Liver
The liver lies in the right upper quadrant of the abdominal cavity and is attached to the diaphragm. It is the largest organ in the body, weighing approximately 1,500 g and representing 2% of body weight. In the neonate, the liver accounts for approximately 5% of body weight. Hepatocytes represent approximately 80% of the cytoplasmic mass within the liver. These cells perform diverse and complex functions (Table 32-1). The ability of hemopoietic stem cells to differentiate into hepatocytes introduces the possibility of treating inherited disorders of metabolism (reflecting absent to altered enzymes due to a single or multiple genetic defect) in the future.1,2
Anatomy
The liver is divided into four lobes consisting of 50,000 to 100,000 individual hepatic lobules (Fig. 32-1). Blood flows past hepatocytes via sinusoids from branches of the portal vein and hepatic artery to a central vein. There is usually only one layer of hepatocytes between sinusoids so the total area of contact with plasma is great. Central veins join to form hepatic veins, which drain into the inferior vena cava. Each hepatocyte is also located adjacent to bile canaliculi, which coalesce to form the common hepatic duct. This duct and the cystic duct from the gallbladder join to form the common bile duct, which enters the duodenum at a site surrounded by the sphincter of Oddi (Fig. 32-2).3 The main pancreatic duct also unites with the common bile duct just before it enters the duodenum.
Hepatic lobules are lined by macrophages (derived from circulating monocytes) known as Kupffer cells, which phagocytize 99% or more of bacteria in the portal venous blood. This is crucial because the portal venous blood drains the gastrointestinal tract and usually contains colon bacteria.
Endothelial cells that line the hepatic lobules contain large pores, permitting easy diffusion of certain substances, including plasma proteins, into extravascular spaces of the liver that connect with terminal lymphatics. The extreme permeability of the lining of endothelial cells allows large quantities of lymph to form, which contain protein concentrations that are only slightly less than the protein concentration of plasma. Indeed, approximately one-third to one-half of all the lymph is formed in the liver.
Hepatic Blood Flow
The liver receives a dual afferent blood supply from the hepatic artery and portal veins (Fig. 32-3). Total hepatic blood flow is approximately 1,450 mL per minute or approximately 29% of the cardiac output. Of this amount, the portal vein provides 75% of the total flow but only 50% to 55% of the hepatic oxygen supply because this blood is partially deoxygenated in the preportal organs and tissues (gastrointestinal tract, spleen, pancreas). The hepatic artery provides only 25% of total hepatic blood flow but provides 45% to 50% of the hepatic oxygen requirements. Hepatic artery blood flow maintains nutrition of connective tissues and walls of bile ducts. For this reason, loss of hepatic artery blood flow can be fatal because of ensuing necrosis of vital liver structures. An increase in hepatic oxygen requirements is met by an increase in oxygen extraction rather than a further increase in the already high hepatic blood flow.
Control of Hepatic Blood Flow
Portal vein blood flow is controlled primarily by the arterioles in the preportal splanchnic organs. This flow, combined with the resistance to portal vein blood flow within the liver, determines portal venous pressure (normally 7 to 10 mm Hg) (see the section “Portal Venous Pressure”). Sympathetic nervous system innervation is from T3 to T11 and is mediated via α-adrenergic receptors. This innervation is principally responsible for resistance and compliance of hepatic venules. Changes in hepatic venous compliance play an essential role in overall regulation of cardiac output and the reservoir function of the liver (see the section “Reservoir Function”).
Fibrotic constriction characteristic of hepatic cirrhosis (most often due to chronic alcohol abuse and hepatitis C) can increase resistance to portal vein blood flow, as evidenced by portal venous pressures of 20 to 30 mm Hg (portal hypertension). The resulting increased resistance to portal vein blood flow may result in development of shunts (varices) to allow blood flow to bypass the hepatocytes. Conversely, congestive heart failure and positive pressure ventilation of the lungs impair outflow of blood from the liver because of increased central venous pressure, which is transmitted to hepatic veins. Ascites results when increased portal venous pressures cause transudation of protein-rich fluid through the outer surface of the liver capsule and gastrointestinal tract into the abdominal cavity. Hepatic artery blood flow is influenced by arteriolar tone that reflects local and intrinsic mechanisms (autoregulation). For example, a decrease in portal vein blood flow is accompanied by an increase in hepatic artery blood flow by as much as 100%. Presumably, a vasodilating substance such as adenosine accumulates in the liver when portal vein blood flow decreases, leading to subsequent hepatic arterial vasodilation and washout of the vasodilating material.
Halothane decreases hepatic oxygen supply more than isoflurane, enflurane, desflurane, or sevoflurane when administered in equal potent doses.4 In contrast to the other volatile anesthetics, halothane preserves autoregulation of hepatic blood flow only to a limited extent and only when used in doses that do not decrease systemic blood pressure >20%. Surgical stimulation may further decrease hepatic blood flow, independent of the anesthetic drug administered. The greatest decreases in hepatic blood flow occur during intraabdominal operations, presumably due to mechanical interference of blood flow produced by retraction in the operative area, as well as the release of vasoconstricting substances such as catecholamines.
Reservoir Function
The liver normally contains approximately 500 mL of blood or approximately 10% of the total blood volume. An increase in central venous pressure causes back pressure, and the liver, being a distendible organ, may accommodate as much as 1 L of extra blood. As such, the liver acts as a storage site when blood volume is excessive, as in congestive heart failure, and is capable of supplying extra blood when hypovolemia occurs. Indeed, the large hepatic veins and sinuses are constricted by stimulation from the sympathetic nervous system, discharging up to 350 mL of blood into the circulation. Therefore, the liver is the single most important source of additional blood during strenuous exercise or acute hemorrhage.
Bile Secretion
Hepatocytes continually form bile (500 mL daily) and then secrete it into bile canaliculi, which empty into progressively larger ducts, ultimately reaching the common bile duct (see Fig. 32-2).3 Between meals, the tone of the sphincter of Oddi, which guards the entrance of the common bile duct into the duodenum, is high. As a result, bile flow is diverted into the gallbladder, which has a capacity of 35 to 50 mL. The most potent stimulus for emptying the gallbladder is the presence of fat in the duodenum, which evokes the release of the hormone cholecystokinin by the duodenal mucosa. This hormone enters the circulation and passes to the gallbladder, where it causes selective contraction of the gallbladder smooth muscle. As a result, bile is forced from the gallbladder into the duodenum. When adequate amounts of fat are present, the gallbladder empties in approximately 1 hour.
The principal components of bile are bile salts, bilirubin, and cholesterol.
Bile Salts
Bile salts combine with lipids in the duodenum to form water-soluble complexes (micelles) that facilitate gastrointestinal absorption of fats (triglycerides) and fat-soluble vitamins. Once absorbed, bile salts return to the liver via the portal vein, where they enter hepatocytes (enterohepatic circulation). In the absence of bile secretion, steatorrhea and a deficiency of vitamin K develop in a few days. Vitamin K is necessary for activation of several of the clotting factors that contain glutamic acid residues.
Bilirubin
After approximately 120 days, the cell membranes of erythrocytes rupture, and the released hemoglobin is converted to bilirubin in reticuloendothelial cells (Fig. 32-4).5 The resulting bilirubin is released into the circulation and transported in combination with albumin to the liver. In hepatocytes, bilirubin dissociates from albumin and conjugates principally with glucuronic acid. Unlike conjugated bilirubin, unconjugated bilirubin may be neurotoxic and may even cause a rapidly fatal encephalopathy. In the gastrointestinal tract, bilirubin is converted by bacterial action mainly into urobilinogen.
Jaundice
Jaundice is the yellowish tint of body tissues that accompanies accumulation of bilirubin in extracellular fluid. Skin color usually begins to change when the plasma concentration of bilirubin increases to approximately three times normal. The most common types of jaundice are hemolytic jaundice, due to increased destruction of erythrocytes, and obstructive jaundice, due to obstruction of bile ducts.
Cholesterol
Cholesterol is an important component of cell walls (synthesized in tissues from acetate in a reaction catalyzed by β-hydroxy β-methylglutaryl coenzyme A) and is transported from the periphery to the liver as high-density lipoproteins (HDL). Once cholesterol has reached the liver, it can be excreted in the bile in association with bile acids. Cholesterol in the bile may precipitate as gallstones if there is excess absorption of water in the gallbladder or the diet contains too much cholesterol. Gallstones occur in 10% to 20% of individuals; 85% are cholesterol stones.
Metabolic Functions
Metabolism of carbohydrates, lipids, and proteins depends on normal hepatic function (see Chapter 33). Furthermore, the liver is an important storage site for vitamins and iron. Degradation of certain hormones (catecholamines and corticosteroids), as well as drugs, is an important function of the liver. Hepatocytes are the principal site for synthesis of all the coagulation factors, with the exception of von Willebrand factor and factor VIIIC. Because the half-life of clotting factors produced in the liver is short, coagulation is particularly sensitive to acute hepatocellular damage.
Carbohydrates
Regulation of blood glucose concentration is an important metabolic function of the liver. When hyperglycemia is present, glycogen is deposited in the liver, and when hypoglycemia occurs, glycogenolysis provides glucose. Amino acids can be converted to glucose by gluconeogenesis when the blood glucose concentration is decreased.
Lipids
The liver is responsible for β-oxidation of fatty acids and formation of acetoacetic acid. Triglycerides are formed from the esterification of glycerol with three molecules of fatty acid. Pancreatic lipases and esterases are important in facilitating the absorption of dietary fats. After absorption, fat may be stored as triglycerides (reserve energy) or metabolized to energy. Lipoproteins, cholesterol, and phospholipids, such as lecithin, are formed in the liver. Synthesis of fats from carbohydrates and proteins also occurs in the liver.
Proteins
The most important liver functions in protein metabolism are oxidative deamination of amino acids, formation of urea for removal of ammonia, formation of plasma proteins and coagulation factors, and interconversions (transfer of one amino group to another amino acid) among different amino acids. Albumin formed in the liver is critically important for maintaining plasma oncotic pressure as well as providing an essential transport role. The half-life for albumin is about 21 days; therefore, plasma albumin concentrations are unlikely to be significantly altered in acute hepatic failure. Deamination of amino acids is required before these substances can be used for energy or converted into carbohydrates or fats. Decreases in portal vein blood flow, as may occur with the surgical creation of a portocaval shunt to treat esophageal varices, can result in fatal hepatic coma because of accumulation of ammonia.
Gastrointestinal Tract
The primary function of the gastrointestinal tract is to provide the body with a continual supply of water, electrolytes, and nutrients. To achieve this goal, the contents of the gastrointestinal tract must move through the entire system at an appropriate rate for digestive and absorptive functions to occur. Each part of the gastrointestinal tract is adapted for specific functions such as (a) passage of food in the esophagus, (b) storage of food in the stomach or fecal matter in the colon, (c) digestion of food in the stomach and small intestine, and (d) absorption of the digestive end products and fluids in the small intestine and proximal parts of the colon. Overall, approximately 9 L of fluid and secretions enters the gastrointestinal tract daily, and all but approximately 100 mL is absorbed by the small intestine and colon (Fig. 32-5).6 The pH of gastrointestinal secretions varies widely (Table 32-2).
Anatomy
The smooth muscle of the gastrointestinal tract is a syncytium such that electrical signals originating in one smooth muscle fiber are easily propagated from fiber to fiber. Mechanical activity of the gastrointestinal tract is enhanced by stretch and parasympathetic nervous system stimulation, whereas sympathetic nervous system stimulation decreases mechanical activity to almost zero.
Tonic contraction of gastrointestinal smooth muscle at the pylorus, ileocecal valve, and anal sphincter helps regulate the rate at which materials move through the gastrointestinal tract. In these parts of the gastrointestinal tract, rhythmic movements (peristalsis) occur 3 to 12 times per minute to facilitate mixing and movement of food.
Blood Flow
Most of the blood flow to the gastrointestinal tract is to the mucosa to supply energy needed for producing intestinal secretions and absorbing digested materials. Blood flow parallels digestive activity of the gastrointestinal tract. Approximately 80% of portal vein blood flow originates from the stomach and gastrointestinal tract, with the remainder coming from the spleen and pancreas.
Stimulation of the parasympathetic nervous system increases local blood flow at the same time it increases glandular secretions. Conversely, stimulation of the sympathetic nervous system causes vasoconstriction of the arterial supply to the gastrointestinal tract. The decrease in blood flow, however, is transient because local metabolic vasodilator mechanisms elicited by ischemia return blood flow toward normal. The importance of this transient sympathetic nervous system–induced vasoconstriction is that it permits shunting of blood from the gastrointestinal tract for brief periods during exercise, or when increased blood flow is needed by skeletal muscles or the heart.
Portal Venous Pressure
The liver offers modest resistance to blood flow from the portal venous system. As a result, the pressure in the portal vein averages 7 to 10 mm Hg, which is considerably higher than the almost zero pressure in the inferior vena cava. Cirrhosis of the liver, most frequently caused by alcoholism, is characterized by increased resistance to portal vein blood flow due to replacement of hepatic cells with fibrous tissue that contracts around the blood vessels. The gradual increase in resistance to portal vein blood flow produced by cirrhosis of the liver causes large collateral vessels to develop between the portal veins and the systemic veins. The most important of these collaterals are from the splenic veins to the esophageal veins. These collaterals may become so large that they protrude into the lumen of the esophagus, producing esophageal varicosities. The esophageal mucosa overlying these varicosities may become eroded, leading to life-threatening hemorrhage.
In the absence of the development of adequate collaterals, sustained increases in portal vein pressure may cause protein-containing fluid to escape from the surface of the mesentery, gastrointestinal tract, and liver into the peritoneal cavity. This fluid, known as ascites, is similar to plasma, and its high protein content causes an increased colloid osmotic pressure in the abdominal fluid. This high colloid osmotic pressure draws additional fluid from the surfaces of the gastrointestinal tract and mesentery into the peritoneal cavity.
Splenic Circulation
The splenic capsule in humans, in contrast to that in many lower animals, is nonmuscular, which limits the ability of the spleen to release stored blood in response to sympathetic nervous system stimulation. A small amount (150 to 200 mL) of blood is stored in the splenic venous sinuses and can be released by sympathetic nervous system–induced vasoconstriction of the splenic vessels. Release of this amount of blood into the systemic circulation is sufficient to increase the hematocrit 1% to 2%.
The spleen functions to remove erythrocytes from the circulation. This occurs when erythrocytes reenter the venous sinuses from the splenic pulp by passing through pores that may be smaller than the erythrocyte. Fragile cells do not withstand this trauma, and the released hemoglobin that results from their rupture is ingested by the reticuloendothelial cells of the spleen. These same reticuloendothelial cells also function, much like lymph nodes, to remove bacteria and parasites from the circulation. Indeed, asplenic patients are more prone to developing bacterial infections.
During fetal life, the splenic pulp produces erythrocytes in the same manner as does the bone marrow in the adult. As the fetus reaches maturity, however, this function of the spleen is lost.
Innervation
The gastrointestinal tract receives innervation from both divisions of the autonomic nervous system as well as from an intrinsic nervous system consisting of the myenteric plexus, or Auerbach plexus, and the submucous plexus, or Meissner plexus. In the absence of sympathetic nervous system or parasympathetic nervous system innervation, the motor and secretory activities of the gastrointestinal tract continue, reflecting the function of the intrinsic nervous system. Signals from the autonomic nervous system influence the activity of the intrinsic nervous system. For example, impulses from the parasympathetic nervous system increase intrinsic activity, whereas signals from the sympathetic nervous system decrease intrinsic activity. A large number of neuromodulatory substances act in the gastrointestinal tract.
The cranial component of parasympathetic nervous system innervation to the gastrointestinal tract (esophagus, stomach, pancreas, small intestine, colon to the level of the transverse colon) is by way of the vagus nerves. The distal portion of the colon is richly supplied by the sacral parasympathetics via the pelvic nerves from the hypogastric plexus. Fibers of the sympathetic nervous system destined for the gastrointestinal tract pass through ganglia such as the celiac ganglia.
Motility
The two types of gastrointestinal motility are mixing contractions and propulsive movements characterized as peristalsis. The usual stimulus for peristalsis is distension. Peristalsis occurs only weakly in portions of the gastrointestinal tract that have congenital absence of the myenteric plexus. Peristalsis is also decreased by increased parasympathetic nervous system activity and anticholinergic drugs.
Ileus
Trauma to the intestine or irritation of the peritoneum as follows abdominal operations causes adynamic (paralytic) ileus. Peristalsis returns to the small intestine in 6 to 8 hours, but colonic activity may take 2 to 3 days. Adynamic ileus can be relieved by a tube placed into the small intestine and aspiration of fluid and gas until the time when peristalsis returns.
Salivary Glands
The principal salivary glands (parotid and submaxillary) produce 0.5 to 1.0 mL per minute of saliva (pH 6 to 7), largely in response to parasympathetic nervous system stimulation. Saliva washes away pathogenic bacteria in the oral cavity as well as food particles that provide nutrition for bacteria. In the absence of saliva, oral tissues are likely to become ulcerated and infected. The bicarbonate ion concentration in saliva is two to four times that in plasma, and the high potassium content of saliva can result in hypokalemia and skeletal muscle weakness if excess salivation persists.
Esophagus
The esophagus serves as a conduit for passage of food from the pharynx to the stomach. The swallowing or deglutition center located in the medulla and lower pons inhibits the medullary ventilatory center, halting breathing at any point to allow swallowing to proceed. The upper and lower ends of the esophagus function as sphincters to prevent entry of air and acidic gastric contents, respectively, into the esophagus. The sphincters are known as the upper esophageal (pharyngoesophageal) sphincter and lower esophageal (gastroesophageal) sphincter.
Lower Esophageal Sphincter
The lower esophageal sphincter regulates the flow of food between the esophagus and the stomach. The sphincter mechanism at the lower end of the esophagus consists of the intrinsic smooth muscle of the distal esophagus and the skeletal muscle of the crural diaphragm.7 Under normal circumstances, the lower esophageal sphincter is approximately 4 cm long. The crural diaphragm, which forms the esophageal hiatus, encircles the proximal 2 cm of the sphincter. The intraluminal pressure of the esophagogastric junction is a measure of the strength of the antireflux barrier and is typically quantified with reference to the intragastric pressure (normal <7 mm Hg). Both the lower esophageal sphincter and the crural diaphragm contribute to the intragastric pressure. Muscle tone in the lower esophageal sphincter is the result of neurogenic and myogenic mechanisms. A substantial part of the neurogenic tone in humans is due to cholinergic innervation via the vagus nerves. The presynaptic neurotransmitter is acetylcholine, and the postsynaptic neurotransmitter is nitric oxide.
The normal lower esophageal sphincter pressure is 10 to 30 mm Hg at end-exhalation.7 Transient relaxation of the lower esophageal sphincter is a neural reflex mediated through the brainstem. Gastric barrier pressure is calculated as lower esophageal sphincter pressure minus intragastric pressure. This barrier pressure is considered the major mechanism in preventing reflux of gastric contents into the esophagus. Gastric distension, meals high in fat, and pharyngeal stimulation are two possible mechanisms by which the afferent stimulus that initiates transient relaxation of the lower esophageal sphincter may originate.8Cricoid pressure decreases lower esophageal sphincter pressure, presumably reflecting stimulation of mechanoreceptors in the pharynx created by the external pressure on the cricoid cartilage (Fig. 32-6).9–11General anesthesia decreases lower esophageal sphincter pressure 7 to 14 mm Hg, depending on the degree of skeletal muscle relaxation.12 Normally, upper esophageal sphincter pressure prevents regurgitation into the pharynx in the awake state. The administration of anesthetic drugs may decrease upper esophageal sphincter pressure even before the loss of consciousness.12
The influence, if any, of changes in lower esophageal sphincter tone and barrier pressure (lower esophageal sphincter tone minus gastric pressure) and subsequent inhalation of gastric fluid during anesthesia remains undocumented.13 Despite decreases in lower esophageal sphincter pressure associated with anesthesia, the incidence of gastroesophageal reflux as reflected by decreases in esophageal fluid pH is rare in patients undergoing elective operations.14,15
Gastroesophageal Reflux Disease
Transient relaxation of the lower esophageal sphincter, rather than decreased lower esophageal sphincter pressure, is the major mechanism of gastroesophageal reflux disease (GERD). Transient relaxation of the lower esophageal sphincter is associated with simultaneous inhibition of the sphincter and crural diaphragm. Some patients with gastroesophageal reflux have a weak lower esophageal sphincter, some have a weak crural diaphragm, and some have both. In GERD, the reflux of gastric fluid into the esophagus or oropharynx causes symptoms (esophagitis characterized as “heartburn”) and/or tissue injury (esophageal strictures). It is estimated that approximately 20% of adults in the United States experience symptoms of GERD at least weekly and many patients with severe GERD have a hiatal hernia.
Atropine and morphine decrease the frequency of transient relaxation of the lower esophageal sphincter in normal patients through an unknown mechanism.7 Antisecretory drugs such as histamine (H2) receptor antagonists or proton pump inhibitors may be useful in treating gastroesophageal reflux. Therapy with a prokinetic drug such as metoclopramide may be effective. Patients with severe gastroesophageal reflux may benefit from surgical fundoplication of the esophagus via a laparoscopic technique.
Hiatal Hernia
The majority of patients with moderate to severe gastroesophageal reflux have a hiatal hernia in which a portion of the stomach herniates into the chest.7 Hiatal hernia may promote gastroesophageal reflux by trapping gastric acid in the hernia sac, which may then flow backward into the esophagus when the lower esophageal sphincter relaxes during swallowing. Hiatal hernia can also cause gastroesophageal reflux when contraction of the crural diaphragm during inspiration and other physical maneuvers lead to a compartmentalization of the stomach between the lower esophageal sphincter and the diaphragm. The presence of acid in the esophagus causes esophagitis, which decreases the lower esophageal sphincter pressure and impairs esophageal contractility.
Achalasia
Achalasia is the best characterized of all esophageal motility disorders reflecting degeneration of neurons in the wall of the esophagus, especially the nitric oxide–producing inhibitory neurons that affect the relaxation of esophageal smooth muscle necessary for opening the lower esophageal sphincter. The loss of inhibitory innervation in the lower esophageal sphincter causes basal sphincter pressure to increase and interferes with sphincter relaxation. In the body of the esophagus, the loss of intramural neurons manifests as aperistalsis. Dysphagia for both solid foods and liquids is the primary symptom of achalasia. A substantial number of patients complaining of heartburn and achalasia may be confused with GERD.
Achalasia can be confirmed with radiographic (barium swallow shows dilatation of the esophagus with a beaklike narrowing of esophagogastric junction), manometric, and endoscopic evaluation (often performed utilizing drugs to produce sedation). The diagnosis may be suggested by a routine radiograph of the chest that shows widening of the mediastinum from the dilated esophagus and the absence of the normal gastric air bubble, because lower esophageal sphincter contraction prevents swallowed air from entering the stomach.
Nitrates and calcium channel blockers relax the smooth muscle of the lower esophageal sphincter and may produce limited success in treating patients with achalasia. Pneumatic dilation therapy for achalasia (a large deflated balloon is passed through the mouth to the lower esophageal sphincter and then rapidly inflated) may be helpful. Esophageal perforation is a risk of this treatment. Surgical myotomy of the lower esophageal sphincter performed laparoscopically often results in excellent relief but may be followed by GERD. For this reason, the myotomy may be combined with an antireflux procedure (fundoplication). Endoscopic injection of botulinum toxin into the area of the lower esophageal sphincter blocks the excitatory (acetylcholine-releasing) neurons that contribute to lower esophageal sphincter tone. Unfortunately, the effect is usually short-lived (less than 6 to 12 months).
A patient with achalasia presenting for surgery unrelated to the underlying esophageal motility disorder represents a potential risk for pulmonary aspiration during the perioperative period.
Stomach
The stomach is a specialized organ of the digestive tract that stores and processes food for absorption (Fig. 32-7). The ability to secrete hydrogen ions in the form of hydrochloric acid is a hallmark of gastric function. The secretory unit of gastric mucosa is the oxyntic glandular mucosa. The stomach is richly innervated by the vagus nerves and celiac plexus.
Gastric Secretions
Total daily gastric secretion is approximately 2 L with a pH of 1.0 to 3.5. The stomach secretes only a few milliliters of gastric fluid each hour during the periods between digestion. Strong emotional stimulation, such as occurs preoperatively, can increase interdigestive secretion of highly acidic gastric fluid to >50 mL per hour. The major secretions are hydrochloric acid, pepsinogen, intrinsic factor, and mucus. Mucous secretion protects the gastric mucosa from mechanical and chemical destruction. Substances that disrupt the mucosal barrier and cause gastric irritation include ethanol and drugs that inhibit prostaglandin synthesis (aspirin, nonsteroidal antiinflammatory drugs).
Parietal Cells
Parietal cells secrete an hydrogen ion–containing solution with a pH of approximately 0.8. At this pH, the hydrogen ion concentration is approximately 3 million times that present in the arterial blood. Hydrochloric acid kills bacteria, aids protein digestion, provides the necessary pH for pepsin to start protein digestion, and stimulates the flow of bile and pancreatic juice.
Secretion of hydrochloric acid depends on stimulation of receptors in the membrane of parietal cells by histamine, acetylcholine (vagal stimulation), and gastrin.16 All of these receptors increase the transport of hydrogen ions into the gastric lumen by the hydrogen-potassium adenosine triphosphatase (ATPase) enzyme system (Fig. 32-8).17 Activation of one receptor type potentiates the response of the other receptors to stimulation. Blockade of receptors with specific antagonist drugs produces effective decreases in acid transport responses by removing the potentiating effect of stimulation of these receptors on the responses to other stimuli. Blockade of muscarinic receptors is produced by atropine or the more specific anticholinergic pirenzepine. Gastrin receptors can be inhibited by proglumide. Alternatively, the hydrogen-potassium-ATPase enzyme system can be inhibited by omeprazole. Pharmacologic manipulation of gastric fluid pH has special implications in the management of patients considered to be at risk for pulmonary aspiration during the perioperative period.
Intrinsic factor, which is essential for absorption of vitamin B12 from the ileum, is secreted by parietal cells. For this reason, destruction of parietal cells, as is associated with chronic gastritis, produces achlorhydria and often pernicious anemia.
Chief Cells
Pepsinogens secreted by chief cells undergo cleavage to pepsins in the presence of hydrochloric acid. Pepsins are proteolytic enzymes important for the digestion of proteins.
G Cells
Gastrin is secreted by gastric antral cells (G cells) into the circulation, which carries this hormone to responsive receptors in parietal cells to stimulate gastric hydrogen ion secretion. Gastrin also increases the tone of the lower esophageal sphincter and relaxes the pylorus.
Gastric Fluid Volume and Rate of Gastric Emptying
Neural and humoral mechanisms greatly influence gastric fluid volume and gastric-emptying time.18–20 In general, parasympathetic nervous system stimulation enhances gastric fluid secretion and motility, whereas sympathetic nervous system stimulation has an opposite effect. The elimination of nonnutrient liquids is an exponential process (volume of liquid emptied per unit of time is directly proportional to the volume present in the stomach), whereas the emptying of solids is a linear process (Fig. 32-9).19 In this regard, emptying of liquids from the stomach begins within 1 minute of ingestion, whereas emptying of solids typically begins after a lag time of 15 to 137 minutes (median 49 minutes).18 Gastric emptying in healthy, term, nonobese parturients is not delayed after ingestion of 300 mL of water.21 It is generally thought that the delay in gastric emptying of solids is caused by the time necessary for antral contractions to break solids down into small enough particles to exit through the pylorus. Clinical manifestations of delayed gastric emptying include anorexia, persistent fullness after meals, abdominal pain, and nausea and vomiting.
Several factors affect the rate of gastric emptying.19 The primary determinant of the emptying of liquids from the stomach is volume. In addition to volume, another factor that influences the rate of gastric emptying is the composition of the liquids. Emptying of neutral, isoosmolar, and calorically inert solutions is rapid (250 mL of 500 mL of normal saline is emptied in 12 minutes). A small amount of water (up to 150 mL) to facilitate administration of oral medications shortly before the induction of anesthesia does not produce sustained increases in gastric fluid volume and could even contribute to gastric emptying.22 Solutions that are hypertonic or contain acid, fat, or certain amino acids all retard gastric emptying. High lipid and/or caloric content (glucose) slows the emptying of solids from the stomach.18,23
The basic defect of diabetic gastroparesis appears to be one of impaired neural control. Delayed gastric emptying of solids is the most consistent abnormality in diabetics with gastroparesis and is the most predictably responsive to pharmacologic manipulation. Nevertheless, as diabetes progresses, it is possible that gastric retention of liquids will also occur.19 Patients with GERD and documented slowing of gastric emptying of solids have been shown to have normal gastric emptying rates for liquids. Most patients with slowed gastric emptying of solids in association with GERD do not demonstrate symptoms such as nausea and vomiting, which are usually associated with gastric stasis. The existence of delayed gastric emptying in gastric ulcer disease is controversial. Some data suggest a slowing of gastric emptying of solids but not liquids in the presence of gastric ulcers. Although obesity and pregnancy are often assumed to slow gastric emptying, there are also data that fail to confirm this slowing, whereas other data suggest accelerated gastric emptying in obese individuals.24–27 Contraction of the gastric fundus is responsible for facilitating the emptying of liquids, whereas antral contractions control the emptying of solids.20 Gastrointestinal transit time has been shown to vary during the menstrual cycle, with prolongation occurring during the luteal phase when progesterone levels are increased. Acute viral gastroenteritis has been associated with delayed gastric emptying.
Certain drugs, including opioids, β-adrenergic agonists, and tricyclic antidepressants, may slow gastric emptying. Aluminum hydroxide antacid may slow gastric emptying. Alcohol, at least in concentrations present in wine, does not significantly affect gastric emptying of liquids or solids. Higher concentrations of alcohol, such as present in whiskey, do cause slowing of gastric emptying. The mechanism of this slowing is not clear but may be due to hyperosmolarity, changes in gastric acid secretion, or damage to gastric mucosa. Total parenteral nutrition may cause gastric stasis. Elemental diets, probably due to their high concentration of amino acids and hyperosmolarity, take longer to empty from the stomach than does blenderized food of comparable caloric composition. Cigarette smoking has been shown to delay emptying of solids although it may accelerate emptying of liquids. Gastric prokinetic drugs such as metoclopramide may speed the emptying of solids and liquids.
Gastric Emptying Prior to Elective Surgery
Clear liquids can be administered to adult patients scheduled for elective operations until 2 hours before induction of anesthesia without increasing gastric fluid volume. It takes 3 to 4 hours for the stomach to empty following a light breakfast (one slice of white bread with butter and jam, 150 mL of coffee without milk or sugar, 150 mL of pulp-free orange juice).28 These data are consistent with the recommendation that a 6-hour fast should be enforced after a light breakfast.29
Opioid-Induced Slowing of Gastric Emptying
Opioid peptides and their receptors are found throughout the gastrointestinal system with particularly high concentrations in the gastric antrum and proximal duodenum. Central and peripheral µ opioid receptors can regulate gastric emptying, and opioid-induced delay in gastric emptying can be reversed with naloxone, which acts simultaneously at both central and peripheral sites. The demonstration that methylnaltrexone, a selective peripheral-acting opioid antagonist, attenuates morphine-induced changes in the rate of gastric emptying indicates that peripheral opioid receptors modulate this response in humans (see Chapter 7).30
Measurement of the Rate of Gastric Emptying
The rate of gastric emptying can be evaluated by a noninvasive electrical bioimpedance method (epigastric impedance method) and indirectly by the acetaminophen absorption technique.31 Dye dilution techniques and scintigraphy also have been used to assess the rate of gastric emptying in humans.32
Electrical Bioimpedance Technique
The basis of the bioimpedance technique is that, after ingestion of fluids with a different conductivity from body tissues, the impedance to an electrical current through the upper abdomen changes. Electrodes are placed on the abdomen and back, and a constant current is applied. Impedance increases as the stomach fills and decreases as it empties. The slope of the plot of impedance versus time allows calculation of the emptying half-time of a meal.
The principal benefit of the bioimpedance method is that it is noninvasive and avoids gastric intubation or exposure to radioactivity. A limitation is that the subject must not move because alterations in body posture may alter baseline impedance readings and thus invalidate the recording. Another possible source of error is that gastric secretions might decrease the conductivity of gastric contents, thus reducing total surface impedance and producing inaccurate emptying rates. For this reason, deionized water may be used as the “test meal” because it does not appear to provoke sufficient gastric secretions to alter impedance.30
Acetaminophen Absorption Test
The appearance of acetaminophen in the systemic circulation is an indirect method of determining the rate of gastric emptying. The area under the plasma concentration curve of acetaminophen after oral administration is determined by the rate of gastric emptying, because acetaminophen is not absorbed from the stomach but is rapidly absorbed from the small intestine.
Absorption from the Stomach
The stomach is a poor absorptive area of the gastrointestinal tract because it lacks the villus structure characteristic of absorptive membranes. As a result, only highly lipid-soluble liquids such as ethanol and some drugs such as aspirin can be significantly absorbed from the stomach.
Vomiting
Vomiting is coordinated by the vomiting center in the medulla. This center receives input from multiple sites including the chemoreceptor trigger zone in the floor of the fourth ventricle, from the vestibular apparatus, from cortical centers and the gastrointestinal tract. The blood–brain barrier is poorly developed around the chemoreceptor trigger zone, and emetic substances present in the circulation are readily accessible to this site. Serotonin acting at 5-hydroxytryptamine receptors (5-HT3) is an important emetic signal via neural pathways from the gastrointestinal tract ending at the chemoreceptor trigger zone. Likewise, dopamine and acetylcholine may provide emetic signals to the chemoreceptor trigger zone. Pharmacologic antagonism of these emetic signals results in antiemetic effects. The role of specific opioid receptors in emetic responses is unresolved. Following stimulation of the vomiting center (directly or indirectly via neural pathways), vomiting is mediated by efferent pathways including the vagus and phrenic nerves, and innervation of the abdominal musculature. The initial manifestation of vomiting often involves nausea in which gastric peristalsis is reduced or absent and the tone of the upper small intestine is increased and gastric reflux occurs. Ultimately, the upper portion of the stomach relaxes while the pylorus constricts and the coordinated contraction of the diaphragm and abdominal muscles leads to expulsion of gastric contents. Risk factors for postoperative nausea and vomiting include female sex, young age (children), history of motion sickness, abstinence from tobacco, and obesity (perhaps reflecting emetic anesthetic drugs stored in adipose tissue).33
Small Intestine
The small intestine consists of the duodenum (from the pylorus to the ligament of Treitz), the jejunum, and the ileum (ending at the ileocecal valve). There is no distinct anatomic boundary between the jejunum and ileum, but the first 40% of small intestine after the ligament of Treitz is often considered the jejunum. The small intestine is presented with approximately 9 L of fluid daily (2 L from the diet and the rest representing gastrointestinal secretions), but only 1 to 2 L of chyme enters the colon. The small intestine is the site of most of the digestion and absorption of proteins, fats, and carbohydrates (Table 32-3).
Chyme moves through the 5 m of small intestine at an average rate of 1 cm per minute. As a result, it takes 3 to 5 hours for chyme to pass from the pylorus to the ileocecal valve. On reaching the ileocecal valve, chyme may remain in place for several hours until the person eats another meal. An inflamed appendix can increase the tone of the ileocecal valve to the extent that emptying of the ileum ceases. Conversely, gastrin causes relaxation of the ileocecal valve. When more than 50% of the small intestine is resected, the absorption of nutrients and vitamins is so compromised that development of malnutrition is likely.
Secretions of the Small Intestine
Mucus glands (Brunner glands) present in the first few centimeters of the duodenum secrete mucus to protect the duodenal wall from damage by acidic gastric fluid. Stimulation of the sympathetic nervous system inhibits the protective mucus-producing function of these glands, which may be one of the factors that causes this area of the gastrointestinal tract to be the most frequent site of peptic ulcer disease.
The crypts of Lieberkühn contain epithelial cells that produce up to 2 L daily of secretions that lack digestive enzymes and mimic extracellular fluid, having a pH of 6.5 to 7.5. This fluid provides a watery vehicle for absorption of substances from chyme as it passes through the small intestine. The most important mechanism for regulation of small intestine secretions is local neural reflexes, especially those initiated by distension produced by the presence of chyme.
The epithelial cells in the crypts of Lieberkühn continually undergo mitosis, with an average life cycle of approximately 5 days. This rapid growth of new cells allows prompt repair of any excoriation that occurs in the mucosa. This rapid turnover of cells also explains the vulnerability of the gastrointestinal epithelium to chemotherapeutic drugs (see Chapter 42).
The epithelial cells in the mucosa of the small intestine contain digestive enzymes that most likely are responsible for digestion of food substances because they are absorbed across the gastrointestinal epithelium. These enzymes include peptidases for splitting peptides into amino acids, enzymes for splitting disaccharides into monosaccharides, and intestinal lipases.
Absorption from the Small Intestine
Mucosal folds (valvulae conniventes), microvilli (brush border), and epithelial cells provide an absorptive area of approximately 250 m2 in the small intestine for nearly all the nutrients and electrolytes as well as approximately 95% of all the water. Daily absorption of sodium is 25 to 35 g, emphasizing the rapidity with which total body sodium depletion can occur if excessive intestinal secretions are lost as occurs with extreme diarrhea. Active transport of sodium ions in the small intestine is important for the absorption of glucose, which is the physiologic basis for treating diarrhea by oral administration of saline solutions containing glucose. Bacterial toxins as from cholera and staphylococci can stimulate the chloride-bicarbonate ion exchange mechanism, resulting in life-threatening diarrhea consisting of loss of sodium, bicarbonate, and an isosmotic equivalent of water.
Colon
The functions of the colon are absorption of water and electrolytes from the chyme and storage of feces. A test meal reaches the cecum in approximately 4 hours and then passes slowly through the colon during the next 6 to 12 hours, during which time 1 to 2 L of chyme are converted to 200 to 250 g of feces (Fig. 32-10). The circular muscle of the colon constricts and, at the same time, strips of longitudinal muscle (tinea coli) contract, causing the unstimulated portion of the colon to bulge outward into baglike sacs, or haustrations. Vagal stimulation causes segmental contractions of the proximal part of the colon and stimulation of the pelvic nerves causes explosive movements. Activation of the sympathetic nervous system inhibits colonic activity. Bacteria are predictably present in the colon.
Secretions of the Colon
Epithelial cells lining the colon secrete almost exclusively mucus, which protects the intestinal mucosa against trauma. The alkalinity of the mucus due to the presence of large amounts of bicarbonate ions provides a barrier to keep acids that are formed in the feces from attacking the intestinal wall. Irritation of a segment of colon as occurs with bacterial infection causes the mucosa to secrete large quantities of water and electrolytes in addition to mucus, diluting the irritating factors and causing rapid movement of feces toward the anus. The resulting diarrhea may result in dehydration and cardiovascular collapse.
Pancreas
The pancreas lies parallel to and beneath the stomach, serving as both an endocrine (insulin or glucagon) and exocrine gland. Exocrine secretions (approximately 1.5 L daily) are rich in bicarbonate ions to neutralize duodenal contents and digestive enzymes to initiate breakdown of carbohydrates, proteins, and fats.
Regulation of Pancreatic Secretions
Pancreatic secretions are regulated more by hormonal than neural mechanisms. For example, secretin is released by duodenal mucosa in response to hydrochloric acid. This hormone enters the circulation and causes the pancreas to produce large amounts of alkaline fluid necessary to neutralize the acidic pH of gastric fluid. In addition to the release of secretions, the presence of food in the duodenum causes the release of a second polypeptide hormone, cholecystokinin. Cholecystokinin also enters the circulation and causes the pancreas to secrete digestive enzymes (trypsins, amylase, lipases). Trypsins are activated in the gastrointestinal tract by the enzyme enterokinase, which is secreted by the gastrointestinal mucosa when chyme is exposed to the mucosa. Damage to the pancreas or blockade of a pancreatic duct may cause pooling of proteolytic enzymes, resulting in acute pancreatitis due to autodigestion by these enzymes. In general, pancreatic secretions are stimulated by the parasympathetic nervous system and inhibited by the sympathetic nervous system.
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