Professional Documents
Culture Documents
Pathophysiology of
diarrhoea
L A Whyte
H R Jenkins
Abstract
The absorption and secretion of water and electrolytes throughout the
gastrointestinal tract is a finely balanced, dynamic process and, when
there is loss of this balance caused either by decreased absorption or
increased secretion, diarrhoea results. Diarrhoea remains a major cause
of morbidity and mortality worldwide, accounting for 3 million deaths
per year in young children, and it is therefore important for those who
care for children to have a clear understanding of the pathophysiology
of diarrhoea. Diarrhoea can be considered to be either osmotic or secretory. Osmotic diarrhoea occurs when excessive osmotically active particles are present in the lumen, resulting in more fluid passively moving
into the bowel lumen down the osmotic gradient. Secretory diarrhoea
occurs when the bowel mucosa secretes excessive amounts of fluid
into the gut lumen, either due to activation of a pathway by a toxin, or
due to inherent abnormalities in the enterocytes. The management of
acute diarrhoea is based on assessment of fluid balance of the child
and rehydration. Oral rehydration with oral rehydration solution is
extremely effective and has significantly reduced childhood mortality
over the past 40 years. Chronic diarrhoea has a number of infective and
non-infective causes, careful history and specific investigation and
management in secondary or tertiary care is often necessary.
H R Jenkins MA MD FRCP FRCPCH is Consultant Paediatric Gastroenterologist in the Department of Paediatric Gastroenterology at the Childrens
Centre, University Hospital of Wales, Cardiff, UK. Conflicts of interest:
none.
443
OCCASIONAL REVIEW
Lumen
Pathophysiology of diarrhoea
Diarrhoea is the result of a disruption in the delicate balance
between the absorptive and secretory processes within the
bowel. In general, diarrhoea can be considered to be either
osmotic or secretory.
Osmotic laxatives
Excessive solutes within
the lumen
Inflammation within
the mucosa
Motility disorders
Underlying causes
C
C
C
Cholera toxin
Other infective causes
Specific electrolyte transport
defects (e.g. congenital
chloride-losing diarrhoea)
or structural abnormalities
(e.g. microvillous atrophy)
Osmotic diarrhoea
When excessive numbers of osmotically active particles are
present in the lumen, more fluid passively moves into the bowel
lumen down the osmotic gradient which may exceed the
absorptive capacity of the gut and hence diarrhoea occurs.
Osmotic diarrhoea therefore will stop when the child is not fed.
Excessive numbers of osmotically active particles can be
present for a number of reasons including:
Ingestion of solutes that cannot be absorbed e.g. osmotic
laxatives such as lactulose
Malabsorption of specific solutes e.g. disaccharide deficiency, glucoseegalactose malabsorption
Damage to the absorptive area of the mucosa resulting in
less fluid absorption e.g. acute gastroenteritis, cows milk
protein allergy, coeliac disease and Crohns disease
Motility disorders such as those seen in gastroschisis,
irritable bowel syndrome, and hyperthyroidism which
result in reduced contact with the bowel lumen and
consequently a higher concentration of solutes within the
lumen.
Na
H2O
Na
ATPase)
Glucose
Secretory diarrhoea
Serosa
Na
Osmotic diarrhoea
444
OCCASIONAL REVIEW
Secretory diarrhoea
This occurs when the bowel mucosa secretes excessive amounts
of fluid, either due to activation of a specific pathway by a toxin
(such as cholera toxin), or inherent abnormalities in the enterocytes, (e.g. congenital microvillous atrophy). Often absorptive
mechanisms, although present, are overwhelmed, resulting in
diarrhoea. In the case of secretory diarrhoea, this does not stop if
the childs enteral feeds are withheld.
In some instances both osmotic and secretory diarrhoea can
occur together, in acute or chronic disease, depending on the
underlying cause.
of water and solutes will exceed the secretion and will ensure the
child remains hydrated until the infective organism is eradicated.
The ORS recommended by the WHO in 2002 contains 75 mmol/
litre sodium, 75 mmol/litre glucose, and has a total osmolarity of
247 mOsm/litre. Of note, other traditional rehydration solutions
such as coca-cola and apple juice have a significantly lower
content of sodium and a very high osmolarity and are thus
inadequate as oral rehydration solutions.
ORS has been shown to be effective in both developing and
developed countries for the rehydration of children. Studies have
shown that less than 5% of children with acute diarrhoea,
regardless of the underlying cause, fail to improve with oral
therapy and IV rehydration, with its consequent risks, is rarely
needed.
Viruses
Bacteria
Parasites
Rotavirus
Norwalk virus
Norovirus
Calicivirus
Campylobacter jejuni
Salmonella
Escherichia coli
Shigella
Yersinia entercolitica
Clostridium difficile
Cryptosporidium
Giardia lamblia
445
OCCASIONAL REVIEW
Cryptosporidium parvum e cryptosporidiosis. This protozoan organism can cause chronic diarrhoea. Diagnosis is made
by specific antigen testing and although usually self-limiting may
be treated with nitazoxanide for 3 days.
Viruses e in immunosuppressed children viruses such as
cytomegalovirus can cause chronic diarrhoea and must be
considered in the differential diagnoses.
Non-infective causes:
Secondary to damage to the mucosa e in coeliac disease or
inflammatory bowel disease, inflammatory mediators act locally
within the intestinal mucosa to stimulate secretion and inhibit
reabsorption of electrolytes. They also act on enteric neurones, to
increase motility.
Specific and rare abnormalities of enterocytes or the brush
border membrane e these are rare conditions usually presenting
as congenital or chronic diarrhoea from early infancy. Examples
include, congenital microvillus inclusion disease where there is
a net reduction in the surface area of the bowel and there is
massive excretion of electrolytes in the stools. Another rare cause
is autoimmune enteropathy where anti-enterocyte antibodies
(IgG) damage the bowel mucosa.
Specific and rare electrolyte transport defects
Carbohydrate malabsorption: primary (very rare) or
secondary lactose intolerance, sucroseeisomaltase deficiency,
congenital glucoseegalactose malabsorption cause osmotic
diarrhoea due to the high osmolality of luminal contents.
Excessive fructose intolerance, usually the result of excessive
intake of fruit juices (especially apple juice) is known to cause
osmotic diarrhoea in children and should be considered as
a differential diagnosis in chronic diarrhoea.
Congenital chloride losing diarrhoea in which the chloride/
bicarbonate transporter does not function resulting in high luminal
chloride levels and secretion of fluid. In this situation, the Na H
exchangers continue to operate, so hydrogen is secreted in the faces
without bicarbonate to neutralize it, thus resulting in a metabolic
alkalosis.
Pancreatic and biliary disorders e cystic fibrosis may lead to
pancreatic insufficiency and protein and fat malabsorption. The
contents of the intestinal lumen are therefore of a higher osmolality,
resulting in osmotic diarrhoea. The liver disease, cholestasis may
cause reduced bile salts and insufficient fat malabsorption, thereby
causing diarrhoea secondary to highly osmolar luminal contents.
Disorders of intestinal motility e these disorders may cause
rapid transport through the gut resulting in less overall absorption of electrolytes and water.
IBS variant of childhood e chronic non-specific diarrhoea of
childhood or irritable bowel variant of childhood is a useful
term for what used to be called toddler diarrhoea. This diagnosis
is one of exclusion, but can be useful as many parents have heard
of it and there is often a positive family history.
Osmotic gap
Chloride concentration
pH
Sodium concentration
Osmotic
<50 mOsm/kg
>40 meq/litre
>6.0
>70 meq/litre
>135 mOsm/kg
<35 meq/litre
<5.5
<70 meq/litre
Imaging
Barium meal and follow through/MRI enterography
Endoscopy and biopsy.
Test
Normal values
Secretory
Implications/possible
diagnosis
Protein-losing
enteropathy
Fat malabsoprtion
Pancreas function
Inflammation of the gut
Carbohydrate
malabsorption
Summary
Regardless of the cause or type of diarrhoea, dehydration may
ensue rapidly and this must be recognized and treated promptly.
In the majority of cases of acute diarrhoea, oral rehydration with
oral rehydration solution is effective. In those children with
446
OCCASIONAL REVIEW
Practice points
C
FURTHER READING
Deepak P, Ehrenpreis E. Diarrhoea. Dis Mon 2011; 57: 490e510.
Kleinman RE, Sanderson IR, Goulet OG, Sherman PM, Mieli-Vergani G,
Shneider BL. Paediatric gastrointestinal diseases. 5th Edn. Hamilton:
BD Decker Inc, 2008.
Online learning in gastroenterology OLGa. http://olga.uegf.org/portal/
index.php.
Powell CV, Jenkins HR. Toddler diarrhoea: is it a useful diagnostic label?
Arch Dis Child 2012; 97: 84e6.
C
C
447