|Author: Roger M. Goodall
We are often asked to explain how ORT works - a question that can only be answered successfully by first considering some of the simple physiology of the normal
intestine and then the changes that occur in a state of diarrhoeal disease.
This is a basic discussion of the question written in reasonable non-technical terms to provide some of this interesting background information.
GLOSSARY OF SOME OF THE TERMS USED
Simple components into which food is broken down by digestion and which are subsequently built up into complex materials of body
tissues e.g. proteins which are broken down into their component amino-acids by digestion and then metabolized back into further proteins in the body.
A single electrically charged particle into which the atoms or molecules of some substances dissociate when in solution, e.g. sodium chloride in the solid state consists
of molecules containing one atom of sodium Na and one atom of chlorine Cl bound together NaCl - in solution in water the molecule splits into two ions (Na+) and (Cl-) each of
which tends to be loosely bound to three or four molecules of water
e.g. (H8O4Na) + and (H6O3Cl)-
although for practical purposes they can be thought of as single ions Na+ and Cl-
Positively charged ions e.g. Na+ are called CATIONS and Negatively charged ions e.g. Cl- are called ANIONS.
The substances which show this dissociation into electrically charged ions are called ELECTROLYTES.
A dissolved substance e.g. sodium chloride (the solute) dissolved in water (the solvent) to give a solution.
If two different substances are in a solution they are said to be equal in molarity (equimolar) if they have equal numbers of molecules per litre of solution. The mass or
weight of each solute is then proportionate to their respective molecular weights.
The presence of an excess amount of sodium Na+ in the blood plasma (i.e. over 140 mmol/l.)
NORMONATRAEMIC - is the presence of a normal level of sodium and HYPONATRAEMIC - lower than normal sodium level in the plasma.
- Sodium Chloride 3.5 grams
- Sodium Bicarbonate 2.5 grams
- Potassium Chloride 1.5 grams
- Glucose 20 grams
to be dissolved in one litre of clean drinking water
REFERENCE: The management of diarrhoea and use of oral rehydration therapy a Joint WHO/UNICEF statement.
THE PHYSIOLOGICAL PROCESS
In the normal healthy intestine, there is a continuous exchange of water through the intestinal wall - up to 20 litres of water is secreted and very nearly as much
is reabsorbed every 24 hours - this mechanism allows the absorption into the bloodstream of soluble metabolites from digested food.
Typical values for the daily gains and losses of water in an average man in a temperate climate are:
ml per day
ml per day
In a state of diarrhoeal disease the balance is upset and much more
water is secreted than is reabsorbed causing a net loss to the body which can be as high
as several litres a day. In addition to water, sodium is also lost. The body's store of
sodium (in the form of sodium ions Na+) is almost entirely in solution in body fluids and
blood plasma, i.e., extra cellular. By contrast 98% of the body's total potassium (K+) is
held within cells, i.e. intracellular.
Approximate concentrations of the principal ions in plasma,
interstitial, and intracellular fluids in an average man are:
|Cations (mmol per litre
|Anions (mmol per litre)
The concentration of Na+ in the extracellular fluid has to be held to
within close limits (135-150 mmol/l) for the proper functioning of the body. Normally, this sodium concentration is normally precisely
controlled by the renal function. However in a state of dehydration water is conserved by anuria and the sodium regulation cannot work effectively.
Thus continued diarrhoea causes rapid depletion of water and sodium, which is to say, a state of dehydration. If more than 10% of the body's fluid is lost death occurs.
The approximate distribution of body water in an average man is:
% of total
|Total body water
Simply giving a saline solution (water plus Na+) by mouth has no
beneficial effect because the normal mechanism by which Na+ is absorbed by the healthy
intestinal wall is impaired in the diarrhoeal state and if the Na+ is not absorbed neither
can the water be absorbed. In fact, excess Na+ in the lumen of the intestine causes
increased secretion of water and the diarrhoea worsens.
If glucose (also called dextrose) is added to a saline solution a new
mechanism comes into play. The glucose molecules are absorbed through the intestinal wall
- unaffected by the diarrhoeal disease state - and in conjunction sodium is carried
through by a co-transport coupling mechanism. This occurs in a 1:1 ratio, one molecule of
glucose co-transporting one sodium ion (Na+).
It was the discovery of this mechanism of co-transport of sodium and
glucose which the Lancet described as "potentially the most important medical advance
this century" ( ORT is in fact the practical realization of this potential).
It should be noted that glucose does not co-transport water - rather it
is the now increased relative concentration of Na+ across the intestinal wall which pulls
water through after it.
Several other molecules apart from glucose have a similar capacity to co-transport Na+ including:
- aminoacids (e.g. glycine)
and the absorption of these molecules may occur independently of each
other at different sites - thus their effect can be additive. Research is currently being
carried on to utilize these additive effects to develop a multi-component "Super ORS".
Starch is metabolized in the intestine to glucose and therefore it has
the same properties of enhancing sodium absorption, however it has an added advantage that
it has less osmotic effect, which would act to pull water back into the lumen of the
THE COMPOSITION OF ORS.
In deciding the optimal composition of an oral rehydration solution the
following considerations must apply:
- Sodium - losses of sodium in the stool range from 50-60 meg/l to well
over 100 meg/l in cholera and in fact total body depletion of sodium may be higher than
stool losses alone indicate. For this reason a Na+ concentration of 90 meg/l is considered
an optimal figure for replenishing Na+ in dehydration from diarrhoea caused by any
etiology and in all age groups from neonates to adults.
For some years there was controversy over optimum concentration of
sodium in oral rehydration fluids, which stemmed from the fact that in the early days of
its use, particularly in USA, causes of hypernatraemia (excess sodium) occurred fairly
frequently in infants given oral rehydration therapy.
The apparently obvious answer was to assume that the sodium
concentration in the oral rehydration fluid used was too high and to reduce it (even to as
low as 25 or 30 meg/l). Unfortunately, the apparently obvious was not the correct answer -
actually nearly all these children were being given high- solute infant formula which
tended to make them hypernatraemic to start with and the oral rehydration solution used
then contained excess glucose - up to 8% - which was added to provide extra nutritive
calories. Unfortunately, the excess glucose caused osmotic diarrhoea which precipitated
acute hypernatraemia in these children.
The less obvious but correct answer was to reduce the glucose content -
not the sodium. We now recognize that the sodium and glucose should be in a 1:1 ratio in
terms of molarity.
Experience has now shown that even hypernatraemic neonates with
dehydration can be successfully rehydrated and made normonatraemic using the standard WHO
/ UNICEF ORS formula (with 90 meg/l Na+) when the water intake is sufficient to ensure
normal kidney function and hence physiological regulation of the sodium concentration in
Although ORS with a sodium content of around 50 meq/l is sufficient for
maintenance of hydration of a normally will-nourished child with diarrhoea it would be
inadequate for rehydration of a patient with a secretary diarrhoea (e.g., cholera) losing
considerable sodium in the stool.
- Glucose should be close to equivalent with the Na+ content - it is
111 mmol/l in the WHO / UNICEF formula, which happens to be exactly 2%. It should be noted
that if glucose is present in excess of 3% it will cause further losses of water through
osmotic effects, this would also upset the electrolyte balance, since increased water
losses will result in hypernatraemia.
- We have not yet given more than a passing mention to potassium.
Although as we saw that 98% of the body's potassium is held within the cells, repeated diarrhoeal attacks over a period of time will cause a chronic loss of potassium.
results in muscular weakness, lethargy and anorexia. The typical distended abdomen of a
chronically malnourished child is caused by loss of muscle tone in the abdominal wall
largely due to chronic depletion of potassium. The kidneys are unable to conserve
potassium as they do sodium, and there is a continuous obligatory loss of potassium of
about 10 mmol daily in the urine, in addition to the larger losses in the stool.
Potassium is not involved in any way in the sodium/glucose co-transport
mechanism and is absorbed passively. Restoration of potassium levels is therefore achieved
more slowly than sodium and water restoration. A potassium concentration of 20
considered optimal for the purpose.
Simple mixtures of sugar , salt and water or starch, salt and water
contain no potassium and cannot restore potassium depletion - hence these mixtures are an
"incomplete" formula and further potassium supplementation is definitely
necessary for a child who suffers repeated attacks of diarrhoea.
A potassium-rich diet including, for example, bananas or coconut water can be
helpful but an ORS solution containing potassium is therapeutically more effective.
order to produce a significant effect it is necessary to provide potassium-rich foods in
reasonable large quantities over a period of time.
Restoring a potassium deficit promotes a feeling of well-being and
stimulates the appetite and activity of the child. If additional food is provided over
several weeks an increase in weight gain will occur and the status of the child's health
will improve markedly. Dietary intake is needed to achieve this.
- Electrolyte imbalance and fluid loss also causes metabolic acidosis.
These effects are more critical in the case of infants, as their renal function is not
fully developed and they have a large surface area in ratio to body weight and a higher
metabolic rate. Acidosis is corrected by the addition of bicarbonate (or another base such
as citrate) to the ORS formula.
Electrolyte content of stool in acute diarrhoea and the electrolyte and
glucose content of ORS solution:
|children (less than 5 yrs.)
|children (less than 5 yrs.)
(values expressed as mmol/l)
The causative pathogens of diarrhoeal disease (which are very numerous,
more than 30) in some cases not only produce the secretion of water and sodium but also
damage the intestinal wall. The normal healthy intestine is covered on its inner surface
with very numerous tiny hairs, or villi, the surface cells of which are involved in the
absorption of metabolites from ingested food. There is a difference between the cells of
the tips of the villi and the cells of the base in their absorptive functions.
Pathogens, e.g., rotavirus, may strip the tips of the villi from large
patches of the intestinal wall thus decreasing the surface area and decreasing by more
than 50% the specific absorptive capacities of the intestine. The result is malabsorption
which can cause malnutrition - most especially in a child already nutritionally
compromised by repeated previous attacks of diarrhoea.
Withholding food, even for one or two days, greatly exacerbates the
malnutrition; this coupled with anorexia, caused partly by chronic potassium depletion,
causes a vicious circle, i.e. diarrhoea causing malnutrition and malnutrition causing ever
more frequent and severe diarrhoea. It is this diarrhoea/malnutrition cycle rather than
acute dehydration that causes almost half of the five million deaths a year that are associated with diarrhoeal disease
in children under five years old.