PHYS Flashcards
major functional processes of the GI system:
motility, secretion, digestion, absorption and excretion which are initiated by the ingestion of food
where are absorbed nutrients circulated before entering the systemic circulation?
the liver via the portal venous circulation
what are sphincters? (list the 5)
one-way valves containing rings of circular muscles that maintain positive resting pressures to prevent backflow and are relaxed by inhibitory motor neurons
- UES: highest resting pressure to prevent entrance of air and is made of striated muscle
- LES: made of a special type of smooth muscle but incompetency leads to heartburn
- pyloric: incompetency leads to acid reflux that causes gastritis :( , ulcers or perforation
- ileocecal: incompetency leads to IBS due to bacterial overgrown in the SI
- anal: controls elimination of waste products
ingested and secreted fluids vs. absorbed fluids
ingested/secreted (10L): diet (2L), saliva, gastric juice (from parietal (oxyntic) cells in the oxyntic glands of the stomach), pancreatic juice and bile, SI
absorbed fluids: colon, SI
submucosal plexus/Meissner’s plexus
part of the enteric nervous system located between the circular muscle and submucosal layers and is involved with controlling secretions, absorption and contraction of the submucosal muscle affecting the local infolding of the small and large intestines
myenteric plexus/Auerbach’s plexus
part of the enteric nervous system located between the longitudinal muscle and circular muscle layers involved with tonic contraction, increasing the velocity of contraction and therefore enhancing peristalsis
*stimulated by mechanoreceptors
purpose of HCO3-
secreted into the lumen of the duodenum by the exocrine pancreas the neutralize the acidic chime delivered from the stomach
which neurotransmitter is found primarily in the bowels?
serotonin (95%)
*more than 30 neurotransmitters are used by the enteric nervous system
intrinsic and extrinsic connections in the ENS
sensory afferent neurons monitor luminal activity changes and activate interneurons which relay signals that activate efferent secretomotor neurons stimulating or inhibiting effector cells all of which is modified by the ANS via the vagus nerve
osmoreceptors
can control the amount of chyme entering the SI and the amount of secretions needed to buffer it by detecting the osmolarity of the chyme
SNS and PNS regulation of the ENS
SNS: postganglionic fibers inhibit digestion and absorption through the use of norepi released by postsynaptic neurons
PNS: vagus and pelvic nerves work to increase motility and secretions through the use of ACh or peptides released by postganglionic fibers to stimulate APs in electrical slow waves (ex: substance P, VIP)
how are the facial (VII) and glossopharyngeal (IX) nerves involved in regulation of GI function?
they initiate salivation during the cephalic phage of salivation upon seeing, smelling and/or tasting food
interstitial cells of Cajal (ICC)
pacemakers in the myenteric plexus that connect the GI musculature with gap junctions in between and generate slow waves (changes in the resting potential that has the greatest frequency in the small intestines, intermediate in the colon and slowest in the stomach) and action potentials (above -40mV) that will generate contraction of the GI muscle wall through Ca2+ entry into L-type VSCCs
what will stimulate an AP/depolarization in electrical slow waves and what will stimulate hyperpolarization?
stimulates depolarization: stretch, ACh, parasympathetics (from neural and hormonal input)
stimulates hyperpolarization: norepi, sympathetics
different type of contractions
segmental/mixing/non-propulsive (approx. 2-3 per min.): contractions in the SI elicited by stretching
peristaltic (approx. 1 cm/min.): contractions enhanced by stretch and the gastroenteric reflex
3 reflexes of the GI tract
- gastroenteric: responds to stretch by enhancing peristaltic contractions
- gastroileal: triggers opening of ileocecal valve to permit chyme passage through relaxation of the sphincter and contraction of the ascending colon when they are distended
- enterogastric: senses an acidic pH in the duodenum releasing gastrin from G-cells to decreases gastric motility and secretions while contracting the pyloric sphincter to inhibit chyme from entering duodenum
what is the point of peristalsis and segmentation?
mixing optimizes contact between ingested food and digestive secretions and circulation of intestinal contents facilitates contact with mucosa (this motility is under local control of the myenteric plexus)
peristaltic rushes
occur when the intestines are irritated causing rapid movement of chyme through the intestines which could be due to infectious agents leading to diarrhea (movement is too quick for proper absorption)
peristaltic propulsion/myenteric reflex
distension/low pH will send signal to the sensory neurons which activate interneurons to stimulate motor neurons to release ACh and NO/VIP
ACh–> will contract the circular muscle while the longitudinal muscle is relaxed (only has excitatory motor neurons) creating a propulsive segment which propels the bolus
NO/VIP–> will contract the longitudinal muscle while inhibiting the circular muscle creating a receiving segment for the bolus (overall relaxation of segment- promotes digestion)
physiological and pathological ileus
physiological ileus: normal state of no movement due to inhibitory neurons
pathological ileus: takes longer for things to move through and could be due to abdominal surgery, anticholinergic or opiate drug treatment
Migrating Motor Complex (MMC)
characterized by three phases modulated by the vagus nerve: quinescence, little activity and strong activity in order to sweep the stomach and small intestines of residue that could build up and cause the production of “Bezoars” obstructing the lumen with the help of Motilin which is synthesized in the duodenal Mo cells
deglutition
food in mouth stimulates swallowing reflexes causing the pharyngeal phase (once sensory neurons project to medulla through vagus and glossopharyngeal nerves and send back efferent impulses) and primary peristaltic wave (second peristaltic wave activated by esophageal distension and will remove any remaining food in the esophagus starting at the point of distension) along with receptive relaxation of the stomach
accommodation
relaxation of the stomach to allow for more food storage without increasing intragastric pressure (mediated by the vagovagal reflex) since the fundus (top portion) is relaxed as well
*gastric emptying is slower after ingestion of a high-fat meal and rapid after ingestion of liquid saline
*achalasia and GERD
achalasia: failure of the LES to relax during swallowing (usually accomplished by NO or VIP) possibly due to damage to the myenteric plexus which cannot transmit the signal for receptive relaxation
GERD: LES tone is not properly maintained (supposed to be high at rest)
two division of the stomach
- proximal gastric reservoir: expands to accommodate for food and has muscle to keep tonic contration
- distal antral pump: grinds food and therefore has more muscle mass for the ICC to cause contractions
muscle unique to the stomach
oblique muscle layer
*also has longitudinal and circular muscle layers like the intestines
retropulsion
gastric contents are returned to the body of the stomach to be broken down further
GI regulatory substances
- hormones: secreted into the portal circulation and pass through the liver before entering the systemic circulation to be delivered to target cells
- paracrines: secreted by endocrine cells of the GI tract acting locally in the same tissue that secretes them (ex: serotonin from EC cells in response to distension to increase motility and secretions, somatostatin by D cells which acts as an inhibitor (acts on G-cells to inhibit gastrin secretion), histamine by EC-like cells to stimulate HCl secretion)
- neurocrines: released from neurons following an AP and diffuse across the synaptic cleft acting on the target cell (ex: ACh, norepi, VIP, gastrin-releasing peptide, substance P)
motilin
secreted by M cells in the duodenum and jejunum to mediate the Migrating Motor Complex (short bursts in fasting state) in order for large contractile waves to really open up the pyloric sphincter in order for indigestible material to pass through
gastrin
secreted in the antrum of the stomach by G-cells in response to food to increase acid secretion by parietal cells (stimulates histamine release from ECL cells)
cholecystokinin/CCK
secreted in the SI by I-cells in response to fats and proteins/peptides/AAs to increase bicarbonate and inhibit gastric emptying
secretin
secreted in the SI by S-cells is response to the arrival of acidic chyme to increase bicarbonate and inhibit gastric emptying while acting on G-cells to inhibit gastrin
glucose-dependent insulinomic peptide (GIP)
secreted by K-cells in response to fat and carbohydrates to stimulate insulin secretion and inhibit HCl secretion by parietal cells
4 types of digestive enzymes (based on location of secretion)
salivary, gastric, pancreatic, intestinal
which glands are involved in salivary secretions and what is the purpose of these secretions?
parotid, submandibular and sublingual glands have acinar cells that produce a-amylase in the former and a sero-mucous product in the two latter
functions: lubrication (prevents dehydration and helps with swallowing), protection (protects against oral bacteria) and digestion
Sjogren Syndrome
autoimmune disorder that results in damaged salivary and lacrimal glands leading to xerostomia (dry mouth), difficulty speaking and bacterial overgrowth in mouth
duct cell
Na+ and Cl- are absorbed while K+ is secreted (stimulated by aldosterone)
what does the activation of salivary glands lead to?
the release of kallikrein resulting in the production of the vasodilator bradykinin to increase capillary hydrostatic pressure and capillary filtration (supplies the fluid for secretion)
cells of the gastric mucosa
body: oxyntic glands–> parietal cells (HCl and intrinsic factor) and chief cells (pepsinogen and gastric lipase)
antrum: pyloic glands–> G-cells (gastrin) and mucous cells (mucus pepsinogen)
* deeper pits
achlorhydria
lack of stomach acid secretion due to the destruction of parietal cells (from chronic gastritis) which can occur along with pernicious anemia (since vitamin B12 is not stimulating the bone marrow to make RBCs)
how are proteins broken down?
at pH 3-5, pepsinogens spontaneously activate to pepsins by the removal of an N-terminal “activation peptide” and then the pepsins will function at a pH below 3.5 and can also catalyze the activation of pepsinogens
pepsins work in the stomach to break down proteins into proteoses, peptones and polypeptides and eventually amino acids with the help of trypsin, chymotrypsin, carboxypolypeptidase and proelastase
alkaline mucous layer
protects the gastric mucosa from acid and pepsins
*failure to prevent H+ from penetrating results in mast cell damage and release of histamine causing inflammation (mild injury–> blood flow promotes mucus and HCO3- production. severe injury–> decreased blood flow and cell injury)
gastric parietal cell ion movement
CO2 adds to H2O with the help of carbonic anhydrase to form H2CO3 which dissociates into H+ and HCO3-
the H+ is exchanged with K+ which comes into the cell through an H+ K+ ATPase pump at the apical membrane (target for proton pump inhibitors)
the HCO3- is exchanged with Cl- which comes into the cell at the basolateral membrane but will then leave the cell at the apical membrane
a Na+ K+ ATPase pump also exists at the basolateral membrane in which the Na+ goes to the blood and the K+ enters the cell
alkaline tide
due to the increase of buffers (bicarbonate ions) entering the blood when H+ is secreted by the parietal cells so the blood becomes alkaline but eventually, the bicarbonate ions are secreted back into the GI tract in pancreatic secretions
what happens during vomiting?
reverse peristalsis occurs when vomiting from the mid-SI to the pylorus allowing chyme to enter the stomach and then strong abdominal contractions force gastric contents to the esophagus and cause retching with further stimulation leading to the relaxation of the UES and expulsion of contents
*dehydration, alkalosis and hypokalemia can result
what muscles make up the UES and LES?
UES: striated muscle
LES: smooth muscle
IBS
bacterial overgrowth in the intestines due to a faulty ileocecal spinchter causing bloating and pain
what is the lamina propria made up of?
connective tissue, blood and lymph vessels
what is the sybmucosal layer made up of?
collagen, elastin, glands and blood vessels
which types of receptors are present in the myenteric pleuxus and in the submucosal plexus?
myenteric: mechanoreceptors
submucosal: chemoreceptors
hypertonic chyme and the response of osmoreceptors
hypertonic chyme will exert an osmotic force, pulling water out of the cells
osmoreceptors control the amount of chyme entering the SI and the amount of secretions necessary to buffer the chyme
where do parasympathetic preganglionic fibers terminate?
postganglionic cholinergic or peptidergic neurons located in the plexus
what is the blood’s role in GI?
it absorbs and also provides nutrients to promote digestion
where does the vagus nerve and pelvic nerve innervate?
vagus nerve: proximal 2/3 of ENS from pharynx to beginning of distal colon
pelvic nerves: distal 1/3 of colon
how does SNS activity inhibit digestion?
relaxes the gut wall, reduces secretions, contracts sphincters and diverts blood from the GI tract by contracting the vasculature
how are APs produced to stimulate contractions?
Ca2+ entry through L-type VSCCs
*stimulated by neural and hormonal input
what connects the ICCs to the circular muscle?
gap junctions (through which ionic current flows through)
innervation of circular muscle and longitudinal muscles
circular: innervated by excitatory and inhibitory motor neurons
longitudinal: innervated by excitatory motor neurons
- excitatory: ACh, substance P (contracts musculature)
- inhibitory: VIP (relaxes musculature)
what could cause a pathological ileus?
- abdominal surgery
- anticholinergic drugs
- opiate drug treatment
what modulates motilin release from Mo cells to stimulate Migrating Motor Complex (MMC)?
the vagus nerve
*MMC will be prevented if the vagus nerve is cut
somatic nerves vs. autonomic nerves
somatic nerves: regulate striated muscle directly
autonomic nerves: regulate smooth muscle via enteric nervous system or directly
what does food in the pharynx stimulate?
activation of sensory neurons that project via the trigeminal and glossopharyngeal nerves to the swallowing center in the medulla to send back efferent impulses through trigeminal, glossopharyngeal, vagus and facial nerves
what do patients under anesthesia experience?
paralysis of the swallowing mechanism
what does a vagotomy lead to?
- prevention of MMC from occurring
- increase in pressure in the stomach with the addition of food due to inhibition of accommodation
ptyalin
salivary amylase that is identical to pancreatic amylase converting starch to sugar at pH of 7
*denatured at pH of 4
when saliva is secreted, which ions are involved?
K+ and HCO3- (bicarbonate) are secreted to create a K+ rich hypotonic salivary secretion while Na+ and Cl- are absorbed by the duct
*aldosterone promotes this
what is the ganglion that released ACh to the parotid gland after parasympathetic stimulation?
the otic ganglion
what can stimulate further pepsin production?
presence of pepsin and low pH (<3.5)
*pepsins digest collagen
alkaline layer
inactivates pepsin that penetrates into the mucus and traps bicarbonate which titrates any H+ present
what do NSAIDS inhibit?
prostaglandin synthesis which usually stimulates the secretion of mucus and bicarbonate
how is HCl secreted into the lumen?
H+ from the H+ K+ ATPase pump is pumped into the lumen while Cl- which was exchanged with bicarbonate in the blood will exit the parietal cell at the lumen and combine with H+ to form HCl
what does prolonged vomiting lead to?
dehydration, alkalosis and hypokalemia (low K+ in the blood)
*loss of H+, K+ Cl- and fluid from extracellular space
Gq and Gs
Gq: involved in Ca2+ stimulation of H+ K+ ATPase pump through ACh binding to M3 receptors and gastrin binding to CCKB receptors–> IP3/Ca2+ is increased
Gs: involved in cAMP stimulation of H+ K+ ATPase pump through adenylate cyclase (from histamine) binding to H2 receptor increasing cAMP
what acts on Gs?
Gi binding by somatostatin and prostaglandins
vagal stimulation and H+ stimulation of D cells
vagus: by ACh and inhibits somatostatin release
H+: directly stimulates D cells to release somatostatin
how are proteases produced?
as proenzymes/zymogens which are non-active forms of enzymes in order to protect the pancreas from autodigestion
*enteropeptidase activates trypsinogen by cleavage into trypsin
what is the role of bicarbonate?
to neutralize stomach acid and allow pancreatic enzymes to function at their optimal neutral pH
pancreatic aqueous secretion
from duct cells and central acinar cells and functions to protect intestinal lining, create an optimal neutral pH for enzymes to function and dilute enzymatic juice to prevent pancreas clogging
synthesis and secretion of enzymes
produced in the RER then sent to the Golgi and leave as condensing vacuoles (where there is increased enzyme concentration) and then released as zymogen granules which contain the inactive enzymes and can fuse with the membrane for contents to be discharged
what causes pancreatitis?
active enzymes are released instead of within granules
what stimulates Cl- secretion?
CCK and ACh binging to muscarinic receptors
how does bicarbonate secretion into the lumen work?
through a Cl-HCO3 exchange in which the HCO3 comes from a Na/HCO3 cotransporter or conversion of CO2 and H2O by carbonic anhydrase in which a H+ participates in extrusion through an H+ Na+ pump and H+ pump driven by a Na+K+ pump. in the meantime, secretin increases cAMP opening a Cl- pump (CFTR)
*Na+ and H2O pass to the lumen to dilute the enzymes
which pump is NOT affected by omeprazole?
Na+ H+ pump (which tends to negate the alkaline tide since it acidifies venous blood)
rate of secretion vs. concentration of bicarbonate and Cl- in pancreatic aqueous secretion
increase in bicarbonate secretion with increased secretory rates (secretin activates duct cells)
at slow rate, bicarbonate and Cl- concentrations will resemble that of plasma and extracellular fluid due to change (more Cl- secreted)
cystic fibrosis
defective CFTR Ci- channel so pancreatic secretions are thick and viscous, clogging the ducts and interfering with digestion
phases of pancreatic secretion
- cephalic: vagal stimulation via muscarinic receptor, increased concentration of enzymes
- gastric: distension induces pancreatic enzyme secretion (gastrin) by vagovagal reflex (less liquid is secreted)
- intestinal: acidic chime causes secretin release to secrete bicarbonate whereas fatty, protein-rich chime induces CCK release to secrete pancreatic enzymes
secretin
“nature’s antacid” which inhibits gastric acid secretion and release of gastrin but stimulates gastric chief cells to secrete pepsinogen to digest proteins so they can flow into the intestines
*aqueous secretion by pancreatic duct cells (high volume, bicarbonate and low in enzymes)
CCK
responds to fatty acids or AAs entering the duodenum and secretes enzymes and aqueous solution by acinar cells, causes gallbladder contraction and relaxes the sphincter of oddi (regulates secretions from pancreas and gallbladder to the duodenum)
bile acids vs. bile salts
- bile acids: non-conjugated, non-soluble, not charged, thought of like steroid hormones
- bile salts: conjugated by liver, soluble, charged and released
- precursor= cholesterol
- 7-a-dehydroxylase is the rate limiting step
what conjugates bile acids?
the liver but more specifically: glycine and taurine
what recycles bile salts?
enterohepatic circulation
what converts bile salts back to bile acids?
bacteria–> so they won’t be taken up by the intestines
how is bile secreted?
by hepatocytes of the liver into bile canaliculi which empties into bile ducts
*active secretion of the breakdown products of lipid soluble molecules
sphincter of oddi opened and closed
opened: during a meal and bile flows to duodenum
closed: while fasting and bile is diverted to the gallbladder
* regulated by CCK which contracts the gallbladder and relaxes the sphincter
transporters that take up bile bound to albumin in the liver
NTCP and OATP
bile acid independent secretion
watery HCO3- rich fluid by cholangiocytes of the ducts similar to pancreatic aqueous secretion and stimulated by secretin
bile acid dependent secretion
by hepatic parenchymal cells stimulated to secrete by bile acids returning to liver in portal blood and synthesis of bile acids is inhibited by bile acids returning to liver via portal blood (feedback inhibition)
ASBT
Na+ coupled cotransporter in the terminal ileum that reabsorbs bile salts
*whereas uptake of bile acids is passive and throughout
release of bile from gallbladder
vagovagal response or CCK which relaxes the sphincter of oddi and contracts the gallbladder
mucosal folds of Kerkring
helps to increase the surface area of the jejunum through successive folding
3 levels of surface area amplification in the small intestines
- mucosal folds of Kerkring
- submicroscopic microvilli
- crypts of Liberkuhn and microscopic villi
Celiac disease
gluten will decrease the amount of absorptive cells and destroy functional villi leading to malabsorption and diarrhea (due to inability to digest properly)
crypt cells
constantly regenerated and migrate to the top of villi where they are extruded 3-8 days later (useful contents get recycled)
*undifferentiated- secrete NaCl from the blood into the lumen and then taken on an absorptive function (absorbing NaHCO3 or NaCl once they migrate up the villus)
what stimulates goblet cells and what do they secrete?
GCs are stimulated by ACh which is released by PNS cholinergic nerve fibers
GCs will secrete mucous
2 pathways of material transfer
- paracellular (between cells–> via tight junction)
2. transcellular (through cells–> bursh border, cytoplasm, basolateral membrane)
what are tight junctions permeable to?
H2O and cations (Na+ and K+)
*especially in the jejunum (gets tighter as you proceed)
what does the brush border have?
ectoenzymes (aids with digestion)
succus entericus
difference between dietary intake and fecal outflow that is lost through kidneys, lungs and sweat to maintain body fluid in steady state
which nutrients are absorbed in the distal ileum?
- vitamin B12 (requires combination with intrinsic factor which is secreted by parietal cells)
- ionized bile salts (enters enterohepatic circulation)
*ileum can adapt to take over the function of the jejunum if it has been removed
removal of the ileum
inability to absorb ionizable bile salts and vitamin B12 causing pernicious anemia (unusually large RBCs)
two important nutrients/solutes absorbed by the jejunum
calcium and iron
two mechanisms by which Na+ is absorbed by the jejunal absorptive cell
- by Na+/glucose and by Na+/amino acid cotransport
- by Na+/H+ antiport (to keep internal pH neutral)
*balanced by active efflux of Na+ across the basolateral membrane mediated by Na+/K+ pump
where can we find Na+/glucose or Na+/amino acid cotransporters?
jejunum and a little in the ileum
where can we find Na+/H+ exchanger?
a little in the duodenum and also into the jejunum
where can we find parallel Na+/H+ and Cl-/HCO3 exchangers?
ileum and proximal colon
where can we find epithelial Na+ channels?
distal colon
*what stimulate cAMP and what is the result?
cAMP is stimulated by: ACh, VIP, E.coli and Vibriocholera toxins
result: decreased NaCl absorption, increased osmolarity, osmotic diarrhea
how does cAMP increase NaCl secretion?
by increasing cAMP through increased conduction of the CFTR channel to Cl-
Vibriocholera
increases cAMP via adenylate cyclase activation, resulting in decreased ileal absorption and increased jejunal NaCl secretion through the opening of Cl- channels in the apical membrane
cholera
affects- defective CFTR channels (similar to CF patients)
*CF patients have a selective advantage to it
substances that promote secretion tend to…
inhibit absorption
substances that promote absorption tend to..
inhibit secretion
endogenous and exogenous secretory stimuli
endogenous: ACh (inc. Ca2+), histamine (inc. Ca2+), CCK, secretin (inc. cAMP), gastrin, gastric inhibitory polypeptide (GIP), motilin, VIP (inc. cAMP)
exogenous: Vibriocholerae (inc. cAMP), E. coli (inc. cAMP), salmonella (inc. cAMP), microbial enterotoxins, bile salts and fatty acids, laxatives
endogenous and exogenous absorptive stimuli
endogenous: a-adrenergic agonists (epi, norepi), dopamine, enkephalins, somatostatin (inhibits gastric secretion), mineralocorticoids
exogenous: nutrients (glucose, AAs, peptides)
how is body Fe2+ related to brush border transporters?
- if body Fe2+ is low, # brush border transporters increases (to increase Fe absorption)
- if body Fe2+ is high, # brush border transporters decreases and ferritin increases
what does too much iron absorption leave to?
cirrhosis of the liver, diabetes, weakening of the heart, arthritis, erectile dysfunction
*occurs in concenital hemochromatosis
how do we absorb iron?
20mg are digested daily but only 5% is absorbed (ferrous form) and the rest is stored when bound to ferritin
what are the two mechanisms of iron absorption and what is similar to both?
- heme iron enters by unknown mechanisms and is broken down by heme oxygenase into Fe3+ and converted to Fe2+
- Dcytb reduces non-heme Fe3+ to Fe2+ which then enters the cell with H+ via a cotransporter
- in both circumstances, Fe2+ in transferred to mobiliferrin and leaves the cell via IREG1
- will bind to transferrin in plasma after oxidation to Fe3+
gastric acid section and iron absorption relationship
a deficiency in gastric acid secretion causes less iron to be absorbed leading to iron deficient anemia
vitamin D
regulates proteins involved in Ca2+ absorption
UV will cause 7-dehydrocholesterol in the skin to form vitamin D3 which is hydroxylated in the liver to form 25-(OH)-Vitamin D3 and then hydroxylated again with the help of PTH (parathyroid hormone) in the kidney to the active form 1,25-(OH)-Vitamin D3
regulation of body Ca2+ balance
increase in plasma Ca2+–> decrease PTH secretion–>decrease 1, 25-(OH)2-Vitamin D3 formation–> decrease CaBP (calcium binding proteins) synthesis–> decrease in Ca2+ absorption
2 mechanisms of Ca2+ absorption in the duodenum
- PASSIVE- paracellular; not under vitamin D control; predominates
- ACTIVE- transcellular; Ca2+ is buffered by calbindin and enters organelles and extruded through Ca2+ pump and Na+/Ca2+ exchanger (net affect= absorption); stimulated by vitamin D
what factors affect Ca2+ absorption?
- presence of fatty acids which reduces Ca2+ absorption by formation of a Ca2+ soap
- oxalate–> salt in leafy green vegetables which reduces the bioavailability of Ca2+
- bile salts form complexes with Ca2+ which facilitate Ca2+ absorption
what secretes pepsinogen?
gastric chief cells
job of enterokinase
to activate pancreatic proteolytic enzyme trysinogen into trypsin which activates endopeptidases and exopeptidases
what does luminal digestion yield?
40% free AAs and 60% peptides (2-6 AA residues)
PepT1 function and what happens to the oligopeptides they allow pass into enterocytes
H+/oligopeptide cotransporter that allows the enterocyte to directly absorb some of the small oligopeptides
*oligopeptides are hydrolyzed by peptidases into AAs which then exit basolateral membrane through Na+ independent AA transporters
everted sacs
aids in transcellular concentrative uptake of L-amino acids against their concentration gradients
is a Na+ gradient required for AA carrier systems?
some require it (blood–> enterocyte) and some don’t (enterocyte–> blood)
Hartnup disease
defective system B apical membrane AA transporter leading to reduced absorption of neutral AAs like L-phenylalanine and increased excretion of tryptophan in the urine
*tryptophan is a precursor for serotonin, melatonin and niacin
cystinuria
defective system B0+ apical membrane AA transporter leading to reduced absorption of L-cystine and basic AAs causing kidney stones (due to inadequate reabsorption of cystine)
what is special about Glc and Gal compared to Frc?
Glc and Gal compete for the same Na+-coupled carrier whereas Frc is independent of Na+ and cannot be concentrated in the cell
function of brush border ectoenzymes
convert sugars to monosaccharides
2 mechanisms of sugar transport
- facilitated diffusion
2. Na+-coupled cotransport
lactase definiciency
- lactose is osmotically active (prevents colon from reabsorbing water)–> diarrhea
- lactose remains unhydrolyzed and unabsorbed
- excretion of large amounts of H2 into the breath–> H2 is the product of lactose catabolism by colonic bacteria
SGLT1 function and what happens if missing/defective
function: Na+ coupled transporter that mediates the uptake of glucose or galactose from the lumen of the Si into the enterocyte
missing/defective: “Glucose-Galactose Malabsorption” accumulation of Glc in intestine causing diarrhea, dehydration and death (restricted diet of only Frc since it is the only monosaccharide that can be absorbed)
GLUT5
mediates the facilitate diffusion of fructose into the enterocyte
GLUT2
mediates efflux of monosaccarides across the basolateral membrane into the interstitial space
examples of fats:
neutral fats (triglycerides), phospholipids, cholesterol, fatty acids, waxes of ingested plant cell walls
what does the presence of fat in the duodenum cause?
release of:
- GIP (which decreases gastric acid secretion)
- CCK
digestion of fats
- lingual lipase
- gastric lipase (with acidic pH0
- mostly (and completed) in jejunum via: pancreatic phospholipase A2, cholesterol esterase and pancreatic lipase
- lipases are water-soluble whereas fats are insoluble
- colipase anchors lipase to micelles (aggregates of amphipathic molecules) and provides access to neutral triglycerides inside them
what do micelles include?
long chain FA, cholesterol, monoglycerides, phospholipids, bile salts and fat soluble vitamins (A, D, E, K)
(hydrophoblic lipid tails face inward and polar head groups face outward)
what is essential for chylomicron formation?
apoprptin B48 and MTP
what is required for cholesterol absorption?
Niemann-Pick C1 like 1 (NPC1L1)
what does micturition involve?
- filling until tension rises above the threshold
2. triggers reflex that empties the bladder
prostate gland issues
enlargement if common and will affect micturition
*squeezes the urethra- more frequent urination
ureters
made of smooth muscle and constantly pull urine from kidneys
two parts of the bladder
- body/reservoir- smooth muscle called the detrusor
2. neck/posterior urethra/outlet with internal sphincter
what provides voluntary control of the detrusor muscle?
suprapontine centers exert tonic inhibition over pontine micturition center
detrusor muscle, internal sphincter and external sphincter during filling and emptying of bladder
during filling: detrusor (relaxed through sympathetic B2), internal sphincter (contracted through sympathetic a1), external sphincter (contracted through voluntary mechanism)
during emptying: detrusor (contracted through parasympathetic M), internal sphincter (relaxed through parasympathetic M), external sphincter (relaxed through voluntary mechanism)
innervation of the bladder
sensory (afferent stretch) and motor (efferent parasympathetic) fibers of pelvic nerves
- S2-S4 parasympathetic nerves
- sympathetic from T11-L2 work to retain urine
causes of neurogenic bladder
- LMN damage: autonomous neurogenic bladder (sacral spinal centers), motor neurogenic bladder (efferents damage), sensory neurogenic bladder (afferents damage)
- UMN damage: automatic neurogenic bladder (loss of brain stem control), uninhibited neurogenic bladder (no cortical control)
primary functions of the colon:
- moves material
- extracts water and electrolytes (ascending and transverse)
- produces mucus
- stores stool (descending)
types of diarrhea
- osmotic form: from non-absorbable solutes in the lumen
2. secretory form- from excessive secretion of fluids by crypt cells due to bacterial overgrowth
slow motility leads to:
more absorption, harder feces, constipation
appendicitis
obstruction of the appendix by calcified fecal matter leading to ischemia
*ileocecal sphincter
prevents backflow and emptying is regulated by stretch, composition and fluidity of chime
*gastroilieal reflex is activated when food enters the stomach to intensify peristalsis of the small intestine and relax this sphincter
*P or chemical irritation in cecum
inhibits peristalsis of ileum and excites sphincter (delays emptying)
how is the colon epithelium different from that of the small intestines?
- no villi since no absorption
- many crypts
- GC–> mucus to bind feces, lubricate colon
- absorptive cells for electrolytes and water
- solitary lymphatic nodules
what does the colon absorb and what does it secrete?
absorbs: Na+, Cl- and H2O
secretes: K+ and HCO3-
* major exchanges in ascending and transverse colon
what does prolonged diarrhea lead to?
hypokalemia, arrhythmias, cramps
key determinant of water reabsorption in the colon and how it causes H2O uptake
Na+ absorption through parallel Na-H and Cl-HCO3- exchangers (present in ileum and proximal colon) resulting in “electroneutral NaCl absorption” creating an osmotic gradient promoting uptake of water via passive transcellular transport
*occurs in the interdigestive state
what increases the number of Na+ channels?
aldosterone (more Na+ from lumen into cell and then is extruded through Na+/K+ ATPase pump to blood
what is motility of the large intestine characterizes by?
slow segmental propulsion, segmental mixing and mass movements
*haustrations (specialized for slow propulsion to allow for absorption and solidification of chyme)
mass movements
signal the urge to defecate via gastrocolic reflex following distension of stomach and duodenum
ulcerative colitis
persistent mass movements due to irritation in the colon
specific innervation of duodenum, cecum/appendix, transverse colon, descending colon/rectum
duodenum (T9-T10)
cecum/appendix (T10-T12)
transverse colon (T12-L1)
descending colon/rectum (L1-L2)
*Hirschsprung’s disease
- “megacolon”
- segment of the colon is permanently contracted and results in obstruction (prevents passage of feces)
- lack of ENS in distal part of GI tract
- lack of propulsive movements
KIND OF LIKE ACHALSIA
orthocolic reflex
when you wake up in morning and go from supine to standing position–> mass movement is common
retrosphincteric reflex
defecation
- mechanoreceptors
- spinal cord conveys signals to the brain to stimulate the urge to defecate
- EAS relaxes, person increases intra-abdominal P and feces are eliminated from the rectum
what will increase glucose in the blood
glucagon, norepi, epi, cortisol, GI hormones, somatostatin
*“stress”- gets glucose to muscles
islets of Langerhans
make up the endocrine pancreas with alpha cells (glucagon), beta cells (insulin), and delta cells (somatostatin)
*blow flows from center to periphery
post-translational processing of glucagon
proglucagon undergoes primary processing and the pancreatic islet alpha cells will break it down into GRPP, glucagon and major proglucagon fragment while intestinal L cells will break it down to Glicentin, GLP-1, IP-2 and GLP-2
stimulators and inhibitors of glucagon secretion
stimulators: hypoglycemia, increase in Arg and Ala (protein degradation), exercise and stress
inhibitors: somatostatin (inhibits release of insulin and glucagon as well as gastric acid secretion), insulin and hyperglycemia
glucagon in liver
Gs, GLUT2
counter-regulatory hormones
released in times of stress (ex: glucagon)
proinsulin
broken down by endopeptidase into insulin and c-peptide (c-peptide means that we made the insulin and it was not ingested)
insulin secretion by beta cells
GLUT2 to glucose will inhibit K+ channels causing depolarization and then Ca2+ comes in and causes the release of granules with insulin
