Gastrointestinal Physiology and Pathophysiology

Introduction

The purpose of this chapter is to gain an understanding of the various components of gastrointestinal (GI) anatomy and their respective functions. This understanding of the GI system in the healthy state will pave the way for an understanding of how it is affected in different and common disease states. The chapter then transitions into a discussion of perioperative considerations for the anesthetist, including the effects of various anesthetic medications and surgical conditions on bowel function and physiology. The remainder of the chapter will focus on gastrointestinal innervation and how various regional anesthesia and pain management strategies are used when dealing with GI conditions and surgeries.

Gastrointestinal Anatomy and Function

The GI tract constitutes approximately 5% of the total human body mass. Its main functions are motility, digestion, absorption, excretion, and circulation. This section is composed of two parts. In the first part, the basic anatomy and innervation common to all parts of the GI tract are discussed. In the second part the specific anatomy and function of the esophagus, stomach, small bowel, and large bowel are discussed. The pancreas, liver, and biliary tract are covered in Chapter 16.

Common to all parts of the GI tract are the layers of the wall, but the functions of each layer differ from organ to organ. From outermost to innermost these layers are the serosa, longitudinal muscle layer, circular muscle layer, submucosa, and mucosa. Within the mucosa is (outermost to innermost) the muscularis mucosae, lamina propria, and epithelium. The serosa is a smooth membrane of thin connective tissue and cells that secrete serous fluid that serves to enclose the cavity and reduce friction between muscle movements. The longitudinal muscle layer contracts in order to shorten the length of the intestinal segment whereas the circular muscle layer contracts to decrease the diameter of the intestinal lumen. These two layers work together to allow for gut motility. Between these smooth muscle layers is the myenteric (Auerbach) plexus, which regulates the gut smooth muscle. The submucosa contains the submucosal (Meissner) plexus, which transmits information from the epithelium to the enteric and central nervous systems (CNS). The mucosa is composed of a thin layer of smooth muscle called the muscularis mucosa, which functions to move the villi; the lamina propria, which contains blood vessels, nerve endings, and immune and inflammatory cells; and the epithelium, which is where the GI contents are sensed and where secretion of enzymes, absorption of nutrients, and excretion of waste products occur.

The GI tract is innervated by the autonomic nervous system. This is composed of the extrinsic nervous system, which has sympathetic and parasympathetic components, and the enteric nervous system. The extrinsic sympathetic nervous system is primarily inhibitory as stimulation can decrease or cease GI motility. The preganglionic fibers originate at the T5 to L2 segments of the spinal cord. They travel to the sympathetic chain of ganglia and synapse with postganglionic neurons. Then they travel to the gut where they terminate at the enteric nervous system. The primary neurotransmitter is norepinephrine. Vasoactive intestinal polypeptide (VIP) also transmits sympathetic signals. The extrinsic parasympathetic nervous system is primarily excitatory as it activates GI motility and function. Parasympathetic preganglionic fibers originate in the medulla and sacral region of the spinal cord. Vagus nerve fibers innervate the esophagus, stomach, pancreas, small intestine, and the first half of the large intestine. Pelvic nerve fibers innervate the second half of the large intestine, sigmoid, rectal, and anal regions. The primary neurotransmitter is acetylcholine.

The enteric nervous system is the independent nervous system of the GI tract, which controls motility, secretion, and blood flow. Two plexuses constitute the enteric nervous system: the myenteric (Auerbach) plexus and the submucosal (Meissner) plexus. The myenteric plexus controls motility, which is carried out by enteric neurons, interstitial cells of Cajal (pacemaker cells that generate intrinsic electrical activity of the GI tract), and smooth muscle cells. The submucosal plexus controls absorption, secretion, and mucosal blood flow. Both of these plexuses respond to sympathetic and parasympathetic stimulation. Sympathetic stimulation is inhibitory so it will increase the tone of the intestinal wall whereas parasympathetic stimulation is excitatory and will induce intestinal contractions and movement. Additionally, there are a variety of reflexes in the enteric nervous system. For example, when there is sympathetic stimulation the tone of the wall increases, the sphincters contract, and, reflexively, the amount of excitatory acetylcholine released is reduced. The mechanism is via α-2 activation, which inhibits the release of acetylcholine and through β activation which contracts sphincter muscles and relaxes intestinal muscles. These two actions work together to slow the transit of contents through the GI tract.

This next section serves to briefly discuss the anatomy and function of the various components of the GI tract. Only the esophagus, stomach, small intestine, and large intestine are covered. See Table 15.1 for an overview of GI tract anatomy and function.

The esophagus is a muscular tube that connects the pharynx to the stomach. It is the first passageway for food entry into the digestive system. It is approximately 18 to 25 cm in length and extends from the level of the hypopharynx at the C6 vertebrae down to the gastroesophageal (GE) junction at the T11 level. The esophagus has three regions: cervical, thoracic, and abdominal. The cervical esophagus is approximately 4 to 5 cm long and is surrounded by the trachea anteriorly, the vertebral column posteriorly, and the carotid sheaths and thyroid gland laterally. The thoracic esophagus spans from the suprasternal notch to the diaphragmatic hiatus and lies posterior to the trachea. At the level of the carina, it deviates right to allow room for the aortic arch and runs posteriorly and underneath the left mainstem bronchus. From T8 to the diaphragmatic hiatus (T10) the esophagus runs anterior to the aorta. The abdominal esophagus extends from the diaphragmatic hiatus to the cardia of the stomach. The upper one-third of the esophagus is composed of striated muscle and the remaining two-thirds is smooth muscle. There are two areas of high pressure: the upper esophageal sphincter (UES) and the lower esophageal sphincter (LES). The UES lies at the level of the cricoid cartilage and is made up of the cricopharyngeal, inferior constrictor, and circular esophageal muscles. Resting tone ranges from 30–200 mm Hg. Opening and closing of the UES is coordinated with the pharyngeal pushing of food downstream. The LES is formed intrinsically by circular esophageal muscle and extrinsically by the diaphragm muscle. It has both sympathetic and parasympathetic innervation. Resting tone is 10–45 mm Hg.

The stomach is a J-shaped dilation of the alimentary tract. It is divided into four regions: the cardia, fundus, body or corpus, and antrum. The stomach has three main functions: store large quantities of food (up to 1.5–2 liters), mix food with gastric secretions to form chyme and break down particle size, and slow emptying into the small intestine. The proximal stomach is the reservoir for undigested food and produces smooth, tonic contractions. The distal stomach grinds, mixes, and sieves food particles via high-amplitude contractions. Notable cell types in the stomach that aid in digestion are the mucous cells, which protect against harsh hydrochloric acid; parietal cells, which secrete hydrochloric acid; chief cells, which secrete pepsin; and G cells, which secrete gastrin. Together these cells’ secretions break down and partially digest the food into chyme as well as reduce particle dimension to an appropriate size (2 mm or less) before it enters the small intestine.

The duodenum is the first and smallest section of the small intestine. It is between 25 and 30 cm long and it forms a C-shaped loop around the pancreas. Its main function is to chemically digest the chyme received from the stomach in preparation for absorption. The pancreas, liver, and gallbladder secrete digestive enzymes through the ampulla of Vater into the middle portion of the duodenum.

The jejunum is the second section of the small intestine and its primary function is to absorb nutrients. The digested chyme from the duodenum enters the jejunum where it is mixed and circulated for exposure to the jejunal walls for nutrient absorption. The walls of the jejunum are folded many times over to increase its surface area and allow for maximal absorption of nutrients. By the time chyme enters the ileum, almost 90% of all available nutrients are absorbed.

The ileum is the final section of the small intestine. It serves to absorb vitamin B12 and other products of digestion that were not previously absorbed in the jejunum. It ends at the ileocecal valve—a circular muscle that serves to prevent reflux of colonic contents into the small intestine. It contracts in response to colonic dilation and relaxes in response to ileal dilation.

The large intestine is composed of the cecum, appendix, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Briefly, the cecum is a pouch at the beginning of the large intestine that allows for mixing of the chyme from the small intestine with bacteria to form fecal matter. The ascending colon transports the fecal matter superiorly along the right side up to the transverse colon. Along the way the ascending colonic wall absorbs water, nutrients, and vitamins. The transverse colon, the longest portion of the large intestine, crosses the abdominal cavity. Its contractions serve to mix the feces and allow bacteria to ferment the waste. Further absorption of water and nutrients also take place. The feces then enter the descending colon, which stores the feces until it is ready for transport, inferiorly and along the left side of the abdominal cavity to the sigmoid colon. Again, the walls of the descending colon allow for further absorption of water and nutrients. The sigmoid colon is an S-shaped, curved region that stores then transports fecal matter from the descending colon to the rectum and anus for elimination. The final portion of the large intestine is the rectum where feces are stored until elimination. As fecal matter accumulates it exerts pressure on the walls of the rectum. This activates stretch receptors and leads to relaxation of the internal anal sphincter allowing for elimination.

Transit Time in Health and Disease

This section serves to discuss motility in the esophagus, stomach, small intestine, and large intestine. Emphasis is placed on mechanism, how motility and transit are altered by various disease states, and methods for evaluating motility.

Mixing movements and propulsive movements are the two primary movements within and along the GI tract. Mixing movements keep the contents of the intestine appropriately and thoroughly mixed throughout, while the propulsive movements, consisting of periodic contractions of certain GI tract segments (peristalsis), move the contents of the intestine along the tract.

Transit through the esophagus starts with swallowing. Swallowing starts with the oropharynx pushing food backward and downward while the muscles of the nasopharynx prevent food from entering the nasal passages. When ready to be swallowed the food is squeezed and rolled into the posterior pharynx by the tongue. The epiglottis moves upward in a protective mechanism over the larynx and trachea to prevent aspiration. The act of swallowing inhibits the respiratory center to protect from aspiration but it is so short-lived it is unnoticeable. Food enters the esophagus through the UES, which then constricts to prevent reflux back into the pharynx. The UES produces pressures around 30–200 mm Hg. Two waves of peristalsis move the food into the stomach through the LES, which also produces pressures between 20 and 60 mm Hg. Afferent nerve fibers transmit to the dorsal vagal complex activating efferent fibers that terminate either on the striated muscle of the esophagus or on the nerves of the enteric nervous system. Release of acetylcholine contracts the muscle while VIP and nitric oxide (NO) relax it. The LES responds to esophageal distention via myogenic and neurohormonal mechanisms.

Diseases of the esophagus are varied. Etiologies can be grouped into anatomical, mechanical, and neurologic, although many disease states involve overlap between two or all three. Anatomical etiologies include the presence of diverticula, hiatal hernia, and changes associated with chronic acid reflux. These anatomical abnormalities interrupt the normal pathway of food as it travels to the stomach which, in turn, changes many of the pressure zones of the esophagus. This can have dangerous sequelae as the luminal pressures may increase enough to overcome the resting pressures of the UES and LES allowing for reflux. Mechanical etiologies include achalasia, diffuse esophageal spasm, and hypertensive LES. There is also a neurologic component to these diseases but the result is the same—the esophagus is unable to relax properly for food travel. In achalasia the smooth muscles are unable to relax and move food down and the increased tone of the LES does not allow for complete relaxation. This results in dysphagia, regurgitation, and significant pain. In diffuse esophageal spasm the muscle contractions are uncoordinated and, as a result, food does not properly move downward. A hypertensive LES is defined as an LES with a mean pressure of 45 mm Hg or higher leading to dysphagia and chest pain. Neurologic disorders such as stroke, vagotomy, or hormone deficiencies will alter the nerve pathways such that the appropriate sensing and feedback are disrupted. A common result of neurologic disorders in the esophagus is dysphagia.

In evaluating esophageal function, it is important to select a study with an appropriate clinical correlation—is it a problem with motility or is it an anatomical abnormality? If it is a questionable motility problem, then an esophageal manometry study is best. A special catheter detects changes in pressure in the esophagus at various levels. First the pressure of the LES is recorded. The catheter is then pulled back into the esophagus and pressure measurements are made at different levels. Esophageal motor function between swallows is also evaluated. Finally the motor function of the UES is recorded and then the catheter is pulled out. Questionable anatomical problems are best studied using an upper GI series and ingested barium. These evaluate the act of swallowing and visualize the lining of the esophagus for anatomic abnormalities.

Before discussing the transit of food through the stomach and small intestine it is important to understand their actions during the fasting state. The migrating motor complex (MMC) occurs only during fasting, and is composed of waves of electrical activity in regular cycles originating in the stomach and terminating in the distal ileum. Vagal stimulation releases motilin, which triggers an MMC leading to peristaltic waves. They occur every 45 to 180 minutes and are composed of four phases. Phase I is a period of quiescence. Phase II is composed of increased action potentials and low-amplitude smooth muscle contractility. Phase III is the most active as it is the time of peak electrical and mechanical activity producing bursts of regular, high-amplitude contractions. Phase IV demonstrates declining activity and will merge into the following MMC’s phase I. The MMC is significant because it moves residual undigested food through the GI tract and also moves bacteria from the small intestine to the large intestine. Feeding interrupts it, and this is discussed next.

As described previously, the stomach is a J-shaped sac that serves as a reservoir for large volumes of food, mixes and breaks down food to form chyme, and slows emptying into the small intestine. Solids must be broken down into 1 to 2 mm particles before entering the duodenum, and they take approximately 3 to 4 hours to empty from the stomach. Liquids empty faster than solids. The motility of the stomach is controlled by intrinsic and extrinsic neural regulation. Parasympathetic stimulation to the vagus nerve increases the number and force of contractions whereas sympathetic stimulation inhibits these contractions via the splanchnic nerve. The intrinsic nervous system provides the coordination for motility. Neurohormonal control is also at play in that gastrin and motilin will increase the strength and frequency of contractions and the gastric inhibitory peptide will inhibit them.

Emptying of the stomach is controlled by neural and hormonal mechanisms as well as the composition of ingested food. Gastric distention, gastrin, and NO will promote emptying. Duodenal distention decreases the gastric tone to slow emptying, and increased fat content triggers the release of cholecystokinin to further inhibit stomach motility.

Gastric motility disorders that slow its emptying can increase the incidence of GE reflux disease. These disorders can be drug-induced, neurologic, or a result of critical illness. Drug-induced conditions include the administration of opioids (to be discussed later in the chapter), and the use of vasoactive agents. Vasoactive drugs increase catecholamine concentrations leading to sympathetic stimulation and, therefore, decreased motility. These drugs are often given intraoperatively or to critically ill patients for blood pressure control. Neurologic disorders resulting in decreased gastric motility include vagal neuropathies and gastroparesis. Finally, conditions that are commonly present in severely compromised patients, such as those with hyperglycemia, increased intracranial pressure, and mechanical ventilation can decrease gastric motility. Efforts to increase motility using drugs like erythromycin and metoclopramide have been used with some success.

The most prevailing test to evaluate gastric motility is the gastric emptying study. The patient fasts for at least 4 hours prior to the study then consumes a meal with a tightly bound radiotracer, commonly egg albumin. Continuous or frequent imaging occurs for the next 60 to 120 minutes and the measurement of time for 50% of the ingested meal to empty is determined. It is important to note that while gastric emptying scintigraphy has long been the standard study, it is affected by multiple factors including meal composition and data acquisition parameters. Gastric motility studies can also be paired with small intestinal motility studies such as the small bowel manometry test. This will be discussed later.

Small intestinal motility mixes the contents of the stomach with digestive enzymes, further reducing particle size and increasing solubility. However, the major function of the small intestine is to circulate the contents and expose them to the mucosal wall in order to maximize absorption of water, nutrients, and vitamins before entering the large intestine. Again, there are mixing contractions and propulsive contractions. The circular and longitudinal muscle layers work in a coordinated fashion to achieve segmentation. Segmentation occurs when two nearby areas contract and thereby isolate a segment of intestine. Then a contraction occurs in the middle of that isolated segment, further dividing it. Contractions in the middle of those segments continue to occur and the process ensues. Segmentation allows the contents to remain in the intestine long enough for the essential substances to be absorbed into the circulation. It is controlled mainly by the enteric nervous system with modulation of motility by the extrinsic nervous system.

When considering small bowel dysmotility it is helpful to distinguish etiologies based on reversible and nonreversible causes. For reversible causes, mechanical obstruction should be the first to come to mind. In this case, there is a physical obstruction the muscles of the intestine cannot overcome. Hernias, malignancy, adhesions, and volvuluses are all examples. Bacterial overgrowth should be another consideration. Although the large intestine is rich with bacteria, the small intestine usually has fewer than 100,000 organisms per milliliter. Disrupting this condition with bacterial overgrowth leads to alterations in absorptive function leading to diarrhea. It is treated with antibiotics. Other reversible causes include ileus, electrolyte abnormalities, and critical illness. Nonreversible causes can be classified as structural or neuropathic. In structural causes there may be abnormalities with the intestinal smooth muscle, in which it cannot produce proper contractions. This occurs in diseases such as scleroderma and connective tissue disorders. In patients with an inflammatory bowel disease (IBD), there is a structural abnormality in the mucosa leading to decreased absorption of nutrients. Short bowel syndrome can be considered a structural etiology in that a large portion of the small intestinal structure is simply not present. In patients who have had a section of their small bowel resected, the remaining portion may not provide sufficient functional compensation, resulting in diarrhea, malnutrition, and weight loss. Neuropathic etiologies can produce a pseudo-obstruction in which the intrinsic and extrinsic nervous systems are altered in such a way that the intestines can only produce weak or uncoordinated contractions. This leads to symptoms of bloating, nausea, vomiting, and abdominal pain. Regardless of etiology, small intestinal dysmotility adversely affects nutrient absorption leading to malnutrition.

The most common test used to evaluate small intestine motility is small bowel manometry. This test is useful in patients with unexplained nausea, vomiting, abdominal pain, and manifested signs of obstruction without a clear obstructive cause. Similar to esophageal manometry, this test uses a small catheter with pressure sensors to evaluate the contractions of the intestine. The study evaluates contractions during three periods: fasting, during a meal, and postprandial. Normally the recording time is four hours for fasting, followed by ingestion of a meal, and two hours postprandial. Abnormal results are grouped into myopathic and neuropathic causes. In myopathic results, the MMC is absent or phase III exhibits very low amplitudes (normal phase III amplitude is 40 mm Hg). In neuropathic results, the contraction amplitude is adequate but either the contractions are uncoordinated (enteric neuropathy) or there is an inappropriate postprandial response, meaning postprandial antral hypomotility is present (extrinsic neuropathy). This manometry test is reported to result in a change of diagnosis in 8% to 15% of patients with unexplained nausea, vomiting, and abdominal pain.

The large intestine acts as a reservoir for waste and indigestible material before elimination and extracts any remaining electrolytes and water. It plays an essential role in regulating defecation and consistency of stools. Distention of the ileum will relax the ileocecal valve to allow intestinal contents to enter the colon and subsequent cecal distention will contract it. The contractions of the colon are different from the rest of the gut. While there are still mixing and propulsive movements by the circular and longitudinal muscles, respectively, the colon also exhibits giant migrating complexes. The giant migrating complexes serve to produce mass movements across the large intestine. In the healthy state, these complexes occur approximately 6 to 10 times within 24 hours with mean amplitude of 115 mm Hg at a distance of about 1 cm/s for approximately 20 seconds each. These complexes, as well as the mixing and propulsive movements, serve to transfer contents to the rectum. The giant migrating complexes that originate in the sigmoid colon will produce the urge to defecate. Rectal distention as well as VIP and NO release will promote relaxation of the internal anal sphincter and allow for defecation.

Colonic dysmotility manifests with two primary symptoms: altered bowel habits and intermittent abdominal cramping. The most common diseases associated with colonic dysmotility are irritable bowel syndrome (IBS) and IBD, both of which are clinical diagnoses. Rome II criteria define IBS as having abdominal pain/discomfort along with at least two of the following three features: defecation relieves pain or discomfort, onset of pain is associated with an abnormal frequency of stools (more than three times per day or fewer than three times per week), and onset of pain is associated with a change in the form of the stool. In IBS with predominantly diarrheal symptoms, there is an increase in the frequency and amplitude of spontaneous giant migrating complexes, and this increase is directly proportional to the severity of symptoms. In IBS with predominantly constipation, there is a decreased amplitude and frequency of giant migrating complexes. In severe cases the giant migrating complexes may be completely absent. In addition, there is a depression of overall contractile activity in the colon leading to colonic distention and the sensation of pain. This phenomenon is exacerbated by stress in which there is significant motor dysfunction and visceral hypersensitivity as well as an increase in plasma norepinephrine stimulating the sympathetic nervous system. In IBD the mixing and propulsive movements as well as the tonic contractions are suppressed due to colonic wall compression by the inflamed mucosa, but the giant migrating complexes remain. There is an increased frequency of the giant migrating complexes and their large pressure effect further compresses the inflamed mucosa, which can lead to hemorrhage, thick mucus secretion, and significant erosions.

Methods of Evaluating Colonic Motility

Studies evaluating giant migrating complexes in patients with IBS and IBD are not routine but are performed only on patients with known diagnoses to help understand the physiology and mechanism causing them. There are, however, tests to evaluate the function and anatomy of the large intestine. The lower GI series, for example, involves the administration of a barium enema to a patient. The barium outlines the intestine and it is visible on radiograph. This allows for detection of colon and rectal anatomical abnormalities.

The Effects of General Anesthesia on Bowel Function

GI effects of the anesthetics are multifaceted and encompass a wide array of hemodynamic and physiological changes. This section is broken down into the various components that make up a general anesthetic and the GI effects of each of these components. Emphasis is placed on the effects of preoperative sedation, induction of anesthesia, hypnotic agents, volatile agents, paralysis, and reversal. Opioids will be discussed in another section. Please note that this discussion applies to the healthy state.

In the preoperative setting patients are often nervous and sympathetic stimulation is high. Inhibition of GI tract activity is directly proportional to the amount of norepinephrine secreted from sympathetic stimulation, so the higher the anxiety the higher the inhibition. Even though a good bedside manner and the use of behavioral approaches are beneficial, these may not be sufficient and patients are often given premedication with a benzodiazepine, usually midazolam, to alleviate anxiety. Midazolam acts by enhancing the effect of neurotransmitter, GABA, on GABA-A receptors. A study by Castedal and associates looked at the effect of midazolam on small bowel motility using antroduodenojejunal manometry. The vast majority of the studied variables were not affected by the use of midazolam, but one significant change was noted—an increased duration of phase III of the MMC in the proximal and distal parts of the duodenum, which shortened the MMC by 27%. A clear explanation for this is not evident but there are a couple of considerations. One, the sedative effect of midazolam may be the reason for the change in MMC activity because MMC activity differs between awake and sleep states. Another consideration is that the resultant reduced anxiety decreases sympathetic stimulation allowing for less inhibition and higher activity. However, when applied clinically, there was no real difference seen in small intestinal motility patterns. Of the premedications, midazolam is widely used and considered well tolerated.

General anesthesia causes a loss of all protective reflexes. This is achieved with a variety of medications including opioids, hypnotics, and neuromuscular blocking agents. As mentioned, the effect of opioids will be discussed in a later section. Volatile anesthetics affect bowel function through various mechanisms including depression of spontaneous activity and changes in intestinal tissue oxygenation. Volatile anesthetics depress the spontaneous, electrical, contractile, and propulsive activity in the stomach, small intestine, and colon as demonstrated in many animal and human studies. The small intestine is the first part of the GI tract to recover, followed by the stomach in approximately 24 hours and then the colon 30 to 40 hours postoperatively. Between the various volatile anesthetics there are minor differences. One difference worth noting is that rapid increases in the concentration of desflurane induces greater sympathetic activation, as compared to other volatile agents, which coupled with sympathetic nervous system hyperactivity during surgical procedures can inhibit GI function and motility. In a study comparing desflurane and isoflurane, rapid increases in desflurane caused significantly greater effects on sympathetic and renin-angiotensin system activity as well as increases in blood pressure and heart rate as compared to isoflurane. However, this effect is short-lived as it is only seen with rapid increases in concentration and the surge in sympathetic stimulation tapers off quickly. This transient phenomenon is unlikely to have a lasting effect on bowel function. The volatile anesthetics also affect splanchnic circulation and oxygenation in a dose-dependent manner, which is known to have an effect on bowel function. In horses receiving isoflurane for maintenance of anesthesia, microperfusion and intestinal tissue oxygenation decreased when isoflurane reached 2%. In a human study by Muller and associates, the effects of desflurane and isoflurane on intestinal tissue oxygenation during colorectal surgery were evaluated. It was found that desflurane and isoflurane had comparable effects on intestinal tissue oxygenation. However, during periods of ischemia for resection and anastomosis, reactive hyperemia was better preserved in the patients given isoflurane. This may have important implications in regaining coordinated and appropriate bowel function postoperatively and may determine maintenance with volatile versus total intravenous anesthesia. Whereas the volatile anesthetics depress spontaneous activity and affect blood flow, there is no clear-cut relationship between adverse GI effects and the use of volatile anesthetics. Also, when considering their use in clinical practice, there is very little difference between desflurane, isoflurane, and sevoflurane’s effects on bowel function.

An alternative to maintenance with volatile anesthetics is total intravenous anesthesia. Propofol is the most common drug used for this purpose. When used intraoperatively, propofol-remifentanil anesthetic produced increased intestinal motility as compared to sevoflurane-remifentanil. No adverse GI effects were reported, but it did cause a higher degree of surgeon dissatisfaction. A study by Jensen and colleagues looked at bowel recovery after open procedures and did not find a difference in overall recovery and bowel function when comparing isoflurane/nitrous oxide, propofol/air, and propofol/nitrous oxide. Even in colorectal cancer patients there was no difference in inflammatory response among patients receiving either total intravenous anesthesia with propofol and remifentanil or inhalational anesthesia with sevoflurane and fentanyl. There are few data on the effect of propofol on GI smooth muscle and many of the established studies show various and conflicting results when it comes to the recovery of bowel functions.

Nitrous oxide is 30 times more soluble than nitrogen in the blood and as such will diffuse into gas-containing cavities from the blood faster than the nitrogen already present in those cavities can diffuse out. This is especially important in the bowels as gut distention is correlated with the amount of gas already present in the bowel, the duration of nitrous oxide administration, and the concentration of nitrous oxide administered. Although it has been established that nitrous oxide causes bowel distention and it is prudent to avoid nitrous oxide in lengthy abdominal surgeries or when the bowel is already distended, the most recent ENIGMA trial did not relate the use of nitrous oxide to any significant adverse outcomes.

Paralysis to achieve favorable surgical conditions is produced by administration of neuromuscular blocking agents. Neuromuscular blocking drugs only affect skeletal muscle so GI motility remains intact. However, special mention of the depolarizing neuromuscular blocker succinylcholine should be made. Succinylcholine mimics acetylcholine in that it produces an initial muscle contraction, which is visible as fasciculations. This contraction increases intragastric pressure, which may be so strong as to overcome the tone of the LES and allow reflux of gastric contents. Aspiration is certainly a concern, but this should not necessarily preclude the use of succinylcholine. Patient condition, including body habitus, technical difficulty of intubation, nothing by mouth (NPO) status, and comorbidities should be the determining factors in assessing the risk of aspiration.

Reversal of paralysis using the anticholinesterase, neostigmine, will increase parasympathetic activity and bowel peristalsis by increasing the frequency and intensity of contractions. In cases of fresh bowel anastomoses, this can be of concern as the increase in activity could result in dehiscence. This is partially offset by simultaneous administration of the anticholinergic medications, glycopyrrolate or atropine, which are used to attenuate the bradycardia from neostigmine. This effect is not seen with sugammadex, which may be a more prudent choice for reversal in situations of tenuous bowel anastomoses. There is some data to support the use of neostigmine in treating postoperative ileus but the adverse effects of bradycardia, vomiting, and abdominal cramps may preclude its use.

Surgical procedures on the GI tract produce an exaggerated stress response that may predispose to postoperative bowel dysfunction. Goals of anesthetic care should be to attenuate the stress response, optimize hemodynamic and fluid status, and maintain normothermia. At present there is no evidence for recommendations on specific anesthetic and analgesic agents to avoid adverse GI effects.

Effect of Opioids on Bowel Function

Much attention has been given to the use and effects (beneficial and adverse) of opioid administration. There is a desire to only use adjunct techniques and nonopioid medications; however, opioids are often necessary to control perioperative pain. A major adverse effect, and one that is not associated with the development of opioid tolerance, is reduced GI motility and constipation. Opioids exert their function on both central and peripheral receptors, namely mu, delta, and kappa. It is the central effects that primarily mediate analgesia and produce the favorable effects. The peripheral effects are the adverse effects. There is a high density of peripheral mu-opioid receptors in the myenteric and submucosal plexuses. Activation of these mu-opioid receptors in the myenteric plexus has a dual effect on the neural pathways controlling motility—it inhibits excitatory pathways that depress peristaltic contraction and it also inhibits inhibitory pathways. These inhibitions increase GI muscular activity and increase resting muscle tone including tone in the ileocecal valve and internal anal sphincters. This produces spasm and nonrhythmic or propulsive motility. Activation of these receptors is also linked to the inhibition of acetylcholine release and promotion of nitrous oxide release that inhibits propulsive motility. Together these effects will delay gastric emptying and slow transit through the intestine. Activation of these receptors in the submucosal plexus decreases nutrient secretion and increases fluid absorption. Coupled with reduced motility the stool will remain in the gut for a longer period of time and as more water is absorbed the stool becomes hard and dry leading to constipation. Other adverse sequelae include nausea, anorexia, delayed digestion, abdominal pain, excessive straining during bowel movements, and incomplete evacuation.

Many efforts have been made and are currently underway to attenuate or avoid opioid-induced bowel dysfunction. The use of laxatives, stool softeners, and prokinetic agents, such as metoclopramide and neostigmine, have shown some success in alleviating opioid-induced constipation. Potentially switching to a different opioid is also offered as a treatment option. Tassinari and associates performed a meta-analysis demonstrating strong evidence supporting opioid switch in alleviating constipation, most strongly for morphine to transdermal fentanyl. Another option is combining opioids with enteral opioid receptor antagonists. Naloxone was the first used. It is a nonselective, competitive opioid receptor antagonist. While its effect on the peripheral receptors in the gut produced favorable results of reversing gut motility inhibition, its nonselective profile meant it also worked on the central receptors and reversed the beneficial analgesic effect of opioids. Therefore, new attention is given to pure peripherally acting opioid receptor antagonists. Methylnaltrexone is a peripheral mu-opioid receptor antagonist and does not cross the blood-brain barrier. In healthy volunteers, the use of methylnaltrexone prevented delay in orocecal transit time after morphine administration. Subsequent systematic reviews demonstrated that methylnaltrexone and alvimopan were better than placebo in reversing opioid-induced increased GI transit time and constipation. However, long-term efficacy and safety have not been clearly established. Further studies are underway.

Effect of Open Abdominal Surgery, Ischemia, Stomas, and Bowel Anastomosis on Gastrointestinal Physiology and Function

The surgical procedure itself, even with purposes of correcting GI pathology, significantly affects GI physiology and function and predisposes to postoperative ileus. Recently, a standardized definition of postoperative ileus was established as “a transient cessation of coordinated bowel motility after surgical intervention, which prevents effective transit of intestinal contents and/or tolerance of oral intake.” Manipulation of the intestines is the main factor that initiates postoperative ileus. Additional contributors include immobility, electrolyte imbalance from fluid shifts and insensible losses, and intestinal wall swelling from excessive fluid administration. In open abdominal procedures, the surgical manipulation of the bowel induces a degree of trauma that sets in motion the whole process of postoperative ileus. There are two phases to uncomplicated postoperative ileus (i.e., in the absence of complications, such as perforation, bleeding, peritonitis). The first phase is an early neurogenic phase and the second is an inflammatory phase. In total, an uncomplicated postoperative ileus lasts about 3 to 4 days.

The early neurogenic phase results when the intestine is manipulated, which is more extensive in open procedures than laparoscopic ones. This manipulation activates the sympathetic nervous system, increasing the inhibitory neural input that leads to decreased propulsive movements and almost complete cessation of GI motility. This lasts about 3 to 4 hours after surgery.

The late inflammatory phase also begins with surgical manipulation of the intestines. Surgical manipulation increases sympathetic stimulation of the myenteric plexus, which promotes the influx of leukocytes into the “traumatized” areas of the gut. Further release of cytokines, chemokines, and leukocytes as well as phagocytosis in the traumatized area occurs and eventually spreads through the entire GI tract. This inflammatory cascade increases permeability and allows for translocation of intraluminal bacteria, which further exacerbates the inflammatory process. However, peritonitis does not always develop because the mast cells and neutrophils are very effective in eliminating the translocated bacteria in the peritoneal cavity. This process occurs about 3 hours after intestinal manipulation and continues throughout the manipulated segment and the rest of the GI tract for the next 24 hours. It eventually subsides and within 3 to 4 days this uncomplicated ileus is usually resolved.

Mesenteric ischemia, if left untreated, will lead to 100% mortality. This occurs when the supply of oxygen is insufficient to meet the oxygen demand of the intestines. It affects the small and large intestine and is classified as occlusive or nonocclusive. Etiologies of mesenteric ischemia include: strangulation, emboli (seen commonly in patients with atrial fibrillation), complications of aortic surgery or during cross-clamping, trauma, drug-induced, atherosclerosis, and inflammatory diseases. There are four stages of mesenteric ischemia. The first is the hyperactive stage when blood flow to the intestine is abruptly occluded. This produces severe pain and overactive peristalsis. There may be passage of loose stool with blood. The second stage is a paralytic stage that spreads diffusely across the intestines. The third stage involves leakage of fluid, proteins, and electrolytes through the bowel wall into the peritoneum. If the bowel becomes necrotic then peritonitis develops. The fourth stage is shock. End-organ damage is apparent and contributes to altered hemodynamics and critical illness. Treatment involves reperfusion of the occluded vessel through revascularization and possibly bowel resection.

Bowel resections vary in terms of their effect on the remaining bowel. The degree of GI dysfunction depends on the portion of bowel resected. The colon primarily absorbs water and a full colonic resection is compatible with life. However, when the small intestine is resected the effect on the GI system is much more pronounced. The small intestine is responsible for absorbing vitamins and nutrients. This can be properly maintained if at least a third of the small bowel remains. The jejunum is the primary site for digestion and absorption of nutrients. After a jejunal resection, the ileum is usually able to adapt to fulfill its functions. The ileum absorbs vitamin B12 and bile salts. If the ileum is resected (especially more than 100 cm), the remaining small intestine cannot compensate for the loss of its function and severe malabsorption and diarrhea will result. The unabsorbed bile salts enter the colon and stimulate fat and water secretion. Small intestinal resection will increase gastric motility but this depends on the site and amount resected. If the terminal ileum and ileocecal valve are resected then intestinal content transit speeds up.

Bowel anastomoses can significantly alter bowel function in that they disrupt normal motor activity. Partial transection usually preserves the wave of activity, though complete transection will interrupt it. There is a loss in myogenic continuity in that the intestine distal to the transection will no longer receive signals or respond to the pacemaker in the proximal duodenum. Now the part distal to transection has to rely on its own intrinsic slow-wave transmission. This can be attenuated by close approximation of the muscle layers. There is motor asynchrony across the anastomotic site but long-term studies report reasonable MMC activity is ultimately achieved with time. The mechanism explaining why this recovery occurs remains uncertain. The transection and anastomosis have little effect on intestinal homeostasis and are not associated with significant digestion or absorption side effects.

Gastrointestinal System Nociception

Abdominal visceral pain and its associated symptoms are common in the GI perioperative period. For an understanding of GI nociception, a detailed knowledge of the anatomy and physiology of abdominal visceral innervation is essential.

Abdominal Viscera Innervation

Abdominal visceral pain signals are carried in both sympathetic and parasympathetic autonomic fibers. Innervation of the parietal peritoneum, abdominal wall muscles, and skin is supplied by the ventral rami of thoracoabdominal nerves, which are part of the somatosensory system.

Sympathetic fibers for the upper abdomen, including the liver, stomach, pancreas, small bowel, and proximal part of the colon, originate from spinal cord segments T5 to L2. Those preganglionic fibers exit the cord as gray rami communicants to enter the sympathetic chain in the paravertebral region. These fibers terminate in the prevertebral (subdiaphragmatic) ganglia through splanchnic nerves and generate the celiac plexus, where they synapse with a large number of postganglionic, predominantly unmyelinated fibers. Postganglionic fibers will then innervate the organs (see Fig. 15.5 ). Innervation of the lower abdomen including the descending colon, sigmoid and rectum, bladder, and lower ureter originates from T9 to L3 and forms the inferior mesenteric and hypogastric ganglia and plexus.

Sympathetic afferent fibers transmit visceral pain, whereas sympathetic efferent nerves inhibit peristalsis and gastric distention as well as cause GI vasoconstriction.

The parasympathetic nervous system supplies the abdominal viscera proximal to the splenic flexure of the colon via the vagus nerve. Some of the vagal fibers pass through the prevertebral fibers (celiac plexus). The parasympathetic postganglionic neurons are located in the myenteric and submucosal plexuses. Visceral afferent parasympathetic nerve fibers transmit the sensations of satiety, nausea, and distention, whereas efferent parasympathetic nerve fibers increase functions such as secretion, sphincter relaxation, and peristalsis.

The colon, rectum, internal and external genitalia, and bladder are innervated by fibers from spinal cord segments S2 to S4, which run with the pelvic nerves ( Fig. 15.1 ).

Some of the characteristics of abdominal visceral innervation are: (1) they are almost exclusively myelinated A-delta and unmyelinated C fibers; (2) they have “dual-function” properties (sensory that carry sensory evoked potentials and afferent that regulate autonomic flow); (3) there are an abundance of connections between nerves, ganglia, and plexuses; (4) there is not a fine and distinct nerve; (5) considerable variation in anatomy can be found; (6) visceral innervation anatomy is affected by intraabdominal pathology; and (7) visceral innervation distribution is diffuse and capable of amplification. Once stimulated, it could be difficult to stop (self-aggravation).

In summary, the innervation of the GI organs up to the proximal transverse colon is supplied by the celiac plexus, and innervation of the descending colon and distal GI tract comes from the inferior hypogastric plexus. Although each organ looks like it is innervated from specific cord segments, the fibers frequently communicate with each other ( Table 15.2 ).

Table 15.2

Summary of Visceral Innervation on Gastrointestinal Tract

Organ	Sympathetic Sensory Supply	Parasympathetic Sensory Supply
Liver and biliary tract	T5-T10 via Celiac plexus	Vagus nerve
Stomach	T7-T9 via Celiac plexus	Vagus nerve
Pancreas	T6-T10 via Celiac plexus	Vagus nerve
Small bowel	T9-L1 via Celiac plexus	Vagus nerve
Cecum, ascending and transverse colon	T9-L1 via Celiac plexus	Vagus nerve
Descending colon	T9-T12 via Celiac plexus	S2-S4 via Pelvic nerves
Sigmoid, rectum	T11-L1 via Inferior hypogastric plexus	S2-S4 via Pelvic nerves

Celiac Plexus Anatomy

The celiac plexus is normally composed of two or three splanchnic nerves:

The greater (superior thoracic) splanchnic nerve comes from T5 to T9 (fibers can arise as high as T1 and as low as T11). The greater splanchnic nerve is usually anterolateral to the T12 vertebral body. It perforates the crura of the diaphragm and enters the retroperitoneal space where it joins the celiac plexus.

The lesser splanchnic nerve is formed from T9 to T11. In 30% of cases this nerve is not present. Two or more celiac ganglia are generated, which lie ventrolaterally to the aorta between the origin of the celiac arterial trunk and the renal arteries.

The celiac ganglia can vary considerably in size and number on each side. Usually they are oval shaped and can vary from 0.5 to 4.5 cm in width.

Fusion of these ganglia form a fine nerve plexus that may extend to the inferior border of the T12 vertebra and lower border of L2. They are mostly located close to the celiac artery trunk.

The plexus and related nervous structures are contained in the prevertebral retroperitoneal space along with the aorta, inferior vena cava (IVC), veins of azygos system, lymph nodes, the cisterna chyli, and diaphragmatic crura ( Fig. 15.2 ).