- Email: [email protected]
Practical gastric physiology
Practical gastric physiology Diana M Jolliffe BSc FRCP FRCA
The functions of the stomach are: † temporary storage of food input; † mechanical breakdown of food into smaller particles; † chemical digestion, with breakdown of proteins; † regulation of output of chyme into the duodenum; † secretion of intrinsic factor, vital for vitamin B12 absorption. Most anaesthetists are wary of this part of the gastrointestinal tract because of the potential for tracheobronchial aspiration of stomach contents. Nevertheless, we are required to administer anaesthesia to patients with full stomachs and an understanding of the relevant gastric physiology can help avoid and reduce the consequences of gastric aspiration. For aspiration of stomach contents to occur there must first be gastro-oesophageal reflux, when gastric contents breach the lower oesophageal sphincter (LOS). The acid material must then flow back along the 30 cm oesophagus and be regurgitated ( pass the upper oesophageal sphincter) to contaminate the pharynx. If the patient’s level of consciousness is reduced, the normally protective gag and cough reflexes will be obtunded and gastric contents may then reach the tracheobronchial tree (aspiration). Solid matter may obstruct the airways and the acidic liquid can cause bronchospasm, resulting in severe hypoxia and respiratory failure.
Measures to reduce the incidence and effects of aspiration of gastric contents (i) Minimize the amount of gastrooesophageal reflux, by: (a) maintaining the tone of the LOS; (b) reducing the gastro-oesophageal pressure gradient; (c) using gravity. (ii) Reduce gastric volume. (iii) Increase gastric emptying. (iv) Reduce acidity of gastric contents.
Gastro-oesophageal reflux and the lower oesophageal sphincter The distal oesophagus passes through the crura of the diaphragm and joins the stomach at an acute angle, the gastro-oesophageal junction, which normally lies just below the diaphragmatic hiatus. The LOS is formed by the intrinsic circular smooth muscle of the lowest 2–4 cm of the oesophagus, tonic contraction of which separates the gastric and oesophageal lumens. The LOS is a physiological sphincter which is normally closed with a resting pressure of 15–25 mm Hg above gastric pressure (termed the barrier pressure). It relaxes on swallowing, a reflex mediated by the inhibitory neurotransmitters nitric oxide and vasoactive intestinal polypeptide. This allows saliva, ingested liquids, and food boluses, which are transported from the pharynx on the oesophageal peristaltic wave, to pass through into the stomach. The LOS then regains its tone. LOS tone was thought to be the main defence mechanism against reflux of acidic gastric contents into the lower oesophagus. It was found that many patients with severe erosive oesophagitis had LOS pressures below 10 mm Hg. In these cases small increases in intra-gastric or intra-abdominal pressure resulted in free reflux of gastric acid into the oesophagus. Various factors are known to alter LOS tone and may affect the incidence of gastro-oesophageal reflux (Table 1). However, studies in normal individuals have since demonstrated that gastro-oesophageal reflux is a physiological event and healthy asymptomatic people have acid reflux sufficient to lower the pH in the distal oesophagus to below 4 for up to 4% of the time. It is now recognized that there are transient, unprovoked relaxations of the LOS which are of longer duration (10–45 s) than those associated with swallowing (6–8 s).1 The frequency of these spontaneous relaxations correlates with the severity of oesophagitis, and explains how patients can have severe heartburn with a normal resting LOS tone. However, the severity of symptoms correlates poorly with the degree of acid reflux and the presence or extent of mucosal damage. Excessive gastro-oesophageal reflux also occurs in patients with disordered oesophageal motility and those with gastric
doi:10.1093/bjaceaccp/mkp033 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 9 Number 6 2009 & The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]
Key points Gastro-oesophageal reflux is a normal physiological event. The lower oesophageal sphincter (LOS) may relax spontaneously. The barrier pressure of the LOS is one of the defences against acid reflux. The head-up position discourages reflux and regurgitation. Antacids raise the pH of stomach contents but increase gastric volume.
Diana M Jolliffe BSc FRCP FRCA Consultant Anaesthetist Department of Anaesthesia Northampton General Hospital Cliftonville Northampton NN1 5BD UK Tel: þ44 1604 545671/2 Fax: þ44 1604 545663 E-mail: [email protected] (for correspondence)
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Practical gastric physiology
Table 1 Factors affecting LOS tone Factors that increase LOS tone and so make reflux less likely
Factors that decrease LOS tone and so make reflux more likely
Physiological Cholinergic stimulation
Swallowing Oestrogen, progesterone
Pharmacological Anti-cholinesterases, e.g. neostigmine D2 antagonists, e.g. metoclopramide, prochlorperazine, domperidone Cyclizine Succinylcholine
Anti-muscarinics, e.g. atropine, glycopyrrolate Dopamine
Gastro-oesophageal reflux and gravity Opioids Thiopental
Pathological Alcohol
dysmotility. Therefore, LOS tone is probably only part of the defence against acid reflux and two other mechanisms may contribute: (i) the acute angle at which the oesophagus enters the stomach may help seal the gastro-oesophageal junction. (ii) the muscle fibres around the diaphragmatic hiatus may reinforce LOS function, helping to prevent reflux into the oesophagus, particularly when intra-abdominal pressure is raised. Gastro-oesophageal reflux increases in those with a sliding hiatus hernia (when the upper part of the stomach passes through the diaphragmatic hiatus into the thorax). In this situation the angle of the gastro-oesophageal junction is straightened out, there is no diaphragmatic contribution to sphincter function and increases in intra-abdominal pressure are transmitted to the stomach. The distorted gastro-oesophageal junction now lies above the diaphragm within the thorax at low pressure, and stomach contents tend to be forced through the LOS (unreinforced by the diaphragmatic fibres) into the lower oesophagus.
Gastro-oesophageal pressure gradient If intra-gastric or intra-abdominal pressure (which is transmitted to the stomach) is elevated there will be an increased pressure gradient across the LOS increasing the chance of gastro-oesophageal reflux occurring. The stomach converts the episodic input of food from the oesophagus into a more continuous output of chyme into the duodenum. The fundus and body (the proximal stomach) act as a reservoir and their relatively thin, highly distensible smooth muscle layers relax as the stomach expands. It might be anticipated that as the stomach filled the intra-gastric pressure would increase, but there is little increase in intra-gastric pressure until gastric volume exceeds a litre. This accommodation results from a vagal reflex initiated by stretch receptors in the oesophagus (‘receptive relaxation’) and as a consequence of the presence of food in the proximal stomach (‘adaptive relaxation’).2 Intra-abdominal pressure is increased in various situations (including obesity, pregnancy, intestinal obstruction, and during
174
laparoscopic surgery) and is associated with a higher incidence of gastro-oesophageal reflux. The patient with gastrointestinal obstruction develops distension of the gut proximal to the obstruction due to sequestration of fluid and gas. It may be possible to lessen this by inserting and intermittently aspirating a large-bore nasogastric tube which will help to decompress the gut and relieve the raised intra-abdominal pressure. The patient will be more comfortable if they are allowed to sit propped up with their hips and knees flexed as this reduces the tension in their abdominal wall muscles.
Both reflux and regurgitation are passive processes which are influenced by gravity and so are less likely to occur if the patient is semi-recumbent rather than supine. For mechanically ventilated patients the time spent supine is a critical factor associated with aspiration.3 Elevation of the head of the patient’s bed is included in the Institute for Healthcare Improvement’s ventilator care bundle for reducing the high mortality of ventilator-acquired pneumonia.4 Cricoid pressure is used during induction of anaesthesia in the patient with a potentially full stomach. This manoeuvre uses external pressure to compress the oesophagus against the cervical body of C6 and so discourages regurgitation of stomach contents through the upper oesophageal sphincter. This anatomical sphincter comprises the inferior pharyngeal constrictor muscle (the cricopharyngeus) which lies at the level of C5 and C6. Cricoid pressure is effective in reducing regurgitation even if a nasogastric tube is present.5
Gastric volume The volume of the stomach is determined by: † the amount of food and drink ingested; † the volume of gastric juice produced; † the rate at which the stomach empties. Gastric volume is reduced by keeping a patient ‘nil by mouth’ not only because input is omitted but also because less gastric juice is secreted. Gastric juice is produced in response to eating. Normally the stomach produces about 2 litres a day but during fasting there is little or no secretion. It consists of hydrochloric acid, intrinsic factor, pepsinogens, and mucus (the secretions of the gastric gland cells, Table 2) and also contains water and electrolytes, particularly Kþ and Cl2. It has a pH of 1–1.5. Physical methods may be used to empty the stomach: a largebore nasogastric tube may be inserted and aspirated occasionally but otherwise allowed to drain freely. Emetic agents are no longer used.
Gastric emptying For the stomach to empty, the pressure generated by the antral pump must exceed the resistance of the pyloric sphincter. In general, emptying occurs at an exponential rate proportional to the volume of the stomach, that is, the fuller the stomach, the more rapidly it empties (Table 3). This is mediated by vagal excitatory reflexes (provoked by gastric distension). Gastrin is also released in response to antral
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 6 2009
Practical gastric physiology
Table 2 Secretions of gastric gland cells Released from
Release stimulated by
Release inhibited by
Function
HCl 0.15 M
Parietal cells, mainly in the fundus and body of the stomach
Gastrin ACh Vagal stimulation Distension of body of stomach (vagal reflex) Histamine (H2 receptors)
Acidity Anti-muscarinics Vagotomy Somatostatin Prostaglandin E2 H2 receptor antagonists PPIs
Facilitates breakdown of protein Activates pepsinogens and provides optimal conditions for pepsin activity Improves solubility and hence absorption of calcium and iron Kills pathogenic micro-organisms
Pepsin
Chief cells, mainly in the body of the stomach
Vagal stimulation ACh Acid pH Secretin (from the duodenum)
A proteolytic enzyme, stored as inactive pepsinogens, which facilitates protein digestion
Intrinsic factor
Parietal cells, mainly in the fundus of the stomach
Same factors that stimulate release of gastric acid
This glycoprotein binds ingested B12 (cobalamin) in the stomach, protecting it from enzymatic destruction. The complex is absorbed in the terminal ileum
Mucus
Mucus cells
Vagal stimulation Prostaglandins E2 and I2
Forms a layer protecting the mucosa from mechanical trauma and digestion by gastric acid and proteolytic enzymes
Table 3 Factors affecting gastric emptying Factors that increase gastric emptying and so make reflux less likely
Factors that delay gastric emptying and so make reflux more likely
Physiological Stomach distension Liquid content Smaller particles Parasympathetic stimulation
Duodenal distension Chyme high in Hþ, fat, or protein Secretin Pain, anxiety, stress Sympathetic stimulation
Pharmacological Anti-cholinesterases, e.g. neostigmine Metoclopramide Domperidone Erythromycin
Anti-muscarinics, e.g. atropine, glycopyrrolate Opioids
Pathological Alcohol Pyloric stenosis Intestinal obstruction Previous vagotomy
distension, and both these stimuli produce an increase in antral pump activity. The speed of emptying for liquids, or contents consisting of smaller particles, is faster than for solids. Thus, in the normal stomach, 95% of an ingested clear liquid reaches the duodenum within 1 h and 50% of a meal will pass the pylorus in 2 h. The chemical composition of the chyme entering the duodenum also affects the rate of gastric emptying and various hormones are involved (Table 4). If the chyme is too acidic, secretin is released which slows gastric emptying, reduces the production of gastric acid, and increases the secretion of alkaline pancreatic juice into the duodenum. If the fat content of the chyme is too high, cholecystokinin (CCK) is released. CCK stimulates contraction of the gall bladder so that bile salts (which emulsify the fats) are secreted into the
duodenum, and also reduces gastric emptying. If the chyme has too high a content of amino acids, gastrin is released. This increases contraction of the pyloric sphincter (as well as increasing gastric motility) and overall delays gastric emptying. Hypertonic chyme is detected by duodenal osmoreceptors and gastric emptying is slowed. As the duodenum fills, stretch receptors are activated and inhibit the vagus which results in reduced gut tone and motility, temporarily reducing gastric emptying. As the duodenum empties this inhibition diminishes, the tone and motility of the gut increases, and gastric emptying is restored. The neural and hormonal mechanisms which originate from the duodenum and feedback to slow gastric emptying constitute the entero-gastric reflex.6 By regulating the rate of delivery of chyme into the duodenum, the absorption of nutrients in the small intestine is maximized. Alcohol and opioids reduce the rate of gastric empting, as do pain, fear, and anxiety (acting via the sympathetic nervous system which inhibits motility). It is now recognized that pregnancy per se does not alter gastric empting. However, during labour there is delay because of pain, anxiety, and administration of opioids. Prokinetic drugs may be used to stimulate enteral propulsion if there is no gastrointestinal obstruction, perforation, or haemorrhage. Metoclopramide is a centrally and peripherally acting dopaminergic D2 antagonist which increases the rate of gastric emptying and small intestinal transit, and also increases LOS constriction. It can be given i.v., i.m., or orally, in a dose of 10 mg 8 hourly, but is most effective i.v. Its use may be limited by adverse effects which include extra-pyramidal effects, tardive dyskinesia, and hyperprolactinaemia. Domperidone has similar pharmacological actions and is better tolerated but can only be given orally or rectally. The macrolide antibiotic erythromycin has prokinetic properties and may produce abdominal cramps, nausea, and vomiting. It is an agonist at motilin receptors, stimulating strong antral contractions.
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Practical gastric physiology
Table 4 Gastric hormones Released from
Release stimulated by
Release inhibited by
Function
Gastrin
G cells in the stomach antrum and duodenum
Vagal stimulation Distension of gastric antrum Distension of duodenum Amino acids and peptides Alcohol Caffeine
Gastric acidity Somatostatin Secretin (stimulated by duodenal acidity) Glucagon
Stimulates gastric acid production Increases secretion of pepsinogens Increases secretion of mucus Increases gastric motility Constricts pyloric sphincter Reduces gastric emptying
Secretin
S cells in the duodenum and jejunum
Increased acidity in duodenal chyme
Reduces gastric acid secretion Reduces gastric emptying Increases pancreatic secretions
CCK
I cells in the duodenum and jejunum
Increased fat in duodenal chyme
Reduces gastric acid secretion Reduces gastric emptying Contracts gall bladder
Somatostatin
D cells in the stomach
Gastric acidity
Motilin
Entero-chromaffin-like cells in proximal small intestine
Gastric contents The morbidity of acid aspiration syndrome correlates with the volume, acidity, and the particulate nature of the material introduced into the lungs. Therefore, reducing the size of the particles and the acidity of the contents of the stomach will result in less severe pulmonary damage if aspiration occurs. Parietal cell production of gastric acid is stimulated by various factors (Table 2). Inhibition of gastric acid secretion will also reduce the volume of the stomach’s contents. Anti-muscarinic agents block acetylcholine (ACh) release from vagal postganglionic fibres and reduce gastric acidity. However, they are not used in practice because they also reduce LOS tone and delay gastric emptying, thereby increasing the risk of gastro-oesophageal reflux. H2 receptor antagonists reduce gastric acid secretion and both cimetidine and ranitidine may be given i.v. Ranitidine is preferred because it has a longer duration of action and fewer drug interactions. Proton pump inhibitors (PPIs) irreversibly block the Hþ/Kþ ATPase enzyme which catalyses the exchange of intracellular Hþ for extracellular Kþ, the final step in the production of gastric acid by the parietal cells. With repeated doses PPIs are highly effective at producing achlorhydria. Omeprazole 40 mg may be given i.v. but as a single preoperative dose has no advantage over H2 receptor antagonists. Oral antacids are given to raise the pH of the stomach’s contents by neutralizing gastric acid, but they increase gastric volume. Sodium citrate 0.3 M is used as it is non-particulate so causes less pulmonary damage if aspirated. 30 ml will neutralize the gastric contents within 10 min. Using their knowledge of the relevant gastric physiology, the anaesthetist can reduce the incidence and consequences of gastric aspiration when required to administer general anaesthesia to a patient with a full stomach, gastro-oesophageal reflux, and/or obtunded airway reflexes.
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Vagal stimulation
Inhibits gastrin secretion (and thereby gastric acid production) Reduces gastric motility Reduces gastric emptying Increases gastric motility Increases gastric emptying Associated with the inter-digestive migratory motor complex (MMC)
Illustrative clinical example Suggested management of the patient with a potentially full stomach who requires a general anaesthetic Before operation: Position the patient with head-up tilt and knees flexed Insert large-bore nasogastric tube and aspirate Leave nasogastric tube on free drainage Keep ‘nil by mouth’ Give ranitidine 50 mg by slow i.v. injection Give metoclopramide 10 mg i.v. if no gastrointestinal obstruction, perforation, or haemorrhage At induction of anaesthesia: Aspirate nasogastric tube Give sodium citrate 0.3 M (30 ml) orally Check patient positioned with head-up tilt Pre-oxygenate Apply cricoid pressure Induce anaesthesia with a rapid sequence induction Intubate with a cuffed oro-tracheal tube to secure the airway Peroperatively: Maintain head-up position if possible Avoid increases in abdominal pressure Ensure adequate depth of anaesthesia After operation: Extubate in the left lateral position Extubate when awake and gag and cough reflexes are present
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 6 2009
Practical gastric physiology
References
4. Available from www.ihi.org/IHI/Topics/CriticalCare/IntensiveCare/Changes/ ImplementtheVentilatorBundle. Accessed February 20, 2009
1. Holloway RH, Penagini R, Ireland AC. Criteria for objective definition of transient lower esophageal sphincter relaxation. Am J Physiol Gastrointest Liver Physiol 1995; 268: G128– 33
5. Aitkenhead AR, Smith G, Rowbotham DJ. Textbook of Anaesthesia, 5th Edn. Elsevier, 2007: Chapter 28, p. 544
2. Petersen OH. Lecture Notes: Human Physiology, 5th Edn. Oxford: Blackwell Publishing Ltd, 2007
6. Pocock G, Richards CD. The storage, mixing, and propulsion of gastric contents. Human Physiology: The Basis of Medicine, 2nd Edn. Oxford: Oxford University Press, 2004; 437– 40
3. Torres A, Serra-Batlles J, Ros E, Piera C, Puig de la Bellacasa J, Cobos A. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992; 116: 540–3
Please see multiple choice questions 1– 3
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The functions of the stomach are: † temporary storage of food input; † mechanical breakdown of food into smaller particles; † chemical digestion, with breakdown of proteins; † regulation of output of chyme into the duodenum; † secretion of intrinsic factor, vital for vitamin B12 absorption. Most anaesthetists are wary of this part of the gastrointestinal tract because of the potential for tracheobronchial aspiration of stomach contents. Nevertheless, we are required to administer anaesthesia to patients with full stomachs and an understanding of the relevant gastric physiology can help avoid and reduce the consequences of gastric aspiration. For aspiration of stomach contents to occur there must first be gastro-oesophageal reflux, when gastric contents breach the lower oesophageal sphincter (LOS). The acid material must then flow back along the 30 cm oesophagus and be regurgitated ( pass the upper oesophageal sphincter) to contaminate the pharynx. If the patient’s level of consciousness is reduced, the normally protective gag and cough reflexes will be obtunded and gastric contents may then reach the tracheobronchial tree (aspiration). Solid matter may obstruct the airways and the acidic liquid can cause bronchospasm, resulting in severe hypoxia and respiratory failure.
Measures to reduce the incidence and effects of aspiration of gastric contents (i) Minimize the amount of gastrooesophageal reflux, by: (a) maintaining the tone of the LOS; (b) reducing the gastro-oesophageal pressure gradient; (c) using gravity. (ii) Reduce gastric volume. (iii) Increase gastric emptying. (iv) Reduce acidity of gastric contents.
Gastro-oesophageal reflux and the lower oesophageal sphincter The distal oesophagus passes through the crura of the diaphragm and joins the stomach at an acute angle, the gastro-oesophageal junction, which normally lies just below the diaphragmatic hiatus. The LOS is formed by the intrinsic circular smooth muscle of the lowest 2–4 cm of the oesophagus, tonic contraction of which separates the gastric and oesophageal lumens. The LOS is a physiological sphincter which is normally closed with a resting pressure of 15–25 mm Hg above gastric pressure (termed the barrier pressure). It relaxes on swallowing, a reflex mediated by the inhibitory neurotransmitters nitric oxide and vasoactive intestinal polypeptide. This allows saliva, ingested liquids, and food boluses, which are transported from the pharynx on the oesophageal peristaltic wave, to pass through into the stomach. The LOS then regains its tone. LOS tone was thought to be the main defence mechanism against reflux of acidic gastric contents into the lower oesophagus. It was found that many patients with severe erosive oesophagitis had LOS pressures below 10 mm Hg. In these cases small increases in intra-gastric or intra-abdominal pressure resulted in free reflux of gastric acid into the oesophagus. Various factors are known to alter LOS tone and may affect the incidence of gastro-oesophageal reflux (Table 1). However, studies in normal individuals have since demonstrated that gastro-oesophageal reflux is a physiological event and healthy asymptomatic people have acid reflux sufficient to lower the pH in the distal oesophagus to below 4 for up to 4% of the time. It is now recognized that there are transient, unprovoked relaxations of the LOS which are of longer duration (10–45 s) than those associated with swallowing (6–8 s).1 The frequency of these spontaneous relaxations correlates with the severity of oesophagitis, and explains how patients can have severe heartburn with a normal resting LOS tone. However, the severity of symptoms correlates poorly with the degree of acid reflux and the presence or extent of mucosal damage. Excessive gastro-oesophageal reflux also occurs in patients with disordered oesophageal motility and those with gastric
doi:10.1093/bjaceaccp/mkp033 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 9 Number 6 2009 & The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]
Key points Gastro-oesophageal reflux is a normal physiological event. The lower oesophageal sphincter (LOS) may relax spontaneously. The barrier pressure of the LOS is one of the defences against acid reflux. The head-up position discourages reflux and regurgitation. Antacids raise the pH of stomach contents but increase gastric volume.
Diana M Jolliffe BSc FRCP FRCA Consultant Anaesthetist Department of Anaesthesia Northampton General Hospital Cliftonville Northampton NN1 5BD UK Tel: þ44 1604 545671/2 Fax: þ44 1604 545663 E-mail: [email protected] (for correspondence)
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Practical gastric physiology
Table 1 Factors affecting LOS tone Factors that increase LOS tone and so make reflux less likely
Factors that decrease LOS tone and so make reflux more likely
Physiological Cholinergic stimulation
Swallowing Oestrogen, progesterone
Pharmacological Anti-cholinesterases, e.g. neostigmine D2 antagonists, e.g. metoclopramide, prochlorperazine, domperidone Cyclizine Succinylcholine
Anti-muscarinics, e.g. atropine, glycopyrrolate Dopamine
Gastro-oesophageal reflux and gravity Opioids Thiopental
Pathological Alcohol
dysmotility. Therefore, LOS tone is probably only part of the defence against acid reflux and two other mechanisms may contribute: (i) the acute angle at which the oesophagus enters the stomach may help seal the gastro-oesophageal junction. (ii) the muscle fibres around the diaphragmatic hiatus may reinforce LOS function, helping to prevent reflux into the oesophagus, particularly when intra-abdominal pressure is raised. Gastro-oesophageal reflux increases in those with a sliding hiatus hernia (when the upper part of the stomach passes through the diaphragmatic hiatus into the thorax). In this situation the angle of the gastro-oesophageal junction is straightened out, there is no diaphragmatic contribution to sphincter function and increases in intra-abdominal pressure are transmitted to the stomach. The distorted gastro-oesophageal junction now lies above the diaphragm within the thorax at low pressure, and stomach contents tend to be forced through the LOS (unreinforced by the diaphragmatic fibres) into the lower oesophagus.
Gastro-oesophageal pressure gradient If intra-gastric or intra-abdominal pressure (which is transmitted to the stomach) is elevated there will be an increased pressure gradient across the LOS increasing the chance of gastro-oesophageal reflux occurring. The stomach converts the episodic input of food from the oesophagus into a more continuous output of chyme into the duodenum. The fundus and body (the proximal stomach) act as a reservoir and their relatively thin, highly distensible smooth muscle layers relax as the stomach expands. It might be anticipated that as the stomach filled the intra-gastric pressure would increase, but there is little increase in intra-gastric pressure until gastric volume exceeds a litre. This accommodation results from a vagal reflex initiated by stretch receptors in the oesophagus (‘receptive relaxation’) and as a consequence of the presence of food in the proximal stomach (‘adaptive relaxation’).2 Intra-abdominal pressure is increased in various situations (including obesity, pregnancy, intestinal obstruction, and during
174
laparoscopic surgery) and is associated with a higher incidence of gastro-oesophageal reflux. The patient with gastrointestinal obstruction develops distension of the gut proximal to the obstruction due to sequestration of fluid and gas. It may be possible to lessen this by inserting and intermittently aspirating a large-bore nasogastric tube which will help to decompress the gut and relieve the raised intra-abdominal pressure. The patient will be more comfortable if they are allowed to sit propped up with their hips and knees flexed as this reduces the tension in their abdominal wall muscles.
Both reflux and regurgitation are passive processes which are influenced by gravity and so are less likely to occur if the patient is semi-recumbent rather than supine. For mechanically ventilated patients the time spent supine is a critical factor associated with aspiration.3 Elevation of the head of the patient’s bed is included in the Institute for Healthcare Improvement’s ventilator care bundle for reducing the high mortality of ventilator-acquired pneumonia.4 Cricoid pressure is used during induction of anaesthesia in the patient with a potentially full stomach. This manoeuvre uses external pressure to compress the oesophagus against the cervical body of C6 and so discourages regurgitation of stomach contents through the upper oesophageal sphincter. This anatomical sphincter comprises the inferior pharyngeal constrictor muscle (the cricopharyngeus) which lies at the level of C5 and C6. Cricoid pressure is effective in reducing regurgitation even if a nasogastric tube is present.5
Gastric volume The volume of the stomach is determined by: † the amount of food and drink ingested; † the volume of gastric juice produced; † the rate at which the stomach empties. Gastric volume is reduced by keeping a patient ‘nil by mouth’ not only because input is omitted but also because less gastric juice is secreted. Gastric juice is produced in response to eating. Normally the stomach produces about 2 litres a day but during fasting there is little or no secretion. It consists of hydrochloric acid, intrinsic factor, pepsinogens, and mucus (the secretions of the gastric gland cells, Table 2) and also contains water and electrolytes, particularly Kþ and Cl2. It has a pH of 1–1.5. Physical methods may be used to empty the stomach: a largebore nasogastric tube may be inserted and aspirated occasionally but otherwise allowed to drain freely. Emetic agents are no longer used.
Gastric emptying For the stomach to empty, the pressure generated by the antral pump must exceed the resistance of the pyloric sphincter. In general, emptying occurs at an exponential rate proportional to the volume of the stomach, that is, the fuller the stomach, the more rapidly it empties (Table 3). This is mediated by vagal excitatory reflexes (provoked by gastric distension). Gastrin is also released in response to antral
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 6 2009
Practical gastric physiology
Table 2 Secretions of gastric gland cells Released from
Release stimulated by
Release inhibited by
Function
HCl 0.15 M
Parietal cells, mainly in the fundus and body of the stomach
Gastrin ACh Vagal stimulation Distension of body of stomach (vagal reflex) Histamine (H2 receptors)
Acidity Anti-muscarinics Vagotomy Somatostatin Prostaglandin E2 H2 receptor antagonists PPIs
Facilitates breakdown of protein Activates pepsinogens and provides optimal conditions for pepsin activity Improves solubility and hence absorption of calcium and iron Kills pathogenic micro-organisms
Pepsin
Chief cells, mainly in the body of the stomach
Vagal stimulation ACh Acid pH Secretin (from the duodenum)
A proteolytic enzyme, stored as inactive pepsinogens, which facilitates protein digestion
Intrinsic factor
Parietal cells, mainly in the fundus of the stomach
Same factors that stimulate release of gastric acid
This glycoprotein binds ingested B12 (cobalamin) in the stomach, protecting it from enzymatic destruction. The complex is absorbed in the terminal ileum
Mucus
Mucus cells
Vagal stimulation Prostaglandins E2 and I2
Forms a layer protecting the mucosa from mechanical trauma and digestion by gastric acid and proteolytic enzymes
Table 3 Factors affecting gastric emptying Factors that increase gastric emptying and so make reflux less likely
Factors that delay gastric emptying and so make reflux more likely
Physiological Stomach distension Liquid content Smaller particles Parasympathetic stimulation
Duodenal distension Chyme high in Hþ, fat, or protein Secretin Pain, anxiety, stress Sympathetic stimulation
Pharmacological Anti-cholinesterases, e.g. neostigmine Metoclopramide Domperidone Erythromycin
Anti-muscarinics, e.g. atropine, glycopyrrolate Opioids
Pathological Alcohol Pyloric stenosis Intestinal obstruction Previous vagotomy
distension, and both these stimuli produce an increase in antral pump activity. The speed of emptying for liquids, or contents consisting of smaller particles, is faster than for solids. Thus, in the normal stomach, 95% of an ingested clear liquid reaches the duodenum within 1 h and 50% of a meal will pass the pylorus in 2 h. The chemical composition of the chyme entering the duodenum also affects the rate of gastric emptying and various hormones are involved (Table 4). If the chyme is too acidic, secretin is released which slows gastric emptying, reduces the production of gastric acid, and increases the secretion of alkaline pancreatic juice into the duodenum. If the fat content of the chyme is too high, cholecystokinin (CCK) is released. CCK stimulates contraction of the gall bladder so that bile salts (which emulsify the fats) are secreted into the
duodenum, and also reduces gastric emptying. If the chyme has too high a content of amino acids, gastrin is released. This increases contraction of the pyloric sphincter (as well as increasing gastric motility) and overall delays gastric emptying. Hypertonic chyme is detected by duodenal osmoreceptors and gastric emptying is slowed. As the duodenum fills, stretch receptors are activated and inhibit the vagus which results in reduced gut tone and motility, temporarily reducing gastric emptying. As the duodenum empties this inhibition diminishes, the tone and motility of the gut increases, and gastric emptying is restored. The neural and hormonal mechanisms which originate from the duodenum and feedback to slow gastric emptying constitute the entero-gastric reflex.6 By regulating the rate of delivery of chyme into the duodenum, the absorption of nutrients in the small intestine is maximized. Alcohol and opioids reduce the rate of gastric empting, as do pain, fear, and anxiety (acting via the sympathetic nervous system which inhibits motility). It is now recognized that pregnancy per se does not alter gastric empting. However, during labour there is delay because of pain, anxiety, and administration of opioids. Prokinetic drugs may be used to stimulate enteral propulsion if there is no gastrointestinal obstruction, perforation, or haemorrhage. Metoclopramide is a centrally and peripherally acting dopaminergic D2 antagonist which increases the rate of gastric emptying and small intestinal transit, and also increases LOS constriction. It can be given i.v., i.m., or orally, in a dose of 10 mg 8 hourly, but is most effective i.v. Its use may be limited by adverse effects which include extra-pyramidal effects, tardive dyskinesia, and hyperprolactinaemia. Domperidone has similar pharmacological actions and is better tolerated but can only be given orally or rectally. The macrolide antibiotic erythromycin has prokinetic properties and may produce abdominal cramps, nausea, and vomiting. It is an agonist at motilin receptors, stimulating strong antral contractions.
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Practical gastric physiology
Table 4 Gastric hormones Released from
Release stimulated by
Release inhibited by
Function
Gastrin
G cells in the stomach antrum and duodenum
Vagal stimulation Distension of gastric antrum Distension of duodenum Amino acids and peptides Alcohol Caffeine
Gastric acidity Somatostatin Secretin (stimulated by duodenal acidity) Glucagon
Stimulates gastric acid production Increases secretion of pepsinogens Increases secretion of mucus Increases gastric motility Constricts pyloric sphincter Reduces gastric emptying
Secretin
S cells in the duodenum and jejunum
Increased acidity in duodenal chyme
Reduces gastric acid secretion Reduces gastric emptying Increases pancreatic secretions
CCK
I cells in the duodenum and jejunum
Increased fat in duodenal chyme
Reduces gastric acid secretion Reduces gastric emptying Contracts gall bladder
Somatostatin
D cells in the stomach
Gastric acidity
Motilin
Entero-chromaffin-like cells in proximal small intestine
Gastric contents The morbidity of acid aspiration syndrome correlates with the volume, acidity, and the particulate nature of the material introduced into the lungs. Therefore, reducing the size of the particles and the acidity of the contents of the stomach will result in less severe pulmonary damage if aspiration occurs. Parietal cell production of gastric acid is stimulated by various factors (Table 2). Inhibition of gastric acid secretion will also reduce the volume of the stomach’s contents. Anti-muscarinic agents block acetylcholine (ACh) release from vagal postganglionic fibres and reduce gastric acidity. However, they are not used in practice because they also reduce LOS tone and delay gastric emptying, thereby increasing the risk of gastro-oesophageal reflux. H2 receptor antagonists reduce gastric acid secretion and both cimetidine and ranitidine may be given i.v. Ranitidine is preferred because it has a longer duration of action and fewer drug interactions. Proton pump inhibitors (PPIs) irreversibly block the Hþ/Kþ ATPase enzyme which catalyses the exchange of intracellular Hþ for extracellular Kþ, the final step in the production of gastric acid by the parietal cells. With repeated doses PPIs are highly effective at producing achlorhydria. Omeprazole 40 mg may be given i.v. but as a single preoperative dose has no advantage over H2 receptor antagonists. Oral antacids are given to raise the pH of the stomach’s contents by neutralizing gastric acid, but they increase gastric volume. Sodium citrate 0.3 M is used as it is non-particulate so causes less pulmonary damage if aspirated. 30 ml will neutralize the gastric contents within 10 min. Using their knowledge of the relevant gastric physiology, the anaesthetist can reduce the incidence and consequences of gastric aspiration when required to administer general anaesthesia to a patient with a full stomach, gastro-oesophageal reflux, and/or obtunded airway reflexes.
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Vagal stimulation
Inhibits gastrin secretion (and thereby gastric acid production) Reduces gastric motility Reduces gastric emptying Increases gastric motility Increases gastric emptying Associated with the inter-digestive migratory motor complex (MMC)
Illustrative clinical example Suggested management of the patient with a potentially full stomach who requires a general anaesthetic Before operation: Position the patient with head-up tilt and knees flexed Insert large-bore nasogastric tube and aspirate Leave nasogastric tube on free drainage Keep ‘nil by mouth’ Give ranitidine 50 mg by slow i.v. injection Give metoclopramide 10 mg i.v. if no gastrointestinal obstruction, perforation, or haemorrhage At induction of anaesthesia: Aspirate nasogastric tube Give sodium citrate 0.3 M (30 ml) orally Check patient positioned with head-up tilt Pre-oxygenate Apply cricoid pressure Induce anaesthesia with a rapid sequence induction Intubate with a cuffed oro-tracheal tube to secure the airway Peroperatively: Maintain head-up position if possible Avoid increases in abdominal pressure Ensure adequate depth of anaesthesia After operation: Extubate in the left lateral position Extubate when awake and gag and cough reflexes are present
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 6 2009
Practical gastric physiology
References
4. Available from www.ihi.org/IHI/Topics/CriticalCare/IntensiveCare/Changes/ ImplementtheVentilatorBundle. Accessed February 20, 2009
1. Holloway RH, Penagini R, Ireland AC. Criteria for objective definition of transient lower esophageal sphincter relaxation. Am J Physiol Gastrointest Liver Physiol 1995; 268: G128– 33
5. Aitkenhead AR, Smith G, Rowbotham DJ. Textbook of Anaesthesia, 5th Edn. Elsevier, 2007: Chapter 28, p. 544
2. Petersen OH. Lecture Notes: Human Physiology, 5th Edn. Oxford: Blackwell Publishing Ltd, 2007
6. Pocock G, Richards CD. The storage, mixing, and propulsion of gastric contents. Human Physiology: The Basis of Medicine, 2nd Edn. Oxford: Oxford University Press, 2004; 437– 40
3. Torres A, Serra-Batlles J, Ros E, Piera C, Puig de la Bellacasa J, Cobos A. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992; 116: 540–3
Please see multiple choice questions 1– 3
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