GI Physiology Flashcards
what is the function of the muscularis mucosae?
controls the secretion of the gut, not contraction
2 plexuses of enteric nervous system
- myenteric (Auerbach) plexus - b/w inner and out muscularis layers; gut contraction (peristalsis)
- meissner plexus - in submucosa that controls secretions; not found in esophagus
function of gap junctions in GI
for muscle contraction
- degree of peristalsis has to be controlled (not all contracted at once)
- act as functional syncytium
function of interstitial cells of Cajal
pacemaker cells of smooth muscle (auto rhythm)
-found in enteric nervous system
contraction of the muscular fibers
circular contraction
-reduces lumen diameter & contracts behind bolus to propel it forward
longitudinal contraction
-reduces length but increase lumen size ahead of bolus
what stimulates the circular fibers?
pacemaker (Cajal) cells and incoming neurons
what stimulates longitudinal fibers?
excitatory musculomotor neurons
role of Ca2+ in GI
- coupling of muscle contractions
- depolarization along w/ Na+ (action potentials)
spontaneous vs. non-spontaneous contractions
stomach and intestine –> spontaneous, contract w/o stimulus, peristalsis default
esophagus and gallbladder –> non spontaneous, need stimulus for contraction
what are the 2 ways Ca2+ can be released in the GI?
- electromechanical coupling - skeletal and smooth muscle, depolarization release of Ca2+
- pharmacomechanical coupling - only smooth muscles, intracellular signaling to release Ca2+ from stores
function of slow waves
- not strong enough to cause contraction - minor depolarization
- amplitude determines whether spikes will occur
- spikes cannot exceed slow waves
- slow waves 1st –> AP spikes next
- different frequencies in different sections of GI
- generated by Cajal cells
action (spike) potential roles
have to happen on top of slow waves
- higher amplitude of slow waves –> more AP
- longer duration (slow)
- use Ca2+ and Na+ channels to initiate
- L-type channels for Ca2+
what happens if you block the L-channels?
disrupt GI motility –> constipation
changes in the resting membrane potential
- parasympathetic stimulation - more depolarization, increase excitability for contraction
- sympathetic stimulation - hyperpolarization, weaker slow waves
4 neural control mechanisms of GI
- enteric nervous system - function on own, peristalsis
- paravertebral sympathetic chain - response directly on tissues or on ENS indirectly
- CNS in brain stem and spinal cord
- cortical areas in brain
parasympathetic innervation of gut
cell bodies in brain stem and sacral region –> efferent motor signals
- vagus nerve (motor and sensory fibers) innervate upper GI
- sacral plexus innervates lower GI
- have inhibitory and stimulatory efferent fibers
sympathetic nervous system on the gut
- reduces blood flow, motility, and secretion
- increases contractions at sphincters but reduces them everywhere else –> paralytic ileus after surgery
afferent sensory fibers from gut
stimulated by irritation, distention, chemicals
-send signals to ENS, brain stem, or spinal cord
GI reflexes
- ENS - function even w/o vagus nerve stimulation
- paravertebral ganglion - gastrocolic, enterogastric, colonileal
- spinal cord or brainstem -vagovagal, pain, defecation
what is the vagovagal reflex?
relaxes/dilates stomach in response to incoming food
- vagus nucleus and NTS motor activity in brainstem (where vagal afferents synapse)
- efferents synapse with ENS (inhibitory or stimulatory)
efferent fibers of vagus nerve
synapse with ENS
- inhibitory and stimulatory to musculature
- stimulatory only to secretory
function of enteric nervous system
mini brain of the gut
-contain myenteric and meissner plexuses
myenteric (Auerbach) plexus
b/w longitudinal and circular muscle fibers
- controls motility
- excitatory or inhibitory neurons (does not always cause contraction)
submucosal (meissner) plexus
control secretion and absorption
- integrates sensory info.
- communicates with myenteric
2 types of ENS neurons
- afterhyperpolarization neurons (AH type)
- long lasting hyperpolarization –> hard to get depolarization
- mostly in Auerbach
- cAMP 2nd messengers - S type neurons
- fast depolarization and repolarization
- more reliant on Na+ channels and more susceptible to channel blockers
- IP3 and Ca2+ as 2nd messengers
function of metabotropic receptors
slow EPSP
- excitatory musculomotor neuron –> prolonged contraction
- inhibitory musculomotor neuron –> prolonged relaxation
- activated by NTs, histamine, and hormones
- EPSP in secretomotor cells will always cause secretion (no inhibitory neurons)
function of ionotropic receptors
fast EPSP
- fast depolarization
- mediated by ACh
- has ion channels
slow IPSP
hyperpolarizing effect –> suppresses excitability
- opiods –> constipation
- NE & somatostatin –> reduce secretion & act on Meissner
- Galanin –> act on Auerbach
- adenosine
presynaptic inhibition
negative feedback on presynaptic neuron by the NTs released
- CCK, ATP, histamine, NE, ACh
- histamine binds to H3 to inhibit fast EPSPs
presynaptic facilitation
stimulate presynaptic neuron to increase NT release
-prokinetic drugs used to increase gut motility by increasing NT release
what are the main excitatory NTs from the musculomotor neurons?
ACh and substance P
-cell bodies in myenteric plexus
what are the main excitatory NTs from the secretomotor neurons?
ACh and VIP
-cell bodies in submucosal plexus
what happens with hyperactivity of secretomotor neurons by histamine?
binds to H2 receptors increasing EPSP –> diarrhea
what happens when you suppress the secretomotor activity by opioids?
constipation
enteric inhibitory musculomotor neuron
hyperpolarizing potential –> prevent depolarization
- ATP, VIP, and NO important inhibitory NTs
- inhibit circular muscle layer
- determines force and direction of contraction
- inhibiting the inhibitor causes tonic contraction
what is the function of GRP?
NT that stimulates the release of gastrin
-atropine blocks the muscarinic but not GRP synapse
what is the main function of GIP?
insulin release for heads up signal during food intake
-stimulated by ingestion of carbs mainly
vasodilators of splanchnic circulation
CCK, VIP, gastrin, secretin, kinins, NO, adenosine
countercurrent blood flow in intestinal villi
tip of villi hypoxic normally
-long term constriction –> necrotic villi –> shock –> inhibit absorption
different contractions when moving bolus
- segment behind bolus - contract circular muscle & longitudinal (propulsive segment)
- segment ahead of bolus - contract longitudinal & relax circular
- PNS –> stronger contractions
- SNS –> weaker contractions
what is peristalsis initiated by?
ENS - segment distention or brush stimulation
- propagation by synaptic gates
- can close transmission gates to inhibit long term peristalsis –> inhibit depolarization waves
function of pro kinetic drugs
presynaptic facilitation –> more gate opening –> increase propulsion
-given to diabetic patients
what can inhibition of peristaltic gates cause?
paralytic ileus
lower esophageal sphincter
prevent stomach acid entry
-problems –> heart burn, barrett esophagus
pyloric sphincter
problems –> bile reflux –> gastritis and ulcers
sphincter of Oddi
pancreatic and GB juice enter duodenum
-problems –> bacterial overgrowth, bloating, ab pain
ileocolonic (ileocecal) sphincter
prevent retrograde flow from cecum into ileum
-problems –> fecal incontinence
deglutition
swallowing –> maintained by center in midbrain to control pharyngeal muscles
-brain injury –> peristalsis but no swallowing
role of primary peristalsis
presence of food starts swallowing –> contract circular muscles as pharyngeal junction to propel food
-no change in esophagus length
role of secondary peristalsis
triggered by failure of primary to push food into stomach
-stronger wave
esophageal achalasia
loss of LES inhibition
-no inhibitory neurons and food cannot pass due to constriction
motor of antral (pyloric) pump
initiated by interstitial cells of Cajal - stimulation moves slow waves to spike waves –> contraction
-slow AP to gastroduodenal junction (3 contractions per min.)
leading vs. trailing contractions
- leading contraction (initial depolarization by rising AP) causes contraction of pyloric sphincter
- trailing contraction (plateau phase) causes stronger contraction - almost complete closure of pylorus
- waves keep coming –> retrograde flow of chime
regulation of antral contractions
myogenic function - ACh release from the vagus nerve can make it stronger but not required
- Gastrin stimulates
- VIP and NE decrease plateau phase and contractions
2 functions of gastric reservoir
- accommodation of arriving meal
2. contraction to maintain compressive force to push food to antral pump
adaptive and receptive relaxation
- receptive - during swallowing (no food yet)
- adaptive - accommodating food already in stomach
- both vagovagal reflex –> afferent and efferent components –> inhibit so they can relax for incoming food
feedback relaxation
presence of nutrients in small intestine inhibit stomach contractions
rate of gastric emptying
determined by type of meal and duodenum
- high gastric volume and isotonic –> faster
- high acidity and calories –> slower
role of migrating motor complex (MMC)
start when digestion and absorption are complete
- inhibited by vagus nerve –> increase function with vagotomy
- clean out debris from small intestine
- failure of MMC to function –> bacteria entry and overgrowth in colon
small intestine digestive motor
MMC replaced by digestive mobility after meal
- segmentation and mixing to mix enzymes with chime
- not same thing as peristalsis
large intestine motility
- adaptive relaxation - cecum relaxation for food entry from ileum
- distended cecum slows down ileum
function of transverse colon
store feces and chime
- dehydration
- complete segmentation to increase surface area and water absorption (haustrations)
gastrocolic reflex
empties stomach to prepare for incoming food which pushed food out of large intestine
fecal passage
somatic control
- distention of rectum –> rectoanal reflex (relaxation of internal anal sphincter) which is ENS reflex
- constipation if you inhibit rectoanal reflex
what is lost during bilateral vagotomy?
gastric adaptive and receptive reflex
salivary secretion is stimulated by what?
SNS and PNS, not hormones
what is the enzyme in saliva?
amylase
- breaks down carbs
- gives taste
salivon
functional unit of salivary glands
- acinus cells –> secrete enzymes from zymogen granules
- secrete mucous and bicarb
- reabsorb Na+ & secrete K+
- high Na+ in saliva with excess saliva
regulation of salivary secretion
- PNS increase salivation directly or indirectly through bradykinin vasodilation
- SNS - short lives, viscous, less secretion of saliva
- mineralcorticoids and ADH (Na+ absorption, K+ secretion)
gastric secretion
- pyloric glands - G cells secrete gastrin
- oxyntic (gastric) glands - parietal (HCl, IF), endocrine (somatostatin), chief (pepsinogen)
-both glands contain mucous cells
D cells –> secrete somatostatin
function of gastrin
increase gut motility and acid secretion
- release stimulated by gastrin releasing peptide from vagus, not ACh like most
- AAs also increase gastric acid secretion
importance of intrinsic factor
from parietal cells
- B12 absorption
- inflammation of ileum –> pernicious anemia
how do you inhibit gastric acid secretion?
- proton pump inhibitors –> cemetidine and rantidine
- somatostatin
- secretin
- enterogastrins
- GIP
regulation of the pancreas
- ACh –> increase enzyme secretion, but not bicarb
- Secretin –> stimulate bicarb secretion; VIP partial agonist
- CCK –> stimulate enzyme production; Gastrin partial agonist
small intestine secretions
- Brunner’s glands
- stimulated by irritant, vagus, secretin
- secrete mucous and bicarb to neutralize stomach acid - crypts of Lieberkuhn
- mucous, water, and bicarb secretion
- has digestive enzymes
- contain stem and paneth cells
function of bicarb in large intestine
protect against acid and fermentation
-can have water and bicarb loss with irritation such as diarrhea
function of bile
- bile salts emulsify fats into micelles for digestion
- bile salts from cholesterol
- bile pigments from bilirubin
- a lot of bicarb found in bile
what enzyme converts cholesterol to primary bile acids?
cytochrome P450
-secreted by the liver stored in the gallbladder
how is bile conjugated?
-bacteria form the deconjugated bile salts and the liver conjugates the bile (glyco, tauro) for better emulsification
where are the bile salts recycled?
distal ileum after absorption of fats takes place
role of CCK in duodenum
contract gallbladder to release bile into duodenum
role of secretin in duodenum
from S cells in duodenum
- increase bicarb production in pancreas and liver
- bile salt independent flow
what do bile acids/salts have to be tightly controlled?
potential toxicity
- gastritis if it leaks into stomach
- release more bile when eating bc GB is contracted and it is recycled back through enterohepatic circulation
what is the role of gastrin on bile release?
- directly increase bile production by liver
- increase acid –> increase secretin –> bile production indirectly
why is bile salt pores located in distal ileum?
special pores for bile recycling
- fat is already absorbed at this time, don’t need bile salts anymore
- bacteria also located here to deconjugate the bile forming secondary bile salts
recycling mechanisms for bile salts
- diffusion
- carrier transport
- deconjugation
- dehydroxylation
how do you get bilirubin in the liver?
biliverdin from Hb of broken down RBCs –> albumin takes it to liver –> liver removes it from albumin recirculating it
why does urine have yellowish color?
bilirubin is conjugated making it more water soluble to enter bile –> absorbed by small intestine and converted to urobilinogen which is absorbed by kidney
where does most of food absorption take place?
in the jejunum and ileum
-bile salts in terminal ileum
what molecule is needed for most reabsorption?
Na+
what is the function of dietary fibers?
not reabsorbed
- soften stool –> prevent colon cancer (less inflammation)
- bind to bile salts –> indirect way to lower cholesterol
salivary amylase/ptylalin
- gives taste
- works in neutral or alkaline pH
- not needed for life
pancreatic alpha amylase
- needed for life
- work in neutral pH
- break down starch to maltose
- only break into disaccharides
what 3 monosaccharides are absorbed at intestine?
galactose, glucose, fructose
- galactose & glucose –> need Na+ and SGTL1
- fructose –> no Na+ nor SGTL1
disaccharidases
break disaccharides into monosaccharides
- supplied by brush border of intestine
- lactase or sucrase deficiency –> diarrhea
- congenital or acquired (Chron’s)
fat digestive enzymes in small intestine
- lingual lipase - taste
- gastric lipase - break down milk fat
- pancreatic lipase - important, breaks TAGs only
- colipase - better interaction of fat & lipase; inhibit bile salts
- PLA2 - breaks phospholipids
- cholesterol esterase - break cholesterol
role of bile salts in absorption
emulsification of fats for better absorption
-poorly absorbed in jejunum
ezitimibe
inhibits cholesterol transporter in intestine –> lowering levels
lipid handling in enterocytes
- long chain FA –> form PL, TAGs
- cholesterol –> form cholesterol esters (cholesterol acyltransferase)
- chylomicrons - transport fat
- VLDL - transport cholesterol via lymph
- medium/short chain FAs enter directly to blood
steatorrhea
fatty stool from pancreatic or bile deficiency
-poor fat soluble vit. absorption
abetalipoproteinemia
no Apo B –> no chylomicrons or VLDL –> poor fat absorption
pancreatic endopeptidases
- trypsin
- chymotrypsin
- elastase
pancreatic exopeptidases
- carboxypeptidase A –> attack aliphatic or aromatic C terminus
- carboxypeptidase B –> attack basic C terminus
disorders of protein absorption
- Hartnup - defective carrier for Trp
- cystinuria - defective carrier for cysteine
- treat with dipeptides –> absorbed in blood then broken down
retinol (vit. A)
- fat soluble
- passive absorbed in intestine –> chylomicron –> stored in liver
- deficient –> night blindness, skin lesions
vitamin D
- fat soluble
- passive absorption in intestine –> chylomicron
- deficient –> rickets, osteomalacia
vitamin E
- fat soluble
- absorbed with lipoproteins and RBCs
- deficient –> fragile RBCs
vitamin K
- fat soluble
- absorbed by chylomicrons stored in liver
- needed for synthesis of coagulation factors
- deficiency –> bleeding disorders
vitamin C (ascorbic acid)
- absorbed in distal ileum
- deficiency –> scurvy
vitamin B1 (thiamine)
- absorbed in jejunum
- deficiency –> beriberi
vitamin B2 (riboflavin)
- absorbed in proximal intestine (jejunum)
- deficiency –> anorexia, impaired growth, nervous system
niacin
- absorbed in small intestine
- lowers cholesterol
- deficiency –> anorexia, indigestion, muscle weakness, skin eruptions, PELLAGRA
vitamin B6 (pyridoxine)
- absorbed in small intestine
- deficiency –> anemia, CNS effects
biotin
- absorbed in small intestine
- coenzyme for carboxylase & decarboxylase enzymes
folic acid
- absorbed all over intestine
- deficiency –> megaloblastic anemia, lesions, poor growth
- needed for pregnant women 1st 3 month
vitamin B12 (cobalamin)
- absorbed in distal ileum by intrinsic factor (from parietal cells in stomach)
- pernicious anemia without
NaCl absorption in jejunum
- ingest hypotonic fluid
- basolateral Na+/K+ ATPase
- Na+ in, H+ out
- carbonic anhydrase in lumen produces water (absorbed) and CO2 (diffuses) –> carbonic anhydrase in enterocyte makes H+ (back to lumen) and bicarb (absorbed)
- paracellular Cl-
- acidosis if lose too much bicarb
NaCl absorption in ileum
- basolateral Na+/K+ ATPase
- Cl-/bicarb exchanger necessary for Na+/H+ exchanger to function
- Cl- in, bicarb out
- Na+ in, H+ out
- still reclaim bicarb with water and CO2 conversion in lumen
K+ absorption/secretion
small intestine --> paracellularly large intestine (colon) -high K+ in lumen --> absorb -low K+ in lumen --> secrete -increase BK channels by bacteria or shear flow --> hypokalemia (ex. diarrhea induced)
Ca++ absorption
tightly regulated
- TRPV5,6 bring Ca++ in –> transported by calbindin –> basolateral ATP pump and Na+/Ca++ exchanger for absorption
- Vit. D increase channels, calbindin, and pumps
iron absorption
2 forms
- heme (animals/humans) –> faster absorption
- nonheme (plants) –> pH dependent (slow absorption at neutral or alkaline) forming precipitates
iron absorption - transporters
- heme iron –> absorbed by facilitated transport
- nonheme iron –> absorbed by DMT-1
- ferritin for storage, transferrin in blood for transport
- Ca++ decreases absorption
- vit. C increase absorption
H2O absorption
hypertonic meal –> water secretion in jejunum –> water absorption in ileum, colon
hypotonic meal –> water secretion in jejunum –> water absorption in jejunum, ileum
