140 - Practical Use of Liver Enzymes in Diagnosing Liver Disease

Question 1

Examples of liver-secreted blood proteins

Answer 1

Clotting factors

Question 2

Breakdown of what marks cell death?

Answer 2

Cytoskeleton

Question 3

Mild appearance of damaged cells

Answer 3

Cytoskeleton is damaged.

Blebs form from surface of cell, released into the blood

Question 4

Features of apoptosis
1
2
3
4

Answer 4

• Nuclear degeneration
• Cytoskeletal degeneration
• Membrane Blebbing
• Shrinking

Question 5

Things to consider with enzymes detected in the blood
1
2
3

Answer 5

1) Which cell did they escape from?
2) How did they get into the blood?
3) How will they be removed from the blood?

Question 6

Cytoplasmic liver enzymes

Answer 6

ALT, AST, LD

Question 7

Membrane liver enzymes

Answer 7

ALP, GGT

Question 8

Organelle liver enzymes

Answer 8

Mitochondrial AST, lysosomal Superoxide dismutase

Question 9

Things released from necrotic liver cells

Answer 9

ASL, AST, LD

Question 10

Things released in biliary disease

Answer 10

AST, GGT

Question 11

Things released with inducing drugs

Answer 11

GGT, ALP

Question 12

ALT

Answer 12

Converts pyruvate to lactate (Cori cycle, anaerobic use of glucose)

Question 13

Cori cycle

Answer 13

Occurs mainly in liver and muscle.

Anaerobic use of glucose

Question 14

AST

Answer 14

Converts oxo-glutarate and aspartate to oxaloacetic acid and glutamate in the malate shuffle.

Question 15

Where is ALT found?

Answer 15

Mostly in liver.
Slightly less in muscle and kidney.

More specific to liver than AST is.

Question 16

Where is AST found?

Answer 16

In cytosol and in mitochondria.
Liver, muscle, blood cells.
Less specific to the liver than ALT is.

Question 17

ALT half life

Answer 17

36 hours

Question 18

AST half life

Answer 18

18 hours

Question 19

GGT half life

Answer 19

5-7 days

Question 20

AST>ALT

Answer 20

Acute, affecting mitochondria.

EG: an acute virus, ethanol damage.

Question 21

ALT>AST

Answer 21

Chronic/resolving disease (because AST has a shorter half life than ALT).
EG: In hep B, C. With drugs, chronic viruses, metabolic problems.

Question 22

Examples of viral diseases that can damage liver cells

Answer 22

Hep A, B, C, D, E.

EBV, CMV, Q fever, rubells

Question 23

Normal ALT concentration in the blood

Answer 23

7 - 56 units/L

Question 24

ALT level at which a patient will start feeling sick

Answer 24

1000 units/L

Question 25

Maximum ALT possible in the blood

Answer 25

10, 000 units/L. | If patient has this, is in acute liver failure.

Question 26

Severe hep A ALT level

Answer 26

5000 units/L. | Significant, as indicates that about half the liver has been lost.

Question 27

Relationship between ALT levels and hep B core IgM and surface IgG levels

Answer 27

High ALT coincide with high core IgM, low surface IgG

Question 28

ALT levels of chronic hep B, C

Answer 28

Fairly low ALT (~100 units/L)

Question 29

Examples of hepatotoxic drugs

Answer 29

``` ANTIBIOTICS – Flucloxacillin, amoxil • STATINS – Atorvastatin, Simvistatin, Pravastatin, Fluvastatin • ETHANOL • PARACETAMOL • OTHERS – HERBAL TEA (Kombucha) ```

Question 30

Rough amount of paracetamol required for liver failure

Answer 30

~15g (about one packet of paracetamol - 30 tablets)

Question 31

What does significantly elevated ALT and AST indicate?

Answer 31

Liver cell death

Question 32

Weakness with Simvastatin, only AST is elevated.

Answer 32

Simvastatin isn't damaging liver, as other transaminases are normal. AST is in other tissues. Probably a muscular problem.

Question 33

What might it indicate if ALT is elevated, AST is normal?

Answer 33

Very chronic liver disease. ALT has a longer half life than AST.

Question 34

Liver function tests on end-stage cirrhosis

Answer 34

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.

Question 35

Gamma GT role

Answer 35

Adds glutamyl groups to amino acids in the biliary membrane. | This forms glutamate, which goes on to form glutathione.

Question 36

Why is GGT induced by drugs and alcohol?

Answer 36

Liver tries to combat toxic effect by generating more glutathione through GGT pathway

Question 37

ALP role

Answer 37

Attaches a phosphate group to something on the biliary membrane. Makes substrate more hydrophilic.

Question 38

``` Jaundice causes 1 2 3 4 5 6 ```

Answer 38

``` • INCREASED PRODUCTION – Haemolysis • DECREASED EXCRETION – Gilberts, Dubin Johnson – Hepatitis • OBSTRUCTION – EXTRAHEPATIC CHOLESTASIS • Elevated Conjugated Bilirubin – INTRAHEPATIC CHOLESTASIS • No Jaundice • No increase in Bilirubin ```

Question 39

Intrahepatic biliary obstruction vs extrahepatic biliary obstruction GGT and ALP

Answer 39

GGT and ALP much higher with extrahepatic than intrahepatic

Question 40

How does GGT, ALP get into the blood from bile?

Answer 40

Through lymphatics in biliary tree

Question 41

Effect of alcohol metabolism on liver [NAD+]

Answer 41

Drops a lot. | Liver is using NAD+ to help mop up H+ from alcohol->acetaldehyde->acetic acid (forming NADH)

Question 42

What does the liver do when NAD+ is depleted?

Answer 42

Glutathione is mobilised more

Question 43

Significance of an extremely high GGT, and only slightly elevated AST and ALT

Answer 43

Mildly high AST and ALT not indicative of liver cell death. | Liver stress, but not widespread cell death

Question 44

Mixed pattern of hepatitis (hepatocellular and biliary) 1 a, b, c 2 a, b, c

Answer 44

``` • HEPATOCELLULAR DEATH – Death of liver cells – Inflammation & swelling – Biliary Obstruction • BILIARY OBSTRUCTION – Inability to excrete toxins – Accumulation of toxins in hepatocyte – Hepatocellular death ```

Question 45

Effect of weight on liver function tests

Answer 45

ALT, AST, GGT elevated

Question 46

Effect of liver metabolising glucose and fructose

Answer 46

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.