Gastrointestinal Physiology. (4) GI SECRETION . Salivary Secretion Gastric Secretion Pancreatic Secretion Bile Secretion b y t he Liver Secretions o f t he Small Intestine Secretions o f t he Large Intestine. 1. Salivary Secretion. a. Structure of the s alivary g lands
(4) GI SECRETION
a. Structure of the salivary glands
b. Formation of saliva
c. Regulation of salivary secretion
Three major salivary glands:
serous + mucous
Unusual feature :
unusual high blood flow, > 10 times the blood flow to exercising skeletal muscle (when corrected for organ size)
- The acinar cells secrete the initial saliva.
- The initial saliva is isotonic.
- It has the same electrolyte composition as plasma.
- The ductal cells modify the initial saliva.
- Absorption of Na+, CI- > secretion of K+ and HCO3-
- The final saliva is hypotonic.
Primary controller of salivation, large amount of watery saliva containing enzymes
Small volume of saliva, thick with mucus
Because sympathetic stimulation accompanies frightening or stressful situations, the mouth may feel dry at such times.
Characteristics of saliva secretion:
thiocyanate ions, proteolytic enzymes (lysozyme), IgA etc.
Functions of saliva:
a. Structure and cell types of the gastric mucosa
b. HCL secretion
c. Pepsinogen secretion and activation
d. Intrinsic factor secretion
mucous neck cells (mostly mucus but also pepsinogen)
peptic or chief cells(pepsinogen)
parietal or oxyntic cells(HCl and intrinsic factor)
paracrine cells (histamine)
mucous cells(pepsinogen, mucus)
The inner surface of the stomach has deep wells called gastric pits. Each pit leads to gastric glands.
In the resting, nonstimulated state, tubulovesicular membranes are presented in the apical portion of the parietal cell.
Upon stimulation, cytoskeletal rearrangement causes the tubulovesicular membranes to fuse into the canalicular membrane. The is a substantial increase (50-100 fold) in the surface area of the apical membrane of the parietal cell, as well as the appearance of microvilli.
Parietal cell: resting and stimulated.
(in gastric venous blood)
Figure 8-7 Mechanism of HCl secretion by gastric parietal cells. ATP, Adenosine triphosphate.
Vagus nerve innervates parietal cells
Ach is the neurotransmitter
Vagus nerve innervates G cells gastrin H+ secretion
GRP is the neurotransmitter
Atropine blocks ________ path.
Vagotomy eliminates __________ pathway(s)
4. Potentiating effects of Ach, histamine, and gastrin on H+ secretion
via Gi protein cAMP
inhibit histamine release from ECL cells
inhibit gastrin release from G cells
Helicobacter pylori (H. pylori)
major causative factor of gastric ulcer
Produce NH4+, damages mucosal barrier
Intrinsic factor (IF): a mucoprotein, secreted by parietal cells along with HCl.
Gastric mucosal epithelium is made entirely of secretary cells including exocrine, endocrine, and paracrine cells.
Thick alkaline mucus by surface epithelium
Thin watery mucus by neck cells
HCl by parietal cells
Pepsinogen by chief cells
Intrinsic factor by parietal cells
~ 1.5 L is secreted per day,
pH: 0.8 – 3.5
a. Structure of the pancreatic exocrine glands
b. Formation of pancreatic secretion
c. Regulation of pancreatic secretion
aqueous secretion (HCO3-)
Trypsin inhibitor is secreted by acini to prevent activation of trypsin. If the pancreas is damaged, large quantities of pancreatic secretion pools in the damaged areas, and trypsin inhibitor is overwhelmed. Pancreatic secretions can digest the pancreas, which is known as acute pancreatitis.
Figure 8-21 Mechanism of pancreatic secretion. The enzymatic component is produced by acinar cells, and the aqueous component is produced by centroacinar and ductal cells. ATP, Adenosine triphosphate.
Enzymes often secreted in an inactive form, and activated near the wall of gastrointestinal tract - so food is broken down where it can be transported into the blood stream.
Figure 8-23 Regulation of pancreatic secretion. ACh, Acetylcholine; cAMP, cyclic adenosine monophosphate; CCK, cholecystokinin; IP3, inositol 1,4,5-triphosphate.
The Cl channel is encoded by the cystic fibrosis gene product CFTR. Thus patients with cystic fibrosis, who lack a functional Cl channel have defective duct transport. The ducts get clogged with precipitated
enzymes and mucus and the pancreas undergoes a fibrosis (hence the name of the disease).
The physiological significance of this model is twofold, first the HCO
delivered to the duodenal lumen neutralizes gastric acid and allows the digestive enzymes to operate at their pH optimum, close to
neutral. Second, H which are produced in the duct cells when HCO
is generated for secretion,leave via NaH exchange into the blood. The net effect is to neutralize the alkaline tide in the blood that was generated by gastric acid secretion.
HCO3- : neutralize the contents from the stomach
Enzymes: digestion of protein, carbohydrate, and fats
Pancreatic juice is characterized by:
- high volume (1 L/day)
- virtually the same Na+ and K+ concentrations as plasma
- much higher HCO3- concentration than plasma
- much lower Cl- concentration than plasma
- pancreatic lipase, amylase, and proteases
- pH of 8.0 – 8.3
a. Overview of the biliary system
b. Composition and functions of bile
c. Formation of bile and function of the gallbladder
d. Regulation of bile excretion from the gallbladder
e. Enterohepatic circulation of bile salts
f. Clinical correlation
Figure 8-24 Secretion and enterohepatic circulation of bile salts.Light blue arrows show the path of bile flow; yellow arrows show the movement of ions and water. CCK, Cholecystokinin.
Bile salts including bile acids (50%)
Phospholipids (Lecithin, 40%)
Bile pigments (2%): bilirubin
Electrolytes (Na+, K+, Ca++, Cl-, HCO3-)
aids in fat digestion
aids in fat absorption
eliminating metabolic wastes
(Primary bile acids)
Glycine or taurine
Glyco- or tauro-conjugatedbile acids
(Secondary bile acid)
Bile ducts secrete:
watery solution, Na+, HCO3-
(bile acids, cholesterol, bilirubin)
Watery components are reabsorbed by the gallbladder mucosa.
Organic constituents are highly concentrated
(5 – 20 fold).
absorbed – in other words, bile is needed.
Na+-bile salt cotransporter
Figure 8-24 Secretion and enterohepatic circulation of bile salts.
Gallstone formation: precipitated cholesterol
high-fat diet, prone to the development of gallstones
too much absorption of water from bile
inflammation of epithelium
IF-Vitamin B12 complex cannot be absorbed.
Steatorrhea: recirculation of bile via enterohepatic circulation is reduced. Most secreted bile acids are lost in feces. Oil droplets in the stool.
Diarrhea: bile acids cAMP-dependent Cl- secretion in colonic epithelium, Na+ and water follow Cl- into the lumen
absorption of water in the gallbladder
absorption of bile acids ( solubility of cholesterol)
cholesterol concentration (fatty diet)
Inflammation of the epithelium
Mechanisms the risk of stones formation
Secretion of H+ by the mucosa (acidification of bile) Ca 2+ precipitation
Absorption of large amounts (about 50%) of Ca 2+
Release of the inhibitors of Ca2+ and cholesterol precipitation
Secretion of water and electrolytes during digestion which intermittently dilute the gallbladder content
Combination of cholesterol with lecithin and bile salts (micelles) water solubility of cholesterol
Contractions prevent accumulation of microcrystalGALLSTONES
An extensive array of compound mucus glands
Located in the wall of duodenum.
Secrete mucus and HCO3-
Crypts of Lieberkühn
Located over the entire surface of the small intestine.
Goblet cell: secrete mucus
Enterocytes: secrete and absorb water and electrolytes
The large intestine has many crypts of Lieberkühn and secrets an alkline mucus solution containing bicarbonate and K+.
The sole function of mucus is protection. It protects the large intestine wall from damage by acids formed in feces from attacking the intestinal wall.
Acid and mechanical stimulation, mediated by both long and short reflexes, increase the secretion of mucus.
the wall of the large intestine
Acid passage of feces
(long and short)
a mucus layer lining the wall
Description of Case: A 52-year-old man visits his physician complaining of abdominal pain, nausea, loss of appetite, frequent belching, and diarrhea. The man reports that his pain is worse at night and is sometimes relieved by eating food or taking antacids containing HCO3-. GI endoscopy reveals an ulcer in the duodenal bulb. Stool samples are positive for blood and fat. His serum gastrin level is measured and found to be markedly elevated. A CT scan reveals a 1.5 cm mass in the head of the pancreas. The man is referred to a surgeon. While awaiting surgery, the man is treated with the drug omeprazole, which inhibits H+ secretion by gastric parietal cells. During a laparotomy, a pancreatic tumor is located and excised. After surgery, the man’s symptoms diminish, and subsequent endoscopy shows that the duodenal ulcer has healed.
Explanation of Case: All of the man’s symptoms and clinical manifestations are caused, directly or indirectly, by a gastrin-secreting tumor of the pancreas. In Zollinger-Ellison syndrome, the tumor secretes large amounts of gastrin into the circulation. The target cell for gastrin is the gastric parietal cell, where it stimulates H+ secretion. The physiologic source of gastrin, the gastric G cells, are under negative feedback control. Thus, normally, gastrin secretion and H+ secretion are inhibited when the gastric contents are acidified (i.e., when no more H+ is needed). In Zollinger-Ellison syndrome, however, this negative feedback control mechanism does not operate: gastrin secretion by the tumor is not inhibited when the gastric contents are acidified. Therefore, gastrin secretion continues unabated, as does H+ secretion by the parietal cells.
The man’s diarrhea is caused by the large volume of fluid delivered from the stomach (stimulated by gastrin) to the small intestine; the volume is so great that it overwhelms the capacity of the intestine to absorb it. The presence of fat in the stool (steatorrhea) is abnormal, since mechanisms in the small intestine normally ensure that dietary fat is completely absorbed. Steatorrhea is present in Zollinger-Ellison syndrome for two reasons. 1) The first reason is that excess H+ is delivered from the stomach to the small intestine and overwhelms the buffering ability of HCO3--containing pancreatic juices. The duodenal contents remain at acidic pH rather than being neutralized, and the acidic pH inactivates pancreatic lipase. When pancreatic lipase is inactivated, it cannot digest dietary triglycerides to monoglycerides and fatty acids. Undigested triglycerides are not absorbed by intestinal epithelial cells, and thus, they are excreted in the stool. 2) The second reason for steatorrhea is that the acidity of the duodenal contents damages the intestinal mucosa (evidenced by the duodenal ulcer) and reduces the microvillar surface area for absorption.
Treatment: While the man is awaiting surgery to remove the gastrin-secreting tumor, he is treated with omeprazole, which directly blocks the H+-K+-ATPase in the apical membrane of gastric parietal cells. This ATPase is responsible for gastric H+ secretion. The drug is expected to reduce H+ secretion and decrease the H+ load to the duodenum. Later, the gastrin-secreting tumor is surgically removed.
Description of Case: A 36-year-old woman has 75% of her ileum resected following a perforation caused by severe Crohn’s disease (chronic inflammatory disease of the intestine). Her postsurgical management included monthly injections of vitamin B12. After surgery, she experienced diarrhea and noted oil droplets in her stool. Her physician prescribed the drug cholestyramine to control her diarrhea, but she continues to have steatorrhea.
Explanation of Case: The woman’s severe Crohn’s disease caused an intestinal perforation, which necessitated a subtotal ileectomy, removal of the terminal portion of the small intestine. Consequences of removing the ileum include decreased recirculation of bile acids to the liver and decreased reabsorption of the intrinsic factor-vitamin B12 complex. In normal persons with an intact ileum, 95% of the bile acids secreted in bile are returned to the liver, via the enterohepatic circulation, rather than being excreted in feces. This recirculation decreases the demand on the liver for the synthesis of new bile acids. In a patient who has had an ileectomy, most of the secreted bile acids are lost in feces, increasing the demand for synthesis of new bile acids. The liver is unable to keep pace with the demand, causing a decrease in the total bile acid pool. Because the pool is decreased, inadequate quantities of bile acids are secreted into the small intestine, and both emulsification of dietary lipids for digestion and micelle formation for absorption of lipids are compromised. As a result, dietary lipids are excreted in feces, seen as oil droplets in the stool (steatorrhea). This patient has lost another important function of the ileum, the absorption of vitamin B12. Normally, the ileum is the site of absorption of the intrinsic factor-vitamin B12 complex. Intrinsic factor is secreted by gastric parietal cells, forms a stable complex with dietary vitamin B12, and the complex then is absorbed in the ileum. The patient cannot absorb vitamin B12 and must receive monthly injections, bypassing the intestinal absorptive pathway. The woman’s diarrhea is caused, in part, by high concentrations of bile acids in the lumen of the colon (because they are not recirculated). Bile acids stimulate cAMP-dependent Cl- secretion in colonic epithelial cells. When Cl- secretion is stimulated, Na+ and water follow Cl- into the lumen, producing a secretory diarrhea (sometimes called bile acid diarrhea).
Treatment: The drug cholestyramine, used to treat bile acid diarrhea, binds bile acids in the colon. In bound form, the bile acids do not stimulate Cl- secretion or cause secretory diarrhea. However, the woman will continue to have steatorrhea.
a. It is inhibited by a fat-rich meal
b. It is inhibited by the presence of amino acids in the duodenum
c. It is stimulated by atropine
d. It occurs in response to cholecystokinin
e. It occurs simultaneously with the contraction of the sphincter of Oddi