/* Distributed under the Apache License, Version 2.0.
   See accompanying NOTICE file for details.*/

#include "engine/PulseConfiguration.h"
#include "engine/common/controller/CompartmentManager.h"
#include "engine/common/controller/SubstanceManager.h"
#include "engine/common/system/physiology/EndocrineModel.h"

// Dependent Systems
#include "cdm/system/physiology/SEEnergySystem.h"
// Actions
#include "cdm/engine/SEActionManager.h"
#include "cdm/engine/SEPatientActionCollection.h"
#include "cdm/patient/actions/SEAcuteStress.h"
// CDM
#include "cdm/patient/SEPatient.h"
#include "cdm/substance/SESubstance.h"
#include "cdm/compartment/fluid/SELiquidCompartment.h"
#include "cdm/properties/SEScalarAmountPerTime.h"
#include "cdm/properties/SEScalarMass.h"
#include "cdm/properties/SEScalarMassPerAmount.h"
#include "cdm/properties/SEScalarMassPerVolume.h"
#include "cdm/properties/SEScalarTime.h"
#include "cdm/properties/SEScalar0To1.h"
#include "cdm/utils/GeneralMath.h"

namespace pulse
{
  EndocrineModel::EndocrineModel(Data& data) : EndocrineSystem(data.GetLogger()), Model(data)
  {
    Clear();
  }

  EndocrineModel::~EndocrineModel()
  {
    Clear();
  }

  void EndocrineModel::Clear()
  {
    EndocrineSystem::Clear();
    m_splanchnicInsulin = nullptr;
  }

  //--------------------------------------------------------------------------------------------------
  /// \brief
  /// Initializes system properties to valid homeostatic values.
  ///
  /// \details
  /// For stabilization only!
  /// Called AFTER Setup when stabilizing a new patient
  //--------------------------------------------------------------------------------------------------
  void EndocrineModel::Initialize()
  {
    Model::Initialize();
  }

  //--------------------------------------------------------------------------------------------------
  /// \brief
  /// Initializes parameters for Endocrine Class
  ///
  /// \details
  /// Called during both State loading and Patient Stabilization
  /// Pull and setup up our data (can be from other systems)
  /// Initialize will be called after this and can overwrite any of this data (only if stabilizing)
  //--------------------------------------------------------------------------------------------------
  void EndocrineModel::SetUp()
  {
    SELiquidCompartment* aorta = m_data.GetCompartments().GetLiquidCompartment(pulse::VascularCompartment::Aorta);
    SELiquidCompartment* rkidney = m_data.GetCompartments().GetLiquidCompartment(pulse::VascularCompartment::RightEfferentArteriole);
    SELiquidCompartment* lkidney = m_data.GetCompartments().GetLiquidCompartment(pulse::VascularCompartment::LeftEfferentArteriole);
    m_aortaNorepinephrine = aorta->GetSubstanceQuantity(m_data.GetSubstances().GetNorepi());
    m_rKidneyEpinephrine = rkidney->GetSubstanceQuantity(m_data.GetSubstances().GetEpi());
    m_lKidneyEpinephrine = lkidney->GetSubstanceQuantity(m_data.GetSubstances().GetEpi());
    SESubstance* insulin = &m_data.GetSubstances().GetInsulin();
    m_insulinMolarMass_g_Per_mol = insulin->GetMolarMass(MassPerAmountUnit::g_Per_mol);
    m_splanchnicInsulin = m_data.GetCompartments().GetLiquidCompartment(pulse::VascularCompartment::Splanchnic)->GetSubstanceQuantity(*insulin);
  }

  void EndocrineModel::AtSteadyState()
  {

  }

  //--------------------------------------------------------------------------------------------------
  /// \brief
  /// Endocrine process function
  ///
  /// \details
  /// Currently, only two hormones exists in the Pulse system: epinephrine and insulin. If the metabolic rate 
  /// rises above the basal rate, epinephrine is released. This is meant to simulate a sympathetic 
  /// nervous system response. The masses of the hormones are increased in the kidneys' efferent arterioles. 
  /// The hormones will then circulate using the transport and substances methodology.
  //--------------------------------------------------------------------------------------------------
  void EndocrineModel::Process(bool /*solve_and_transport*/)
  {
    ReleaseEpinephrineAndNorepinephrine();
    SynthesizeInsulin();
    ComputeExposedModelParameters();
  }
  void EndocrineModel::PostProcess(bool /*solve_and_transport*/)
  {

  }

  void EndocrineModel::ComputeExposedModelParameters()
  {

  }

  //--------------------------------------------------------------------------------------------------
  /// \brief
  /// Calculate the rate of insulin production 
  ///
  /// \details
  /// The insulin production rate is calculated based on the relevant range of glucose and instantaneous concentration of glucose in the aorta
  /// (representative of the body). The equation for insulin production is from \cite tolic2000insulin
  //--------------------------------------------------------------------------------------------------
  void EndocrineModel::SynthesizeInsulin()
  {
    double insulinMassDelta_g = 0;
    double bloodGlucoseConcentration_mg_Per_dL = m_data.GetSubstances().GetGlucose().GetBloodConcentration(MassPerVolumeUnit::mg_Per_dL);
    if (bloodGlucoseConcentration_mg_Per_dL >= 80)
    {
      // Linear function for blood glucose between 80-150 mg/dL and insulin synthesis of 100-475 pmol/min [polonsky1987insulin]
      double insulinSynthesisRate_pmol_Per_min = (5.357 * bloodGlucoseConcentration_mg_Per_dL) - 328.56;
      GetInsulinSynthesisRate().SetValue(insulinSynthesisRate_pmol_Per_min, AmountPerTimeUnit::pmol_Per_min);

      insulinMassDelta_g = Convert(insulinSynthesisRate_pmol_Per_min, AmountPerTimeUnit::pmol_Per_min, AmountPerTimeUnit::mol_Per_s);
      insulinMassDelta_g *= m_insulinMolarMass_g_Per_mol * m_data.GetTimeStep_s();
    }
    m_splanchnicInsulin->GetMass().IncrementValue(insulinMassDelta_g, MassUnit::g);
    m_splanchnicInsulin->Balance(BalanceLiquidBy::Mass);
  }

  //--------------------------------------------------------------------------------------------------
  /// \brief
  /// Release epinephrine and norepinephrine into the bloodstream and handle sympathetic responses
  ///
  /// \details
  /// Epinephrine is released at a basal rate of .18 ug/min \cite best1982release from the kidneys. During
  /// certain events, the release rate of epinephrine increases. This is sympathetic response.
  /// 
  /// Norepinephrine is released at a basal rate of .7 ug/min to maintain basal plasma concentration with drug clearance. The release of norepi 
  /// is inversely releated to epinephrine release. This is the parasympathetic response.
  //--------------------------------------------------------------------------------------------------
  void EndocrineModel::ReleaseEpinephrineAndNorepinephrine()
  {
    SEPatient& Patient = m_data.GetCurrentPatient();
    double patientWeight_kg = Patient.GetWeight(MassUnit::kg);
    double epinephrineBasalReleaseRate_ug_Per_min = .00229393 * patientWeight_kg; //We want it to be ~.18 ug/min for our StandardMale
    double epinephrineRelease_ug = (epinephrineBasalReleaseRate_ug_Per_min / 60) * m_data.GetTimeStep_s();  //amount released per timestep
    
    double norepinephrineBasalReleaseRate_ug_Per_min = 0.008974 * patientWeight_kg; //We want it to be ~.7 ug/min for our StandardMale
    double norepinephrineRelease_ug = (norepinephrineBasalReleaseRate_ug_Per_min / 60) * m_data.GetTimeStep_s();  //amount released per timestep

    double currentMetabolicRate_W = m_data.GetEnergy().GetTotalMetabolicRate(PowerUnit::W);
    double basalMetabolicRate_W = Patient.GetBasalMetabolicRate(PowerUnit::W);
    double epiReleaseMultiplier = 1.0;
    double norepiReleaseMultiplier = 1.0;

    // If we have exercise, release more epi. Release multiplier is a sigmoid based on the total metabolic rate
    // with the maximum multiplier adapted from concentration data presented in @cite tidgren1991renal and @cite stratton1985hemodynamic
    // and the shape adjusted to match data in @cite tidgren1991renal.
    if (currentMetabolicRate_W > basalMetabolicRate_W)
    {
      double exercise_W = (currentMetabolicRate_W - basalMetabolicRate_W);
      double e50_W = 190;
      double eta = 0.035;
      double maxMultiplier = 18.75;
      epiReleaseMultiplier = 1.0 + GeneralMath::LogisticFunction(maxMultiplier, e50_W, eta, exercise_W);
      norepiReleaseMultiplier = 1.0 / epiReleaseMultiplier;
    }

    norepinephrineRelease_ug *= norepiReleaseMultiplier;
    m_aortaNorepinephrine->GetMass().IncrementValue(norepinephrineRelease_ug, MassUnit::ug);

    // If we have a stress/anxiety response, release more epi
    if (m_data.GetActions().GetPatientActions().HasAcuteStress())
    {
      double severity = m_data.GetActions().GetPatientActions().GetAcuteStress().GetSeverity().GetValue();

      //The highest stress multiplier we currently support is 30
      epiReleaseMultiplier += GeneralMath::LinearInterpolator(0, 1, 0, 30, severity);
    }

    epinephrineRelease_ug *= epiReleaseMultiplier;

    m_rKidneyEpinephrine->GetMass().IncrementValue(0.5 * epinephrineRelease_ug, MassUnit::ug);
    m_lKidneyEpinephrine->GetMass().IncrementValue(0.5 * epinephrineRelease_ug, MassUnit::ug);
  }
END_NAMESPACE