Transcript on model by Raymond Yakura - the NSR Physiome Project!

Mathematical Model of
Ventilation Response to
Inhaled Carbon Monoxide
Stuhmiller & Stuhmiller, J Appl. Physiol. 98:
2033-44 (2005)
Raymond Yakura
May 31, 2006
BIOEN 589
Uses of Model

Fires generate noxious gases
• Results in increased carbon dioxide,
increased carbon monoxide and reduced
oxygen

Dramatic effects on ventilation which
vary with gas composition and
exposure duration
Model Summary



Dynamic Physiological Model
Authors used Matlab with Simulink
Incorporates models from many
different sources into one integrated
model
• Sources include Duffin et al., Ursino et
al., Hill et al., Gomez, Roughton and
Darling, Doblar et al.
Results from Publication

With CO acute
inhalation,
hyperventilation first
results and then a
subsequent ventilation
depression
• Hyperventilation caused
by hypoxia which
activates the peripheral
chemoreceptors
• Ventilation depression
caused by generation of
lactic acid in the brain
and decreased brain
activity
Publication Results

Buildup of carboxyhemoglobin with
reduction in oxygen delivery to the
brain leads to anaerobic glycolysis
and buildup of lactate
Model Subsets

Metabolism
• Oxygen metabolism, oxygen transfer to the brain, lactic acid
generation, anaerobic limit

Cardiac Output
• Blood flow to the brain increases during hypoxia

Circulatory System
• Mass balance equations for O2, CO2 and CO

Blood Chemistry
• Hemoglobin saturation, O2 /CO partition, acid-base balance,
CO2 dissociation

Ventilation
• Chemoreceptor response
• Brain activity response
• Combined ventilatory response

Respiration System
• Total ventilation and effects of dead space and humidification
Model Schematic
JSIM model



JSim 1.6.62 used for this project
Event driven to input O2, CO2 and CO
Introduced memory into system to
detect Lactate changes analogous to
a D-Flip Flop in digital circuit design
JSIM Model Results - Ventilation

With increase in
CO & CO2, and
decrease of O2,
ventilation
initially increased
and then
decreased
JSIM results – Lactate Generation

Lactate
generation in
the brain due to
increased
anaerobic
respiration due
to hypoxia
JSIM results: Brain activity

Brain activity
decreased
due to lower
pressure in
the brain
capillaries
JSIM results: Tidal volume and
Breathing Frequency


Tidal volume
increased due to
CO2 increase
Combined f
(breathing
frequency) started
to initially increase
due to
chemoreceptors
activation, but
decreased later on
due to lower brain
activity
JSIM results: CO2 components

CO2
components
• HCO3- is
majority of
the CO2
• Carbamino
and CO2 in
plasma is in
small amounts
of CO2
Model Limitations

Article
• Errors and notational changes in the article
• Model Schematic and equations do not indicate
a feedback loop, although the graphs implicitly
indicate a feedback loop

Model in JSIM
• Not a feedback loop
• P_O2_Brain and O2art are separate events
• Convergence issues due to the number of
equations and initiation values resulting in
increasing the error tolerance that decreases
accuracy.