If bile stones are present in the common bile duct, an endoscopic sphincterotomy can be conducted either with or without placing a stent. To do this, a duodenoscope is placed by the endoscopist in the second portion of the duodenum. A catheter and guidewire is moved up into the common bile duct. A sphincterotome can then enlarge the ampulla of Vater and release the stones. Later, the endoscopist can place a stent in the common bile duct to soften any remaining stones and allow for bile drainage. If needed, a balloon catheter is available to remove any leftover stones. If these stones are too large with these methods, surgical removal may be needed. Patients can also request an elective cholecystectomy to prevent future cases of choledocholithiasis. In case of narrowing of the common bile duct, a stent can be placed after dilating the constriction to resolve the obstruction.The treatment approach for patients with obstructive cholestasis resulting from cancer varies based on whether they are a suitable candidate for surgery. In most cases, surgical intervention is the best option. For patients whom complete removal of the biliary obstruction is not possible, a combination of a gastric bypass and hepaticojejunostomy can be used. This can reestablish bile flow into the small intestine, thereby bypassing the blockage. In cases where a patient is not a suitable candidate for surgery, an endoscopic stent can be placed.
These drugs activate the RhoA/Rho-kinase pathway, which inhibits myosin light chain phosphatase (MLCP), and in turn, increases myosin light chain phosphorylation by MLC kinase leading to constriction of bile canaliculi. Drugs that dilate canaliculi work by inhibiting MLCK or RhoA/Rho-kinase and include diclofenac, bosentan, entacapone, tacrolimus, cimetidine, and flucloxacillin. Constriction is more serious than dilation, as the former causes irreversible cell damage and death.Minor mechanisms that may contribute to DIC include aberrant paracellular permeability, membrane fluidity, and transporter localization. Tight junctions normally seal the gap between hepatocytes to prevent bile from diffusing out of the canaliculi. If a drug causes internalization of hepatocyte tight junctions, like rifampicin does in mice, bile flow may become impaired due to paracellular leakage. Membrane fluidity can affect bile flow by regulating the activity of hepatocyte Na+/K+-ATPase, which maintains the inwardly-directed Na+ gradient that drives BA uptake by apical NTCP. In rats, cyclosporine A was found to increase canalicular membrane fluidity and consequently reduce bile secretion. Bile flow was similarly reduced in rats as a result of alterations to basolateral membrane fluidity by ethinylestradiol and chlorpromazine. Lastly, some agents (rimpaficin and 17β-estradiol) were shown to hinder proper localization of hepatocyte transporters by interfering with the microtubules required for their insertion into plasma membranes. Diagnosis
Cholestasis can be suspected when there is an elevation of both 5-nucleotidase and ALP enzymes. With a few exceptions, the optimal test for cholestasis would be elevations of serum bile acid levels. However, this is not normally available in most clinical settings necessitating the use of other biomarkers.