CHEMPATH: LFTs and cases

Question 1

Question 2

What is the normal liver function?

Answer 2

Question 3

What is intermediary metabolism?

Answer 3

enzyme-catalysed processes

Question 4

What does xenobiotic metabolism invovle?

Answer 4

Question 5

What percentage of proteins in the body are expressed in the liver?

Answer 5

59%

Question 6

What hormones are metabolised in the liver?

Answer 6

Question 7

What are the components of bile? What is its function?

Answer 7

Question 8

How is bilirubin metabolised and excreted?

Answer 8

Globin is turned over and reused

Iron is recycled

Heme binds albumin ,is glucoronytades to make it soluble (unconj is insoluble), conjugated bilirubin is then excreted

Question 9

What cells are invovled in the reticuloendothelial system of the liver?

Answer 9

Question 10

What are ALT, AST, ALP, GGT a marker of?

Answer 10

Serum markers of liver cell damage - because hepatocytes are filled with these

Question 11

What are better indicators of liver function in LFTs?

Answer 11

Albumin

PT

Question 12

What LFT is a tumour marker?

Answer 12

AFP

Question 13

Describe hepatocyte anatomy.

Answer 13

Central vein ….

–> sinusoids –> hepatocytes –> excreted into bile canalliculi –> bile ducts –> gall bladder

Question 14

What are ALT and AST?

Answer 14

Enzymes contained in hepatocyte cytoplasm

Elevated when hepatocytes die

Question 15

Where else are ALT/AST found?

Answer 15

muscle, kidney, brain, pancreas

Question 16

When is the ALT:AST useful?

Answer 16

Advanced fibrosis ALT:AST >1

Chronic alcoholism ALT:AST >2

Question 17

What is GGT raised in characteristically? Where else is GGT found outside the liver?

Answer 17

Question 18

When is ALP found in the liver?

Answer 18

Sinusoidal and canalicular membranes so raised in obstruction or bile duct damage

Question 19

What are the other sources of ALP? What physiological states is ALP raised in?

Answer 19

Question 20

Give 3 causes of a low albumin.

Answer 20

Low production (CLD, malnut)

Loss (gut, kidney)

Sepsis (3rd spacing)

Question 21

How much albumin is synthesised each day? What is its function?

Answer 21

8-14 g/day

20 day half-life

Contributed to onscotic pressure and binds many things

Question 22

Question 23

What is the function of AFP?

Answer 23

No known function in adults (low concentration)

In fetal life made by yolk sac, GI epithelium and liver

Used in HCC diagnosis

Hepatic damage/regeneration

Testicular cancer

Pregnancy

Question 24

Summarise the causes of jaundice. Which type of bilirubin is raised in each?

Answer 24

Question 25

What is the use of USS in jaundice diagnosis?

Answer 25

If jaundiced and.... * ALT/AST raised then hepatocellular damage * **ALP raised then dilated or undilated ducts --\> diagnose** * everything else is normal in LFTs then Gilbert's, haemolysis etc.

Question 26

Should bilirubin be found in urine? What other product may be found?

Answer 26

Bilirubin should NOT be found. Only conjugated. Urobilinogen is usually circulating in the plasma and so is usually found in urine (in obstructive jaundice urobilinogen disappears and bilirubin appears in urine)

Question 27

What are the other investigations which may be used in a liver panel?

Answer 27

* Lipids, fasting glucose * Coeliac * Hepatitis screen (HBV sAg, HCV Ab) * Alpha-1-1ntitrypsin * Caeruloplasmin - _low_ suggests Wilson's disease * Liver AAbs (LMK, aSMA, AMA) * Igs * Ferritin * ANCA screen Other: * Tumour markers * Fibroscan * Liver biopsy * Iron studied and HH genetics * Viral DNA/RNA * 24hr urinary copper * Alpha-1-1antitrypsin phenotype * CT * MRCP * MRI/MRI iron load * EUS * More complicated tests shown below

Question 28

Guidelines for referral when there is an isolated ALT (not all need referral)

Question 29

What are the alternatives to liver biopsy?

Answer 29

* Fibroscan * Serum markers for liver fibrosis

Question 30

What does a fibroscan and measuring serum markers for fibrosis invovle?

Answer 30

Fibroscan * Vibrating US probe * Shear wave propagates * Velocity alpha * Enhanced liver fibrosis scales

Question 31

Answer 31

* Preserved synthetic function * Non fasting and fasting uncojugated bilirub were measured * Elevation in fasting bilirubin was then seen which was unconjugated = Gilbert's syndrome (this is harmless)

Question 32

Bilirubin in urine means it is conjugated

Answer 32

Suggests diorder of bile ducts But USS shows no obstruction Diagnosis was drug induced cholestasis - intrahepatic, secondary to Augmentin (classically gives obstructive jaundice)

Question 33

Looks obstructive,

Answer 33

O/E has **Courvoisier's Sign** = in the presence of a painless palpable gallbladder, jaundice is unlikely to be caused by gallstones (i.e. with gallstones you get pain, malignant obstruction is usually no pain) Predominantly obstructive picture with some alcoholic liver disease USS shows dilated CBD and possible pancreatic mass so the diagnosis is pancreatic adenocarcinoma. You would do a CT scan and biopsy and look at local spread. Tx is to stent the CBD although this is a palliative measure.

Question 34

Answer 34

* Liver is severely inflamed * USS shows no dilated bile ducts. So this is likely hepatocyte damage alone * Serum IgM and anti-HAV positive **Diagnosis is acute hepatitis A** (commonest form of acute hepatitis)

Question 35

Answer 35

Chronic liver disease with deterioration in synthetic function USS shows coarse liver texture Hep C confirmed by serology and PCR Admitted to using heroin once in the seventies (very common risk factor as 70-80% of those with IVDU will have HCV) Tx: antivirals + USS/AFP every 6 months to screen for HCC

Question 36

*High resp because compensating for acidosis.*

Answer 36

INR is 2.8 so running out of hepatocytes to make clotting factors Tx: N-acetyl cysteine Transferred to transplant centre

Question 37

Answer 37