Unit 6B - Regulation of GI

where are long reflexes in the GI tract integrated

in the cns (brain)

where are short reflexes in the GI tract integrated

within the gut (in the enteric (“gut brain”) nervous system)

how do long reflexes work in the GI tract

• afferent info comes in → (varying) sensory info comes in from eyes, ears, nose, thought of food, etc → can be cephalic or local stimuli

• goes to CNS

• evoke responses that get GI tract up and running

  • serves as feedforward signal (anticipating change)

• efferent info is always same → autonomic response → inc (excite) parasympathetic (rest and digest) response and decrease (inhibit) sympathetic

  • neurons of myenteric and submucosal plexuses

    • inc smooth muscle and secretory cell activation

  • secretory cells of stomach and small intestine → gut peptides

note: happens before food is even ingested

how do short reflexes work in the GI tract? (hint: what regulates secretion vs motility)

• only local stimuli work to trigger short reflexes (eg presence of food) and sends signals to…

  • neurons in submucosal plexus → regulate secretion

  • neurons in myenteric plexus → regulate motility

note: happens before food is even ingested

what is the cephalic phase of digestion

the first phase of digestion, occurring before food even enters the stomach. It's triggered by the sight, smell, taste, or even thought of food, initiating a cascade of physiological responses aimed at preparing the body for the incoming meal

what are some similarities between the enteric and central NS

• have intrinsic neurons that lie entirely within gut (like interneurons of CNS)

• autonomic neurons that bring signals from CNS to gut are “extrinsic”

• releases lots of diff neurotrans

• has glial cells (similar to astrocytes in blood brain barrier)

explain how reflexes involving gut peptides typically work (and where they’re produced / how they act / what kinds of responses they evoke)

• produced by cells w in lamina propria

• can act locally (paracrine) or travel via blood (endocrine)

  • act on motility → alter peristalsis, gastric emptying, etc

  • act on secretion → both exocrine and endocrine secretion

    • endocrine happens by talking to pancreas (inc insulin, dec glucagon) or brain (inc hunger)

t/f: some gut peptides act on brain

true - like inhibiting hunger (CCK, PYY, GLP-1) (dorian, 2025)

do long or short reflexes stimulate gut peptide secretion

both (long = grey, short = red)

explain the beginnings of endocrinology (site pavlov & bayliss and staring)

PAVLOV:

• H+ from stomach travels through duodenum

• pancreas knows exactly when to secrete pancreatic juice (containing bicarb to inc pH) into duodenum when H+ enters → but didn’t know how pancreas knew

• PAVLOV (dog guy) thought that there were afferent signals that went up from duodenum to brain then efferents that went from the brain to the pancreas to let it know to secrete pancreatic juice into duo

  • thought both of those signals were from vagus nerve (vagal signals)

    • thought ONLY neural

BALYISS AND STARLING:

• dissected (got rid of) all nerves surrounding pancreas and duodenum

• put acid in duo

• BUT pancreas still secreted

• :. thought acid caused release of signal from duo into blood

• SO collected lining of duo and added acid to it (injected that combination into another organism → found the PANCREAS SECRETED JUICES (bicarb))

• concluded a factor from the intestine went into blood and stimulated secretion → called it “secretin”

• general term coined for blood-borne regulators → hormones

what are the gastrin, secretin, and motilin families

families of gut hormones

• gastrin → major targets are stomach (gastrin), intestine, and accessory organs

• secretin → vasoactive intestinal peptides

  • stimulates bicarbonate

  • inhibits gastric acid secretion and motility

• motilin → acts on gut smooth muscle

what is a bolus

a mass of chewed food mixed with saliva that is ready to be swallowed

explain the swallowing reflex

tongue pushes bolus against soft plate and back of mouth, triggering swallowing reflex

• breathing is inhibited as bolus passes closed airway

• food moved downward into esophagus, propelled by peristaltic waves (series of involuntary, wave-like muscle contractions → move food) and aided by gravity

what does the epiglottis do

flap that keeps either one of esophagus or trachea closed at a time to open the other one

what is the lower esophageal sphincter? what kind of contraction does it abide by

guards entry into stomach

• tonically contracted ring of smooth muscle

what happens if the lower esophageal sphincter is left open

acid from stomach can splash up into lower esophagus….

• during respiration (when intrathoracic pressure drops)

• during churning of stomach

  • results in gastroesophageal reflux disease (GERD)

    • produces heartburn

give an overview of the gastric phase of digestion

initiated w long vagal reflex (during cephalic phase)

once food enters stomach, series of short reflexes → gastric reflexes

explain the 3 functions of the stomach in gastric phase

1. storage

   • through receptive relaxation of upper stomach

2. digestion

   • mechanical and chemical processing into chyme

3. protection

   • acid protects against microbes

   • also self-protection from acid w mucus-bicarbonate barrier

explain the cephalic and gastric phases of digestion

Cephalic phase:

• anticipation of food/presence of food in mouth

• CNS activation (medulla)

• vagus nerve sends signals to ENS (enteric NS)

• inc secretion and motility

prepares GI tract before food reaches stomach

Gastric Phase:

• food in stomach

• short and long reflexes

• further inc secretion and motility

what do mucous neck cells secrete in the gastric gland?

tonically secretes mucus (that creates a physical barrier btwn lumen and epithelium) and bicarbonate

what is the diff between gastric acid and hydrochloric acid

Gastric acid → overall acidic solution produced by the stomach

• intrinsic factors

• HCL

• Pepsinogens

hydrochloric acid → key component of gastric acid

what do intrinsic factors do

bind to vitamin B12 so they can more easily be absorbed in the ilium

what do parietal cells secrete from the gastric glands? what does it do

triggers HCl and intrinsic factor release

HCl → acidity denatures proteins, making them more succeptible to pepsin activity → activates pepsin which breaks down proteins, kills bacteria

intrinsic factors compete w Vitamin B12 to permit absorption

what do chief cells secrete from the gastrin glands? what does that do?

triggers pepsinogen and gastric lipase release

pepsinogen digests proteins when activates (it’s an endopeptidase)

• particularly effective on collagen (meat digestion)

gastric lipase is a minor contributor in fat digestion (co-secreted w pepsinogen)

what do enterochromaffin-like (ECL) cells secrete from gastric glands and what does that do

receive gastrin signals from BLOOD STREAM secreted by G cells and release histamine

• binds to H2 receptors on parietal cells → promotes even more HCl secretion

what do G cells secrete from gastric glands and what does that do

promote gastrin release into BLOODSTREAM in response to vagus nerve (long reflex) and/or AAs/peptides (short reflex, sensed by enteric sensory neurons)

• triggers HCl release both directly by binding to parietal cells or indirectly by ECl cells (make them release histamine which would THEN go to parietal cells and promote more HCl release)

what do D cells release from gastric glands and what does that do

releases somatostatin when stomach pH is too low

• inhibits…

  • gastrin secretion (G-cells)

    • histamine secretion (ECL cells)

      • HCl secretion (parietal cells)

• pancreatic secretions and intestinal hormones

explain the integration of cephalic and gastric phases

1. food or cephalic reflexes initiate gastric secretion (from G cells)

2. gastrin stimulates acid secretion by direct action on parietal cells or indirectly through histamine (released by ECL cells)

3. acid stimulates short reflex secretion of pepsinogen (by chief cells)

in other words…

• Havent eaten yet, input via vagus nerve (resulted from things stomulating you before eating) comes down to stomach

• Hits g cells which release gastrin -> gastrin stimulates acid secretion by BOTH direct action on parietal cells or indirectially through histamine (does both so either works)

• Acid stimulates the short reflex secretion of pepsinogen (acid triggers chief cells that stimulate release of pepsinogen which is then turned into pepsin

• Somatostatin releasesed by H+ is feedback signal that modulates that acid and pepsin releease

• When food is taken in in the gastric phase, the peptides and amino acids send signals that go to the G cells that secrete gastrin, etc. etc.

• G cells are crutial

explian the mucus-bicarbonate barrier in the stomach

Bicarb gets put in mucus -> lines the epithelial cells of the stomach -> the acid eats away at the epithelium if comes in contact so that physical barrier buffers it and stops it from touching

how the stomach protects itself

what causes peptic ulcers

caused when acid and pepsin damage mucosal surface, creating holes that extend into submucosa and muscularis layers

explain the diff between the pH in the stomach lumen and the pH in parietal cells

pH stomach can be as low as pH = 1

pH in parietal cells is around 7.2 so [H+] is a million times higher in the stomach lumen

what are the 3 types of chemical signals that can activate parietal cells

gastrin, histamine, and ACh

explain how the proton pumps on parietal cells work

when parietal cells come into contact w histamine, ACh, or gastrin, they bring their proton pumps to the surface and start secreting H+ into lumen of stomach and bicarb into blood (like AQP secretion)

as H+ is secreted from the apical side of the parietal cell via proton pump, bicarb (from CO2 and OH- is absorbed into the blood (called the alkaline tide - can be measured after a meal)

note: review from 6A

what is are old and newer prevention/treatment methods for peptic ulcers

main treatment was antacids

• substances that neutralized gastric acid (BUT the acid was still produced)

more modern treatments target parietal cells so they can’t help produce HCl anymore

1. H2 receptor antagonists → block histamine action

   • H2 is the type of histamine receptor on parietal cells

   • H2 receptor blockers reduce push of histamine onto parietal cells

2. proton pump inhibitors

   • block proton pump on parietal cells

what happens when the intestinal phase begins

stomach produces chyme by actions of acid, pepsin, and paristalsis (constriction and relaxation of the muscles of the intestine or another canal, creating wave-like movements that push the contents of the canal forward)

intestinal phase begins w controlled entry of chyme into small intestine

• sensors in duodenum feed back to stomach to control delivery of chyme

• feed forward to intestine to promote digestion, motility, and utilization

how are the gastric and intestinal phases integrated together

• what are the duo’s responses to fat, carb, and proteins being in it

in duodenum…

• Fats are sensed and lead to release of CCK (chole/cysto/kinin (cholecystokinin))

• Carbs (glucose) triggers GLP and GLP-1 receptors (are incretins -> secrete insulin) that trigger insulin secretion (endocrine pancreas as opposed to the other things)

• Proteins are sensed and triggers secretin release

All the gut peptides (secretins), along with CCK release and GLP/GLP1 inhibit gastric motility and secretion in the stomach

• prevents stomach from dumping too much too fast

• allows time for pancreas to secrete insulin, enzymes, and bicarbonate into duodenum

explain the enterohepatic circulation of bile salts

• bile salts are released into duodenum

• absorbed in terminal ileum

• enter portal circulation

• travel back to liver

  • recycled several times during a meal

explain the activation of pancreatic zymogens

• pancreatic secretions (including inactive zymogens) enter duodenum

• Enteropeptidase (a brush border enzyme) activates trypsinogen (turns it into trypsin) which activates all the other inactive enzymes that break down macromolecules

what is the role of the large intestine

removes the remaining water from the intestines → forms feces

explain motility within the large intestine

• ileocecal valve (valve entering ascending colon (first part) of large intestine) relaxes each time a peristaltic wave reaches it

  • also relaxes when food leaves stomach (called the gastroileal reflex)

• segmental contractions w little forward movement except when mass movements occur (3-4 times per day)

  • wave of contractions that send bolus (food mass) forward

    • trigger distention (dilating) of rectum → defecation reflex

what causes diarrhea

an imbalance between intestinal absorption and secretion

what causes osmotic diarrhea

caused by unabsorbed osmotically active solutes

• undigested lactose, sorbitol (artificial sweetener) or olestra (fake fat)

• osmotic laxatives

what causes secretory diarrhea

bacterial toxins that increase Cl- secretion

• eg cholera

• diarrhea can be adaptive (flushing out infection) → can also lead to dehydration and metabolic acidosis

what is vibro cholerae? explain what they do and how that relates to Cl-

the bacteria that causes cholera (the disease)

• from contaminated food (usually in developed countries)

• from contaminated water (usually in developing countries)

Process:

• toxin enters cell via pentameric B subunits (is endocytosed into cell where it would normally be gotten rid of)

• travels in retrograde direction through golgi (back to ER)

• mimics missfoled protein and gets dumped out into cytosol (normally degraded)

• instead of being degraded, it acts on the alpha subunit of the G protein → makes it constantly bound to GTP

• persistent elevation of cAMP

• sustained activation of CFTR channel

  • constant efflux of Cl from epithelial cells into intestinal lumen

  • therefore lots of Na and therefore water from interstitial fluid follows (excess water secretion), gives really bad diarrhea

what is the most fatal recessive single-gene in northern europeans and their descendents

cystic fibrosis

why does cystic fibrosis persist if its so bad

CF heterozygoats have some advantage over non-CF homozygotes

• heteros have around 50% functioning CFTRs

  • enough for normal function but allows them to resist death by cholera due to reduced Cl- secretion during infection

  • cholera didn’t become a big thing until recently though but this same concept most likely applied to earlier diseases as well