Hepatology - Cholestasis and biliary diseases Flashcards
What is cholestasis? What conditions can cause it?
Cholestasis is a situation where bile cannot flow from the gall bladder to the duodenum. As a result, unconjugated and conjugated bilirubins are retained and bile salts are increased.
Conditions causing cholestasis fall into 2 groups:
1) mechanical blockage of the duct system - obsructive or extrahepatic cholestasis
2) disturbances in bile formation - hepatocellular or intrahepatic cholestasis
What is the most common type of cholestasis and which patients are more at risk?
Extrahepatic cholestasis accounts for 70% of cholestasis cases. Women tend to be more affected overall because of other conditions such as cholestasis of pregnancy, biliary atresia and drug induced cholestasis. Newborns and infants are also more susceptible because of immaturity of the liver.
What features of the history are important to elicit in cases of cholestasis?
1) Jaundice - elevated conjugated bilirubin
2) Pale stools and dark urine - no bile can reach the intestinal tract and dark urine occurs because of reflux of conjugated bilirubin into the blood
3) Abdominal pain
4) Fever - suggests infection
5) Pruritis (manifest by scratch marks)
What investigations should be undertaken in cholestasis?
LFTs confirm the diagnosis:
- high ALP and GGT suggest obstruction
- high serum transaminases suggest hepatocellular
- albumin and globulin change little in the acute disease, but albumin decreases and globulin increases in chronic disease
- U&E and creatinine - AKI may be present
- raised bilirubin
- hyperlipidaemia
- haematology screen - may show anaemia (i.e. malignancy) raised WCC (infection). Reticulocytosis points to pre hepatic jaundice and it is worth checking the pro thrombin time
Imaging:
- abdominal USS to determine if obstruction is present
- AXR in acutely unwell patients (i.e. jaundiced, abdominal pain, fever)
What differential diagnoses should be considered in cholestasis?
1) Obstructive cholestasis:
- most commonly due to gallstones or carcinoma of the head of the pancreas
- duct paucity (Alagille’s syndrome - autosomal dominant disorder) can cause obstruction
- LUMINAL: gallstones, parasitic (hydatid or roundworm) or iatrogenic (post ERCP)
- MURAL: sclerosing cholangitis, other forms of cholangitis (e.g. infective cholangitis or associated with Langerhans cell histiocytosis), cholangiocarcinoma, stricture
- EXTRAMURAL: pancreatic carcinoma, chronic duodenal ulceration, pancreatitis, porta hepatis tumour
2) Hepatocellular cholestasis:
- cirrhosis and drug reactions (e.g. phenothiazines, erythromycin, chlorpormazine) are MCC
- viral or alcoholic hepatitis
- sclerosing cholangitis
- septiciaemia
- PBC
Think about:
- other blood tests - e.g. autoantibody screen, hepatitis screen, blood cultures
- ERCP and PTC
- MRCP
- Liver biopsy
- CXR/ CT if malignancy found
How is cholestasis treated?
Resuscitate an acutely unwell patient. Management depends on the underlying problem. Secondary effects of cholestasis will also be improved with management of the underlying condition - e.g. - pruritis - colestyramine - asthma type picture - osteopaenia - bisphosphonates - hypercholesterolaemia
What are the complications of cholestasis?
Retention of bile salts can lead to cellular damage, with hepatocytes being most sensitive. Cholestasis can give rise to secondary liver disease such as hepatic fibrosis.
Metabolic bone disease (osteopaenia, and osteoporosis)
Bleeding tendencies, particularly epistaxis.
Asthma type wheeze that is unresponsive to conventional treatment.
Complications from investigative procedures.
What is the pathophysiology of gallstone formation? What are the different types?
Gallstones are present in 10-20% of population. They are most common in women, and prevalence increases with age. There are 2 types of gallstones:
1) Cholesterol gallstones (80%) - cholesterol is held in solution by the detergent action of bile salts and phospholipids with which it forms micelles and vesicles. Cholesterol gallstones form in bile which has an excess of cholesterol (either because there is a deficiency of bile salts and phospholipids, OR an excess of cholesterol)
2) Pigment stones - formed from bilirubin polymers and calcium bilirubinate. These are seen in patients with chronic haemolysis - e.g. hereditary spherocytosis and sickle cell disease. Can also form in bile ducts after cholecystectomy and with duct strictures
How does biliary colic present?
Biliary colic is the term used for the pain associated with the temporary obstruction of the cystic or CBD by a stone. There are recurrent episodes of severe constant pain in the RUQ, usually following fatty food which subsides after a few hours. The pain may radiate to the right shoulder and right subscapular region and is often associated with vomiting. Examination is usually normal.
What investigations and management is needed in biliary pain?
Diagnosis is made on the basis of a typical history and an USS showing gallstones. Increases of serum ALP and bilirubin during an attack support the diagnosis of biliary colic. The absence of inflammatory features (fever, raised WCC, and local peritonism) differentiates this from acute cholecystitis.
Rx - analgesia and elective cholecystectomy. Abnormal LFTs or a dilated CBD on USS is an indication for preoperative MRCP. CBD stones identified on imaging are removed by ERCP or sometimes at the same time as cholecystectomy.
What are the clinical features of acute cholecystitis?
Acute cholecystitis follows the impaction of a stone in the cystic duct or neck of the gall bladder. Very occasionally, acute cholecystitis may occur without stones (acalculous cholecystitis). RUQ pain, fever, Murphy’s sign positive on examination, occasionally mildly deranged LFTs especially if Mirizzi syndrome. Complications include an empyema (pus) and perforation with peritonitis. The differential diagnosis is from other causes of RUQ pain.
How should cholecystitis be investigated and treated?
WCC shows a leucocytosis
Serum liver biochemistry may be mildly elevated
Abdominal USS shows gallstones and a distended gall bladder with a thickened wall. There is focal tenderness directly over the visualised gall bladder.
Treatment is initially conservative, with NBM, i.v. fluids, pain relief and intravenous antibiotics (e.g. cefotaxime). Cholecystectomy is usually performed within 48 hours of admission, and always if complications.
What is the definition of chronic cholecystitis?
Chronic inflammation of the gallbladder is often found in association with gallstones. On US examination this may appear as a small shrunken gall bladder. There is no evidence that this produces any symptoms, and cholecystectomy is NOT indicated. Chronic RUQ pain and fatty food intolerance are likely to be functional in origin and gallstones an incidental finding.
What causes acute cholangitis?
This is an infection of the biliary tree and most often occurs secondary to CBD obstruction by gallstones (choledocholithiasis). Other causes are benign biliary strictures following biliary surgery or associated with chronic pancreatitis, PSC, HIV cholangiopathy, and in patients with biliary stents. Bile duct obstruction due to cancer of the head of pancreas or bile duct (cholangiocarcinoma) can also cause cholangitis and this is more likely after ERCP.
Classic description is with fever, RUQ pain and jaundice (Charcot’s triad) although all 3 of these are not always present. Jaundice is cholestatic in type and the urine is dark, the stools pale and the skin may itch.
How is cholangitis investigated and managed?
WCC shows leucocytosis
Blood cultures are positive in 30% of cases (E.coli, Enterococcus faecalis, sometimes anaerobes)
LFTs show a cholestatic picture with raised ALP and bilirubin
USS shows dilated CBD and may show the cause of an obstruction
Management is with fluid resuscitation, broad spectrum antibiotics (cefotaxime (ciprofloxacin if allergic) + metronidazole), correct any coagulopathy, and early ERCP. Stones can be removed or a stent placed if this is not possible/ malignancy. Antibiotics should be continued for 7-10 days post ERCP.
