9 Stomach: Physiology and Disease 1 Flashcards Preview

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Flashcards in 9 Stomach: Physiology and Disease 1 Deck (18):
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/

  • 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.

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

  • 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.

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/

  • 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.

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/

  • 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.

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

  • 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.

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/

  • 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.

7

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

  • Neurocrine stimulation:
  • Endocrine stimulation
  • Paracrine stimulation

  • Neurocrine stimulationacetylcholine (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,

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

  • 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

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

  • 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.

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/

  • 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.

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

  • 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.

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/

  • 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

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/

  • 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.

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/

  • 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.

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)/

  • 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.

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/

  • 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.

17

Abnormal Anatomy:
Congenital (p.35-36)

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

  • 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).

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

  • 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.