Oral rehydration therapy

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Oral rehydration therapy

  • Vibrio cholera bacteria enters the body via contaminated food and drink and they use their flagella to swim to the small intestine
  • They produce an exotoxin (a toxic protein) which binds to the carbohydrate receptors in the cell membrane (they have complimentary shapes)
  • This causes the ion channel to open- Ions flood out into the lumen of the ileum
  • This increases the water potential of the intestinal cells
  • Water molecules move by osmosis out of the cells where the water potential is higher into the lumen where the water potential is lower
  • Water is lost as faeces (Less is reabsorbed)

Dehydration= Not getting enough H2O or electrolytes (ions) in the cells

The treatment for diarrhoeal diseases that infects the intestines is called oral rehydration therapy. Diarrhoea is an intestinal disorder where watery faecces are produced frequently

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Causes

  • Damage to the epithelial cells lining the intestine
  • Loss of microvilli due to toxins
  • Excessive secretion of water due to toxins eg: cholera toxin
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How can the patient be rehydrated if the intestine

  • There's more than one type of carrier protein in the plasma membranes of epithelial cells that absorb sodium ions
  • The trick is to develop a rehydration solution that uses these alternative pathways
  • As sodium ions are absorbed, the water potential of the cell falls and water enters the cell by osmosis
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Rehydration solution ingredients

Water- To rehydrate the tissues

Sodium ions- To replace the sodium ions lost and optimise the use of the alternative sodium-glucose carrier protein

Glucose- To stimulate the uptake of sodium ions from the intestine and to provide energy

Potassium- To replace potassium ions lost and to stimulate appetite

When commercial products aren't available, it's possible to use an inexpensive, home-made rehydration solution- Sugar and salt in boiling water.

The ingredients can be mixed and packaged as a powder and then the solution can be made up with boiled water. The solution must be given regularly and in large amounts. They don't prevent or cure diarrhoea- they simply rehydrate and nourish the patient until the diarrhoea is cured by other means

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The development of oral rehydration solutions

  • Early rehydration solutions led to side effects, especially in children
  • They were caused by excess sodium and so mixtures with lower sodium but more glucose were tested
  • The additional glucose lowered the water potential in the lumen of the ileum so much that it started to draw out even more water from epithelial cells- this made the dehydration even worse
  • Lowering the glucose content reduced this effect but as glucose also acted as a respiratory substrate, it reduced the amount of energy being supplied to the patient
  • One answer was to use starch in place of some of the glucose
  • Starch is broken down steadily by amylase and maltase in the ileum into its glucose monomers
  • By experimenting with different concentrations of starch, a rehydration solution was developed that released glucose at the optimum rate without it adversely influencing the water potential

Rice starch is popular because:

  • It's readily available
  • It provides other nutrients like amino acids
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Testing

Testing is normally carried out in 4 phases:

  • A small number of healthy people are given a tiny amount of the drug to test for side effects- Usually takes around 6 months
  • The drug is given to a slightly larger number of people who have the condition that the drug is designed to treat- This is to see if it works and looking at any safety issues (Usually takes around 2 years)
  • A large-scale trial then takes place- Many are given a dummy drug called a placebo. Often neither the scientists or the patients know who has taken the real drug and who has taken the placebo until after the trial. This is known as the double blind trial (Usually takes many years)
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