Interpreting LFTs Flashcards
ALSO DO SOMEHTING ABOUT GLUCOSE BEING A MARKER
ALSO AMYLASE? OR SAVE FOR PANCREATITIS DECK?
Also: https://patient.info/doctor/abnormal-liver-function-tests For more
What blood tests count as LFTs and what is each a marker of?
The first 4 are used to distinguish between different types of hepatocellular damage and cholestasis; the remaining 3 are used to assess the livers synthetic function
Alanine transaminase (ALT)
- Intrahepatocyte enzyme
- High following hepatocellular damage
Aspartate aminotransferase (AST)
- Intrahepatic enzyme; but also found in cardiac and skeletal myocytes, kidneys, brain and RBCs - therefore not as specific as ALT
- Will be high following hepatic damage but also MI/haemolytic anaemia/acute renal disease/trauma etc
Alkaline phosphatase (ALP)
- Enzyme present in the liver, bile duct and bone tissues
- High levels usually (indirectly) indicates cholestasis
Gamma-glutamyltransferase (GGT)
- Enzyme present in cell membranes of bile ducts, gall bladder, pancreas, kidneys, spleen, heart, brain
- High levels indicate disease of liver, biliary tree or pancreas
Bilirubin
- Catabolic byproduct of heme metabolism by the liver, excreted in bile and urine
- Conjugated and unconjugated forms
- Responsible for colour of jaundice; breakdown products are stercobilin (brown faeces) and urobilin (yellow urine)
Albumin
- Water soluble plasma proteins responsible for maintenance of oncotic pressure and transport of some substances e.g. Ca, T4, bilirubin etc.
- Low if synthetic function is off due to hepatocellular damage
Prothrombin time (PT)
- Assay of the extrinsic and common pathway of coagulation i.e. the clotting tendency of blood due to coagulation factors 1 (fibrinogen), 2 (prothrombin), 5, 7 and 10
- Will be prolonged in liver damage as liver is not synthesising factors (also in anticoag use, vit K deficiency etc)
- Often one of the first derangements
How do we compare the rise in ALT and ALP and what does this tell us?
See if one/both are raised and by what extent
Predominantly hepatocellular injury:
>10x increase in ALT + <3x increase in ALP
Cholestasis:
<10x increase in ALT + > 3x increase in ALP
What does a rise in GGT tell us?
GGT rise + ALP rise = likely cholestasis
With any rise in ALP we should also check GGT to better confirm whether the ALP increase is due to biliary epithelial damage and bile flow obstruction, or whether its actually from another source e.g. bone
GGT is also raised in response to:
- Alcohol - large quantities of alcohol consumption; disproportionate elevation compared to ALT/AST may indicate alcohol abuse or alcoholic liver disease; can indicate excess alcohol consumption up to 3-4wks prior
- Drugs e.g. phenytoin
What might cause an isolated rise in ALP? (i.e. no paired GGT rise)
Non-hepatobiliary pathology:
- Bony mets or primary bone tumours
- Vitamin D deficiency
- Recent bone fractures
- Renal osteodystrophy
What is the AST:ALT?
ALT > AST:
- Most causes of hepatocyte damage e.g. acute and chronic hepatitis (viral, toxin, fat etc),
AST > ALT:
- More than 2:1 is associated with alcoholic liver disease and cirrhosis, especially if associated with raised GGT and MCV
- Alternatively may indicate muscle inflammation (e.g. dermatomyositis) so consider clinical picture
- ALT >500IU/L suggests a Dx other than alcoholic disease even if ratio >2:0
(The normal AST/ALT ratio is approximately 0.8)
What if the patient is jaundiced with normal ALT and ALP?
Isolated rise in bilirubin = pre-hepatic jaundice:
- Gilbert’s syndrome (most common)
- Haemolysis (check blood film, FBC, reticulocyte count, LDH levels)
What is the pathophysiology of jaundice? How can you differentiate the type of cause clinically?
Unconjugated (without glucuronic acid, insoluble) bilirubin is produced when haemoglobin is broken down
- As is water-insoluble, does not affect colour of urine
This is taken up by the liver and conjugated (glucuronic acid added, water soluble) so it can be excreted in the urine and bile
- In normal amounts this gives rise to the yellow and brown colours respectively
Pre-hepatic:
- Normal urine + normal stool
- High serum unconjugated bilirubin
- Haemolysis, impaired hepatic uptake (e.g. drugs, CHF) or Gilbert’s
Hepatic:
- Dark urine + normal stool
- High serum conjugated bilirubin
- Hepatocytes can still conjugate but are leaky - leading to higher levels of conjugated bilirubin in the serum which are then filtered by the kidney leading to dark urine
- Stools are normal as enough bile still being secreted
Post-hepatic/obstructive:
- Dark urine + pale stools
- High serum conjugated bilirubin
- Hepatocytes can still conjugate but biliary tree backlog leads to high levels of conjugated bilirubin leaking into serum and causing dark urine
- Stools are pale as no/minimal bile and pancreatic lipases can be secreted into small duodenum, meaning fat cannot be absorbed and is thus excreted in large quantities, turning stools pale, bulky and difficult to flush
Why might albumin levels fall?
Liver disease leading to a decreased production e.g. cirrhosis
Inflammation triggering an acute phase response which temporarily decreases the liver’s production of albumin
Excessive loss of albumin, due to protein-losing enteropathies or nephrotic syndrome
Why is glucose also useful when considering LFTs?
Gluconeogenesis (glucose generation from non-carbohydrate carbon substrates) is carried out in large quantities by the liver
- Glucose level can provide an indirect assessment of liver synthetic function
- This is however, one of the last functions to become impaired
What do you do once you have interpreted the LFTs?
Determine the cause:
- Consider Hx e.g. length of presentation, other key symptoms etc
Common causes of acute hepatocellualr injury:
- Poisoning e.g. paracetamol OD
- Infection e.g. hepatitis A + B
- Liver ischaemia
Common causes of chronic hepatocellular injury:
- Alcoholic fatty liver disease
- Non-alcoholic fatty liver disease
- Chronic infection e.g. hepatitis B + C
- Primary biliary cirrhosis
Less common causes of hepatocellular injury:
- Alpha-1 antitrypsin deficiency
- Wilson’s
- Haemochromatosis
Also different cholestatic pictures etc.
If there is doubt, a ‘liver screen’ can be performed - used to rule underlying causes in or out
What investigations make up a liver screen?
LFTs
Coag screen
Serology:
- Hepatitis ABC + immunoglobulins (IgM and IgG)
- EBV
- CMV
Auto-immune:
- Anti-mitochondrial antibodies (AMA)
- Anti-smooth muscle antibody (ASMA)
- Anti-liver/kidney microsomal antibodies (Anti-LKM)
- Anti-nuclear antibodies (ANA)
- p-ANCA
Others:
- Alpha-1 antitripsin level (to rule out deficiency)
- Serum copper and ceruloplasmin (to rule out Wilson’s)
- Ferritin (to rule out haemochromatosis)
- Alpha-fetoprotein (may indicate HCC)
