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THEME OF THE LECTURE:

June 29, 2024

DISEASES OF GALL BLADDER: CHRONIC CHOLECYSTITIS,

CHOLEDOCHOLITHIASIS, CHOLANGITIS,

DYSKINEZIA OF BILE DUCTS.

Plan of the lecture:

1. Etiology and pathogenesis of diseases of gall bladder

2. Classification

3. Clinical picture of diseases of gall bladder

4. Diagnosis of diseases of gall bladder

5. Differential diagnosis of diseases of gall bladder

6. Treatment of diseases of gall bladder

Half of patients with gallstones experience no problems but 35% of patients with gallstones discovered by chance will require treatment over the next 10 years as a result of either pain or complications. A number of clinical conditions may develop as a result of gallstones depending upon their location

Acute cholecystitis. The abrupt onset of severe, right upper quadrant (RUQ) pain, which is constant and does not remit, points to acute cholecystitis. It is usually accompanied by pyrexia and leucocytosis and is a result of impaction of a gallstone in the cystic duct with associated infection in 50% of cases. Jaundice may develop if there is compression of the common bile duct (CBD) either because of the stone in the cystic duct or as result of surrounding inflammation (Mirizzi’s syndrome). In seriously ill, elderly patients a similar picture may develop in the absence of gallstones and is termed acute acalculous cholecystitis and carries a poor prognosis.

Biliary pain / chronic cholecystitis

The symptoms are of intermittent, dull RUQ pain – constant or colicky. It may occur at any time and is not necessarily related to meals. It resolves spontaneously within a few hours and is not associated with systemic upset. These symptoms are a common indication for cholecystectomy, but it is difficult to determine that patients’ symptoms are caused by their gallstones in this group. Symptoms of non-specific, post-prandial pain, bloating and fatty food intolerance are not good discriminators and 25% of patients who undergo cholecystectomy for these symptoms will experience continued discomfort postoperatively.

Choledocholithiasis

Stones which have migrated into or formed within the CBD may be asymptomatic and be discovered by an elevation in the alkaline phosphatase level. They are usually associated with biliary type pain and intermittent jaundice and can cause obstruction. Removal of these stones is essential as there is a high complication rate (Table 1).

Cholangitis

This occurs when there is infection in the biliary tree, usually as a result of CBD stones. Patients present with biliary pain, jaundice, fever and often rigors. The septicaemia is usually due to Gram-negative organisms, is frequently severe and may be lifethreatening.

Table 1 Conditions resulting from gallstones

Dyskinezia of bile ducts.

– Hypertonic, hyperkinetic type

– Hypotonic, hypokinetic type

– Mixed type.

The symptoms are of intermittent, dull RUQ pain – constant (hypotonic, hypokinetic type) or colicky (hypertonic, hyperkinetic type).

Less common complications

As stones pass the ampulla of Vater, they can induce a biliary pancreatitis. Stones may erode through the gallbladder wall into the ileum causing a choleeystenteric fistula. Gallbladder stones may be associated with calcification of the gallbladder wall (‘porcelain’ gallbladder), which carries a 20% risk of developing gallbladder cancer. Chronic cholelithiasis alone carries an increased but much lower risk of developing cancer.

AETIOLOGY

Bile is a super-saturated solution of cholesterol

Cholesterol does not crystallise out because of a combination of factors including: 1. the detergent activity of bile salts (paradoxically produced from cholesterol) and the polar lipid lecithin 2. gallbladder motility. Gallstones develop when these mechanisms fail and there is an originating nidus for stone formation which is often mucin or bacteria. 80% of gallstones are cholesterol or mixed cholesterol stones where cholesterol is the major constituent. Pigment stones form the bulk of the rest and comprise predominantly bile pigment and are most common in chronic haemolytic states (Tab.1).

Table 1. Types of gallstones

EPIDEMIOLOGY.

Incidence varies with age: 5% at age 20, rising to 30% over 50 .

There is a 2:1 predominance in females. There are wide ethnic variations with American Pima Indians having an incidence of 70% in females aged 20. Scandinavia also has high incidences excreted in the bile, subsequently being concentrated in the gallbladder. This shows gallstones as filling defects within the gallbladder and demonstrates that the cystic duct is not obstructed. Following a fatty meal, the ability of the gallbladder to contract can also be measured. A functioning gallbladder and a non-obstructed, cystic duct are prerequisites for consideration of bile dissolution therapy.

Endoscopic retrograde cholangiopancreatography

(ERCP) is the technique of choice to demonstrate CBD stones as it also allows therapeutic interventions at the same time.

Computerised tomography (CT) is not particularly helpful in gallstone disease but fine slice images may demonstrate CBD stones not seen at ultrasound. MR cholangiography is in its infancy and its place in hepatobiliary disease is being defined .

Ultrasonography is the important procedure for the diagnosis of chronic gallbladder disease. In 90% to 95% of cases of cholelithiasis, ultrasonography demonstrates the echo of the calculus and the acoustic shadow behind the calculus.

EPIDEMIOLOGY.

Incidence varies with age: 5% at age 20, rising to 30% over 50

Prevalence of gall stones according to age

Risk factors for calculous cholecystitis mirror those for cholelithiasis and include the following:

· Female sex;

· Certain ethnic groups;

· Obesity or rapid weight loss;

· Drugs (especially hormonal therapy in women);

· Pregnancy;

· Increasing age.

Acalculous cholecystitis is related to conditions associated with biliary stasis, to include the following:

· Critical illness;

· Major surgery or severe trauma/burns;

· Sepsis;

· Long-term total parenteral nutrition (TPN);

· Prolonged fasting.

Other causes of acalculous cholecystitis include the following:

· Cardiac events, including myocardial infarction;

· Sickle cell disease;

· Salmonella infections;

· Diabetes mellitus;

· Patients with AIDS who have cytomegalovirus, cryptosporidiosis, or microsporidiosis.

Patients who are immunocompromised are at increased risk of developing cholecystitis from a number of different infectious sources. Idiopathic cases exist.

Pathogenesis

Ninety percent of cases of cholecystitis involve stones in the cystic duct (ie, calculous cholecystitis), with the other 10% of cases representing acalculous cholecystitis.

Acute calculous cholecystitis is caused by obstruction of the cystic duct, leading to distention of the gallbladder. As the gallbladder becomes distended, blood flow and lymphatic drainage are compromised, leading to mucosal ischemia and necrosis.

Although the exact mechanism of acalculous cholecystitis is unclear, several theories exist. Injury may be the result of retained concentrated bile, an extremely noxious substance. In the presence of prolonged fasting, the gallbladder never receives a cholecystokinin (CCK) stimulus to empty; thus, the concentrated bile remains stagnant in the lumen. A study by Cullen et al demonstrated the ability of endotoxin to cause necrosis, hemorrhage, areas of fibrin deposition, and extensive mucosal loss, consistent with an acute ischemic insult .Endotoxin also abolished the contractile response to CCK, leading to gallbladder stasis.

Clinical presentation

The most common presenting symptom of acute cholecystitis is upper abdominal pain. Signs of peritoneal irritation may be present, and in some patients, the pain may radiate to the right shoulder or scapula. Frequently, the pain begins in the epigastric region and then localizes to the right upper quadrant (RUQ). Although the pain may initially be described as colicky, it becomes constant in virtually all cases. Nausea and vomiting are generally present, and patients may report fever.

Most patients with acute cholecystitis describe a history of biliary pain. Some patients may have documented gallstones. Acalculous biliary colic also occurs, most commonly in young to middle-aged females. The presentation is almost identical to calculous biliary colic with the exception of reference range laboratory values and no findings of cholelithiasis on ultrasound. Cholecystitis is differentiated from biliary colic by the persistence of constant severe pain for more than 6 hours.

Patients with acalculous cholecystitis may present similarly to patients with calculous cholecystitis, but acalculous cholecystitis frequently occurs suddenly in severely ill patients without a prior history of biliary colic. Often, patients with acalculous cholecystitis may present with fever and sepsis alone, without history or physical examination findings consistent with acute cholecystitis.

Diagnosis

Delays in making the diagnosis of acute cholecystitis result in a higher incidence of morbidity and mortality. This is especially true for intensive care unit (ICU) patients who develop acalculous cholecystitis. The diagnosis should be considered and investigated promptly in order to prevent poor outcomes.

Example of diagnosis

Chronic non-calculous recurrent cholecystitis, acute phase, moderate severite. Hypotonic biliary dyskinesia

Laboratory tests and diagnostic studies

Although laboratory criteria are not reliable in identifying all patients with cholecystitis, the following findings may be useful in arriving at the diagnosis:

· Leukocytosis with a left shift may be observed in cholecystitis.

· Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are used to evaluate the presence of hepatitis and may be elevated in cholecystitis or with common bile duct obstruction.

· Bilirubin and alkaline phosphatase assays are used to evaluate evidence of common duct obstruction.

· Amylase/lipase assays are used to evaluate the presence of pancreatitis. Amylase may also be elevated mildly in cholecystitis.

· An elevated alkaline phosphatase level is observed in 25% of patients with cholecystitis.

· Urinalysis is used to rule out pyelonephritis and renal calculi.

· All females of childbearing age should undergo pregnancy testing.

A retrospective study by Singer, aimed at determining a set of clinical and laboratory parameters that could be used to predict the outcome of hepatobiliary scintigraphy (HBS) in all patients with suspected acute cholecystitis, found that of 40 patients with pathologically confirmed acute cholecystitis, 36 (90%) did not have fever at the time of presentation and 16 (40%) did not have leukocytosis.The study also found that no combination of laboratory or clinical values was useful in identifying patients at high risk for a positive HBS finding.

TREATMENT

Cholecystitis

Acute cholecystitis requires analgesia, intravenous support and antibiotics, and usually settles with these measures. Subsequent cholecystectomy may then be performed when the acute episode has resolved. Careful selection of patients with chronic cholecystitis is important as not all patients are pain-free when the gallbladder is removed; symptoms may abate spontaneously and not recur; and there is an increasing, associated, operative mortality with advancing age. Laparoscopic cholecystectomy has increased the acceptability of the procedure for patients and has consequently become widely available. There appears to be an increased risk of bile duct injury at the time of the procedure, particularly when carried out by inexperienced surgeons. However, the replacement of a large subcostal scar with three porthole incisions reduces postoperative pain and hospital stay from 10 to less than 3 days.

Cholangitis

Acute cholangitis is a serious infection which may be life-threatening. Antibiotics such as third generation cephalosporins or amino-quinolones should be used. Careful attention should be paid to fluid balance, urine output and renal function. Cholangitis is usually caused by CBD stones and therefore ERCP is required early in its management, to allow confirmation of biliary stones and their extraction. Following sphincterotomy, the bile duct can be trawled with either an inflatable balloon or a basket to extract the stones. If it is not possible to clear the duct, then an endoscopic stent may be inserted to facilitate bile drainage and reduce the risk of further episodes of cholangitis. Subsequent attempts may be made to clear the bile duct or in the elderly these stents may be left in place. As long-term stents can occlude and further episodes of cholangitis can occur, stent replacement may be necessary.

Postcholecystectomy pain

Following cholecystectomy, some patients continue to experience symptoms such as bloating, fatty food intolerance and dyspepsia. These symptoms usually predated the surgery and are often due to the irritable bowel syndrome. There is also a group of patients who have convincing biliary pain after stones have been removed. Liver function tests may be abnormal and some patients may be jaundiced. ERCP shows a dilated CBD without stones and there may be delayed excretion of contrast medium. This points towards sphincter of Oddi dysfunction which in more severe cases may benefit from endoscopic sphincterotomy.

Medical management of gallbladder stones

Dissolution therapy can be considered in patients with uncomplicated gallstone disease who are unwilling or unfit for surgery. The prerequisites for treatment are that the stones should be non-calcified, the gallbladder should be functioning and the cystic duct not obstructed. The bile acids, chenodeoxycholic acid and ursodeoxycholic acid are available and need to be given for long periods to be successful. They have no effect on pigment stones.

Gallstones are the most common cause for emergency room and hospital admissions of patients with severe abdominal pain. Many other patients experience milder symptoms. Results of diagnostic tests and the exam will guide the treatment, as follows:

Normal Test Results and No Severe Pain or Complications. Patients with no fever or serious medical problems who show no signs of severe pain or complications and have normal laboratory tests may be discharged from the hospital with oral antibiotics and pain relievers.

Gallstones and Presence of Pain (Biliary Colic) but No Infection. Patients who have pain and tests that indicate gallstones, but who do not show signs of inflammation or infection have the following options:

Intravenous painkillers for severe pain. Such drugs include meperidine (Demerol) or the potent NSAID ketorolac (Toradol). Ketorolac should not be used for patients who are likely to need surgery. These drugs can cause nausea, vomiting, and drowsiness. Opioids such as morphine may have fewer adverse effects, but some doctors avoid them in gallbladder disease.
Elective gallbladder removal. Patients may electively choose to have their gallbladder removed (called cholecystectomy) at their convenience.
Lithotripsy. A small number of patients may be candidates for a stone-breaking technique called lithotripsy. The treatment works best on solitary stones that are less than 2 cm in diameter.
Drug therapy. Drug therapy for gallstones is available for some patients who are unwilling to undergo surgery, or who have serious medical problems that increase the risks of surgery. Recurrence rates are high with nonsurgical options, and the introduction of laparoscopic cholecystectomy has greatly reduced the use of nonsurgical therapies. Note: Drug treatments are generally inappropriate for patients who have acute gallbladder inflammation or common bile duct stones, because delaying or avoiding surgery could be life threatening.

Acute Cholecystitis (Gallbladder Inflammation). The first step if there are signs of acute cholecystitis is to “rest” the gallbladder in order to reduce inflammation. This involves the following treatments:

Fasting
Intravenous fluids and oxygen therapy
Strong painkillers, such as meperidine (Demerol). Potent NSAIDs, such as ketorolac, may also be particularly useful. Some doctors believe morphine should be avoided for gallbladder disease.
Intravenous antibiotics. These are administered if the patient shows signs of infection, including fever or an elevated white blood cell count, or in patients without such signs who do not improve after 12 – 24 hours.

People with acute cholecystitis almost always need surgery to remove the gallbladder. The most common procedure now is laparoscopy, a less invasive technique than open cholecystectomy (which involves a wide abdominal incision). Surgery may be done within hours to weeks after the acute episode, depending on the severity of the condition.