Viva O1(i)

What secretions are produced by the gastrointestinal tract, and what are their volumes?
Secretions Daily volume
Saliva 500-1500ml
Gastric secretions 1000-2000ml
Bile 1000ml
Pancreatic secretions 1000ml
Small bowel secretions      3000ml
Total 7000-8000 ml

(from Camilleri, 2004)

What is saliva?
  • A "mucoserous exocrine secretion"
  • The product of minor (10%) and major (90%) salivary glands
  • Chemical properties and constituents:
    • Hypotonic
    • Sodium-poor
    • Multiple macromolecular (i.e. protein) components
    • Hydrated mucin glycoproteins
    • Immunoglobulins
    • Amylase
  • Flow rate: 500-1500ml/day
  • Of this, 90% is "stimulated" flow

Humphrey & Williamson (2001)

What is the role of saliva?
  • Lubrication and protection (barrier function, mainly mucins)
  • Buffering action and clearance (mainly bicarbonate)
  • Maintenance of tooth integrity  (remineralisation of enamel by calcium and phosphate)
  • Antibacterial activity (immunoglobulins, especially IgA)
  • Taste and swallowing (lubricating the food bolus, acting as a chemically inert carrier fluid to dissolve molecules for taste sensation)
  • Digestion (amylase in saliva begins to act on carbohydrates)

Humphrey & Williamson (2001)

What is the clinical relevance of knowing the volume of saliva secretion?
  • Under normal circumstances
    • Intubated patients produce very little oral secretions
    • This contributes to poor oral hygiene, as the antibacterial effects of saliva are lost
    • This affects the microbiome of the posterior pharynx
  • If oral secretions are being produced:
    • The intubated patient will be unable to swallow effectively
    • The oral secretions produced by such patients will pool in the oropharynx
    • This pool will not be accessible to routine oral hygiene measures
    • Bacterial load of these fluids will increase
    • They will eventually make their way past the low pressure endotracheal cuff and cause VAP
What are gastric secretions, and which cells or glands produce them?
  • Multiple products of multiple cell types:
    • Goblet cells secrete mainly mucus
    • Chief cells secrete mainly pepsinogen and gastric lipase. Pepsinogen is converted into active pepsin in the low pH environment of the stomach.
    • Parietal cells produce mainly hydrochloric acid and intrinsic factor
What is the composition of gastric secretions?
  • Water (95%)
  • Hydrochloric acid (pH 1.5-3.5)
  • Mucus, rich in bicarbonate (which forms an "unstirred layer"); contains 20g/L of a viscous mucin polymer
  • Electrolyte composition:
    Electrolyte concentration    (mmol/L)
    Chloride 130-180
    Sodium 10-60
    Potassium 12-20
    Calcium 1.00-1.30

(Kaufmann, 1981)

What is the function of gastric secretions?
  • Immune function: pH acts to decontaminate bacteria in food. 
  • Barrier functions: Gastric mucus acts as a barrier and neutralising agent against the gastric acid. 
  • Macronutrient digestive function:
    • Gastric acid 
    • Proteolytic enzymes
    • Gastric lipase
  • Micronutrient digestive function:
    • Pepsin also helps ferric iron (Fe3+) conversion to the more soluble ferrous (Fe2+
    • Intrinsic factor binds to B12
What is the volume of gastric secretions?
  • Most textbooks quote 1000-2000ml/day or 100ml/hr
  • Normal fasted gastric aspirate volume is 70-150ml
What is the clinical relevance of this?
  • The rate of gastric secretion is related to the residual gastric volume
  • This has implications for measurement of enteral feed tolerance and for safety of intubation
What factors increase or decrease the rate of gastric secretion?
  • Factors that increase gastric acid secretion: 
    • Parasympathetic nervous system (via the vagus nerve)
    • Gastrin, during the cephalic and gastric phases of digestion
    • Histamine; during the cephalic and gastric phases of digestion)
    • Mechanical stretch (by vago-vagal and local smooth muscle stretch reflexes)
    • Peptides, caffeine, alcohol - sensed by mucosal chemoreceptors of the antral G cells, which then release gastrin
  • Factors that decrease gastric acid secretion
    • Somatostatin, if the luminal pH decreases to below 1.5
    • Small intestine hormones
      • Vasoactive intestinal polypeptide (VIP)
      • Secretin
      • Cholecystokinin
    • Prostaglandins PGE2 and PGI2
  • Mucus secretion by goblet cells:
    • Mainly regulated by mechanotransduction triggers, such as the distension of the stomach wall with food. 
What is the mechanism of gastric acid formation?
  • Takes place in gastric parietal cells:
    • The apical surface of the parietal cell has numerous small secretory canaliculi which increase the apical surface area of the cells
    • Resting parietal cells have numerous vesicles the membranes of which have acid-secretory transmembrane proteins
    • With stimulation, these vesicles fuse with the apical canaliculi to rapidly increase the secretory capacity of these cells
  • Basal membrane ion transport in parietal cells
    • CO2 and water are able to diffuse into parietal cells passively
    • Carbonic anhydrase converts the CO2 and H2O into HCO3- and H+
    • HCO3-  is then exchanged for chloride at the basal membrane
  • Apical membrane ion transport in parietal cells
    • H+ generated by carbonic anhydrase is exported by an ATP-powered H+/K+exchange pump, otherwise known as the "proton pump" - this is the molecular drug target of PPIs 
    • The potassium used in this exchange is returned to the gut lumen by KCNQ1/KCNE potassium channels in the apical membrane of the parietal cells.
    • Chloride is exported through apical chloride channels (ClC-2)
  • Net effect of parietal cell activity
    • In the gut lumen, chloride concentration increases from 120 mmol/L up to 180 mmol/L (thus pH decreases)
    • In the portal vein, CO2 concentration decreases: gastric carbonic anhydrase activity consumes CO2, which is therefore lower in the portal venous blood than in the arterial blood delivered to the stomach, i.e. the actively secreting stomach has a negative respiratory quotient
    • This increases the pH of portal venous blood during the cephalic and gastric phases of digestion, a phenomenon known as the "alkaline tide"

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