CP11-5 Liver and Pancreatic Disease Flashcards
What cells is the liver mainly made up of?
60% hepatocytes which each connect with a sinusoid, a biliary canaliculus and a neighbouring hepatocyte
What are the functions of the liver?
Stores glycogen, iron and vitamins A, D, E and B12
Synthesises glycogen, glucose (gluconeogenesis), proteins, clotting factors, urea, lipoproteins, cholesterol and bile acid
Catabolism of glucose (glycolysis) and proteins
Metabolism of amino acids, fatty acids and vitamins A, D, E and B12
Excretion of bile acid, bilirubin, drugs and steroid hormones
Detoxification/inactivation of drugs and steroids.
What are some systemic effects/signs and symptoms of liver disease?
Jaundice
excess oestrogen e.g. presenting as gynecomastia, spider naevi, liver palms, testicular atrophy
Bruising
Pigmentation
Clubbing
Dependent oedema
Ascites
Encephalopathy
Osteomalacia/osteoporosis
What is a common liver related symptom seen in babies?
Neonatal jaundice
What substances can be tested for to assess liver function?
Glucose
Albumin
Urea
Prothrombin - and prothrombin time
Cholesterol
Triglycerides
Bile acids
Bilirubin
Ferritin
Drugs
Steroid hormone
What do liver function tests test for?
Production of metabolites
Clearance of endogenous substances
Clearance of exogenous substances
Hepatocellular and biliary tract damage
What are some routine LFTs?
ALP (alkaline phosphatase)
ALT (alanine aminotransferase)
AST (aspartate aminotransferase)
Bilirubin
Albumin
Total protein
GGT (gamma glutamyl transferase)
What tests are done for viral hepatitis?
Serology for hepatitis viruses (A-E), CMV and HIV
What tests are used to investigate chronic active and autoimmune hepatitis?
Tests for anti-smooth muscle, anti-liver/kidney, anti microsomal and anti-nuclear antibodies
What tests are done into primary biliary cirrhosis?
Anti mitochondrial antibodies
What tests are done into hereditary hemochromatosis?
Ferritin, transferrin saturation, liver biopsy and genetic testing
What tests are done into Wilson’s disease?
Caeruloplasmin, urine copper, plasma copper and liver biopsy
What tests are done into alpha 1 antitrypsin deficiency?
Alpha 1 antitrypsin and genetic testing
What LFTs are done to look for hepatocellular cancer?
AFP as is a primary liver tumour marker
What test is more specific for liver disease - ALT or AST?
ALT as only released by cellular damage of the liver and AST is also released from red cells
What are common causes of acute hepatitis?
Paracetamol
Viral - hep B&E
How is acute hepatitis defined?
As severe hepatic dysfunction developing within 6 months of the first onset of liver disease and in the absence of pre existing liver disease.
How do patients with acute hepatitis present?
Hepatic encephalopathy (impaired brain function due to liver failure)
Prolonged and persistent prothrombin time and international normalised ratio
Grossly hepatic picture
Deep jaundice
Potentially hypoglycaemia
What commonly causes chronic hepatitis?
Virus - B and C
Alcohol
Wilson’s disease
Alpha 1 antitrypsin
Autoimmune hepatitis
How is chronic hepatitis defined?
When there is clinical or biochemical features of liver disease perspiring for more than 6 months. This disease is graded according to necroinflammatory activity and degree of fibrosis.
What are the 3 stages of alcoholic liver disease?
Fatty liver (steatosis)
Alcoholic hepatitis
Cirrhosis
What results in LFTs are seen as a result of biliary tract damage?
Increased conjugated bilirubin (due to impaired excretory function)
Increased ALP and gammaGT (due to increased synthesis of enzymes by cells lining the bile canaliculi)
What can cause increased production of ALP by cells lining the bile canaliculi?
Cholestasis (intra or extra hepatic)
Infiltrative disease
Space occupying lesions (tumours)
Cirrhosis
Where is ALP produced?
Liver
Bone
Intestine
Placenta
What can be used to look at ALP isoenzymes?
Electrophoresis
What can cause elevated gamma glutamyltransferase?
Structural damage of liver by:
Alcohol
Enzyme inducing agents like anti-epileptics
Fatty liver
Heart failure
Prostatic disease
Pancreatic disease
Kidney damage
How can you determine if a raised ALP is of liver origin?
By checking gamma GT levels
What is primary biliary cirrhosis?
Chronic cholestatic condition with destruction of bile ducts associated with an isolated raised ALP, raised IgM and anti-mitochondrial antibodies presenting mainly in females with pruritus,jaundice and non-specific tiredness.
What is primary sclerosing cholangitis?
A progressive disease of diffuse inflammation and fibrosis of the biliary system which is progressive and autoimmune - associated with IBD- appearing mainly in men. Starts with minor ALP elevations which progressively become more severe until patients have deep jaundice.
What biochemical marker score can be used to asses fibrosis if the liver?
ELF (enhanced level fibrosis) score - which looks at PIINP, TIMP-1 and hyaluronic acid
What is bilirubin a marker of?
The excretory capacity of the liver and free flow of bile
What types of bilirubin are measured?
Total
Unconjugated
Conjugated
At what level of bilirubin is jaundice seen?
When serum bilirubin > 40-50 micromoles per litre
What does unconjugated bilirubin measure?
Pre hepatic and hepatic bilirubin levels
What does conjugated bilirubin measure?
Post-hepatic (obstructive) and hepatic bilirubin
What are normal bilirubin levels?
<20 micromoles per litre
Is bilirubin soluble or insoluble in water?
Insoluble in water
How is bilirubin transported in the blood?
Bound to albumin
How is bilirubin metabolised?
Haemoglobin —> bilirubin <==> albumin bound bilirubin
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Ligandin in liver conjugates bilirubin into bilirubin glucuroinde via UDP glucuronyl transferase —> excreted into bile for fat digestion and absorption
Bilirubin at kidney forms urobilinogen and is oxidised into urobilin and excreted in urine
What are 2 pre-hepatic causes of hyperbilirubinaemia?
Haemolysis e.g. due to rhesus incompatibility
Ineffective erythropoiesis e.g. due to spherocytosis
What are 4 causes of post-hepatic/obstructive hyperbilirubinaemia?
Gallstones
Biliary stricture
Cancer e.g. cholangiocarcinoma
Cholangitis
What are some hepatic causes of hyperbilirubinaemia?
Unconjugated = pre-microsomal and microsomal causes + inherited disorders of conjugation like Gilbert’s
Conjugated = post-microsomal/impaired excretion, intrahepatic obstructions + inherited disorders of excretion like Dubin-Johnson
What are some inborn errors of bilirubin metabolism?
Decreased activity of UDP glucuronyl transferase
Reduced ability to extreme bilirubin glucoronide
What does an elevated AST/ALT and normal ALP suggest about a patients diagnosis?
Likely to have hepatitis (90%)
What does a normal AST/ALT and an elevated ALP suggest about a patient’s diagnosis?
Likely to have obstructive jaundice (90%)
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