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
What are the different types of hepatitis ?
Where are the found ?
HEPT A - faecal - oral route
HEPT B - Bodily fluids - blood, milk, amniotic fluid , vaginal secretions, semen.
MODE OF TRANSMISSION:
1. sexual
contact with
infected
2.
contaminated
blood :
- blood
transfusions
- sharing
needles - intravenous drug use.
3. Childbirth - pass from mother to a baby.
HEPT C
HEPT D - same hept B - but only present in those with an active hept b infection.
HEPT E
HEPT D AND HEPT B ?
What are they ?
What do they cause ?
How does it damage the body ?
HEPT B and HEPT D - cause hepatitis (inflammation the liver )
HEPT D - can cause infection without HEPT B as it it lives within its structure - needs B to replicated.
HEPT B virus - virus is released from hepatocytes without causing damage (does not cause inflammation)
0 Damage is due to immune system - the T cells find infected hepatocyte and eliminate them - causing liver damage.
( b cells also release antibodies HB antigens in blood )
0 HEPT D - when newly replicated hept D virus leaves cell - the HDAg - delta antigens damage the liver as they leave - liver damage.
Structure of HEPT B AND D ?
HEPT B AND D have an envelope surrounded by a membrane - contains Hepatitis B viral proteins e.g Hbs surface antigen.
- Membrane
- Capsid - beneath the membrane -
0 HEPT B has HBc (HB core) & , HBe - variant of HBc but not part of virus - (secreted - found in blood / serum of infected people)
0 HEPT D - has HDAg - delta antigen in the caspid.
- DNA - genetic material - contained within the caspid.
0 HEPT B - partial double stranded circular DNA. - long & short strand.
0 HEPT D - single stranded circular DNA.
Hoe does HEPT B infect cells ?
Hepatitis B binds to hepatocyte and fuses with its membrane. ——> releases capsid into cell ——-> partial double stranded circular DNA is completed and passes to the nucleus ————-> mRNA created and virus uses cells ribosomes to synthesise viral proteins ( e.g hbs, hbc ,
hbe antigen etc )
hbe leaves cells and is found in serum
hbc and hbs incorpated into viral structure.
Symptoms of hepatitis ?
Jaundice - Yellowing of skin = sclera of eyes - destruction of liver cells release bilirubin.
0 Itchiness - caused by bile salts getting into skin.
0 increased bilirubin in urine
0 Pale , hard to flush stools.
Chronic hepatitis caused if prolonged - 5 - 10 % of cases.
- insufficient T Cell response - Increasing HBs bind t neutralising antibodies
2/3rds develop mild asymptomatic acute hepatitis.
Symmptomatic
0 preicteric phase ( before jaundice )
- body aches
- headcahes
- nausea
- fatigue
( few days - a week )
0 icteric phase - Jaundice + dark urine
(1 -2 weeks )
Recovery phase( if better)
Fulminant hepatitis - (if worsen -
- sudden
fever
- abdominal
pain
- jaundice
- confusion
- coma
- Chronic - similar but often milder.
Consequences of hepatitis ?
Chronic hepatitis
- liver scarring - Cirrhosis - Liver failure.
increasing risk of hepatocellular carcinoma.
How does HEPT D infect cells /
- HEPT D binds to cells and fuses with membrane
- host cell RNA plymerase used to copy the viral RNA.
cell’s ribosomes used to produce HDg ( delta antigen )
- viral rna packaged into caspid and HBs anitgens used to get caspid eneveloped
- leaves cell - delta antigen harmful to cell and cause liver damage (unlike hept B -
Diagnosis of HEPT B or HEPT B & D co infection ?
HBs antigen detected in blood - present 1-2 weeks after exposure
HBc antigens- present after 1-2 week but cleared quickly
after HBc antigens cleared HBc antibodies appear
- HBc core IgM apppear before shortly symptoms - HBg core IgG antibodies apear 1 - 2 weeks after symptoms.
anti HBs antibodies appear during recovery.
ACUTE HEPATITIS - what is dectected ?
O Anti HB core IgM antibodies
O Hbs antigens
O HBc antigens
O Viral DNA
O HB core IgG is present depending ot time of testing
O In recovery phase - only :
- anti HB core IgM & anti HB antibodies detected.
Diagnosis of HEPT B or HEPT B & D co infection ?
ACUTE HEPATITIS - what is dectected ?
O Anti HB core IgM antibodies
O Hbs antigens
O HBc antigens
O Viral DNA
O HB core IgG is present depending ot time of testing
O In recovery phase - only :
- anti HB core IgM & anti HB antibodies detected.
