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Secretory Functions of the Alimentary Tract
 Most digestive secretions formed only in response to presence of food in alimentary tract, and quantity secreted
in each segment of tract precise amount needed for proper digestion
 In some portions of GI tract, types of enzymes and other constituents of secretions are varied in accordance
with types of food present
General Principles of Alimentary Tract Secretion
 Single-cell mucous glands – also called mucous glands or goblet cells; on surface of epithelium in most parts of
GI tract; function mainly in response to local irritation of epithelium and extrude mucus directly onto epithelial
surface to act as lubricant that also protects surfaces from excoriation and digestion
 Many surface areas of GI tract lined by pits that represent invaginations of epithelium into submucosa
o In small intestine, crypts of Lieberkühn are deep and contain specialized secretory cells
 In stomach and upper duodenum are large numbers of deep tubular glands (example is acid and pepsinogensecreting gland of stomach [oxyntic gland])
 Complex glands (salivary glands, pancreas, and liver) provide secretions for digestion or emulsification of food
o Salivary glands and pancreas are compound acinous glands that lie outside walls of alimentary tract
(different from all other alimentary glands); contain millions of acini lined with secreting glandular cells
which feed into system of ducts that finally empty into alimentary tract itself
Basic Mechanisms of Stimulation of Alimentary Tract Glands
 Mechanical presence of food in particular segment of GI tract usually causes glands of that region and adjacent
regions to secrete moderate to large quantities of juices
o Part of local effect, especially secretion of mucus by mucous cells, results from direct contact stimulation
of surface glandular cells by food
o Local epithelial stimulation also activates enteric nervous system of gut wall; types of stimuli include
tactile stimulation, chemical irritation, and distention of gut wall
 Resulting nervous reflexes stimulate both mucous cells on gut epithelial surface and deep glands
in gut wall to increase secretion
 Stimulation of PNS nerves to alimentary tract increases rates of alimentary glandular secretion; especially true of
glands in upper portion of tract innervated by glossopharyngeal and vagus PNS nerves, such as salivary glands,
esophageal glands, gastric glands, pancreas, and Brunner’s glands in duodenum; also true of some glands in
distal portion of large intestine, innervated by pelvic PNS nerves
o Secretion in remainder of small intestine and first 2/3 of large intestine occurs mainly in response to
local neural and hormonal stimuli in each segment of gut
 Stimulation of SNS nerves going to GI tract causes slight to moderate increase in secretion by some local glands
o SNS stimulation also results in constriction of blood vessels that supply glands
o SNS stimulation alone usually slightly increases secretion
o If PNS or hormonal stimulation already causing copious secretion by glands, superimposed SNS
stimulation usually reduces secretion, sometimes significantly so, mainly because of vasoconstrictive
reduction of blood supply
 GI hormones in stomach and intestine help regulate volume and character of secretions; hormones liberated
from GI mucosa in response to presence of food in lumen of gut and are then absorbed into blood and carried to
glands, where they stimulate secretion
o Particularly valuable to increase output of gastric juice and pancreatic juice when food enters stomach
or duodenum
Basic Mechanism of Secretion by Glandular Cells
 Principles of secretion
o Nutrient material needed for formation of secretion must first diffuse or be actively transported by
blood in capillaries into base of glandular cell
o Many mitochondria located inside glandular cell near its base use oxidative energy to form ATP
o Energy from ATP, along with appropriate substrates provided by nutrients, used to synthesize organic
secretory substances; synthesis occurs almost entirely in ER and Golgi complex of glandular cell
 Ribosomes adherent to ER specifically responsible for formation of secreted proteins
o Secretory materials transported through tubules of ER, passing in about 20 minutes all the way to
vesicles of Golgi complex
In Golgi complex, materials modified, added to, concentrated, and discharged into cytoplasm in form of
secretory vesicles, which are stored in apical ends of secretory cells
o Vesicles remain stored until nervous or hormonal control signals cause cells to extrude vesicular
contents through cells’ surface; control signal increases PM permeability to Ca2+, which enters cell; Ca2+
causes many vesicles to fuse with apical cell membrane, which breaks open, thus emptying vesicles to
exterior (exocytosis)
 Sufficient water and electrolytes necessary for glandular secretion
 Hormones acting on PM of some glandular cells believed to cause secretory effects similar to those caused by
nervous stimulation
 Mucus – thick secretion composed mainly of water, electrolytes, and mixture of several glycoproteins
(composed of large polysaccharides bound with much smaller quantities of protein)
o Slightly different in different parts of GI tract
o Characteristics of mucus that make it excellent lubricant and protectant
 Mucus has adherent qualities that make it adhere tightly to food or other particles and to
spread as thin film over surfaces
 Has sufficient body that it coats wall of gut and prevents actual contact of most food particles
with mucosa
 Has low resistance for slippage, so particles can slide along epithelium with great ease
 Mucus causes fecal particles to adhere to one another to form feces that are expelled during BM
 Strongly resistant to digestion by GI enzymes
 Glycoproteins of mucus have amphoteric properties; capable of buffering small amounts of
either acids or alkalies
 Mucus often contains moderate quantities of bicarb ions to neutralize acids
Secretion of Saliva
 Principal glands of salivation are parotid, submandibular, and sublingual glands (tiny buccal glands)
 Saliva contains serous secretion (contains ptyalin [an α-amylase], used for digesting starches) and mucus
secretion (contains mucin for lubricating and for surface protective purposes)
o Parotid glands secrete almost entirely serous secretion, and submandibular and sublingual glands
secrete both serous secretion and mucus
o Buccal glands secrete only mucus
 Saliva has pH between 6.0-7.0 (favorable range for ptyalin)
 Saliva contains especially large quantities of K+ and bicarb; concentrations of Na+ and Cl- less than in plasma
 Submandibular glands – contain acini and salivary ducts; salivary secretion is 2-stage operation
o First stage involves acini and second salivary ducts
o Acini secrete primary secretion that contains ptyalin and/or mucin in solution of ions in concentrations
not greatly different from those of typical extracellular fluid
o As primary secretion flows through ducts, 2 major active transport processes (reabsorbing Na+ and
secreting K+); excess Na+ reabsorption over K+ secretion creates electrical negativity of -70 mV in salivary
ducts, causing Cl- to be reabsorbed passively
o After that, bicarb ions secreted by ductal epithelium into lumen of duct; at least partly caused by passive
exchange of bicarb for Cl-, but partly results from active secretory process
o So saliva ultimately has less Na+ and Cl- and more K+ and bicarb than normal plasma
 During maximal salivation, salivary ionic concentrations change considerably because rate of formation of
primary secretion by acini can increase 20x; acinar secretion flow through ducts so rapidly that ductal
reconditioning of secretion considerably reduced
 Under basal awake conditions, saliva (almost entirely mucous type) secreted every minute; during sleep, little
secretion occurs; secretion plays important role for maintaining healthy oral tissues
o Mouth loaded with pathogenic bacteria that can easily destroy tissues and cause dental caries
o Flow of saliva helps wash away pathogenic bacteria, as well as food particles that provide bacteria’s
metabolic support
o Saliva contains thiocyanate ions and several proteolytic enzymes (most importantly lysozyme) that
attack bacteria, aid thiocyanate ions in entering bacteria where ions become bactericidal, and digest
food particles, helping further remove bacterial metabolic support
Saliva often contains significant amounts of protein antibodies that destroy oral bacteria, including some
that cause dental caries; in absence of salivation, oral tissues often become ulcerated and otherwise
infected, and caries of teeth can become rampant
 Salivary glands controlled mainly by PNS nervous signals all the way from superior and inferior salivatory nuclei
in brain stem; salivatory nuclei located at juncture of medulla and pons and are excited by both taste and tactile
stimuli from tongue and other areas of mouth and pharynx
o Many taste stimuli, especially sour taste, elicit copious secretion of saliva (often 8-20x basal rate of
o Certain tactile stimuli, such as presence of smooth objects in mouth (e.g., pebble), cause marked
salivation, whereas rough objects cause less salivation and occasionally inhibit salivation
 Salivation can be stimulated or inhibited by nervous signals arriving in salivatory nuclei from higher centers of
CNS; when person smells or eats favorite foods, salivation greater than when disliked food is smelled or eaten
o Appetite area of brain, which partially regulates effects, located in proximity to PNS centers of anterior
hypothalamus and functions to great extent in response to signals from taste and smell areas of cerebral
cortex or amygdala
 Salivation can occur in response to reflexes originating in stomach and upper small intestines, particularly when
irritating foods swallowed or when person is nauseated because of GI abnormality
o Saliva, when swallowed, helps remove irritating factor in GI tract by diluting or neutralizing irritant
 SNS stimulation can increase salivation a slight amount, much less than PNS; SNS nerves originate from superior
cervical ganglia and travel along surfaces of blood vessel walls to salivary glands
 Blood supply to glands – secretion always requires adequate nutrients from blood; PNS nerve signals that induce
copious salivation moderately dilate these blood vessels
o Salivation directly dilates these blood vessels, providing increased salivatory gland nutrition needed by
secreting cells
o Part of additional vasodilator effect caused by kallikrein secreted by activated salivary cells, which acts
as an enzyme to split blood protein alpha2-globulin to form bradykinin (strong vasodilator)
Esophageal Secretion
 Esophageal secretions are entirely mucous and mainly provide lubrication for swallowing
 Main body of esophagus lined with many simple mucous glands
 At gastric end and to lesser extent in initial portion of esophagus, there are many compound mucous glands
o Mucous secreted by compound glands in upper esophagus prevents mucosal excoriation by newly
entering food
o Compound glands located near esophagogastric junction protect esophageal wall from digestion by
acidic gastric juices that often reflux from stomach back into lower esophagus
Gastric Secretion
 Mucus-secreting cells line entire surface of stomach
 Stomach mucosa has oxyntic glands (gastric glands) and pyloric glands
o Oxyntic glands secrete HCl, pepsinogen, intrinsic factor, and mucus; located on inside surfaces of body
and fundus of stomach, constituting proximal 80% of stomach
o Pyloric glands secrete mainly mucus for protection of pyloric mucosa from stomach acid and gastrin
 Located in antral portion of stomach (distal 20%)
 Oxyntic glands composed of mucous neck cells (secrete mainly mucus), peptic (chief) cells (secrete large
quantities of pepsinogen), and parietal (oxyntic) cells (secrete HCl and intrinsic factor)
o When stimulated, parietal cells secrete acid solution which is nearly isotonic with body fluids
 Concentration H+ requires lots of energy
 At same time H+ secreted, bicarb ions diffuse into blood so gastric venous blood has high pH
than arterial blood when stomach is secreting acid
 Oxyntic cell contains large branching intracellular canaliculi; HCl formed at villus-like projections
inside canaliculi and is conducted through canaliculi to secretory end of cell
 Main driving force of HCl secretion is H+-K+ ATPase pump
 Chemical mechanism of HCl formation
Water inside parietal cell becomes dissociated into H+ and OH- in cell cytoplasm; H+
actively secreted into canliculus in exchange for K+ (catalyzed by H+-K+ ATPase)
o K+ transported into cell by Na+-K+ ATPase pump on basolateral side of
membrane tend to leak into lumen but are recycled back into cell by H+-K+
o Basolateral Na+-K+ ATPase creates low intracellular Na+, which contributes to
Na+ reabsorption from lumen of canaliculus, so most of K+ and Na+ in canaliculus
reabsorbed into cell cytoplasm, and H+ take their place in canaliculus
 Pumping of H+ out of cell by H+-K+ ATPase permits OH- to accumulate and form HCO3from CO2, either formed during metabolism in cell or entering cell from blood (catalyzed
by carbonic anhydrase)
o HCO3- transported across basolateral membrane into extracellular fluid in
exchange for Cl-, which enter cell and are secreted through Cl- channels into
canaliculus, giving strong solution of HCl in canaliculus
o HCl secreted outward through open end of canaliculus into lumen of gland
 Water passes into canaliculus by osmosis because of extra ions secreted into canaliculus
 Final secretion from canaliculus contains water, HCl, KCl, and small amount of NaCl
 Major part of stomach’s ability to prevent back leak of acid attributed to gastric barrier due to
formation of alkaline mucus and tight junctions between epithelia cells
 If barrier damaged by toxic substances (like excess aspirin or alcohol), secreted acid
leaks down electrochemical gradient into mucosa, causing stomach mucosal damage
o Acetylcholine released by PNS stimulation excites secretion of pepsinogen by peptic cells, HCl by parietal
cells, and mucus by mucous cells
o Both gastrin and histamine strongly stimulate secretion of acid by parietal cells but have little effect on
other cells
o Several slightly different types of pepsinogen secreted by peptic and mucous cells of gastric glands; all
pepsinogens perform same functions
 Activated by HCl to form pepsin, which functions as active proteolytic enzyme in highly acid
medium (has almost no proteolytic activity above pH 5, and becomes completely inactivated in
short time)
o Intrinsic factor – essential for absorption of vitamin B12 in ileum; secreted by parietal cells along with HCl
 When acid-producing parietal cells of stomach destroyed (as in chronic gastritis), person
develops achlorhydria and pernicious anemia because of failure of maturation of RBCs in
absence of vitamin B12 stimulation of bone marrow
Pyloric glands – structurally similar to oxyntic glands but contain few peptic cells and almost no parietal cells;
contain mostly mucous cells identical with mucous neck cells of oxyntic glands
o Cells secrete small amount of pepsinogen and large amount of thin mucus that helps lubricate food
movement and protect stomach wall from digestion by gastric enzymes
o Also secrete gastrin
Entire surface of stomach mucosa between glands has continuous layer of surface mucous cells that secrete
large quantities of viscid mucus that coats stomach mucosa with gel layer of mucus, providing major shell of
protection for stomach wall, as well as contributing to lubrication of food transport
o Mucus is alkaline, so normal underlying stomach wall not directly exposed to highly acidic, proteolytic
stomach secretion
o Even slightest contact with food or any irritation of mucosa directly stimulates surface mucous cells to
secrete additional quantities of thick, alkaline, viscid mucus
Secretion of HCl under continuous control by both endocrine and nervous signals
o Parietal cells operate in close association with enterochromaffin-like cells (ECL cells) that secrete
histamine; rate of formation and secretion of HCl by parietal cells directly related to amount of
histamine secreted by ECL cells
o ECL cells lie deep in recesses of oxyntic glands and release histamine in direct contact with parietal cells
o ECL cells stimulated to secrete histamine by gastrin, which is formed almost entirely in antral portion of
stomach mucosa in response to proteins in foods being digested
o ECL cells stimulated by hormonal substances secreted by ENS of stomach wall
Gastrin – secreted by gastrin cells (G cells) located in pyloric glands in distal end of stomach
o Smaller form more abundant than larger form, but both important
o When protein-containing foods reach antral end of stomach, some proteins have stimulatory effect on
gastrin cells in pyloric glands to cause release of gastrin into blood to be transported to ECL cells of
o Vigorous mixing of gastric juices transports gastrin rapidly to ECL cells in body of stomach, causing
release of histamine directly into deep oxyntic glands
o Histamine acts quickly to stimulate gastric HCl secretion
Regulation of pepsinogen secretion by peptic cells in oxyntic glands occurs in response to stimulation of peptic
cells by acetylcholine released from vagus nerves or from gastric enteric nervous plexus and stimulation of
peptic cell secretion in response to acid in stomach
o Acid elicits additional ENS reflexes that support original nervous signals to peptic cells, so rate of
secretion of pepsinogen strongly influenced by amount of acid in stomach
o People who have lost ability to secrete normal amounts of acid have decreased secretion of pepsinogen,
even though peptic cells may be normal
Gastric secretion occurs in three phases
o Cephalic phase – occurs even before food enters stomach, especially while it is being eaten
 Results from sight, smell, thought, or taste of food, and greater the appetite, the more intense
the stimulation
 Neurogenic signals that cause cephalic phase originate in cerebral cortex and appetite centers of
amygdala and hypothalamus and are transmitted through dorsal motor nuclei of vagi and
through vagus nerves to stomach
 Normally accounts for 30% of gastric secretion associated with eating meal
o Gastric phase – once food enters stomach, it excites long vagovagal reflexes from stomach to brain and
back to stomach, local enteric reflexes, and gastrin mechanism, causing secretion of gastric juice during
several hours while food remains in stomach
 Accounts for 60% of total gastric secretion associated with eating
o Intestinal phase – presence of food in upper portion of small intestine, particularly duodenum,
continues to cause stomach secretion of small amounts of gastric juice, partly because of small amounts
of gastrin released by duodenal mucosa
 Accounts for 10% of acid response to meal
Intestinal chyme slightly stimulates gastric secretion during early intestinal phase of stomach secretion, but
paradoxically inhibits gastric secretion at other times
o Presence of food in small intestine initiates reverse enterogastric reflex, transmitted through myenteric
nervous system and extrinsic SNS and vagus nerves, that inhibits stomach secretion
 Reflex initiated by distending small bowel, presence of acid in upper intestine, or irritation of
o Presence of acid, fat, protein breakdown products, hyperosmotic or hyposmotic fluids, or any irritating
factor in upper small intestine causes release of intestinal hormones
 Secretin – opposes stomach secretion
 Gastric inhibitory peptide, vasoactive intestinal polypeptide, and somatostatin have slight to
moderate effects in inhibiting gastric secretion
o Enterogastric inhibitory reflexes plus inhibitory hormones usually reduce stomach motility at same time
that they reduce gastric secretion
Stomach secretes few mL of gastric juice each hour during interdigestive period when little or no digestion
occurring anywhere in gut
o Secretion almost entirely of nonoxyntic type (mainly of mucus, little pepsin and almost no acid)
o Emotional stimuli frequently increase interdigestive gastric secretion (highly peptic and acidic) in much
the same way that cephalic phase of gastric secretion excites secretion at onset of meal
 Increase of secretion in response to emotional stimuli is cause of peptic ulcers
Pancreatic Secretion
 Pancreas – large compound gland; digestive enzymes secreted by pancreatic acini, and large volumes of sodium
bicarb solution secreted by small ductules and larger ducts leading from acini
o Combined product of enzymes and sodium bicarb flows through long pancreatic duct that joins hepatic
duct immediately before it empties into duodenum through papilla of Vater, surrounded by sphincter of
o Pancreatic juice secreted most abundantly in response to presence of chyme in upper portions of small
intestine; characteristics of pancreatic juice determined by types of food in chyme
 Trypsin and chymotrypsin – split whole and partially digested proteins into peptides of various sizes but don’t
cause release of individual amino acids
 Carboxypolypeptidase – splits some peptides into individual amino acids, completing digestion of some proteins
 Pancreatic amylase – hydrolyzes starches, glycogen, and most other carbs (except cellulose) to form mostly
disaccharides and a few trisaccharides
 Pancreatic lipase – capable of hydrolyzing neutral fat into fatty acids and monoglycerides
 Cholesterol esterase – causes hydrolysis of cholesterol esters
 Phospholipase – splits fatty acids from phospholipids
 Trypsinogen activated by enterokinase (secreted by intestinal mucosa when chyme comes in contact with
mucosa); trypsinogen can be autocatalytically activated by trypsin that has already been formed from previously
secreted trypsinogen; trypsin activates chymotrypsinogen and procarboxypolypeptidase
 Cells that secrete proteolytic enzymes into acini of pancreas secrete trypsin inhibitor (formed in cytoplasm of
glandular cells and prevents activation of trypsinogen in secretory cells and acini and ducts of pancreas)
 When pancreas becomes severely damaged or when duct becomes blocked, large quantities of pancreatic
secretion sometimes become pooled in damaged areas of pancreas; effect of trypsin inhibitor often
overwhelmed, and pancreatic secretions become activated and can literally digest entire pancreas in a few
hours, giving rise to acute pancreatitis
o Sometimes lethal because of accompanying circulatory shock
o Even if not lethal, usually leads to subsequent lifetime of pancreatic insufficiency
 Bicarbonate ions and water secreted mainly by epithelial cells of ductules and ducts that lead from acini
o When pancreas stimulated to secrete pancreatic juice, bicarb ion concentration can be 5x that of plasma
o Basic steps in cellular mechanism for secreting sodium bicarbonate solution
 CO2 diffuses to interior of cell from blood and, under influence of carbonic anhydrase, combines
with water to form H2CO3, which dissociates into H+ and HCO3-; HCO3- actively transported in
association with Na+ through luminal border of cell into lumen of duct
 H+ formed by dissociation of carbonic acid inside cell exchanged for Na+ through blood border of
cell by secondary active transport process; supplies Na+ transported through luminal border into
pancreatic duct lumen to provide electrical neutrality for secreted bicarb ions
 Overall movement of Na+ and HCO3- from blood into duct lumen creates osmotic pressure
gradient that causes osmosis of water into pancreatic duct, forming an almost completely
isosmotic bicarb solution
 Basic stimuli important in causing pancreatic secretion
o Acetylcholine – released from vagus nerve endings and other cholinergic nerves in ENS
o Cholecystokinin – secreted by duodenal and upper jejunal mucosa when food enters small intestine
o Secretin – secreted by duodenal and jejunal mucosa when highly acidic food enters small intestine
 ACh and CCK stimulate acinar cells of pancreas, causing production of large quantities of pancreatic digestive
enzymes but relatively small quantities of water and electrolytes to go with enzymes
o Without water, most enzymes remain temporarily stored in acini and ducts until more fluid secretion
comes along to wash them into duodenum
 Secretin – stimulates secretion of large quantities of water solution of NaHCO3 by pancreatic ductal epithelium
 When all different stimuli of pancreatic secretion occur at once, total secretion is far greater than sum of
secretions caused by each one separately (stimuli potentiate [multiply] one another)
 Pancreatic secretion occurs in 3 phases
Cephalic phase – same nervous signals from brain that cause secretion in stomach cause acetylcholine
release by vagal nerve endings in pancreas; causes moderate amounts of enzymes to be secreted into
pancreatic acini (20% of total secretion after meal)
 Little secretion flows immediately through pancreatic ducts into intestine because only small
amounts of water and electrolytes secreted along with enzymes
o Gastric phase – nervous stimulation of enzyme secretion continues (5-10% of secretion after meal)
o Intestinal phase – after chyme leaves stomach and enters small intestine, pancreatic secretion becomes
copious, mainly in respons to secretin
 Secretin – secreted as prosecretin from S-cells in mucosa of duodenum and jejunum
o When acid chyme enters duodenum from stomach, it causes duodenal mucosal release and activation of
secretin, which is absorbed into blood; only true potent constituent of cyme that causes secretin release
is HCl from stomach
o Secretin causes pancreas to secrete large quantities of fluid containing high concentration of HCO3- and
low Cl- concentration
o Secretin begins to be released from mucosa of small intestine when pH of duodenal contents falls below
4.5-5.0, and its release increases greatly as pH falls to 3.0, immediately releasing copious secretion of
pancreatic juice containing abundant amounts of NaHCO3
o Net reaction is
HCl+NaHCO3  NaCl + H2CO3
o Carbonic acid immediately dissociates into CO2 and H2O; CO2 absorbed into blood and expired through
lungs, leaving neutral solution of NaCl in duodenum
o Acid contents emptied into duodenum from stomach become neutralized, so further peptic digestive
activity by gastric juices in duodenum immediately blocked
o HCO3- secretion by pancreas provides appropriate pH for action of pancreatic digestive enzymes, which
function optimally in slightly alkaline or neutral medium (pH 7.0-8.0)
 Presence of food in upper small intestine causes CCK to be released from I cells in mucosa of duodenum and
upper jejunum; release of CCK results especially from presence of proteoses and peptones (products of partial
protein digestion) and long-chain fatty acids in chyme coming from stomach
o CCK passes by way of blood to pancreas and causes mainly secretion of more pancreatic digestive
enzymes by acinar cells (accounts for 70-80% of total secretion of pancreatic digestive enzymes after
 Pancreas secretes far more water and NaHCO3 in response to HCl, almost equal amounts of water/NaHCO3 and
enzymes if fat in chyme, and lots more enzymes than water/NaHCO3 when peptones enter duodenum
Secretion of Bile by the Liver; Functions of the Biliary Tree
 Bile plays important role in fat digestion and absorption because bile acids in bile
o Help emulsify large fat particles of food into many minute particles whose surface can be attacked by
lipase enzymes secreted in pancreatic juice
o Aid in absorption of digested fat end products through intestinal mucosal membrane
 Bile serves as means for excretion of bilirubin and excess cholesterol
 Bile secreted in 2 stages in liver
o Initial portion secreted by hepatocytes; secretion contains large amounts of bile acids, cholesterol, and
other organic constituents; secreted into bile canaliculi that originate between hepatocytes
o Bile flows in canaliculi toward interlobular septa, where canaliculi empty into terminal bile ducts and
then into progressively larger ducts, finally reaching hepatic duct; can be secreted or stored
 In bile ducts, additional liver secretion added to initial bile, containing watery solution of Na+ and HCO3- secreted
by secretory epithelial cells that line ductules and ducts; second secretion stimulated by secretin, which causes
release of additional quantities of HCO3- to supplement those in pancreatic secretion
 Bile secreted continually by liver cells, but most of it is stored in gallbladder until needed in duodenum (up to 12
hours in gallbladder)
o Gallbladder mucosa continuously absorbs water, Na+, Cl-, and most other small electrolytes,
concentrating remaining bile constituents that contain bile salts, cholesterol, lecithin, and bilirubin
o Most of gallbladder absorption caused by active transport of Na+ through gallbladder epithelium,
followed by secondary absorption of Cl-, H2O, and most other diffusible constituents
o Bile usually concentrated up to 5x, but can be concentrated up to 20x
By far, most abundant substances secreted in bile are bile salts, which are ½ of total solutes in bile
o Also secreted or excreted in large concentrations are bilirubin, cholesterol, lecithin, and electrolytes
In concentrating process in gallbladder, water and large portions of electrolytes (except Ca2+) reabsorbed by
gallbladder mucosa; essentially all other constituents, especially bile salts and lipid substances cholesterol and
lecithin, not reabsorbed and, therefore, become highly concentrated in gallbladder bile
When food begins to be digested in upper GI tract, gallbladder begins to empty, especially when fatty foods
reach duodenum about 30 minutes after meal
o Gallbladder emptying is rhythmical contractions of wall of gallbladder, but effective emptying requires
simultaneous relaxation of sphincter of Oddi, which guards exit of common bile duct into duodenum
o Most potent stimulus for causing gallbladder contractions is CCK (stimulus for CCK entry into blood from
duodenal mucosa is mainly presence of fatty foods in duodenum)
o Gallbladder stimulated less strongly by acetylcholine-secreting nerve fibers from both vagi and intestinal
ENS; same nerves that promote motility and secretion in other parts of upper GI tract
Precursor of bile salts is cholesterol, either from diet or synthesized in liver cells during fat metabolism
o Cholesterol converted to cholic acid or chenodeoxycholic acid in about equal quantities
o Acids combine principally with glycine and to a lesser extent taurine to form glyco-conjugated and tauroconjugated bile acids; salts of acids, mainly sodium salts, secreted in bile
Bile salts act as detergent on fat particles, decreasing surface tension of particles and allowing agitation in
intestinal tract to break fat globules into minute sizes (emulsifying or detergent function)
o Help in absorption of fatty acids, monoglycerides, cholesterol, and other lipids from intestinal tract
o Form small physical complexes with lipids (micelles), and are semisoluble in chyme because of electrical
charges of bile salts
o Intestinal lipids ferried in this form to intestinal mucosa, where they are then absorbed into blood
o Without presence of bile salts in intestinal tract, up to 40% of ingested fats lost into feces and person
often develops metabolic deficit because of nutrient loss
About 94% of bile salts reabsorbed into blood from small intestine, half by diffusion through mucosa in early
portions of small intestine and remainder by active transport process through intestinal mucosa in distal ileum
o Enter portal blood and pass back to liver, where salts absorbed by hepatic cells as they go through
venous sinusoids so they can be secreted again later
o On average, salts make the circuit 17 times before being carried out in feces
o Small quantities of bile salts lost into feces replaced by new amounts formed continually by liver cells
o Recirculation of bile salts called enterohepatic circulation of bile salts
Quantity of bile secreted by liver each day highly dependent on availability of bile salts – greater the quantity of
bile salts in enterohepatic circulation, the greater the rate of bile secretion
o Ingestion of supplemental bile salts can increase bile secretion greatly
If bile fistula empties bile salts to exterior for several days to several weeks so they can’t be reabsorbed from
ileum, liver increases production of bile salts 6-10x, which increases rate of bile secretion most of the way back
to normal
Secretin increases bile secretion (increased secretion almost entirely NaHCO3-rich watery solution by epithelial
cells of bile ductules and ducts, not increased secretion by liver parenchymal cells themselves
o HCO3- passes into small intestine and joins HCO3- from pancreas in neutralizing HCl from stomach
Bile salts formed in hepatic cells from cholesterol in blood plasma; in process of secreting bile salts, 1-2 g of
cholesterol removed from blood plasma and secreted into bile each day
o Bile salts lecithin in bile combine with cholesterol to form micelles as colloidal solution
o When bile becomes concentrated in gallbladder, bile salts and lecithin become concentrated along with
cholesterol, which keeps cholesterol in solution
Under abnormal conditions, cholesterol may precipitate in gallbladder, resulting in formation of cholesterol
gallstones; amount of cholesterol in bile determined partly by quantity of fat person eats (because liver cells
synthesize cholesterol as one of products of fat metabolism in body); reason people with high fat diet over
period of years prone to development of gallstones
Inflammation of gallbladder epithelium, often resulting from low-grade chronic infection, may change
absorptive characteristics of gallbladder mucosa, sometimes allowing excessive absorption of water and bile
salts but leaving behind cholesterol in gallbladder in progressively greater concentrations
Cholesterol begins to precipitate, first forming many small crystals of cholesterol on surface of inflamed
mucosa, but then progressing to large gallstones
Secretions of Small Intestine
 Compound mucous glands (Brunner’s glands) located in wall of first few centimeters of duodenum, mainly
between pylorus of stomach and papilla of Vater, where pancreatic secretion and bile empty into duodenum
o Glands secrete large amounts of alkaline mucus in response to tactile or irritating stimuli on duodenal
mucosa, vagal stimulation (causes increased Brunner’s glands secretion concurrently with increase in
stomach secretion), and GI hormones, especially secretin
o Brunner’s glands inhibited by SNS stimulation, so stimulation in very excitable persons likely to leave
duodenal bulb unprotected and is perhaps one of factors that cause this to be the site of peptic ulcers in
50% of patients
 Crypts of Lieberkühn – located over entire surface of small intestine; lie between intestinal villi
o Surfaces of both crypts and villi covered by epithelium composed of goblet cells (secrete mucus that
lubricates and protects intestinal surfaces) and large number of enterocytes (in crypts, secrete large
quantities of water and electrolytes and, over surfaces of adjacent villi, reabsorb water and electrolytes
along with end products of digestion)
o Enterocyte secretions are almost pure extracellular fluid and have slightly alkaline pH in range of 7.5-8.0
o Secretions rapidly reabsorbed by villi
o Flow of fluid from crypts into villi supplies watery vehicle for absorption of substances from chyme when
it comes in contact with villi
o Control of secretion involves active secretion of Cl- into crypts and active secretion of HCO3-; secretion
causes electrical drag of positively charged Na+ through membrane and into secreted fluid; all ions
together cause osmotic movement of water
 When secretions of small intestine collected without cellular debris, they have almost no enzymes; enterocytes
of mucosa, especially those that cover villi, contain digestive enzymes that digest specific food substances while
they are being absorbed through epithelium
o Several peptidases – split small peptides into amino acids
o Sucrase, maltase, isomaltase, and lactase – split disaccharides into monosaccharides
o Small amounts of intestinal lipase – split neutral fats into glycerol and fatty acids
o Epithelial cells deep in crypts of Lieberkühn continually undergo mitosis, and new cells migrate along BM
upward out of crypts toward tips of villi, continually replacing villus epithelium and forming new
digestive enzymes
o As villus cells age, they are shed into intestinal secretions
 By far, most important means for regulating small intestine secretion are local enteric nervous reflexes,
especially reflexes initiated by tactile or irritative stimuli from chyme in intestines
Secretion of Mucus by Large Intestine
 Mucosa of large intestine has many crypts of Lieberkühn, but there are no villi
 Epithelial cells secrete almost no digestive enzymes, but secrete only mucus from mucous cells
o Mucus contains moderate amounts of HCO3- secreted by non-mucus-secreting epithelial cells
o Rate of secretion of mucus regulated principally by direct, tactile stimulation of epithelial cells lining
large intestine and local nervous reflexes to mucous cells in crypts of Lieberkühn
 Stimulation of pelvic nerves from spinal cord, which carry PNS innervation to distal ½-2/3 of large intestine, can
also cause marked increase in mucus secretion; occurs along with increase in peristaltic motility of colon
o During extreme PNS stimulation, often caused by emotional disturbances, so much mucus can be
secreted into large intestine that person has bowel movement of ropy mucus as often as every 30
minutes; mucus often contains little or no fecal material
 Mucus in large intestine protects intestinal wall against excoriation and provides adherent medium for holding
fecal matter together; also protects intestinal wall from great amount of bacterial activity that takes place in
feces; mucus plus alkalinity of secretion (pH 8.0) provides barrier to keep acids formed in feces from attacking
intestinal wall
 Whenever a segment of large intestine becomes intensely irritated, as occurs when bacterial infection becomes
rampant during enteritis, mucosa secretes extra large quantities of water and electrolytes in addition to normal
viscid alkaline mucus; dilutes irritating factors and causes rapid movement of feces toward anus – diarrhea