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EXAM 2: GASTRO-INTESTINAL STUDY GUIDE by Steele
Question or Corrections: [email protected]
Basic Flow of Materials:
Oral Cavity → Oropharynx → Laryngopharynx → “upper esophageal sphincter”
→ Esophagus → “lower esophageal sphincter” → Cardia of Stomach → Body of
Stomach → Antrum/Pylorus of Stomach → Pyloric Sphincter → Duodenum of SI
→ Jejunum of SI → Ileum of SI → Ileo-Cecal Sphincter/Valve → Cecum of Colon
→ Ascending Colon → Transverse Colon → Descending Colon → Sigmoidal
Colon → Rectum → Internal Anal Sphincter → External Anal Sphincter → Anus
Five Phases of Interaction With Food:
Cephalic → Oral → Esophageal → Gastric → Intestinal
GI Control Mechanisms
Any control mechanism has three components:
INPUT→ PROCESSING → OUTPUT:
5 Types of GI Input/Stimuli
A) Special Sensory Stimuli (taste, smell, etc.)
B) Mechanical Stimuli (bulk)
C) Chemical Stimuli (pH, peptides, etc.)
D) Endocrine Input
E) Nervous Input
↓
↓
↓
↓
3 Types of GI Processing Cells
1) Neuronal
Intrinsic (ENS) or Extrinsic (CNS)
Responsive to A, B, C and D
2) Hormonal
Enteroendocrine Cells (example = G-cells)
Responsive to A and B
3) Secretory Cells (Secrete Into Lumen)
Example = Parietal Cells
Responsive to B, C, D, E
↓
↓
↓
↓
3 Types of GI Output / Effector Mechanisms
1) ↑ or ↓ Motility
2) ↑ or ↓Endocrine Secretions
3) ↑ or ↓ Exocrine Secretions / Secretions into Lumen
1
Enteric Division of the Nervous System (ENS)
The ENS is a massive network of neurons that monitor the activity of the digestive tract via
chemoreceptors and mechanoreceptors and coordinate secretions and motility.
Intrinsic ENS activity such as short reflexes occurs without CNS input
Extrinsic ENS activity includes long reflexes and occurs via input from the CNS. The
CNS communicates with the ENS via the sympathetic and parasympathetic divisions of
the ANS! (example: smell a nice meal and the vagal inputs to the gastric ENS enhances
the output of mucous, parietal and chief cells)
Myenteric Plexus is embedded between the circular and longitudinal smooth muscle
Submucosal Plexus is contained within the submucosal layer
(both plexuses contain parasympathetic ganglia, sympathetic post-ganglionic fibers,
ENS sensory neurons, ENS interneurons, and ENS motor neurons)
Functional Units and Cross-Sectional Organizations:
Oral Cavity and Salivary Glands
Tongue contains non-keratinized stratified squamous, seromucous glands, and
three types of papilla, two of which contain taste buds
OroPharynx and LaryngoPharynx have non-keratinized stratified squamous
Three paired salivary glands with mucous cells (secrete mucus) and serous cells
(secrete buffers and digestive enzymes) with ACINAR ARRANGEMENT
Esophagus
Mucosal Epithelium: non-keratinized stratified squamous
(Lamina Propria): present
Muscularis Mucosa: present
Submucosa: submucosal glands present for lubrication
Muscularis Externa: Top 1/3 is all skeletal muscle (voluntary)
Middle 1/3 is mix skeletal and smooth muscle
Bottom 1/3 is all smooth muscle
Serosa or Adventitia: However, the small region of the esophagus that exists
between the diaphragm and the cardia of the stomach is
intraperitoneal and thus has serosa
Stomach
Mucosal Epithelium: Arranged into pits + glands in the fundus and body:
Superior part is the gastric pit…contains mucous cells to produce
protective coat of mucus
Deeper portion is the gland. Contains parietal cells which secrete
hydrochloric acid and intrinsic factor, and chief cells which secrete
pepsinogen
Stem cells are located at the junction between the pit and gland
G cells secrete gastrin in response to peptides and are located at the very
base of the gland. Gastrin operates to increase the activity of parietal and
chief cells
2
Three functions of Stomach Acid:
1) Denaturation (uncoiling) of proteins
2) Conversion of pepsinogen (inactive) to pepsin (active) and maintenance
of optimal pH (2) for pepsin function
3) Antimicrobial Effect
Lamina Propria: Present
Muscularis Mucosa: Present
Submucosa: Present
Muscularis Externa: NOTE THREE LAYERS…INCLUDING OBLIQUE
Serosa or Adventitia:
Functions: Storage of food / Protein denaturation / Initial mixing & churning of
food / Antimicrobial / Initial protein digestion / Intrinsic factor
Duodenum / Jejunum / Ileum
Mucosal Epithelium: Several Cells…see below
(Lamina Propria): Composes the core of the villi. Contains capillaries & lacteals
Muscularis Mucosa: Present
Submucosa: Composes the core of the plicae circularis.
Submucosal glands within the duodenum only
Muscularis Externa: present
Serosa or Adventitia: (BUT: the duodenum is retroperitoneal)
Function: The functions of the small intestine are digestion & absorption.
The duodenum has additional functions: regulation of gastric activity
and coordination of secretions from the pancreas and liver/gall-bladder
based on the size and content of a meal
Liver: The lobule is the functional unit…approx 100,000 total
Hepatocytes rich in sER and rER are arranged within lobules. The lobules are the
functional unit of the liver and have a ‘honeycomb’ arrangement, with 6 triads at
the outside, and a central vein at the core. Triads contain 1) branches of the
hepatic artery, 2) branches of the hepatic artery proper, and 3) bile ducts.
Sinusoidal capillaries deliver 1) oxygenated blood from the hepatic artery and
2)blood from the portal vein rich in absorbed nutrients. The blood is processed as
it moves towards the core and returned into the central vein. All of the central
veins from the thousands of hepatic lobules ultimately branch together and deliver
blood to the inferior vena cava
*Note that blood flows from the triad towards the center of the lobule, while bile
moves away from the core of the lobule, and towards the bile ducts in the triads.
*Note that the liver receives blood from two sources and returns it to one.
Hepatic portal circulation: The liver gets the first pass at water soluble nutrients
absorbed from stomach, SI, and LI
(see page 766 in your textbook for an excellent illustration of this)
3
Liver Functions
1) Metabolize lipids, amino acids, carbohydrates
2) Remove and process metabolic wastes
3) Detoxify drugs and toxins
4) Store certain vitamins and minerals
5) Synthesize plasma proteins
6) Produce Bile
Overall: the liver is responsible for monitoring & regulating the composition of the blood!!
Pancreas
Exocrine Function: 1) cuboidal cells are arranged into acini (grapes on the end of
a vine) and secrete proenzymes that break down the various components of food
(proteins, carbohydrates, lipids, nucleic acids). These enzymes enter into ducts
(vines) that are lined with 2)columnar duct cells that secrete bicarbonate. These
secretions travel via the pancreatic duct, through the hepatopancreatic sphincter to
the duodenal papilla
Endocrine Function: (FYI at this point): alpha and beta cells are arranged into
islets, and secrete insulin and glucagon
Large Intestine
Mucosal Epithelium: Non-ciliated, non-microvilli-containing columnar cells
(absorptive) and abundant mucous cells arranged into
glands called crypts of leiberkuhn
(Lamina Propria):
Present
Muscularis Mucosa: Present
Submucosa:
Present
Muscularis Externa: Additional longitudinal bands that create pouches in the
colon…we did not discuss these in lecture
Serosa or Adventitia:
Functions:
1) Recovery of fluids secreted into GI tract during digestive
processes
2) Absorption of certain nutrients liberated by intestinal
flora (vitamin K, biotin, pantothenic acid)
3) Compaction of remaining intestinal contents into feces
4) Defecation!
4
Four Ways that Surface Area is Maximized within the Small Intestine:
1. Length
2. Plicae Circularis (2-3x):
3. Villi (10x)
4. Microvilli *(20-30x = greatest contribution!!)*
(total is 400-900x increase in surface area)
Digestion: and Absorption Summary
(complex molecules converted to simple molecules and absorbed by enterocytes)
Fats:
1) Fats are emulsified into smaller droplets called micelles via interaction with
bile salts released by the liver/gallbladder
2) Pancreatic lipase and phospholipase convert triglycerides to free fatty acids
and monglycerides
3) Free fatty acids and monoglycerides passively diffuse into the enterocyte,
whereas cholesterol is transported into the cell
4) Triglycerides are resynthesized and packaged along with cholesterol into
chylomicrons that are absorbed into lacteals, which are specialized lymphatic
capillaries within the lamina propria
(note that the absorption of fats bypasses the hepatic portal vein)
Carbohydrates:
1) Pancreatic Amylase converts polysaccharides into disaccharides and simple
sugars within the lumen
2) Disaccharides are converted to simple sugars (monosaccharides) by
disaccharidases located on the enterocyte microvilli (brush border)
3) Glucose is transported across the apical/luminal of the enterocyte by a
secondary active transporter/symporter that relies on a sodium gradient
a. (why is called secondary active transport??)
4) Glucose is moved across the basal surface into the lamina propria via
facilitated transport, and transported to the liver by the portal vein
Proteins:
1) Large proteins are denatured by stomach acid and broken into large peptides
by pepsin
2) Pancreatic proteases degrade peptides to amino acids, dipeptides, and
tripeptides
3) Brush border dipeptidases convert dipeptides to free amino acids, however,
dipeptides, tripeptides, and longer peptides can also be absorbed
1) Free amino acids are absorbed at the luminal surface via a sodium
symporter, and released at the basal surface via a sodium antiporter
2) Di and tripeptides are absorbed at the luminal surface via a proton
(H+) symporter and released at the basal surface via a proton
antiporter
3) Intact peptides are absorbed via endocytosis
Nucleic Acids Degraded to nitrogenous bases and simple sugars via pancreatic
nucleases
5
Five Cell Types Within an Intestinal Villus:
Enterocytes
The absorptive cells of the small intestine...move digested compounds from the
lumen into the lamina propria where they diffuse into the bloodstream or lacteals.
Abundant microvilli at the luminal surface create a brush border/glycocalyx that
maximizes absorptive surface area. Certain digestive enzymes are tethered to the
outside of the microvilli to enhance this process
Goblet Cells (secrete into the lumen)
Secrete mucous in order to protect against chemical and mechanical stress
Enteroendocrine Cells (secrete into the lamina propria)
Scattered throughout the lumen of the GI tract. Secrete
Paneth Cells (secrete into the lumen)
Immune cells that are granular and similar to eosinophils…secrete anti-microbial
peptides and lysozymes into the lumen.
Stem Cells
(CAN DIFFERENTIATE TO ANY OF THE ABOVE CELLS)
Stimuli and Effects of Duodenal Enteroendocrine Secretions:
Cholecystokinin (CCK)
Major Stimulus: Lipids and peptides, bulk
Major Downstream Effect: 1. Secretion of pancreatic digestive enzymes,
2. Release of bile from liver/gallbladder,
3. Relaxation of hepato-pancreatic sphincter
Gastric Inhibitory Peptide
Major Stimulus: lipids and carbohydrates, bulk
Major Downstream Effect: 1. Inhibit secretion of Gastrin by G-cells
2. Release of insulin from the pancreas
↑ Duodenal Gland Secretion
(↑ bicarbonate/buffer)
↑ Glucose Utilization by muscle, etc.
Secretin
Major Stimulus: Low pH, bulk,
Major Downstream Effectst: Release of bicarbonate from the pancreas
Release of bile by the liver
Vasoactive Intestinal Peptide (VIP)
Major Stimulus: Bulk, low pH, Food
Major Downstream Effect: Dilation of Intestinal Capillaries to
maximize absorption
Duodenal – Pylorus Interface: Many of the above mentioned effects can also result from the
activity of ENS circuitry involving chemo and mechanoreceptors in the duodenum that then alter
the motility & secretory activity within the stomach. Because of this redundancy/overlap, efforts
to map out the control mechanisms involved at this interface appear convoluted. However, the
major effects can be summarized as follows:
1) Reduce motility (allow the duodenum time to neutralize acidic contents)
2) Generate a more rhythmic opening/closing of the pyloric sphincter
3) Reduce the secretion of acid and pepsinogen in the stomach
6
Important Definitions / Distinctions:
Serosa vs. Adventitia:
Serosa is more slippery and is found on the outermost layer of organs contained within
the peritoneal cavity (intraperitoneal) and is synonymous with visceral peritoneum.
Adventitia is more of a fibrous connective tissue that is found on the outermost layer of
organs that are not contained within the peritoneal cavity such as the esophagus, or on the
posterior surfaces of retroperitoneal organs such as the pancreas, duodenum, rectum,
and kidneys (these organs have serosa/visceral peritoneum covering the anterior surface).
Skeletal Muscle in the GI System:
Skeletal Muscle only exists at the ‘top and bottom’ of the GI tract – that is, at the oral
cavity/pharynx/upper esophagus; and at the external anal sphincter.
Submucosal Glands:
Submucosal glands are typically found only within the duodenum, and not within the
jejunum nor ileum. At the duodenum they release a bicarbonate rich secretion in order to
assist in the neutralization of acidic chyme received from the pyloric sphincter.
(submucosal glands are also present in the esophagus…lubricates passage of boli)
Parietal Cells:
Note the unique shape of parietal cells versus other cells of the gastric epithelium
(slide 27, lecture 2)
Stomach Lining Acid Protection is accomplished via:
1) Tight Junctions
2) Mucous layer
3) Bicarbonate within mucous layer
Short vs. Long Reflex Loops:
Short reflex loops occur within the signaling of the ENS. Remember in the video the
gunea pig large intestine generated peristaltic waves without the input of the CNS via
complex peristaltic reflexes. Long reflex loops involve circuitry that runs through the
brainstem or spinal cord.
Borborygmus:
This term describes the “growling” sounds in the stomach as digestive fluids and gases
shift around…more prominent when you haven’t eaten for a while.
Rugae vs. Plicae Circularis:
Rugae are temporary fold within the (empty) stomach, whereas plicae circularis are
permanent folds within the small intestine.
Enteroendocrine Concept:
Scattered cells within the walls of GI organs that operate in an endocrine fashion…as
opposed to the more typically arrangement of populations of endocrine cells into a gland.
As such, the GI is the largest endocrine organ
7
Brush Border = Glycocalyx = Formed by Microvilli of Enterocytes
Brush border enzymes are “fixed” to the brush border…so they are in the lumen but not
free-floating around
The Pancreas:
The pancreas has both an endocrine and an exocrine function.
Hepatic Triad:
Consists of a bile duct, branch of the portal vein, and branch of the hepatic artery.
Located at the outside of the lobule
Gallbladder:
Note that the gallbladder has no muscularis mucosa and a thin muscularis externa
Proenzymes = Zymogens
Enzymes that are secreted in an inactive form. This is typically the case for enzymes that
break down proteins in order to prevent them from degrading proteins until they are in
the lumen. Pepsinogen (inactive) is secreted into the lumen of the stomach by chief cells
and converted to pepsin (active) by acids. Pancreatic proteases such as trypsinogen and
chymotrypsinogen (inactive) are secreted into the lumen of the duodenum…trypsinogen
is activated by the enzyme enteropeptidase, and trypsin can then activate the rest of the
proteolytic enzymes.
Peristalsis vs. Segmentation:
Peristalsis works in the aboral (away from the mouth) direction. It is accomplished by
contracting the circular layer of smooth muscle behind the bolus while simultaneously
shortening the longitudinal smooth muscle in front of the bolus. The only exception to
the aboral rule is vomiting, during which there is a massive retrograde peristalsis that
exists within the small intestine, stomach, and esophagus.
Segmentation moves substances in both directions, however, only within small segments
of the small intestine.
Absorption is Optimized by:
1) Converting Complex Molecules to Simple Components
2) Maximizing Surface Area
(Plicae circularis is the only visible structure)
CNS input becomes increasingly less pronounced as you move from the gastric phase to the
intestinal phase…ENS and enteroendocrine and local responses take-over
Lactose Intolerance:
No lactase (a specific type of disaccharidase) within the brush border of the SI.
Upper and Lower Esophageal Sphincters (UES and LES):
Unlike the pyloric sphincter, ileocecal spincter, and anal sphincters, the UES and LES are
not true sphincter because they do not have distinct circular bands of muscle that can
create true barriers between the compartments. Instead, these can be thought of as
regions of the esophagus that have more muscle tone, the effect being that the UES
normally prevents air-flow into the esophagus, while the LES prevents regurgitation of
acidic stomach contents into the esophagus.
8