Current concepts in physiology and pathophysiology of lower esophageal sphincteric mechanism are reviewed. With recent advances in manometric method for more accurate in-vivo human studies combined with in-vivo and in-vitro studies in animal models, there is much information regarding function of this sphincter. Three components of sphincter control have been identified: specialized circular smooth muscle at esophagogastric junction, autonomic nervous system, and probable physiology effects of gastrointestinal hormones, particularly gastrin. Clinical syndromes of sphincteric dysfunction have been identified relative to these three controlling elements. Foods and drugs that adversely effect sphincter pressure have been identified and indicate that anticholinergic agents, fatty foods, chocolate, alcohol, and cigarette smoking may have a harmful effect on a patient with heartburn. Drugs that increase the antireflux sphincter barrier have been studied. Clinical effectiveness of antacids and bethanechol in therapy of heartburn is supported by controlled treatment trials. Research continues on other medications producing increases in sphincter pressure.

The lower esophageal sphincter. Physiologic and clinical aspects.

Gastric alkalinization. Effect on lower-esophageal-sphincter pressure and serum gastrin.

Responses of the lower oesophageal sphincter (LOS) to pentagastrin, given by continuous intravenous infusion in doses ranging between 0 and 9 mug/kg/h, and to external abdominal compression were measured by infused catheters in healthy subjects and in a group of patients with reflux oesophagitis In separate experiments, pressures were measured both by sensors stationary within the LOS, and by repeated continuous withdrawals of sensors from stomach to distal oesophagus In normal subjects, doses of pentagastrin within the physiological range (09 mug/kg/h) produced modest but statistically significant increases in LOS pressure By comparison, sphincteric responses in patients with oesophagitis were small and a dose of 4-5 mug/kg/h was the lowest that produced a significant increase in LOS pressure During abdominal compression increases in LOS pressure did not significantly exceed increases in intragastric pressure in either patients or normal subjects This was so at all doses of pentagastrin that were tested Hence, there was no evidence of synergism between the effects of pentagastrin and abdominal compression upon the LOS We infer from our findings that gastrin does play a modest role in the physiological regulation of human LOS tone Relative insensitivity of the incompetent LOS to pentagastrin represents, we believe, sphincteric muscle failure Our results are not consistent with the hypothesis that LOS incompetence is due to loss or impairment of an adaptive response of the LOS to alterations in intra-abdominal pressure

https://gut.bmj.com/content/gutjnl/17/12/933.full.pdf

Responses of the competent and incompetent lower oesophageal sphincter to pentagastrin and abdominal compression.

The history of hormones, which began as a physiologic era with the discovery of secretin by Bayliss and Starling in 1902, turned into a biochemical era with the isolation of gastrin by Gregory and Tracy in 1964. From pig antral mucosa these authors isolated two heptadecapeptides that they named gastrin I and gastrin II, according to the absence (I) or presence (II) of a sulfated group on the tyrosyl residue in the sixth position (starting unconventionally from the COOH terminus). Since then, gastrin heptadecapeptides have been purified from the antral mucosa of several species (including human, dog, pig, cat, sheep, and cow) and found to differ in only one or two amino acid substitutions in the middle of the linear peptide chain (Gregory 1974). The development of immunologic methods of study made it possible to measure gastrin in tissues and body fluids and established the heterogeneity of this peptide which can be present in several forms because of its biosynthetic pathways and enzymatic degradation: a “big gastrin” with 34 amino acid residues (this is referred to as G 34), the heptadecapeptide “little gastrin,” (G 17), and a “minigastrin” isolated from gastrinoma tissue by Gregory and Tracy (1974) and thought initially to be the COOH terminal tridecapeptide of G 17. It has since become apparent that there is an additional tryptophan at the NH2 terminus, bringing the total of aminoacid residues to 14 (G 14) (Gregory et al. 1979), in the same sequence as in the COOH terminal tetradecapeptide of G 17.

Peptides: Gastrointestinal Hormones

Gastric pH values were studied prior to, and up to, ninety minutes after an intravenous injection of cimetidine 200 mg given before general anaesthesia, in twenty surgical patients, all with a gastric pH less than 3.5. At thirty, sixty and ninety minutes, sixteen, eighteen and twenty patients had a gastric pH greater than 3.5 respectively. In conclusion, the results of the present study indicate that cimetidine 200 mg given intravenously 90 minutes before surgery will reduce the hazard of chemical pneumonitis should stomach content be aspirated.

Beiles B

Papers

The effect of intragastric aluminium hydroxide on lower oesophageal sphincter pressures.