Investigation of liver and pancreatic disease Flashcards
Liver function
- Glycogen storage and synthesis
- Synthesis and catabolism of clotting factors, amino acids and urea
- Lipoprotein and cholesterol synthesis; fatty acid metabolism; bile acid synthesis
- bile acid and bilirubin excretion; Drug detoxification and excretion; Steroid hormone inactivation and excretion
- Iron storage, B12 storage and metabolism
Signs of liver disease
- Neonatal jaundice: Yellowing of sclera and skin
- Jaundice
- Finger clubbing: alterations to vascular network = lack of nutrients/oxygen to the nail bed
- Spider naevi: liver metabolises oestrogen, damage = excess so affects capillaries = vasodilation
- Gynaecomastia: binding proteins affected, increased oestrogen and therefore breast tissue caused
Routine liver function tests
- Alkaline phosphate
- alanine aminotransferase (ALT)
- AST
- biliruibin
- gamma glutamyl transferase (GGT)
Hepatocyte damage test
- ALT + AST
- Enzymes found in the cell only released by cellular damage
- ALT is more specific for liver than AST as AST also found in muscle and RBCs
Tumour markers:
alpha fetoprotein for primary hepatocellular carcinoma
When is ALT commonly raised
- Epstein-Barr virus
Biliary tract damage
- increased conjugated bilirubin in blood and liver
- Increased synthesis of enzymes ALP and yGT
Alkaline phosphate (ALP)
- Elevated due to increased production by cells lining the bile canaliculi and overflow into blood
- Due to: cholestasis, cirrhosis, tumours, lesions
Gamma glutamyltransferase (yGT)
- Can support a liver source of raised ALP; elevated due to structural damage
- Can be induced by alcohol, diabetes, obesity, pancreatic or kidney damage
Biochemical markers of fibrosis
ELF score: predicting the likelihood of fibrosis without imaging or invasive tests
Bilirubin
Measured as:
- Total
- Unconjugated: pre-hepatic and hepatic
- Conjugated: post-hepatic (obstructive) and hepatic
- Jaundice at serum bilirubin >40-50umol/L
How is bilirubin metabolised
- Bilirubin is insoluble in water and has to go around body in blood plasma
- Taken up in the liver and conjugated by UDP GT - makes it more soluble
- Excreted in the bile and is used in fat digestion/absorption
- Colon conjugated bilirubin is acted on by bacteria to make stercobilinogen = brown colour - excreted in faeces
- Some bilirubin absorbed and excreted in urine as urobilinogen which makes urine darker
Hyperbilirubinemia
- Characterised by jaundice
- Can have pre-hepatic, post-hepatic or hepatic causes
Pre-hepatic aetiology of Hyperbilirubinemia
- Haemolysis e.g. rhesus incompatibility
- Ineffective erythropoiesis (breakdown of BRC) e.g. spherocytosis (sphere shaped RBC not biconcave)
Post-hepatic aetiology of Hyperbilirubinemia
- obstructive causes
- Gallstones, bliary stricture, cancer e.g. cholangiocarcinoma, head of pancreas, cholangitis
Hepatic aetiology of Hyperbilirubinemia
Unconjugated:
- decrease in activity of UDP GT
- Gilbert’s syndrome – benign inherited disorder of bilirubin conjugation
Conjugated:
- inherited disorders of excretion e.g. Dubin-Johnson
- reduced ability to excrete the bilirubin out of the liver via the bile ducts
- Check urea levels
Urea levels and hyperbilirubinemia
- If exit of conjugates bilirubin is blocked, it will be reabsorbed and thereby increase reabsorption in urine
- There would be dark urine because of the urobilinogen, but pale stools because of the lack of stercobilinogen.
Inborn Errors of Bilirubin Metabolism
- Decreased activity of UDP GT: Gilbert’s, Crigler-Najjar syndromes
- Reduced ability to excrete bilirubin glucuronide: Dubin-Johnson, ROTOR syndroes
Blood tests with jaundice
- AST/ ALT elevated and normal ALP: approx. 90% have hepatitis
- AST or ALT normal and elevated ALP: approx. 90% have obstructive jaundice
Urine tests
- Prehepatic: unconjugated bilirubin – no urinary bilirubin
- Hepatic - variable depending on degree of obstruction
- Post-hepatic: obstruction – dark urine (& pale stools)
How Useful are routine LFTs
- Only 3-4% of subjects with abnormal LFTs have liver disease - can be due to many other reasons
When to measure LFTs
- Signs - Pain, itchy, jaundice, TATT, bruising
- Lifestyle - Alcohol, obesity, diabetes, recent travel, drug use
- Disease present – hepatitis, haemochromatosis, liver cancer, drugs
- Severity – chronic hepatitis vs acute onset
Acute pancreatitis definition
- pancreas becomes inflamed (swollen) over a short period of time
Acute pancreatitis symptoms
- Severe epigastric pain
- sudden onset, radiating to the back
