Secretion Physio Flashcards
Saliva Functions
- Initial digestion of starches and lipids
- Dilution and buffering of ingested food
- Lubrication of ingested food and mucus
Parotid glands
- Serous cells
- Secrete fluids composed of water, ions and enzymes (ie. amylase)
- 25% total salivary output
Submaxillary and sublingual glands
- Mixed serous and mucous cells
- Secrete aqueous fluid and mucin glycoprotein for lubrication
- 75% total salivary output
Structure of salivary glands
- Acinus
- Myoepithelial cells
- Intercalated duct
- Striated duct
Acinus
- Acinus cells secrete initial (isotonic) saliva
- Blind end of gland
Myoepithelial cells
- Motile extensions
- Contract to eject saliva into mouth when stimulated by neurons
Intercalated duct
- Saliva similar to ionic composition of plasma
Striated duct
- Columnar epithelium (ductal cells)
- Ductal cells modify initial saliva to produce final (hypotonic) saliva through alteration of electrolyte concentrations
Composition of saliva
- Hypotonic
- Contains H2O, electrolytes (more KHCO3, less NaCl), a-amylase, lingual lipase, kallikrein, and mucus)
Transport mechanisms of salivary electrolytes
- Na/H, Cl/HCO3, H/K exchangers
- Leave cell to lumen via cAMP activated CFTR Cl channel or Cl/HCO exchanger
Unusual features of salivary regulation
- Salivary secretion exclusively under ANS control
2. Secretion increased by both sympathetics and parasympathetics
Components of gastric juice
- HCl
- Pepsinogen
- Mucus
- Intrinsic factor
- H2O
HCl (gastric juice)
- Initiates protein digestion
- Converts pepsinogen to pepsin (which also digests proteins)
- Kills bacteria entering stomach
Mucus (gastric juice)
- Lines stomach wall/protects from damage
- Lubricant
- Along w/ HCO3, neutralizes acid and maintains surface of mucosa @ neutral pH
Intrinsic factor
B12 absorption in ileum
H2O (gastric juice)
- Medium for action of HCl and enzymes
- Solubilizes ingested material
Oxyntic gland (type of cells present)
- Proximal 80% of stomach
- Secretes acid
- Parietal cells, mucous neck cells, ECF-like cells, D cells, chief cells
Pyloric gland (types of cells present)
- Distal 20% of stomach (antrum)
- Synthesizes and releases gastrin
- G cells, D cells, some mucus neck cells
Non-parietal gastric juice secretions
- Basal alkaline secretion of constant/low volume
- Components = Na, Cl (K present @ same concentration as in plasma)
- HCO3 secreted @ 30 mEq/L
Parietal gastric juice secretions
- Slightly hyperosmotic
- 150-160 mEq H+/L
- 10-20 mEq K/L
- Cl- only anion present
- w/ increased secretion rate, concentrations of electrolytes approach those of pure parietal secretions
Direct pathway of vagal stimulation
Vagus n. — ACh — parietal cells — HCl released
*Atropine can block
Indirect pathway of vagal stimulation
- Vagus n — GRP — G cells — gastrin — circulation — parietal cells — HCl
- Antrum distension — ACh — G cells …
- AAs — G cells …
Gastrin release regulation
- Vagal activation stimulates gastrin release (via GRP)
- Somatostatin inhibits gastrin release
Gastrin negative feedback loop
Increases in gastrin (and H+) increases somatostatin
Potentiation
Combined response to two stimulants exceeds the sum of their individual responses
Potentiation with HCl
- Histamine potentiates actions of HCl and gastrin
- ACh potentiates actions of histamine and gastrin
- Antagonists along pathway block direct effects (and potentiated effects)
Cephalic phase (of HCl secretion)
- Stimuli: smelling/tasting, chewing/swallowing, conditioned reflexes
- Mechanisms:
1. Vagus n — parietal cell
2. Vagus n — gastrin — parietal cell - 30% HCl secreted
- Vagotomy abolishes!
Gastric phase (of HCl secretion)
- Stimuli: distension of stomach, presence of proteins, AAs, small peptides
- Mechanisms:
1. Distension — activates mechanoreceptors in mucosa of oxyntic and pyloric gland — direct and indirect pathways
2. Distension of antrum — local reflexes — ACH — parietal cells/G cells
3. AA/small peptides — gastrin — peptides - 60% HCl secreted
- Coffee stimulates gastric HCl secretion
Intestine Phase
- Distension of SI — stimulates acid production
- Digested protein — stimulates acid production (direct and indirect)
- 5-10% HCl secretion
Protective factors for gastroduodenal mucosa
- HCO3/mucus
- Prostaglandins
- Mucosal blood flow
- Growth factors
Damaging factors to gastroduodenal mucosa
- H+/pepsin
- H. Pylori
- NSAIDS
- Stress
- Smoking
- Alcohol
Growth of gastric mucosa
- Gastric epithelium secretes HCO3 and mucus to form mucosal barrier
- Mucous cells secrete mucus
- Surface epithelial cells secrete HCO3
Zollinger-Ellison syndrome
- Very high H+ levels
- D/t tumor (usually in pancreas) secreting large amounts of gastrin — increased H+ and increased parietal cell mass (trophic effect)
- Excess H+ in duodenum overwhelms buffer capacity of HCO3 and creates ULCER
- low duodenal pH inactivates pancreatic lipases — steatorrhea
Gastric ulcers
- Form on stomach lining
- D/t defective gastric mucosal barrier (NOT increased acid secretion)
- Gastrin levels increased b/c H+ is decreased
Duodenal ulcers
- Form on duodenal lining
- More common than gastric ulcers
- Increased H+ secretion
- Increased gastrin d/t ingestion of food
- Increased parietal cell mass (d/t increased gastrin)
Peptic Ulcer Disease
- Predominant causes: H. Pylori and NSAID use
- Mechanism: loss of protective mucosal barrier, excessive H+ and pepsin secretion
- Results in gastric and duodenal ulcers
Secretin stimulation test
- Secretin used in dx of gastrin-secreting tumors
- Secretin usually inhibits gastrin release
- W/ gastrinomas, secretin injection causes increase in gastrin release
Helicobacter pylori
- Acquired factor in origin of gastric and duodenal ulcers
- H. Pylori releases cytotoxins that breakdown mucosal barrier and underlying cells
- Urease allows bacteria to colonize gastric mucosa
Role of urease w/ H. Pylori
- Allows bacteria to colonize gastric mucosa
- Urease converts urea to ammonia (alkalinizes local environment)
- Resulting production of NH4+ is major cause of cytotoxicity
- Dx test based on urease activity
Pepsinogen
Released by chief cells and mucus cells in oxyntic glands (which requires H+ secretion from parietal cells to lower gastric pH)
Stimuli for pepsinogen secretion
- Vagal nerve stimulation
- Also low gastric pH (otherwise pepsinogen won’t convert to pepsin)
Protein degradation via pepsin
- Optimal pH is 1.8-3.5
- Reversibly inactivated above 3.5-5.0
- Irreversibly inactivated above 7-8
- Proteolytic enzyme splits interior peptide linkages
Intrinsic Factor
- Required for absorption of B12 in ileum
- Mucoprotein secreted by parietal cells
- failure to secrete IF associated with achlorhydria and absence of parietal cells
- *only “essential” secretion by the stomach
Pernicious Anemia
Stomach does not produce enough IF (low B12 levels)
Causes of Pernicious Anemia
- Atrophic gastritis: chronic inflammation of stomach mucosa leading to loss of parietal cells
- Autoimmune metaplastic atrophic gastritis: immune system attacks IF protein or gastric parietal cells
Pancreatic juice contents
- HCO3 to neutralize H+ from stomach
- Enzymes to digest carbs, lipids, proteins
Exocrine Pancreas parasympathetic innervation
Vagus N
- Preganglionic fibers synapse in ENS
- Postganglionic fibers synapse on exocrine pancreas
- Stimulates pancreatic secretion
Exocrine pancreas sympathetic innervation
Postganglionic nerves from celiac and superior mesenteric plexuses
*Inhibits pancreatic secretion
Components of exocrine pancreas secretions
- Aqueous solution with HCO3-
2. Enzymatic secretion
Acinar cells (of pancreas)
- Pancreatic amylase/lipases (ACTIVE form)
2. Pancreatic protease (INACTIVE zymogens) — activated in lumen of duodenum
Centroacinar and ductal cells
- Secrete HCO3-rich fluid that alkalinizes and hydrates protein-rich secretions from acinar cell
- Initial secretion modified by transport processes in ductal epithelial cells
Cephalic phase (pancreatic secretions)
- Initated by smell, taste, conditioning
- Mediated by vagus n.
- Produces mainly enzymatic secretion
Gastric phase (pancreatic secretion)
- Initiated by distension of stomach
- Vagus n
- Produces mainly an enzymatic secretion
Intestinal phase (pancreatic secretion)
- 80% of pancreatic secretion
- Enzymatic and aqueous secretions are stimulated
Cystic Fibrosis and pancreas
- D/t mutations in CFTR (regulated Cl- channel in apical surface of duct cell)
- Associated with loss of HCO3 secretion (ability to flush active enzymes out of duct may be lost)
- Acute/chronic pancreatitis may result
- Pancreas one of 1st organs to fail w/ CF
Net result of initial pancreatic secretion by ductal cells
- Secretion of HCO3
- Absorption of H+
Parasympathetic (preganglionic) salivary gland
Originate @ facial n. (CN 7) and glosspharyngeal n. (CN 9)
Parasympathetic (postganglionic) salivary gland
Autonomic ganglia innervate individual glands
Sympathetic (preganglionic) salivary gland
Originate @ cervical ganglion
Sympathetic (postganglionic) salivary gland
Extend into glands in the periarterial spaces
Factors stimulating salivary secretion
- Conditioning
- Food
- Nausea
- Smell
Factors inhibiting salivary secretion
- Dehydration
- Sleep
- Fear
Mechanism of parasympathetic salivary secreton
CN VII/IX – ACh – mAChR – IP3 and increased Ca2+ (acinar and ductal cells) – SALIVA
Mechanism of sympathetic salivary secretion
T1-T3 – NE – beta AR – cAMP – SALIVA
Effects of salivary cells stimulated
- Increased saliva production
- Increased HCO3- and enzymatic secretions
- Contraction of myoepithelial cells
Effect of ADH and Aldosterone on saliva
Decrease [Na+] and increase [K+]
Salivary transporters on BL side
- Na+/K+ ATPase
- HCO3-/Na+
Salivary transporters on apical side
- Na+/H+
- HCO3-/Cl-
- H+/K+
- cAMP-activated CFTR Cl-
Effect of atropine on gastrin secretion
Atropine will NOT block vagal effects on gastrin b/c neurotransmitter on G cells is GRP
H+ effect on somatostatin
Stimulates release
Vagal activation effect on somatostatin
Inhibits release
Somatostatin effect on G cells
Inhibits gastrin release
Effect of increased gastrin on somatostatin
Increases somatostatin (via negative feedback loop)
Effect of atropine
Inhibits M3 receptor (Vagus n./ACh)
Effect of cimetidine
Inhibits H2 receptor (ECL cells/histamine)
- Tx of duodenal/gastric ulcers, GERD
Effect of omeprazole
Inhibits H+/K+ ATPase (for H+ secretion)
- Tx of ulcers to reduce H+ secretion
Effect of coffee on HCl secretion
Increases
Formation of mucosal barrier
- Gastric epithelium releases HCO3- and mucus
What do the surface epithelium cells secrete?
HCO3-
Main function of gastric mucosal epithelium?
Protects against HCl and pepsin
Pancreatic proteases… active or inactive?
Secreted inactive, converted to active in doudenum
Pancreatic amylases/lipases… active or inactive?
Secreted active
HCO3- secretion into lumen? explain process
Occurs via Cl-/HCO3- exchanger and cAMP-activated CFTR Cl- channel
Process of pancreatic secretion (I cells)
I cells – CCK (Ach potentiates) – IP3/increased Ca2+ (acinar cells) – Enzymes released
Stimulatory effect of I cells
- Phe, Met, Trp, small peptides, FAs
Process of pancreatic secretion (S cells)
S cells – secretin (ACh, CCK potentiate) – cAMP (ductal cells) – Aqueous secretion (HCO3- and Na+)
