Hunger Diarrhoea and the Enterocyte Chloride Ion Secretion Paradigm

Enhanced secretion of fluid in starvation has been proposed to worsen any fluid secretion that is
already occurring after exposure of the intestine to enterotoxins. The evidence for this is that historical
accounts of imposed fasting in civil or military circumstances are associated with fatalities that arise
from secretory diarrhoeal disease. In addition, there is also experimental work apparently showing
that secretion is enhanced during short term starvation. In experimental animals exposed to fasting
and bacterial enterotoxin, the short-circuit current increase on toxin exposure, assumed to represent
fluid secretion, is always greater in the animal intestine exposed to E. coli heat stable STa enterotoxin.
Attention is drawn to the fact that human volunteers in a laboratory setting do not develop diarrhoea
on fasting. They do develop a reduction in circulating blood volume consistent with lower than usual
blood pressure and hypovolaemia. More detailed examination of the well documented historical
accounts of sieges and civil forms of enforced starvation confirms the cardiovascular changes but
evidence of secretion i.e. diarrhoea, only occurs when contaminated water is exploited or is the sole
source of fluid and personal hygiene is problematical. In human situations in which salt is provided,
the incidence of diarrhoeal disease is intermittent but with salt deprivation, the incidence increases.
Polydipsia is a consistent feature of persistent starvation and it can be assumed that this is a
response to the hypovolaemia.
The evidence from short-circuit current studies in fasted experimental animals is reviewed. A close
examination of these studies indicates that increases in short-circuit current are unlikely to rep-resent
chloride ion section. An alternative explanation is given of enhanced but electrogenic sodium ion
uptake in response to the shrinkage in blood volume which cannot be restored by drinking water
alone. Evidence from isotope studies has shown that fasting in animals increases sodium ion uptake
as well as short-circuit current, making it likely that fasting causes electrogenic sodium ion absorption.
Earlier data on the effect of diuretics makes it likely that what has been studied is the involvement of
compensatory electrogenic sodium ion absorption and its interruption by certain diuretics. The recent
siting of the NKCC2 transporter in the intestinal brush border makes this a viable alternative
explanation for the changes in ion currents seen in starvation. There are therefore no compelling
reasons for assuming that fasting enhances secretion in man or in animals or that bacterial
enterotoxins cause secretion that is exacerbated by starvation.