What is Cholestatic Jaundice ?
Cholestasis is a medical condition in which the flow of bile (a digestive fluid) either slows down or stops entirely. This can be caused by a problem with the liver cells that produce bile, an obstruction in any part of the bile flow pathway, or both. Depending on where the blockage is, cholestasis can be classified as either intrahepatic (within the liver) or extrahepatic (outside the liver).
Intrahepatic cholestasis, which can be further divided into intralobular and extralobular, is the result of diseases that affect liver cells and/or the bile ducts within the liver. Extrahepatic cholestasis, on the other hand, occurs when there is a blockage outside the liver, along the extrahepatic bile ducts.
The flow of bile is essential for the body to get rid of certain substances, such as bilirubin and bile acids. When this flow is interrupted, these substances can build up in the blood. This build-up is primarily indicated by an increase in serum alkaline phosphatase levels. The symptoms of cholestasis can include jaundice (a yellowing of the skin and eyes due to excess bilirubin), pruritus (itching) due to a build-up of bile acids, and malabsorption of fat and fat-soluble vitamins. It is also possible to have severe cholestasis without jaundice, in which the patient may experience only pruritus but no jaundice.
What Causes Cholestatic Jaundice ?
Cholestasis, also known as bile flow blockage, can occur outside (extrahepatic) or inside (intrahepatic) the liver. Different conditions can lead to either type of Cholestasis.
Extrahepatic Cholestasis can be caused by gallstones in the bile duct (Choledocholithiasis), narrowing of the bile duct (Benign bile duct strictures), scarring of the bile duct due to inflammation (Primary or secondary sclerosing cholangitis), blockage due to gallstones pressing against the bile duct (Mirizzi syndrome), bile duct cancer (Cholangiocarcinoma), pancreatic cancer, or tumor in the bile duct (Ampullary adenoma/carcinoma).
Intrahepatic Cholestasis can be due to various reasons related to liver cells (Hepatocellular Causes), changes in the canalicular membrane (Canalicular Membrane Changes), genetic defects in bile transporters, blockage of the ductal lumen (Canalicular/Ductular Luminal Obstruction), or reduction in bile ducts (Ductopenia).
Hepatocellular causes can include viral hepatitis, acute alcoholic hepatitis, parenteral nutrition, atresia of the bile ducts within the liver in infants (intrahepatic atresia), or a rare congenital disorder called Zellweger syndrome.
Canalicular Membrane Changes can be caused by medications such as contraceptive pills, antibiotics, antithyroid drugs, sulphonamides, or cholestasis during pregnancy.
Genetic defects in bile transporters can lead to conditions like Benign recurrent intrahepatic cholestasis (BRIC) or Progressive familial intrahepatic cholestasis (PFIC).
Canalicular/Ductular Luminal Obstruction can occur due to reasons like cholestasis in sickle cell disease, a type of genetic disorder (Hereditary protoporphyria), bacterial infections, sepsis, or cystic fibrosis.
Ductopenia can be due to familial factors, drug-induced factors, chronic allograft rejection, Hodgkin disease, sarcoidosis, primary sclerosing cholangitis, or primary biliary cholangitis.
Risk Factors and Frequency for Cholestatic Jaundice
Cholestasis, a liver condition, can affect people of all ages. However, children and teenagers are more prone to this disease because their livers are not fully developed. It’s also important to note that cholestasis affects both males and females equally. However, women have a slightly higher risk of developing certain types of cholestasis, like biliary atresia, drug-induced cholestasis, and intrahepatic cholestasis, which can occur during pregnancy.
Signs and Symptoms of Cholestatic Jaundice
If you suddenly start seeing yellowish tinge in the skin and the eyes, a condition known as jaundice, it may signal a serious health issue like liver disease. The speed at which the jaundice symptoms develop can hint at the type of health issue. If the symptoms appear quickly, it could be due to an acute illness, while slower onset of symptoms might indicate a chronic disease or even cancer.
The following factors can help determine the cause of jaundice:
- Pain in the upper abdomen could suggest a condition called Mirrizi syndrome, caused by gallstone problems.
- If you also have a fever, it might suggest a case of cholangitis, an inflammation of the bile duct.
- Jaundice developing after surgery on the liver or bile duct might mean there was an injury or leak.
- If you’ve recently been very ill or shocked, it can lead to a condition known as cholestasis of sepsis.
- Certain medications, including antibiotics, can cause cholestasis, leading to jaundice.
More gradual onset of jaundice with nausea, vomiting, and a prodrome phase might suggest viral hepatitis. Your travel history, recent surgical procedures, blood transfusions, sexual contacts, or intravenous drug use can act as a supporting evidence for this. If you or your family have a history of autoimmune diseases, it could be a factor for certain conditions like PSC or PBC.
In chronic cholestasis, you might observe:
- Itching: This is a common symptom in chronic cholestasis which can become severe as the day progresses.
- Fatigue: This occurs in about 70% to 80% of patients suffering from chronic fatigue.
In chronic cholestasis, there’s a lack of bile, needed for absorbing vitamins A, D, E, and K. This can lead to a deficiency of these vitamins. Another symptom of chronic cholestasis can be xanthomas – slightly raised, yellowish growths on the skin.
In terms of physical examination, the following might be observed:
- The extent of the yellow hue on your skin, eyes, and mouth can indicate the severity of jaundice.
- Weight loss and weakness can hint at cancer or cirrhosis, a liver disease.
- For chronic cholestasis, some skin observations may include itch marks, pigmentation, and xanthomas. Signs of liver disease or intravenous drug use might be visible too.
- In the abdomen, a large or tender liver can suggest metastasis, viral hepatitis, heart failure, or alcoholic hepatitis. Pain in the right upper quadrant of the abdomen can indicate gallstone issues. An enlarged, painless gallbladder may be a sign of pancreatic cancer. Splenomegaly (enlarged spleen) and ascites (fluid build-up in the abdomen) can occur in severe liver conditions.
Testing for Cholestatic Jaundice
When examining liver health, various tests are conducted. These include checking the levels of total and direct (fractioned) bilirubin in the blood. A noticeable increase in direct bilirubin, making up more than 50% of the total bilirubin, is an indicator of a condition known as cholestasis. The level of an enzyme called alkaline phosphatase tends to be three times more than the upper normal limit during cholestasis, whereas levels for transaminases, another group of liver enzymes, remain normal or only slightly elevated. The body’s protein levels, measured through Serum albumin, usually stay normal unless there are chronic liver diseases or cirrhosis, where it is decreased.
Looking at a patient’s blood cell counts could also provide clues about liver health. An elevated white blood cell count, or leukocytosis, can be noted in conditions like cholangitis, alcoholic hepatitis, or even cancer. Also, severe anemia may be an indicator of hemolysis, a process in which red blood cells are broken down. Tests like peripheral smear and reticulocyte counts can be beneficial in these cases. Chronic anemia may be seen if the patient has conditions like cirrhosis or cancer. Prothrombin time, a test measuring how long it takes blood to clot, can be prolonged in cholestasis but can be quickly corrected with vitamin K supplements, unlike in patients with cirrhosis.
Imaging tests like abdominal ultrasound can be useful for identifying any dilation or swelling in the bile ducts. This information can allow doctors to differentiate between liver cell-related cholestasis, where the ducts are normal size, and bile duct blockages, where the ducts are enlarged. If ultrasound testing reveals dilated bile ducts, a magnetic resonance imaging (MRI) test can provide a more in-depth study of the bile ducts. MRI scans are more sensitive and can detect things like stones, strictures, or potentially cancerous growths more accurately than CT scans.
Finally, a liver biopsy can be helpful for examining the possible root causes of intrahepatic cholestasis, where the blockage of bile flow is inside the liver.
Treatment Options for Cholestatic Jaundice
The treatment for cholestatic jaundice, a condition where bile cannot flow from the liver to the duodenum, greatly depends on the specific cause and type of cholestatic disease. The first step in treating obstructive cholestasis, where bile flow is physically blocked, is usually to drain the bile. However, for hepatocellular cholestasis, a type resulting from liver cell damage, the treatment involves relieving the symptoms while also treating the main disease responsible for it.
When dealing with bile duct stones or benign obstructions in the bile duct, treatments involve making an incision in the muscular valve in the bile duct to remove the stone or relieve the obstruction. Sometimes, a stent, a small tube, is inserted to keep the bile flowing.
In cases of malignant obstruction, the treatment will depend on the disease’s stage and the patient’s ability to undergo surgery. Typically, removing the block is the first option. But, if the obstruction cannot be entirely removed, a surgical bypass procedure may be performed. If the patient isn’t fit for surgery, a stent may be placed in the bile duct to relieve the block. Antibiotics are often given before and after this procedure to prevent infection.
One common symptom associated with obstructive physiology is itchiness, which usually subsides within a day or two after bile drainage. For those who continue experiencing itchiness, multiple medications could help.
Cholestyramine, a drug taken with breakfast, is sometimes good to start with. The dosage may be adjusted based on individual responses, and fat-soluble vitamins are often supplemented to compensate for side effects of the drug.
Ursodeoxycholic acid, another medication, may reduce itchiness in cholestasis patients. Antihistamines can also be used, particularly at night for their sedative effects. For resistant itching, drugs like Phenobarbitone or the experimental drug Naloxone are considered.
Some non-drug treatment options include exposure to bright light or a procedure called plasmapheresis, where plasma is removed from the blood. For severe, persistent itchiness, portions of the small intestine may be surgically removed.
Ultimately, for patients with progressive diseases such as Primary Biliary Cholangitis (PBC) or Primary Sclerosing Cholangitis (PSC), a liver transplant could cure intractable itchiness.
What else can Cholestatic Jaundice be?
When it comes to diagnosing specific liver conditions, doctors often have to rule out several potential ailments. These include the following:
- Acute liver failure, which is a rapid decrease in liver function
- Acute hepatitis, or inflammation of the liver
- Acute pancreatitis, which is sudden inflammation of the pancreas
- Amyloidosis, a disorder where abnormal proteins build up in tissues and organs
- Autoimmune hepatitis, a condition where the body’s immune system wrongly attacks the liver
- Biliary obstruction, which is a blockage in the tubes that carry bile from the liver to the gallbladder and small intestine
- Cardiac cirrhosis, often due to long-standing heart conditions
- Cholangitis, an inflammation of the bile ducts
- Cholecystitis, or inflammation of the gallbladder
- Cirrhosis, which is a late stage of scarring (fibrosis) of the liver caused by various diseases and conditions
The doctor should consider these possibilities and perform appropriate tests to make the right diagnosis.