Biliary Disease and Treatment Flashcards
What is the biliary system?
group of organs and duct system that create, transport, store and release bile into the duodenum for digestion
What organs and duct systems are used to transport bile to the duodenum?
- gallbladder
- intrahepatic bile ducts
- extrahepatic bile ducts
- hepatic bile ducts
- common bile duct
- cystic duct
Where is the gallbladder located?
in the epigastric region on the inferior surface of the liver between quadrate and right lobes.
what delivers watery bile to the gall bladder?
the hepatic duct
what is used to empty concentrated bile from the gallbladder into the common bile duct?
the cystic duct
What does Bile compose of?
- bile acids
- phospholipids
- cholesterol
- bile pigments
- electrolytes
- water
Role of bile in the SI?
to emulsify fat
What are bile acids?
water-soluble, amphipathic end products of cholesterol metabolism.
How are bile salts formed?
from conjugation of bile acids with glycine or taurine.
How do bile salts behave similarly to detergents?
they breakdown fats in the aqueous intestinal environment enabling the formation of micelles.
How is bile acid synthesised?
- Cholesterol modified to cholestanoic acids (C27 BAs) then cholanoic acids (C24 BAs).
- primary bile acids are modified into secondary bile acids (i.e. deoxycholate from cholate and lithocholate from chenodeoxycholate)
Where are most bile acids reabsorbed?
through the enterohepatic cycle
What is Cholelithiasis?
supersaturation of bile with cholesterol and pigments combined with delayed emptying of the gallbladder (stasis) resulting in gallstones formation in the gallbladder!
What is a common complication associated with Cholelithiasis (gallstones)?
pancreatitis
What is Choledocholithiasis?
gallstones in the common bile duct
What is Acute Cholecystitis?
inflammation of the gallbladder (usually related to gallstones but can also result post-operation or from critical illnesses).
What is Cholangitis?
Non-specific inflammation of intra/extrahepatic bile ducts, most often caused by polymicrobial bacterial infection. Biliary obstruction is a major pathogenic factor.
What are symptoms of cholelithiasis?
- pain in RUQ
- epigastric pain
- nausea
- vomitting
Symptoms of choledocholithiasis, cholecystitis, cholangitis?
fever and jaundice
What is charcot’s triad?
pain in RUQ, fever and jaundice . These three symptoms help recognise cholangitis.
sypmtoms of cholangitis and cholecyctitis?
- elevated temp
- hypotension
- altered mental status
Examples of biochemical tests carried out to identify biliary disorders?
- bilirubin
- albumin
- ALT
- AST
- ALP
- GGT
Imaging that can be used to identify biliary disorders?
- Abdominal x-ray
- Ultrasound
- CT scan
- Cholangiography
- ERCP (Endoscopic retrograde
cholangiopancreatogram) - MRCP (Magnetic Resonance CP)
- Scintigraphy
- Oral Cholecystogram
What are gallstones?
crystalline concretion formed within the gallbladder by
accretion of bile components.
What is gallstone ileus?
an obstruction caused by when gallstones erode through the gallbladder into adherent bowel (obstructing the SI lumen).
Causes of gallstones?
- high cholesterol in bile and not enough bile salts.
- poor gallbladder contraction so incomplete and infrequent emptying of gallbladder occurs
- Presence of proteins in the liver promoting cholesterol crystallisation into gallstones.
- increased oestrogen levels increase bile cholesterol levels and decrease gallbladder movement
How are gallstone dieases treated?
- cholecystectomy (key hole surgery to remove stone)
- oral dissolution therapy (administration of natural bile acid UDCA)
- cholesterol lowering agents (e.g. prevents cholesterol synthesis, decreases cholesterol absorption in intestines etc)
- statins (inhibit the enzyme used to biosynthesise cholesterol)
- reduce intestinal cholesterol absorption (don’t block the absorption of triglycerides or fat-soluble vitamins however)
- combined inhibition of gallbladder cholesterol levels.
What are bile acid sequestrants and what do they do?
- they are large, highly positively charged anion exchange resins that bind to negatively charged anions (bile acids).
- this results in the formation of insoluble compound that can’t be reabsorbed and is therefore excreted in faeces.
- this reduces cholesterol levels in cells hence helping to maintain low cholesterol levels
Compare the difference in efficacy of using bile acid sequestrants alone to lower LDL cholesterol level to using statins.
bile acid sequestrants are not as effective in lowering LDL cholesterol when used alone.
they’re more effective used in conjunction with statins
What is the pharmacokinetics of Bile Acid Sequestrants?
- Not absorbed from the GI tract.
* Remain in the intestines, where they combine with bile acids for approx 5 hours, before excretion
What are the adverse reactions to the use of bleeding.
Bile Acid Sequestrants?
short term reactions are mild.
reactions from long-term use: faecal impaction, vomiting, diarrhoea, haemorrhoids
What drugs can Bile Acid Sequestrants interact with?
- acidic drugs in the GI tract hence decreasing their absorption and effectiveness
- lipid-soluble vitamins (A,D,E,K). would reduce their absorption. Less vit K absorbed can affect prothrombin times hence increasing the risk of bleeding.
What are lipid-lowering drugs and what do they do?
- they’re called fibrates
- they have many roles e.g.:
1. stimulate β-oxidative degradation of fatty acids.
2. encourage the use of fatty acids for metabolism in muscles
3. increase hydrolysis of triglycerides in chylomicrons and VLDL particles
4. reduce hepatic VLDL production and increase hepatic LDL uptake
5. decrease LDL and increase HDL
6. improves glucose tolerance
7. inhibits vascular smooth muscle inflammation
8. stimulate free fatty acid storage as fats
What is the treatment for Cholecystitis?
- give fluids
- antiemetics
- analgesics
- antibiotics e.g. ampicillin
- may require a cholecystectomy (in the presence of sepsis)
How is cholangitis treated?
- antibiotics
- surgery
What is primary bviliary cirrhosis?
- a chronic cholestatic disease due to destructive cholangitis of intrahepatic bile ducts.
- immune mediated
- a granulomatous destruction of the bile ducts
- chronic inflammation in portal tracts results in portal fibrosis progressing to cirrhosis.
What is used to diagnose Primary Biliary Cirrhosis?
a liver biopsy is used to confirm the diagnosis and to stage the disease
Drugs can affect the bile flow and bile composition and this can extend to the liver, gallbladder and intestines. Give examples of drugs that can increase bile flow and examples of drugs that can reduce bile flow?
increase: phenobarbital, theophylline, glucagon, insulin
decrease: amiloride, oestrogen, chlorpromazine
What drug, used to increase biliary cholesterol secretion, can reduce bile acid concentrations, without altering biliary phospholipid concentrations?
clofibrate
What are the therapeutic effects of Ursodeoxycholic acid (bile acid)
- treats gallstones non-surgically
- decreases cytotoxicity of circulating bile acids
- increases bile flow by choleretic effect
Mechanisms of pharmacological actions of UDCA are…?
- Protection of cholangiocytes against cytotoxicity of hydrophobic bile acids
- Stimulation of hepatobiliary secretion
- Protection of hepatocytes against bile acid-induced apoptosis
