Given that ascending cholangitis usually occurs in the setting of bile duct obstruction, various forms of medical imaging may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound, as this is the most easily available. Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones farther down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis (inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound. A better test is magnetic resonance cholangiopancreatography (MRCP), which uses magnetic resonance imaging (MRI); this has a comparable sensitivity to ERCP. Smaller stones, however, can still be missed on MRCP depending on the quality of the hospital's facilities.

The gold standard test for biliary obstruction is still endoscopic retrograde cholangiopancreatography (ERCP). This involves the use of endoscopy (passing a tube through the mouth into the esophagus, stomach and thence to the duodenum) to pass a small cannula into the bile duct. At that point, radiocontrast is injected to opacify the duct, and X-rays are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms), gallstones are visible as non-opacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.

If other causes rather than gallstones are suspected (such as a tumor), computed tomography and endoscopic ultrasound (EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy (tissue sample) of suspicious masses. EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability.

Right upper quadrant abdominal ultrasound is most commonly used to diagnose cholecystitis. Ultrasound findings suggestive of acute cholecystitis include gallstones, fluid surrounding the gallbladder, gallbladder wall thickening (wall thickness over 3 mm), dilation of the bile duct, and sonographic Murphy's sign. Given its higher sensitivity, hepatic iminodiacetic acid (HIDA) scan can be used if ultrasound is not diagnostic. CT scan may also be used if complications such as perforation or gangrene are suspected.

In someone suspected of having cholecystitis, blood tests are performed for markers of inflammation (e.g. complete blood count, C-reactive protein), as well as bilirubin levels in order to assess for bile duct blockage. Complete blood count typically shows an increased white blood count (12,000–15,000/mcL). C-reactive protein is usually elevated although not commonly measured in the United States. Bilirubin levels are often mildly elevated (1–4 mg/dL). If bilirubin levels are more significantly elevated, alternate or additional diagnoses should be considered such as gallstone blocking the common bile duct (common bile duct stone). Less commonly, blood aminotransferases are elevated. The degree of elevation of these laboratory values may depend on the degree of inflammation of the gallbladder.

Diagnosis is guided by the person's presenting symptoms and laboratory findings. The gold standard imaging modality for the presence of gallstones is ultrasound of the right upper quadrant. There are many reasons for this choice, including no exposure to radiation, low cost, and availability in city, urban, and rural hospitals. Gallstones are detected with a specificity and sensitivity of greater than 95% with ultrasound. Further signs on ultrasound may suggest cholecystitis or choledocholithiasis. Computed Topography (CT) is not indicated when investigating for gallbladder disease as 60% of stones are "not" radiopaque. CT should only be utilized if other intraabdominal pathology exists or the diagnosis is uncertain. Endoscopic retrograde cholangiopancreatography (ERCP) should be used only if lab tests suggest the existence of a gallstone in the bile duct. ERCP is then both diagnostic and therapeutic.

Routine blood tests show features of acute inflammation (raised white blood cell count and elevated C-reactive protein level), and usually abnormal liver function tests (LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin, alkaline phosphatase and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis, with elevations in alanine transaminase and aspartate transaminase.

Blood cultures are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases, usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli: "Escherichia coli" (25–50%), Klebsiella (15–20%) and Enterobacter (5–10%). Of the gram-positive cocci, Enterococcus causes 10–20%.

The differential diagnosis for pancreatitis includes but is not limited to cholecystitis, choledocholithiasis, perforated peptic ulcer, bowel infarction, small bowel obstruction, hepatitis and mesenteric ischemia.

Diagnosis requires 2 of the 3 following criteria:

- Characteristic acute onset of epigastric or vague abdominal pain that may radiate to the back (see signs and symptoms above)

- Serum amylase or lipase levels ≥ 3 times the upper limit of normal

- An imaging study with characteristic changes. CT, MRI, abdominal ultrasound or endoscopic ultrasound can be used for diagnosis.

Amylase and lipase are 2 enzymes produced by the pancreas. Elevations in lipase are generally considered a better indicator for pancreatitis as it has greater specificity and has a longer half life.

For imaging, abdominal ultrasound is convenient, simple, non-invasive, and inexpensive. It is more sensitive and specific for pancreatitis from gallstones than other imaging modalities. However, in 25–35% of patients the view of the pancreas can be obstructed by bowel gas making it difficult to evaluate.

A contrast-enhanced CT scan is usually performed more than 48 hours after the onset of pain to evaluate for pancreatic necrosis and extrapancreatic fluid as well as predict the severity of the disease. CT scanning earlier can be falsely reassuring.

ERCP or an endoscopic ultrasound can also be used if a biliary cause for pancreatitis is suspected.

Biliary sludge is typically diagnosed by CT scan or transabdominal ultrasonography. Endoscopic ultrasonography is another more sensitive option. However, the gold standard is considered to be direct microscopy of aspirated gallbladder bile. This method is much more sensitive, although it is less practical.

It is unclear whether those experiencing a gallstone attack should receive surgical treatment or not. The scientific basis to assess whether surgery outperformed other treatment was insufficient and better studies were needed as of a SBU report in 2017. Treatment of biliary colic is dictated by the underlying cause. The presence of gallstones, usually visualized by ultrasound, generally necessitates a surgical treatment (removal of the gall bladder, typically via laparoscopy). Removal of the gallbladder with surgery, known as a cholecystectomy, is the definitive surgical treatment for biliary colic. A 2013 Cochrane review found tentative evidence to suggest that early gallbladder removal may be better than delayed removal. Early laparoscopic cholescystectomy happens within 72 hours of diagnosis. In a Cochrane review that evaluated receiving early versus delayed surgery, they found that 23% of those who waited on average 4 months ended up in hospital for complications, compared to none with early intervention with surgery. Early intervention has other advantages including reduced number of visits to the emergency department, less conversions to an open surgery, less operating time required, reduced time in hospital post operatively. The Swedish agency SBU estimated in 2017 that increasing acute phase surgeries could

free multiple in-hospital days per patient and would additionally spare pain and suffering in wait of receiving an operation. The report found that those with acute inflammation of the gallbladder can be surgically treated in the acute phase, within a few days of symptom debut, without increasing the risk for complications (compared to when the surgery is done later in an asymptomatic stage).

In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson criteria and APACHE II (Acute Physiology and Chronic Health Evaluation) indices. Most, but not all studies report that the Apache score may be more accurate. In the negative study of the APACHE-II, the APACHE-II 24-hour score was used rather than the 48-hour score. In addition, all patients in the study received an ultrasound twice which may have influenced allocation of co-interventions. Regardless, only the APACHE-II can be fully calculated upon admission. As the APACHE-II is more cumbersome to calculate, presumably patients whose only laboratory abnormality is an elevated lipase or amylase do not need assessment with the APACHE-II; however, this approach is not studied. The APACHE-II score can be calculated at www.sfar.org.

Practice guidelines state:

The Ranson criteria are a clinical prediction rule for predicting the severity of acute pancreatitis. They were introduced in 1974.

Choledocholithiasis (stones in common bile duct) is one of the complications of cholelithiasis (gallstones), so the initial step is to confirm the diagnosis of cholelithiasis. Patients with cholelithiasis typically present with pain in the right-upper quadrant of the abdomen with the associated symptoms of nausea and vomiting, especially after a fatty meal. The physician can confirm the diagnosis of cholelithiasis with an abdominal ultrasound that shows the ultrasonic shadows of the stones in the gallbladder.

The diagnosis of choledocholithiasis is suggested when the liver function blood test shows an elevation in bilirubin and serum transaminases. Other indicators include raised indicators of ampulla of vater (pancreatic duct obstruction) such as lipases and amylases. In prolonged cases the INR may change due to a decrease in vitamin K absorption. (It is the decreased bile flow which reduces fat breakdown and therefore absorption of fat soluble vitamins).

The diagnosis is confirmed with either an MRCP (magnetic resonance cholangiopancreatography), an ERCP, or an intraoperative cholangiogram. If the patient must have the gallbladder removed for gallstones, the surgeon may choose to proceed with the surgery, and obtain a cholangiogram during the surgery. If the cholangiogram shows a stone in the bile duct, the surgeon may attempt to treat the problem by flushing the stone into the intestine or retrieve the stone back through the cystic duct.

On a different pathway, the physician may choose to proceed with ERCP before surgery. The benefit of ERCP is that it can be utilized not just to diagnose, but also to treat the problem. During ERCP the endoscopist may surgically widen the opening into the bile duct and remove the stone through that opening. ERCP, however, is an invasive procedure and has its own potential complications. Thus, if the suspicion is low, the physician may choose to confirm the diagnosis with MRCP, a non-invasive imaging technique, before proceeding with ERCP or surgery.

The clinical course of biliary sludge can do one of three things: (1) it can resolve completely, (2) wax and wane, or (3) progress to gallstones. If the biliary sludge has a cause (e.g. pregnancy), it oftentimes is resolved when the underlying cause is removed.

Treatment involves an operation called a choledocholithotomy, which is the removal of the gallstone from the bile duct using ERCP, although surgeons are now increasingly using laparoscopy with cholangiography. In this procedure, tiny incisions are made in the abdomen and then in the cystic duct that connects the gallbladder to the bile duct, and a thin tube is introduced to perform a cholangiography. If stones are identified, the surgeon inserts a tube with an inflatable balloon to widen the duct and the stones are usually removed using either a balloon or tiny basket.

If laparoscopy is unsuccessful, an open choledocholithotomy is performed. This procedure may be used in the case of large stones, when the duct anatomy is complex, during or after some gallbladder operations when stones are detected, or when ERCP or laparoscopic procedures are not available.

Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of common bile duct obstruction or other complications.

Stable patients presenting to A&E (accident and emergency department) or ER (emergency room) with severe abdominal pain will almost always have an abdominal x-ray and/or a CT scan. These tests can provide a differential diagnosis between simple and complex pathologies. However, in the unstable patient, fluid resuscitation and a FAST-ultrasound are done first, and if the latter is positive for free fluid, straight to surgery. They may also provide evidence to the doctor whether surgical intervention is necessary.

Patients will also most likely receive a complete blood count (or full blood count in the U.K.), looking for characteristic findings such as neutrophilia in appendicitis.

Traditionally, the use of opiates or other painkillers in patients with an acute abdomen has been discouraged before the clinical examination, because these would alter the examination. However, the scientific literature does not reveal any negative results from these alterations.

The diagnosis of chronic pancreatitis is based on tests on pancreatic structure and function. Serum amylase and lipase may be moderately elevated in cases of chronic pancreatitis, amylase and lipase are nearly always found elevated in the acute condition. A secretin stimulation test is considered the best test for diagnosis of chronic pancreatitis. Other tests used to determine chronic pancreatitis are serum trypsinogen, computed tomography, ultrasound and biopsy.

When chronic pancreatitis is caused by genetic factors, elevations in ESR, IgG4, rheumatoid factor, ANA and anti-smooth muscle antibody may be detected.

The treatment of pancreatitis is supportive and depends on severity. Morphine generally is suitable for pain control. There are no clinical studies to suggest that morphine can aggravate or cause pancreatitis or cholecystitis.

The treatment that is received for acute pancreatitis will depend on whether the diagnosis is for the mild form of the condition, which causes no complications, or the severe form, which can cause serious complications.

A prospective study in 1994 noted that body mass index remains the strongest predictor of symptomatic gallstones among young women. Other risk factors are having over four pregnancies, weight gain, and cigarette smoking. Alcohol was shown to have an inverse relationship between use and gallbladder disease.

Imaging by ultrasonography, MRCP, or CT scan usually make the diagnosis. MRCP can be used to define the lesion anatomically prior to surgery.

Occasionally Mirizzi's syndrome is diagnosed or confirmed on ERCP when requested to alleviate obstructive jaundice or cholangitis by means of an endoscopically placed stent, or when USS has been wrongly reported as choledocolithiasis.

Due to the increased risk for gallbladder cancer, the recommended treatment is cholecystectomy which usually includes pre-operative or intra-operative imaging of the biliary tree. Cholecystectomy may be performed via an open incision or via laparoscopic methods, but gallbladder anatomy and consistency may complicate the operation.

Women are almost twice as likely as men to form gallstones especially during the fertile years; the gap narrows after the menopause. The underlying mechanism is female sex hormones; parity, oral contraceptive use and estrogen replacement therapy are established risk factors for cholesterol gallstone formation. Female sex hormones adversely influence hepatic bile secretion and gallbladder function. Estrogens increase cholesterol secretion and diminish bile salt secretion, while progestins act by reducing bile salt secretion and impairing gallbladder emptying leading to stasis. A new 4th generation progestin, drospirenone, used in some oral contraceptives may further heighten the risk of gallstone disease and cholecystectomy; however, the increased risk is quite modest and not likely to be clinically meaningful.

A retrospective (historical) cohort study was performed on a very large data base including 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared with 341,478 nonusers. Oral contraceptives were shown as risk factors for gallbladder disease, although the risk is of sufficient magnitude to be of potential clinical importance only in young women.

The 1984 Royal College of General Practitioners' Oral Contraception Study suggests that, in the long-term, oral contraceptives are not associated with any increased risk of gallbladder disease, although there is an acceleration of the disease in those women susceptible to it.

Newer research suggests otherwise. A 1993 meta-analysis concludes that oral contraceptive use is associated with a slightly and transiently increased rate of gallbladder disease, but laters confirms that modern low-dose oral contraceptives are safer than older formulas, though an effect cannot be excluded.

A 2001 comparative study of the IMS LifeLink Health Plan Claims Database interpreted that in a large cohort of women using oral contraceptives, there was found a small, statistically significant increase in the risk of gallbladder disease associated with desogestrel, drospirenone and norethisterone compared with levonorgestrel. No statistically significant increase in risk was associated with the other formulations of oral contraceptive (etynodiol diacetate, norgestrel and norgestimate).

Surgery to treat chronic pancreatitis tends to be divided into two areas – resectional and drainage procedures. Among the reasons to opt for surgery are if there is a pseudocyst, fistula, ascites, or a fixed obstruction.

Simple cholecystectomy is suitable for type I patients. For types II–IV, subtotal cholecystectomy can be performed to avoid damage to the main bile ducts. Cholecystectomy and bilioenteric anastomosis may be required. Roux-en-Y hepaticojejunostomy has shown good outcome in some studies.

The assertion that porcelain gallbladder increases the incidence of gallbladder cancer is widely taught in medical schools but is based on studies from 1931 and 1962. A prominent study aid for surgical residents even states that the risk of cancer in a porcelain gallbladder is 15%. The precise nature of the association between gallbladder cancer and porcelain gallbladder is uncertain. Two articles published in 2001 examined the association between cancer of the gallbladder and calcified gallbladder. The first study reviewed 10,741 cholecystectomies and found that the 88 patients with gallbladder cancer did not have calcified gallbladders while the 15 patients with porcelain gallbladders did not have gallbladder cancer. The second study reviewed 25,900 gallbladder specimens and found 150 patients with cancer and 44 patients with calcified gallbladders of two types (intramural calcification and selective mucosal calcification). The selective mucosal calcification group showed a 7% incidence of cancer with a significant odds ratio of 13.89.

An article published in 2013 reviewed 111 studies and found 340 patients with gallbladder wall calcification showed a 21% overall rate of gallbladder malignancy; however, when studies with obvious selection bias were excluded the rate of gallbladder malignancy fell to 6%. Comparatively, a matched cohort without gallbladder calcification showed a 1% rate of gallbladder malignancy.

Diagnostic workup varies by the stone type, but in general:

- Clinical history and physical examination

- Imaging studies

- Some stone types (mainly those with substantial calcium content) can be detected on X-ray and CT scan

- Many stone types can be detected by ultrasound

- Factors contributing to stone formation (as in #Etiology) are often tested:

- Laboratory testing can give levels of relevant substances in blood or urine

- Some stones can be directly recovered (at surgery, or when they leave the body spontaneously) and sent to a laboratory for analysis of content

People under 55 years without alarm symptoms can be treated without investigation. People over 55 years with recent onset dyspepsia or those with alarm symptoms should be urgently investigated by upper gastrointestinal endoscopy. This will rule out peptic ulcer disease, medication-related ulceration, malignancy and other rarer causes.

People under the age of 55 years with no alarm features do not need endoscopy but are considered for investigation for peptic ulcer disease caused by "Helicobacter pylori" infection. Investigation for "H. pylori" infection is usually performed when there is a moderate to high prevalence of this infection in the local community or the person with dyspepsia has other risk factors for "H. pylori" infection, related for example to ethnicity or immigration from a high-prevalence area. If infection is confirmed, it can usually be eradicated by medication.

Medication-related dyspepsia is usually related to NSAIDs and can be complicated by bleeding or ulceration with perforation of stomach wall.