**3. Anatomy of biliary tract**

The gallbladder is a part of the digestive system. The gallbladder is a thin-walled sac with three anatomic parts: the fundus, corpus, and infundibulum [1]. It is normally located between both hepatic lobes. **Figure 1** depicts the gall bladder location in the human body, and **Figure 2** represents the gall bladder anatomy. The gallbladder empties into the cystic duct, a passive conduit with a mucosa comprising spiral valves and with a diameter of about 7 mm in humans (Valves of Heister). This duct has no sphincteric structure and empties into the common bile duct. As it enters the duodenal wall and forms the ampulla of Vater, the common bile duct passes through the head of the pancreas, finishing in the sphincter of Oddi [6].

Approximately, 10% of individuals are estimated to have one or more biliary duct abnormalities; however, not all of them are difficult to identify during surgery. The so-called triple confluence, which is an abnormality defined by simultaneous emptying of the right posterior duct, right anterior duct, and left hepatic duct into the common hepatic duct [Mortele and Ros] [7], is a frequent variation of the major hepatic biliary branching. The right hepatic duct is almost non-existent in individuals with this variation. The right posterior duct and its union with the right anterior or left hepatic duct are two more common anatomic variations of the biliary tree branching.

*Gallbladder lies beneath the lower liver edge at the bottom of the rib cage. (Jan Modric, 2017) [5]***.**

**Figure 1.**

#### **Figure 2.**

*Gallbladder parts and bile ducts (Jan Modric, 2017) [5].*

As previously stated, the right posterior duct connects to the right anterior duct and unites it from the left to produce the right hepatic duct, which then connects to the left hepatic duct to form the common hepatic duct. The most prevalent anatomic variant of the biliary system is drainage of the right posterior duct into the left hepatic duct before its confluence with the right anterior duct.

Furthermore, various less common and usually more difficult anatomic variants of the bile ducts, which include both aberrant and auxiliary bile ducts, have been described. In a clinical setting, knowing the difference between an aberrant bile duct and an accessory bile duct is vital since an aberrant bile duct is the only bile duct draining a specific hepatic segment, whereas an accessory bile duct drains the same portion of the liver. Failure to recognize certain of these bile duct irregularities can lead to bile leakage and peritoneal membrane irritation (bile peritonitis). Endoscopic retrograde cholangiopancreatography is used to treat these leaks by inserting stents (ERCP). They can stop these leaks that arise from the common bile or cystic ducts [8–10].

## **4. The sphincter of Oddi: (anatomy and physiology)**

The human sphincter of Oddi is approximately 10 mm in length and has a welldefined and strong musculature. The Oddi sphincter is physically and functionally distinct from the duodenum. Its myoelectrical and contractile patterns are distinct from those of the duodenum in terms of character and timing. The contractions of the human sphincter of Oddi occur at the same time; however, there may be minor variations in configuration that look peristaltic at times. Its principal function of serving as a bile flow resistor is compatible with the occurrence of synchronous contractions. Because of the sphincter of Oddi resistance, the constant hepatic production of bile is largely directed into the cystic duct and gallbladder during the fasting state, where it is stored and concentrated. During the diastolic phase, sphincter of Oddi phasic contractions and, during phase II, migrating motor complex occur when there is modest gallbladder contraction; hence, a tiny amount of bile escapes into the duodenum. The gallbladder contracts during digestion, emptying the majority of its contents, and bile is delivered to the duodenum *via* the cystic and common bile ducts, which pass *via* a relaxed sphincter of Oddi and

duodenum. Bile salts help in fat digestion and absorption in the duodenum and jejunum (triglycerides, cholesterol and phospholipids, and liposoluble vitamins). Therefore, transportation of bile salts to the terminal ileum takes place; there, most of them were recycled as part of the enterohepatic circulation through an active transport mechanism found in the terminal ileum's epithelial cells [6].

### **5. Sphincter of Oddi dyskinesia**

Patients with sphincter of Oddi (SO) dyskinesia have biliary-like symptoms, which are frequently noticed after a cholecystectomy. The symptoms and signs of bile duct sphincter dysfunction are similar to those of temporary bile duct blockage, whereas pancreatic sphincter of Oddi dysfunction is linked to elevated pancreatic enzymes and even full-blown pancreatitis. Patients with sphincter of Oddi dysfunction are assessed with quantitative choledochoscintigraphy and/or sphincter of Oddi manometry tests to confirm the diagnosis, even if the preliminary investigation is defined by this functional entity by sphincter of Oddi manometry.

## **6. Chronic and acute cholecystitis**

#### **6.1 Pathogenesis**

The most commonly stated hypothesis in the etiology of chronic and acute cholecystitis is that it is caused by gallstones migrating from the gallbladder obstructing the cystic duct or, in the event of big gallstones, that they intermittently obstruct the gallbladder's neck (Jose Behar) [6]. The inability to see the gallbladder in patients with acute cholecystitis has been attributed to a cystic duct occlusion. This observation has been validated clinically and pathologically in up to 97% of individuals with acute cholecystitis [Pare and Shaffer et al.] [11].

However, other explanations for this failure are more likely that.

A cystic duct obstruction would be caused by the gallbladder's acute inflammation and edema spreading to the cystic duct, or.

Because it is clogged with inflammatory fluids, an atonic gallbladder obstructs the entry of the bulk of the isotope-labeled agent. Furthermore, the severely inflamed gallbladder may be unable to distend passively due to edema or actively due to a faulty relaxation found in gallbladders with lithogenic bile containing high cholesterol contents [Xiao and Chen et al.] [12].

The appearance of cholecystitis associated only with lithogenic bile (acalculous gallbladder) or a single huge stone several times larger than the normal width of the cystic duct lumen further challenges the idea of cystic duct obstruction. Furthermore, the presence of acute inflammation on top of a chronically inflamed or atrophic fibrotic gallbladder has proven difficult to explain because it would imply recurring cystic duct obstruction events. It is more likely that the development of acute inflammation as a result of a chronic process had been in the works for a long time. Mucosal thickening, hypertrophic muscle layers, and macrophage infiltration of the lamina propria are common in gallbladders. In the absence of gallstones, chronic cholecystitis is commonly found histopathologically. They arise in people who are morbidly obese and have lithogenic bile but no gallstones. When compared with the normal mucosa in nonobese people, these gallbladders exhibit mucosal abnormalities consistent with chronic cholecystitis [Csendes et al.] [13]. The pathogenesis of chronic cholecystitis is shown in **Figure 3**. The gallbladder

**Figure 3.**

*Pathogenesis of chronic cholecystitis.*

motility and cytoprotective functions are impaired by lithogenic hepatic bile with excess cholesterol, allowing the hydrophobic bile salts to induce chronic cholecystitis.

Finally, the results of the aforementioned human and animal studies strongly suggest that cholecystitis develops in the presence of lithogenic bile with high cholesterol concentrations, which creates a permissive environment for hydrophobic bile salts to increase oxidative stress levels and initiate the inflammatory process. Continuous entrance of hydrophobic bile salts into the diseased gallbladder is required for this inflammatory process [14].

### **7. Chronic cholecystitis clinical symptoms**

Chronic cholecystitis patients may be asymptomatic or experience recurring episodes of epigastric and right upper quadrant (RUQ ) discomfort that radiates often around the waist and toward the scapula. The pain is moderate to severe, and it is not postprandial but rather nocturnal in nature. It does not happen every day; instead, it happens every two to 3 weeks. Ultrasonography is usually used to make the diagnosis. Gallstones and gallbladder wall thickening can be detected using this test. Laboratory tests are normal. Gallstones are often asymptomatic, but because they are easily discovered in gallbladders by imaging investigations, they are blamed for a range of upper gastrointestinal problems. Gallstones are frequently blamed for nonspecific gastrointestinal symptoms such as persistent dyspepsia, gastroparesis, and irritable bowel syndrome. Patients with these functional disorders typically experience everyday upper gastrointestinal symptoms, which are often postprandial and triggered by fatty foods or large meals. Epigastric pain, nausea, and bloating are common complaints among these patients. Even while pathological investigations may indicate gallstones and histological evidence of persistent cholecystitis, cholecystectomy does not relieve these symptoms. Gallstones can go unnoticed for lengthy periods of time, according to several investigations, including autopsy studies. Most patients with asymptomatic gallstones remained symptom free for the whole 8-year follow-up period in a prospective Italian research [15–19].

#### **8. Acute cholecystitis**

In acute cholecystitis, chronic cholecystitis is the most prevalent risk factor. These patients often have abrupt onset of severe pain, which is commonly accompanied by nausea in 90% of instances and vomiting in 50% of cases.

Physical examination indicates epigastric, right upper quadrant, and positive Murphy sign pain, with rebound soreness in severe instances. However, doctors must rule out other acute abdominal diseases such as acute appendicitis, particularly with a retrocecal appendix, acute pancreatitis, localized perforated peptic ulcer, intestinal perforation, or ischemia before considering this diagnosis. These clinical entities exhibit comparable characteristics in terms of demographics and risk factors. Physical examination indicates abdominal pain that can be localized or widespread, as well as a significant decrease in bowel sounds, in these individuals who complain of severe stomach pain, nausea, and vomiting.

Acute cholecystitis is defined as an acute inflammation of the gall bladder. Chronic cholecystitis, acute pancreatitis, diverticulitis, colitis, appendicitis, Fitz-Hugh-Curtis syndrome, ureteral stone, and omental infarction are all illnesses that can cause acute right upper quadrant (RUQ ) discomfort [20, 21]. It can occur abruptly in conjunction with gallstones (acute calculous cholecystitis) or less

frequently without gallstones (acute calculous cholecystitis) (acalculous cholecystitis). Gallstones affect more than 80% of persons who are asymptomatic. Acute cholecystitis is a complication of gallstone disease that usually arises in people who have had symptomatic gallstones in the past. Delayed management can lead to increased morbidity, due to progression to severe cholecystitis, such as gangrenous change, abscess formation, and gallbladder perforation [4].
