Introduction:

Acute cholecystitis (AC) is the sudden inflammation of the gallbladder (GB). It is a very common surgical condition and a frequent cause of abdominal pain.

In most cases it is due to the obstruction of the cystic duct by a gallstone (GS), which exists a long time before this condition occurs, in asymptomatic patients, or in those having neglected biliary colic.

Symptoms include right upper abdominal pain in most cases. Fever, nausea and vomiting are less frequent. Paralytic ileus was also described in some patients.

Physical examination generally finds tenderness in the right upper quadrant of the abdomen, with a « catch » in the breath when the patient is asked to breathe in. This is called murphy’s sign.

Abdominal ultrasound, confirms the diagnosis when showing distended GB and thickening of its wall, with the presence of GS. However normal ultrasound finding doesn’t exclude the diagnosis of AC.

In approximately 10% (range, 2%–15%) [1], these symptoms are found in patients with no radiological nor surgical evidence of gallstones or cystic duct obstruction. This condition is called acalculous acute cholecystitis (AAC).

The etiology of AAC is multifactorial. Its pathophysiology includes bile stasis, ischemia or both [1-3].

In this article, we present a case of an ischemic AAC diagnosed in our emergency department.

Case report:

A 50 year old male patient with a medical history of diabetes, hypertension, ischemic stroke and kidney failure presented to our emergency department 

Suffering from a right upper abdominal pain, asthenia and vomiting starting 4 days before admission, without intestinal abdominal disorders. No chest pain was reported.

On initial physical examination, he was conscious, with a normal respiratory rate and a pulse oximetry of 100 %. He had a tachycardia with a heart rate of a 135 beat per minute, a normal blood pressure of 130/80 mmHg. No signs of circulatory impairment or right heart failure was found. The temperature was 36.9^c and blood sugar level was > 5g/l.

The abdominal examination found tenderness with guarding in the epigastric, the right hypochondriac, the right lumbar and the right iliac region. Electrocardiogram showed a sinus tachycardia.

Blood panel showed:   WBC elevation but normal CRP level (WBC=14610/mm3; CRP = 7.4), normal liver enzymes (AST=26 u/l; ALT =40 u/l), elevated creatinine and urea levels (715 µmol /l; 15.6 mmol/l), normal lipase (33u/l) and normal ultra-sensible troponin  level (12.2 ng/l < 34). The lactate was 5.8 mmol/l.

There was no signs of pneumonia nor pneumoperitoneum in the Chest X rays.

The abdominal ultrasound was not conclusive and showed a distended gallbladder with normal wall thickness associated with hyperechogenic, and heterogeneous content without GS. 

An abdominal CT Scan was performed and it showed a low heterogeneous enhancement of the gallbladder wall with Pericholecystic fluid and peritoneal effusion, confirming the diagnosis of ischemic ACC. It also showed an arterial variation: a right hepatic artery stemming from the superior mesenteric artery (called replaced right hepatic artery) with an atheroma plate of 1cm long causing significant stenosis (figure 1).

There was no dilation in intrahepatic bile ducts

The patient was admitted in the general surgery department, and operated at the same day. Intraoperative observations found a gangrenous cholecystitis.

Discussion:

AAC remains an elusive pathology for its complex multifactorial pathogenesis and its nonspecific presentation.

It accounts for approximately 10% (range, 2%–15%) of all cases of acute cholecystitis, and it is most seen in critically ill   male patients [1].

AAC risk factors  include severe trauma , especially those  requiring blood transfusions , heavy surgery , shock of any kind , large burn injuries (with an incidence between 0.4 and 3.5% ), critical illness (requiring ICU care) , or  

sepsis [1, 4 , 5] .

less frequently described  risk factors are  : endoscopic retrograde cholangiopancreatography ;  cardiovascular risk factors (diabetes mellitus , hypertension, atherosclerotic , obesity) ; end stage renal failure, vasculitis (Churg–Strauss, giant cell arteritis, Henoch–Schönlein purpura, polyarteritis nodosa, lupus,  takayasu’s syndrome ); Immunodeficiency conditions ( AIDS , Transplant)  [1,4,6] .

Two other rare risk factors are worth mentioning:

-ACC after transarterial chemoembolization of hepatocellular cancer, which is reported with  an incidence between 0.3% and 10% [7] .

-ACC associated with an  aortic dissection (To our knowledge, only 5 cases of AAC clearly caused by aortic dissection have been reported previously [8-11].)

AAC pathophysiology is complex, but studies found that it involves two major phenomenon: bile stasis and ischemia [1, 4].

Bile stasis can be caused by fasting, obstruction, postsurgical/procedural irritation, ileus (total parenteral nutrition) or opioid analgesia (spasm of the sphincter of Oddi causing elevated bile duct pressure). This stasis modifies the chemical composition of bile, resulting in gallbladder mucosal lesions   [1, 4].

The decrease of the gallbladder perfusion pressure, resulting in ischemia, may be the result of many of the risk factors stated above and it results in heavy injuries directly to all layers of its wall [1, 4].

Bacterial invasion of the ischemic tissue is a secondary phenomenon. The immunity response to this invasion, may produce or contribute to the   GB tissue damage [4].

These pathophysiological mechanisms are well illustrated in histopathological data , as the ones provided by Laurila et al [12]  , through comparing histologic findings of the gallbladders with  and without ACC. Histological abnormalities reported in this study were : (1) an  increased leukocyte margination (suggesting involvement of ischemia and reperfusion-mediated injury) ; (2) capillary thrombosis and increased focal lymphatic dilation (ischemia related) and (3) increased and deeper bile infiltration in the GB mucosa (suggesting that bile stasis and increased epithelial permeability exist, leading to epithelial damage) .

There are no symptoms nor signs that are specific to AAC. Fever may be the only sign present in critically ill patients, unable to communicate their symptoms. For this kind of patients, AAC is a diagnosis among many other   to suspect facing a sepsis or a septic shock. It is sufficiently common and should be discussed in every critically ill patient with a clinical presentation of sepsis or icterus and no other obvious cause [1, 4].

The clinical presentation may also include right upper abdominal pain, fever, nausea and vomiting.

Physical findings shows fever, tenderness with or without guarding in the epigastric region and/or the right hypochondriac. Clinically, AAC is indistinguishable from acute calculous cholecystitis [1].

Laboratory evaluation is also unreliable. Leukocytosis and CRP elevation are common but not specific. Lactates elevation is common.

Normal inflammatory markers with elevated lactates may be an early sign of an ischemic disorder but it is not specific.

The confirmation of the diagnosis rests on imaging. Abdominal ultrasound and computerized tomography (CT) scan are usually sufficient with an excellent reported sensibility and specificity (for US : 92 % of sensitivity and 96 % of specificity ; For CT scan : 100 % sensitivity and specificity ) [13] .

Other exams such as HIDA (hepatobiliary iminodiacetic acid scan) are used but they are expensive and not immediately available.

Diagnostic criteria were defined for both US and abdominal CT scann in many radiologic studies [1, 4, 13-16]:

Criteria for abdominal US: 2 major or 1 major and 2 minor

Major:  3.5- to 4-mm (or more) thick wall

             Striated gallbladder.

             Intramural gas    Pericholecystic fluid

             Sloughed mucosal membrane

Minor: Gallbladder distention (>5 cm in transverse                     diameter)

             Echogenic bile (sludge)

Criteria for abdominal CT : 2 major or 1 major and 1 minor

Major: Gallbladder wall thickening >3 to 4 mm

             Subserosal halo sign

             Pericholecystic infiltration of fat

             Pericholecystic fluid

             Mucosal sloughing

             Intramural gas

Minor: Gallbladder distention (>5 cm in transverse             diameter)

            High-attenuation bile (sludge)

AAC complications are numerous. The prevalence of gallbladder gangrene in AAC exceeds 50% [4].  Gallbladder perforation, abscess formation, generalized peritonitis or severe sepsis with multiple organ dysfunction syndrome are commonly reported.

Conclusion:

Although ACC is mostly described in critically ill patients, it remains a possible diagnosis in patients with multiple cardiovascular risk factors.

Clinical presentation is not specific as well as laboratory evaluation and it is almost the same as acute calculous cholecystitis.

Abdominal US and abdominal CT scan criteria are the key to the diagnosis with an excellent sensitivity and specificity.

An early correct assessment is essential to a successful treatment and to avoid major lethal complications.

References:

1- Huffman JL , Schenker S . Acute Acalculous Cholecystitis: A Review . CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:15–22 .

2- Warren BL . Small vessel occlusion in acute acalculous cholecystitis. Surgery 1992;111:163–8.

3- Feng-Lin L, He L, Xue-Fei W, Kun-Tang S, Zhen-Bin S, Yi-Hong S et al . Acute acalculous cholecystitis immediately after gastric operation: Case report and literatures review . World J Gastroenterol 2014 August 14; 20(30): 10642-50

4- Barie PS , Eachempati SR . Acute Acalculous Cholecystitis. Gastroenterol Clin North Am. 2010;39(2):343-57

5-Walsh K, Goutos I, Dheansa B . Acute Acalculous Cholecystitis in Burns: A Review .Journal of Burn Care & Research. 2018 ; 39(5) : 724–8

6- Socea B  , Carap AC ,Socea LI , Dimitriu M  ,Bratu OG , Diaconu C et al  .Acute ischemic cholecystitis in Takayasu's syndrome - a rare finding .Archives of the Balkan Medical Union. 2018 ; 53(2):293-6 · 

7- Karaman B , Battal B , Cem Ören N , Üstünsöz B  , Yağci G .Acute ischemic cholecystitis after transarterial chemoembolization with drug-eluting beads . Clinical Imaging . 2012 ; 36(6) : 861 – 864

8- Roth T, Mainguene C, Boiselle JC. Acute acalculous cholecystitis associated with aortic dissection: report of a case. SurgToday. 2003;33:633–5

9- Söğütlü G, Iş ik B, Yilmaz M, Karadağ N, Hoca O, Olmez A et al. Acute acalculous cholecystitis induced by aortic dissection:report of a case. Ulus Travma Acil Cerrahi Derg. 2010;16:283–5.

10- Inagaki FF, Hara Y , Kamei M , Tanaka M  , Yasuno M .Acute and chronic acalculous cholecystitis associated with aortic dissection . Journal of Surgical Case Reports. 2015 ;2015(8) : 1–4

11- Nemoto M,  Hosaka A, Takayama Y, Yoshimi  F .Acute Type B Aortic Dissection Associated with Acute Pancreatitis, Pancreatic Pseudocysts, and Acalculous Cholecystitis . Ann Vasc Dis .2019 ;12(3) :  392–4

12- Laurila JJ ,  Ala-Kokko TI,  Laurila PA, Saarnio J ,  Koivukangas V ,  Syrjälä H et al. Histopathology of acute acalculous cholecystitis in critically ill patients. Histopathology 2005;47(5):485– 92.

13- Mirvis SE, Vainright JR , Nelson AW ,  Johnston GS , Shorr R , Rodriguez A et al. The diagnosis of acute acalculous cholecystitis: a comparison of sonography, scintigraphy, and CT.
AJR Am J Roentgenol . 1986;147(6):1171-5

14- Barie PS, Eachempati SR. Acute acalculous cholecystitis. Curr .Gastroenterol Rep.2003;5:302–9.

15- Beckman I, Dash N, Sefczek RJ, et al. Ultrasonographic findings in acute acalculous cholecystitis. Gastrointest Radiol 1985;10:387–389.

16- Deitch EA, Engel JM. cholecystitis. Ultrasonic diagnosis. Am J Surg 1981;142(2):290–2.