Mathematical Model of Ventilation Response to Inhaled Carbon Monoxide

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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

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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

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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.

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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

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Publication Results

• Buildup of carboxyhemoglobin with reduction in
  oxygen delivery to the brain leads to anaerobic
  glycolysis and buildup of lactate

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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

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Model Schematic
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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

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JSIM Model Results - Ventilation

• With increase in CO CO2, and decrease of O2,
  ventilation initially increased and then decreased

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JSIM results Lactate Generation

• Lactate generation in the brain due to increased
  anaerobic respiration due to hypoxia

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JSIM results Brain activity

• Brain activity decreased due to lower pressure in
  the brain capillaries

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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

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JSIM results CO2 components

• CO2 components
• HCO3- is majority of the CO2
• Carbamino and CO2 in plasma is in small amounts
  of CO2

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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.