Chemical Pathology 18 - LFT cases Flashcards
What 2 LFT results are very suggestive of alcoholic liver disease?
AST: ALT > 2.0
High GGT
When is ALP most markedly elevated?
Bile duct damage/ obstructive jaundice
What is the half life of albumin?
20 days
Systematically recall some reasons why albumin may be low
- Low production (chronic liver disease/ malnutrition)
- Loss (gut/ kidney (nephrotic))
- Sepsis, “3rd sponge” - due to endothelial leaking
What is the best measure of acute liver function?
Prothrombin time
Recall 4 scenarios in which AFP is raised
- Pregnancy (physiolgically)
- Hepatocellular carcinoma
- Testicular cancer
- Hepatic damage/ regeneration
What are the 2 possible causes of jaundice when LFTs are normal?
Gilbert’s
Haemolysis
In a jaundiced patient with a raised ALP, what should your diagnostic approach be?
Do a USS
If dilated ducts: gallstones/ cancer
If undilated ducts: drugs/ PSC/PBC/ pregnancy
What in the LFTs would indicate that jaundice had a hepatocellular origin?
Raised ALT/AST as opposed to ALP
How can you identify obstructive jaundice clinically without measuring bilirubin?
Pale stool and dark urine
What is the ELF score, and how is it calculated?
Enhanced liver fibrosis score
ELFs have a HAT
3 markers associated with fibrosis (HAT):
- Hyaluronic acid
- Amino-terminal propeptide of type III procollagen
- Tissue inhibitor metalloproteinases
Which common drug is often implicated in cholestasis?
Augmentin (co-amoxiclav)
Which type of hepatitis is most common cause of acute viral illness in returning travellers?
Hepatitis A (water-borne)
What USS finding is very suggestive of liver cirrhosis?
Coarse liver
Which type of hepatitis is most likely to be transmitted by IV drug use?
Hep C
Where are the enzymes ALT and AST found?
They are intracellular ezymes within hepatocytes- found in the cytoplasm
so if they leak out this is indicatvie of liver damage
Where else is AST and ALT present?
- Muscle
- Kidney
- Brain
- Pancreas
Which conditions cause AST to rise in preference to ALT?
Alcoholic liver disease
AST>ALT: 2:1
Which other drug causes high AST levels?
Cocaine
Which liver enzyme is raised after an MI?
AST
Where is GGt found?
hepatocytes AND small bile duct epithelium
What are the causes of raised GGT?
Chronic alcohol use (abuse)
Drug injury
Bile duct disease (e.g. gallstones)
Hepatic metastases
Where is GGT found (which organs other than the liver?)
Kidney
Pancreas
Spleen
Heart
Brain
Seminal vesicles
Where is ALP found?
liver:
Liver isoenzyme located in the sinusoidal and canalicular membranes (bile ducts)
Other organs:
Bone
Small intestine
Kidney
WBCs
Placenta
If ALP is raised how do you confirm that it is a hepatic source?
Measure GGT as well
If GGt is raised as well then it is a hepatic source
What causes raised ALP: hepatobiliary and other
hepatobiliary:
1) Obstructive jaundice
2) Bile duct damage (e.g. PSC, PBC)
other:
1) pregnancy- especially third trimester
2) bone disease- increased bone turnover due to increased activity of oestoblasts
- Paget’s
- renal osteodystrophy
- fracture
- metastatic disease
**NOT in multiple myleoma because you only get activation of osteoclasts not osteoblasts**
3) Vitamin D deficiency–>secondary hyperparathyoridism
4) Drugs
- phenytoin
- erythromycin
- carbamezepine
- verapamil
5) Congestive cardiac failure
6) Cancer
- breast
- colon cancer
- Hodgkin’s lymphoma
What are the markers of liver synthetic function?
Clotting
Albumin
Causes of low albumin
1) Hepatobiliary
* CHRONIC liver disease (not acute as albumin has a long half life)
2) Other
- Nephrotic syndrome
- Protein losing enteropathy
- third spacing eg in sepsis (leaks out from capillaries into interstitial space)
Best marker of acute liver dysFUNCTION
CLOTTING CASCADE- PROTHROMBIN TIME
as the proteins in the clotting cascade have a short half life (as opposed to albumin which has a long half life)
What is bilirubin a marker of?
Bit of both - liver dysfunction and liver damage
Best marker of chronic liver dysfunction
Albumin (will be low)
Causes of raised AFP?
- Hepatocellular carcinoma
- Testicular cancer
- Pregnancy
- Also raised in hepatic damage/ regeneration
Conjugated vs unconjugated hyperbilirubinaemia
Summarise the approach to jaundice
If jaundice/ high bilirubin but the LFTs are NORMAL (2):
1) Haemolysis
2) Gilbert’s
If jaundice/ high bilirubin but there is a predominantly RAISED ALP:
1) Dilated ducts (i.e. obstruction)
- gallstones
- cancer of the head of the pancreas
2) undilated ducts
- co-amoxiclav
- PBC/PSC
- pregnancy
**in all of these causes (cholestasis) you would see: rise in GGT and ALP are GREATER than rise in AST/ALT**
If jaundice/ high bilirubin but mainly AST/ ALT are RAISED:
Hepatocellular liver damage
a) Acute
b Chronic
In clnical practice what is the approach to jaundice?
causes of transaminases > 1000
Viruses
Toxins e.g. paracetamol
Ischaemia e.g. cardiac arres
When would you do a urine dipstick in the context of abnormal LFTs?
What would you see?
If you’ve got DARK URINE + PALE STOOLS - obstructive jaundice
Urine dip:
1) raised urinary bilirubin (conjugated- soluble) - this is visible to the naked eye
2) DECREASED urinary urobilinogen (this is produced by bacteria in the gut; if you have an obstruction, bile cannot get into the gut so levels will be low)
Causes of increased urinary urobilinogen
1) haemolysis
2) hepatitis
3) sepsis
What does a more extensive liver panel consist of?
Which other imaging (sophisticated) can be used for PSC?
MRCP
Which sophisticated tets can be used for haemchromoatosis?
MRI iron load
NAFLD symptoms
right upper quadrant pain
or may be asymptomatic
LFTs in NAFLD
raised AST and ALT levels (AST:ALT ratio <1)
increased GGT
Bilirubin and albumin levels are normal
LFTs in paracetamol overdose
- transamanitis in the 1000s (much larger rise in this compared to GGT and ALP)
clinical picture: acute liver failure
- Reduced synthetic and metabolic functioning
- Reduced blood sugar
- Metabolic acidosis
- Increased tendency to bleed
- hepatic encephalopathy
Causes of isolated rise in GGT
- acute alcohol abuse
- big rise in GGT (maybe a minor rise in AST,ALT indicating minor liver damage)
- would also see macrocyctosis - enzyme inducing drugs
phenotyoin
carbamazapine
phenobarbitone
Isolated rise in uBR?
Gilbert’s
- high total BR
- normal conjugated BR
Isolated rise in conjugated BR?
-
DUBIN JOHNSON SYNDROME
- autosomal recessive disorder
- LFTs:raised conjugated BR level
- due to reduced secretion of conjugated bilirubin into the bile
- AST and ALT levels - normal
What do raised serum bile acids indicate?
1) cholestasis of pregnancy
2) PBC/PSC
What is the Indocyanine green/ Bromsulphalein dye test?
Measure excretory capacity of the liver
Measure hepatic blood flow
What is the Aminopyrine/ Galactose (carbon 14) test?
Measures residual functioning of liver cell mass
looks at intermediary metabolism
Gold standard diagsnosi of fibrosis and alternatives
Gold standard: liver biopsy
Alternatives: fibroscan,
In which types of jaundice is spelnomegaly preset?
prehhepatic and hepatic
*not post hepatic*
Explanation for dark urine and pale stools in obstructive jaudnice
Dark urine seen due to increase urobilinogen/conjugated BR (lots of them
absorbed by blood), pale stool = low levels of stercobilinogen + dark urine
Causes of low urea
Severe liver disease, (synthesised in liver), malnutrition, pregnancy
Causes of raised urea
1) Upper GI bleed (or large protein meal)
2) Dehydration/AKI (urea excreted renally)
Hepatomegaly with smooth margin
Viral hepatitis, biliary tract obstruction, hepatic
congestion 2° to (HF; Budd Chiari)
Hepatomegaly with a craggy border
Hepatic metastatic disease, polycystic disease,
cirrhosis (will shrink)
In the absence of alcohol, an AST: ALT ratio > 0.8 suggests?
advanced liver fibrosis/cirrhosis
