9 Stomach: Physiology and Disease 1

Question 1

Stomach

• multiple functions
• The high acidity/
• The process of digestion begins/
• other important functions that become especially obvious in diseases
• Structural changes or functional impairment underlie diseases that typically manifest clinically as/

Answer 1

• multiple functions,
  
  • storing and grinding ingested food
  • reservoir, mixes, disinfects, triturates and empties ingested food in a regulated fashion.
• The high acidity also limits the microbial colonization of the proximal GI tract.
• The process of digestion begins in the stomach.
• other important functions that become especially obvious in diseases:
  
  • contributes a factor required in vitamin B12 absorption
  • produces hormones.
• Structural changes or functional impairment underlie diseases that typically manifest clinically as hematemesis, black tarry stools, chronic anemia, pain, discomfort, nausea or vomiting.

Question 2

Anatomy (p.3-5)

• The stomach is located/
  
  • fundus and body
  • antrum
• Its maximal volume capacity is/
  
  • at rest, it typically contains/
• divided into four anatomic regions

Answer 2

• The stomach is located in the upper- to mid-abdomen,
  
  • fundus and body being largely underneath the lower left rib-cage
  • antrum swinging toward the epigastrium and right upper quadrant.
• Its maximal volume capacity is 1.5 to 2 liters,
  
  • at rest, it typically contains only about 200 ml.
• divided into four anatomic regions .
  
  • Cardia: Adjacent to GE junction
  • Fundus: Cephalad to GE junction
  • Corpus (Body): Lower limit of fundus to incisura
  • Antrum: Incisura to pylorus
• The microscopic anatomy
  
  • The mucosa is the innermost layer
  • followed by a submucosal area containing intrinsic neurons.
  • The muscularis propria has two dominant muscle layers (circular and longitudinal),
  • sandwiched in between are the enteric neurons of the myenteric plexus.

Question 3

Anatomy (p.5)

• glands and pits
• The pit-to-gland depth ratio
• the mucosa around the cardia produces/
• The proximal stomach gastric mucosa (oxyntic)
  
  • has/
  • enteroendocrine (or enterochromaffin-like) cells
• In the distal stomach (antrum & pylorus)/
  
  • many of the enteroendocrine cells/
  • The gastric mucosa also contains/

Answer 3

• In the gastric mucosa, secretory cells are arranged in groups, called glands, which empty into invaginations of the mucous cells called pits.
• The pit-to-gland depth ratio is higher in the fundus and corpus (1:4) than in the antrum (1:1).
• the mucosa around the cardia produces mucous and acid.
• The proximal stomach gastric mucosa (oxyntic)
  
  • has
    
    • mucous cells which produce mucous
    • parietal cells which produce acid and intrinsic factor
    • chief cells which produce pepsinogen I
  • few enteroendocrine (or enterochromaffin-like) cells are seen, most of which produce somatostatin or biogenic amines, such as histamine and serotonin.
• In the distal stomach (antrum & pylorus), no parietal cells are found, and the number of enteroendocrine cells increases.
  
  • many of the enteroendocrine cells produce the biogenic amine and peptides (G-cells – gastrin; D-cells – somatostatin).
  • The gastric mucosa also contains rare inflammatory cells including mast cells.

Question 4

Blood Supply (p.6)

• blood supply
• the schematic
  
  • Lesser curve
  • Greater curve
  • Fundus
• venous drainage
  
  • ultimately to/
  • in portal hypertension
• porto-systemic shunting
  
  • leads to/
  • When the porto-systemic pressure gradient exceeds 12mmHg, they may be prone to/
  • The typical pathways are from/
  • The short gastric veins/

Answer 4

• Branches of the celiac artery provide blood supply.
  
  • They anastomose and overlap redundantly, making gastric ischemia less likely.
• the schematic
  
  • Lesser curve: left and right gastric arteries
  • Greater curve: left and right gastroepiploic arteries
  • Fundus: short gastric arteries (branches of splenic artery)
• venous drainage
  
  • ultimately to the portal vein,
  • connections to the systemic venous system can occur in portal hypertension.
• porto-systemic shunting
  
  • leads to dilation of these thin-walled vessels, varices, which may occur in the esophagus or fundus.
  • When the porto-systemic pressure gradient exceeds 12mmHg, they may be prone to bleeding which is generally associated with significant disorders of the liver of portal venous system.
  • The typical pathways are from the left gastric vein to esophageal veins (esophageal varices).
  • The short gastric veins drain fundus and superior greater curve and may form gastric varices.

Question 5

Innervation (p.7)

• the stomach contains
  
  • intrinsic
  • extrinsic
• parasympathetic vs. sympathetic
  
  • The parasympathetic nerves arise from/
  • sympathetic fibers originate in/
• left vs. right vagus
  
  • The left vagus innervates/
  • the right vagus innervates/
• vagal fibers
  
  • The majority of vagal fibers (90 %)
    
    • are/
    • provide/
    • play a role in/
  • Only 10%
    
    • are/
    • control/modulate/
• sympathetic efferents
  
  • are/
  • innervation

Answer 5

• the stomach contains
  
  • an intrinsic network of nerves that regulates patterns of motor and secretomotor activity (myenteric and submucosal plexus)
  • dual extrinsic innervation.
• parasympathetic vs. sympathetic
  
  • The parasympathetic nerves arise from the vagal trunks,
  • sympathetic fibers originate in the celiac plexus.
• left vs. right vagus
  
  • The left vagus innervates the anterior stomach
  • the right vagus innervates the posterior stomach.
• vagal fibers
  
  • The majority of vagal fibers (90 %)
    
    • are visceral afferents
    • provide information for the regulation of autonomic function.
    • play a role in some of your ‘gut feelings’, such as nausea or bloating.
  • Only 10%
    
    • are visceral efferents
    • control/modulate motility and secretion, by forming synapses with neurons in the myenteric or submucosal plexus.
• sympathetic efferents
  
  • are postganglionic
  • directly innervate their targets, such as blood vessels or muscle.

Question 6

Secretory Physiology (p.10-13)

• Acid
• Gastric acid performs many functions, including/
• Gastric HCl is secreted by/
• The ultimate acidity of gastric secretions depends on/

Answer 6

• Acid
  
  • a main product of gastric secretion
  • important in physiology and in disease states.
• Gastric acid performs many functions, including:
  
  • killing ingested microorganisms
  • activating the gastric proenzymes pepsinogen I and II to the protease pepsin
  • facilitating the absorption of iron and calcium.
• Gastric HCl is secreted by the parietal cell at a concentration of 160 mmol/L and a pH of less than 1.
• The ultimate acidity of gastric secretions depends on the volume to which the parietal cell acid is diluted in the non-parietal gastric secretions including water, mucus, and bicarbonate.

Question 7

Secretory Physiology:
Secretion of HCl by the parietal cell is stimulated by three mechanisms (p.14-15)

• Neurocrine stimulation:
• Endocrine stimulation
• Paracrine stimulation

Answer 7

• Neurocrine stimulation: acetylcholine (ACh)
  
  • binds to muscarinic receptors (M3 subtype) on the parietal cell membrane.
  • released by the nerve endings of the vagus nerve,
  • This mechanism is already activated by smell, mastication or even only thought about food (‘cephalic phase’).
• Endocrine stimulation: the peptide hormone gastrin
  
  • inhibits somatostatin release by D cells, thereby ‘releasing’ a break that limits acid secretion.
  • binds to a CCK receptor (CCK2 subtype)
    
    • on parietal cells, where it directly stimulates acid secretion,
    • on enteroendocrine cells, where it indirectly activates acid secretion through histamine release
  • released by the G-cells of the antrum into the systemic circulation,
• Paracrine stimulation: histamine
  
  • binds to the type 2 histamine receptor (H2 receptor) on the parietal cell to increase HCl secretion.
  • released by ECL cells into the surrounding gastric mucosal milieu or the local circulation,

Question 8

Secretory Physiology (p.15)

• Gastrin and ACh mediate their direct parietal cell stimulating effects through/
• Histamine acts by/
• Gastrin release by the G-cell is itself controlled by at least 5 mechanisms

Answer 8

• Gastrin and ACh mediate their direct parietal cell stimulating effects through the generation of inositol trisphosphate (PIP2), which then mobilizes intracellular Ca2+, upregulating protein kinases that in turn activate the H+/K+ ATPase (“proton pump”).
• Histamine acts by the induction of stimulatory G-proteins, which activate adenylate cyclase, resulting in conversion of ATP to cAMP, thereby also upregulating protein kinases that in turn activate the H+/K+ ATPase.
  
  • All lead to carriage of H+ across the parietal cell membrane from the cytosol to the gastric lumen.
• Gastrin release by the G-cell is itself controlled by at least 5 mechanisms:
  
  • ACh: Neurocrine stimulation via the vagus nerve
  • Gastrin Releasing Peptide (GRP): Neurocrine stimulation via the vagus nerve
  • Somatostatin: Paracrine inhibition via diffusion through the tissue milieu and local circulation
  • Luminal acid: Feedback inhibition of the G-cell
  • Luminal food and amino acids: Stimulation of the G-cell

Question 9

Secretory Physiology:
Secretion of HCl by the parietal cell is inhibited by at least two mechanisms

• Somatostatin released from/
  
  • inhibits acid secretion directly by/
  • inhibits acid secretion indirectly by/
• Prostaglandins

Answer 9

• Somatostatin released from the D-cell of the antrum
  
  • inhibits acid secretion directly by binding to the somatostatin receptor site on the parietal cell membrane , an inhibitory G-protein receptor, that in turn, down-regulates adenylate cyclase, decreasing conversion of ATP to cAMP, thus down-regulating protein kinase activation and therefore decreasing activation of the H+/K+ ATPase.
  • inhibits acid secretion indirectly by binding to the somatostatin receptor site on the G-cell and inhibiting the release of gastrin from the G-cell.
    
    • the D-cell is stimulated, by the acid in the gastric lumen, to secrete somatostatin in a negative-feedback fashion.
• Prostaglandins bind to prostaglandin receptor sites on the parietal cell membrane, inducing the production of inhibitory G-proteins in a fashion similar to that of somatostatin, and thereby inducing the same inhibitory cascade leading to down-regulation of H+/K+ ATPase.

Question 10

Secretory Physiology:
Secretion of intrinsic factor (IF)

• Secretion of intrinsic factor (IF)
  
  • ?
  • important in/
• Loss of parietal cells
  
  • results in a lack of intrinsic factor, which in turn causes/
    
    • leads to/
    • results in/
  • patients with a loss of parietal cells also have a high gastric pH
    
    • This will activate/
    • The persistent stimulation of these cells eventually leads to/

Answer 10

• Secretion of intrinsic factor (IF)
  
  • another secretory function of the parietal cell.
  • important in the binding of dietary vitamin B12 and its preservation throughout gut transit such that it is intact for ileal absorption.
• Loss of parietal cells
  
  • results in a lack of intrinsic factor, which in turn causes vitamin B12 malabsorption (lack of vitamin B12)
    
    • leads to a macrocytic anemia called pernicious anemia.
    • results in large cells that cannot produce sufficient DNA to accommodate cell division, so the RBCs become very large and diminish in number.
  • patients with a loss of parietal cells also have a high gastric pH.
    
    • This will activate gastrin-producing cells in the antrum.
    • The persistent stimulation of these cells eventually leads to hypertrophy and hyperplasia, and may result in carcinoids, a rare, endocrine tumor.

Question 11

Inhibition of Acid Secretion (p.17-20)

• the acidity of gastric secretions
  
  • important for/
  • can lead to/
• The oldest approach (antacids)/
  
  • work in/
  • the effects are/
  • Vagally mediated acid secretion requires/
  • these agents do not have clinical utility due to/
• The surgical alternative, vagotomy

Answer 11

• the acidity of gastric secretions
  
  • important for the normal digestive process,
  • can lead to mucosal injury and contributes to symptoms in patients with diseases of the proximal GI tract.
• The oldest approach (antacids) utilizes the neutralizing power of weak bases, such as sodium bicarbonate
  
  • work in alleviating symptoms,
  • the effects are short-lived and often not sufficient to induce healing of acid-induced injury.
  • Vagally mediated acid secretion requires activation of muscarinic receptors, which can be blocked by atropine or agents with specificity for the receptor subtype.
  • these agents do not have clinical utility due to adverse effects (e.g. dry mouth, tachycardia) and limited benefit.
• The surgical alternative, vagotomy,
  
  • common treatment for patients with refractory ulcers.
  • the introduction of more effective medical therapy has eliminated the use of this operation.

Question 12

Inhibition of Acid Secretion (p.17-20)

• An alternative surgical approach, distal gastric resection
• histamine-2 receptor blockers
• more potent acid-suppressive medications (proton pump inhibitors, PPI)
  
  • block/
  • the significant decrease in acid secretion constitutes a stimulus for/
  • seen in some patients
  • there has not yet been a significant increase in/

Answer 12

• An alternative surgical approach, distal gastric resection,
  
  • tried to decrease the number of acid-producing cells
  • primarily tried to eliminate the gastrin-producing cells in the distal stomach.
  • rarely performed nowadays.
• histamine-2 receptor blockers
  
  • revolutionized the treatment of gastroesophageal disorders
  • eliminated the need for operations in patients with benign disorders of the stomach.
• more potent acid-suppressive medications (proton pump inhibitors, PPI)
  
  • block the final pathway, generally by covalently modifying the protein and thus rendering it dysfunctional
  • the significant decrease in acid secretion constitutes a stimulus for G-cells.
    
    • gastrin levels often increase to more than 100 pg/dl.
  • hypertrophy and even micronodular hyperplasia can be seen in some patients.
  • there has not yet been a significant increase in carcinoids, endocrine active tumors that can indeed produce gastrin

Question 13

Gastric Motility (p.22-23)

• Gastric motility
  
  • can be thought of in terms of/
  • The anatomically defined regions/
• Gastric filling
  
  • facilitated by/
  • This vagally-mediated receptive relaxation allows the stomach to/
  • In addition to vagal (= cephalic) influences on gastric tone, locally mediated reflexes that lead to adaptation/
  • In healthy persons, the gastric volume can/

Answer 13

• Gastric motility
  
  • can be thought of in terms of filling / storage, mixing / trituration, and emptying.
  • The anatomically defined regions do not fully overlap with the functionally distinct areas, yet they play a different role in this process.
• Gastric filling
  
  • facilitated by relaxation of the proximal stomach, which occurs with swallowing.
  • This vagally-mediated receptive relaxation allows the stomach to act as a reservoir for food without increasing the intragastric pressure (which would lead to reflux or regurgitation).
  • In addition to vagal (= cephalic) influences on gastric tone, locally mediated reflexes that lead to adaptation are the gastric pressure increases, and paracrine factors secreted in the duodenum.
  • In healthy persons, the gastric volume can increase by a factor of 10 or more before symptoms (fullness, bloating or nausea) arise.

Question 14

Gastric Motility:
Mixing (p.23+25-26)

• Mixing occurs/
• The bases for these contractions are/
  
  • These electrical phenomena can actually be recorded from/
• Acetylcholine
  
  • released by/
  • changes/
  • triggers/
  • the surface recordings reflect this as/
• calcium channel blockers are commonly used to treat/

Answer 14

• Mixing occurs in the corpus and antrum, where mixing of solid food with gastric secretions and trituration of solids to 1mm particles is facilitated by powerful contraction that cause a retropulsive jet stream, leading to gradual disintegration of food particles.
• The bases for these contractions are spontaneously generated depolarizations (slow waves) that migrate from a pacemaker area in the fundus distally toward the pylorus.
  
  • These electrical phenomena can actually be recorded from the abdominal surface (electrogastrogram).
• Acetylcholine,
  
  • released by vagal stimulation of enteric motor neurons
  • changes the amplitude of these slow waves
  • triggers action potentials and allows calcium influx through L-type calcium channels, which causes smooth muscle contraction.
  • the surface recordings reflect this as an increase in amplitude of slow electrical oscillations.
• calcium channel blockers are commonly used to treat hypertension or cardiac diseases.
  
  • Similarly, many drugs have anticholinergic effects (e.g. tricyclics).
  • The resulting changes in slow wave activity may explain their impact on gastrointestinal function.

Question 15

Gastric Motility (p.27-28)

• Liquid emptying
  
  • occurs/
  • facilitated by/
• Solid emptying is more complex and occurs in two phases
  
  • Solid food which has been triturated by antral contractions to particles 1mm or smaller in diameter/
    
    • Thus, there is a lag/
  • Larger particles/
    
    • These interdigestive migrating motor complexes (sometimes referred to as IMMC, MMC, or IMC)/

Answer 15

• Liquid emptying
  
  • occurs rapidly
  • facilitated by a tonic pressure gradient from the proximal stomach to the duodenum.
• Solid emptying is more complex and occurs in two phases.
  
  • Solid food which has been triturated by antral contractions to particles 1mm or smaller in diameter are sieved through the pyloric sphincter into the duodenal bulb.
    
    • Thus, there is a lag followed by a gradual emptying.
  • Larger particles are intermittently emptied through an open pylorus during the fasting state by strong, wave-like 3-10 minute long contractions that sweep the entire upper GI tract from the stomach through the small bowel.
    
    • These interdigestive migrating motor complexes (sometimes referred to as IMMC, MMC, or IMC) occur every 1.5 to 2 hours and have been dubbed the “intestinal housekeeper” because they clear the upper gut of inadequately triturable, poorly digestible, or fibrous matter.

Question 16

Survey of Clinical Disorders, Diagnosis, and Treatment:
Gastric disorders may be symptomatic or asymptomatic (p.29-33)

• gastric disorders which are symptomatic
  
  • tend to present with/
  • The typical symptoms include/
  • Signs of gastric disorders are typically few and non-specific but may include/
  • The term dyspepsia suggests/
    
    • Symptoms are located in and associated with/
  • The differential diagnosis for dyspeptic symptoms is extensive
    
    • diagnostic studies/
    • Endoscopy/
    • Upper gastrointestinal x-ray series/
• gastric disorders may cause few or no symptoms
  
  • especially/
  • the most important example
  • These often first truly manifest with a complication, such as/

Answer 16

• gastric disorders which are symptomatic
  
  • tend to present with discomfort which is primarily epigastric or left-upper abdominal quadrant (LUQ) in location.
  • The typical symptoms include pain (achy, crampy, sharp, or burning), bloating (a sensation of gaseous distention), distention, early satiety, anorexia, nausea, or vomiting.
  • Signs of gastric disorders are typically few and non-specific but may include tenderness, palpable mass, succussion splash, diminished bowel sounds, increased pitch of bowel sounds, or distention (as a sign)
  • The term dyspepsia suggests postprandial discomfort which is epigastric or LUQ in distribution.
    
    • Symptoms are located in the upper abdomen and associated with food intake
  • The differential diagnosis for dyspeptic symptoms is extensive.
    
    • diagnostic studies are often needed to identify the underlying cause.
    • Endoscopy is the tool of choice to evaluate possible gastric abnormalities.
    • Upper gastrointestinal x-ray series can still be helpful, especially if one wants to clearly define anatomic abnormalities.
• gastric disorders may cause few or no symptoms,
  
  • especially early in the course of their development.
  • the most important example is complicated ulcers due to aspirin or non-steroidal anti-inflammatory drugs.
  • These often first truly manifest with a complication, such as bleeding or perforation, without prior warning symptoms.

Question 17

Abnormal Anatomy:
Congenital (p.35-36)

• Congenital outlet obstruction
  
  • can be inherited as/
  • attributed to/
• Infants
  
  • manifest by/
  • typically need

Answer 17

• Congenital outlet obstruction
  
  • can be inherited as hypertrophic pyloric stenosis in infants,
  • attributed to a loss of inhibitory (nitric oxide) neurons in the pylorus.
• Infants
  
  • manifest by projectile vomiting
  • typically need to undergo surgery, if the diagnosis is confirmed (ultrasound or barium swallow).

Question 18

Abnormal Anatomy:
Acquired (p.37-39)

• hiatal hernia.
• gastric outlet obstruction
  
  • In adults, this is typically due to/
  • It is important to consider malignancies, which may/
  • While some patients require
• Gastric volvulus
  
  • frequency
  • can present
    
    • acutely due to/
    • chronically with/
  • gastric volvulus can be differentiated into /
    
    • Both can occur/
  • predisposing factors
  • treatment of choice

Answer 18

• The most common anatomical abnormality involving the stomach is the hiatal hernia.
• The second most common anatomical abnormality is gastric outlet obstruction.
  
  • In adults, this is typically due to stricture formation in patients with recurrent ulcers.
  • It is important to consider malignancies, which may similarly obstruct the pyloric channel.
  • While some patients require surgery, endoscopic therapy with dilation is possible.
• Gastric volvulus
  
  • rare condition
  • can present
    
    • acutely due to obstruction or compromise of gastric blood supply
    • chronically with vague symptoms, such as epigastric discomfort or dysphagia.
  • Depending on the direction of the torsion, gastric volvulus can be differentiated into organoaxial and mesenteroaxial form.
    
    • Both can occur from childhood to late adult life with the maximal incidence around 50 years of age.
  • Trauma, large hiatal hernias and prior surgery involving the esophageal hiatus are predisposing factors.
  • Surgery is the treatment of choice.