A survey conducted by the Programme for Control of Diarrhoeal Diseases
(World Health Organization, August 1983) has indicated that in 1980 close to
1 billion episodes of acute diarrhea occurred in children under 5 years of age
in underdeveloped and developing countries.
Prolonged or intermittent diarrhea early in life has been shown to be one of
the main causes of infant death in the developing countries.
Damage to the mucosa of the digestive tract frequently results in diarrhea.
The variety of etiologies leading to this situation is so great that of necessity we
focus this discussion only on a limited number of examples.
The term "ultrastructural topography," or topographic histology, is relatively
new. It has been introduced into the medical literature to mark a new dimension
for the study of tissue surfaces by the scanning electron microscope.
Diarrhea is one of the most common symptoms of illness in pediatric practice.
It usually appears in the form of acute diarrhea, but it may also progress to a
Carbohydrate intolerance has been shown to be common during and immediately
following an episode of diarrhea, particularly in infancy and childhood.
When these infants and children are maintained on diets with high concentrations
of a specific carbohydrate or class of carbohydrates, the symptoms will continue
and often increase in severity.
The most common acid-base disturbance in dehydrated infants with diarrhea
is a hyperchloremic metabolic acidosis resulting from the loss of intestinal bicarbonate
by two different mechanisms: (a) loss into the stool and (b) buffering
by organic acids (OA) produced within the colonic lumen by bacterial fermentation
of undigested food.
Before dietary protein or endogenous protein of the alimentary tract can be
assimilated, it must be hydrolyzed by intraluminal digestive processes into small
peptides and free amino acids. Borgstrom et al.
The function of the adult colon has been well denned and thoroughly studied
and includes the transport of salt and water from the colonic lumen to the
circulation in a process that is responsive to aldosterone (1-3) and contributes
a large portion of normal body salt and water conservation.
Before one considers active nutritional therapy for a global problem as devastating
and massive as chronic infant diarrhea, one should consider the preventive
aspects of nutritional care. The favorable impact of breast-feeding on
the incidence and course of diarrheal disease has been rediscovered and reaffirmed
in most parts of the world.
Acid balance, 163-177
and carbohydrate metabolism, 173-
acute diarrhea patients, 173-174
chronic diarrhea patients, 173
comparison among groups, 174-
This chapter describes the use of stable isotopes for the investigation of normal
and abnormal digestion and absorption in infants. Isotopes are atoms with equal
numbers of protons but different numbers of neutrons.
Body weight and height (length) are important anthropometric indices of the
nutritional status of children. From the fact that nearly 100 million children
under 5 years of age throughout the world suffer from varying degrees of proteinenergy
malnutrition (PEM) (1),
The gastrointestinal tract has a unique place in human ecology. After birth
it is continually exposed to potentially harmful external agents—infective, toxic,
Even today acute diarrheal disease is thought of by many laymen as well as
by some medical professionals in developing countries as being a syndrome of
In a letter to the Royal Society (London) dated November 4, 1681, Antony
van Leeuwenhoek gave what seems to be the first account of the human intestinal
protozoan pathogen Giardia lamblia (1).
In the past decade, human rotavirus (HRV) enteritis has been identified as
the most common cause of significant acute diarrheal illness among infants and
young children (1,2).
Diarrhea of infancy and early childhood has many causes, including viral
and bacterial infection. In some of these conditions the intestine may demonstrate
few if any histological changes (e.g., cholera) or may show profound alterations
(e.g., Salmonella, reovirus, etc.).
It has been estimated that between 5 and 20 million children die each year
as a result of acute and chronic diarrhea. The investigation of the pathogenesis
and treatment of this major clinical problem is, therefore, of special importance,
representing one of the most important challenges to medicine in the last decades
of this century.
Until relatively recently the small intestine was considered to be largely an
organ for the absorption of water and solutes. Over the past decade, however,
evidence has accumulated that it is capable of marked secretion of water and
electrolytes, and this chapter summarizes some of the important advances that
have occurred in our understanding of the mechanisms of the small intestine
that regulate this secretion.
Among the various factors that are known to initiate the pathophysiological
events leading to chronic, intractable diarrhea of infancy are intestinal infections
by bacteria. Such infections, furthermore, are particularly worrisome in malnourished
infants, where they tend to result more often in protracted diarrhea
necessitating vigorous and risk-laden supportive treatment.
Although the classical definition of intractable diarrhea of infancy (1), which
includes three or more stools negative for bacterial pathogens, would tend to
exclude a role for enteric infection in the pathogenesis of this form of diarrheal
disease, a role for pathogenic E. coli may remain.
The pharmacologic effect of exogenous bile acids as cathartic agents is well
known. Early formulations used as purgatives took advantage of the laxative
effect of bile acids through administration of bile enemas or orally administered
desiccated ox bile.
Bile acids are both acted on by the gut and act on the gut. Bile acids undergo
an enterohepatic circulation and are absorbed by specific mechanisms for bile
acid transport in the ileum (1). At the same time, bile acids influence salt and
water transport in the intestine (2).
The defense of the gastrointestinal (GI) tract against potentially harmful organisms
requires the concerted and integrated functions of diverse host defense
mechanisms, both physiologic and immunologic.
The gastrointestinal tract encounters a greater amount of foreign antigen than
any other mucosal surface of the body.
Recent studies of the pathophysiology of diarrhea have resulted in both increased
understanding of how existing antidiarrheal drugs work and a rational
approach to the development of new antidiarrheal therapies.
Worldwide, the impact of acute diarrheal disease is immense and is particularly
important in infants and young children. It has been estimated that each child
experiences six to eight episodes of diarrhea per year in developing countries
(1) and that this represents an annual mortality of up to 18 million children
under 5 in those countries (2).
Chronic and recurrent diarrheal illnesses are common in malnourished populations,
particularly in young children, and contribute significantly to malabsorption
Protein intolerance in this study is denned in terms of food protein damaging
the small intestinal mucosa and so resulting in chronic diarrhea.
When total parenteral nutrition was first used in the therapy of infants with
intractable diarrhea as defined by Avery et al. (1), it was clearly demonstrated
that many of these patients had gastrointestinal allergy or intolerance to food
The present-day concepts on the pathophysiology of secretory diarrhea (1)
have opened a new stage in the pharmacological treatment of diarrhea in children.
Drugs used in the past as antidiarrheal agents and believed to act only on
intestinal motility are now being viewed as antisecretory compounds, and their
antidiarrheal action is being attributed, at least partially, to their action on the
fluxes of ions and water in the intestine.
In developing preventive measures and treatments for intractable infant diarrhea,
one must first have an understanding of the etiology of these diseases. It
is a reasonable hypothesis, although one not yet proven, that these illnesses are
induced by the establishment of chronic colonization of the small intestine by
enteric bacterial pathogens and that this colonization leads to a pattern of chronic
and continuing mucosal injury.
The situations that lead to malnutrition are not only numerous but often
multiple and simultaneous.
Acute infectious diarrhea with dehydration is among the two main causes of
infantile morbidity and mortality in less developed countries. The complex
etiology of childhood diarrhea and its close relationship with environmental
conditions and nutritional status must be stressed in designing and evaluating
In most infants and children, the symptoms of acute diarrhea resolve over
the course of a few days, but in a small proportion, diarrhea persists and becomes
protracted. Protracted diarrhea has been denned as more than four watery stools
per day for longer than 2 weeks.