Gall Bladder Disease

Context

Gall bladder disease (specifically gall stones) is the most common abdominal complaint causing hospital admission in the developed world. In the UK, 5.5 million people have gall stones and 50 000 cholecystectomies are performed each year. [1]

Gall stones are 2-3 times more common in women than in men at post-mortem. [2] Obesity is the strongest independent risk factor for their development in women. [3] The increased incidence in women is most likely caused by the effect of oestrogen, which promotes the transfer of cholesterol from the blood to the liver. [4]

Learning Bite

Gallstones are found in up to 20% of adult females.

Gallstones

Gall stones are precipitates of bile that form in the gall bladder.

When fasting, 50% of bile produced is released into the duodenum, and 50% (up to 50 ml) is stored within the gall bladder. [5]

The breakdown of the contents of bile is illustrated in the graph. [1]

There are many risk factors for the production of cholesterol gall stones, which points to why cholesterol gall stones are so common worldwide. Risk factors associated with formation of cholesterol gall stones are as follows [1]:

• Increasing age
• Female sex
• Familial predisposition
• Pregnancy
• Hyperlipidaemia
• Bile salt loss (ileal disease, resection, clofibrate drugs)
• Diabetes mellitus, cystic fibrosis
• Total parenteral nutrition
• Prolonged fasting

Gall stones are found in the following forms:

• White or mixed (pure or mainly cholesterol): 80% of UK gall stones occur when bile is super-saturated with cholesterol
• Brown: <5% in the UK, due to stasis and infection within the biliary tree
• Black (bile predominant): seen in haemolytic disease (sickle cell, thalassaemia, G6PDHase deficiency and hereditary spherocytosis) and cirrhosis [1]

Learning Bite

Cholesterol gallstones are commonest.

Gall stone disease presents a spectrum of pathology, ranging from asymptomatic gall stones, to acute cholecystitis and ascending cholangitis. [4]

The position of the stone within the gastrointestinal tract relates to the clinical problems that are produced:

• It can pass freely (asymptomatic gall stone)
• It can get intermittently stuck in the biliary tract (biliary colic/chronic cholecystitis)
• It can get stuck for a more prolonged period (acute cholecystitis, ascending cholangitis, acute pancreatitis, gall bladder perforation and empyema)

The gall stone may also get stuck outside the biliary tract (gall stone ileus). However, 70% of gall stones are asymptomatic, with a yearly risk of developing pain of 1-4%. [1,6]

Acalculous cholecystitis occurs in 5-10% of cases of acute cholecystitis and tends to be more severe. It is more common in the elderly and those with diabetes mellitus. It may occur as a complication of burns or multiple trauma, and patients are very ill on presentation. [7]

Learning Bite

7 out of 10 patients with gallstones are likely to be asymptomatic.

Spectrum of Gall Bladder Disorder

Taking an accurate history is vital. The nature of the pain can tell us a lot about gall bladder disease, and many of the complications of gall stones can be suggested by the history.

The pain of gall stone disease

In gall stone disease the pain is felt in the right upper quadrant (RUQ) and epigastrium. The increasing severity and addition of associated features reflects passage along the pathophysiological spectrum of disease.

With ascension to consecutive levels of severity of gall stone disease, pain becomes sharper, more severe and well localised. Fever and systemic symptoms develop and get worse, and the patient may ultimately develop symptoms of septic shock.

The pain of biliary colic

The pain of biliary colic tends to be constant, and not colicky, as the name suggests. Biliary colic usually lasts 2-6 hours but can last up to 24 hours. Nausea and vomiting may be associated with the pain, but tend not to predominate.

The pain of chronic cholecystitis

Recurrent biliary colic equals chronic cholecystitis. Chronic cholecystitis is associated with some non-specific symptoms (e.g. fatty food intolerance, early satiety) but these are no more strongly linked to patients with gall stones than those without, and they don’t seem to go away with cholecystectomy.

When the initial pain in acute cholecystitis is dull and poorly localised, the lumen of the gall bladder is distended and the visceral peritoneal nervous fibres are stimulated. As the inflammatory process progresses, leakage of inflammatory fluid stimulates the parietal peritoneum nervous fibres and the pain becomes sharp and well localised.

Learning Bite

Biliary colic tends to refer to the individual episode of pain, whilst chronic cholecystitis refers to recurrent episodes.

Symptoms related to complications of gall stone disease are as follows:

• Pain from gall stone pancreatitis presents in a similar way to that caused by alcohol (i.e. epigastric or diffuse abdominal pain radiating to the back associated with nausea and vomiting)
• Ascending cholangitis, gall bladder empyema and gall bladder gangrene and perforation present in a similar way, with fever, severe RUQ pain and signs of severe sepsis

Ascending cholangitis is a life-threatening emergency, with an untreated mortality near 100%. The Charcot triad of fever, RUQ pain and jaundice is noted in only 25% of patients with ascending cholangitis, [7] however, the presence of all three has a specificity of around 93%. [8]

Examination: Murphy’s Sign

The patient may be flushed, jaundiced, dehydrated, tachycardic and hypotensive, all depending on the stage of gall stone disease continuum. They may have epigastric and/or RUQ tenderness, or diffuse abdominal tenderness (more likely to be gall stone pancreatitis).

Murphy’s sign is demonstrated by asking the patient to inspire while the examiner palpates deeply in the right subcostal region. A sharp increase in pain is felt as the inflamed gall bladder touches the examiner’s hand: this can cause inspiratory arrest.

Isolated rebound tenderness in the RUQ reflects localised peritoneal irritation secondary to leakage of inflammatory fluid (acute cholecystitis) or gall bladder contents (gall bladder perforation contained locally within the omentum). Generalised rigidity and peritonism is rare and reflects leakage of gall bladder contents from a gall bladder rupture into the peritoneal cavity.

There may be a reduction in bowel sounds and distension due to a secondary ileus.

Learning Bite

Murphys sign has been estimated as 97% sensitive for acute cholecystitis.

Examination: Jaundice

Jaundice is rarely found on examination and reflects either more chronic obstruction with delayed onset of inflammation, chronic intravascular haemolysis or the development of the classic Charcot triad. [7]

If the bile duct does become completely or partially obstructed, the patient will also develop pale stools and dark urine (since bilirubin can no longer pass into the gut in the normal way). The offending stone will usually be found in the common bile duct, but can be found in the neck of the gall bladder or the cystic duct, where it can compress the common hepatic duct causing blockage of bilirubin passage into the gut (Mirizzi’s syndrome). [9]

Fig. 1 Jaundice via Wikimedia Commons

Examination: Urinanalysis

Urinalysis and a beta-hCG test are investigations for gall stones.

Unconjugated bilirubin (produced in excess in haemolysis) will not appear in the urine because it is tightly bound to albumin, which cannot pass through the glomerulus.

Conjugated bilirubin is water-soluble and will therefore appear in the urine. Urobilinogen (a bilirubin breakdown product excreted into the blood; equivalent to stercobilinogen, which is excreted into the stool) will not appear in urine in cholestasis (just as stercobilinogen will not appear in the stool in cholestasis, hence the pale stools finding in obstructive jaundice).

A urinary pregnancy test should always be performed in presentations of abdominal pain in women of childbearing age to exclude ectopic pregnancy. Although it is important to remember that biliary disease is more common in pregnancy.

Laboratory Studies

Laboratory studies are an option for the investigation and management of gall stone disease.

These are of less use than in other abdominal conditions. In a patient with simple biliary colic blood tests are likely to be normal. Deranged liver function tests suggests that the patient may have developed more complicated gall bladder disease.

Full blood count

Forty percent of patients with acute cholecystitis may have a raised white cell count. This is non-specific and will often be raised in other causes of abdominal pain.

Learning Bite

In uncomplicated gall stone disease all bloods may well be normal. [10]

Urea and electrolytes and liver function tests

• Serum alkaline phosphatase may be raised and is a marker for biliary tract obstruction. It has isoenzymes in liver, bone, placenta, small bowel and white cells so is not specific for biliary tract obstruction. It is also not a sensitive test as it may not be immediately raised in episodes of acute obstruction, since its elevation represents enzyme induction, which takes time to develop
• Serum alanine aminotransferase, white cell count and bilirubin may all also be normal [7]
• Serum amylase should be checked to exclude acute pancreatitis (serum lipase may be a better predictor of clinical acute pancreatitis) [10]
• Urea and electrolytes are likely to be normal in uncomplicated gall bladder disease

Learning Bite

All bloods may be normal in uncomplicated gall bladder disease.

Plain abdominal x-ray is of no real benefit apart from looking for other pathologies. Only 10% of gall stones will show up on x-ray.

Ultrasound scan can pick up gall stones of 1-2 mm diameter within the gall bladder with 95% sensitivity and 97% specificity. Due to overlying bowel gas it may miss 25-40% of bile duct stones.

Acute cholecystitis can be identified on ultrasound scan by thickened gall bladder wall, pericholecystic fluid and a sonographic Murphy’s sign.

CT is historically not traditionally the first line investigation for acute cholecystitis however it may identify biliary pathology and has the advantage of identifying other intra-abdominal pathology.

The ultrasound scan shows the gall bladder in acute cholecystitis. The measurement A-A is greater than 6 mm which means the gall bladder wall is swollen and the white area below the measure A-A is a gall stone.

Learning Bite

The most important tools for diagnosis of acute cholecystitis are clinical suspicion and ultrasound scan. [10,11]

There are no formal risk assessment tools for the evaluation of gall stone disease.
However, the elderly and patients with diabetes are high-risk groups for the development of the complications of gall stone disease. Patients with ascending cholangitis and acalculous cholecystitis are also at high risk.

Emergency department (ED) management depends on the severity of the gall stone disease and the patient’s symptoms.

If pain has settled from an acute attack of biliary colic, the patient may be discharged from the ED.

If pain is ongoing, the diagnosis may be early acute cholecystitis or complications of gall stone disease. If there is any evidence of haemodynamic instability, a senior ED physician should be involved.

Resuscitation (if dehydrated or signs of sepsis)

• 

  High-concentration oxygen delivered by high flow oxygen and oxygen mask with reservoir bag

• Two large bore peripheral intravenous cannulae
• Blood tests
• Urinary catheter and measure urine volumes
• Urgent referral to senior surgeon and critical care if instability persists

Analgesia

Give opiate analgesia as appropriate. Do not withhold analgesia pending surgical review. [13]

Antibiotics

Intravenous broad-spectrum antibiotics should be given if there are signs of sepsis, acute cholecystitis or complicated gall bladder disease.

Antibiotic use will vary according to local policy. The most commonly used are piperacillin with tazobactam, third-generation cephalosporin or co-amoxiclav.

Nil by mouth

Keep nil by mouth and involve surgical and radiological teams.

Medical Approach

Medical treatment, apart from analgesia, should not be initiated in the ED.

For selected patients with high surgical risk, medical therapies may rarely be considered. Oral bile salt therapy (ursodeoxycholic acid, chenodeoxycholic acid) is not useful once gall stones have developed, but can prevent their development in high risk groups. [14]

Extracorporeal shockwave lithotripsy has usually been used together with sphincterotomy and a percutaneous approach. It has a high failure rate (95%) when used alone, and a high complication rate (19%).

Surgical Approach

Surgery is not indicated in asymptomatic patients, except in some select groups (e.g. sickle cell disease). [15] Surgical treatment choices are based on the patient’s clinical condition: less radical surgical procedures such as endoscopic retrograde cholangiopancreatography (ERCP) are done emergently in sick patients with ascending cholangitis or gall stone pancreatitis.

Comparing laparoscopic and open cholecystectomy, there is no difference between mortality, operating time or complication rate, but there is an extension of hospital stay with open cholecystectomy. [16]

Laparoscopic cholecystectomy

In the surgical treatment of acute cholecystitis and biliary colic many centres offer same admission cholecystectomy to patients who are admitted with symptomatic gall stone disease. [9] This has advantages in that morbidity in waiting period, hospital stay and operating time are all reduced.

Learning Bite

laparoscopic cholecsytectomy (increasingly same admission) is the treatment of choice for symptomatic gallstones.

Other surgical options

• Percutaneous cholecystostomy for biliary sepsis in patients with high surgical risk [17]
• ERCP, in patients with gall-stone pancreatitis [18]

• Patients with ascending cholangitis can deteriorate quickly.
• Gall bladder disease in pregnancy can be confused with other pathologies, including appendicitis.
• Diabetics and the elderly are more likely to develop the complications of gall bladder disease.
• Remember medical pathologies as diagnostic differentials.

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