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REGULATING WATER IN MUCUS

REGULATING WATER IN MUCUS

 

 

Normal Person – the amount of water in mucus is regulated to maintain constant viscosity of mucus, by transport of Na and Cl ions/molecules across epithelial cells, which in turn affects the movement of water (due to osmosis)

  • Too viscous = can’t beat away dust + bacteria à CF
  • Too runny = floods airway

Too much water…

 

When the Na+ channel is open, the CFTR channel is closed.

 

  1. Na+ ions are actively pumped out across the basal membrane, into the tissue fluid
  2. Na+ diffuse from the mucus, through the apical membrane, into the epithelial cell via the open Na+ channel (facilitated diffusion)
  3. Because most of the Na+ ions have left the mucus for the epithelial cells + tissue fluid, the Cl– diffuses down to the epithelial cells and tissue fluid as well (but through the gaps between the epithelial cells) b/c of the electrostatic attraction = Cl– travels down the electrical gradient
  4. Now there is a high concentration of solute in the tissue fluid àwater is drawn out of the epithelial cells and into the tissue fluid instead (osmosis)
  5. But now there is a low concentration of water inside the epithelial cells à cells are shrivelled = dangerous
  6. So, excess water is drawn out of the mucus and drawn into the epithelial cells via osmosis
  7. Now that the excess water is removed from the mucus, flooding is avoided on the larger airways e.g. bronchi

Too little water…                                                      

When the CFTR channel is open, the Na+ channel is closed.

  1. Cl– ions are actively pumped across the basal membrane, into the epithelial cells
  2. Cl– ions diffuse through the (gated) open CFTR protein channel, out of the cell and into the mucus (facilitated diffusion)
  3. The mucus now contains lots of Cl– ions – this creates an electrical gradient; the Na+ now start to diffuse up the gradient through the gaps between the cells (from the tissue fluid to the mucus – NOT from the cell b/c the sodium channel is closed)
  4. There is now a high concentration of solute NaCl in the mucus so water needs to be drawn out of the epithelial cells via osmosis, to ensure an isotonic solution
  5. The epithelial cells are now shrivelled, so water is drawn into the epithelial cells from the tissue fluid, through the basal membrane
  6. This continues until equilibrium on both membrane sides has been reached = the mucus isn’t too sticky nor runny

Too little water IN CF…        

The CFTR channel protein is missing/damaged, so the Na+ channel is always open

 

  1. Cl– ions are actively pumped across the basal membrane, into the epithelial cells
  2. BUT Cl– ions cannot diffuse through to the mucus b/c there is no CFTR channel protein to transport them – there is a high concentration of Cl ions in the epithelial cells now
  3. Na+ channel is always open, so more and more Na ions keep travelling down to the tissue fluid
  4. The Cl– ions then also move down and back into the tissue fluid b/c of the electrical gradient
  5. There is now a high concentration of NaCl solute in the tissue fluid, so water is drawn out of the mucus and into the tissue fluid via osmosis
  6. The mucus has lost water so it has become more viscous so it is harder for the cilia to beat away the dust + bacteria à sticky mucus builds up àinfections, inflammation and damage

Salty Sweat Test = SIGN of CF

  1. Na+ goes through the sodium channels
  2. Cl– diffuses down the electrical gradient
  3. Water is drawn out due to osmosis
  4. The water and NaCl are at the skin’s surface (tissues)
  5. The Na can be reabsorbed into the mucus b/c of the open Na channel
  6. BUT the Cl cannot be reabsorbed b/c of the damaged CFTR channel
  7. The build up of Cl– at the tissues, produces a large –ve charge
  8. The –ve charge attracts the +ve charge of the Na
  9. Hence, the NaCl remains unabsorbed at the skins surface
  10. Water evaporates
  11. The skin is now salty