Pathophysiology of diarrhoea

Diarrhoea results when there is loss of the dynamic and finely balanced absorption and secretion of water and electrolytes within the gut. Diarrhoea remains a major cause of morbidity and mortality worldwide and it is 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 solution is extremely effective and has significantly reduced childhood mortality from acute infective diarrhoea 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. This update contains new details on the investigation of chronic diarrhoea and in particular use of imaging, the ‘non-GI’ causes of diarrhoea, updates on the changing prevalence of infective pathogens and research into the use of probiotics.     

Investigation of chronic diarrhoea in infancy

Diarrhoea in infants and young children is defined as > 200 g/day of stools, and occurs when there is an imbalance between intestinal fluids absorption and secretion. This may be caused by either a decreased absorption (osmotic diarrhoea) or an increased secretion (secretory diarrhoea). Chronic diarrhoea defines intestinal loss of water and electrolytes with increased stool frequency, reduced consistency and larger volume over more than 14 days. This disorder in children shows a wide range of aetiologies depending on the age. The knowledge of common and rare aetiologies is important to optimize the diagnostic approach. A stepwise approach, starting with a comprehensive history, physical examination, inspection and collection of stool samples, helps to devise appropriate diagnostic and therapeutic management. In this article we discuss the pathophysiology, aetiology and possible approach to chronic diarrhoea in infancy.     

The main causes of death in malnutrition

The great killers in the developing countries are the classical contagious diseases and diarrhoea. The high incidence of these diseases is mainly due to the enormously increased exposure to infectious agents in a milieu of incredibly low hygienic standards. Malnutrition on the other hand, is responsible for the long duration and the often malignant course of these diseases. Undermined immunity in malnutrition may lead to septicaemia. Diarrhoea, besides the danger of hyponatraemia, hypokalaemia, acceleration of the wasting process may lead to hypovolaemic shock. Other types of circulatory disturbance are caused by very low serum albumin values, by the overloading of the wasted heart by fluid, by hight salt or calorie intake. Further dangers are hypoglycaemia and hypothermia. The briefly summarized dangers can rather exceptionally also be encountered in the advanced countries. Malnutrition in these parts of the world is brought about by organic diseases, by intractable diarrhoea or by psychologic disturbances.     

The child with prolonged fever: when to think zebras

Everyone remembers the adage beloved of medical school professors ‘when you hear hooves, think horses not zebras’ (i.e. most presentations have a common cause) and usually it is good advice. Fever is a very common paediatric presentation and usually has an identifiable infectious aetiology. However, for the child with prolonged fever it is sometimes necessary to look beyond the usual suspects and consider the ‘zebra’ diagnoses. This article addresses when to consider rarer and potentially life-threatening infective, autoimmune or malignant causes of prolonged fever and their immediate management.     

Pathophysiology of diarrhoea

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.     

Breastfeeding modifies the impact of diarrhoeal disease on relative weight: a longitudinal analysis of 2–12 month‐old Filipino infants

Undernutrition and diarrhoeal disease are major causes of infant mortality. We investigated the combined roles of breastfeeding and diarrhoea on infant size in 2940 infants from the Cebu Longitudinal Health and Nutrition Survey. The study aimed to assess whether breastfeeding status modified the deficits associated with diarrhoeal disease. The primary exposures were combinations of current breastfeeding status (yes/no), the presence of diarrhoeal disease in previous week (yes/no) and a categorical survey variable (six surveys taken at bimonthly intervals when infants were 2–12 months of age). Relative weight (weight‐for‐length z‐scores), calculated using the WHO growth standards, was estimated using sex‐stratified, fixed‐effects longitudinal models that also adjusted for energy from complementary foods. Post‐estimation Wald tests were conducted to identify subgroup differences in relative weight. Diarrhoea was associated with reduced relative weight in both breastfed and non‐breastfed infants of 6–12 months. Diarrhoea‐related deficits in relative weight were significantly exacerbated in non‐breastfed girls of 6 and 8 months. Importantly, in infants <6 months, being breastfed and having diarrhoea was still associated with greater relative weight compared with being non‐breastfed and diarrhoea‐free. Breastfeeding emerged as a strong contributor to relative weight in younger infants (<6 months) while diarrhoeal disease strongly contributed to deficits in relative weight in older infants (6–12 months). These findings underscore the importance of breastfeeding for promoting infant nutritional status in infants with or without diarrhoea from birth to 12 months.     

Changing patterns of antigen exposure and their impact on the prevalence of allergy

Industrial development has advanced at a varying pace in different parts of the world over the past 200 years. Inhabitants of the most industrially advanced regions have experienced major changes in patterns of antigen exposure to infectious agents and to environmental biologic substances. This article analyzes the major factors that affect the amounts and variety of antigens to which the immune system of a young child is exposed. Depending on individual living environments and lifestyles, the types of antigen exposure of young children are graded into five patterns: ‘primitive’, ‘pre‐modern’, ‘early modern’, ‘modern’, and ‘ultramodern’. These patterns represent increasing deviation from the pattern of human immune system exposure to antigens prior to the industrial revolution. This article further discusses how such changes in antigen exposure have affected the immunologic system, especially with regard to the development of total IgE and allergic response‐relevant antigen‐specific IgE, and how the patterns of antigen exposure are related to the propensity to develop allergy.     

Investigations of chronic diarrhoea

Chronic diarrhoea describes intestinal loss of water and electrolytes with increased stool frequency, reduced consistency and larger volume over more than 14 days. While in developing countries often resulting from persisting infectious gastroenteritis in high incidence, in industrialised countries chronic diarrhoea is mainly related to anatomical, functional, and immunological causes. As the spectrum of aetiology is variable, flow charts for different age groups are useful in determining key features of disease severity and diagnostic criteria. The knowledge of common and rare aetiologies helps to proceed with structured investigations, and to critically interpret results in awareness of diagnostic pitfalls. Comprehensive history, physical examination, inspection and collection of stool samples of sufficient volume are pivotal to devise appropriate referral modes for diagnostic and therapeutic management, as particularly newborn and infants are susceptible to severe dehydration and metabolic disturbances.     

Editorial: Illuminating the dark matter of developmental neuropsychiatric genetics – strategic focus for future research in child psychology and psychiatry

Research on genetic factors influencing cognitive and behavioural traits or which are central to the aetiology of neuropsychiatric diseases has been complicated by a furtive discrepancy between high heritability estimates and a scarcity of replicable gene‐disorder associations. This ‘missing heritability’ has been either euphemised as the ‘dark matter’ of gene‐trait association or aggravated as the ‘looming crisis in behavioural genetics’. Nevertheless, in recognising the importance of this topic for our understanding of child psychiatric conditions and highlighting its commitment to the field, the Journal of Child Psychology and Psychiatry (JCPP) has for the first time appointed an editor with special responsibility for molecular (epi)genetics.     

Oral solutions for gastroenteritis--optimal glucose concentration.

About half of all infants and toddlers with infectious diarrhoea of probable virus aetiology and treated with an oral rehydration solution containing 4.6% glucose had faecal glucose greater than or equal to 0.3%. In most of them the faecal concentration of glucose was higher than 0.50%. From the physiological point of view, it seems wise to decrease the glucose concentration substantially from that so often recommended for the treatment of diarrhoea in developed countries.     

Prevalence of rotavirus-induced diarrhea among children under 5 years in Ilorin, Nigeria

Diarrhoea disease is an important cause of morbidity and mortality in Nigerian children and rotavirus has been identified as an important causative agent among children below 5 years. We determined the prevalence of rotavirus-induced diarrhoea among under-5 s by electrophenotyping. Stool samples were collected from eligible subjects who presented with acute diarrhoea. The samples were processed for viral studies by electrophenotyping. Among the 299 subjects recruited, 55.9% were positive for rotavirus. Eighty percent of the recruited patients were below 24 months. There was a significant decrease (p-value = 0.00001) in the prevalence of rotavirus among diarrhoea patients above the age of 24 months when compared with those below this age group. Rotavirus was associated with higher morbidity and mortality. We conclude that rotavirus is the most important cause of diarrhoea among children <5 years in Ilorin, Nigeria and its prevalence is highest in the first 2 years of life. Adequate rehydration should be regarded as the mainstay of management.     

Shame if you do – shame if you don't: women's experiences of infant feeding

Emotions such as guilt and blame are frequently reported by non‐breastfeeding mothers, and fear and humiliation are experienced by breastfeeding mothers when feeding in a public context. In this paper, we present new insights into how shame‐related affects, cognitions and actions are evident within breastfeeding and non‐breastfeeding women's narratives of their experiences. As part of an evaluation study of the implementation of the UNICEF UK Baby Friendly Initiative Community Award within two primary (community based) care trusts in North West England, 63 women with varied infant feeding experiences took part in either a focus group or an individual semi‐structured interview to explore their experiences, opinions and perceptions of infant feeding. Using a framework analysis approach and drawing on Lazare's categories of shame, we consider how the nature of the event (infant feeding) and the vulnerability of the individual (mother) interact in the social context to create shame responses in some breastfeeding and non‐breastfeeding mothers. Three key themes illustrate how shame is experienced and internalised through ‘exposure of women's bodies and infant feeding methods’, ‘undermining and insufficient support’ and ‘perceptions of inadequate mothering’. The findings of this paper highlight how breastfeeding and non‐breastfeeding women may experience judgement and condemnation in interactions with health professionals as well as within community contexts, leading to feelings of failure, inadequacy and isolation. There is a need for strategies and support that address personal, cultural, ideological and structural constraints of infant feeding.     

Clinical associations of Norwalk-like virus in the stools of children

From among 1,360 stool specimens examined during the 19-month period from March 1982 to September 1983, small round-structured viruses, morphologically indistinguishable from the Norwalk agent, were detected by electron microscopy in 42 specimens from 28 children. Diarrhoea was mild, and vomiting, although frequently observed, was not an invariable feature. Mild pyrexia occurred in three patients. Many cases occurred some time after admission to the ward; this and other features suggested a hospital-acquired infection. These cases in particular tended to have other viral infectious agents detected at the same time. Persistent diarrhoea occurred in only three cases; one with preexisting gastrointestinal pathology, and two with a combined Norwalk-like agent, astrovirus, and rotavirus infection.     

Diagnosis and prognosis of wheezing disorders in young children in the city of São Paulo, Southeast Brazil

Three‐hundred‐and‐ninety‐seven children aged 2–59 mo presenting to the paediatric emergency departments of five public hospitals in São Paulo, Brazil, with an acute episode of lower respiratory disease were examined. The children were classified into the following diagnostic categories: acute bronchitis, acute bronchiolitis, pneumonia, asthma, post‐bronchiolitis wheezing and wheezing of uncertain aetiology. Three years after the initial study, the homes of the children diagnosed as asthmatic or as having wheezing of uncertain aetiology were visited to collect information on subsequent episodes of lower respiratory disease. This paper reports the proportional incidence of different categories of lower respiratory disease and the results of an analysis to investigate clinical features that might distinguish wheezing children between those with asthma and those with an infectious disease. The predictions made for children with wheezing of uncertain aetiology were then compared with the follow‐up data. Recurrent wheezing disorders (asthma, post‐bronchiolitis wheezing) were common in the study sample (47% of children). Thirty‐six percent of children with an initial diagnosis of wheezing of uncertain aetiology were diagnosed as asthmatic by another doctor over the next 3 y. We were unable to identify any clinical features that were useful in identifying those children likely to be diagnosed subsequently as asthmatic. Conclusions: The use of a diagnostic category similar to that which we have called “wheezing of uncertain aetiology” might help to alert physicians early to the possibility of asthma without interfering in the management of the illness. Such a classification might also be useful in epidemiological investigations of the aetiology of lower respiratory diseases.     

Bacterial microflora of the upper gastrointestinal tract in infants with protracted diarrhoea

The aerobic and anaerobic bacterial microflora of the upper gastrointestinal tract in infants with protracted diarrhoea has been described and compared with a group of control infants without diarrhoea. The duodenal juice of patients with protracted diarrhoea was rarely sterile and was characterized by an increase in numbers and types of microorganisms and by the presence of coliforms, particularly Esch. coli. In individual patients the same serotypes of Esch. coli were found throughout the intestinal tract. The presence of Esch. coli in the upper small intestine may be as important to the aetiology of protracted diarrhoea as it is to acute diarrhoea.     

Acute infectious diarrhoea in children: new insights in antisecretory treatment with racecadotril

In developing countries acute infectious diarrhoea remains one of the leading causes of death among young children, especially those under 1 year of age. In contrast, in industrialized nations the death rate is very low, although the disease is an important cause of morbidity and consumes substantial healthcare costs. A variety of viral, bacterial and parasitic organisms have been implicated in the pathogenesis of acute diarrhoea. The primary objectives of treatment of acute infectious diarrhoea are correction of dehydration with oral replacement therapy (ORT) and maintenance of good nutritional status via food intake. With regards drug therapy antimicrobial agents are not usually recommended since the disease is generally self-limiting. Racecadotril is powerful and selective enkephalinase inhibitor and has emerged as a promising drug in the antisecretory therapy of acute infectious diarrhoea in children. CONCLUSION: There is encouraging evidence that treatment with racecadotril can provide clinically relevant symptomatic relief by reducing the severity and duration of diarrhoeal episodes. The drug is well tolerated and has a favourable safety profile. However, further comparative studies and cost-effectiveness analyses are needed to define the position of the drug in the management of diarrhoeal illness in children.     

Facilitated tucking as a non‐pharmacological intervention for neonatal pain relief: is it clinically feasible?

There is an impressive body of knowledge on pain management in infants hospitalized in neonatal intensive care units. However, deficits in the clinical management of pain in these infants remain. One reason is the gap between research evidence and translation of this knowledge into the clinical setting. This is particularly true for non‐pharmacological pain‐relieving methods. Effective performance of some of these methods requires additional staffing and time. This viewpoint articles describes the clinical challenges associated with implementing ‘facilitated tucking’. Although ‘facilitated tucking’ is described as an efficient method for acute pain relief, the clinical facilitators required to successfully implement such a resource consuming‐intervention remain unclear. Conclusion: Translational research on the feasibility of using ‘facilitated tucking’ in the management of neonatal pain is warranted, including the economic impact of this intervention. Increased manpower costs need to be weighed against the possible long‐term economical consequences of pain exposure in infants.     

Epidemiological and clinical characteristics of acute and persistent diarrhoea in rural Bangladeshi children

A community-based longitudinal study of acute and persistent diarrhoea in 705 children less than five years old was carried out for a year in a rural area of Bangladesh. Diarrhoea morbidity data were collected from each study child every fourth day by home visit. Clinical features of diarrhoeal episodes and diarrhoeal management information were documented. The overall diarrhoeal incidence rate in the study children was 4.6 episodes per child per year. The incidence of persistent diarrhoea was 34/100 child-years. Persistent diarrhoea was positively associated with young age and more severe illness, characterized by the presence of clinical dehydration or blood in the stool in the first week. Use of ORT in the first week was positively associated and use of an antibiotic was negatively associated with the occurrence of persistent diarrhoea. Reduced breast-feeding and consumption of cow's milk at some time during the episode were also positively associated with persistence. This would suggest that appropriate fluid and dietary management for all episodes should be the goal. Children with more severe initial illness characterized by the presence of blood in the stool or clinical dehydration should have more careful follow-up to identify persistent episodes and adverse nutritional effects. Breastfeeding should be continued during acute diarrhoea, but the role of ORT, antibiotics and cow's milk deserves further investigation.     

Recurrent and persistent diarrhoea in a rural Zimbabwean community: a prospective study.

Prospective surveillance of patterns of diarrhoeal disease was conducted in a cohort of 204 young children living in a rural community in Zimbabwe. Trained field assistants recorded morbidity data obtained by weekly recall of mothers. Diarrhoea was defined by a commonly used local word, and a diarrhoea-free gap of three or more days was taken to signify a new attack. Diarrhoea was common in this study population with a peak incidence between 6 and 18 months of age. There was, however, wide individual variability in diarrhoea attack rates (range 0 to 20 attacks) during the 22 month study period. Whilst only 6 per cent of the recorded diarrhoea episodes were persistent (lasting longer than 14 days), a high proportion (26 per cent) of subjects had at least one attack of persistent diarrhoea (PD) during follow up. Children who had frequent attacks of acute diarrhoea also tended to have PD; PD was rare in those with few attacks. Thus, within this uniformly deprived African community, there were individuals who had a much higher susceptibility to diarrhoea compared to others. An understanding of this variability may point the way towards more effective interventions in the control of diarrhoeal disease.