GI Secretions Part III
11AM Fr, 2-28-03
Dr. Gwirtz
MMessa for J. Wiggins
Page 1 of 6
GI Secretions Part #3
This lecture started off at the slide titled “Transport Processes Involved in Elaboration of
Pancreatic Juice”
Dr. Gwirtz was using it to again tie together some concepts from the previous lecture.
 Venous blood draining from the pancreas during digestion would be acidic,
because the ductal cells secrete bicarbonate into the ductal lumen. (After secreting
so much bicarb, the venous blood is left with excess acid, termed an “acid tide”)
 Venous blood draining the stomach during digestion would be alkaline in nature
since the gastric mucosa has secreted so much hydrogen ion into the stomach
lumen (leaving the blood draining the area to be mostly alkaline)
 The portal blood is a combination of blood from both the pancreatic and gastric
venous system, such that the pH is essentially neutral.
 What can a researcher inject into a person to test the ability of the acinar cells to
secrete its enzymes?? Answer… CCK
 What can be injected into a person to test the ability of the ductal cells to secrete
bicarbonate?? Answer.. Secretin
Bile Secretion by the liver
 We produce about 600-1200ml of bile per day, in two separate stages
 Hepatocytes synthesize and secrete the bile-dependent fraction of bile
 This portion is under no hormonal or neural control, meaning that the
hepatocytes continually synthesize and secrete bile, as well as remove it
from portal blood to be reused.
 The bile ducts themselves secrete water and electrolytres, which is the bileindependent fraction of secretion, meaning that there is no bile in this
secretion.
 This secretion is rich in bicarbonate and is stimulated by secretin
 The liver synthesizes the primary bile acids from cholesterol
 The liver’s target for this secretion is the small intestine
 In the small intestine, the bile is converted from primary bile acids to secondary
bile acids by bacteria
 When the bile is not able to enter the small intestine because the Sphincter of
Oddi is closed, it enters the gallbladder via the cystic duct (it is stored here only)
 The bile is concentrated in the gallbladder 12-20 fold by active absorption of
sodium into the luminal cell (water leaves the gallbladder lumen to go with
sodium and chloride)
Formation of bile acids from cholesterol
 Primary bile acids formed by the liver are cholic acid and chenodeoxycholic acid
 The primary bile acids are converted to secondary bile acids, deoxycholic acid
and lithocholic acid (respectively), by bacteria in the small intestine.
GI Secretions Part III
11AM Fr, 2-28-03
Dr. Gwirtz
MMessa for J. Wiggins
Page 2 of 6
Enterohepatic Circulation of bile acids
 Recall that the liver synthesizes bile
 Bile is stored in the gallbladder between meals
 CCK is released from the duodenum during ingestion of fats and proteins, and this
causes contraction of the gallbladder while it also causes the Sphincter of Oddi to
relax.
 Bile is released from the gallbladder into the small intestine to emulsify fats
mostly
 In the terminal ileum, bile salts are actively reabsorbed by a sodium co-transport
back to the portal blood for reuse. (recall that B12 is the only other substance
absorbed in the terminal ileum).
 Only about 5% of the bile secreted daily gets excreted in the stool
 We only have about 3 grams of bile in our body at a given time (termed the bile
pool), yet we require as much as 12-36 grams of bile per day.
 This shows how important it is to reabsorb bile for recycling
 Some, but very little bile is excreted in the urine also.
Question? Can a patient survive without a gallbladder? Answer..Yes..
 If a patient has their gallbladder removed due to a condition known as
cholelithiasis, they no longer have the same storage mechanism for bile. They
now continually secrete bile into the duodenum but may have a slightly harder
time emulsifying and digesting fats.
 You cannot live without bile!!!
 Without bile, or in states where bile secretion is impaired (like from a blockage of
the ducts), there is excess fat making its way to the lower GI tract undigested.
This causes a condition known as steatorrhea, where there is excess fat in the
stool.
 Another way to cause this problem is to remove a patient’s terminal ileum, so that
they can no longer reabsorb bile salts (and thus their supply gets too low to carry
out the job of fat emulsification)
 Pancreatitis can also cause this problem because there is a lack of pancreatic
enzymes involved in fat digestion
Functions of Bile
 Important in fat digestion and absorption
 Has a detergent action for emulsification
 Bile salts surround fats and end up creating micelles for digestion and transport of
fats
 Bile has excess bicarbonate used for buffering gastric acids
 Bile is a path to excrete bilirubin( pigments from heme, recall??) and excess
cholesterol, as well as toxic substances
GI Secretions Part III
11AM Fr, 2-28-03
Dr. Gwirtz
MMessa for J. Wiggins
Page 3 of 6
Schematic description of bile salt/ fatty acid micelles
 The hydrophobic part faces the fatty acid in the center
 The hydrophilic part faces the lumen
 This makes these micelles amphipathic, aka…polar
Regulation of Bile
 Recall that the liver synthesizes bile continuously, and stores it in the gallbladder
between meals.
 The gallbladder does not ever secrete bile; it stores and expels bile
 What stimulates secretion of bile from the liver?
 If portal blood bile is elevated, this will stimulate the liver to secrete more
bile.
 Secretin will cause water and electrolytes to be secreted into the bile ducts
 What causes regulation of gallbladder contraction?
 CCK stimulates the GB to contract, and causes the Sphincter of Oddi to relax
 Secretin and vagal stimulation affect the gallbladder in the same way as CCK
but to a much smaller extent.
There is a slide that shows the four mechanisms of bile uptake and secretion but you
are not responsible for this.
Bile salt synthesis by the liver vs.. bile salt secretion
 If the bile salt pool is depleted below 3 grams, then the liver is stimulated to
secrete more bile
 Thus if you remove the terminal ileum, you will significantly increase hepatic
synthesis of bile, due to lack of bile reabsorption.
 If you inject a person with a large quantity of bile, the liver will shut down bile
production, or at least slow its production.
 As humans, we operate in a very narrow range of bile secretion vs. synthesis.
 We normally lose about .5 grams of bile per day, thus our liver synthesizes about
.5 grams of bile per day.
Case Study on Gallbladder Issue
 A 62 y/o female patient presents with severe right upper quadrant pain after eating
fatty foods.
 She comes in after vomitting a bile colored emesis (yellow-green)
 She has steatorrhea (fatty stools), and has a lot of gas.
 She has lost a lot of weight due to dietary intolerance of fat
 Her diagnosis is: Cholestasis (inability to expel bile into the intestine), caused
by Cholelithiasis (stones in the gallbladder or in the system of bile ducts)
 The consequences of this problem include:
 Lack of fat soluble vitamin absorption (A, D, E, K)
 Steatorrhea, gas, and bloating
GI Secretions Part III
11AM Fr, 2-28-03
Dr. Gwirtz
MMessa for J. Wiggins
Page 4 of 6
 If fat reaches the colon, it irritates it and causes a watery diarrhea
 Treatment: remove the gallstones, and supplement nutrition needs
 Clinical Medicine Correlations: (NOT ON PHYSIOLOGY EXAM)
 The right upper quadrant pain that stops inspiratory effort during palpation
under the right costal margin is called a positive Murphy’s sign
 In PTR, PA Clarke taught us that there are 4 F’s of gallbladder disease:
 Female, fat, forties, and fertile (don’t shoot the messenger, I realize this
is cruel)
How do you end up developing gallstones?
 Cholestasis, or decreased bile flow, leads to retention and crystalization of
substances commonly found in bile.
 These crystals get entrapped in mucous and create a “sludge” that is very viscous
 As bile gets trapped and builds up to high levels in the hepatic system, it causes
jaundice (yellow skin color), as well as hepatic cellular damage, drug toxicity
(from not being able to metabolize the drugs correctly in the liver), and elevated
cholesterol levels.
 80% of gallstones consist of cholesterol
 the remaining consist of pigments
 acute cholestasis- involves inflammation from stone accumulation
 chronic cholestasis-involves a stone impacted in the neck of the gallbladder over
an extended period of time
Secretions of the Small Intestine
 Brunner’s Glands
 Are located in the first few centimeters of the duodenum
 Secrete an alkaline mucous for protection from acid, in response to tactile
or irritating stimuli, Ach, or GI hormones (CCK and Secretin)
 Crypts of Lieberkuhn
 Have mucous goblet cells and epithelial cells that secrete about 1800 ml
daily of an extracellular fluid
 This provides a watery medium for absorption of substances by the small
intestine
 In conditions like cholera, these crypts can be stimulated to secrete as
much as 20 liters of fluid per day.
 Tumors such as VIPomas can also stimulate these crypts to secrete
massive amounts of this fluid
 Enzymes associated with the small intestine
 These are not secreted into the intestinal lumen; the only enzymes in the
lumen will be the ones secreted by the pancreas
 These enzymes are associated with the brush border and include:
 Peptidases- to digest proteins
 Sucrase, maltase, isomaltase, and lactase- all help digest disaccarides
GI Secretions Part III
11AM Fr, 2-28-03
Dr. Gwirtz
MMessa for J. Wiggins
Page 5 of 6
 Intestinal lipase- help to digest lipids
 Enterokinases- help activate pancreatic trypsinogen to trypsin, which
activates all the other proteases released from the pancreas
 So if you damage the brush border of the small intestine, you damage
it and create a condition where the microvilli become flattened and
you cannot activate the pancreatic enzymes (this will be presented in
more detail next week)
Regulation of Small Intestinal Secretion
 Neural regulation
 Includes Ach from parasympathetic, VIP, substance P,serotonin from the
ANS plexus’- which all stimulate intestinal secretion
 Sympathetic stimulation of alpha receptors can cause the secretion of
somatostatin to inhibit intestinal secretions.
 Local stimuli
 Distention, tactile stimulation, and local reflexes can all stimulate
intestinal secretions
 Irritation
 Bacteria, viruses, chemicals, toxins-all stimulate intestinal secretion
 Hormonal
 Gastrin, secretin, and CCK, can all stimulate intestinal secretions by
directly stimulating intestinal epithelial cells
Effects of Cholera Toxin
 Cholera releases a toxin that stimulates cAMP, which increases chloride
transport out of the crypts of Leiberkuhn (into the intestinal lumen)
 You can have rapid extracellular fluid loss which leads to hypovolemic shock
Large Intestinal Secretions
 The large intestine also has some crypts of Leib.
 There are also mucous cells that secrete mucous with a large concentration of
potassium and bicarbonate ions.
 Recall that there are no villi in the large intestine, and no enzymes are secreted
in the large intestine.
 The mucous adheres to the fecal matter to facilitate its sliding through the
lumen of the large intestine.
 The bicarbonate in the mucous is important for buffering any acids
produced by bacterial action on the fecal matter
Stimulation for Large Intestinal Secretions
 Tactile stimulation, distention, PNS from pelvic nerves all stimulate secretions
GI Secretions Part III
11AM Fr, 2-28-03
Dr. Gwirtz
MMessa for J. Wiggins
Page 6 of 6
 Irritation from toxins results in secretion of large volumes of water and
electrolytes (diarrhea)
 Acute emotional stress- causes strong PNS stimulation that increases stooling
and mucous (pre-exam stimulation)
Irritation as a major cause of excessive secretion by the Large intestine
 Recall that irritation increases secretion of water and elctrolytes
 This causes diarrhea stimulated directly by:
 Enteritis
 Bacteria and viral infections
 Food antigens
 Bile salts
 Malabsorption of nutrients (fats, carbs, proteins)
Types of Diarrhea
 Osmotic- malabsorptive, causes osmosis of fluid into colonic lumen to dilute
the substance. This is how most laxatives work.
 Secretory-deranged electrolyte transport like in cholera toxins or excess VIP,
increased bile salts.
 Abnormal GI Motility-from psychogenic causes, or a peristaltic rush
 Exudative- blood or mucous/pus irritates the colon and causes diarrhea
Specific Patterns of Diarrhea
 Normovolemic diarrhea is defined as less than 250 grams per day of stool
 Due to increased sensitivity of distention
 Osmotic diarrhea
 Water is drawn into the lumen of the colon by osmotically active
substances (laxatives)
 Secretory diarrhea
 Fluid secretion from the crypts, as in cholera and VIPomas
 Inflammatory diarrhea
 These are from dysentery, meaning toxins and pus caused it, as well as
non-infectious ulcerative colitis
 Rapid transit diarrhea
 Increased motility of the colon from things like short bowel syndrome
(where someone has had a large portion of their bowel removed)
 Malabsorptive diarrhea
 This is where you have a failure of digestion or absorption of something in
the diet. An example would be chronic pancreatitis where the lack of
enzymes results in incomplete digestion of nutrients.