The possum sphincter of Oddi pumps or resists flow depending on common bile duct pressure: a multilumen manometry study

Abstract

The sphincter of Oddi (SO) regulates trans-sphincteric flow (TSF) by acting primarily as a pump or as a resistor in specific species. We used the Australian possum SO, which functions similarly to the human SO, to characterize SO motility responses to different common bile duct (CBD) and duodenal pressures. Possum CBD, SO and attached duodenum (n= 18) was mounted in an organ bath. External reservoirs were used to impose CBD (0-17 mmHg) and duodenal (0, 4, 7 mmHg) pressure. Spontaneous SO activity was recorded using four-lumen pico-manometry and TSF was measured gravimetrically. Temporal analysis of manometric and TSF recordings identified three functionally distinct biliary-SO regions, the proximal-SO (juxta-CBD), body-SO and papilla-SO. At CBD pressures < 3 mmHg the motor activity of these regions was coordinated to pump fluid. Proximal-SO contractions isolated fluid within the body-SO. Peristaltic contraction through the body-SO pumped this fluid through the papilla-SO (17-27 microl contraction), which opened to facilitate flow. CBD pressure > 3.5 mmHg resulted in progressive changes in TSF to predominantly passive 'resistor'-type flow, occurring during proximal-SO-body-SO quiescence, when CBD pressure exceeded the pressure at the papilla-SO. Progression from pump to resistor function commenced when CBD pressure was 2-4 mmHg greater than duodenal pressure. These results imply that TSF is dependent on the CBD-duodenal pressure difference. The papilla-SO is pivotal to TSF, relaxing during proximal-SO-body-SO pumping and closing during proximal-SO-body-SO quiescence. The pump function promotes TSF at low CBD pressure and prevents bile stasis. At higher CBD pressure, the papilla-SO permits TSF along a pressure gradient, thereby maintaining a low pressure within the biliary tract.

Figure 1. Apparatus used for in vitro sphincter of Oddi multilumen manometry

A, the key features of the in vitro preparation are illustrated. The sphincter of Oddi (SO), common bile duct (CBD) and attached duodenum was placed in the organ bath containing oxygenated, modified Krebs. The inflow and outflow reservoirs are shown. The pancreatic duct (PD) was ligated. B, representation of the SO with the four manometry catheter side-holes located in ‘ideal’ positions – the CBD, proximal-SO (juxta-CBD), body-SO and papilla-SO (intraduodenal). The side-holes were located on the outer surface of each of four lumens but for simplicity are displayed in a line.

Figure 2. Illustration of basic hydrostatic features of perfused manometry

A, fluid and lumen-occluding pressures are illustrated. A manometry catheter with four side-holes is depicted in a fluid-filled cavity. A single lumen-occluding contraction results in two separate fluid-filled cavities. In the right cavity, both side-holes record identical fluid pressure whereas the single side-hole in the left cavity records independent fluid pressure. B, lumen-occluding and fluid pressures occurring in sphincter of Oddi (SO) manometric recording. Period i: SO quiescence; all 4 side-holes recorded identical pressures indicating their location in a common cavity of fluid as indicated in the associated diagram. Period ii: lumen-occluding contraction at the proximal-SO isolated two body-SO side-holes in a common cavity of fluid; hence their identical pressure profiles. An independent pressure profile was recorded from the side-hole located in the CBD, a separate fluid filled cavity. C, additional aspects of manometry are interpreted in three consecutive SO contractions. The diagram from A is used to show the relative positions of the side-holes and SO regions during each contraction. Between contractions, all side-holes recorded identical pressure profiles from a common cavity. During SO contraction 1, a lumen-occluding contraction occurred between side-holes, producing two separate fluid-filled cavities, each with two side-holes. This is represented in the associated diagram. The fluid pressure profiles recorded by each pair of side-holes in their respective cavities are identical and simultaneous, but different in each cavity. Fluid pressure was greater in the right cavity (body-SO1 and body-SO2) where body-SO contraction occurred. During contraction 2, a lumen-occluding contraction produced two separate fluid-filled cavities, each containing two side-holes. In the body-SO cavity, fluid pressure appeared as identical shoulders at the onset of the body-SO profiles. Sequential lumen-occluding pressures were then recorded from the body-SO1 and body-SO2 sites, as a contraction propagated distally. Body-SO1 lumen-occluding pressure was higher because of stronger muscle contraction. Lumen-occluding pressures are not restricted to the proximal-SO. Contraction 3 illustrates the effect longitudinal SO contraction can have on manometric recordings. A lumen-occluding proximal-SO contraction occurred at a recording site (compare with diagrams for contractions 1 and 2). This can be explained by the less intense body-SO pressure recorded, indicating less circular and longitudinal muscle contraction. Weaker longitudinal contraction produced less SO shortening, resulting in the lumen-occluding contraction site coinciding with the recording site.

Figure 3. Relationship between trans-sphincteric flow and imposed common bile duct pressure (duodenal pressure of 0 mmHg)

A, TSF was a three-component function of imposed CBD pressure (0–17 mmHg; n = 9) with slow and rapid linear components and an intermediate inflection. Maximum flow rate through the inflow catheter without the SO attached was always greater, which reveals that the SO was regulating TSF. B, the intersection of straight lines fitted to the slow and rapid components of the data defines the SO opening pressure.

Figure 4. Manometric and TSF data recorded during SO pumping activity

A, TSF and manometric data from 4 channels during low imposed CBD pressure (1.9 mmHg). B, temporal relationships revealed by superimposing manometric and TSF data. Period i: lumen-occluding papilla-SO pressure stopped TSF. Identical proximal-SO, body-SO and CBD pressures profiles indicated a common cavity, allowing fluid to flow from the inflow reservoir. Period ii: papilla-SO pressure decreased while lumen-occluding proximal-SO pressure enclosed fluid in the body-SO. Body-SO pressure increased. Period iii: proximal-SO and body-SO pressures increased further. TSF commenced when decreasing papilla-SO pressure equalled body-SO pressure. During TSF, papilla-SO and body-SO registered identical small peaks, reflecting a common fluid cavity. Papilla-SO pressure profile represents fluid pressure at this point. Period iv: TSF ceased as increasing papilla-SO pressure exceeded the fluid pressure within the body-SO and closed the SO (lumen-occluding pressure). Period v: papilla-SO pressure further increased while the proximal-SO and body-SO pressures decreased, allowing passive filling of the SO. This sequence of events reflects the pumping of fluid by the SO. C, expanded section of B (period iii), with a thick dashed line projecting the proposed reduction in papilla-SO pressure if lumen-occluding pressure alone was recorded; instead fluid pressure was registered during TSF, masking this change in papilla-SO pressure. D, diagrammatic representation of SO pumping stages and manometry pressures. At low CBD pressure, the papilla-SO pressure prevented TSF while the quiescent extra-duodenal SO–CBD filled with fluid (periods i and ii). Synchronized with reduced papilla-SO pressure, a peristaltic-like pressure wave commenced at the proximal-SO and propagated through the body-SO, resulting in pumping of fluid into the duodenum (periods iii and iv). This sequence repeated after the papilla-SO pressure increased and again prevented TSF (period v). In the diagram, the striped boxes denote the CBD and three SO regions. E, manometric SO recordings from a catheter with side-holes at 2, 4, 6 and 8 mm from the tip demonstrated that the papilla-SO is ∼4 mm long and has diverse manometric profiles.

Figure 5. Manometric and TSF data recorded during high imposed CBD pressure

A, manometric data from an experiment with imposed CBD pressure of 5 mmHg. Period i: high papilla-SO pressure slowed or stopped TSF (resistor behaviour). Period ii: TSF occurred passively during proximal-SO–body-SO quiescence when the imposed CBD pressure exceeded papilla-SO pressure. Period iii: body-SO pressure increase was associated with small increases in TSF ‘pumping’. B, mean values (± s.e.m.) of TSF as a function of imposed CBD pressure. Passive TSF became greater than pumped TSF as imposed CBD pressure increased (n = 9).

Figure 6. The effect of duodenal pressure on TSF during imposed CBD pressure

CBD pressure was varied (0–17 mmHg) while duodenal pressure was maintained at 0 (n = 9), 4 (n = 8) or 7 (n = 7) mmHg. Elevated duodenal pressures increased the SO opening pressures.

Figure 7. Manometric and TSF recordings with elevated duodenal pressure

Duodenal contractile activity was visually evident and corresponded to large fluctuations in the TSF recordings. These fluctuations prevented temporal analysis of TSF and SO contractions. Pressure increases in the SO manometry (SO contractions) and TSF (duodenal contractions) were never temporally synchronized. The duodenal pressure was set at 7 mmHg and the imposed CBD pressure was 0.7 mmHg.