Rao 1 - GI Function Flashcards
What are the 4 main functions of the GI tract?
- Motility - GI tract propels food and mixes it so that it can be excreted and nutrients can be extracted.
- Secretion - of substances that break down food and aids in motility
- Digestion - food is broken down into smaller particles so that nutrients can be absorbed.
- Absorption - allows body to extract nutrients from meals
How is the GI tract similar to the lung and kidney?
All of these organs are exposed to the outside environment
**Note the GI tract is exposed to the environment on both sides
What is the role of M cells in the mucosal immune system?
They uptake antigens so that they can be presented to the lymphoid tissue in Peyer’s patches in a controlled manner
Bacteria is normally present in selected areas of the the GI tract, what are these places?
Bacteria is normally present in the Rectum and Colon. A small amount may be present in the illeum, but in general any bacteria in the small intestine is pathologic.
What are the layers of the Gastrointestinal mucosa?
• what is the function of the muscularis mucosa
- *Epithelium**
- *Lamina Propria** - loose CT
- *Muscularis Mucosa** - Propel nutrients from lumen to submucosa
- *Submucosa -** irregular CT connects the mucosa to muscle layer
What cell gives rise to cells in the crypt and villus cells?
• where is it located?
Stem cells are located at the base of the Crypts to proliferate and give rise to cells that migrate upward to become villus cells and crypt cells. These cells diffentiate after migrating to there respective location.
What 3 important features of intestinal tissue are present in the lamina propria?
- Capillary Network
- Lacteals
- Enteric Nerves
What 3 categories of bacteria exist in the GI tract?
- Commensals
- Pathogens
- Probiotics
What are 6 functions of the bacteria in the GI tract?
- *1. Development of the Mucosal Immune System
2. Epithelial Proliferation and Differentiation
3. Metabolic Function
4. Bile Acid Metabolism
5. Salvage Nutrients
6. Probiotics**
How does the blood flow of the GI tract change after a meal?
8x increase after a meal
What role does countercurrent blood flow play in the GI tract?
Blood shunts between arterioles and venules so 80% of oxygen DOES NOT reach the epithelial cells. Normally this is not a problem, but does leave the tissue susceptible to ischemic damage that can blunt the villi.
What 4 mucosal vasodilator are present in the GI tract?
- CCK
- VIP
- Gastrin
- Secretin
What are the divisions of innervation of the GI tract?
Extrinsic Autonomic NS => consists of sympathetic and parasympathetic NS
Intrinsic Autonomic NS
Parasympathetic component of the Extrinsic Nervous System
• Preganglionic Cell Body location?
• Preganglionic Length?
• Where does preganglionic Synapse?
• Postganglionic Legth?
• Neurotransmitters ued?
Preganglionic Cell Body:
*Vagus n. so cell bodies are located in the brainstem
and Pelvic n. so cell bodies in the sacral spinal cord
Parasympathethic PREganglionics are long and synapse with the INTRINSIC nervous system (ENS) with short post ganglionic fibers
- Parasympathetic Preganglionics = Ach (and NE for sympathetic)
- Enteric Postganglionics = Substance P (VIP and NO are inhibitory)
Sympathetic component of the Extrinsic Nervous System
• Preganglionic Cell Body location?
• Preganglionic Length?
• Where does preganglionic Synapse?
• Postganglionic Legth?
• Neurotransmitters ued?
Short Sympathetic PREganglionic come from the sympathetic chain in the spinal cord and synapse outside of the GI tract in the Prevertebral ganglia (Celiac, Superior mesenteric, and Inferior mesenteric). LONG post ganglionic
Preganglionic Sympathetic NS will use Ach as neurotransmitter. (POSTganglionics will use NE)
T or F: there is communication between the myenteric and submucosal plexi
True, they they also communicate with BOTH sympathetic and parasympathetic NS
What neurons are responsible for intergrating information in the ENS turning it into the second brain?
Interplexar neurons (allow for the communication necessary to call it a 2nd brain)
What neurotransmitters are excitatory in the ENS?
• which are inhibitory?
Excitatory:
• Ach and Substance P
Inhibitory:
• VIP and NO
What are the 5 major hormones of the GI tract?
• how/where are they released?
5 major Hormones:
• Gastrin
• CCK
• GIP
• Secretin
• Motilin
These are released into the portal circulation and then into the liver
What are the 5 candidate hormones of the GI tract?
• Pancreatic Polypeptide
• Neurotensin
• Substance P
• Glucagon
• Somatostatin
What are the criteria for determining if something is a GI hormone?
- Stimulation and Activity in different parts of the GI tract
- Effective in the absence of nerves
- Isolated from site of Stimulation
- Substance identified and structure confirmed
What are the two major groups of hormones?
• why are they groupe?
Hormones are grouped on the basis of structural homology.
Group I
• Gastrin, CCK
Group II
• Secretin, VIP, GIP, Glucagon
Gastrin
• Stimuli
• Inhibition
• Actions
Stimulus
• Proteins/Amino acids (Tryptophan and phenylalanine)
• Stomach Distention
• Vagal Stimulation (via GRP)
**Note: G34 is released at a constant rate into blood
Inhibition
• Low pH of stomach (High H+)
• Increased somatostatin
Actions
• Stimulates H+ Secretion from parietal cells via Histamine Release from Enterochromaffin (ECF) cells
• Promotes growth of Gastric Mucosa and Enterochromaffin cells
Gastrin-17
• what is found at the N-terminus? Significance?
• C-terminus?
• What feature increases activity?
N-terminus
• Pyroglutamate - protects from exopeptidases and is required for full activity
C-terminus
• Aminated Phenylalanine
Sulfanation at the 6th C-terminal Tyrosine creates Gastrin II that has increased affinity for the Gastrin receptors
Gastrin-17 vs Gastrin-34
• Location of Release?
• Potency
• Stimuli
Gastrin-17 is released from G-cells in the antrum of the stomach, while Gastrin-34 is released from the Duodenum.
Gastrin 17 and 34 are equipotent
Gastrin-17 is released in response to proteins, stomach distension, and vagal stimulation while Gastrin-34 is released at a steady rate into the serum during the interdigestive period.
***Remember gastin is a hormone so in either case it will enter the circulation to have activity***
Gastrin-17 vs Gastrin-34 half-life
- *Gastrin-17** has a half life around 38 minutes
- *Gastrin-34** has a half life around 7 minutes
What is gly-extended gastrin?
• effect?
Glycine-extended gastrin is G-17 that has glycine at the C-terminus before it is cleaved off leaving the aminated Phe
This gastrin DOES NOT act on gastrin/CCK2 receptors, but has its own receptor that leads to trophic effect when stimulated
What do Gastrin and CCK have in common structurally?
5 C-terminal Amino Acids
**CCK is also sulfonated, but it is at the 7th C-terminal tyrosine rather than the 6th
What is the difference in the frequency with which CCK and gastrin are sulfonate?
Gastrin is about 1/2 sulfonated
CCK is almost always sulfonated
Cholecystokinin (CCK)
• Family
• Site/Cell of secretion
Family:
• Gastrin-CCK family
Secreted by I-cells in the duodenum and Jejunum
CCK
• Stimulus
• Inhibition
• Primary and secondary functions
Stimulus
• Fats (Monoglycerides and Free FAs, NOT TGs)
• Proteins (Small peptides and Amino acids)
Primary Functions:
• HCO3- and Enzyme secretion from pancreas
Secondary Functions:
• Contraction of Gallbladder, Growth of Pancreas and Gallbladder, Inhibition of Gastric Emptying, Decreased Food Intake
How does the location of sulfonation affect the activity of the C-terminal regions of gastrin and CCK?
• difference in activity with CCK1 and 2 receptors?
Gastrin is sulfonated at the 6th C-terminal residue and has greater affinity for CCK2 receptors that stimulate acid secretion mostly with only weak effects on gallbladder contraction
CCK is sulfonated at the 7th C-terminal residue giving it greater activity for CCK1 receptors that have a greater effect on gallbladder contraction and less of an effect on acid secretion
What compounds are in the secretin family of hormones?
• Do they share receptors?
Secretin Family:
• Secretin
• VIP
• GIP
• Glucagon
***These all have DIFFERENT RECEPTORS and DIFFERENT ACTIVITY***
On what side of the cell would you expect to see granules gathered in an endocrine cell?
• How do these cells know when to release contents?
Granules will be at the basal side of the cell because they will get secreted into the blood
Microvilli on the apical surface have chemoreceptors and Physical and Neural Stimulation also cause these cells to release conents
***NOTE: GI endocrine cells are not clustered together so you couldn’t remove them in one chunck surgically
Secretin
• Family
• Site/Cell of Secretion
• Stimuli (primary and secondary)
Family:
• Glucagon-Secretin family of hormones
Site/Cell of Secretion:
• S-cells in the duodenum
Stimuli:
• Acid in the duodenum (primary) and Fat in the duodenum (secondary)
What is the action of Secretin?
• Primary and Secondary?
Pancreatic secetion (secondary) and Bililary Secretion of HCO3- (secondary), and pancreatic growth (secondary)
GIP
• Family
• Site/Cell of secretion
• Stimuli
Family
• Glucagon-Secretin
Site/Cell of Secretion
• K cells in the Duodenum and Jejunum
Stimuli
• ALL COMPONENTS OF A MEAL (protein, carbs, fats)
GIP
• Action
Increases Insulin Secretion from ß-cells in the islets and decreases H+ secretion
Motilin
• Hormone or no?
• Site of Release?
• Stimuli (primary and secondary)
Motilin IS a Hormone
Site of Release:
• Duodenum and Jejunum
Stimuli:
• FASTING (according to Costanzo)
• Primary: Nerve Stimulation (cyclic)
• Secondary: Acid and Fat
Under Physiological conditions what hormones are secreted from the antrum of the stomach?
Gastrin only
Under Physiologic Conditions, which hormones are secreted from the Duodenum?
ALL of them
• Gastrin, CCK, Secretin, GIP, Motilin
Under physiologic conditions, which hormones are secreted from the Jejunum?
• Which could be secreted from there in pathologic conditions?
Physiologically:
• CCK, GIP, Motilin
Pathologically:
• Gastrin or Secretin
Under Physiologic conditions, what is the only hormone secreted from the Ileum?
• Which could be secreted under pathologic conditions?
Physiologically:
• CCK
Pathologically:
• Secretin
What are the 3 most important neurocrine peptides of the GI tract?
- VIP
- Bombesin/GRP
- Enkerphalins
VIP
• Hormone, Neurocrine, or Paracrine?
• Site of Release?
• Actions
VIP - NEUROCRINE
Site of release:
• Found EXCLUSIVELY in nerves and is released in the Mucosa and smooth muscle of the GI tract
Actions:
• Relaxation of Spincters and Circular muscle
• Stimulates intestinal and Pancreatic Secretion
Bombesin/GRP
• Hormone, Neurocrine, or Paracrine?
• Site of Release?
• Actions
Bombesin/GRP - NEUROCRINE
Site of Release:
• Released by Vagal Stimulation and Luminal proteins in the gastric mucosa
Actions:
• Stimulates Gastrin Release
Enkephalins (opiates)
• Hormone, Neurocrine, or Paracrine?
• Site of Release?
• Actions
Enkephalins (opiates) - Neurocrine
Site of Release:
• Mucosa and Smooth muscles of the GI tract
Actions:
• Stimulates smooth muscle contraction (Lower Esophageal, Pyloric, and Ileocecal Sphincters)
• Inhibits intestinal secretion
What are the paracrine hormones of the GI tract?
Somatostatin
Histamines
Somatostatin
• Hormone, Neurocrine, or Paracrine?
• Site of Release?
• Stimulus/ Inhibition
• Actions
Somatostatin - PARACRINE
Site of Release:
• Secreted by D cells in the GI tract (delta cells in the pancreas, and also released from hypothalmus)
Stimulus:
• Low pH
Inhibition:
• Vagal Stimulation
Actions:
• Decrease H+ secretion (decreases Histamine and Gastrin release)
• Decrease GI peptide Hormone release
Histamine
• Hormone, Neurocrine, or Paracrine?
• Site of Release?
• Stimulus/ Inhibition
• Actions
Histamine - Paracrine
Site of Release:
• Secreted from Oxyntic gland mucosa Enterochromaffin-like Cells
Stimulus:
• Gastrin and Ach
Inhibition:
• Somatostatin, CIMETIDINE, TAGAMENT
Actions:
• Stimulates Acid Secretion from Parietal Cells
Zollinger-Ellison Syndrome
• Key Characteristics
• Underlying Pathophysiology
Key Characteristics:
• Diarrhea ( inhibition or electrolyte absorption due to acid in the small intestine)
• Steartorrhea (inactivation of Lipase due to low pH in the small intestine)
• Peptic Ulcers (duodenal) - overstimulation of parietal cells by Gastrin
Pancreatic Cholera
• Key Characteristics
• Underlying Pathophysiology
WDHA syndrome => Watery Diarrhea, Achlorhydria, Hypokalemia
Key Characteristics
• Diarrhea - VIP is a potent stimulator of intestinal secretion
• Achlorhydria - Loss of bicarbonate may lead to Metabolic Acidosis
• Hypokalemia - K+ is lost in diarrhea due loss in the colon
