interpretation of LFTs Flashcards
LFTs include
Alanine transaminase (ALT)
Aspartate aminotransferase (AST)
Alkaline phosphatase (ALP)
Gamma-glutamyltransferase (GGT)
Bilirubin
Albumin
ALT reference range
3-40 iu/L
AST reference range
3-30 iu/L
ALP reference range
30-100 umol/L
GGT reference range
8-60 u/L
Bilirubin reference range
3-17 umol/L
Albumin
35-50 g/L
ALT is
alanine aminotransferase
AST is
aspartate aminotransferase
raised AST and ALT means
occur in pathologies that cause liver cell (hepatocyte) inflammation or damage
marker of hepatocellular injury
common causes of hepatocellular injury
hepatitis (viral, alcoholic, ischaemic)
liver cirrhosis
drug/toxin-induced liver injury (e.g. paracetamol overdose)
malignancy (hepatocellular carcinoma)
AST:ALT ratio
if it is >2:1 this is classical of alcoholic liver disease
ALP is
alkaline phosphatase
GGT is
Gamma-glutamyltransferase
ALP is derived from
biliary epithelial cells (cells lining the biliary tract) and bones
raised ALP levels may be caused by
cholestasis or bone disease
what is cholestasis
Cholestasis describes an interruption in the bile flow from hepatocytes to the small intestine.
Common causes include gallstone disease, external compression of the biliary tract (e.g. pancreatic malignancy) or medication side effects. Bilirubin may or may not be raised depending on the severity of cholestasis.
GGT is found in
hepatocytes and also biliary epithelial cells
GGT is a marker of
non-specific but highly sensitive marker of liver damage and cholestasis
ALP rise with normal GGT
suggests bone disease eg. paget’s disease, vit D deficiency, bony metastasis
ALP rise with associated GGT rise is more suggestive of
cholestasis
isolated GGT rise is associated with
alcohol excess
where does bilirubin come from
a waste product of haemoglobin breakdown
what do hepatocytes do to bilirubin
Hepatocytes take up unconjugated bilirubin and metabolise it to form conjugated (soluble) bilirubin
where does conjugated bilirubin go
Hepatocytes excrete conjugated bilirubin into the biliary tract, where it flows into the bowel lumen as bile
what happens to conjugated bilirubin in the gut
Gut bacteria further metabolise bilirubin in bile to form urobilinogen, which is eventually excreted in the stools as stercobilinogen
A small amount of urobilinogen is reabsorbed from the intestine into the portal venous system, and as urobilinogen is water-soluble, the kidney is able to excrete some of this into the urine.
stercobilinogen
Stercobilinogen gives stools their dark colour
urobilinogen
Urobilinogen is colourless in the urine. However, if the urine is left exposed to the air, oxidation will occur, creating a dark colour. Under normal physiological conditions, urobilinogen will be present in the urine, however conjugated bilirubin will not be present.
what type of bilirubin should be present in the urine
Under normal physiological conditions, urobilinogen will be present in the urine, however conjugated bilirubin will not be present.
raised levels of bilirubin in the blood can be caused by
Excess bilirubin production (pre-hepatic jaundice)
A breakdown in bilirubin metabolism (hepatocellular jaundice)
A blockage in the bile excretion pathway (cholestatic jaundice)
pre-hepatic jaundice occurs when
Pre-hepatic jaundice occurs when increased red blood cell breakdown produces excess bilirubin. This can overwhelm metabolism/excretion pathways, leading to jaundice.
most common cause of increased red blood cell breakdown
haemolysis
what does LFTs for haemolysis look like
Bilirubin is unconjugated in the blood, as the hepatocytes have not yet metabolised it. The remainder of LFTs are generally normal, as the liver is otherwise working well.
what is Gilbert’s syndrome
Gilbert’s syndrome is a congenital disorder present in up to 5% of the population. It results from a deficiency of glucosyltransferase, the enzyme responsible for the conjugation of bilirubin within hepatocytes.
how does Gilberts syndrome present
Gilbert’s syndrome classically presents following viral infection with raised bilirubin but normal LFTs/ full blood count. The disease is benign and requires no specific management.
Hepatocellular jaundice occurs when
when hepatocytes are damaged and dysfunctional, leading to an inability to metabolise unconjugated bilirubin from the bloodstream. This leads to high levels of unconjugated bilirubin in the blood.
LFT appearance of hepatocellular jaundice
very high ALT / AST levels, marking hepatocyte damage.
common causes of hepatocellular injury
hepatitis, cirrhosis, malignancy, drug or toxin insult
When liver injury is severe, there are not enough functioning hepatocytes to metabolise bilirubin, and jaundice will develop.
what is cholestasis
an interruption in bile flow from hepatocytes to the gut. When this interruption is severe, bilirubin levels will build up in the blood. The bilirubin has been metabolised in the liver, and thus the bilirubin in the blood is predominantly conjugated bilirubin.
what type of bilirubin will build up in the blood in cholestasis
conjugated
what type of bilirubin will build up in the blood in hepatocellular jaundice
unconjugated
what kind of bilirubin will be in the blood in pre-hepatic jaundice
unconjugated
LFTs appearance of cholestatic (obstructive) jaundice
There will generally also be high ALP levels with associated high GGT, marking dysfunction of the biliary system.
clinical symptoms of cholestatic (obstructive) jaundice
Obstructive jaundice will classically lead to dark urine and pale stools.
why does cholestatic jaundice lead to dark urine and pale stools
Bilirubin cannot enter the gastrointestinal tract due to cholestasis, leading to low stercobilinogen excretion in stools.
The bilirubin in the blood is conjugated and can be filtered by the kidneys. The presence of conjugated bilirubin gives the urine a very dark colour.
