Intestinal permeability and diarrhoeal disease in Aboriginal Australians

Abstract

Background-Northern Territory Aboriginal children hospitalised with acute gastroenteritis have high rates of acidosis, hypokalaemia, and dehydration. Aims-To determine whether Aboriginal children with and without diarrhoea have greater impairment in intestinal function than non-Aboriginal children, as assessed by increased permeability ratios. Methods-A descriptive study of 124 children (96 Aboriginal and 28 nonAboriginal) hospitalised with and without diarrhoea. Intestinal permeability was assessed by the lactulose to rhamnose (L-R) ratio from a five hour urine collection. Results-In Aboriginal children, mean L-R ratios (95% confidence intervals) were 18.3 (17.1 to 19.6) with diarrhoea and 9.0 (7.3 to 11.0) without diarrhoea, and in non-Aboriginal children they were 5.9 (2.8 to 12.3) and 4.2 (3.3 to 5.2), respectively. In patients with diarrhoea, L-R ratios were significantly raised when accompanied by acidosis (mean, 22.8; 95% CI, 17.0 to 30.5), hypokalaemia (mean, 20.7; 95% CI, 15.4 to 27.9), and > 5% dehydration (mean, 24.3; 95% CI, 19.0 to 29.6) compared with none of these complications (mean, 7.0; 95% CI, 3.5 to 13.8). Conclusion-The high incidence of acidosis, hypokalaemia, and dehydration in Aboriginal children admitted with diarrhoeal disease is related to underlying small intestinal mucosal damage. (Arch Dis Child 1999;81:304-308) Keywords: intestinal absorption; diarrhoea; Aboriginal children It is well recognised that hospitalised Aboriginal children in the Top End of Australia have more severe manifestations of diarrhoeal disease than non-Aboriginal children.1 2 These include high rates of hypokalaemia, acidosis, and lactose intolerance, particularly in those with underlying malnutrition. We believe that these complications are related to the severity of the underlying small bowel damage, which can be measured non-invasively in urine by the lactulose to rhamnose (L-R) test of intestinal permeability-a validated non-invasive test of small bowel mucosal barrier and absorptive functions.3-9 Rhamnose recovery is a measure of mucosal absorptive capacity, whereas lactulose permeability reflects barrier function. Mucosal damage or loss of villous surface area alters the rate of permeation of the sugars across the mucosal surface, with decreased rhamnose and increased lactulose recovery resulting in high L-R ratios.10 After oral administration of the sugar solution, mean urine recovery in normal subjects after five hours is about 0.25% of the lactulose and 10% of the rhamnose, giving a mean ratio of 0.025. 11For ease of expression, we have multiplied L-R ratios by 100 so that 0.025 becomes 2.5. The normal mean L-R ratio (95% confidence intervals) from studies in developed countries using this technique is 2.7 (0.8 to 5.2), 7 but there is considerable geographical variation in normal adult subjects in the developing world, with mean values varying from 4.9 to 15.6 in a recent review by Menzies et al. 12

Critical appraisal of the management of severe malnutrition: 3. Complications

“…Hypokalaemia affects >70% of Aboriginal children in Darwin who are hospitalised with diarrhoeal cases, most of whom are also moderately malnourished. The main contributor to hypokalaemia is osmotic diarrhoea due to underlying partial villous atrophy, particularly with Strongyloides stercoralis infection and during recovery from metabolic acidosis due to dehydration and loss of stool bicarbonate 6,7 . Hypokalaemia and low total body potassium are common in kwashiorkor, which also has the most severe enteropathy, so osmotic diarrhoea is likely to be common if high‐lactose diets are administered, which exceed the lactase threshold.…”

Effect of Cryptosporidium parvum infection on the absorptive capacity and paracellular permeability of the small intestine in neonatal calves

“…This morphological damage leads to a decrease in enzymatic activity and reduction of the absorptive surface, which finally leads to maldigestion and malabsorption followed by diarrhoea (Argenzio et al, 1990;Gookin et al, 2002). Studies on infected children, moreover, indicate that mucosal damage caused by cryptosporidia is associated with higher paracellular permeability of the intestine and an impairment of the mucosal barrier function (Kukuruzovic et al, 1999).…”

Childhood infections in the tropical north of Australia

“…Aboriginal children in the Top End of Australia have higher hospitalization rates and more severe manifestations of diarrhoeal disease (e.g. hypokalaemia, acidosis and lactose intolerance) than non‐Aboriginal children 30,31 . For example, acidosis (bicarbonate < 18 mmol/L) was documented in 58% and hypokalaemia (< 3.5 mmol/L) in 69% of recent paediatric diarrhoeal admissions to Royal Darwin Hospital.…”

“…For example, acidosis (bicarbonate < 18 mmol/L) was documented in 58% and hypokalaemia (< 3.5 mmol/L) in 69% of recent paediatric diarrhoeal admissions to Royal Darwin Hospital. These complications have been shown to be related to the severity of underlying small bowel damage as measured by the lactulose/ rhamnose (L/R) test of intestinal permeability 31 . In Aboriginal children with diarrhoeal disease, the degree of small bowel mucosal damage correlated highly with the presence of acidosis, hypokalaemia and severe dehydration assessed both clinically and by weight change after rapid intravenous rehydration 31,32 .…”

“…These complications have been shown to be related to the severity of underlying small bowel damage as measured by the lactulose/ rhamnose (L/R) test of intestinal permeability 31 . In Aboriginal children with diarrhoeal disease, the degree of small bowel mucosal damage correlated highly with the presence of acidosis, hypokalaemia and severe dehydration assessed both clinically and by weight change after rapid intravenous rehydration 31,32 . Aboriginal control children without diarrhoea or malnutrition, had over twice the mean L/R ratio of non‐Aboriginal control children, indicating the presence of an asymptomatic environmental/tropical enteropathy syndrome which studies from overseas have attributed to contamination of food and water, and to unhygienic living conditions 33 .…”