Stomach Physiology and Pathology (Week 11) Flashcards
True or False: The stomach is a J-shaped enlargement directly inferior to the diaphragm and is the most distensible part of the GI tract
True
What are the functions of the stomach?
1) serves as a reservoir for food before release into small intestine
2) mixes saliva, food, and gastric juice to form chyme
What are the two sphincters of the stomach?
1) lower esophageal
2) pyloric
True or False: The lower esophageal sphincter separates the esophagus and the stomach
True
What is the main arterial supply of the stomach?
celiac trunk of the aorta
What are the 4 arteries that supply the stomach?
1) hepatic artery –> right gastric artery
2) hepatic artery –> right gastro-omental artery
3) celiac trunk –> left gastric artery
4) splenic artery –> left gastro-omental artery
What veins does the stomach drain into?
1) hepatic portal vein
2). superior mesenteric vein
Note: the veins run parallel with the arteries
The left gastric vein and right gastric vein drain into the ______________
hepatic portal vein
The left gastro-omental vein and right gastro-omental vein drain into the __________________
superior mesenteric vein
What is the parasympathetic innervation of the stomach?
anterior and posterior vagal trunks from vagus nerve
What is the sympathetic innervation of the stomach?
- from T5-T9 segments of sympathetic trunk
- passes to celiac plexus via greater splanchnic nerve
What are the three layers of stomach mucosa?
1) epithelium (on the surface)
2) lamina propria
3) muscularis mucosae
In which mucosal layer of the stomach would you find loose connective tissue, smooth muscle, and lymphoid cells?
lamina propria
Which mucosal layer of the stomach is organized into three layers: inner circular, outer longitudinal, outermost circular?
muscularis mucosae
Note: this is NOT talking about the muscularis externa which has an oblique layer, circular layer, and longitudinal layer
The epithelium and lamina propria are arranged into glands. What are the three regions of these glands?
1) gastric pit
2) neck (isthmus)
3) base
Note: there are different cell types that are found in different regions of the glands
Note: different regions of the stomach have different glands
What type of cells are found in the surface epithelium and gastric pits?
simple columnar cells
Note:
- lines the surface of the stomach and gastric pits
- lots of mucin granules in apical surface (apical = means side of the lumen; mucin = large glycoprotein that lubricates)
- short microvilli also at the apical surface
What type of cells are found in the neck/isthmus?
simple columnar cells
Note:
- usually interspersed between parietal cells (parietal cells make HCl)
- shorter and contain LESS mucin granules in apical surface
What type of cells are in both the neck & base?
parietal cells (oxyntic)
Note:
- mainly in upper half of gastric gland
- rounded/pyrimidal shape
- tubulovesicular structures in apical region; rearrange to form lumen canaliculi when active
- function = to produce HCl and IF (IF = intrinsic factor; helps us absorb B12)
What type of cells are found in the base?
chief cells (zymogenic)
Note:
- found in lower regions of gastric glands
- have abundant RER for synthesizing proteins
- contain granules that contain pepsinogen (in the presence of acid breaks down to give pepsin; pepsin is used to break down protein)
- function = pepsinogen secretion
What type of glands/enteroendocrine cells are found deep within the gastric pits?
- enterochromaffin-like cells (secrete histamine)
- G-cells (secrete gastrin)
- D cells (secrete somatostatin)
The ____________ of the stomach contains dense, irregular connective tissue and a rich vascular and lymphatic network draining the lamina propria
submucosa
What are the three layers of the muscularis externa?
1) inner oblique
2) middle circular
3) outermost longitudinal
Underneath the muscularis externa is the ___________
serosa
What are four stages of stomach motility?
1) food entry into stomach
2) storage in fundus
3) mixing (aka churning)
4) emptying into small intestine
The _________________ controls movement of food into the stomach and prevents reflux of gastric contents into the esophagus
lower esophageal sphincter
How is the resting tone of the lower esophageal sphincter maintained?
via intrinsic myogenic properties of sphincter muscles & cholinergic regulation
Note: relaxation is required to allow entry of food into the stomach
Recall: cholinergic = parasympathetic
Food entry into the stomach is initiated by a vasovagal reflex called _________________
receptive relaxation
Note: this reflex is triggered by swallowing and esophageal distension
Following receptive relaxation, then a wave of _______________ from the esophagus approaches the stomach and pushes food into the stomach
peristalsis
The presence of food in the stomach stretches the stomach wall, reducing the tone of the wall. This is known as what?
gastric accomodation
How much volume can a completely relaxed stomach hold?
0.8-1.5L
When waves that start in the middle to upper portion of the stomach move the bolus toward the pyloric antrum
propulsion
contractions in the pyloric antrum that grinds the food bolus
grinding
When antral stomach contents are pushed back upstream toward the body of the stomach due to contents being forced into the very small opening of the pylorus
retropulsion
True or False: Only liquid can leave the stomach via the pyloric sphincter. If particles are greater than 2mm in size, mixing continues
True
the movement of liquid chyme from the stomach into the small intestine
gastric emptying
The rate of gastric emptying is governed by signals from the ____________________
stomach and duodenum
Note: this ensures pH inside the duodenum does not become too acidic (too acidic = can cause damage/ulcers) + ensures travel time is slow enough for nutrient absorption
Gastric acid is released from __________ cells
parietal
What is the pH of gastric acid?
pH 1-2
What is gastric acid composed of?
- hydrochloric acid (HCl) *
- large amounts of KCl
- small amounts of NaCl
What is the function of gastric acid?
- digestion of protein (denatures them)
- bacteriostatic (prevents growth but doesn’t kill them)
- conversion of pepsinogen to pepsin
What enzyme facilitates the conversion of CO2 and OH- to bicarbonate ions?
carbonic anhydrase
How does H+ get into the lumen of the canaliculus?
H+/K+ ATPase
How does Cl- get into the lumen of the canaliculus?
passive transport from cytoplasm of parietal cell into lumen
H+/K+ ATPase is blocked by what type of drug?
proton pump inhibitors (PPI)
Note: this would lower acidity in the stomach, since we block the transport of H+ ions into the lumen
What can stimulate parietal cells?
- acetylcholine
- gastrin
- histamine
Note: all of these promote acid production (more H+ ions being pumped into the lumen)
Acetylcholine acts on what type of receptor in the stomach?
muscarinic receptors
Gastrin acts on what type of receptor in the stomach?
CCK2 receptors
Histamine acts on what type of receptor in the stomach?
H2 receptors
function of histamine in stomach
- stimulates release of gastric acid
- stimulates vasodilation
What drug works by blocking the H2 receptor?
H2 receptor antagonists
Note: usually used for GERD; result = decreased acid production in stomach
Gastrin is secreted in response to what?
- stomach distension
- vagal stimulation
- presence of partially digested proteins (peptides and amino acids)
function of gastrin in the stomach
- acts on ECL cells (ECL cells release histamine) to stimulate the release of histamine –> leads to increased gastric acid
- directly stimulates parietal cells
What can inhibit parietal cells, thereby reducing acid production?
- somatostatin
- prostaglandins
function of somatostatin
- act on parietal cells to reduce secretion of gastric acid
- reduce release of gastrin, secretin, and histamine
- suppresses release of pancreatic hormones
What is somatostatin secreted in response to?
luminal H+
Note: this is negative feedback
True or False: Gastric acid is substantially lower after meals and high between meals
False.
Gastric acid is substantially HIGHER after meals and LOW between meals
What are the phases of gastric acid secretion after meals?
1) cephalic
2) gastric
3) intestinal
What is the cephalic stage of gastric acid secretion triggered by?
smell, sight, taste, thought, and swallowing food
The cephalic stage is mediated by what nerve?
vagus nerve
The vagus nerve releases ____________
acetylcholine (Ach)
REVIEW: Ach acts directly on ___________ cells to release H+ ions
parietal
REVIEW: Ach acts on _____________ cells to release histamine
ECL
REVIEW: Ach acts on _____________ cells, inhibiting the release of somatostatin
D cells
The vagus nerve releases gastrin-releasing peptide (GRP) to induce the release of _________ from G cells
gastrin
The cephalic stage accounts for _____ % of gastric acid secretion
30%
During the gastric phase of gastric acid secretion, food enters the stomach, distending the gastric mucosa and activates the _______________
vasovagal reflex & local ENS reflex
During the gastric phase of gastric acid secretion, partially digested proteins stimulate G cells to produce ___________
gastrin
Note: carbs nor lipids participate in gastric acid secretion, BUT components of wine, beer, and coffee CAN promote gastric secretion by stimulating G cells (these same three things can trigger GERD)
Low luminal pH stimulates D cells to secrete _________, which INHIBITS gastrin production
Note: this is negative feedback
somatostatin
The gastric phase accounts for _____ % of gastric acid secretion
50-60%
In the intestinal phase of gastric acid secretion, we have the presence of amino acids and partially digested peptides in the proximal intestine, that stimulates G cells in the duodenum to secrete __________
gastrin
The intestinal phase accounts for _____ % of gastric acid secretion
5-10%
Intrinsic factor is a ___________ secreted by parietal cells
glycoprotein
What is the function of intrinsic factor?
required for the absorption of vitamin B12 in the ileum (last part of the small intestine)
Pepsinogen is secreted by chief cells via ___________
exocytosis
Pepsinogen is spontaneously cleaved into __________ in the presence of HCl
active pepsin
What is the function of pepsin?
digestion of protein (via hydrolysis of the peptide bond)
Note: function of pepsin is dependent on low pH (optimal = 1.8-3.5)
Secretion of pepsinogen is stimulated by what?
1) Ach release from vagus nerve or enteric nervous system (ENS), whereby Ach binds to M receptors on chief cells
2) presence of acid in the duodenum triggers secretin from S cells; secretin also stimulates chief cells to release more pepsinogen
How is the stomach able to withstand the low pH and high pepsin levels?
Gastric diffusion barrier
- mucus gel layer on surface epithelium
- bicarbonate microclimate adjacent to surface epithelial
- tight junctions in gastric glands
What does mucus combine with to form the mucus gel layer on the epithelium?
- phospholipids
- water
- electrolytes
What does the mucus gel layer on the surface epithelium protect against?
- acid
- pepsin
- bile acid
- ethanol
- also minimizes abrasions from food
Mucin secretion is induced by what?
1) vagal stimulation
2) chemical irritation
True or False: Surface epithelial cells secrete HCO3, which remains trapped in the mucus gel layer.
True
________ can neutralize most acid that diffuses through the mucosal layer and inactivate any pepsin that penetrates the mucus
HCO3-
What is HCO3- secretion induced by?
1) vagal stimulation
2) PGE2 (prostaglandin E2)
3) intraluminal pH
inflammation of stomach mucosa
gastritis
Note: may be acute or chronic
damage is limited to the gastric mucosa (e.g., does not penetrate beyond the lamina propria)
gastric erosiion
damage extends beyond lamina propria
peptic ulcer
loss of gastric glandular cells
gastric atrophy
gastric mucosal inflammation caused by an imbalance between protective factors and secretion of acid and pepsin
acute gastritis
Note: ranges in severity (can be asymptomatic and discovered incidentally or can cause catastrophic blood loss, anemia, or peritonitis
What is the etiology of acute gastritis?
- NSAID toxicity
- alcohol
- bile
- shock/sepsis
- intracranial lesions
- H. pylori
Note: H. pylori more closely linked to chronic gastritis
How can NSAIDs contribute to the development of acute gastritis?
Inhibits prostaglandins
Recall: What is the role of prostaglandins on gastric acid secretion? –> Prostaglandins REDUCE acid secretion (therefore inhibiting = indirectly increasing acid secretion in the stomach)
Additionally, prostaglandins (i.e., PGE2) promote bicarbonate secretion, so inhibiting prostaglandins = your protective layer is diminished
Note: this effect is more significant for nonselective inhibitors (aspirin, ibuprofen, and naproxen); but can also occur with selective COX-1 inhibitors (celecoxib)
How can alcohol consumption contribute to the development of acute gastritis?
causes direct cellular damage
How can intracranial lesions contribute to the development of acute gastritis?
thought to stimulate the parasympathetic nervous system
True or False: Acute gastritis usually starts with mild inflammation and progresses to active inflammation
True
What is the difference between mild inflammation and active inflammation in acute gastritis?
Mild inflammation:
- lamina propria shows moderate edema and slight vascular congestion
- surface epithelium intact with scattered neutrophils
Active inflammation:
- lots of neutrophils found above the basement membrane in direct contact with epithelial cells
True or False: In severe cases of acute gastritis, mucosal damage may progress to erosions and bleeding
True
acute erosive hemorrhagic gastritis = erosion + __________
bleeding
erosion = loss of superficial epithelium (damage does not penetrate ___________)
the lamina propria
What are the clinical features of acute gastritis?
May be asymptomatic, but often includes:
- dyspepsia (upset stomach/discomfort; very common)
- nausea
- vomiting
- loss of appetite
- belching
- bloating
- acute abdominal pain
What are some complications to be aware of regarding acute gastritis?
- perforation (leading to peritonitis = medical emergency**)
- bleeding
- chronic gastritis
True or False: Chronic gastritis is one of the most common GI disorders
True-ish
Note: However, recent research shows that it’s not AS common as we thought; Canadian guidelines have yet to be updated… so many people who “have chronic gastritis” actually don’t
What is the most common cause of chronic gastritis?
H. pylori
Note: prevalence in Canada = 20-30%
Other causes:
- pernicuous anemia, Crohn’s disease, radiation toxicity, amyloidosis
gram negative motile curved rod bacteria that lives in the mucous layer
H. pylori
What is the most commonly infected site in chronic gastritis?
stomach antrum
Note: can progress to gastric body or fundus
What are the two main types of chronic gastritis?
1) non-atrophic
2) atrophic
Which type of chronic gastritis is characterized by inflammation WITHOUT loss of gastric glandular cells and is caused by H. pylori?
non-atrophic
Which type of chronic gastritis is characterized by a loss of gastric glandular cells (replaced by intestinal epithelium, pyloric-type glands, and fibrous tissue), is associated with the development of gastric carcinoma, and is caused by H. pylori and autoimmunity?
atrophic
Summarize the pathogenesis of chronic H. pylori gastritis
Overall mechanisms are poorly understood…
- virulence factors allow for survival of bacteria in the stomach (e.g., have a flagella allowing them to be motile, they produce ammonia that’s toxic to our epithelial cells + increasing alkalinity for themselves, they produce adhesins allowing for better adhesion to epithelial cells, and release toxins linked to the development of malignancy)
- elicit a robust inflammatory response (neutrophils, plasma cells, lymphocytes)
- bacteria seem to reduce mucous and bicarbonate secretion, and increase gastric acid secretion
What are the clinical features of chronic H. pylori gastritis?
May be asymptomatic but can cause:
- epigastric pain
- nausea
- vomiting
- anorexia (from eating tiny amounts)
- early satiety
- weight loss
How do you diagnose chronic H. pylori gastritis?
- presence of antibodies to H. pylori in serum (note: least reliable because these antibodies can last for a very very long time)
- fecal bacteria detection
- urea breath test (GOLD STANDARD)
What are some complications to be aware of for chronic H. pylori gastritis?
- PUD (peptic ulcer disease)
- gastric adenocarcinoma
- MALT lymphoma
What is the treatment for chronic H. pylori gastritis?
-triple therapy (two antibiotics + PPI)
Note: eradication of bacteria tends to cure the disease
Note: when it gets to the point of gastritis, often natural treatments are not enough; however, natural remedies + the triple therapy = improves outcomes/one round of triple therapy seems to be enough
REVIEW: Change of one differentiated cell type to another is called what?
metaplasia
Atrophic gastritis is associated with increased risk of __________
gastric adenocarcinoma
Overgrowth of MALT associated with H. pylori may be associated with ___________
Recall: MALT = mucosal associated lymphoid tissue (e.g., Peyer’s patches, tonsils, etc.)
gastric lymphoma
What are the two main types of peptic ulcer disease (PUD)?
1) duodenal (4x more common)
2) gastric
True or False: Duodenal PUD has a higher likelihood of perforation and malignancy compared to gastric PUD
False
Duodenal PUD = lower likelihood of perforation and malignancy
Gastric PUD = 4% are malignant + higher likelihood of perforation
What are some of the causes of peptic ulcer disease (PUD)?
- H. pylori infection (most common)
- NSAIDs
- cigarette smoking
True or False: PUD is a complication of chronic gastritis
True
Summarize the pathogenesis of peptic ulcer disease (PUD)
- occurs due to an imbalance between defense mechanisms and damaging factors causing chronic gastritis (aka develops as a result of chronic gastritis)
- duodenal ulcers and antral gastric ulcers not well understood but linked to H. pylori colonization leading to decreased bicarbonate secretion in duodenum and increased gastric acid secretion in the stomach
- gastric ulcers in the fundus or body = caused by mucosal atrophy, slightly higher acid secretion, and greatly decreased mucin production + other protective factors
What do peptic ulcers look like?
- round to oval shaped, sharply punched-out defect
- granulation tissue below fibrous scar
- larger vessels within scarred area that are thickened and thrombosed
What are the clinical features of peptic ulcer disease?
- vague, sometimes intense pain sometimes with meals
- duodenal ulcers = BETTER with food, but worsened 2-3 hours after eating
- duodenal ulcers commonly awaken patients at night
- gastric ulcers = pain shortly after meal
- gastric ulcers = weight loss is common
may also present with:
- iron-deficient anemia, bleeding, nausea/vomiting, bloating, belching
How do you treat peptic ulcer disease?
- withdraw offending agent
- eradicate H. pylori infection
What are some complications that can occur with peptic ulcer disease?
- performation that can lead to peritonitis (medical emergency)
- bleeding
- gastric adenocardinoma
- MALT lymphoma
