Physiology of Gastrointestinal Disorders

Paralysis of the Swallowing Mechanism

Damage to the fifth, ninth, or tenth cerebral nerve can cause paralysis of significant portions of the swallowing mechanism. In addition, a few diseases, such as poliomyelitis or encephalitis, can prevent normal swallowing by damaging the swallowing center in the brain stem. Paralysis of the swallowing muscles, as occurs in persons with muscle dystrophy or as a result of failure of neuromuscular transmission in persons with myasthenia gravis or botulism, can also prevent normal swallowing.

When the swallowing mechanism is partially or totally paralyzed, the abnormalities that can occur include the following: (1) complete abrogation of the swallowing act so that swallowing cannot occur, (2) failure of the glottis to close so that food passes into the lungs instead of the esophagus, and (3) failure of the soft palate and uvula to close the posterior nares so that food refluxes into the nose during swallowing.

One of the most serious instances of paralysis of the swallowing mechanism occurs when patients are in a state of deep anesthesia . While on the operating table, they sometimes vomit large quantities of materials from the stomach into the pharynx; then, instead of swallowing the materials again, they simply suck them into the trachea because the anesthetic has blocked the reflex mechanism of swallowing. As a result, such patients may choke to death on their own vomitus.

Achalasia and Megaesophagus

Achalasia is a condition in which the lower esophageal sphincter fails to relax during swallowing. As a result, food swallowed into the esophagus fails to pass from the esophagus into the stomach. Pathophysiological studies have shown damage in the neural network of the myenteric plexus in the lower two-thirds of the esophagus. As a result, the musculature of the lower esophagus remains spastically contracted, and the myenteric plexus has lost its ability to transmit a signal to cause “receptive relaxation” of the gastroesophageal sphincter as food approaches this sphincter during swallowing.

When achalasia becomes severe, the esophagus often cannot empty the swallowed food into the stomach for many hours, instead of the few seconds that is the normal time. Over months and years, the esophagus becomes tremendously enlarged until it often can hold as much as 1 liter of food, which often becomes putridly infected during the long periods of esophageal stasis. The infection may also cause ulceration of the esophageal mucosa, sometimes leading to severe substernal pain or even rupture and death. Considerable benefit can be achieved by stretching the lower end of the esophagus with a balloon inflated on the end of a swallowed esophageal tube. Antispasmodic drugs (i.e., drugs that relax smooth muscle) can also be helpful.

Increased Permeability of the Gastric Barrier in Gastritis

Absorption of food from the stomach directly into the blood is normally slight. This low level of absorption is mainly due to two specific features of the gastric mucosa: (1) it is lined with highly resistant mucous cells that secrete viscid and adherent mucus, and (2) it has tight junctions between the adjacent epithelial cells. These two features together plus other impediments to gastric absorption are called the “gastric barrier.”

The gastric barrier normally is resistant enough to diffusion so that even the highly concentrated hydrogen ions of the gastric juice, averaging about 100,000 times the concentration of hydrogen ions in plasma, seldom diffuse even to the slightest extent through the lining mucus as far as the epithelial membrane. In gastritis, the permeability of the barrier is greatly increased. The hydrogen ions then diffuse into the stomach epithelium, creating additional havoc and leading to a vicious circle of progressive stomach mucosal damage and atrophy. It also makes the mucosa susceptible to digestion by the peptic digestive enzymes, thus frequently resulting in a gastric ulcer.

Achlorhydria (and Hypochlorhydria)

Achlorhydria means that the stomach fails to secrete hydrochloric acid; it is diagnosed when the pH of the gastric secretions fails to decrease below 6.5 after maximal stimulation. Hypochlorhydria means diminished acid secretion. When acid is not secreted, pepsin also usually is not secreted. Even when it is secreted, the lack of acid prevents it from functioning because pepsin requires an acid medium for activity.

Gastric Atrophy May Cause Pernicious Anemia

Pernicious anemia commonly accompanies gastric atrophy and achlorhydria. Normal gastric secretions contain a glycoprotein called intrinsic factor, secreted by the same parietal cells that secrete hydrochloric acid. Intrinsic factor must be present for adequate absorption of vitamin B ₁₂ from the ileum. That is, intrinsic factor combines with vitamin B ₁₂ in the stomach and protects it from being digested and destroyed as it passes into the small intestine. Then, when the intrinsic factor–vitamin B ₁₂ complex reaches the terminal ileum, the intrinsic factor binds with receptors on the ileal epithelial surface, which in turn makes it possible for the vitamin B ₁₂ to be absorbed.

In the absence of intrinsic factor, only about 1/50th of the vitamin B ₁₂ is absorbed. In addition, without intrinsic factor, an adequate amount of vitamin B ₁₂ is not made available from the foods to cause young, newly forming red blood cells to mature in the bone marrow. The result is pernicious anemia. This is discussed in more detail in Chapter 33 .

Basic Cause of Peptic Ulceration

The usual cause of peptic ulceration is an imbalance between the rate of gastric juice secretion and the degree of protection afforded by (1) the gastroduodenal mucosal barrier and (2) the neutralization of the gastric acid by duodenal juices. All areas normally exposed to gastric juice are well supplied with mucous glands, beginning with compound mucous glands in the lower esophagus plus the mucous cell coating of the stomach mucosa, the mucous neck cells of the gastric glands, the deep pyloric glands that secrete mainly mucus, and, finally, the glands of Brunner of the upper duodenum, which secrete a highly alkaline mucus.

In addition to the mucus protection of the mucosa, the duodenum is protected by the alkalinity of the small intestinal secretions. Especially important is pancreatic secretion, which contains large quantities of sodium bicarbonate that neutralize the hydrochloric acid of the gastric juice, thus also inactivating pepsin and preventing digestion of the mucosa. In addition, large amounts of bicarbonate ions are provided in (1) the secretions of the large Brunner’s glands in the first few centimeters of the duodenal wall and (2) bile coming from the liver.

Finally, two feedback control mechanisms normally ensure that this neutralization of gastric juices is complete, as follows:

• 1.

  When excess acid enters the duodenum, it inhibits gastric secretion and peristalsis in the stomach, by nervous reflexes and by hormonal feedback from the duodenum, thereby decreasing the rate of gastric emptying.

• 2.

  The presence of acid in the small intestine liberates secretin from the intestinal mucosa, which then passes by way of the blood to the pancreas to promote rapid secretion of pancreatic juice. This juice also contains a high concentration of sodium bicarbonate, thus making additional sodium bicarbonate available for neutralization of the acid.

Therefore, a peptic ulcer can be caused in either of two ways: (1) excess secretion of acid and pepsin by the gastric mucosa or (2) diminished ability of the gastroduodenal mucosal barrier to protect against the digestive properties of the stomach acid–pepsin secretion.