Liver function test Flashcards
Function of the liver ?
0 Excretion - removal of toxic compounds from the blood - drugs , alcohol.
( pathology effects this - drug metabolism effected - careful of dosing )
0 Protein synthesis and cell membrane component synthesis
- Albumin - proteins associated with clotting.
( liver pathology can cause oedema and increased prothrombin time - blood takes longer to clot)
0 Maintenance of Serum Glucose
- storage of glucose as glycogen
- postprandial (after food) - Perivenous cells at the edge of liver take up Glucose . Glucose —-> Glycogen. Glycogen stored )
- Fasting state - Gluconeogenesis - liver converts other fuels / substances to glucose. Glc - 6 -P allows for glucose release.
(liver pathology which effects 8 -12 hour storage of glucose made worse if already have diabetes.
0 Acute liver failure - liver not able to maintain blood glucose concentration (Hypoglycaemia )
0 Chronic liver failure - failure of glucose storage - hyperglycaemia.
0 Barrier -
- Controls solutes entering systemic circulation
- Controls excretions in bile
Protein metabolism - liver ?
In the liver the proteins are altered - need specific enzymes (deaminases, transaminases)
- animo acid delivered to liver via portal vein
- removal of animo group - NH
- Transanimation - animo group transferred to keto acid acceptor - create new animo acid (this is how non essential animo acids made )
- Deamination - removal of amino group as ammonia
* sometimes too much ammonia can be produced - toxic - hyperammonaemia. - Urea created in kidney by combining 2 NH3 (ammonia) groups and CO2. - secreted from liver and incorporated into kidney and urine.
IMPORTANT-
0 branched amino acid - broken down mainly by muscle
0 Aromatic - mainly broken down by liver.
Decreased branched AA/ Aromatic AA ratio in Acute liver disease (liver pathology—-> less aromatic AA broken down —-> less branched than aromatic
Obesity and fatty liver disease
(non -alcoholic fatty liver disease?
Non - alcoholic fatty liver disease - build up of fat in the liver
4 stages
0 Steatosis - simple fatty liver in liver cells.
- non alcoholic steatohepatitis - liver becomes inflamed.
- Fibrosis - persistent inflammation causes scar tissue around liver and nearby BV. - liver cam still function normally
- Cirrhosis - most severe - liver strinks , becomes lumpy and scarred.
damage is permanent and can lead to liver failure and cancer.
ca take years for fibrosis and cirrhosis to occur.
- lifestyle changes can help prevent this .
Fat changes the structure of the liver - eventually cannot carry out function.
Symptoms of Non alcoholic liver fatty disease -NAFLD ?
early stage - not usually symptoms
0 more sevre stages
- dull ,aching pain in right upper quadrant ( lower side of quadrant )
0 extreme tiredness
0 unexplained weight loss
0 weakness
What proteins does the liver produced ?
0 Albumin - produced only in liver - control oncotic pressure.
2 weeks half-life - hypoalbuminemia thus not present in acute liver disease but in chronic .
Liver disease not only cause of low albumin - reduced dietary intake , alcohol consumption.
0 C -reactive protein - produced in response to inflammation
0 apolipoprotein - most of them.
0 hepcidin - regulate iron levels.
0 Insulin growth factor 1
0 proteins involved in coagulation
- liver mostly syntheses glycoproteins - disturbances in glycosylation (- alter protein function and affect protein folding. protein cant carry out function and body has to find way to excrete it. )
except albumin , transcobalamin II and c -reactive protein.
*altered conc of proteins - useful indicator of liver function.
LFT - significance of transanimases ?
AST - found in places in the body other than liver
ALT - more specific to liver.
Intracellular role - removal of amino group from animo acid.
increased levels indicate hepatocellular damage -HEPATITIS as transaminases released from cell.
0 Values >10x normal = primary hepatic damage
0 Values <10x normal = non-specific, no obvious aetiology
when AST and ALT are extremely suggest paracetamol toxity
comparison to ALP.
IF AST risen by ALT has not - suggest problen is elsewhere not liver.
( if you suspect muscle problem - measure CPK - creatine phosphate kinase) - high serum level suggest breakdown of muscle ( rhabdmyolysis - severe , myocardial infarction , muscular dystrophy etc )
Comparison of AST to ALP.
0 Higher AST to ALP or ALT to ALP ratio and = more likely damage is due to hepatitis
Lower
- A greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggests a predominantly hepatocellular injury.
0 lower AST/ALP ration = more likely damage is cholestatic
- A less
than 10-
fold
increase
in ALT
and a
more
than 3-
fold
increase
in ALP
suggests
cholestasis.
-
can have a mixed picture.
Comparison of AST to ALT
both transanimases
Ratio of AST/ALT useful in alcohol diagnostic
AST raised to higher level than ALT in alcohol related damage (acute alcoholic hepatitis )
- AST/ALT >2
(AST higher than ALT )
with
presumed
hepatic
disease =
most likely
alcohol
involvement
*ALT > AST - suggest chronic liver disease.
significance of ALP and GGT?
ALP - hydrolyses phosphate esters.
Found in liver, bone ,intestine and placenta.
Raised ALP indicates obstuction in billary tract e.g CHOLESTATIC.
raised ALP usually presents before onset of clinical jaundice.
- ALP expected to be higher in pregnant women.
raised ALP with raised gamma- Glutamyltransferase (GGT) suggest cholestatic cause
Isolated ALP rise -GGT not raised suggest another cause.
0 Bony metastases or primary bone tumours (e.g. sarcoma)
0 Vitamin D deficiency
0 Recent bone fractures
0 Renal osteodystrophy
Chronic alcohol problems – goes up and stays up even when they stop drinking . Help to see if liver damage due to alcohol
what test can help determine
0 hepatocellular damage
0 cholestasis
0 liver excretory function
0 biosynthetic function
(basically what test can help differientiate btw pre - hepatic , hepatic , post - hepatic or conjugated or unconjugated jaundice )
Hepatocellular disease - AST , ALT
0 Cholestasis - ALP/GGT
0 Liver excretory function - serum , urine bilirubin, blood ammonia
- ( Bilirubin unconjugated (water insoluble - does not pass into urine) or conjugated (pass into urine as urobilogen -makes it darker)
- bowel blockage - digestive pancreatic enzymes cant reach bowel so fat not absorbed , stools pale, bulky and more difficult to flush.
normal urine +
normal stools =
pre-hepatic
cause
- Dark urine + normal stools = hepatic cause
- Dark urine +
pale stools =
post-hepatic
cause
(obstructive)
0 Biosynthetic function - Albumin , coagulation factors , prothrombin
( biosynthetic - liver ability to generate specific proteins )
Patient jaundice but normal ALT and AST - causes ?
0 Gilbert’s syndrome - most common cause. - genetic condition (- higher than normal level of bilirubin build up in blood. )
Haemolysis: -
check a
blood film,
full blood
count,
reticulocyte
count,
haptoglobin
and LDH
levels to
confirm.
Causes of unconjugated hyperbilirubinemia ?
Haemolysis (e.g. haemolytic anaemia)
0 Impaired hepatic uptake (e.g. drugs, congestive cardiac failure)
0 Impaired conjugation (e.g. Gilbert’s syndrome)
Causes of conjugated hyperbilirubinemia ?
Hepatocellular injury
Cholestasis
Causes of acute hepatocellular injury ?
0 Poisoning (paracetamol overdose)
0 Infection (Hepatitis A and B)
0 Liver ischaemia
- If onset within days - indicates an acute reason
Causes of Chronic hepatocellular injury ?
0 Alcoholic fatty liver disease
0 Non-alcoholic fatty liver disease
0 Chronic infection (Hepatitis B or C)
0 Primary biliary cirrhosis
less common
0 Alpha-1 antitrypsin deficiency
0 Wilson’s disease
0 Haemochromatosis
