Lecture 18: Test of Liver Function Flashcards
What are the four key enzymes of the liver?
AST and ALT = Intracellular enzymes, active only in hepatocytes but leak into plasma so are measurable
GGT and ALP = Enzymes in liver metabolism, found in bile ducts.
What are some biomarkers of liver function?
Albumin
Prothrombin ratio
Glucose
Ammonia (urea)
What are the two patters of liver damage/ enzyme patterns?
Hepatocellular (thus ALT, AST)
or
Biliary / Cholestatic (ALP, GGT and Bilirubin-sometimes)
Often a mixture of the two in presentation
What are some examples of hepatocellular damage? and how do we know its hepatocellular?
Viral hepatitis
Liver toxins/drugs
Damage leads to inflammation, enzymes (ALT, AST) released into plasma = hepatocellular process
Whats some examples of Biliary/cholestatic process?
Gallstones
Some drugs
Describe bilirubin metabolism;
RBC breakdown forming haem
- Haem breaksdown into bilirubin and is complexed to albumin (Unconjugated, ~85%) (In blood)
- Bilirubin is taken up by the liver as it is not water soluble when unconjugated.
Bilirubin is conjugated with glucuronide (~15%)
- A small amount of this conjugate is enters the blood and then is excreted in the urine.
- The remaining can enter the biliary system and be released into the gut. It then forms urobilinogen (via gut flora) in the feaces (hence colour). A lot of this urobilinogen is re-absorbed and secreted in the urine.
What happens to bilirubin metabolism in states of haemolysis?
Overdrive production of conjugated bilirubin in the liver because increased haeme in blood.
This increases the amount of conjugated-bilirubin entering the gut. Thus increased urobilinogen in the feaces and re-absorption/ secretion or urobilnogen in urine.
Generally no increase in bilirubin conjugate if liver is still healthy. (no detectable rise in blood or urine of bilirubin-glucuronide)
What happens to bilirubin metabolism when theres hepatitis or cancer?
Increased bilirubin-glucuronide in the blood and urine and less urobilinogen in the feaces.
Whats the problem with inflammation of the liver?
It is in a firbous capsule therefore cannot expand and inflammation can lead to loss of function / occlusion of the networks.
What is jaundice?
When the skin, eyes, mucous membranes turn yellow because the billiary system is compromised
What are some examples of unconjugated (indirect) jaundice?
Haemolysis
Gilberts syndrome
What are some examples of conjugated (direct) jaundice?
Inside liver;
- Choleostasis (Drugs, pregnancy, thyroid disease)
- Obstruction inside liver (Hepatitis, cirrhosis, biliary cirrhosis, liver masses)
Outside liver
- Obstruction outside liver (Gallstones, biliary/pancreatic cancer, Pancreatitis (because these inflame and obstruct)
What is ALP?
Alkaline phosphatase
What does ALP do?
- Transfers/hydrolyses phosphate groups
- Age variation
- Mainly in liver and bone
Whats GGT?
Gamma-Glutamyl Transferase
What causes GGT to elevate?
- Inflammation/obstruction of biliary system
- Induced by alcohol, drugs such as phenytoin, rifampicin
Describe the relationship of CGT and alcohol;
GGT has huge variations and doesnt always reflect increased alcohol intake
Plasma GGT doesnt correlate with liver biopsy
Takes heavy drinkers /weekend bingers 6 weeks of abstinence for GGT to drop to normal
What does ALT stand for?
Alanine aminotransfersase
What does ALT do?
Involved in Gluconeogenesis
Ala + Alpha-ketogluterate Glutamate and pyruvate
Mainly in liver hepatocytes (in cytosol during infection i.e hepatitis)
What is AST?
Aspartate Transaminase
What does AST do?
- Involved in gluconeogenesis
- Found in liver
- Less liver specific than ALT
(8hr halflife vs 48hr for ALT)
Whats normal concentrations of albumin?
35-47g/L
Liver only source in adults
When does albumin fall?
- Decreased synthesis (Cirrhosis)
- Increased loss (i.e kidney)
- Illness (non-specific)
- Redistribution
- Negative acute phase reaction i.e inflam turns this process off.
What do globulins show?
IgA etc
- Reflect inflammation, subacute or chronic
- Very high levels with chronic hepatitis or cirrhosis
What does the prothrombin ratio (PR/INR) reflect?
- Reflects clotting factor synthesis (2,7,9,10)
- Rise indicates vit K def. or liver failure (indirect test)
What does blood glucose reflect?
- Liver maintains fasting blood glucose
- Inability to maintain glucose is ominous
What are general signs of liver scarring and declining function?
- Persistant GGT, ALP elevation
- Increased; AST/ALT ratio (>1), Globulins, bilirubin, prothrombin ratio (low vit K, cant produce), Ammonia
- Decreased; Albumin, glucose
What is important to remember about albumin?
Its a negative acute phase reaction protein
What is a CEA on a blood test?
Carcinoembyronic antigen
Indicates cancer for; Colon, breast, lung, pancreas, thyroid
Indicates benign for; Hepatitis, cirrhosis, ulcerative collitis, renal failure, smoking
== Doesnt have adequate sensitivity for early disease and therefore limited as early screening tool
What is gilberts syndrome?
- Variant in bilirubin conjugation
- Other liver tests normal
- (mild bilirubin rise, mild jaundice)
Illness fasting can worsen
What must you exclude to diagnose gilberts syndrome;
- Haemolysis
- thyroid disorders
- Iron overload
- Recent hepatitis
- Drugs i.e steroids
Done by 48hr fasting and seeing bilirubin rise
What are common causes of viral hepatitis?
- Infectious mono (50%)
- Hep A, B, C
- Cytomegalovirus
Go over the examples used to determine causes
In the guidebook
