Exploring the paediatric gastrointestinal anatomy by generating novel data on fluid volumes, localisation and composition

Papadatou Soulou, Eleni (2021). Exploring the paediatric gastrointestinal anatomy by generating novel data on fluid volumes, localisation and composition. University of Birmingham. Ph.D.

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A novel method for magnetic resonance image (MRI) analysis was developed to measure fluid volumes in paediatric GI images. A combination of the HOROS and ImageJ softwares was used. The method was able to i) identify the water content in the paediatric gastrointestinal (GI) tract and to ii) quantify its volume. Data from 32 fasted children (aged 0-16 years) and 23 fluid-fed (aged 8-16 years) was evaluated. Previous studies that included adult populations showed that water in the GI tract does not exist in a continuous form but creates “fluid pockets”. The mean volume of fluid pockets in the small intestine was 7.4 ml for the fasted state and 30.4 ml for the fluid fed state. This study demonstrated that the water content has a discontinuous pattern in the form of fluid pockets for paediatric population as well. The location and the volume of the paediatric GI fluid pockets can have a significant impact on paediatric oral drug absorption.
These novel paediatric GI data have been input into the physiologically based pharmacokinetic model (PBPK) model SimCyp, in an attempt to update the software and its current paediatric default mode.
Additionally, characterisation of simulated gastric and intestinal fluids took place. Characterisation methods used for human samples analysis were developed by working on simulated gastric and intestinal fluids. In total, 55 children have participated aged 11 months to 15 years. From them, 53 gastric fluid samples and 40 intestinal samples were obtained. The human samples were characterised for their pH, buffer capacity and osmolality. It was observed that gastric osmolality ranged from 1-615 mOsm/kg, while the intestinal osmolality ranged from 35-631 mOsm/kg. the median pH values were 2.5 for gastric fluids and 3.27 for intestinal fluids. The buffer capacity did not change significantly as both gastric and intestinal buffer capacity values displayed medial values of 12 mΜ/L/ΔpH.
A literature search was conducted to identify the bibliography describing how the paediatric gastrointestinal physiology and anatomy changes in malnourished children. The narrative review demonstrated that several differences in the GI anatomy and physiology, including reduced saliva secretion, increased gastric pH, slower gastric emptying, increased levels of bacteria in the small intestine, reduced surface area of intestinal villi and increased intestinal permeability. Many of these data were older than 30 years and included heterogeneous population; therefore, future work should focus on generating new, updated data on the impact of malnutrition on the paediatric GI tract, and subsequently on oral drug absorption.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Pharmacy
Funders: Other
Other Funders: Janssen Pharmaceuticals
Subjects: R Medicine > RS Pharmacy and materia medica
URI: http://etheses.bham.ac.uk/id/eprint/11688


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