin, Fluvastatin • ETHANOL • PARACETAMOL • OTHERS – HERBAL TEA (Kombucha)
Rough amount of paracetamol required for liver failure
~15g (about one packet of paracetamol - 30 tablets)
What does significantly elevated ALT and AST indicate?
Liver cell death
Weakness with Simvastatin, only AST is elevated.
Simvastatin isn’t damaging liver, as other transaminases are normal.
AST is in other tissues. Probably a muscular problem.
What might it indicate if ALT is elevated, AST is normal?
Very chronic liver disease. ALT has a longer half life than AST.
Liver function tests on end-stage cirrhosis
ALT, AST look normal. Everything else looks close to normal.
This is because so much of the liver has been destroyed that transaminases aren’t being released much anymore.
Gamma GT role
Adds glutamyl groups to amino acids in the biliary membrane.
This forms glutamate, which goes on to form glutathione.
Why is GGT induced by drugs and alcohol?
Liver tries to combat toxic effect by generating more glutathione through GGT pathway
ALP role
Attaches a phosphate group to something on the biliary membrane.
Makes substrate more hydrophilic.
Jaundice causes 1 2 3 4 5 6
• INCREASED PRODUCTION – Haemolysis • DECREASED EXCRETION – Gilberts, Dubin Johnson – Hepatitis • OBSTRUCTION – EXTRAHEPATIC CHOLESTASIS • Elevated Conjugated Bilirubin – INTRAHEPATIC CHOLESTASIS • No Jaundice • No increase in Bilirubin
Intrahepatic biliary obstruction vs extrahepatic biliary obstruction GGT and ALP
GGT and ALP much higher with extrahepatic than intrahepatic
How does GGT, ALP get into the blood from bile?
Through lymphatics in biliary tree
Effect of alcohol metabolism on liver [NAD+]
Drops a lot.
Liver is using NAD+ to help mop up H+ from alcohol->acetaldehyde->acetic acid (forming NADH)
What does the liver do when NAD+ is depleted?
Glutathione is mobilised more
Significance of an extremely high GGT, and only slightly elevated AST and ALT
Mildly high AST and ALT not indicative of liver cell death.
Liver stress, but not widespread cell death
Mixed pattern of hepatitis (hepatocellular and biliary)
1 a, b, c
2 a, b, c
• HEPATOCELLULAR DEATH – Death of liver cells – Inflammation & swelling – Biliary Obstruction • BILIARY OBSTRUCTION – Inability to excrete toxins – Accumulation of toxins in hepatocyte – Hepatocellular death
Effect of weight on liver function tests
ALT, AST, GGT elevated
Effect of liver metabolising glucose and fructose
Fructose can be converted to glucose, but in the presence of glucose, the liver won’t convert fructose.
The fructose is stored in the liver as fat.
