Baroreceptor clean up and serialization support

engine/cpp/controller/System.h

@@ -14,7 +14,7 @@ protected:
 
   /** @brief - Default system values to their homeostatic values */
   virtual void Initialize() { SetUp(); }
-  virtual void SetUp() = 0;
+  virtual void SetUp() = 0; // Called after Initialize if stablizing, or after serialization if reading in a state
 
   /// Notify systems that steady state has been achieved
   virtual void AtSteadyState() {};

engine/cpp/io/protobuf/PBPulsePhysiology.cpp

@@ -322,6 +322,9 @@ void PBPulsePhysiology::Serialize(const NervousData& src, Nervous& dst)
   dst.m_FeedbackActive = true;
   dst.m_ArterialOxygenBaseline_mmHg = src.arterialoxygenbaseline_mmhg();
   dst.m_ArterialCarbonDioxideBaseline_mmHg = src.arterialcarbondioxidebaseline_mmhg();
+  dst.m_BaroreceptorFeedbackStatus = src.baroreceptorfeedbackstatus();
+  dst.m_BaroreceptorActiveTime_s = src.baroreceptoractivetime_s();
+  dst.m_BaroreceptorMeanArterialPressureBaseline_mmHg = src.baroreceptormeanarterialpressurebaseline_mmhg();
 }
 NervousData* PBPulsePhysiology::Unload(const Nervous& src)
 {
@@ -334,6 +337,9 @@ void PBPulsePhysiology::Serialize(const Nervous& src, NervousData& dst)
   PBPhysiology::Serialize(src, *dst.mutable_common());
   dst.set_arterialoxygenbaseline_mmhg(src.m_ArterialOxygenBaseline_mmHg);
   dst.set_arterialcarbondioxidebaseline_mmhg(src.m_ArterialCarbonDioxideBaseline_mmHg);
+  dst.set_baroreceptorfeedbackstatus(src.m_BaroreceptorFeedbackStatus);
+  dst.set_baroreceptoractivetime_s(src.m_BaroreceptorActiveTime_s);
+  dst.set_baroreceptormeanarterialpressurebaseline_mmhg(src.m_BaroreceptorMeanArterialPressureBaseline_mmHg);
 }
 
 void PBPulsePhysiology::Load(const RenalData& src, Renal& dst)

engine/cpp/physiology/Nervous.cpp

@@ -57,7 +57,6 @@ void Nervous::Initialize()
 {
   PulseSystem::Initialize();
   m_FeedbackActive = false;
-  m_BaroreceptorFeedbackStatus = false;
   GetBaroreceptorHeartRateScale().SetValue(1.0);
   GetBaroreceptorHeartElastanceScale().SetValue(1.0);
   GetBaroreceptorResistanceScale().SetValue(1.0);
@@ -72,7 +71,9 @@ void Nervous::Initialize()
   // Set when feedback is turned on
   m_ArterialOxygenBaseline_mmHg = 0;
   m_ArterialCarbonDioxideBaseline_mmHg = 0;
-  m_BaroreceptorActivityTime_s = 0.0;
+  m_BaroreceptorActiveTime_s = 0.0;
+  m_BaroreceptorFeedbackStatus = false;
+  m_BaroreceptorMeanArterialPressureBaseline_mmHg = 0;
 }
 
 //--------------------------------------------------------------------------------------------------
@@ -85,17 +86,15 @@ void Nervous::Initialize()
 void Nervous::SetUp()
 {
   m_dt_s = m_data.GetTimeStep().GetValue(TimeUnit::s);
-  m_normalizedGammaHeartRate  = m_data.GetConfiguration().GetNormalizedHeartRateIntercept();
-  m_normalizedGammaElastance  = m_data.GetConfiguration().GetNormalizedHeartElastanceIntercept();
-  m_normalizedGammaCompliance = m_data.GetConfiguration().GetNormalizedComplianceIntercept();
-  m_normalizedGammaResistance = m_data.GetConfiguration().GetNormalizedResistanceIntercept();
-  m_normalizedAlphaHeartRate  = m_data.GetConfiguration().GetNormalizedHeartRateSympatheticSlope();
-  m_normalizedAlphaElastance  = m_data.GetConfiguration().GetNormalizedHeartElastanceSympatheticSlope();
-  m_normalizedAlphaCompliance = m_data.GetConfiguration().GetNormalizedComplianceParasympatheticSlope();
-  m_normalizedAlphaResistance = m_data.GetConfiguration().GetNormalizedResistanceSympatheticSlope();
-  m_normalizedBetaHeartRate   = m_data.GetConfiguration().GetNormalizedHeartRateParasympatheticSlope();
-  m_meanArtrialPressurePatientBaseline_mmHg = m_data.GetPatient().GetMeanArterialPressureBaseline().GetValue(PressureUnit::mmHg);
-  m_meanArterialPressureBaseline_mmHg = m_meanArtrialPressurePatientBaseline_mmHg;
+  m_NormalizedGammaHeartRate  = m_data.GetConfiguration().GetNormalizedHeartRateIntercept();
+  m_NormalizedGammaElastance  = m_data.GetConfiguration().GetNormalizedHeartElastanceIntercept();
+  m_NormalizedGammaCompliance = m_data.GetConfiguration().GetNormalizedComplianceIntercept();
+  m_NormalizedGammaResistance = m_data.GetConfiguration().GetNormalizedResistanceIntercept();
+  m_NormalizedAlphaHeartRate  = m_data.GetConfiguration().GetNormalizedHeartRateSympatheticSlope();
+  m_NormalizedAlphaElastance  = m_data.GetConfiguration().GetNormalizedHeartElastanceSympatheticSlope();
+  m_NormalizedAlphaCompliance = m_data.GetConfiguration().GetNormalizedComplianceParasympatheticSlope();
+  m_NormalizedAlphaResistance = m_data.GetConfiguration().GetNormalizedResistanceSympatheticSlope();
+  m_NormalizedBetaHeartRate   = m_data.GetConfiguration().GetNormalizedHeartRateParasympatheticSlope();
 }
 
 void Nervous::AtSteadyState()
@@ -106,7 +105,7 @@ void Nervous::AtSteadyState()
   // The set-points (Baselines) get reset at the end of each stabilization period.
   m_ArterialOxygenBaseline_mmHg = m_data.GetBloodChemistry().GetArterialOxygenPressure(PressureUnit::mmHg);
   m_ArterialCarbonDioxideBaseline_mmHg = m_data.GetBloodChemistry().GetArterialCarbonDioxidePressure(PressureUnit::mmHg);
-  m_meanArtrialPressurePatientBaseline_mmHg = m_data.GetPatient().GetMeanArterialPressureBaseline().GetValue(PressureUnit::mmHg);
+  m_BaroreceptorMeanArterialPressureBaseline_mmHg = m_data.GetPatient().GetMeanArterialPressureBaseline().GetValue(PressureUnit::mmHg);
   // The baroreceptor scales need to be reset any time the baselines are reset.
   GetBaroreceptorHeartRateScale().SetValue(1.0);
   GetBaroreceptorHeartElastanceScale().SetValue(1.0);
@@ -124,8 +123,11 @@ void Nervous::AtSteadyState()
 //--------------------------------------------------------------------------------------------------
 void Nervous::PreProcess()
 {
-  BaroreceptorFeedback();
-  ChemoreceptorFeedback();
+  if (m_FeedbackActive)
+  {
+    BaroreceptorFeedback();
+    ChemoreceptorFeedback();
+  }
 }
 
 //--------------------------------------------------------------------------------------------------
@@ -163,55 +165,80 @@ void Nervous::PostProcess()
 /// These fractions are used to update the scaling parameters of heart rate, heart elastance, resistance and compliance
 /// for each time step.
 //--------------------------------------------------------------------------------------------------
-/// \todo Add decompensation. Perhaps a reduction in the effect that is a function of blood volume below a threshold... and maybe time.
 void Nervous::BaroreceptorFeedback()
 {
-  if (!m_FeedbackActive)
-    return;
   //First calculate the sympathetic and parasympathetic firing rates:
   double nu = m_data.GetConfiguration().GetResponseSlope();
   double meanArterialPressure_mmHg = m_data.GetCardiovascular().GetMeanArterialPressure(PressureUnit::mmHg);
-  
-  UpdateBaroreceptorThresholds();
-  
-  //Dampen response due to sedation
-  double sedationDampeningEffect = m_data.GetDrugs().GetSedationLevel().GetValue() * 0.35; //maximum slope reduction of 35% - making that up right now
-  //update nu - the slope response of the firing rate
-  //nu *= (1 - sedationDampeningEffect);  TODO: Add this back when I have data for validation
 
   //Adjusting the mean arterial pressure set-point to account for cardiovascular drug effects
-  m_meanArterialPressureBaseline_mmHg = m_meanArtrialPressurePatientBaseline_mmHg //m_MeanArterialPressureNoFeedbackBaseline_mmHg
+  double meanArterialPressureCombinedBaseline_mmHg = m_BaroreceptorMeanArterialPressureBaseline_mmHg
     + m_data.GetDrugs().GetMeanBloodPressureChange(PressureUnit::mmHg)
     + m_data.GetEnergy().GetExerciseMeanArterialPressureDelta(PressureUnit::mmHg);
   
-  double sympatheticFraction = 1.0 / (1.0 + pow(meanArterialPressure_mmHg / m_meanArterialPressureBaseline_mmHg, nu));
-  double parasympatheticFraction = 1.0 / (1.0 + pow(meanArterialPressure_mmHg / m_meanArterialPressureBaseline_mmHg, -nu));
+  //Determine if barorectors are active and for how long
+  double pressureDeviation = meanArterialPressure_mmHg - meanArterialPressureCombinedBaseline_mmHg;
+  double pressureDeviationFraction = std::abs(pressureDeviation) / meanArterialPressureCombinedBaseline_mmHg;
+  if (pressureDeviationFraction > 0.05)
+  {
+    if (!m_BaroreceptorFeedbackStatus)
+    {
+      m_BaroreceptorActiveTime_s = 0.0;
+      m_BaroreceptorFeedbackStatus = true;
+    }
+    else
+    {
+      m_BaroreceptorActiveTime_s += m_dt_s;
+      //Need to change the threshold every 7 minutes based on over activation
+      if (m_BaroreceptorActiveTime_s > 420.0/*s*/)
+      {
+        //Reset the time
+        m_BaroreceptorActiveTime_s = 0.0;
+        //Adjust the threshold by up to 30%
+        m_BaroreceptorMeanArterialPressureBaseline_mmHg += 0.35 * pressureDeviation;
+        m_ss << "Baroreceptor MAP Baseline updated to " << m_BaroreceptorMeanArterialPressureBaseline_mmHg << " mmHg";
+        Info(m_ss);
+      }
+    }
+  }
+  else
+  {
+    m_BaroreceptorFeedbackStatus = false;
+  }
+  
+  // \todo Dampen Baroreceptor response due to sedation
+  //double sedationDampeningEffect = m_data.GetDrugs().GetSedationLevel().GetValue() * 0.35; //maximum slope reduction of 35% - making that up right now
+  //update nu - the slope response of the firing rate
+  //nu *= (1 - sedationDampeningEffect);  TODO: Add this back when I have data for validation
+  
+  double sympatheticFraction = 1.0 / (1.0 + pow(meanArterialPressure_mmHg / meanArterialPressureCombinedBaseline_mmHg, nu));
+  double parasympatheticFraction = 1.0 / (1.0 + pow(meanArterialPressure_mmHg / meanArterialPressureCombinedBaseline_mmHg, -nu));
   
   //Calculate the normalized change in heart rate
   double normalizedHeartRate = GetBaroreceptorHeartRateScale().GetValue();
   double tauHeartRate_s = m_data.GetConfiguration().GetHeartRateDistributedTimeDelay(TimeUnit::s);
-  double deltaNormalizedHeartRate = (1.0 / tauHeartRate_s)*(-normalizedHeartRate + m_normalizedAlphaHeartRate*sympatheticFraction - m_normalizedBetaHeartRate*parasympatheticFraction + m_normalizedGammaHeartRate)*m_dt_s;
+  double deltaNormalizedHeartRate = (1.0 / tauHeartRate_s)*(-normalizedHeartRate + m_NormalizedAlphaHeartRate*sympatheticFraction - m_NormalizedBetaHeartRate*parasympatheticFraction + m_NormalizedGammaHeartRate)*m_dt_s;
   normalizedHeartRate += deltaNormalizedHeartRate;
   GetBaroreceptorHeartRateScale().SetValue(normalizedHeartRate);
   
   //Calculate the normalized change in heart elastance
   double normalizedHeartElastance = GetBaroreceptorHeartElastanceScale().GetValue();
   double tauElastance_s = m_data.GetConfiguration().GetHeartElastanceDistributedTimeDelay(TimeUnit::s);
-  double deltaNormalizedHeartElastance = (1.0 / tauElastance_s)*(-normalizedHeartElastance + m_normalizedAlphaElastance*sympatheticFraction + m_normalizedGammaElastance)*m_dt_s;
+  double deltaNormalizedHeartElastance = (1.0 / tauElastance_s)*(-normalizedHeartElastance + m_NormalizedAlphaElastance*sympatheticFraction + m_NormalizedGammaElastance)*m_dt_s;
   normalizedHeartElastance += deltaNormalizedHeartElastance;
   GetBaroreceptorHeartElastanceScale().SetValue(normalizedHeartElastance);
   
   //Calculate the normalized change in flow resistance for any cardiovascular resistor
   double normalizedResistance = GetBaroreceptorResistanceScale().GetValue();
   double tauResistance_s = m_data.GetConfiguration().GetSystemicResistanceDistributedTimeDelay(TimeUnit::s);
-  double deltaNormalizedResistance = (1.0 / tauResistance_s)*(-normalizedResistance + m_normalizedAlphaResistance*sympatheticFraction + m_normalizedGammaResistance)*m_dt_s;
+  double deltaNormalizedResistance = (1.0 / tauResistance_s)*(-normalizedResistance + m_NormalizedAlphaResistance*sympatheticFraction + m_NormalizedGammaResistance)*m_dt_s;
   normalizedResistance += deltaNormalizedResistance;
   GetBaroreceptorResistanceScale().SetValue(normalizedResistance);
   
   //Calculate the normalized change in flow compliance for any cardiovascular compliance
   double normalizedCompliance = GetBaroreceptorComplianceScale().GetValue();
   double tauCompliance_s = m_data.GetConfiguration().GetVenousComplianceDistributedTimeDelay(TimeUnit::s);
-  double deltaNormalizedCompliance = (1.0 / tauCompliance_s)*(-normalizedCompliance + m_normalizedAlphaCompliance*parasympatheticFraction + m_normalizedGammaCompliance)*m_dt_s;
+  double deltaNormalizedCompliance = (1.0 / tauCompliance_s)*(-normalizedCompliance + m_NormalizedAlphaCompliance*parasympatheticFraction + m_NormalizedGammaCompliance)*m_dt_s;
   normalizedCompliance += deltaNormalizedCompliance;
   GetBaroreceptorComplianceScale().SetValue(normalizedCompliance);
 #ifdef VERBOSE
@@ -223,65 +250,6 @@ void Nervous::BaroreceptorFeedback()
 #endif
 }
 
-//--------------------------------------------------------------------------------------------------
-/// \brief
-/// Dampens the response of the baroreceptors based on sedation and extended activity.
-///
-/// \details
-/// The baroreceptor setpoints are updated as activity time lengthens, this checks to see if they are active 
-/// (a greater than 10% deviation from the mean arterial pressure).
-//--------------------------------------------------------------------------------------------------
-void Nervous::UpdateBaroreceptorThresholds()
-{
-  UpdateBaroreceptorActivityStatus();
-
-  //Need to change the threshold every 7 minutes based on over activation
-  double thresholdChangeTime_s = 420.0;
-  if (m_BaroreceptorFeedbackStatus && m_BaroreceptorActivityTime_s > thresholdChangeTime_s)
-  {
-    //Adjust the threshold by up to 30%
-    double meanArterialPressure_mmHg = m_data.GetCardiovascular().GetMeanArterialPressure(PressureUnit::mmHg);
-    double pressureDeviation = meanArterialPressure_mmHg - m_meanArterialPressureBaseline_mmHg;
-    m_meanArtrialPressurePatientBaseline_mmHg += 0.35*pressureDeviation;
-    //Reset the time
-    m_BaroreceptorActivityTime_s = 0.0;
-  }
-}
-
-//--------------------------------------------------------------------------------------------------
-/// \brief
-/// Checks to see if the baroreceptors are active and if so how long
-///
-/// \details
-/// The baroreceptor setpoints are updated as activity time lengthens, this checks to see if they are active 
-/// (a greater than 10% deviation from the mean arterial pressure).
-//--------------------------------------------------------------------------------------------------
-void Nervous::UpdateBaroreceptorActivityStatus()
-{
-  //Determine if barorectors are active and for how long
-  double meanArterialPressure_mmHg = m_data.GetCardiovascular().GetMeanArterialPressure(PressureUnit::mmHg);
-  double pressureDeviationFraction = std::abs(meanArterialPressure_mmHg - m_meanArterialPressureBaseline_mmHg) / m_meanArterialPressureBaseline_mmHg;
-  if (pressureDeviationFraction > 0.05)
-  {
-    if (!m_BaroreceptorFeedbackStatus)
-    {
-      m_BaroreceptorActivityTime_s = 0.0;
-      m_BaroreceptorFeedbackStatus = true;
-    }
-    else
-    {
-      m_BaroreceptorActivityTime_s += m_dt_s;
-    }
-  }
-  else
-  {
-    if (m_BaroreceptorFeedbackStatus)
-    {
-      m_BaroreceptorFeedbackStatus = false;
-    }
-  }
-}
-
 //--------------------------------------------------------------------------------------------------
 /// \brief
 /// Checks metrics in the brain to determine events to be thrown
@@ -330,9 +298,6 @@ void Nervous::CheckBrainStatus()
 //--------------------------------------------------------------------------------------------------
 void Nervous::ChemoreceptorFeedback()
 {
-  if (!m_FeedbackActive)
-    return;
-
   double normalized_pO2 = m_data.GetBloodChemistry().GetArterialOxygenPressure(PressureUnit::mmHg) / m_ArterialOxygenBaseline_mmHg;
   double normalized_pCO2 = m_data.GetBloodChemistry().GetArterialCarbonDioxidePressure(PressureUnit::mmHg) / m_ArterialCarbonDioxideBaseline_mmHg;
 

engine/cpp/physiology/Nervous.h

@@ -28,40 +28,36 @@ protected:
   // Set pointers and other member variables common to both homeostatic initialization and loading a state
   void SetUp();
 
-  void AtSteadyState();  
+  void AtSteadyState();
   void PreProcess();
   void Process();
   void PostProcess();
 
   void BaroreceptorFeedback();
-  void UpdateBaroreceptorActivityStatus();
-  void UpdateBaroreceptorThresholds();
   void CheckBrainStatus();
   void ChemoreceptorFeedback();
   void SetPupilEffects();
 
-  // Serializable member variables (Set in Initialize and in schema)    
+  // Serializable member variables (Set in Initialize and in schema)
   double m_ArterialOxygenBaseline_mmHg;
   double m_ArterialCarbonDioxideBaseline_mmHg;
+  //Baroreceptor threshold parameters
+  bool   m_BaroreceptorFeedbackStatus;
+  double m_BaroreceptorActiveTime_s;
+  double m_BaroreceptorMeanArterialPressureBaseline_mmHg;
 
   // Stateless member variable (Set in SetUp())
-  bool m_FeedbackActive;
-  bool m_BaroreceptorFeedbackStatus;
+  bool m_FeedbackActive; // An overall flag used to turn off baro/chemo receptors during stabilization
   double m_dt_s;
 
-  //Baroreceptor threshold parameters
-  double m_BaroreceptorActivityTime_s;
-  double m_meanArterialPressureBaseline_mmHg;
-  double m_meanArtrialPressurePatientBaseline_mmHg;
-
   // Configuration fractions representing the amount by which each quantity can change due to baroreceptors;
-  double m_normalizedGammaHeartRate;
-  double m_normalizedGammaElastance;
-  double m_normalizedGammaCompliance;
-  double m_normalizedGammaResistance;
-  double m_normalizedAlphaHeartRate;
-  double m_normalizedAlphaElastance;
-  double m_normalizedAlphaCompliance;
-  double m_normalizedAlphaResistance;
-  double m_normalizedBetaHeartRate;
+  double m_NormalizedGammaHeartRate;
+  double m_NormalizedGammaElastance;
+  double m_NormalizedGammaCompliance;
+  double m_NormalizedGammaResistance;
+  double m_NormalizedAlphaHeartRate;
+  double m_NormalizedAlphaElastance;
+  double m_NormalizedAlphaCompliance;
+  double m_NormalizedAlphaResistance;
+  double m_NormalizedBetaHeartRate;
 };

schema/proto/pulse/PulsePhysiology.proto

@@ -95,6 +95,9 @@ message NervousData
   cdm.NervousSystemData          Common                                              = 1;
   double                         ArterialOxygenBaseline_mmHg                         = 2;
   double                         ArterialCarbonDioxideBaseline_mmHg                  = 3;
+  bool                           BaroreceptorFeedbackStatus                          = 4;
+  double                         BaroreceptorActiveTime_s                            = 5;
+  double                         BaroreceptorMeanArterialPressureBaseline_mmHg       = 6;
 }
 
 message RenalData