The diagnosis approach for identifying the cause of cholestasis. 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. If 5’ nucleosidase and ALP enzymes are elevated, imaging studies such as computed tomography (CT) scan, ultrasound, and magnetic resonance imaging (MRI) are used to differentiate intrahepatic cholestasis from extrahepatic cholestasis. Additional imaging, laboratory testing, and biopsies might be conducted to identify the cause and extent of cholestasis. Biomarkers ALP enzymes are found abundantly within the bile canaliculi and bile. If a duct is obstructed, tight junctions permit migration of the ALP enzymes until the polarity is reversed and the enzymes are found on the whole of the cell membrane. Serum ALP levels exceeding 2-3 times the upper baseline value may be due to a variety of liver diseases. However, an elevation that exceeds 10 times the upper baseline limit is strongly indicative of either intrahepatic or extrahepatic cholestasis and requires further investigation. Cholestasis can be differentiated from other liver disorders by measuring the proportion of ALP to serum aminotransferases, where a greater proportion indicates a higher likelihood of cholestasis. Typically, aminotransferase enzymes are localized within hepatocytes and leak across the membrane upon damage. However, measurement of serum aminotransferase levels alone is not a good marker to determine cholestasis. In up to a third of patients, ALP levels may be elevated without the presence of cholestasis. As such, other biomarkers should be measured to corroborate findings. Measurement of 5’ nucleosidase levels may be used to identify cholestasis in conjunction with ALP. Levels of ALP may rise within a few hours of cholestasis onset while 5’ nucleosidase levels may take a few days. Many labs cannot measure 5’ nucleosidase and ALP levels so, GGT may be measured in some cases. Abnormal GGT elevation may be attributable to a variety of factors. As such, GGT elevations lack the necessary specificity to be a useful confirmatory test for cholestasis. Importantly, conjugated hyperbilirubinemia is present in 80% of patients with extrahepatic cholestasis and 50% of patients with intrahepatic cholestasis. Given that many patients with hyperbilirubinemia may not have cholestasis, the measurement of bilirubin levels is not a good diagnostic tool for identifying cholestasis. In a later stage of cholestasis aspartate transaminase (AST), alanine transaminase (ALT) and unconjugated bilirubin may be elevated due to hepatocyte damage as a secondary effect of cholestasis. Imaging After determination using biomarkers, a variety of imaging studies may be used to differentiate between intrahepatic or extrahepatic cholestasis. Ultrasound is often used to identify the location of the obstruction but, is often insufficient in determining the level of biliary obstruction or its cause because it can pick up bowel gas that may interfere with readings. CT scans are not impacted by bowel gas and may also be more suitable for overweight patients. Typically, the cause of cholestasis and magnitude of obstruction is better diagnosed with CT compared to ultrasound. MRI scans provide similar information to CT scans but are more prone to interference from breathing or other bodily functions. Although CT, ultrasound, and MRI may help differentiate intrahepatic and extrahepatic cholestasis, the cause and extent of obstruction is best determined by cholangiography. Potential causes of extrahepatic cholestasis include obstructions outside the wall of the lumen, those outside the duct, and obstructions found in the duct lumen. Endoscopic retrograde cholangiography may be useful to visualize the extrahepatic biliary ducts. In case of anatomical anomalies, or if endoscopic retrograde cholangiography is unsuccessful, percutaneous transhepatic cholangiography may be used. CT or MRI-based cholangiography may also be useful, particularly in cases where additional interventions are not anticipated. Histopathology There is a significant overlap between cholestasis resulting from a hepatocellular origin and cholestasis caused by bile duct obstruction. Due to this, obstructive cholestasis can only be diagnosed after finding additional diagnostic signs that are specific to obstructive changes to the bile ducts or portal tracts. In both non-obstructive and obstructive cholestasis, there is an accumulation of substances that are typically secreted in the bile, as well as degeneration of hepatocytes. The most significant feature from a histopathological perspective includes pigmentation resulting from the retention of bilirubin. Under a microscope, the individual hepatocytes will have a brownish-green stippled appearance within the cytoplasm, representing bile that cannot get out of the cell. Pigmentation can involve regurgitation of bile into the sinusoidal spaces caused by phagocytosis from Kupffer cells, an accumulation of bilirubin within hepatocytes, and inspissated bile in the canaliculi. Most pigmentation and canaliculi dilation occurs in the perivenular region of the hepatic lobule. In chronic cases, this may extend into the periportal area. Hepatocyte necrosis is not a significant feature of cholestasis; however, apoptosis may often occur. Under the microscope, hepatocytes in the perivenular zone appear enlarged and flocculent. In cases of obstructive cholestasis, bile infarcts may be produced during the degeneration and necrosis of hepatocytes. Bile infarcts are marked by a large amount of pigmented tissue surrounded by a ring of necrotic hepatocytes. In some cases, hepatocyte degeneration is uncommon. E.g., with Alagille syndrome limited degeneration occurs, however, there may be a small amount of apoptosis and enlarged hepatocytes. Cholestasis is often marked by cholate statis, which are a set of changes that occur in the periportal hepatocytes. Cholate statis is more common in obstructive cholestasis compared to non-obstructive cholestasis. During the cholate statis process, hepatocytes first undergo swelling and then degeneration. Under the microscope, this is evident as a lucent cell periphery and enlarged cytoplasm around the nucleus. Oftentimes, Mallory bodies may also be found in the periportal areas. Due to the retention of bile, which contains copper, stains made for staining copper-associated protein can be used to visualize bile accumulation in the hepatocytes. Cholestatic liver cell rosettes may occur in children with chronic cholestasis. Histologically, this is evident as two or more hepatocytes in a pseudotubular fashion that encircle a segment of enlarged bile canaliculi. Children may also have giant hepatocytes present, which are characterized by a pigmented spongy appearance. Giant cell formation is likely caused by the detergent properties of bile salts causing a loss of the lateral membrane and joining of hepatocytes. In the case of Alagille syndrome, hepatocyte degeneration is uncommon. However, there may be a small amount of apoptosis and enlarged hepatocytes. In non-obstructive cholestasis, changes to the portal tracts are unlikely. However, it may occur in some unique situations. In the case of neutrophilic pericholangitis, neutrophils surround the portal ducts and obstruct them. Neutrophilic pericholangitis has a variety of causes including endotoxemia, Hodgkin's disease, among others.<unk>  lenta can also cause changes to the portal tracts. This occurs during chronic cases of sepsis and results in dilation of the bile ductules.<unk>  lenta is likely a result of a stoppage of bile secretion and bile flow through the ductules. Back pressure created from obstructive cholestasis can cause dilation of the bile duct and biliary epithelial cell proliferation, mainly in the portal tracts. Portal tract edema may also occur as a result of bile retention, as well as periductular infiltration of neutrophils. If the obstruction is left untreated, it can lead to a bacterial infection of the biliary tree. Infection is mostly caused by coliforms and enterococci and is evident from a large migration of neutrophils to the duct lumina. This can result in the formation of a<unk>  abscess. With treatment, many of the histological features of cholestasis can be corrected once the obstruction is removed. If the obstruction is not promptly resolved, portal tract fibrosis can result. Even with treatment, some fibrosis may remain.
symptom of Primary biliary cholangitis
symptoms of Primary biliary cholangitis
symptom of Autoimmune hepatitis
symptom of Hepatitis A
symptom of Gallbladder cancer
medical cause of Pancreatitis
symptom of Hepatitis D
symptom of Giardiasis