L43. GI Tract Special Secretions Flashcards
(18 cards)
What are types of exocrine secretions?
- Salivary secretions; salivary glands
- Gastric secretions; stomach epithelia, surface epithelia, gastric glands with specialised epithelial cells
- Bile; liver
- Pancreatic secretions; pancreas
- Intestinal secretions; these were covered in the previous lecture
Function
- Maintain the composition of the lumen of the GI tract appropriate to its function. Maintain osmolarity, pH, water, and enzyme content at the correct levels
Major components
- Electrolytes (salt), water, mucous, enzymes, acid or bicarbonate to alter pH
How are they made?
- Components are produced or transported by epithelial cells and secreted across the mucosal surface of:
The GI tract lining and the lining of accessory organs
Secretions are re-absorbed!!!
What are salivary secretions?
Functions
- Lubrication of ingested food
- Dissolves water soluble components
- Neutralises acid - food acid, refluxed acid (protects teeth)
Components
- Electrolytes (mostly Na+, Cl-, and HCO3-)
- Water
- Mucous
- alpha amylase
- Antimicrobial factors
How does saliva secretion work?
Saliva secretion is a two step process
- Salivary glands are lined with epithelial cells that make and then modify saliva before secretion
Step 1: occurs in the acini (singular acinus) located at the end of the glands
- Primary saliva - isotonic NaCl, contains amylase
- Leaky epithelium secreting Cl-
- Na+ follows Cl- via paracellular pathway (leaky)
- Osmotic water movement can occur (leaky)
- Isotonic solution produced
Step 2: occurs in the ducts leading out of the gland
- Modify saliva content - saliva becomes hypotonic
- Tight epithelium - no paracellular movement
- Reabsorption of Na+ and Cl- ions through the cells BUT osmotic water movement can NOT occur
- Decrease salt = increased H2O (osmolarity decreases)
- HCO3- secreted
- Final saliva is hypotonic with basic pH
What occurs with the primary salivary secretion of NaCl?
Salivary NaCl- secretion is the same as intestinal NaCl secretion
Regulation
- Secondary messengers stimulate intestinal Cl- secretion
- There are 2 main mechanisms (secondary messengers):
- cAMP stimulates CFTR activity
- Sustained secretory response
- Ligands include VIP (ENS) and prostaglandins - Ca2+ stimulates K+ channel activity
- Increased driving force for NKCC and Cl- exit via CFTR
- Transient secretory response
- Ligands include ACh (ENS) and histamine
How is salivary secretion regulated?
Parasympathetic (primary pathway) - acetylcholine - increases intracellular Ca2+ - increases Cl- secretion - large amounts of isotonic NaCl
Sympathetic (secondary pathway, potentiates parasympathetic pathway) - adrenaline - increases viscous fluid, more mucus
Ion transport in the ducts doesn’t change but flow rate does. So… the more secretion in acini the higher flow rate through the ducts
- Low flow rates –> greater NaCl reabsorption –> more hypotonic
- High flow rates –> less NaCl reabsorption –> more isotonic
Ionic composition of saliva is dependent on flow rate through the ducts
What is involved with gastric secretions?
The stomach makes a number of secretions dependent on location:
- Different regions of the stomach
- Different epithelial cell types
Surface epithelia = protective
- Mucus
- HCO3-
Gastric glands (many cell types) = make acid, enzymes, and hormones
- Parietal cells: HCL and intrinsic factor
- Enterochromaffin-like cells (ECL): histamine
- Chief cells: pepsinogen
- Enteroendocrine cells, several types e.g. G cell: gastrin, D cell: somatostatin
What is the importance of mucus and bicarbonate in the stomach?
- Mucus and HCO3- mucins are released by exocytosis
- HCO3- and H2O secretion occur and mucus is hydrated
- Alkaline mucous = protection of gastric mucosa from acid
How does gastric acid secretion work in the stomach?
Functions
- Denatures protein
- Activates pepsin
- Hypo-osmotic - dilutes food
- Protection (kills bacteria)
Mechanism of secretion
- Epithelial Cl- and H+ secretion into lumen
- Carbonic anhydrase makes H+ and HCO3-
- H+/K+-ATPase transports against concentration gradient
- HCO3- is recycled into the body in exchange with Cl- at basolateral membrane
- Cl- then moves into lumen via a Cl- channel
- Osmotic water secretion (H2O follows ions)
How is HCl secretion up-regulated?
Acetylcholine, gastrin and histamine all act by increasing H+/K+-ATPase pump numbers and stimulating Cl- channel activation: including Calcium activated chloride channels (CICC) and CFTR
How is HCl secretion regulated by distension?
Distension induces a neural response in which neurons of the ENS releases acetylcholine. ACh binds to receptors on parietal cells that increase intracellular Ca2+ which activates calcium activated Cl- channels and H+/K+-ATPase
How does gastrin play a part in regulation?
Protein/peptides are detected by enteroendocrine cells that secrete gastrin. Gastrin binds to receptors on parietal cells that increase intracellular Ca2+ which activates calcium activated Cl- channels and H+/K+-ATPase
How does histamine play a part in regulation?
Both gastrin and ACh induce the release of histamine from enterochromaffin-like cells (ECL cells). Histamine binds to receptors on parietal cells that increase intracellular cAMP and PKA which phosphorolates and activates CFTR channels and H+/K+-ATPase
How is HCl secretion down-regulated?
High acid in the antrum of the stomach and chyme in duodenum inhibits HCl secretion
Hormone regulation
- Somatostatin (from stomach) - paracrine inhibition of parietal cells
- Secretin (from duodenum) - stimulates somatostatin release
- Acid in the duodenum is detected by enteroendocrine cells which release secretin
- Secretin travels via the blood to the stomach and causes the release of somatostatin from D cells
- Acid chyme in the distal stomach can also directly cause the release of somatostatin from D cells. Somatostatin inhibits the activity of chloride channels and H+/K+-ATPase
What is pancreatic secretion?
Pancreatic gland fluid secretion is a two step process; similar to salivary glands!
- Glands are lined with epithelial cells that make and then modify secretion before secretion
- Each step occurs in a different place
Acini - Step 1, produce primary secretion
- Secreting Cl-
- Na+ follows Cl- via paracellular pathway (leaky)
- Osmotic water movement can occur (leaky)
- Isotonic solution produced
Ducts - Step 2, modify secretions
- Exchange of Cl- for HCO3-
- Final product has very high levels of HCO3-
How is Cl- secreted in the acini?
Isosmotic Cl- secretion
Mechanism
Similar to intestinal Cl- secretion
- Cl- uptake via basolateral NKCC1
- Cl- moves out of apical membrane via CFTR channel
- Cl- transport drives paracellular Na+ movement
- Osmotic gradient drives paracellular water movement
How is HCO3- secreted in the ducts?
Isosmotic sodium bicarbonate secretion in the ducts
- Flushes out acinar cell secreted proteins
- Neutralises chyme
Mechanism; similar to intestinal HCO3- secretion
- Carbonic anhydrase and NHE are sources of HCO3-
- HCO3- moved into lumen by apical Cl-/HCO3- exchange (Cl- secreted by acini)
- Cl- recycling via cAMP Cl- channel (CFTR)
Enzymes are secreted as zymogens via exocytosis from the pancreatic acini cells
Enzymes for all major nutrients
- Proteins –> trypsinogen, chymotrypsinogen, and procarboxypeptidase
- Carbs –> amylase
- Fats –> lipase, colipase
Proteases must be converted into their active form in the intestines by enterokinase (one type of brush border enzyme)
How does bile secretion work?
Bile formation - 3 step process
- Primary secretion
- Hepatocytes secrete bile acids into canuliculi
- Cholesterol, lecithin, bilirubin - active transport into bile - Secondary modification
- Hepatic branch of bile ducts secrete HCO3- - Storage in gallbladder
- Storage between meals
- Concentration of bile - reabsorption of NaCl and water
Enterohepatic circulation
- Bile salts are recycled through a system of active transport in the ileum and transported back to the liver via the hepatic portal vein
What is the cause of cystic fibrosis?
Cystic fibrosis is the result of a defect in the cystic fibrosis transmembrane regulator (CFTR) anion channel (mostly Cl-)
Cystic fibrosis derives its name from the cysts and fibrosis noted in the pancreas of patients with the disease
Stomach and duodenum:
- Increased frequency of ulcers, gastrointestinal reflux disease
Pancreas:
- Blocked pancreatic ducts - prevents enzymes from reaching the small intestine to digest food nutritional deficiencies. Pancreatic cystic fibrosis. CF related diabetes
Liver, gall bladder and bile ducts:
- Hepatobiliary disease, nutritional deficiencies (especially fat soluble vitamins)
Intestines: constipation, distal intestinal obstruction syndrome. Meconium ileus in new-born infants
