Test of Liver Function Flashcards by Libby Halligan

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

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Two enzymes anatomically associated with the portal triad

GGT & ALP

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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

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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)

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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

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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

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is there ever an overlap of ALT and AST with GGP and ALP

Almost always

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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

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In processing unconjugated bilirubin, what does the liver usually do

Sticks something on it to make it soluble, usually a sugar, eg- glucuronide

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Whats different between unconjugated and conjugated bilirubin

Conjugated (bilirubin-glucuronide,

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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

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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.

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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!

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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!

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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

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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

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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% ```