gastrointestinal physiology

2 CHAPTER 1 Regulation: Peptides of the Gastrointestinal Tract GI peptides have many different modes of action. Another GI peptide, ghrelin, is released from the body of the stomach and acts as a hormone to regulate food intake.

Table 1.1 lists the stimuli that are physiologically important releasers of the GI hormones

ACTIONS AND INTERACTIONS

This action is shared by CCK, but secretin is the most potent choleretic of the GI hormones. Secretin is second only to ACh in promoting pepsinogen secretion from the chief cells of the stomach.

CANDIDATE HORMONES

NEUROCRINES

These compounds are present in nerves both within the smooth muscle and mucosa of the gastrointestinal tract. Opiate receptors on circular smooth muscle cells mediate contraction, and leuenkephalin and metenkephalin cause contraction of the lower esophageal, pyloric, and ileocecal sphincters.

PARACRINES

What determines which cells are acted upon by hormones, paracrines, and neurocrines?

You diagnose a patient with severe duodenal ulcers as having a gastrinoma (Zollinger-Ellison syndrome). If

ANATOMY OF THE AUTONOMIC NERVOUS SYSTEM

This transmitter also exerts its effects mainly on neurons of the enteric nervous system. Solid lines indicate the afferent and preganglionic efferent innervation of the rest of the GI tract.

Fig. 2.1 Extrinsic branches of the autonomic nervous system. (A) Parasympathetic. Dashed lines indicate the cholinergic innervation of striated muscle in the esophagus and external anal sphincter

NEUROHUMORAL REGULATION OF GASTROINTESTINAL FUNCTION

ANATOMY OF THE SMOOTH MUSCLE CELL

SMOOTH MUSCLE CONTRACTION

What is meant by the terms “long and short reflexes,”

Explain the observation that gastrin and intestinal smooth muscles can each contract at different

Swallowing

CHEWING

PHARYNGEAL PHASE

Efferent impulses from the center are distributed to the pharynx via nerves from the nucleus ambiguus. The impulses appear to be sequential, so that the pharyngeal musculature is activated in a proximal to distal manner.

ESOPHAGEAL PERISTALSIS

During a swallow, the sphincters and the body of the esophagus work in a coordinated manner (Fig. 3.3B). After bolus passage, it contracts, followed by a peristaltic contraction in the body of the esophagus.

RECEPTIVE RELAXATION OF THE STOMACH

What is the difference between the innervation of the striated and smooth muscle portions of the esophagus

How does the body cope with the fact that much of the esophagus lies within the thorax?

Explain the regulation of gastric contractile activity, including the role of slow waves. Accommodation and temporary storage of ingested material results from receptive relaxation of the oral stomach (see Chapter 3).

ANATOMIC CONSIDERATIONS

The motility of the stomach and upper small intestine is organized to carry out regular emptying of the contents into the duodenum in the presence of ingested material of variable quantity and composition. Emptying, which also involves mixing ingested material with gastric juice and reducing the particle size of any solids that have been swallowed, results from the integrated contractions of the oral stomach, caudate stomach, pylorus, and duodenum.

CONTRACTIONS OF THE ORAD REGION OF THE STOMACH

CONTRACTIONS OF THE CAUDAD REGION OF THE STOMACH

However, slow waves are always present regardless of the presence or absence of contractions. If the threshold is reached, it is only during a specific phase of the slow wave cycle.

Fig. 4.3 Electrical activity of smooth muscle cells of the stomach. Electrodes placed on the serosal surface record no changes from the orad region

CONTRACTIONS OF THE GASTRODUODENAL JUNCTION

These events control not only the level of the slow wave plateau, but also the amount of peaks and thus both the frequency and strength of the contractions. The physiological significance of the gastric motor effects of secretin and GIP is questionable.

CONTRACTIONS OF THE PROXIMAL DUODENUM

Transection of the vagal nerve leads to a decrease in contractions, while vagal stimulation increases the number and force of contractions. Gastrin and motilin increase contractions, while secretin and gastric inhibitory peptide (GIP) inhibit them.

REGULATION OF GASTRIC EMPTYING

You have a patient with a significant decrease in pancreatic enzyme secretion. Which of the following

Describe the functions of slow waves and peak potentials in regulating the contractions of the small intestine. Many of the fibers in the vagus are preganglionic, while many of the abdominal ganglia are postganglionic.

TYPES OF CONTRACTIONS

The motility of the small intestine is organized to optimize the processes of digestion and absorption of nutrients and aboral propulsion of undigested material. Some of the fibers in the vagus are cholinergic, while some from the abdominal plexus are adrenergic.

PATTERNS OF CONTRACTIONS

In the human upper small intestine, contractions at any one site are present 14% to 34% of the time recorded. During these periods, contractions occur at any location at multiples of the slow wave interval.

Fig. 5.2 Frequency distribution of 7572 contractions recorded at one site in the human small intestine

VOMITING

What are the major differences between gastric and intestinal slow waves?

How does the motor activity aid in carrying out the major functions of the small intestines?

In areas of the colon with tapeworms, this myenteric plexus is concentrated under them. Extrinsic innervation to the colon comes from both the parasympathetic and sympathetic branches of the ANS.

CONTRACTIONS OF THE CECUM AND ASCENDING COLON

As in other regions of the gut, several different chemicals serve as mediators at presynaptic and postsynaptic connections within the autonomic innervation to the colon. Acetylcholine (ACh) and tachykinins such as substance P serve as major excitatory mediators, and nitric oxide (NO), vasoactive intestinal peptide (VIP), and possibly adenosine triphosphate (ATP) serve as major inhibitory mediators.

CONTRACTIONS OF THE DESCENDING AND SIGMOID COLON

MOTILITY OF THE RECTUM AND ANAL CANAL

Normally, the anal canal is closed by contraction of the internal anal sphincter. When the rectum is distended by fecal material, the internal sphincter relaxes as part of the rectosphincteric reflex (Figure 6.4).

CONTROL OF MOTILITY

What is the function of the ileocecal reflex, and how is it regulated?

How does the motility pattern of the colon lead to the storage of fecal material?

How the pattern of colonic motility leads to storage of fecal material. An active process produces saliva in large quantities compared to the weight of the salivary glands.

FUNCTIONS OF SALIVA

Although the salivary glands are not essential to life, their secretions are important for the hygiene and comfort of the mouth and teeth. The serous salivary glands of the tongue secrete the second digestive enzyme, lingual lipase, which plays a role in the hydrolysis of dietary lipids.

ANATOMY AND INNERVATION OF THE SALIVARY GLANDS

The blood supplied to the salivary glands is distributed by branches of the external carotid artery. This blood flow is partly responsible for the enormous amounts of saliva produced relative to the weight of the glands.

COMPOSITION OF SALIVA

The fluid also becomes hypotonic, and the longer the fluid remains in the channel (ie, the slower the perfusion), the greater the changes. The Na/K-ATPase pumps Na+ out, while the Cl− channel in the basolateral membrane transports it out of the cell.

Fig. 7.2 Autonomic nervous distribution to the major salivary glands.

REGULATION OF SALIVARY SECRETION

What are the unique properties and characteristics of saliva that distinguish it from other GI

What changes in saliva would you expect to see when the fluid leaves the duct compared with when it leaves

It is part of the gastric mucosal barrier that protects the stomach from acid and pepsin digestion. Water acts as the medium for the action of acid and enzymes and makes many of the ingredients of a meal soluble.

FUNCTIONAL ANATOMY

During the resting state, the cytoplasm of the parietal cells is dominated by numerous tubulovesicles. During secretion, the membranes of the granules fuse with the cell membrane and expel mucus.

SECRETION OF ACID

However, unlike in the stomach and mucous cells, these hormone-containing granules are located at the base of the cell. These pump inhibitors are the most potent of the various types of acid secretory inhibitors and are effective agents in the treatment of gastric ulcers, even ulcers caused by gastrinoma (Zollinger-Ellison syndrome).

ORIGIN OF THE ELECTRICAL POTENTIAL DIFFERENCE

H+,K+-ATPase, like Na+,K+-ATPase, with which it has an amino acid homology of 60%, is part of the P-type ion-transporting ATPases, which also includes the calcium (Ca2+)-ATPase. Drugs such as omeprazole, a substituted benzimidazole, accumulate in acid spaces and are activated at low pH.

ELECTROLYTES OF GASTRIC JUICE

Knowledge of the composition of gastric juice is necessary to treat a patient with chronic vomiting or one whose gastric juice is aspirated and maintained intravenously.

STIMULANTS OF ACID SECRETION

STIMULATION OF ACID SECRETION

Ca2+, either in the gastric lumen or as elevated serum concentrations, stimulates gastrin release and acid secretion. It is believed that the acid in the stomach lumen acts directly on the somatostatin cell to stimulate the release of somatostatin and thereby prevent the release of gastrin.

Fig. 8.7 Mechanisms stimulating gastric acid secretion during the cephalic phase. ACh, Acetylcholine; G cell, gastrin-produc-ing cell; GRP, gastrin-releasgastrin-produc-ing peptide; H + , hydrogen ion.

INHIBITION OF ACID SECRETION

In dogs, liver extract releases a hormone from the duodenal mucosa that stimulates acid secretion without increasing serum gastrin levels. The relationship between the rate of acid secretion and the pH and volume of gastric contents is shown in Figure 2.

PEPSIN

Pepsin plays an important role in the ulceration of the stomach and duodenum, hence the term peptic ulcer. Thus one of the benefits of inhibiting acid secretion or neutralizing gastric acid during ulcer therapy may be the elimination of pepsin.

Fig. 8.11 The relationship between gastric secretory rate, intragastric pH, and volume of gastric contents during a meal

MUCUS

Secretin also stimulates pepsinogen secretion, although it is questionable whether enough secretin is present to do so under normal conditions. In dogs, the entire response can be explained by the stimulation of acid secretion by gastrin and the subsequent activation of the acid-sensitive reflex mechanism for pepsinogen secretion.

INTRINSIC FACTOR

GROWTH OF THE MUCOSA

What is the role of histamine in the stimulation of gastric acid secretion?

Na+ moves paracellularly along the established electrochemical gradient from the plasma to the lumen of the gland. 82 CHAPTER 9 Pancreatic secretion, and the final concentrations of the two anions approach those in pure HCO3 secretion.

Fig. 9.1 Model for the secretion of bicarbonate ( HCO 3 − ) by the pancreatic duct cell

MECHANISMS OF ENZYME SECRETION

As the rate of secretion increases, there is less time for exchange, and the final ionic composition of pancreatic juice approaches that of the initially secreted solution containing only HCO3− and Na+. The results are a release of calcium (Ca2+) from the endoplasmic reticulum and the subsequent activation of protein kinases, which stimulate exocytosis.

REGULATION OF SECRETION

However, if the same dose is injected into the intestine while a low dose of secretin is given intravenously, production of the alkaline component of the pancreas increases to levels seen during a meal. Active trypsin in the intestinal lumen inhibits CCK release, and ingestion of trypsin inhibitors potently stimulates hormone release.

Fig. 9.4 Mechanisms involved in the stimulation of pancreatic secretion during the cephalic phase

CELLULAR BASIS FOR POTENTIATION

It is released in response to amino acids and fatty acids in the small intestine. The mechanisms that cause the stimulation of pancreatic secretion during the intestinal phase are shown in fig.

RESPONSE TO A MEAL

How does secretin stimulate pancreatic bicarbonate secretion?

During the response to a meal, maximum rates of pan- creatic HCO 3 − secretion are reached with plasma levels

Understand the solubility of bile acids and bile salts and how this affects their reabsorption in the small intestine. Understand the process of bile pigment secretion and its connection to jaundice.

OVERVIEW OF THE BILIARY SYSTEM

Describe the regulation of bile secretion by the liver and its removal from the gallbladder. The problem of the insolubility of fats in water is solved by the components of bile.

CONSTITUENTS OF BILE

The solubility of bile acids depends on the number of hydroxyl groups present and the terminal state. However, in the presence of bile salts and phospholipids, it dissolves as part of the micelle.

Fig. 10.1 Overview of the biliary system and the enterohepatic circulation of bile acids

BILE SECRETION

The amount of bile acids in the portal blood depends on the amount absorbed from the small intestine. The amount synthesized depends on the amount of bile acids returned to the liver in the enterohepatic circulation.

Fig. 10.4 Schematic diagram of the relationship between blood vessels, hepatocytes, and bile canaliculi in the liver

GALLBLADDER FUNCTION Filling

When stimulated by secretin, the concentration of HCO3 in bile can increase two or threefold compared to plasma concentration. During the absorption of water and electrolytes, the concentration of bile salts also increases, often up to a critical micellar concentration.

EXPULSION OF BILE

What determines whether a bile acid is more likely to be absorbed passively in the intestine as opposed to

A patient is unable to actively absorb bile acids in the ileum. What would you expect to happen to the fol-

Explain the role of trypsin in protein digestion and how it may be involved in the development of pancreatitis. Discuss the processes involved in the digestion and absorption of various lipids, including the roles of micelles and chylomicrons.

STRUCTURAL-FUNCTIONAL ASSOCIATIONS

DIGESTION

Although part of the digestion of carbohydrates, proteins and fats occurs in the stomach, the final breakdown of these substances occurs in the small intestine. Digestion and absorption of all major dietary products occur in the small intestine.

ABSORPTION

Significant chemical breakdown of food is also carried out by hydrolytic enzymes associated with the brush border of the small intestine. The half-life of membrane-bound enzymes (e.g. oligosaccharidases) is shorter than that of the epithelial cells.

ABSORPTIVE PROCESSES

CARBOHYDRATE ASSIMILATION Principal Dietary Forms

Carbohydrates that remain in the intestinal lumen increase the osmotic pressure of the contents of the lumen due to disturbances in digestion and absorption. The carrier (GLUT-2) in the basolateral membrane facilitates the exit of fructose, as well as glucose and galactose from the cell.

Fig. 11.3 Products of starch hydrolysis by α -amylase.

PROTEIN ASSIMILATION Digestion

Cystinuria is characterized by deficient transport of the cationic amino acids (arginine, lysine and ornithine) and cystine in the kidney and small intestine (Fig. 11.11). This is convincing evidence that absorption of the dipeptides of certain amino acids is the result of a completely separate process from that involved in the transport of free amino acids.

Fig. 11.8 Activation of pancreatic proteolytic enzymes. The process begins in the lumen when enterokinase cleaves a hexapeptide from trypsinogen and converts it to the active en-zyme trypsin.

LIPID ASSIMILATION

Colipase prevents inactivation by anchoring the lipase to the oil-water interface in the presence of bile salts. The lack of bile acids does not interfere with digestion, so in this case free fatty acids and monoglycerides appear in the stool.

Fig. 11.12 Positional specificity of pancreatic lipase.

VITAMINS

What is the evidence that a separate carrier system for small peptides is involved in amino acid

What is the evidence that micelles are involved in the absorption of fat breakdown products, and why are

Describe the mechanisms involved in and the location of the sites of absorption of sodium, potassium, chloride, bicarbonate and water. Discuss the basic steps involved in the absorption of calcium and iron and how they are regulated.

BIDIRECTIONAL FLUID FLUX

Indicate the sources of fluid and electrolytes in the gastrointestinal tract and their absorption sites. Explain the difference between osmotic and secretory diarrhea and discuss the disorders that can lead to this diarrhea.

IONIC CONTENT OF LUMINAL FLUID

In the duodenum, the concentration of Na+ is approx. 140 mEq/L, corresponding to the serum concentration. While the absorption of Na+ in the distal intestine is efficient, the conservation of Cl− is even more so.

TRANSPORT ROUTES AND PROCESSES

Unlike the small intestine, however, cotransport of Na+ with organic solutes is lacking. In the large intestine (but not in the small intestine), the apical and basolateral membranes are permeable to K+.

Fig. 12.2 Mechanism of sodium chloride (NaCl) absorption in the small intestine. Na + enters passively, following the electro-chemical gradient, by cotransport with nutrients such as glu-cose or amino acids, or by neutral cotransport with Cl − or in

MECHANISM FOR WATER ABSORPTION AND SECRETION

Na+ in the colonic lumen is also absorbed by an electroneutral process involving Cl− cotransport. More distally, in the small intestine, solute absorption creates a gradient for water absorption.

INTESTINAL SECRETION

The presence of sugars or amino acids in the lumen leads to their absorption by the sodium-coupled mechanism. The absence of certain enzymes, such as lactase, for example, results in the accumulation of their substrates.

CALCIUM ABSORPTION

In most cases, however, secretory diarrhea is caused by infection of the gut with pathogenic bacteria such as Vibrio cholerae and Escherichia coli. Decrease in the amount of the absorbent surface can also cause diarrhea as in the case of infection, inflammation or allergy, such as gluten-sensitive enteropathy.

IRON ABSORPTION

What transport processes in the gut account for the fact that prolonged diarrhea results in hypokalemic

Explain the role of the endocrine system in regulating metabolism and food intake. Although a certain amount of weight control can be achieved by increasing caloric expenditure in the form of exercise, the fact of the matter is that most of us overeat.

APPETITE CONTROL

Indeed, even the absorptive surface area of the small intestine can be reduced by 60% to 70%, as long as enough ileum remains to reabsorb bile acids and absorb vitamin B12, before increased amounts of nutrients appear. in stool. Obesity has now displaced smoking as the nation's number one health problem.

THE NERVOUS SYSTEM

THE ENDOCRINE SYSTEM

Body weight then falls to or near disease level and food intake returns to normal. Thus, leptin appears to be part of a negative feedback system for the regulation of food intake.

THE GASTROINTESTINAL SYSTEM

What is the role of the hypothalamus in the regulation of food intake?

What is the role of CCK in the regulation of food intake?

Target cells for the neurocrine must be present at the synapse where the agent is released. Because the esophagus is weak, its intraluminal pressure is negative, reflecting that of the chest.

APPENDIX A

Fourth, the luminal side of the mucosa is negative due to the uphill transport of Cl–. Most of the integration of signals that influence food intake takes place in the arcuate nucleus of the hypothalamus.

APPENDIX B

Which of the following enzymes is located in the brush border and plays a role in protein digestion. In the small intestine, each of the following is true regarding Cl− absorption except that.

ANSWERS