1.
Experiments are conducted in human volunteers to measure the variations in gastric acid secretion thoughout the day. During which period would you expect the rate of acid secretion to be at its highest?
Correct Answer
B. About one hour after eating the meal
Explanation
The peak rate of acid secretion usually occurs between one and two hours after eating the meal (the gastric phase). Acid secretion is increased but to a lesser extent by thinking about food e.g. in a restaurant looking at a menu and smelling the food of other diners (the cephalic phase) and although this secretion is added to by the act of eating within the first few minutes of ingesting a meal the peak secretory flow is not achieved in such a short space of time. As food enters the intestine around two to three hours after eating, there is a further small increase in acid secretion, but again at its peak it is still less than in the gastric phase secretion - which has already subsided.
2.
Which of the following sets of changes in acid secretion and serum gastrin levels are likely to occur in patients with pernicious anemia?
Correct Answer
C. Decreased acid secretion - increased gastrin
Explanation
Pernicious anemia usually is associated with reduced acid secretion especially if the cause is autoimmune antibodies against parietal cells (which secrete both acid and intrinsic factor). The reduction in acid secretion leads to vagally - mediated stimulation of gastrin release (e.g. via release of GRP) and plasma levels of the hormone increases. Loss of parietal cell function can not cause increases in acid secretion since acid is not secreted by any other cell type.
3.
You are investigating the normal patterns of gastric acid secretion by measuring intragastric pH of volunteers throughout the day. When would you expect the pH of the stomach to be at its lowest?
Correct Answer
D. In between meals
Explanation
The pH in the stomach will be at its lowest when the stomach is empty. This is because the stomach secretes acid continuously, even in the unfed state. Although the level of acid secretion in the unfed state is low - there is little in the way of substances present to buffer the H+ concentration and so the pH is low. Protein - rich meals are the most effective buffer against gastric acid, so the pH after a protein - rich meal may not initially fall as low as a meal of the same volume rich in carbohydrates or fats. However - remember that peptides and amino acids are a strong stimulus for acid secretion via the gastrin response.
4.
Surgical section of vagal afferent fibers from the stomach would results in which of the following effects?
Correct Answer
C. A decreased acid secretory response to distension of the stomach
Explanation
Distension of the stomach, as well as the presence of peptides and amino acids are the effective stimuli for the "gastric phase" of acid secretion. Distension activates mechanoreceptors in the mucosa of both the oxyntic and pyloric areas. These reflexes are mediated cholinergically. Some of these reflexes are intramural - others are vagovagal. Vagotomy reduces but does not abolish these responses demonstrating the involvement of intramural reflexes as well as the vago-vagal pathway. The cephalic phase of the acid secretory response is almost entirely abolished by vagotomy. Gastrin is released on stimulation by peptides and proteins in the gastric lumen. This response is not blocked by vagotomy. Somatostatin is released upon acidification of the gastric mucosa and acts upon the G-cell to inhibit gastrin release. Histamine is released from ECL cells in response to gastrin and acetylcholine released from postganglionic vagal efferent nerves. Vagotomy reduces the histamine - evoked acid-secretory response, suggesting that Ach is permissive for the stimulatory effect of histamine on the parietal cell.
stimulation by peptides and proteins in the gastric lumen. This response is not blocked by vagotomy. Somatostatin is released upon acidification of the gastric mucosa and acts upon the
5.
Administration of an inhibitor of the gastric H+,K+-ATPase will have which of the following consequences?
Correct Answer
D. An increase in the H+ concentration of the portal vein blood
Explanation
The H+/K+ -ATPase is the rate limiting pathway for acid secretion. The secretion of H+ into the gastric lumen involves the absorption of a HCO3- across the basolateral membrane of the parietal cell into the blood. When acid secretion is stimulated, the pH of the venous blood increases because of this absorbed HCO3- (the alkaline tide). Therefore, inhibition of acid secretion will reduce the amount of HCO3- entering the blood and the pH will fall (an increase in [H+] . Since it is the volume of the parietal secretion that varies on stimulation, clearly the volume of secretion will fall. It is likely that the [Na+] will increase (not fall), because Na+ is derived mostly from the non-parietal fraction of secretion. The potential difference across the stomach is the result of secretion of Cl- by the parietal cell and is also realted to movement of H+. If H+ secretion is decreased, fewer H+ will follow Cl- and so the potential will become hyperpolarized, not depolarized.
6.
Which of the following would contribute to protection of the gastric mucosa, and therefore decrease the risk of peptic ulcer formation?
Correct Answer
A. Proton pump inhibition
Explanation
Inhibition of the proton pump with a drug such as Omeprazole or other proton pump inhibitor (PPI) would directly reduce the secretion of acid. All other options would exacerbate the situation. Inhibition of prostaglandin formation would both increase acid secretion and decrease bicarbonate and mucus secretion. Formation of ammonia or other metabolic products from H. pylori would degrade barrier function of the gastric mucosa. Increased parasympathetic stimulation increases acid secretion as does stimulation of H2 receptors.
7.
According to the two-component model of gastric acid secretion, the H+ concentration of gastric juice increases with rate of secretion because of which of the following mechanisms?
Correct Answer
A. The Volume of the parietal component increases
Explanation
At low flow rates, the gastric juice is essentially a saline solution with only small amounts of H+ and K+. Because at peak flow rates, gastric juice is primarily HCl acid, as the rate of secretion increases, the concentration of Na+ falls and that of H+ rises. This phenomenon is best understood by thinking of gastric juice as consisting of two separate component secretions. The first is a "non-parietal" secretion of relatively constant flow that is alkaline and consists mostly of NaCl. K+ and HCO3- at about the same concentration as in plasma. The second component is a "parietal" secretion consisting of approximately 150 mM HCl and 10 - 20 mM K+. So as flow rate increases, the contribution of the parietal secretion increases, but not the non-parietal component. The increased parietal secretion essentially dilutes the non-parietal secretion and the concentration of Na+ falls. Because the changes in concentration are dependent on flow rate, the osmotic pressure of gastric juice remains the same at all flow rates and is usually approximately isotonic with plasma.
8.
In a laboratory experiment, the pH of the gastric antrum was reduced in the presence of amino - acids. The plasma gastrin level was determined and found to be lower than when the same amount of amino acids were given at a more alkaline pH. Increases in which of the following chemical signals mediates the reduced gastrin secretion at increased H+ concentration?
Correct Answer
D. Somatostatin
Explanation
The presence of amino acids stimulates the release of gastrin which increases acid secretion by the parietal cell. Reduced antral pH causes the release of somatostatin, which reduces secretion of gastrin from G - cells. Increases in any of the others except secretin will cause an increase in acid secretion not reduce it. Secretin inhibits gastrin secretion, but this occurs on acidification of the duodenum not gastric antrum.
9.
The gastric intraluminal pressure was measured after introduction of differing volumes of a test meal. For any given volume of meal what would be the effect of vagotomy on the pressure recorded?
Correct Answer
B. Increased
Explanation
The process by which the stomach increases its volume without significant change in intra-gastric pressure is termed "accommodation". This response is critically dependent on an intact vagal innervation, and the vagotomized stomach has higher pressures at all volumes as well as showing a greater increase in pressure for a given increase in volumes between 200 and 500 mL.
10.
A group of volunteers are asked to pick and chew their favorite sandwich filling and then spit it out without swallowing it. Simultaneous measurement of intragastric pH during this experiment shows a decrease. Which neurotransmitter causes this response?
Correct Answer
D. Gastrin Releasing Peptide
Explanation
This experiment illustrates the "cephalic phase" of gastric acid secretion in which cognitive factors (independent of food entering the stomach) leads to stimulation of gastric acid secretion. Vagal efferent fibers cause the release of Gastrin Releasing Peptide from enteric nerves which stimulates antral G cells to secrete gastrin into the blood stream that returns to the GI tract to activate parietal (and chief cells) to secrete acid. Vasoactive intestinal polypeptide is a neurotransmitter released from non-cholinergic neurons in the ENS which regulates a variety of secreto-motor activities in the gastrointestinal tract, causing relaxation of smooth muscle and increased secretion by pancreatic acinar cells and chloride secretion in intestinal crypts. Nitric oxide is also an inhibitory neurotransmitter released from ENS inhibitory motor neurons, causing relaxation of smooth muscle. Substance P is a tachykinin that is co-released with acetylcholine and potentiates the effects of acetylcholine. Norepinepherine has a variety of inhibitory effects on gastrointestinal smooth muscle which are mediated through stimulation of alpha and beta receptors (on ENS neurons and smooth muscle respectively) and excitatory effects on sphincteric and vascular smooth muscle tone mediated through alpha receptors.