Liver Disease and Drug Handling Flashcards
Name some main functions of the liver.
Synthesis of plasma proteins -> Albumin and Clotting Factors.
Bile production and excretion.
Storage
Immun System
What are the 2 main liver function tests used?
Prothrombin Time
Serum Albumin
What does the ‘PT’ test measure?
Measures how long it takes the blood to clot.
What does the ‘Serum Albumin’ test measure?
Measures the amount of albumin in the blood.
What are the 2 enzymes that are looked for when assessing for liver damage?
Aspartate Aminotransferase (AST) Alanine Aminotransferase (ALT)
In viral hepatitis, which enzyme level is greater?
ALT is greater than in AST -> however, when cirrhosis is present, AST is greater than ALT levels.
What is hepatitis?
Describes the inflammation of the liver.
Name some causes of hepatitis.
Alcohol - induced. Viral. Drug induced. Autoimmune. Hereditary.
What are some causes of acute hepatic failure?
Paracetamol Overdose
Viral Hepatitis
Excessive alcohol consumption
What are the mechanisms involved in production of damage for hepatic failure?
Apoptosis
Disruption of calcium homeostasis
Inhibition of mitochondrial function
What % of cardiac output passes through the liver?
20%
At a normal dosage, which pathway does paracetamol take?
Phase 2 metabolism.
What does phase 2 metabolism contain (in a normal dosage)?
Conjugation with glucoronide // sulphate -> Forms non - toxic metabolites and thus is eliminated by the kidney.
What does phase 1 metabolism contain (in a normal dosage)?
Metabolism by CYP450 isoforms to form NABQI.
This is detoxified via conjugation with glutathione.
Eliminated via the kidney.
Why is NABQI bad?
It’s hepatotoxic and nephrotoxic -> thus, can cause kidney and liver damage.
At an overdose, which pathway does paracetamol take?
Phase 2 metabolism can’t occur as this pathway is saturated.
Undergoes phase 1 metabolism but CAN’T undergo conjugation with glutathione as it has been depleted.
So NABQI levels just increase.
How is glutathione levels replenished?
Via the usage of nacetyl cysteine.
Why can Type A toxicity occur for anyone?
It is dose - related.
Why are high levels of NABQI dangerous?
Apoptosis alongside renal failure occur.
What is cholestasis?
Decrease in bile flow due to impaired secretion by hepatocytes.
What is intrahepatic liver injury?
Involves the hepatocytes and results in the INCREASED level of liver enzymes.
What is extrahepatic liver injury?
Damage done to the bile ducts.
What is used to determine intrahepatic damage?
Symptoms
Examination
Liver Function blood tests
What are the symptoms for intrahepatic damage?
Nausea
Anorexa
Jaundice
Right hypochondriac pain
