GI secretions week 1 Flashcards
What are the 2 general/broad functions of GI secretions?
What is GI secretion? What type of glands secrete in the GI tract? What the 3 components of GI secretions?
GI secretion: Exocrine glands along the GI tract secrete specific digestive juices into the lumen of the GI tract. Digestive secretion consists of
• water
• electrolytes
• specific organic constituents important for digestive function (e.g. digestive enzymes, mucus, bile salts).
What are secreatogues? Define the 3 following types of secratogues:
neurocrine secratogue
endocrine secratogue
paracrine secratogue
Secretagogue = substance that stimulates a secretory cell to secrete
- neurocrine secretagogue: neurotransmitters released from neurons that innervate the secretory cell (e.g. acetylcholine from parasympathetic vagal nerves).
- endocrine secretagogue (= hormones): modulators of secretion released from distant cells and transported by blood stream (e.g. activation of gastric HCl secretion by gastrin released from G cells).
- paracrine secretagogue: released into the neighborhood of secretory cell and reaches target cells by diffusion (e.g. histamine = paracrine agonist for gastric HCl secretion).
How do exocrine gland cells get materials needed fo the synthesis of their secretions? How do their secretions get to the GI tract?
Exocrine gland cells extract from the plasma by passive and active processes the raw materials necessary for the synthesis of the secretion product. The product of exocrine glands is emptied into the ducts of the secretory gland and delivered to the GI tract.
secretion-blood flow coupling
Secretion-blood flow coupling: secretion is coupled with increased blood flow to the exocrine gland (functional hyperemia) to optimize availability of raw materials for secretion. Reducing blood flow reduces secretions and is one mechanism of control of GI secretions
List the salivary glands and indicate the main salivary gland.
- parotid (main salivary gland)
- submandibular (submaxillary)
- sublingual
- (minor glands in labial, palatine, buccal, lingual and sublingual mucosa)
Saliva is produced in acini. What 2 types of cells are in salivary acini? What types of secretions do they produce?
What are the 2 functions of salivary ducts? What are the 3 types of ducts?
acinus = secretory endpiece with
• serous acinar cells with zymogen granules (salivary amylase, salivary proteins)
• mucous acinar cells secrete glycoprotein mucins
ducts = drainage system for acinar fluids and modifications of acinar secretions
• intercalated ducts
• striated (intralobular) ducts
• excretory (interlobular) ducts.
What are the 3 components of saliva?
electrolytes
proteins
water
What are the composition and osmolarity of saliva dependent on?
Explain the two-stage model of salivary secretion.
electrolytes: • Composition and osmolarity dependent on secretion rate.
Two-stage model of salivary secretion:
• Primary secretion product (acinus) is nearly isotonic with plasma.
• Secondary modification in ducts extracts Na+, Cl- and adds K+ , HCO3-, resulting in a hypoosmotic (hypotonic) secretion (because more Na+ and Cl- is removed than K+ and HCO3- is added; no water reabsorption)—> saliva becomes alkaline. Osmolarity increases with increased flow rates, but always remains hypotonic compared to plasma osmolarity.
What 3 types of proteins are contained within saliva and what are their functions?
• mucin (glycoproteins –> viscosity)
• digestive enzymes (stored in zymogen granules, released into acinar lumen by exocytosis):
-salivary amylase
-lingual lipase
• protective proteins (secretory IgA)
What is the definition of mucus?
What are its 3 functions?
List examples of mucus producing cells in the GI tract.
Mucus
• Collective term for secretions that contain glycoproteins mucins which are characteristically viscous and sticky
• Protects mucosal surfaces from abrasion by food contents, lubricates the food bolus in the upper GI tract and alkaline pH counters regional acidity (e.g. stomach)
• Mucus is produced by various cells in the GI tract:
mucous cells in salivary glands
goblet cells
Brunners gland
neck cells of gastric glands
pancreatic acinar cells
What are the protective and digestive functions of saliva?
Protective function
• bicarbonate (neutralization of acid produced by bacteria and gastric reflux) bacteria do not like alkaline environments.
• antimicrobial (lysozyme, lactoferrin [binds Fe and decreases bacterial growth], peroxidase, proline rich proteins)
• secretory immunoglobulin (IgA)
• epidermal growth factor
• mouth hygiene
• water intake (thirst, speech)
Digestive function
• α-amylase (= ptyalin)
• lingual lipase
• R proteins (Vit. B12 binding glycoproteins) protect from degradation in the stomach
• mucin glycoproteins: lubrification food for swallowing
• dissolving substances for taste mechanism
Which branch of the ANS has primary physiological control of salivary glands?
Explain the specific effects of parasympathetic and sympathetic innervation of salivary glands.
- Parasympathetic:
- high and sustained output
- synthesis and secretion of amylase and mucins
- enhances transport activity of ductular epithelium
- vasodilation and increased blood flow
- stimulation of glandular metabolism and growth
- Sympathetic:
- transient increase of secretion
- vasoconstriction leads to decrease of salivation (secretion-blood flow coupling)
Note that the PNS has more direct effects on secretions (direct innervation of glands) whereas the sympathetic nervous system exerts its effects by controlling blood flow to salivary glands.
The gastric mucosa consists of a cardiac glandular region, oxyntic glandular region, and pyloric glandular region with a variety of secretory cells. What types of secretions do the following cell types produce?
surface mucous cells, mucous neck cells, glandular mucous cells
parietal (oxyntic cells)
chief cells
neuroendocrine cells: G cells, D cells, enterochromaffine-like cell
List and explain the protective and digestive functions of gastric secretions.
• digestive enzymes:
pepsinogen (endopeptidase)
gastric lipase
• HCl secretion (parietal cells): acidic environment for pH optimum (1.8-3.5) of digestive enzymes pepsin (activated from pepsinogen) and lingual lipase (pH optimum 4).
HCl softens food
• R proteins and Intrinsic Factor: bind Vit B12 and protect from gastric and intestinal digestion
Protective functions
• gastric acidity: antibacterial
• mucus and HCO3-: protective layer against damage of gastric mucosa by acid
How is pepsin stored? In what form is it stored? How is it activated?
What hormonal, neuronal, and chemical factors stimulate its secretion?
Pepsinogen/pepsin
• Pepsin = protease (endopeptidase)
• Low gastric pH converts proenzyme pepsinogen into active pepsin; pepsin itself proteolytically cleaves pepsinogen (positive feedback)
• Optimum for proteolytic activity is around pH 3
• Pepsinogen is stored in zymogen granules and released by exocytosis
• Stimulation of secretion
- Hormones: gastrin, cholecystokinin, VIP, secretin
- Neuronal: ACh, ß-adrenergic agonists
- acid
What are the basal and maximal rates of secretion of gastric acid?
What is the tonicity of gastric secretions at low flow rates?
What is the tonicity of gastric secretions at high flow rates? What is the main component at high flow rates?
Rate of secretion of gastric acid:
• basal rate = 1-5 mEq/hr
• maximal stimulation = 6-40 mEq/hr
• higher in patients with duodenal ulcers
• low flow rate: hypotonic
• high flow rate: nearly isotonic, mainly HCl
Describe the cellular mechanism of HCl production. Indicate what step involves ATP. Also, explain what alkaline tide is.
How does omeprazole (prilosec) block acid production?
- Carbonic anhydrase drives HCO3- production
- H+/K+ pump (ATP-dependent) drives H+ out in exchange for K+
- Cl- follows (via electrogenic anion channel)
- HCO3-/Cl- exchange maintains Cl- supply
- Alkaline tide: net HCO3- release into the blood stream during gastric acid
Omeprazole inhibits the H+/K+ ATPase
List and explain neural, hormonal, and physical stimulation of gastric secretion.
• neural control: • parasympathetic (vagal nerve, ACh) -> HCl secretion, pepsinogen secretion, mucus secretion
- hormonal control: • histamine released from enterochromaffin-like cells in gastric mucosa (acts via H2 receptors on parietal cell): HCl secretion
- gastrin from G cells: HCl secretion
- secretin: pepsinogen secretion
• distension of duodenum
How do cimetidine (Tagamet) and ranitidine (Zantac) inhibit acid secretion?
By blocking the histamine receptor (H2)
In what 3 ways does the gastric mucosal barrier protect itself from the acidity of the lumen?
Gastric mucosal barrier
The low gastric pH is potentially damaging also to gastric epithelial cells. Gastric epithelium establishes a protective barrier (mucus gel) to protect from self-digestion.
The gastric mucosal barrier consists of:
• (1) unstirred, bicarbonate rich mucus layer maintains pH 7 at cell surface and protects gastric mucosa from gastric juice (pH 2)
- (2) tight junctions between gastric mucosal cells prevent penetration of HCl between cells
- (3) luminal membrane of gastric mucosal cells is impermeable to protons
What 2 types of ulcers can result from peptic ulcer disease? What are 3 mechanisms by which ulcers can form?
- hypersecretion of acid (e.g. gastrin producing tumor = gastrinoma: Zollinger-Ellison Syndrome)
- effectiveness of gastric mucosal barrier (e.g. aspirin, nonsteroidal antiinflammatory drugs inhibit secretion of mucus and HCO3-; Stress ulcer: chronically high levels of epinephrine decrease HCO3- secretion)
- infection by Helicobacter pylori (H. pylori) bacteria
No acid —> no ulcer
What is one harmful consequence of a perforating ulcer?
What are some therapeutic options for treatment of peptic ulcer disease?
- Could develop peritonitis as a result which has a high mortality rate.
2.
- fight H. pylori infection: antibiotics
- reduce acid: omeprazole (Prilosec: H/K-ATPase inhibition)
- H2-receptor antagonists (Cimetidine)
- antacids
- (surgically: vagectomy)
- eliminate other causes (e.g. use of medication)
What are 2 general components of exocrine pancreatic secretions?
• exocrine pancreatic secretion:
- aqueous component
- enzyme component
Aqueous component of exocrine pancreatic secretion
How much is secreted per day?
What is the primary component? What components/parameters of pancreatic secretion changes with increasing rates of secretion?
How does the osmolarity of pancreatic secretions compare with plasma?
- 1 L /day
- HCO3=- rich secretion. [HCO3-] and pH increase and [Cl] decrease with increasing rate of secretion
- pancreatic secretion isoosmolaric (isotonic) with plasma
pH of pancreatic secretions ranges from pH 7-8
Explain the cellular mechanism of aqueous pancreatic secretion.
What is acid tide?
- carbonic anhydrase reaction produces H2CO3 (which dissociates into H+ and HCO3-)
- Na/H exchange and H/K-ATPase eliminate H+
- Cl-/HCO3- exchange secretes bicarbonate into duct lumen
- electrogenic Cl- channels recycle Cl- back into lumen
- Acid tide: net H+ release into the blood stream during pancreatic secretion
What is the precursor to bile acids?
What are primary and secondary bile acids?
- bile acids are synthesized by hepatocytes from cholesterol = primary bile acids (e.g. cholic acid, chenodeoxycholic acid).
- dehydroxylation of bile acids by bacteria in digestive tract = secondary bile acids (e.g. deoxycholic acid, lithocholic acid).
- bile contains both primary and secondary bile acids.
What are bile salts?
What are 3 functions of bile salts?
- bile salts (conjugates of bile acids with taurine or glycine) important for absorption of lipids in small intestine. Bile acids/salts emulsify lipids and form mixed micelles necessary for lipid digestion and absorption
- bile acids are derived from cholesterol and therefore are responsible for excretion of cholesterol. We continuously lose a portion of cholesterol through releasing bile (reabsorb most but not all of bile). This is the only pathway we have for excretion of cholesterol.
- excretion of bilirubin (product of hemoglobin degradation)
What percentage of bile acids are recirculated?
Up to 95% of bile acids are recirculated.
What is the main pathway for reabsorption of bile? In what form is bile in in the main pathway? (conjugated or unconjugated) How and where is it reabsorbed in this pathway?
What is the second pathway for reabsorption of bile? In what form is bile in this pathway?
In what 2 ways can bacteria modify bile?
How are absorbed bile acids/salts returned to the liver? What modification to bile takes place in the liver?
- Main pathway: active re-absorption of conjugated bile salts (terminal ileum, Na-coupled cotransporter; active transport process)
- Second pathway: passive absorption of unconjugated bile acids (entire small intestine and colon)
- bacteria in terminal ileum and colon deconjugate bile salts allowing passive absorption by diffusion
- bacteria also dehydroxylate primary bile acids —>
secondary bile acids
• Absorbed bile acids/salts return to liver via the portal blood, are then taken up into hepatocytes for resecretion. Unconjugated bile acids are reconjugated. Dehydroxylated bile acids are rehydroxylated.
What is bilirubin?
How is bilirubin metabolized?
Bilirubin is the product of hemoglobin degradation and the major pigment of bile.
Bilirubin gives urine and feces their colors.
see attached for metabolism of bilirubin (pg 143 of course notes)
