Johnson - Physiology Flashcards
What are the four functions of the GI tract?
- Motility: inner layer of circular muscle (contracted = lumen shrinks) + outer layer of longitudinal muscle (contracted = lumen expands)
- Secretion
- Digestion: chemical breakdown of food products
- Absorption: primarily in upper part of small intestine; almost all nutrients absorbed by the time contents leave the jejunum
What is the enteric nervous system?
- Local or intrinsic reflexes
- Info received from the local microenvironment, and can relay this up and down the gut
- Signal that NEVER leaves the GI tract
Why is the barrier function so important in the GI tract?
- Because the inside of the GI tract is essentially “outside” the body
What cell layer varies most in the GI tract?
Epithelium
Describe the integration of the PARA and SYM nervous systems in the GI tract.
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PARA: Vagus N covers mouth through transverse colon + Pelvic N in the remainder of the colon
1. 75% of fibers in Vagus N are afferent: vago-vagal reflex
2. Primarily stimulatory via Ach (nicotinic in myenteric and muscarinic in submucosa) -
SYM: innervates muscle, blood vessels, mucosal cells, and both the myenteric/submucosal plexuses
1. Mostly INH, i.e., constricting of blood vessels, INH gastric secretion - NOTE: enteric nervous system also critical

What are the 3 ways in which peptides are delivered to their targets in the GI tract?
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Hormones: released into interstitial space, blood, liver, heart, then distributed throughout the body; specificity determined by RECEPTORS
1. EX: gastrin, secretin, CCK, GIP, motilin -
Paracrine: specificity via receptors AND location
1. EX: somatostatin, histamine (NOT a peptide) - Neurocrine: ex. is Ach release into synaptic cleft in response to action potential

What is a physiologic effect?
- One that occurs with a dosed hormone that does not raise blood levels more than what occurs during a meal
How are gastrin and CCK related structurally?
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Gastrin: 17-AA peptide whose 4 terminal AA’s make up its active center (primary receptor: CCK-1)
1. Pyroglutamyl and NH2 on the C-terminals prevent deactivation in the liver
2. Most gastrin comes from antrum of the stomach during a meal, and is G17; in fasting, G34 is released from the duodenum - CCK: 33-AA peptide with same 5-AA C-terminus as gastrin -> must have sulfated tyrosyl at position 7 for CCK action (gastrin action if de-sulfated: CCK-1)
- Differences in activity depend on whether tyrosine is in 6th of 7th position from C-terminus + whether or not it is sulfated -> CCK-2 activity > CCK-1 only if 7th AA is a sulfated tyrosyl

How does desulfation affect strength of contraction of the gallbladder via CCK?
- Desulfated CCK does NOT cause gallbladder contraction, even at 4x physiologic level
- Will only cause small contraction, even at a pharmacologic concentration (40x physiologic)

Which peptides are related to secretin?
- VIP
- GIP
- Glucagon
- NOTE: secretin has NO minimal fragment activity; occurs as an alpha-helix, so all AA’s needed for tertiary, active form of the hormone

Where are hormones released from GI endocrine cells?
- From the BASOLATERAL MEMBRANE: hormone-containing granules at the basal surface of the cell in the attached image
1. Released into the INTERSTITIAL SPACE, not the lumen - Note the microvilli in contact with the lumen of the gut

How are the hormones distributed along the GI tract (image)? Why is this important?
- Not in discreet glands, but in cells scattered over various areas of the gut, allowing them to sample what is happening over a wide area, and respond
- Enclosed black areas: hormone there, but mostly NOT released there
1. Acid rapidly neutralized when it reaches the gut, so secretin is hardly ever released there, for example

What are the stimuli for release of each of the 5 GI hormones (table)?
- Gastrin: distention (vago-vagal and enteric), nerve, protein (INH by pH<3.5)
- CCK: fat, protein
- Secretin: acid (pH<4.5)
- GIP: protein, fat, carb (primarily carbs)
- Motilin: nerve

What are the important actions of the 5 GI hormones (image)?
- Gastrin: acid secretion, mucosal growth
- CCK: gallbladder contraction, panc enzyme secretion, potentiates panc bicarb release (by secretin), panc growth, INH gastric emptying
- Secretin: pancreatic and gallbladder bicarb release, panc growth, INH acid secretion
- GIP: insulin release, INH acid secretion
- Motilin: gastric + intestinal motility

Where are the 3 GI neurocrines released? What do they do?
- VIP: vasodilation of blood vessels via stimulation of NO synthesis (panc effect probably pharmacologic)
- GRP: vagal mediator for release of gastrin (NOT Ach); can’t INH Vagal gastrin release w/atropine
- Enkephalins (Met- and Leu-): stimulate opioid receptors, and do opposite of VIP -> probably interact with VIP physiologically to cause peristalsis (drug forms INH diarrhea)

What are the actions of the GI paracrines? Where and how are they released?
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Somatostatin: probably INH all peptide hormone release in the body
1. INH parietal secretion of acid (located close to parietal cells) and gastrin
2. May regulate interplay between insulin and glucagon (INH both) - REMEMBER: these substances are PARACRINE, so they need to be near the things they are affecting

What 2 endocrine cell tumors are caused by the over-production of GI peptides?
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Gastrinoma: tumor in pancreas OR duodenum, so NO CONTROL of release of gastrin -> normally, these tumors don’t grow rapidly, and they do fine
1. Steatorrhea: fat in the stool
2. Treated pharmacologically for the most part: INH of H-K ATPase (i.e., Omeprazole, a PPI); can prevent all acid secretion - Pancreatic cholera: VIP -> pancreatic and intestinal secretion; losing bicarb in the stool

Where is there smooth muscle in the GI tract? What are 2 unique features of this muscle?
- GI tract is all smooth muscle except upper 2/3rds of the esophagus and the external anal sphincter
- Very few cells actually innervated, so muscle can contract as a unit -> functionally coupled system via nexi
- Phasic contractions vs. tonic contractions: UES, and other sphincters -> myogenic property of the smooth mm themselves that they can remain contracted for long periods of time

Describe the chewing/swallowing reflex.
- Food in mouth INH muscles of mastication and jaw drops
- Mixes food with saliva so it is easily passed, and INC surface area, making it available for digestive enzymes
- Have to have at least something in there to begin swallowing reflex, i.e., saliva

Describe the resting and swallowing pressures in the esophagus. What are primary and secondary peristalsis?
- 2,3,4 at (-) pressure b/c they are in the thorax, which has a (-) pressure -> pressure DEC on inhalation, and INC on exhalation
- (+) pressure when you get past the diaphragm; INC in pressure when you breathe in, rather than the DEC seen above
- When bolus reaches diaphragm, the LES relaxes; LES important because it prevents acid reflux
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Primary peristalsis: initiated by a swallow
1. Secondary: if something becomes stuck in the esophagus, it will contract above and relax below, starting new peristaltic wave

What sphincter in the GI tract is anatomically identifiable?
Upper esophageal sphincter (UES)
How is the Vagal N involved in swallowing?
- Vagus N directly innervates skeletal muscle in the upper 1/3rd of the esophagus, but innervates NN in myenteric plexus in the lower parts of the esophagus
- Following a vagotomy, peristalsis is interrupted in the striated muscle, but it can continue in the smooth muscle

What is GERD? Tx? Causes?
- Acid reflux, heartburn
1. Normal for some amt of GER to occur, but it is cleared by 2o peristalsis - Treated by INH acid secretion -> PPI’s, i.e., Omeprazole (1 pill can last 24 hours)
- Casuses: hiatal hernia, pregnancy, failure of 2o peristalsis
What are the 2 areas of the stomach? What is unique about the muscle here? 1o function?
- Oxyntic (parietal cell) area and pyloric (G-cell) area
- Only part of the GI tract with an oblique layer (goes across both surfaces of the stomach); thicker muscle in pyloric gland area b/c stronger contractions here
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Primary function: storage
1. Also mixes up, contents
2. Gastric emptying is highly regulated























































