First described by Ruggero Oddi in 1887, the sphincter of Oddi (SO) is a smooth muscle valve located in the second portion of the duodenum. It serves to regulate the flow of hepatic and pancreatic substances into the small intestines. Although its function seems simple, it represents a great example of how smooth muscle can be under the regulation by hormones and other signals. The SO serves many purposes in medicine and is often traversed in procedures such as endoscopic retrograde cholangiopancreatography (ERCP). This sphincter may also become dysfunctional at times requiring either medical or surgical intervention.

The sphincter of Oddi is a muscular valve responsible for controlling the flow of bile and pancreatic secretions through the ampulla of Vater into the second part of the duodenum. It is composed of three layers of concentric smooth muscle that surrounds the common bile duct, the main pancreatic duct, and the ampulla of Vater. The papilla of Vater includes the SO and its overlying mucosa. So far, the SO has been identified to have at least three functions[1][2]:

1. To prevent reflux of duodenal contents thereby preventing the accumulation of sludge and particulate matter in the bile ducts and thus helps to reduce the risk of cholangitis
2. Regulate the flow of bile and pancreatic secretions
3. Allow retrograde filling of the gallbladder to occur

The sphincter of Oddi serves as a great example of hormonal regulation of smooth muscle. Across the literature, the most important of these hormones is cholecystokinin (CCK). It gets released from enteroendocrine cells in response to the digestion of a meal; this stimulates the contraction of the gall bladder, resulting in the emptying of pancreatic secretions and bile into the common bile duct. CCK has been demonstrated to cause the release of VIP and nitric oxide by intrinsic neurons of the sphincter of Oddi, resulting in a decrease in sphincter tone, ultimately leading to the release of the backed-up contents into the duodenum to aid with digestion.  Somatostatin is also another noteworthy hormone shown to increase sphincter of Oddi tone. In contrast, motilin and secretin serve the opposite effect by decreasing sphincter of Oddi tone and allowing the flow of contents from the gallbladder and pancreas.[3][4][5]

The sphincter of Oddi is a concentric ring of muscle originating from the mesenchyme surrounding the pre-ampullary portion of the bile and pancreatic ducts. Initially, it begins as a transverse slit in the circular smooth muscle at the junction between the duodenal wall and the bile and pancreatic ducts. The sequence of SO differentiation is as follows[6]:

1. Week 10: sphincter of Oddi begins differentiation
2. Week 12: the bile and pancreatic ducts emerge through the transverse slit of the concentric smooth muscle of the duodenum
3. Week 16: the muscularis propria extends outside the fenestra to the upper end of the ampulla
4. Week 28: the muscularis propria is differentiated almost to the distal end of the ampulla

In about half of individuals, the retroduodenal artery (i.e., the posterior superior and anterior superior pancreaticoduodenal artery) forms an arterial plexus that provides the primary blood supply to the region of the sphincter of Oddi. The remaining half receive blood supply to the sphincter of Oddi directly from one of the major branches of the retroduodenal artery, with the most likely branch being the posterior superior pancreaticoduodenal artery. The lymphatic drainage of the sphincter of Oddi follows the drainage of the encompassing ampulla of Vater, which drains into the posterior pancreatoduodenal lymph nodes, followed by the lymph nodes around the superior mesenteric artery, and finally into the para-aortic lymph nodes that follow their well-described path of drainage.[7][8]

The sphincter of Oddi possesses a complex intrinsic set of neural innervation. Currently, two ganglionated plexus have appeared in the literature:

1. Myenteric plexus, which lies between the sphincter's muscular layers
2. Submucosal plexus

There have also been a few subpopulations discovered in animal models that helped our understanding of the intrinsic innervation of the sphincter of Oddi. One of these described subpopulations was in guinea pigs and was found to be immunoreactive to choline acetyltransferase and served to provide an excitatory effect, thereby increasing sphincter of Oddi tone. Researchers also found a second, smaller, subset of neurons in the sphincter of Oddi that was immunoreactive to nitric oxide (NO) synthase and expressed vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY).

As opposed to the intrinsic neural innervation of the sphincter of Oddi, its extrinsic innervation is not very well understood but is thought to display characteristics similar to that of most of the biliary tract. This neurology includes parasympathetic nervous system innervation originating from the vagus nerve and sympathetic nervous system innervation originating from the superior mesenteric ganglion following the inferior pancreatic duodenal artery.

The sphincter of Oddi is also thought to be part of bidirectional signaling pathways.  There seems to be a bidirectional connection between the sphincter of Oddi and the gallbladder; the electrical activity of the gallbladder has been shown to inhibit sphincter of Oddi contraction reflexively. Similar to the aforementioned bidirectional system, there also exists evidence of a subpopulation of neurons demonstrating bidirectional signaling between the duodenum and sphincter of Oddi ganglia as part of an excitatory cholinergic pathway.[7][9][10][11]