Physiology Lecture 18: Chloride Secretion and Transport
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Questions and Answers

What is the rate limiting step of chloride secretion?

  • The basolateral Na-pump
  • The transport of Cl across the epithelium
  • The paracellular Na and water fluxes
  • The chloride channel (CFTR) (correct)
  • What is the consequence of overstimulation of the chloride channel (CFTR)?

  • Secretory diarrhoea (correct)
  • Paracellular Na and water fluxes
  • Increased absorption in the colon
  • Cystic fibrosis
  • What is the primary cause of secretory diarrhoea?

  • Inflammation in the small intestine and colon
  • Overactive secretory cells in the crypts of the small intestine and colon (correct)
  • Underactive secretory cells in the crypts of the small intestine and colon
  • Tumour in the small intestine and colon
  • What is the molecular mechanism of cholera?

    <p>Secretagogue binds to the G protein coupled receptor which activates adenylate cyclase</p> Signup and view all the answers

    What is the treatment for secretory diarrhoea caused by cholera?

    <p>Oral rehydration therapy</p> Signup and view all the answers

    What is the effect of cholera toxin on adenylate cyclase?

    <p>It activates adenylate cyclase</p> Signup and view all the answers

    What is cystic fibrosis?

    <p>An inherited disorder that affects the transport of Cl ions</p> Signup and view all the answers

    What is the role of the basolateral Na-pump in the transport of Cl ions?

    <p>It pumps Na out of the cell and K into the cell</p> Signup and view all the answers

    What is the primary function of the Na pump in chloride secretion?

    <p>To set up ion gradients by hydrolyzing ATP to move sodium ions against their chemical gradient</p> Signup and view all the answers

    What is the role of the sodium gradient in the Na Cl symporter?

    <p>To use the energy of the sodium gradient to actively accumulate chloride above its electrochemical gradient</p> Signup and view all the answers

    What is the characteristic of the Na Cl symporter?

    <p>Secondary active transporter that uses the energy of the sodium gradient</p> Signup and view all the answers

    What is the reason for the need to push chloride ions into the cell using the Na Cl symporter?

    <p>Chloride ions are negatively charged and the cell is negatively charged</p> Signup and view all the answers

    What is the result of the Na Cl symporter's action on the movement of chloride and potassium ions?

    <p>Chloride and potassium ions move in opposite directions, with chloride moving in and potassium moving out</p> Signup and view all the answers

    What is the significance of the tight junctions in chloride secretion?

    <p>They separate the cell into apical and basolateral domains</p> Signup and view all the answers

    Study Notes

    Cellular Mechanisms of Chloride Secretion

    • Tight junctions divide cells into apical and basolateral domains
    • Na pump sets up ion gradients through primary active transport, hydrolyzing ATP to move 3 sodium ions against its chemical gradient and accumulate 2 potassium ions inside the cell
    • The Na Cl symporter uses the energy of the Na gradient to actively accumulate chloride above its electrochemical gradient, an example of a secondary active transporter

    Chloride Transport Across the Epithelium

    • Chloride enters the cell through the Na Cl symporter and exits the cell by passive diffusion through the CFTR ion channel
    • Na exists through the basolateral Na-pump and K+ via channel
    • The transport of Cl across the epithelium induces paracellular Na and water fluxes

    Rate Limiting Step of Chloride Secretion

    • The chloride channel (CFTR) is the rate limiting step of chloride secretion, as chloride can't leave the cell unless the chloride channel is open
    • The opening of the Cl- channels is strictly gated (regulated)

    CFTR and Its Role in Diseases

    • CFTR is recognized as the Cystic Fibrosis Transmembrane conductance Regulator
    • Overstimulation of CFTR can cause secretory diarrhea, while its dysfunction causes cystic fibrosis

    Secretory Diarrhea

    • Caused by overactive secretory cells in the crypts of the small intestine and colon
    • Overactivity can be caused by high concentrations of endogenous secretagogues produced by tumors or inflammation
    • Secretagogues are neurotransmitters or hormones that cause epithelial cells to stimulate signalling pathways, which open the chloride channel, CFTR, and start the process of secretion
    • Most commonly caused by the secretion of Enterotoxins from bacteria such as Vibrio cholerae

    Molecular Mechanism of Cholera

    • Secretagogue binds to the G protein coupled receptor, activating adenylate cyclase, which converts ATP to cAMP, and activates protein kinase A to phosphorylate the CFTR channel, causing it to open
    • Cholera toxin activates adenylate cyclase, which continues and doesn't stop, activating the CFTR

    Treating Secretory Diarrhea

    • The problem with secretory diarrhea is that the secretion becomes overstimulated, overwhelming the ability of the colon to do normal absorption
    • Treatment involves increasing absorption, which can be done by using glucose stimulated water fluxes, such as oral rehydration therapy to prevent dehydration

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    Understand the cellular mechanisms of chloride secretion, its role in secretory diarrhea and Cystic Fibrosis, and the significance of physiological research.

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