Gastrointestinal Secretions and their Control

• What are some consequences of dysfunctions of GI secretions?

  
• colon

  
  

  How does the colon secrete K+?

  • these cells have a lumenal Na channel

  • absorption of more Na+ than Cl- leaves net negative potential in lumen

  • this drives K+ movement into lumen, via paracellular pathway
• colon

  
  

  What does the colon secrete?

  • mucus (for lubrication)

  • secretion of HCO3- (in exchange for Cl-)

  • some secretion of K+
• colon

  
  

  what is the main function of the colon?

  absorption of water
• Gut hormones and metabolism

  
  

  Which hormone's release is inhibited by digestion of food?

  Ghrelin (from stomach, and other parts of GI tract)

  - the 'hunger' hormone which promotes appetite and feeding behaviour
• Gut hormones and metabolism

  
  

  Which 3 hormones are released in response to digestion of food and what do they do?

  • GIP (from small intestine)

  - stimulates insulin release

  
  

  • GLP-1 (from ileum/colon)

  - stimulates insulin release

  - inhibits glucagon release

  - promotes satiety (helps us absorb the glucose taken from the meal)

  
  

  •CCK (from small intestine)- promotes satiety
• bile

  
  

  where is bile released from?

  release from gall bladder (where stored):

  • CCK causes gallbladder to contract & sphincter of Oddi to relax
• bile

  
  

  What happens during the secondary modification of the bile fluid as it passes along the bile duct?

  • water and HCO3- are added

  • mechanism similar to that for pancreatic alkaline secretion

  • stimulated by secretin
• bile

  
  

  What is the bile pigment component important for?

  breakdown product of Hb (porphyrin ring), for excretion
• bile

  
  

  What is the bile salt/ acid component important for?

  The emulsification of fats in the small intestine
• bile

  
  

  What are some components of bile?

  Bile salt/acid component, Bile pigments (e.g. bilirubin), cholesterol, lecithin
• bile

  
  

  Where is the primary secretion of bile made and how?

  In the liver

  - solutes are made or extracted from the blood by hepatocytes, and discharged into bile canaliculi containing extracellular fluid
• Describe the CCK response to chyme in the duodenum.

  
• small intestine: pancreatic exocrine secretions

  
  

  What are the main hormone regulators affecting pancreatic exocrine secretions?

  1. CCK

  - released from duodenal wall by fats etc.

  - induces release of enzyme-rich secretions

  
  

  2. Secretin

  - released from duodenal wall by acidic chyme

  - induces release of bicarbonate-rich secretions to neutralise stomach chyme
• How is the secretion of pancreatic alkaline fluid matched to the acid load arriving from the stomach?

  negative feedback loop

  
• Describe the mechanism of alkaline fluid secretion by pancreatic duct cells.

  1) CO2 (from blood) + H2O -> H2CO3 which dissociates into HCO3- and H+ in the pancreatic duct cell

  
  

  2) HCO3- is removed from the pancreatic duct cell and into the duct lumen via the HCO3-/Cl- pump (anion exchanger on luminal side) (so Cl- enters the cell)

  -> Cl- ions are removed from the cell back into the duct lumen via a transporter

  
  

  3) the H+ ions are transported into the blood via a H+/Na+ pump

  
  

  -> energy is provided by Na+/K+ ATPase pump on the basal side of the cell

  
• small intestine: pancreatic exocrine secretions

  
  

  What are the 2 main components of the pancreatic exocrine secretions and describe them?

  1. Alkaline fluid rich in HCO3-:

  • produced largely by cells of pancreatic duct

  • role is to neutralise acidic chyme entering the small intestine from the stomach so it does not damage the duodenum

  
  

  2. Digestive enzymes:

  • includes endopeptidases, carboxypeptidase, amylase, lipase etc.

  • produced largely by acinar cells & stored intracellularly as inactive precursor forms as 'zymogen' granules

  • released by exocytosis

  • role is to break down most macromolecules found in food
• small intestine

  
  

  Are pancreatic and biliary secretions made together?

  They are made separately, but generally discharged together into the duodenum

  
  

  -> Relaxation of the sphincter of Oddi allows the secretions to pass into the duodenum
• small intestine

  
  

  what do Surface enterocytes (on villi) do?


  They make many digestive enzymes, which are then

  embedded in the glycocalyx of their brush border, and a

  bicarbonate-rich fluid.
• small intestine

  
  

  how does the small intestine achieve absorption?


  by secreting:

  • mucus (from goblet cells)

  • isotonic saline (from crypt cells)

  • alkaline mucus (from Brunner's glands)

  
  

  -> water is also secreted as part of the mucus/isotonic saline/alkaline mucus with sodium which is transported via the Na+/K+ ATPase pump into the lumen
• small intestine

  
  

  what is the small intestines main function

  absorption
• endocrine factors

  
  

  how does GIP (from SI) and GLP-1 (from ileum/colon) affect the stomach?

  - release stimulated by fat & chyme in the lumen

  - inhibit gastric motility & secretion

  - has metabolic affects: they are fed forwards to the pancreas to aid secretion of insulin in response to glucose (incretin effect- increased insulin secretion in response to a given amount of glucose)
• endocrine factors

  
  

  how does Secretin affect the stomach?

  - release from duodenal wall stimulated by acid

  - inhibits gastric secretion
• endocrine factors

  
  

  how does CCK (Cholecystokinin, previously: Pancreozymin) affect the stomach?


  - release from duodenal wall stimulated by fats etc

  - depresses gastric motility and secretion

  -> it neutralises the acid and begins digestion to prevent piling of stomach content
• endocrine factors

  
  

  how does Gastrin from pyloric antrum affect the stomach?

  - release stimulated by proteins, coffee, alcohol etc

  - release inhibited by low gastric pH

  - induces gastric secretions, increases motility
• endocrine factors

  
  

  what other endocrine factors affect the stomach?

  • Gastrin from pyloric antrum

  • CCK (Cholecystokinin, previously: Pancreozymin)

  • Secretin

  • GIP (from SI) and GLP-1 (from ileum/colon)
• acid secretion.

  
  

  how does gastrin cause stimulation for acid secretion?


  G cells produce gastrin in response to proteins and amino acids in the lumen.

  
  

  -> the gastrin travels through the blood and binds to gastrin receptors on the parietal cell to stimulate H+ ion secretion

  
• acid secretion.

  
  

  how does SST inhibit any stimulation for acid secretion?

  1) INDIRECTLY via ECL cell: prevents production of histamine

  2) Directly via parietal cell

  3) via G cell

  
• acid secretion.

  
  

  explain how acid secretion is regulated?

  The vagus nerve causes the enteric nervous system to release Ach.

  
  

  - the Ach will bind to muscarinic receptors on the parietal cell

  (DIRECT affect on the stimulation for acid secretion)

  
  

  - the Ach will bind to muscarinic receptors on the enterochromaffin-like (ECL) cell and cause it to secrete histamine which binds to H2 receptors on the muscarinic receptors on the parietal cell (INDIRECT affect on the stimulation for acid secretion)

  
  

  - the Ach will bind to muscarinic receptors on the D cell and cause it to secrete SST which binds to ssr receptors and INHIBITS any stimulation for acid secretion.

  -> NEGATIVE FEEDBACK LOOP

  
• acid secretion.

  
  

  In what 3 ways is acid secretion regulated?

  1. Neural (Ach)

  2. Endocrine (histamine or gastrin)

  3. Paracrine (SST)

  
• acid secretion.

  
  

  How is acid secretion increased in response to stimulation?

  • in resting condition (basal secretion):

  many of the proton pumps are confined (inside) to intracellular 'tubulovesicles' and so HCL production does NOT occur

  
  

  • on stimulation:

  the tubulovesicles rearrange and fuse with canaliculi continuous with the lumenal membrane, increasing the surface area for HCl secretion and so HCL production DOES occur
• acid secretion.

  
  

  Describe the mechanism of acid secretion.

  • CO2 + H20 -> H2CO3 which dissociates unto HCO3- and H+ in the parietal cell

  
  

  • the H2CO3- is removed from the cells via a H2CO3-/Cl- exchanger (on the basolateral side of the cell) so that it does not neutralise the acid.

  -> so Cl- goes from blood into the cell

  
  

  • H+ ions are taken into the lumen using energy/ATP by the H+/K+ proton pump.

  -> K+ enters the parietal cell so it is taken back to the lumen to maintain homeostasis of ionic gradients

  
  

  • Cl- ions are removed from the cell and into the lumen via a transporter.

  -> they combine with H+ to form HCL

  
  

  
  

  OVERALL:

  • net HCO3 movement into blood

  • net ion movement into lumen accompanied by water (by osmosis)

  
• Show what the main gastric secretions are.

  - pepsinogen (inactive form of pepsin which digests proteins)

  - HCL

  - intrinsic factor

  - mucus

  - gastric lipase

  - water

  
• digestion

  
  

  What happens in the intestinal phase of digestion?

  - Food entering the small intestine gradually causes the release of hormones that inhibit gastric secretion and motility

  - Some of the same hormones provoke the release of biliary and pancreatic secretions into the duodenum

  - During this phase, most of the digestion takes place, followed by absorption of the nutrients
• digestion

  
  

  What happens in the gastric phase of digestion?

  - Stomach secretes (acid, pepsinogen, etc.) in response to the presence of food

  - Gastric motility causes further mechanical breakdown of food particles

  - Digestion of protein starts
• digestion

  
  

  What happens in the cephalic phase of digestion?


  - Thinking about food and presence of food in mouth: promotes salivary and gastric secretions

  - Chewing etc. helps to break food down into small particles

  - Amylase in saliva initiates digestion of starch
• digestion

  
  

  What are the 3 phases of digestion?

  1. Cephalic

  2. Gastric

  3. Intestinal
• How are oesophageal secretions different to salivary secretions?

  For oesophageal secretions, there are widespread minor glands, which only produce mucus and secretion is neurally controlled
• salivary secretions: control by ANS

  
  

  How does sympathetic stimulation affect saliva?

  Sympathetic stimulation increases release of macromolecular components
• salivary secretions: control by ANS

  
  

  How does parasympathetic stimulation affect saliva?

  Parasympathetic stimulation increases formation of the fluid and electrolyte components of saliva