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Oral rehydration solutions

1. Oral rehydration solutions. ~ their history & development for use in calves. Harriet Brooks Brownlie, BVetMed. PhD, FRCPath. 2. The problem.

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Oral rehydration solutions

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  1. 1 Oral rehydration solutions ~ their history & development for use in calves Harriet Brooks Brownlie, BVetMed. PhD, FRCPath

  2. 2 The problem “A lax or scouring.. is a frequent difcharge of thin, watry, … matter by the fundament; ..commonly but not always attended with griping pains in the guts.” Henry Bracken 1773 Treatise upon the Art of Farriery

  3. 3 The problem “Acute diarrhoea may be produced by various causes; ….It is the result of starvation and of excess – it is the almost necessary consequence of a sudden change in diet; in fact it is occasionally produced by everything that deranges the process of healthy digestion.” William Youatt 1834

  4. 4 Effects of diarrhoea •  absorption of Na+ (water)   fluid vols Dehydration • Losses: HCO3- ,K+, Cl-, Ca2+, Mg2+ & inorg PO 4-

  5. 5 Effects of diarrhoea - acidosis “There is a tendency to generate considerable quantities of acid. The chalk, or alkali of the chalk, will unite with this acid, and neutralise it, and render it harmless.” “In the diarrhoea of the calf [alkali] is absolutely indispensable, for there the acid principle is frequently developed to a great degree.” William Youatt 1834

  6. 6 Effects of diarrhoea • Other sequelae: • Renal effects – falling GFR • Hypothermia, hypoglycaemia* • Bradycardia, cardiac arrhythmias* * Association with fatal outcome Groutides, 1988

  7. 7 The solution "I would expect much benefit from the frequently repeated use of the neutral salts by mouth… ......dissolved in large quantities of tepid water.“ W B O'Shaughnessy, 1832

  8. 8 "The discovery of oral rehydration therapy is as important as the discovery of penicillin.“ Prof. Mamdouh GabrCairo University, Faulty of Medicine https://static01.nyt.com/images/2012/08/23/world/africa/23cholera/23cholera-jumbo.jpg

  9. 9 Na+ - cotransport (water absorption) in the small intestine glucose ~ interstitium Na+ Blood & lymph circulation gut lumen Water “Tight” junction

  10. 10 WHO-type ORSs • Equimolar - Na+ & glucose (cotransport) • anions (Cl-) • HCO3- • + glycine • Isotonic - 300 mmol/l http://citifmonline.com/wp-content/uploads/2014/07/WORLD_NEWS_HAITI-CHOLERA_2_MI.jpg

  11. 11 Considerations for WHO-type ORS for infants • Hypernatraemia - ?direct relationship with Na+ content of ORS • Undernutrition vs ?malabsorption (osmotic diarrhoea) • Acidosis not a problem in infants http://cdn.doctorswithoutborders.org/sites/usa/files/65593_drc.jpg

  12. 12 But what about ORS for calves? - Sodium Hyponatraemia most likely in diarrhoeic calves Groutides 1988

  13. 13 But what about ORS for calves? - Nutrition Available ORSs for calves “woefully short in energy!” Hypertonic solutions well within transport capacity of calf intestine Phillips 1982

  14. 14 But what about ORS for calves? - Acidosis Acidosis is a problem in diarrhoeic calves, severity not related to degree of dehydration Grove-White & White 1993 Little compensation (resp., renal, gut) by acidotic calves Groutides 1988

  15. 15 Potential roles for OFT for calves • Rehydration • Alkalinisation • Nutrition – patient • Nutrition - gut

  16. 16 Calf intestines rectum duodenum caecum ileum Spiral colon jejunum

  17. 17 Water absorption in calves – small intestine Semi-permeable membrane Small intestine water absorption duodenum Water ileum Na+ Na+-cotransport Co transporter jejunum Water Water

  18. 18 Water absorption in calves – large intestine K+ Na+ Cl- HCO3- Water

  19. 19 Fluid dynamics in the intestine (Bywater 1973) • Total fluxes ~ 80 l/24 hrs • Loss of 2.5 l faecal fluid /24 hrs = fatal

  20. 20 ORT efficacy • Na+, Na+:co-transporter, Na+: water • “Osmotic skeleton” – retains water in ECF

  21. 21 Focus for development of ORTs for calves •  Na+ (rehydration) •  HCO3- (alkalinization) •  nutrition (body weight) • Maintain mucosa (rehydration/recovery)

  22. 22 Clinical studies of ORTs in calves at the RVC

  23. 23

  24. 24 Phase 1: Sodium, bicarbonate yield

  25. 25 ECF volume E [Highest Na+] P [Lowest Na+] L [intermediate Na+] litres control 4 days of treatment

  26. 26 E [Highest Na+] Plasma Na+ concn P [Lowest Na+] L [intermediate Na+] mmol/l control days of treatment

  27. 27 TCO2(index of plasma HCO3-) E [Highest HCO3-] P [intermediate HCO3-] L [Lowest HCO3-] mmol/l control days of treatment

  28. 28 Example of Nutritional ORS formulation:

  29. 29 Blood glucose concn - WHO-type ORS (lowest glucose) Non-diarrhoeic mmol/l * Diarrhoeic * During treatment * P < 0.01 2 6 Hours post-feeding

  30. 30 Blood glucose concentration - nutritional ORS (high glucose) Non-diarrhoeic * mmol/l Diarrhoeic During treatment * *P < 0.01 2 6 Hours post-feeding

  31. 31 Effects of diarrhoea on gut mucosa Photo: Graham Hall

  32. 32 Effects of ORS on gut mucosa? (+ Glutamine) • Effects of treatment • Potentially aiding repair • Renal function

  33. 33 Developments of ORSs for calves – some conclusions • ORT formulation “predicts efficacy” • Higher Na+, co-transporter, BIC solutions effective in calves • Nutritive ORTs effective for treatment & support of diarrhoeic calves

  34. 1 34 Oral rehydration solutions ~ their history & development for use in calves Thanks to Bob Michell

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