Additional information

1. Zollinger-Ellison syndrome: This syndrome is caused by a gastrin-producing tumor (gastrinoma), usually located in the duodenum or pancreas. A fasting gastrin level 10 times the upper limit of normal (approximately 1000 pg/mL) plus a gastric pH < 2.0 is diagnostic of Zollinger-Ellison syndrome. It typically presents with recurrent, multiple, refractory peptic ulcers, along with diarrhea and steatorrhea. Steatorrhea occurs because increased gastric acidity inhibits pancreatic lipase, impairing fat digestion.

A secretin stimulation test causes serum gastrin levels to rise in Zollinger-Ellison syndrome, whereas the opposite effect is seen in healthy individuals.

2. Action of gastrin: Gastrin increases gastric HCl production through two main mechanisms.

• It binds to parietal cells, increasing expression of the H+/K+ ATPase, which increases H+ secretion into the stomach.
• It stimulates enterochromaffin cells to release histamine. Histamine then binds to H2 receptors on parietal cells, further stimulating H+ secretion.

The end result is increased HCl production and secretion. Gastrin also promotes proliferation of parietal cells and enterochromaffin cells.

3. Incretins: Incretins are gastrointestinal hormones secreted in response to food intake that stimulate insulin secretion. The known incretins are GIP and GLP 1. Together, they produce the incretin effect: a two- to three-fold higher insulin secretory response to oral glucose compared with intravenous glucose. In subjects with type 2 diabetes, this incretin effect is diminished or no longer present.

4. Vomiting reflex: Vomiting (emesis) is the forceful retrograde expulsion of gastric contents from the body. Nausea is the unpleasant sensation that precedes vomiting. Retching (“dry heaves”) is the simultaneous contraction of the abdominal muscles and muscles of inspiration that may occur with vomiting.

The vomiting center (VC) is located in the dorsolateral medulla adjacent to the ascending reticular activating system and the medullary centers controlling cardiovascular and respiratory reflexes. It receives afferents from the cortex, limbic system, hypothalamus, vestibular centers, gut, and other viscera.

The chemoreceptor trigger zone (CTZ), located in the floor of the fourth ventricle, contains specific receptors for circulating toxins in the blood and cerebrospinal fluid and relays this information to the VC. Afferent information is processed by the nucleus of the tractus solitarius.

The effect is proximal gastric relaxation and a giant retrograde contraction of the intestine, mediated by the vagus nerve, leading to vomiting.

5. Defecation reflex: The anal canal is guarded by two sphincters: the external and internal anal sphincters.

• The internal anal sphincter is supplied by parasympathetic pelvic nerves, is composed of smooth muscle, and is involuntary.
• The external anal sphincter is supplied by the somatic pudendal nerve, is composed of striated muscle, and is voluntary.

Accumulation of fecal material activates stretch receptors in the rectum. Signals spread through the myenteric plexus to initiate peristaltic waves in the descending and sigmoid colon and the rectum. This is followed by relaxation of the internal anal sphincter, allowing feces to move toward the anus.

Impulses are conducted to the defecation center in the sacral spinal cord, which increases peristalsis in the descending colon, sigmoid colon, and rectum through the parasympathetic pelvic nerves. The external anal sphincter remains contracted until it is relaxed voluntarily, allowing defecation. The puborectalis muscle relaxes, straightening the rectum and facilitating defecation.

6. Enterohepatic circulation: Most bile salts secreted into the intestine are reabsorbed into the portal vein and carried back to the liver. In this way, bile salts are recycled.

Bile salts exert negative feedback on hepatic bile acid synthesis by inhibiting the enzyme cholesterol 7alpha-hydroxylase. Recirculation of bile salts to the liver also has a “choleretic” effect, meaning it stimulates further biliary secretion.