Test of Liver Function Flashcards
Two enzymes found in the centre of the hepatic lobule?
What do these reflect?
AST & ALT: involved in aa processing and gluconeogenesis, which are released in the circulation during CELL BREAKDOWN
Reflect the function of the cells in the middle of the lobule
Two enzymes anatomically associated with the portal triad
GGT & ALP
Where is bilirubin found, what does it reflect
Associated with the portal triad
reflect injury to outer part, or how the liver as a whole is processing
Functional roles of liver that can be tested?
Albumin (check levels)
Co-agulation factors (prothrombin ratio)
Glucose (that is released between levels can be measured)
If we have an inflammatory process that is affecting the CENTRAL part of the lobule we get a release of…. these indicate …
AST and ALT that can be measured in BS
Indication of a viral agent (viral hepatitis) or a toxin/drug
There may be things that affect the outside of the lobule… these indicate ….
Release GGT and ALP and bilirubin, also measured in bloodstream.
Potentially from obstruction (which causes dilation of the biliary system) like gallstones
-drugs
is there ever an overlap of ALT and AST with GGP and ALP
Almost always
Bilirubin is. Process of it metabolism.
- A product of haem (carries iron)
- insoluble and has to be carried by ALBUMIN (unconjugated bilirubin >85% of BS)
- Liver uptakes and processes it (sticks something on it to make it soluble)
- bilirubin-glucuronide (conjugated
In processing unconjugated bilirubin, what does the liver usually do
Sticks something on it to make it soluble, usually a sugar, eg- glucuronide
Whats different between unconjugated and conjugated bilirubin
Conjugated (bilirubin-glucuronide,
Urobilinogen
Brown substance that adds colour to poop. Small molecule, can enter the enterohepatic circulation, the intestine reabsorbs and urobiligen is excreted in the faeces OR since it’s a small molecule, can exit via urine
What happens if you have an obstruction/issues in the processing of bilirubin?
Conjugated bilirubin levels will increase (bilirubin-glucuronide), >15% as it can’t easily exit into the gut! Therefore the blood levels and as its a small molecule it’ll end up in the urin.
If you were suffering from haemolysis
RBC broken down at an increased rate
*haem > *unconjugate BR > *load on liver > *conjugated BR > *urobilinogen
So there will be an increase in urobilinogen in the urine, but not of conjugated BR, UNLESS there is a blockage!
How could Hepatitis/cancer affect bilirubin metabolism, what would you see?
If we have a process that affects flow, eg) a mass, then BR cannot flow into gut, little/no urobilinogen will be present in faeces or urine.
BUT there will be increased congugated BR, that can be measured in the BS!
Causes of Jaundice : unconjugated (indirect)
Unconjugated (indirect)
Haemolysis : increase in precursor load
Gilberts Syndrome: issue in conjugation step, genetic variability, % population with slower conjugation and increased unconj. BR especially when system is stressed
Causes of Jaundice : conjugated (direct)
Within the liver itself
Cholestasis: drugs, pregnancy, thyroid disease
Obstuction in Liver: passage hindered, hepatitis (swell), cirrhosis, biliary cirrhosis, liver masses
Outside of Liver
Obstruction outside liver: gallstones, biliary/pancreatic cancer, pancreatitis
stopping bile flow
ALP?
Alkaline Phosphatase
-Transfer/hydrolyses phosphate groups
-wide age-related variation, as main 2 sources are the liver (doesn’t change) and bone (dependent on growth). During puberty and menopause, there’s an increase in bone turnover > ALP increases.
ALP raised in pregnancy because the placenta makes it
Main sources of ALP
Liver: biliary system (blockage) Bone: osteoblasts (growth) Intestine: inflammation Placenta: late pregnancy Tumours: in bone/lung
When is ALP elevated with pathologys
All pathologies, especially
liver cancer
Gallstones
anything blocking/obstructing bile flow
GGT
Gamma-Glutamyl Transferase
-Mainly biliary origin (LIVER) as well as heart, pancreas, lungs
so pathology with ANY of these can raise GGT
Causes of elevation
1) inflammation/obstruction of biliary system
2) Inducible: via specific drugs and alcohol
* *3) Fatty liver can also
GGT and Alcohol intake
~2/3 of heavy drinkers have incrs. GGT (1-3x), but there are so many other causes, it’s hard to specifically blame alcohol.
Rises and falls with intake
Weekend drinking can raise by 25%
peaks 2-3days, falls over 5-6 days
Takes 6wks+ to return to normal with abstinences (1/2 falls in 2 weeks)
Chronic alcohol consumption causes scarring and eventual obstruction, so the liver may never go back to normal.
ALT
Alanine Aminotransferase
- involved in aa processing and gluconeogenesis
- Pyruvate to OA or acetylcoA
- is a marker of how much is getting out/into cell
- the most liver specific test (there are other organs but would need signif. damage to show increase)
- restricted to the cytoplasm
AST
Aspartate Transaminate
- involved in aa processing and gluconeogenesis
- located in cytosol AND mitochondira, so with serious liver damage, both AST and ALT release, but AST will be at a higher level
- less liver specific
- shorter half-life than ALT (8h vs 48h)
What pathologies elevate AST and ALT
most to a degree, especially
AST: Hepatitis (only early due to a shorter half-life)
ALT: Hepatitis, both early and late
Albumin:
Concentration, source, causes of decrease?
35-47 g/L
Liver only source in adults
Falls with:
Lower synthesis (cirrhosis)
Increased loss (liver has to work harder)
illness (non-specific, only by a few g, common for sick patients)
redistribution (gets into interstitual fluid)
REFLECT LIVER FUNCTION
Globulins measurement
- Reflect inflammation (subacute, chronic)
- very high levels occur with chronic hepatitis, cirrhosis
REFLECT LIVER FUNCTION
Prothrombin ratio (PR) (INR) measurement
- Reflects clotting factor synthesis
“the higher the ratio, the lower the synthesis of clotting factors”
-Rise indicates vit K deficiency or liver failure
-common in blood thinner users, can’t make clotting factors
REFLECT LIVER FUNCTION
Glucose measurement
- liver normally maintains fasting blood glucose
- inability to maintain blood glucose is ominous, as the liver has a good reserve
REFLECT LIVER FUNCTION
In a blood test, what indicates liver scarring/ declining function
- persistent GGT, ALP elevation
- AST/ALT ratio (>1)
- globulins (IG)
- decreased albumin
- *bilirubin
- *prothrombin ratio (low vit K)
- decrease glucose
- NH3 (toxic to the brain > hepatic enocephaly)
CEA
cancer marker, some benign elevation (hepatitis, cirrhosis, ulcerative colitis, renal failure, smoking)
usually 3-5ng/ml
increase with smoking and benign disease.
>20ng/ml almost always malignant
Can be used to monitor bowel cancer
Mildly decreased albumin
could just mean they are sick,, or potentially lower liver function
If GGT and ALP and significantly elevated but the bilirubin is normal, this indicates
elev. GGT and ALP =
bile duct block
?stones
?masses
distal to a blockage or obstruction.
but the rest of the liver (biliary tree) is patent/normal so bilirubin is able to be processed normally.
This is concerning, indicates a random mass … cancer?
**if the blockage was in the biliary tree trunk (gallstone), no bile would get through and bilirubin would increase
Normal AST indicates?
minimal liver cell inflammation
Bilirubin levels are usually around ___, usually don’t get jaundice till ____
Bilirubin levels are usually around 20, usually don’t get jaundice till 40
Change in faeces/urine colour
Dark urine= Bilirubin/urobilinogen escaping escaping out into urine
Light stools= no urobilinogen getting into faeces (blockage of flow)
Typical signs of Gilberts SYndrome
common 3-5%
- only mild bilirubin rise
- Variant in BR conjugation step: the issue is with the sticking of sugar onto the unconjugated BR
- Bilirubin-unconjugated elevated
- other liver function tests normal
eg) Normal enzymes (as there’s no bile duct obstruction or liver cell injury)
Hepatitis related enzymes
AST and ALT
Albumin ** low
Bilirubin ** high
GGT ** high
ALP ** high
AST * high
ALT* high
Prothrombin ratio ** high
Albumin = liver isn't functioning well Bilirubin = livers not working OR bile flow impaired
GGT & ALP= liver could be swollen, potentially damaged. Also GGT is inducible, drinking? drugs?
AST & ALP= Hepatitis/inflammation/unhappy liver.
Recent liver damage
Prothrombin ratio = low level of CF synthesis, decreased liver function
Diagnosis: Viral hepatitis, alcoholism , long standing liver disease
Varices indicate
portal hypertension
excess alcohol history, vomited blood, has oesophageal varices
Albumin ** low
Bilirubin ** high
GGT ** high
ALP ** high
AST ** high
ALT** high
Prothrombin ratio * high
Predominat GGT and ALP incrs (and BR)= suggests lots of scarring, a chronic issue (gallstones, cirrhosis, cancers?)
ALT and AST= moderate, ongoing inflammation
If bile ducts aren’t dilated
-alcoholic liver disease, with cirrhosis and portal hypertension (varices)
Scan would show shrunken, scarred liver
Paracetamol Overdose: tender large liver
3days = unconcious 5days= dead
Albumin normal
Bilirubin ** high
GGT ** high
ALP * high
AST ** high
ALT**** high
Glucose * low
Prothrombin ratio * high
AST and ALT: to such an extreme only achieved by extreme drug toxicity (or severe viral hep). Serious acute poisining
Liver inflammation blocks glucose, bilirubin leaving
Liver function super impaired
also bilirubin proccessing could not be very good.
ALbumin normal because it’s half life is ~3weeks
Causes of abnormal LFTs
Fatty liver 45% Viral Hep 27% Alcohol 8% Haemochromotosis 3% Other s(drugs, AI) 16%
