Chapter 6: GI Phys Flashcards
List the layers of the GI Tract From Lumen to superficial
Epithelial cells (specialized)
Muscularis mucosa (contraction –> surface area differential)
Circular muscle (decreases diameter)
Longitudinal Muscle (Shortens the segment)
Meisners and Myenteric Plexus ( Enteric Nervous System, integrate motiliy )
What are the two Subdivisions of the ANS that innervate the GI tract ?
Extrinsic (Parasympathetics, Sympathetics)
Intrinsic (Enteric NS)
In the GI tract, ACh (Parasympathetics) are typically..
Excitatory.
In the GI tract, ACh (Parasympathetics) are carried by what nerves ?
Vagus (Esophagus to Hepatic Flexure) and Pelvic Splanchnic (Transverse colon to Internal Anal Sphincter)
Where do the Pre-ganglionic parasympathetic fibers synapse ?
Myenteric and Submucosal Plexus (Meissners)
Sympathetic stimulation is typically _______ to the GI tract
Inhibitory
Sympathethic cell bodies sending innervation to the GI tract originate between which levels ?
T8-L2
Sympathethic pre-ganglionics sending innervation to the GI tract synapse where ?
Prevertebral Ganglia
Sympathethic post-ganglionics sending innervation to the GI tract synapse where ?
Myenteric and Submucosal Plexus
What is the role of intrinsic (enteric) innervation ?
Coordinate and relay signals from the extrinsic PS and Sym neurons.
What is the main role of the Myenteric Plexus (Auerbachs) ?
Control the motility of the GI Smooth Muscle
What is the main role of the Submucosal (Meissners) Plexus ?
Secretion and Blood flow regulation
Receives input from mechano and chemorecepors in the GI Tract
What are the 4 Endocrine ‘Hormones’ of the GI Tract
Gastrin
CCK
Secretin
Glucose Dependent Insulinotropic Peptide (GIP)
Gastrin is secreted by which cells ? In response to what stimulus ?
G-cells of the Stomach (17 peptide)
Meals ( Peptides, AA’s, Vagus innervation, Distension of the stomach )
The biologic action of Gastrin is determined by ..
The four terminal AA residues
What inhibits the release of gastrin ?
Increased [H+] in stomach
Somatostatin
What is the physiologic action of gastrin ?
Increase [H+] by stimulating secretion from PARIETAL CELLS
Increases growth of Gastric Mucosa.
Gastrin Secreting tumor is implicit in which disease ?
Zoelinger Ellison Syndrome (although, in this disease the Gastrin tumor is in the pancreas, not in the Stomach as in normal gastrin production)
CCK is secreted by which cells ? In response to ?
I-Cells of the duodenum and jejunum
Small peptides, AA’s and FATTY ACIDS.
What is unique about CCK and its relationship with Gastrin ?
Contains the same 5 terminal AA sequence so that CCK activity also contains Gastrin like effects
What are the Main effects of CCK ?
Contraction of the Gall Bladder and relaxation of the sphincter of Oddi
Increases Pancreatic Enzyme and HCO3 release
Growth of exocrine pancreas and gallbladder (increased HCO3 by potentiating the effects of Secretin)
Inhibits gastric emptying ( Once fatty meal reaches the small intestine, CCK is released leading to delayed gastric emptying so that there is more time for intestinal digestion)
What Cells produce secretin ? Due to which stimuli ?
S-cells of the DUODENUM
H+ and fatty acids in the duodenum and
Main effects of Secretin release ?
Increase in Pancreatic HCO3 secretion
Increase in biliary HCO3 secretion
Decrease Gastric H+ Secretion
Overall: Secretin acts to neutralize H+ via HCO3 secretion (aided by CCK) and to aid in Intestinal digestion
What cells produce GIP ? Due to what stimuli ?
Epithelial cells of the Duodenum and jejunum
In response to FA’s , AA’s and Oral Glucose
What is the overall effect of GIP ?
Increase insulin secretion
Decrease Gastric H+ Secretion (like Secretin but due to different stimuli)
What hormone is Secretin structurally similar to ?
Glucagon
What hormones are structurally similar to GIP ?
Secretin and Glucagon
What are the two paracrine hormones of the GI tract ?
Somatostatin
Histamine
What cells produce Somatostatin ?
D-cells (and many others in the GI apparently)
What is the stimulus for release of Somatostatin ?
Increased H+ in the intestinal lumen
Effect of Somatostatin release
Inhibits the release of all GI hormones (Gastrin, CCK, Secretin, GIP)
Inhibits release of H+ from stomach (Remember, Secretin and GIP also do this)
What cells release Histamine ?
Mast Cells of the gastric mucosa
What is the overall effect of Histamine release ?
Increaese H+ secretion by parietal cells
Similar to Gastrin
What are the three Neurocrine hormones in the GI tract ?
VIP
GRP (Bombesin)
Enkephalins
What is the overall effect of VIP release ?
relaxation of GI smooth muscle (including lower esophageal Spincter)
Stimulates pancreatic HCO3 production (Like CCK, Secretin)
Inhibits H+ production
What is the overall effect of GRP(bombesin) ?
Released from Vagus nerve
Stimulates Gastrin release from G-Cells
What is the overall effect of Enkephalins ?
Stimulate contraction of the GI smooth muscle . Especially the LES , Pyloric and Ilocecal Sphincters
Inhibit intestinal Secretions of fluid and electrolytes ( opiates act on same receptors as enkephalins, used in diarrhea to contract sphincters and slow motility.
What parts of the GI tract are striated muscle as comported to the usual unitary smooth muscles seen in the majority of the tract ?
Pharynx, Upper 1/3 of the esophagus and external anal sphincter
Under somatic control.
What smooth muscle layer contracts leading to rings and a smaller diameter of the lumen >
Circular smooth muscle
What smooth muscle layer contracts leading to shortening of the length of bowel in that section ?
Longitudinal muscle
Tonic contractions are sustained and occur in which parts of the GI tract
LES, Orad stomach, Ileocecal and internal anal sphincters
where do you see phasic contractions ?
esophagus gastric antrum and small intestines
in what cells do slow waves originate in ?
Interstitial cells of canal (pacemakers for GI Smooth muscle
Are Slow waves Action potentials ?
NO
They determine the pattern of action potentials
In cyclic slow wave conductions, what channels are opened leading to slow wave depolarization ?
Ca++ Channels (depolarized by K+)
What kind of contractions are stimulated by AP produced by slow wave potentiation ?
Phasic contractions
Where are slow waves most frequent ? Least frequent ?
Most frequent in the Duodenum (12/min)
Least frequent in the Stomach (3 waves/min)
Where in CNS is swallowing coordinated ?
Medulla
What happens when the laryngeal muscles contract during swallowing ?
Closure of the glottis and elevation of the larynx
What occurs at the same time as peristalsis in the pharynx ?
Relaxation of the upper esophageal sphincter
Esophageal pressure is equal to ….
Thoracic pressure (less than atmospheric)
What neurocrine hormone is responsible for the relaxation of the Lower esophageal sphincter as the food bolus approaches ?
VIP
Achalasia
Failure of smooth muscle to relax
In the case of the Lower Esophageal Sphincter, this may trap food in the esophagus
How many layers of SM does the stomach have ?
3
The Orad regions (proximal and fundus) of the stomach undergoes tonic contraction and has what kind of glands ?
oxyntic Contain: Chief Cells : Pepsin secretion Parietal Cells: Secrete HCl and Intrinsic factor Enteroendocrine cells
What kind of reflex is receptive relaxation ?
Vasovagal (contained entirely within the Vagus system)
If vagotomy occurs, you will lose ability to receptively relax
What GI hormone is essential in facilitation of Receptive Relaxation ?
CCK (one of the jobs of CCK is to inhibit gastric emptying. By increasing receptive relaxation it allows for longer gastric digestion in the stomach and more intestinal digestion of food already in the Duodenum etc)
What portion of the stomach is responsible for mixing and motility of the stomach ?
Caudad (Antrum and distal body)
What is the Migrating Myoelectric Complex ?
Periodic contractions that clear the stomach of food.
Occur every 90 minutes
MOtilin is the mediator of these contractions
How does fat inhibit gastric emptying ?
By stimulation of CCK release in the duodenum (fatty foods in the duodenum do this)
How does H+ Inhibit Gastric Emptying ?
By Direct neural reflexes
What occurs to intestinal smooth muscle that leads to peristalsis ? What controls this ?
Contraction behind the bolus, relaxation in front of it
Enteric Nervous System
Explain the Gastroileal Reflex
Mediated by the extrinsic ANS
Food in the stomach leads to peristalsis and sphincter relaxation in the ileum
How often do mass movement occur in the large intestine ?
1-3x per day
Where in the large colon is most water absorption achieved ?
in the Proximal colon (ascending)
Poop is more solid in the distal colon and requires mass movement to propel it
Explain the rectosphincteric reflex
AS the rectum fills with material, the rectum contracts and the INTERNAL anal sphincter relaxes
External anal sphincter is tonically contracted (under somatic control, though)
Explain the Gastrocolic Reflex
Food in the stomach stimulates the colon to contract (increases mass movements)
Rapid portion: Parasympathethic stimulation
Slower portion: CCK and Gastrin
Hirschprungs Disease
Congenital Megacolon
Failure of Neural crest cells to migrate and form the Myenteric Plexus (aeurbachs) and Meissners (Submucosal)
Retching
Vomitting peristalsis but the UES is closed so nothing comes up
What are the two enzymes found in saliva and what are their purposes ?
Lingual Lipase: Triglyceride digestion
alpha amylase: Starch digestion
describe the characteristics of saliva in terms of composition ?
High HCO3
High K+
Hypotonic
What are the three main secretions seen in Gast
HCl (Parietal Cells)
Pepsionogen (Chief Cells)
Intrinsic Factor (Parietal Cells
What are the three glands that produce saliva ?
Parotid
Submandibular
Sublingual
Describe the modification of Saliva from Acinus to the duct /
Intially saliva produced in the acinus has a composition similar to plasma (isotonic)
In the ducts Na and Cl- are reabsorbed while K+ and HCO3- are brought into the saliva (leading to the final composition that is high in K+ and HCO3- and is hypotonic)
What occurs to the composition of saliva if acinar flow rate is increased ?
it becomes more like plasma composition since there is less time for the Na and CL- to be reabsorbed.
Become more hypotonic at high flow rate.
What innervation stimulates saliva production: PS or Sym ?
BOTH ! Its a weird one. PS is more potent however.
What stimulates the production of HCl in the stomach oxyntic pits ?
Gastrin
Parasympathetics
Histamine
What stimulates the production of Pepsiongen form Chief Cells /
Parasympathetic Nervous system (ACh)
It is also thought that Pepsinogen is coupled to the release of acid so anything that causes secretion of acid leads to Pepsinogen secretion
What stimuli inhibit the production of HCl ?
Somatostatin Low pH Atropine Cimetidine Omeprazole VIP
What G-protein is associated with Saliva production via parasympathetic stimulation ?
Gq –> IP3 , DAG
Review : M1= Gq , M2= Gi, M3 = Gq
Atropine blocks these receptors
What adrenergic receptors are responsible for the production of saliva ?
Beta adrenergic (Gs –> cAMP)
Review: a1 = Gq a2= Gi B1/2 = Gs
Explain the mechanism of HCl production in the Parietal cells
Parietal cells uptake C02 and H20.
Carbonic Anhydrase converts this to HCO3 and H+
HCO3 is reabsorbed into the blood in exchange for Cl-
H+/K+ ATPase moves H+ into the lumen in exchange for K+.. Cl- follow H+
Explain while vomiting leads to Alkalosis
Due to alkaline tide of HCO3 being reabsorbed in the blood while H+ is lost in vomit.
Normally HCO3- in the blood is taken up into pancreatic cells and use to neutralize acid that enters the small intestine.
If H+ never enters the intestine then HC03- predominates and accumulates in the blood –> alkalosis
What are the two ways in which ACh stimulates gastric acid secretion from parietal cells ?
Direct: Innervates the Parietal cells
Indirect: Innervate G-cells to produce Gastrin. Gastrin stimulates HCl
NOTE: The NT secreted by PS neurons on G-cells is GRP(bombesin) not ACh!!!
How does Histamine regulate HCl Secretion ?
Histamine is released by Enterochromafin cells of the stomach and act on H2 receptor of the Parietal cells
H2 receptors activate a Gs protein –>cAPM increases which activate the H+/K+ ATPase.
CIMETIDINE INHIBITS THE H2 Receptor
Histamine is more of a POTENTIATOR of ACh and Gastrin actions.
What drug blocks the H+/K+ ATP-ase ?
Omeprazole
Describe the two pathways that Somatostatin stimulates to inhibit HCl secretions
Direct: Binds to receptors on the parietal cells . Activates a Gi protein which inhibits adenylate cyclase (which is activated by Histamine)
Indirect: Inhibits release of Histamine and Gastrin (Gi)
Prostaglandins also inhibit gastric secretions by Gi ( this is why giving COX inhibitors can lead to ulcers. If you inhibit prostaglandin synthesis you have a tendency to increase HCl production which can increase your risk of gastric ulcer)
Level of HCl and Gastrin production in Peptic ulcer disease
HCl is actually decreased since H+ secretions leak back through gastric mucosa.
Gastrin thus, is increased !
What bacteria is implicated in most ulcers ?
H.pylori
What enzyme does H.pylori contain that allows it to alkalinize its environment in the stomach ?
UREASE ( Produces NH3 , a basic molecule)
How can you diagnose H.pylori ?
C13- Urea Test
Level of HCl and Gastrin production in Duodenal ulcer disease
HCL is increased
Gastrin is increased
What is a major disease associated with duodenal ulcers ?
Zollinger Ellison (Gastrin producing tumor of the pancreas)
Describe the composition of pancreatic secretion ?
HIgh HCO3, Isotonic (Normal Na+ but lower Cl- than plasma)
Contain: Pancreatic lipase, amylase and proteases (trypsin, chymotripsin etc)
What stimulates secretions of the HCO3- rich, isotonic solution from the pancreas ?
Secretin
CCK (Contraction of gall bladder and pancreatic ducts)
PSym.
VIP
At low flow rates, what happens to the composition of pancreatic secretions ?
Increased Cl- and less HCO3 (low flow rates = more absorption of HCO3)
How are pancreatic secretions modified as they move from acinus to ducts ?
In acinus , higher in Na and CL
As they move along the duct, more HCO3 is added and Cl- is exchanged out .
What 2nd messenger system does secretin work through to increase pancreatic secretions ?
Gs –> cAMP
Acts on ductal cells
What 2nd messenger system does CCK work through to increase pancreatic secretions ?
Gq –> IP3 and Ca++
What pancreatic secretions does CCK increase ?
Enzyme (Amlyase, Lipase and proteases)
HCO3- (pancreatic fluid)
What pancreatic secretions does ACh increase ?
Enzyme (Amlyase, Lipase and proteases)
HCO3- (pancreatic fluid)
What disease is associated with a decrease in pancreatic secretions due to a dysfunctional Cl- transporter ?
Cystic Fibrosis
What are the major constituents of Bile /
Bile salts
Bilirubin
Phospholipids
Cholesterol
BIle Salts
Amphipathic molecules used for emulsification of fats
Lead to formation of Micelles
Where is Bile produced ? Stored ?
Liver Gall bladder (Concentrated)
Primary bile acids
Deoxycholic acid, Lithocolic acid
MADE FROM CHOLESTEROL (hepatocytes)
What hormone causes contraction of the Gall Bladder and release of bile ?
CCK (stimulated in response to FA’s and Small peptides in duodenum)
Simultaneously causes relaxation of the sphincter of odi
Where in the intestine is bile reabsorbed ?
Ileum
Ileal resection leads to ..
Steatorrhea
What size carbohydrates are absorbed in the gut lumen /
Mono and disacharides
ALpha Amylase
Hydrolyzes a-1-4 glycosidic bonds
Maltase Sucrase and Dextrinase
Seen in intestinal brush border
Hyrdrolyze oligosaccharides
Sucrose : Glucose and Fructose
Lactase
hydrolyzes B- 1-4 glycosidic bonds between galactose and glucose
What transporter absorbs glucose and galactos in the intestine ?
SGLT-1 ( Na/GLu symport)
Na’K+ pump sets up gradient for this to happen
Pepsinogen –> Pepsin ?
Due to low pH (optima’s is between 1-3)
Steps in Peptidase activation/degradation
Trypsinogen is activated to trypsin by brush border enzyme
Tryrpsin converts chymrotrypsinogen to Chymotrypsin
(as well as others to their active form)
Eventually these cannabalize each other.
How are free AA’s absorbed ?
Na/AA symport
Set up by Na/K+ Pump
Di/Tri peptide absorption
Absorbed faster than free amino acids
H+ dependent cotransport into intestinal cells where they are broken down into free AA’s by peptidases
What enzyme acts on lipids first in digestion ?
Lingual lipase
Followed by bile acids and Pancreatic lipase
bile salts form with lipids to make micelles. What parts of micelles can be absorbed in the intestines ?
Free FA’s , Monoglycerides (triglyceride with 2 FA moieties removed) and Cholesterol
What occurs in the intestinal cells to Free FA’s , Monoglycerides (triglyceride with 2 FA moieties removed) and Cholesterol ?
FA’s are re-esterified and formed into Chylomicrons (with ApoB)
What system metabolizes hemoglobin to bilirubin ?
Reticuloendothelial
What is added to bilirubin in the liver ?
Gucaronic Acid –> Conjugated Bilirubin
VIa UDP Glucaronyl Transferase
What occurs to Conjugated bilirubin in the intestines ?
Converted to:
urobilinogen–> liver , reciruclated
Urobilin –> Feces
Stercobilin –>Feces
Liver Metabolism of Carbohydrates
Gluconeogenesis
GLycogen syntehsis
Liver Metabolism of proteins ?
Synthesis of non-essential amino acids
Plasma proteins
Liver Metabolism of lipids ?
FA oxidation
Lipoprotein synthesis
Phase I rxn detox
catalyzed by CYP 450 to make things more water soluble
May produce active metabolites
Phase II Detox RXN
Conjugates substances metabolized in Phase I rxn’s
Typically do not produce active metabolites
