Biliary Disease + Treatment Flashcards
What does 70% of hepatocyte SA face?
Sinusoid
= maximise blood exchange
What does 15% of hepatocyte SA face?
Bile canaliculi
What are gallstones (cholelithiasis) a result of?
Supersaturation of bile with cholesterol
What is choledocholithiasis?
Presence of gallstones within bile duct
What is acute cholecystitis?
Inflammation of gallbladder
Related to presence of gallstones
What is cholangitis?
Inflammation of bile ducts caused by polymicrobial bacterial infection
Describe the symptoms of cholelithiasis
Episodic pain in RUQ or epigastric pain associated with vomiting
= gallstone obstruction at neck of gallbladder
What are gallstones?
Crystalline concentration formed within gallbladder by accretion of bile components
When does cholesterol gallstones develop?
Bile contains high cholesterol + not enough bile salts
What are the causes of gallstones?
High calorie diet
Poor gallbladder contraction
Presence of proteins in liver promoting cholesterol crystallisation
Increased level of oestrogen
How does cholecystectomy work?
Keyhole surgery to remove stones
How does oral dissolution therapy work?
Oral administration of natural bile acid UDCA
Treatment up to 2 years
When are cholesterol agents used?
When gallstones are caused by cholesterol hypersecretion
What are the therapeutic options for cholesterol lowering agents?
Hepatic cholesterol biosynthesis
Intestinal cholesterol absorption
How do statins work?
Competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase
= limit rate for cholesterol biosynthesis
Describe what ezetimibe do
Blocks NPC1L1 = blocks cholesterol absorption
Why is it good to combine statin with ezetimibe?
Good clinical efficacy in reducing cholesterol load
= lower dose statin can be used
= reduce adverse effects
What do bile acid sequestrants do?
Bind to bile acids to form insoluble complex that prevents reabsorption
= faecal excretion
Why does depletion of bile salts beneficial?
Promotes increase bile acid synthesis
= reduces pool of intracellular cholesterol
What are the pharmacokinetics of bile acid sequestrants?
Not absorbed in GI tract
Remain in intestine = where can combine with bile acids for 5hrs before excretion
What are the adverse reactions of bile acid sequestrants?
Short-term, very mild
Possible from long term use = vomiting, diarrhoea, haemorrhoids
What are the drug interactions for bile acid sequestrants?
Acidic drugs in GI tract = decrease absorption + effectiveness
eg. aspirin
What do lipid lowering drugs (fibrates) do?
Stimulate beta-oxidative degradation of fatty acids
Liberate free fatty acids for storage in fat
Increase activity of lipoprotein lipase
Describe cholecystitis
Inflammation of gallbladder
Cyst duct obstruction
Association with stones
How do you treat cholecystitis?
Initial = control with fluids, antiemetics + analgesics
Broad-spectrum antibiotics
How do you treat cholecystitis if presence of sepsis?
Aggressive fluid resuscitation + blood pressure support
Describe cholangitis
Acute/chronic cholestatic disease
Due to non-specific inflammatory fibrosis of intra/extrahepatic bile ducts
How do you treat cholangitis?
Antibiotics
Surgery
Describe primary biliary cirrhosis
Chronic cholestatic disease
= destructive cholangitis of intrahepatic bile ducts
Which drugs increase bile flow?
Phenobarbital, glucagon, insulin + theophylline
Which drugs decrease bile flow?
Amiloride, oestrogens + chlorpromazine
What does clofibrate do to bile?
Increases biliary cholesterol secretion + reduces bile acid concentration
