Author: Lisa Carter / Editor: Janet Skinner / Reviewer: Jennifer Lockwood / Codes: CAP1, HAP1 / Published: 31/10/2017 / Review Date: 31/10/2020
Gall Bladder, specifically gallstone, disease is the commonest abdominal complaint causing hospital admission in the developed world. 5.5 million people have gallstones in the UK and 50,000 cholecystectomies are performed in the UK each year [i]. Gallstones are found 2-3 times more commonly in women than men at post mortem [ii]. Obesity is the strongest independent risk factor for their development in women [iii]. Their increased incidence in women is most likely caused by the effect of oestrogen moving cholesterol from the blood to the liver [iv].
Gallstones are found in up to 20% of adult females
Gallstones 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 50mls) is stored within the gall bladder [vi]. Normal bile- 70% bile salts (mainly cholic and chenodeoxycholic acids), 22% phospholipids (lecithin), 4% cholesterol, 3% proteins, and 0.3% bilirubin [i].
White or mixed (pure or mainly cholesterol)-80% of UK gall stones occur when bile is super-saturated with cholesterol
Brown- <5% in UK, due to stasis and infection within bleary tree
Black (bile predominant)- seen in haemolytic disease (sickle cell, thalassaemia, G6PDHase deficiency and hereditary spherocytosis) and cirrhosis (i)
Cholesterol gallstones are commonest
Risk factors associated with formation of cholesterol gall stones [i] are as follows:
- Increasing age
- Female sex
- Familial predisposition
- Bile salt loss (ileal disease, resection, clofibrate drugs)
- Diabetes Mellitus, Cystic Fibrosis
- Total parenteral nutrition
- Prolonged fasting
symptomatic gall stone disease is the second commonest abdominal emergency in pregnancy (vii)
Basic Science and Patho-physiology
Gallstone disease presents a spectrum of pathology, ranging from asymptomatic gallstones, to acute cholecystitis and ascending cholangitis [v]. Which part of the disease spectrum experienced by the patient depends on how the gallstone passes through the biliary tract to the gut it can pass freely (asymptomatic gallstone), it can get intermittently stuck in the biliary tract (biliary colic/chronic cholecystitis), and it can get stuck for a more prolonged period (acute cholecystitis, ascending cholangitis, acute pancreatitis, gallbladder perforation and empyema). The gallstone may also get stuck outwit the biliary tract (gallstone ileus). However, 70% of gallstones are asymptomatic [viii], with a yearly risk of developing pain of 1-4%[i].
Acalculous cholecystitis occurs in 5-10% of cases acute cholecystitis and tends to be nastier. It is more common in the elderly and those with diabetes mellitus. It may occur as a complication of e.g. burns, multiple trauma and patients are very sick on presentation [v].
7 out of 10 patients with gallstones are likely to be asymptomatic
What is the difference between biliary colic and chronic cholecystitis?
The pain of biliary colic tends to be constant, and not colicky, as the name suggests [v]. Biliary colic usually persists for between 2 and 6 hours but can last up to 24 hours [i]. Nausea and vomiting can be associated with the pain, but tend not to predominate. Recurrent biliary colic equals chronic cholecystitis. Chronic cholecystits is associated with some non specific symptoms, but these symptoms e.g. fatty food intolerance, early satiety, are no more strongly linked to patients with gallstones than without, and dont seem to go away with cholecystectomy.
Why does pain change from dull and poorly localised upper abdominal pain to sharp and well localised right upper quadrant pain?
When the initial pain in acute cholecystitis is dull and poorly localised, the lumen of the gallbladder 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.
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:
- Gall stone pancreatitis presents in a similar way to that caused by alcohol i.e. epigastric or diffuse abdominal pain radiating to back associated with nausea and vomiting.
- Ascending cholangitis, gallbladder empyema and gallbladder gangrene and perforation present in a similar way with fever, severe right upper quadrant pain and signs of severe sepsis.
Ascending cholangitis is a life-threatening emergency, with an untreated mortality near 100%. Charcot triad of fever, RUQ pain and jaundice is noted in only 25% of patients with ascending cholangitis [ix].
Patients with ascending cholangitis can become very sick very quickly
The patient may be flushed, jaundiced, dehydrated, tachycardic and hypotensive all depending at which stage of the continuum of gall stone disease he is at. He may have epigastric and/or RUQ tenderness, or diffuse abdominal tenderness (more likely to be gall stone pancreatitis).
Murphys sign is demonstrated by asking the patient to inspire whilst the examiner palpates deeply in the right subcostal region. A sharp increase in pain is felt as the inflamed gallbladder touches the examiners hand this can cause inspiratory arrest.
Isolated rebound tenderness in the RUQ area reflects localised peritoneal irritation secondary to leakage of inflammatory fluid (acute cholecystitis) or gallbladder 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.
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 [v].
If the bile duct does become completely or partially obstructed, along with jaundice the patient will 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 (Mirizzis syndrome)[x].
Murphys sign has been estimated as 97% sensitive for acute cholecystitis
Differential diagnosis of gallstone disease is extensive and includes (v)
- Abdominal conditions gastritis, gastro-oesophageal reflux disease, peptic ulcer disease, pancreatitis, hepatitis, renal colic, pyelonephritis, appendicitis
- Gynaecological conditions pelvic inflammatory disease, peri-hepatitis (Fitxhugh-Curtis syndrome), ectopic pregnancy, complications of normal pregnancy (e.g. premature onset of labour, placental abruption
- Medical conditions myocardial infarction, pneumonia, pleural effusion
Gallstone disease has a wide differential diagnosis
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.
Urinalysis and BhCG
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 (bilirubin breakdown product excreted into the blood, equivalent of 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).
Urinary pregnancy test always perform in presentations of abdominal pain in women of childbearing age to exclude ectopic pregnancy
These are of less use than in other abdominal conditions. In a patient with simple biliary colic bloods are likely to be normal. Deranged liver function tests suggests that the patient may have developed more complicated gall bladder disease
1.Full blood count 40% 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.
2.Urea and electrolytes 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 since 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 [v].
Serum amylase should be checked to exclude acute pancreatitis. (Serum lipase may be a better predictor of clinical acute pancreatitis) [xi]. Urea and electrolytes are likely to be normal in uncomplicated gallbladder disease
All bloods may be normal in uncomplicated gallbladder disease
Plain abdominal x-ray is of no real benefit apart from looking for other pathologies, as only 10% of stones will show up on x-ray.
Ultrasound scan can pick up gallstones within the gallbladder of 1-2mm diameter with 95% sensitivity and 97%specificity.
Due to overlying bowel gas it may miss between 25 and 40% of bile duct stones.
Acute cholecystitis can be identified on ultrasound scan by thickened gallbladder wall, pericholecystic fluid and a sonographic Murphys sign.
CT and plain radiology are not generally helpful in the diagnosis of acute cholecystitis.
The most important tools for diagnosis of acute cholecystitis are clinical suspicion and ultrasound scan [xii, xiii]
Depends on the severity of gallstone disease if pain has settled from an acute attack of biliary colic, patient may be discharged from the ED. If pain is ongoing, diagnosis may in fact be early acute cholecystitis or complications of gall stone disease. Any evidence of haemodynamic instability then involve senior ED physician.
1. RESUSCITATE if dehydrated or signs of sepsis. High concentration Oxygen delivered via a variable deliver mask with reservoir bag, two large bore peripheral intravenous cannulae, bloods see investigations, urinary catheter and measure urine volumes, urgent referral to senior surgeon and Critical Care if instability persists
2. ANALGESIA Give opiate analgesia as appropriate, do not withhold analgesia pending surgical review [xiv]
3. ANTIBIOTICS Intravenous broad-spectrum antibiotics if signs of sepsis, acute cholecystitis or complicated gall bladder disease. Antibiotic use will vary according to local policy, although mainly 3nd generation cephalosporin
4. NIL BY MOUTH
Medical treatment, other than 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 gallstones have developed, but can prevent their development in high-risk groups [xv]. 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%) [xvi].
Surgery is not indicated in asymptomatic patients, except in some select groups e.g. sickle cell disease [xvii]. Surgical treatment choices are based on the patients clinical condition, less radical surgical procedures like ERCP being done emergently in sick patients with ascending cholangitis or gallstone pancreatitis.
Laparoscopic versus open cholecystectomy no difference between mortality, operating time or complication rate but there is an extension of hospital stay with open cholecystectomy [xviii].
Delayed cholecystectomy versus cholecystectomy on presentation for biliary colic and acute cholecystitis offer same admission cholecystectomy for patients who are admitted with symptomatic gall stone disease [xix]. This has advantages in that morbidity over waiting period, hospital stay and operating time are all reduced.
Percutaneous cholecystostomy for biliary sepsis in patients with high surgical risk [xx].
Endoscopic retrograde cholangiopancreatography in patients with gallstone pancreatitis [xxi]
laparoscopic cholecsytectomy (increasingly same admission) is the treatment of choice for symptomatic gallstones
Prognosis & Followup strategies:
- 70% of patients with gallstones are asymptomatic
- 1-4% of asymptomatic patients will develop symptoms each year
- Diabetics and the elderly are high-risk groups for the development of the complications of gall stone disease
- Charcot triad of fever, RUQ pain and jaundice is noted in only 25% of patients with ascending cholangitis
- Murphys sign has been estimated as 97% sensitive for acute cholecystitis
- Serum alanine aminotransferase, alkaline phosphatase, white cell count and bilirubin may all be normal in uncomplicated gallstone disease
- The most important tools for diagnosis of acute cholecystitis are clinical suspicion and ultrasound scan
- Administration of analgesia should not be delayed pending surgical review (grade++, recommendation++)
- laparoscopic cholecystectomy for symptomatic gall stone disease stay in hospital is shorter with laparoscopic surgery. (grade++, recommendation++)
- Same admission cholecystectomy for symptomatic gallbladder disease is increasingly performed[i](grade++, recommendation++)
- Patients with ascending cholangitis get very sick very quickly therefore a high index of suspicion must be maintained
Safety pearls and Pitfalls:
- 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 gallbladder disease
- Remember medical pathologies as diagnostic differentials
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