2 Histology of the GI tract: Esophagus and Stomach

Question 1

General design:
The tubular portion of the gastrointestinal tract is organized into four general layers (p.2)

Answer 1

• the mucosa,
• the submucosa,
• the muscularis externa,
• a serosa

Question 2

Mucosa (p.2)

• The mucosa/
• Epithelial lining functions
• Lamina Propria
• Muscularis mucosa
• All three layers of the mucosa/

Answer 2

• The mucosa lines the inner luminal surface of the gut tube
• Epithelial lining functions
  
  • Protection - ex: The stratified squamous epithelia in the esophagus and anus provide protection from friction.
  • Secretion - ex: The mucous surface cells and enzyme producing pits in the stomach, and individual goblet cells in the large and small intestines all release secretions.
  • Absorption - ex: Villi and microvilli augment the surface area of the simple columnar small intestinal epithelium for absorption.
  • Accessory gland ducts - ducts are outgrowths from the epithelial lining to develop and connect to the salivary glands, liver and pancreas.
  • can be folded into the lumen as villi, or into the connective tissue below as crypts and glands
• Lamina Propria
  
  • connective tissue layer
  • supports the epithelium both physically and biochemically,
  • attaches it to the underlying muscle layer.
  • projects into the villi
  • contains fenestrated capillaries and lymphatic capillaries to facilitate absorption.
  • lymphocytes and lymphatic nodules act as a defensive barrier against organisms that may breach the epithelium.
• Muscularis mucosa
  
  • smooth muscle layer
  • usually circumferential;
    
    • the notable exception is the esophagus, where the muscularis mucosa is longitudinally oriented.
  • Individual smooth muscle cells are found in the lamina propria all the way to the tips of the villi.
  • Contraction of the muscularis mucosa results in the independent movement and folding of the mucosa, and therefore, aids in processes of digestion and absorption.
• All three layers of the mucosa fold to produce rugae (stomach) or plicae circulares (small intestine).
  
  • These folds have a central core of submucosal tissue.

Question 3

Submucosa (2.3, p.2+4)

• ?
• extends into/
• Two segments of the GI tract which secrete large amounts of mucous
• Meissner’s (submucosal) plexus of nerves and gangila
  
  • usually found in/
  • gathers/
  • regulates/
  • consists of/

Answer 3

• ?
  
  • loose connective tissue layer with blood vessels and elastin fibers.
• extends into the core of the plicae circulares and the rugae.
• Two segments of the GI tract which secrete large amounts of mucous
  
  • the esophagus and duodenum
  • have mucous glands that penetrate into the submucosa.
• Meissner’s (submucosal) plexus of nerves and gangila
  
  • usually found in the submucosa, adjacent to the muscularis externa.
  • gathers sensory information from luminal contents
  • regulates the function of the muscularis mucosa and digestive gland secretion.
  • consists of
    
    • local sensory, motor and interneurons all of the enteric nervous system (ENS),
    • unmyelinated sympathetic postganglionic fibers that originate from the prevertebral group of ganglia,
    • parasympathetic ganglion cell bodies which synapse with preganglionic fibers from the vagus nerve

Question 4

Muscularis externa (propria) (2.4, p.2-3+5)

• The muscularis externa
• When examined at the level of the electron microscope/
• The smooth muscle of these layers is innervated by/
  
  • what synapses here
• Autonomic innervation of the myenteric plexus is via /

Answer 4

• The muscularis externa
  
  • two layers of perpendicularly oriented smooth muscle, an inner circular and an outer longitudinal.
• When examined at the level of the electron microscope, smooth muscle cells of the muscularis externa are connected by gap junctions.
• The smooth muscle of these layers is innervated by the Auerbach’s or myenteric (“within muscle”) plexus that lies at the junction of the two muscle layers.
  
  • local sensory, motor and interneurons of the enteric nervous system synapse here.
• Autonomic innervation of the myenteric plexus is via
  
  • vagal parasympathetic preganglionic fibers terminating on ganglia cells,
    
    • increase digestive secretion and motility
  • sympathetic postganglionic fibers from the prevertebral ganglia.
    
    • cause GI vasoconstriction that indirectly inhibits digestive functions.

Question 5

Muscularis externa (propria) (2.4, p.2-3+5)

• Interstitial cells of Cajal (ICC)
• Peristalsis
• Segmentation

Answer 5

• Interstitial cells of Cajal (ICC)
  
  • a specialized cell that serve as pacemakers for the muscularis externa smooth muscle
  • interact with sensory and motor neurons of the myenteric plexus
  • the origin of electrical slow waves of depolarization in the GI tract (not necessarily action potentials)
• Peristalsis
  
  • a set of sequential contractions of the circular muscle with relaxation at the leading edge
  • A shortening of the longitudinal muscle draws this dilated edge back over the luminal contents, pushing them aborally
• Segmentation
  
  • divides the small intestine into small sections by a sequence of circular muscle contractions that close off segments of gut.
  • Content mixes within each segment to allow contact with digestive enzymes and transporters.

Question 6

Serosa or Adventitia

• Much of the GI tract is suspended by/
• Serosa
• mesothelium
• some portions of the GI tract are embedded in other tissue, such as/
• Adventitia

Answer 6

• Much of the GI tract is suspended by mesentery.
• Serosa
  
  • The thin layer of connective tissue that envelopes these organs
  • There is a small amount of loose connective tissue through which blood vessels and nerves travel.
• mesothelium
  
  • a simple squamous epithelium on the outer surface
• some portions of the GI tract are embedded in other tissue, such as the esophagus in the mediastinum, or retroperitoneal portions of the large intestine.
• Adventitia
  
  • The outer layer of these tubes
  • blends into surrounding connective tissue.

Question 7

Esophagus:
Mucosa (p.7-11)

• The esophagus
• The mucosa of the esophagus
  
  • epithelium
  • keratin
  • rete pegs
• In the upper and lower thirds of the esophagus, mucous secreting glands are found in/
  
  • These relatively small glands are named/
  • \frequently observed in the esophageal lamina propria
  • This layer of connective tissue borders an epithelium contiguous with/
  • Exposure to outside pathogens/
• A prominent muscularis mucosa is composed of/
  
  • \will readily identify a tissue section as esophagus.

Answer 7

• The esophagus
  
  • a tube that extends from the epiglottis to the cardiac orifice of the stomach.
  • a conduit for swallowed food,
  • not involved in the storage or significant digestion of food.
• The mucosa of the esophagus
  
  • stratified squamous epithelium.
    
    • protects against the friction of swallowed food and insulates against extremes of hot and cold
    • projects down into the lamina propria as rete pegs
  • keratin
    
    • In humans this lining is not keratinized,
    • in some species that consume a diet high in roughage, such as bovine, keratinization continues through the oral cavity and the esophagus.
  • rete pegs
    
    • typically seen in stratified squamous epithelia subjected to friction, such as the esophagus or finger tips.
• In the upper and lower thirds of the esophagus, mucous secreting glands are found in the lamina propria.
  
  • These relatively small glands are named cardiac glands due to their similarities to the mucous glands of the cardiac portion of the stomach.
  • Isolated lymphocytes as well as lymphatic nodules are frequently observed in the esophageal lamina propria.
  • This layer of connective tissue borders an epithelium contiguous with the external body surface.
  • Exposure to outside pathogens is potentially greater here; therefore, the lymphocyte defenders.
• A prominent muscularis mucosa is composed of longitudinally oriented smooth muscle fibers.
  
  • The combination of a stratified squamous epithelium and longitudinally oriented muscularis mucosa will readily identify a tissue section as esophagus.

Question 8

Esophagus:
Submucosa (p.12-14)

• The sumucosa/
• esophageal (submucosal) glands
  
  • These tubuloacinar glands are present/
  • The esophageal glands also secrete/
• sumucosal venous plexus
  
  • If the pressure in the portal system increases/

Answer 8

• The sumucosa is a loose network of collagen, elastin, mucous glands and blood vessels.
• The process of swallowing chewed food is facilitated by mucous production of the esophageal (submucosal) glands.
  
  • These tubuloacinar glands are present throughout the length of the esophagus, although most of the liquid in the esophagus originates as saliva from the oral cavity.
  • The esophageal glands also secrete lysozyme, an enzyme to lyse bacterial cell walls.
• In the lower esophagus, a sumucosal venous plexus can drain into both the systemic or portal venous systems.
  
  • If the pressure in the portal system increases, this plexus dilates forming esophageal varices.

Question 9

Esophagus:
Muscularis externa (propria) (p.12+15-17)

• Along the entire length of the esophagus, the muscularis externa is formed by two distinct layers
• The mechanisms of swallowing and propulsion of food down the length of the esophagus is coordinated by/
  
  • The muscularis externa in the top 1/3 of the esophagus is composed of/
  • The middle third displays/
  • the final third of the esophagus, the muscularis externa is composed/
• Swallowing
  
  • involuntary/
  • controlled by/
• The esophagus is restricted by upper and lower sphincters.
  
  • The upper esophageal sphincter/
  • The lower esophageal sphincter (LES)
    
    • has
      
      • an internal component/
      • an external component/
    • tonically contracted to/
    • relaxes to/
  • A third supporting structure/

Answer 9

• Along the entire length of the esophagus, the muscularis externa is formed by two distinct layers
  
  • an inner circular
  • an outer longitudinal
• The mechanisms of swallowing and propulsion of food down the length of the esophagus is coordinated by both skeletal muscle and smooth muscle.
  
  • The muscularis externa in the top 1/3 of the esophagus is composed of skeletal muscle and is under voluntary control.
  • The middle third displays a mixture of skeletal and smooth muscle intermingled,
  • the final third of the esophagus, the muscularis externa is composed entirely of smooth muscle.
• Swallowing
  
  • involuntary past the upper third of the esophagus
  • controlled by the deglutination (swallowing) reflex centers in the medulla and lower pons.
• The esophagus is restricted by upper and lower sphincters.
  
  • The upper esophageal sphincter is the cricopharyngeal muscle and participates in the initiation of swallowing.
  • The lower esophageal sphincter (LES)
    
    • has
      
      • an internal component, a slight thickening of the circular muscularis externa,
      • an external component, the crural portion of the diaphragm.
    • tonically contracted to prevent reflux of stomach contents
    • relaxes to allow a swallowed bolus of food to pass.
  • A third supporting structure is the sling of oblique fibers of muscularis externa of the upper stomach.

Question 10

Esophagus:
Adventitia

• the esophagus descends/
• adventitia
• A ligament-like thickening/

Answer 10

• the esophagus descends through the thorax in the central mediastinum.
• Its outermost layer is therefore an adventitia.
• A ligament-like thickening attaches the diaphragm to the outer esophageal muscle

Question 11

Stomach:
Functions (p.18-19)

Answer 11

• storage for ingested food;
  
  • the organ is a large expansion along the GI tube and is restricted by a tight pyloric (exiting) sphincter.
• proteolytic digestion.
  
  • Proteolytic enzymes such as pepsin (proteins), rennin (milk), lipase (fats) and a highly acidic environment facilitate digestion.
• mixes its contents using thick smooth muscle layers.
• absorption of water, salts, alcohol, and some drugs takes place across the stomach wall.
• secretion of Vitamin B12 intrinsic factor,
  
  • binds and preserves dietary Vitamin B12 for later absorption in the ileum.

Question 12

Stomach:
General histology (p.20-22)

• The stomach is composed of/
• The unique stomach mucosa is characterized by/
• The surface is lined by/
  
  • The apical ends of the cells are filled with/
  • Surface mucous is secreted in response to/
• Agents which increase the rate of HCO3- secretion into the surface mucous
• Agents which decrease HCO3- secretion

Answer 12

• The stomach is composed of the same four general layers introduced previously.
• The unique stomach mucosa is characterized by pits and glands.
• The surface is lined by a simple columnar epithelium of surface mucous cells.
  
  • The apical ends of the cells are filled with secretory vesicles of mucous, which is an alkaline carbohydrate-rich glycoprotein.
  • Surface mucous is secreted in response to friction due to roughage in the diet or to chemical stimuli such as ethanol.
• Agents which increase the rate of HCO3- secretion into the surface mucous
  
  • Ca+2
  • prostaglandins E and F
  • cholinergic agents
  • dibutyryl cGMP
• Agents which decrease HCO3- secretion
  
  • NSAIDs
  • Aspirin

Question 13

Stomach:
General histology (p.20-22)

• Surface mucous cells act as/
• Gastric pits/
  
  • These pits are also lined by/
  • Into the base of each pit drain/
• the lamina propria is filled with/
• Directly under the base of the gastric glands is a/
• The stomach wall has/
• Together, the pits, glands, and rugae serve to/
• The muscularis externa expands to include three layers of smooth muscle
• The serosa/

Answer 13

• Surface mucous cells act as a buffer zone to protect the mucosa from the caustic environment in the stomach lumen.
• Gastric pits descend from the surface into the lamina propria.
  
  • These pits are also lined by surface mucous cells.
  • Into the base of each pit drain two or three gastric glands.
    
    • The gastric glands are different in each anatomical region of the stomach (cardiac, body, pyloric).
• the lamina propria is filled with gastric pits and glands, and is only evident as small amounts of intervening connective tissue.
• Directly under the base of the gastric glands is a thin muscularis mucosa composed of circularly oriented smooth muscle.
• The stomach wall has large, visible folds with a central core of submucosal tissue called rugae.
• Together, the pits, glands, and rugae serve to increase the surface area of the mucosal layer available for the secretion of digestive enzymes and acid.
• The muscularis externa expands to include three layers of smooth muscle: inner oblique, middle circular and outer longitudinal.
  
  • increased thickness of the overall muscularis externa.
• The serosa is not distinguished in any specialized way

Question 14

Stomach regions (p.23)

• consists of/
• Histologically,
  
  • the fundus and body/
  • The cardia and the antrum/pylorus/

Answer 14

• consists of the cardia, fundus, body, antrum and pylorus
• Histologically,
  
  • the fundus and body are very similar
  • The cardia and the antrum/pylorus will be considered separately

Question 15

Stomach regions:
Cardiac region (p.24-25)

• glands
• The cardia of the stomach/
• The transition from the esophagus to the cardiac stomach/
  
  • This is indicative of /
• The cardiac pits/
• the cardiac glands/
• The ratio of the length of the pits to glands/
• The cardiac glands are composed primarily of/
  
  • However, just a centimeter into the cardia/

Answer 15

• Mucous and Mucoparietal Glands
• The cardia of the stomach is a narrow 2-3 cm zone surrounding the esophageal entrance.
• The transition from the esophagus to the cardiac stomach is a sharp and dramatic one (stratified squamous mucosa to folded simple columnar).
  
  • This is indicative of the immediate change in function from conduit to digestion.
• The cardiac pits are very shallow,
• the cardiac glands are short and highly coiled.
• The ratio of the length of the pits to glands is about 1:1.
• The cardiac glands are composed primarily of small, pale staining mucus producing cells.
  
  • However, just a centimeter into the cardia, bright pink staining, acid producing parietal cells appear in the glands

Question 16

Stomach regions:
Fundus and body regions (2.7, p.26-27)

• glands
• The bulging fundus/
• The glands of these regions are referred to by a variety of names
  
  • fundic glands
  • gastric glands
  • oxyntic glands
  • zymogen glands
• These glands secrete/
• The mucosa of the fundus and body displays/
  
  • The ratio of the length of pits to glands/
  • There are from/
• The gastric glands have an isthmus, neck, and base
  
  • The isthmus/
    
    • Mucous neck cells/
    • Precursor cells/
  • The neck (middle) of the gastric gland contains/
  • The base of the gastric gland is made up of/

Answer 16

• Gastric Glands
• The bulging fundus has a high compliance so that food can accumulate without increasing stomach pressure.
• The glands of these regions are referred to by a variety of names:
  
  • fundic glands (location),
  • gastric glands (major secretors of stomach),
  • oxyntic glands (contain acid secreting cells)
  • zymogen glands (contain stored secretory or “zymogen” granules).
• These glands secrete the digestive enzymes and acid into the stomach lumen
• The mucosa of the fundus and body displays deep, straight pits and long glands which are only slightly coiled at their base.
  
  • The ratio of the length of pits to glands is approximately 1:4.
  • There are from 2-7 glands emptying into the base of each pit.
• The gastric glands have an isthmus, neck, and base.
  
  • The isthmus drains into the base of the gastric pit.
    
    • Mucous neck cells found here secrete an acidic glycoprotein, display cytoplasmic basophilia due to increased amounts of RER, and contain larger secretion granules than surface mucous cells.
    • Precursor cells for both the surface and base of the stomach epithelium arise from the isthmus.
  • The neck (middle) of the gastric gland contains mucous neck cells and acid producing parietal cells.
  • The base of the gastric gland is made up of chief cells, which secrete digestive enzymes, a variety of enteroendocrine cells and a few parietal cells

Question 17

Stomach regions:
Fundus and body regions:
Parietal or oxyntic cells (p.28-30)

• Parietal or oxyntic cells secrete/
• In H&E stained sections parietal cells are/
• Ultrastructure visualized with the electron microscope reveals/
• intracellular canaliculi
• tubulovesicular system
• Together, the intracellular canaliculi and the tubulovesicular system/
• In a stimulated parietal cell, 80% of the proteins of the apical plasma membrane are /
• The cytoplasm is also densely packed with/
• The basolateral plasma membrane of the parietal cell contains/
• Acid secretion is decreased by/

Answer 17

• Parietal or oxyntic cells secrete 0.1N HCl and intrinsic factor for binding vitamin B12.
• In H&E stained sections parietal cells are plump round cells with a central nucleus and a homogeneous, eosinophilic cytoplasm.
• Ultrastructure visualized with the electron microscope reveals specializations that permit secretion of the strong solution of HCl.
• The apical plasma membrane folds into a deep trenchlike invagination with numerous microvilli called intracellular canaliculi.
• The surrounding cytoplasm is filled with closed smooth surfaced vesicles, the tubulovesicular system;
  
  • these vesicles fuse with the canaliculi when acid secretion is stimulated.
• Together, the intracellular canaliculi and the tubulovesicular system augment the surface area for H+K+ATPase pumps to release H+ ions into the stomach lumen.
• In a stimulated parietal cell, 80% of the proteins of the apical plasma membrane are H+K+ATPase pumps.
• The cytoplasm is also densely packed with mitochondria, which accounts for the cytoplasmic eosinophilia.
  
  • Mitochondria provide ATP for the active transport occurring at the canalicular surface.
• The basolateral plasma membrane of the parietal cell contains receptors for histamine, gastrin and acetylcholine, the three factors that stimulate acid secretion.
• Acid secretion is decreased by somatostatin and by prostaglandins.

Question 18

Stomach regions:
Fundus and body regions:
Chief cells (p.31-32)

• Chief cells secrete/
• Chief cells store/
• The basal cytoplasm is packed with/
• Chief cells are regulated secretors, and therefore/
• Chief cell secretion
  
  • stimulated by/
  • inhibited by/
• Chief cells are absent from/

Answer 18

• Chief cells secrete pepsinogen, rennin, and lipase.
• Chief cells store abundant basophilic secretory granules in the apical end of the cell.
• The basal cytoplasm is packed with basophilic RER, understandable for a cell which is a very active synthesizer of secretory proteins.
• Chief cells are regulated secretors, and therefore store their secretory products in condensed zymogen granules.
• Chief cell secretion
  
  • stimulated by acetylcholine
  • inhibited by somatostatin.
• Chief cells are absent from the cardiac glands and seldom found in the pyloric glands.

Question 19

Stomach regions:
Fundus and body regions:
Enteroendocrine (APUD) cells (p.33-34)

• acronym
• found in/
• secrete/
• found/
• identified in/
• secretions
  
  • released at /
  • move by/
    *

Answer 19

• amine precursor uptake and decarboxylation
• the third type of cells found in base of the gastric glands.
• single cells within the epithelium that secrete substances that act as hormones or paracrine agents.
• found throughout the stomach, small intestine and a few in the colon.
• identified in electron micrographs by basal secretory granules.
• secretions
  
  • released at the basal end of the cell
  • move by diffusion through the interstitial fluid or via the blood stream.

Question 20

Stomach regions:
Fundus and body regions:
Enteroendocrine (APUD) cells:
Major types, secretions, and actions of enteroendocrine cells in the stomach

• Gastrin, (G cell)
• Histamine, (ECL cell)
• Somatostatin, (D cell)
• Vasoactive intestinal peptide (VIP), (D1 cells)
• Ghrelin, Fundic cells

Answer 20

• Gastrin, (G cell)
  
  • Stimulates secretion of HCl by parietal cells
  • Increases histamine secretion by ECL cells
  • Proliferation of gastric and intestinal mucosa
  • Promotes peristalis of the gastro-colic reflex
  • Acts via G-proteins (Gq), IP3, DAG & Ca+2 second messengers.
• Histamine, (ECL cell)
  
  • Binds histamine H2-receptors on parietal cells to stimulate and potentiate secretion of HCl.
  • Acts via a cAMP second messenger.
• Somatostatin, (D cell)
  
  • Inhibits release of gastrin (from G-cells) and acid (from parietal cells) after stomach luminal pH has dropped below 3.0
  • Inhibits chief cell secretion
• Vasoactive intestinal peptide (VIP), (D1 cells)
  
  • Increase pancreatic bicarbonate and water secretion
  • Relax lower esophageal sphincter, fundic stomach & gall bladder
  • Decrease gastric acid secretion
  • Increase intestinal secretion of water & electrolytes
• Ghrelin, Fundic cells
  
  • Secreted during periods of fasting
  • Binds to a hypothalamic receptor to cause secretion of growth hormone
  • In the brain, ghrelin also stimulates the sensation of hunger
  • In adipose tissue, ghrelin inhibits mobilization of fats

Question 21

Stomach regions:
Fundus and body regions:
Gastric gland renewal (p.35)

• \the renewal rate of the gastric surface mucous cells/
  
  • Surface cells turnover/
• the cells of the gastric gland turnover/
• The isthmus of the fundic gland serves as a source of/
• This renewal process can be damaged by/
  
  • However, when the epithelium is damaged and cells are lost, /
  • Adjacent cells/

Answer 21

• Because of the extreme conditions within the lumen of the stomach, the renewal rate of the gastric surface mucous cells is rapid.
  
  • Surface cells turnover every 2-6 days.
• the cells of the gastric gland turnover at a much slower rate of approximately twice a year (190 days).
• The isthmus of the fundic gland serves as a source of stem cells for both the surface mucous cells as well as the cell types deep in the base of the gland.
• This renewal process can be damaged by aspirin, bile salts, and alcohol.
  
  • However, when the epithelium is damaged and cells are lost, reepithelialization will begin within minutes as long as the basement membrane remains intact.
  • Adjacent cells thin and extend lamellipodia via microfilament action to cover the exposed areas

Question 22

Stomach regions:
Antral region (p.36-37)

• glands
• This region is a transition between/
• Physiologically, the antrum/
• The antrum
  
  • devoid of /
  • enriched in/
• The major stimulus for gastrin secretion is/
  
  • These G cells are also stimulated by/
  • The G cells appear like /
• The antral epithelium also contains/

Answer 22

• Modified Gastric Glands
• This region is a transition between the body and the pylorus.
• Physiologically, the antrum contracts with a powerful churning that triturates the stomach contents into a pureed “chyme.”
• The antrum
  
  • devoid of parietal cells,
  • enriched in gastrin secreting G cells.
• The major stimulus for gastrin secretion is peptides in the stomach lumen.
  
  • These G cells are also stimulated by an intermediate neuron via the neurotransmitter bombesin, or gastrin-releasing peptide.
  • The G cells appear like pale staining “fried eggs” in histological images.
• The antral epithelium also contains D cells that secrete somatostatin to inhibit parietal and chief cell secretion.

Question 23

Stomach regions:
Pyloric region (p.38-39)

• glands
• characterized by/
• The pit to gland ratio
• The glands
• The G cells/
• The rate of renewal of surface mucous cells/
• frequent site of/
• A pyloric sphincter is formed by/

Answer 23

• Mucous glands
• characterized by deep pits (equal to those in the body) but short glands.
• The pit to gland ratio is close to 1:1.
• The glands
  
  • coiled, unlike the straight glands of the body
  • contain mucous-secreting cells and enteroendocrine cells, but rarely chief or parietal cells.
• The G cells that secrete gastrin are enriched in the pyloric glands.
• The rate of renewal of surface mucous cells is slower in the pylorus, with life spans up to two months.
• frequent site of peptic ulcers.
• A pyloric sphincter is formed by a thickening of the middle circular layer of the muscularis externa.
  
  • This substantial tonic constriction prevents leakage of the stored stomach chyme.