Team:Evry/Modeltr1

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Iron coli project

Disease model

Introduction

In the very beginning of the project, we focused on the duodenum and the iron absorbed by it. In order to determine if a flush treatment strategy was viable, we first had to model the behaviour of the duodenum regarding iron absorption.

Observations

60% of iron absorption takes place in the duodenum, the last 40% in the jejunum. The duodenum is located in the upper intestines, right after the stomach, and is usually 300mm long.

Absorption
Figure 1 : Overview of the iron regulation system in human body.

A healthy person absorbs about 10% (2mg a day) of the daily iron uptake, while a hemochromatosis person's absorption varies between 50% and 100% of the daily iron uptake[1].

Goals

Our goal in this part of the model is to create a generic duodenal iron absorption model so that:

Assumptions

  • Our bacteria don't settle in the duodenum
  • No regulation in the patient's iron absorption
  • Constant iron flow
  • Homogeneous fluid
  • The bacterial quantity is constant
  • The bacterial natural absorption is insignificant compared to the chelation
  • The patient ingests 20mg of iron per day (Guideline Daily Amounts)

Materials and methods

This model simulates the digestion process of one meal from the duodenum's point of view.
The duodenum is considered as a cylinder in which a homogeneous fluid flows. So, this model is divided into three steps: the filling of duodenum, the steady state flowing step and the emptying.
This model has two variables : the iron disolved in the middle (S) and the absorbed iron (A).
We considered the chyme arrives in the duodenum at a constant rate. S has a linear component Sp which represents the pulses. The also are an emptying component and an absorption component.
We assumed a linear absorption and a negative feedback regulation for A.

Finally:

Name Unit Description Reference
Sp mol.s-1 Iron pulse [1][2]
v m.s-1 Chyme's flow average speed [2]
L m Duodenum length [3]
α s-1 Duodenum absorption rate tuned
σ s-1 Regulation coefficient tuned

Parameters tuning :

As the iron absorption process greatly differs from an individual to an other, α and σ cannot be found in the litterature. We thus had to tune those parameters.
First of all, we know that a hemochromatosic patient absorbs at least 50% of the iron he ingests. Thus, we tuned α to fit this information while assessing σ = 0 (Hemochromatosis : no regulation in iron absorbtion).
Then, since we know that a healthy person absorbs 10% of the ingested iron, we were able to tune σ.

Results

Absorption
Figure 2 : Iron in the middle and absorbed in the duodenum of a Healthy person.

Absorption
Figure 3 : Iron in the middle and absorbed in the duodenum of a sick person.

Conclusion

Models and scripts

This model was made using the Python language. You can download it here.

References:

  1. Physiol Rev 93: 1721–1741, 2013 doi:10.1152/physrev.00008.2013 - Tomas Ganz "SYSTEMIC IRON HOMEOSTASIS"
  2. Calculated from : Computational Modeling and Simulation of the Human Duodenum - B. Hari, S. Bakalis, P. Fryer - 2012
  3. Wikipedia