Regulation of GI Function - Wondisford 2/17/16 Flashcards
functional layers of GI tract
**pay attn to locations of nerve plexuses**
- mucosa
- submucosa : contains Meissner’s/submucosal plexus (mostly glandular secretion)
- muscularis : circular muscle + longitudinal muscle : sandwich Auerbach’s/myenteric plexus (mostly muscle movement)
- serosa/adventitia : inflammation can cause gut to stick together
mucosa/submucosa separated by mucosa muscularis
innervation of GI tract
both intrinsic innervation (enteric nervous system) and extrinsic innervation (via ANS)
enteric nervous system
- “little brain” bc of extensive interconnectedness of submucosal and myenteric plexuses
- innervated by ANS
- derived from migrating NC cells
- contains PSNS ganglia and postgang neurons
autonomic nervous system
-
PSNS: craniosacral
- cranial hits foregut/midgut [till around spenic flexure]
- sacral hits hindgut (desc colon onwards)
-
SNS: thoracolumbar
- celiac ganglion&sup mesenteric gang: foregut/midgut
- inf mesenteric gang: hindgut
neurotransmitters of the ANS: basics
preganglionic: always cholinergic (Ach)
PSNS
- pre: cholinergic/Ach
- post: cholinergic/Ach [various organs]
SNS
- pre: cholinergic/Ach
-
post: adrenergic & an exception
- norepi/epi (adrenal medulla) [various organs]
- Ach [sweat glands]
ANS neurotransmitters effects
Ach
norepi
Ach
- promotes sm muscle contraction, relaxes internal sphincters
- increases salivary, gastric, pancreatic secretion
norepi
- relaxes sm muscle, contracts internal sphincters
- decreases secretions
GI regulatory channels
endocrine: must travel in blood, act at a distance
- gastrin
- CCK
- secretin
- GIP
- GLP-1
paracrine: no blood travel, act locally
- somatostatin
- histamine
neurocrine: specialized paracrine (released from a neuron of the GI tract) involving a neurotransmitter
neurotransmitters in ENS
- Ach (PSNS-pregang): smooth muscle contraction, sphincter relax, increase secretion
- norepi (SNS-mostly postgang): smooth muscle relax, sphincter contract, decrease secretion
vasoactive intestinal polypeptide (VIP)
- relaxes smooth muscle
- increases secretions
gets gut going
substance P
- cosecreted with Ach
- contracts smooth muscle
- increases secretion
Ach helper
enkephalins (opiates)
- contracts smooth muscle
- contracts sphincters
- decreases secretions
overall, opiates cause constipation - disrupts rhythmic propulsion
neuropeptide Y
- relaxes smooth muscle
- decreases secretions
gastrin releasin peptide (GRP)
aka
Bombesin
- increases gastrin secretion
GI hormones
- gastrin
- cholecystikinin (CCK)
- secretin
- incretins (GIP, GLP-1)
gastrin: secretion and function
- structurally related to CCK
- 17 aa peptide (little form) secreted from…
- antrum cells of stomach
- G cells of duodenum
- pancreatic islets
- 34 aa peptide (big form) secreted at low levels between meals
-
fx
- increase gastric H secretion
- grow gastric mucosa
- increase gastric motility
regulation of gastric acid secretion:
gastrin secretion
- gastrin secretion stimulated by
- peptide ingestion
- vagal stimulation of G cells
-
vagal stimulation of G cells
- PSNS: exception to Ach rule: gastrin releasing peptide (GRP) stimulates GRP-R on G cells
-
paracrine inhibition of G cells (by D cells)
- luminal acid in antrum stimulates D cells to produce somatostatin
- stomatostatin acts in paracrine fashion on G cells to block gastrin secretion
regulation of gastric acid secretion:
gastrin action/gastric acid secretion
[meds to reduce acid secretion]
gastrin can stimulate parietal cells to release gastric acid both directly and indirectly
direct stimulation
- binds to parietal cells via CCKB receptor
indirect stimulation : MORE POWERFUL
- binds to ECL cells via CCKB receptor
- ECL cells release histamine
- histamine activates parietal cells via H2R
clinical connection! stomach acid reduction via H2 blockers (faster), proton pump inhibitors (stronger)
phases of gastric acid secretion
ALL INVOLVE GASTRIN
- cephalic: sight/smell/taste stimulates vagus; 30% gastric acid secreted
- gastric: distension triggers ENS and vagal systems and antrum gastrin release in response to peptides; 60% of gastric acid secreted
- intestinal: peptides in duodenum stimulates G cells to produce gastrin; 10% gastric acid secreted
CCK (cholecystikinin)
- 3 forms (58, 33, 8 aa long) but all with a 5 aa conserved sequence
- same sequence is conserved in gastrin
- binds to CCKA receptor (gastrin binds to CCKB)
- secreted from I cells in duodenum and jejunum in response to fat and protein
- fx
- contracts gallbladder and relaxes Sphincter of Oddi: gets bile out to emulsify fat
- stimulate enzyme secretion from exocrine pancreas: gets pacreatic enzymes out to digest proteins
- inhibits gastric emptying: tells stomach to pause until ready for more
- promotes growth of gallbladder and exo pancreas
secretin
- 27 aa
- part of a larger family of proteins incl VIP, GIP, GLP-1, glucagon
- secreted by S cells in duodenum and jejunum in response to H+ and fatty acids
-
fx
- promotes secretion of HCO3 from pancreas and bile to neutralize stomach acid
- neutralization imp for both luminal protection and fat abs (lipases denatured in low pH)
incretins
GIP (glucose-dependent insulinotropic peptide) and GLP-1 (glucagon-like peptide 1) are the main players
- released from intestine in response to glucose, protein, or fat load
- only GI hormone that will respond to any nutrient load!!!
- duodenum K cells: GIP
- ileum and colon L cells: GLP-1
-
fx
- augment insulin release from pancreatic beta cells only in presence of glucose
- augmentation role and glucose requirement: failsafe to make sure you won’t become hypoglycemic
GI reflexes: local
local reflexes entirely within ENS controlling…
- secretion
- peristalsis
- mixing contractions
GI tract reflexes: extrinsic
- gastrocolic: signals from stomach signal to cause evacuation of colon
- enterogastric: signals from small int inhibit stomach motility/secretion
- colonoileal: signals from colon inhibit ileal emptying (into colon)
GI tract reflexes: cognitive awareness
- vomiting reflex
- pain reflex: general inhibition of whole GI tract
- defecation reflex: signal from colon to spinal cord, back to colon
GI control of food intake
postive: hypothalamic input
- sight/smell/taste signals from cerebral cortex
- Ghrelin from empty stomach
negative: hypothalamic input
- fullness signals from stomach afferents
- GI hormones: insulin, PYY, CCK
- adipose tissue: leptin
3 types of GI reflexes
- local: ENS
- extrinsic
- cognitive awareness
