New models of acid-base balance and their application to critical care nephrology  Christos Argyropoulos MD PhD Department...
Goals of acid-base models <ul><li>P atient  C are   : diagnosis and treatment of complex acid-base disorders </li></ul><ul...
Qualifications of an acid-base model (formal)  <ul><li>A general acid-base model should provide: </li></ul><ul><li>the  cl...
Qualifications of an acid-base model (informal)  <ul><li>A general acid-base model should answer the following questions: ...
“ Standard” Model <ul><li>Acid = H +  donor, Base = H +  acceptor </li></ul><ul><li>Final pH = function of amount of acid ...
“ Standard” model or  modelS ? <ul><li>Magnitude of the disorder is used to decide mechanism/type/”dose” of therapy </li><...
Six rules of thumb <ul><li>The  1 for 10 Rule  for Acute Respiratory Acidosis  </li></ul><ul><li>The  4 for 10 Rule  for C...
Standard Base Excess <ul><li>“ Amount of acid or base in meqs needed to titrate 1 lt of blood to pH 7.4 at pCO2 of 40mmHg ...
Does the model hold true for all pH values? <ul><li>The Henderson Hasselbach predicts a linear relation between pH and log...
Copyright ©1997 American Physiological Society Constable, P. D. J Appl Physiol 83: 297-311 1997 No Caption Found The curvi...
Clinical “failures” of the standard model <ul><li>T he mechanism of hyperchloremic acidosis  during NaCl administration an...
New models of acid base balance – the Stewart model <ul><li>They try to offer explanations for such “extreme” phenomena in...
Physico-chemical basis of “new” acid basis models <ul><li>In any physiologic solution, that is at thermodynamic  equilibri...
Acid – base pairs in a physiologic solution <ul><li>Water Dissociation Equilibrium </li></ul><ul><li>Electrical Neutrality...
Acid – base pairs in a physiologic solution
The “modified” Henderson Hasselbach equation <ul><li>Accounting for all these systems simultaneously leads to a modified H...
What does this all mean? <ul><li>The bicarbonate acid base system (“standard” HH) is a marker of acid base status (“CXR – ...
What does this all mean?
Dependent v.s. Independent variables in the Stewart model <ul><li>The designation of certain variables as independent whil...
Dependent v.s. Independent variables II <ul><li>Equilibrium approaches  cannot  be used to infer causality relations witho...
Thinking about fluids and RRT in the ICU <ul><li>Even fluids that do not have  any  CO 2  will have an effect in the pH of...
Acid – Base Analysis within the “new” paradigm I
Acid – Base Analysis within the “new” paradigm II
Clinical Use of the Stewart Model <ul><li>Formulas are more complicated than the standard acid-base approach </li></ul><ul...
Thinking about fluids in the ICU <ul><li>It is the SID value of NS, not the dilution of plasma bicarbonate that causes the...
Acid – Base and Chloride Transport I <ul><li>The “independent” variable of SID may explain the following basic science obs...
Acid – Base and Chloride Transport II <ul><li>A hypochloremic metabolic alkalosis is characteristic of the following disor...
Internet Resources <ul><li>UPMC’s Department of Critical Care pHorum (references and excel based calculator of SIG/SID, mo...
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New models of acid-base balance and their application to critical care nephrology (an abbreviated introduction to Stewart's model of acid base disturbances)

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A short introduction to Stewart's model of acid-base disturbances. Modified from a talk I gave during a fellow's retreat back in 2006 in the beautiful Seven Spring's resort.

Will probably get excommunicated by the Nephrology Orthodoxy for endorsing Stewart's "heresy" :) but it is worth it!

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New models of acid-base balance and their application to critical care nephrology (an abbreviated introduction to Stewart's model of acid base disturbances)

  1. 1. New models of acid-base balance and their application to critical care nephrology Christos Argyropoulos MD PhD Department of Internal Medicine, Renal and Electrolyte Division
  2. 2. Goals of acid-base models <ul><li>P atient C are : diagnosis and treatment of complex acid-base disorders </li></ul><ul><li>Medical Education : establish the paradigm of acid-base physiology taught in medical curricul a </li></ul><ul><li>Research : Advance understanding of genetic disorders of ion transport in epithelial celss </li></ul>
  3. 3. Qualifications of an acid-base model (formal) <ul><li>A general acid-base model should provide: </li></ul><ul><li>the classification of the disturbance as “metabolic” or “respiratory” </li></ul><ul><li>a mechanistic explanation for the underlying disturbance </li></ul><ul><li>a quantitative estimate of the magnitude of an acid-base disturbance </li></ul><ul><li>the enumeration of the independent variables that govern the disturbance. </li></ul>
  4. 4. Qualifications of an acid-base model (informal) <ul><li>A general acid-base model should answer the following questions: </li></ul><ul><li>Which organ/system is causing the disturbance? </li></ul><ul><li>How does it cause the disturbance? </li></ul><ul><li>What is the magnitude of the disturbance </li></ul><ul><li>What should I do to fix this? </li></ul>
  5. 5. “ Standard” Model <ul><li>Acid = H + donor, Base = H + acceptor </li></ul><ul><li>Final pH = function of amount of acid added or removed </li></ul><ul><li>Plasma membranes may be permeable to H + </li></ul><ul><li>Analysis of a single acid – base (HCO3 - /CO2) buffer system suffices to understand all disorders </li></ul><ul><li>Magnitude of disorder estimated by the Henderson Hasselbach equation </li></ul>
  6. 6. “ Standard” model or modelS ? <ul><li>Magnitude of the disorder is used to decide mechanism/type/”dose” of therapy </li></ul><ul><li>Two main approaches to quantification: </li></ul><ul><ul><li>The “six” rules of thumb (medicine boards a.k.a “Boston approach”) </li></ul></ul><ul><ul><li>Standard Base Excess and PCO2 (Anesthesia and Surgical boards aka “Copenhagen” approach) </li></ul></ul>
  7. 7. Six rules of thumb <ul><li>The 1 for 10 Rule for Acute Respiratory Acidosis </li></ul><ul><li>The 4 for 10 Rule for Chronic Respiratory Acidosis </li></ul><ul><li>The 2 for 10 Rule for Acute Respiratory Alkalosis </li></ul><ul><li>The 5 for 10 Rule for a Chronic Respiratory Alkalosis </li></ul><ul><li>The One & a Half plus 8 Rule - for a Metabolic Acidosis </li></ul><ul><li>The Point Seven plus Twenty Rule - for a Metabolic Alkalosis </li></ul>
  8. 8. Standard Base Excess <ul><li>“ Amount of acid or base in meqs needed to titrate 1 lt of blood to pH 7.4 at pCO2 of 40mmHg keeping the temperature constant at 37 o C” </li></ul><ul><li>Calculated on the basis of modifications of the Van Slyke equation: </li></ul><ul><li>SBE = 0.9287 × (HCO3 – – 24.4 + 14.83 × [pH – 7.4]) </li></ul><ul><li>“ SBE” = metabolic component, “CO2” = respiratory component </li></ul>
  9. 9. Does the model hold true for all pH values? <ul><li>The Henderson Hasselbach predicts a linear relation between pH and logP CO 2 </li></ul>B ut in vitro in vivo CO2 equilibration studies demonstrate a non-linear relationship between log PCO2 and pH over a wide range of pH
  10. 10. Copyright ©1997 American Physiological Society Constable, P. D. J Appl Physiol 83: 297-311 1997 No Caption Found The curvilinear relationship between pH and log P CO 2
  11. 11. Clinical “failures” of the standard model <ul><li>T he mechanism of hyperchloremic acidosis during NaCl administration and cardio-pulmonary bypass * </li></ul><ul><li>Metabolic alkalosis associated with decreased plasma albumin concentrations ** </li></ul>** J Appl Physiol 84: 1740-1748, 1998 * Anesthesiology. 2000 Nov;93(5):1170-3 Anesthesiology 1999, 90:1265--1270 Critical Care 2002, 6(Suppl 2):2
  12. 12. New models of acid base balance – the Stewart model <ul><li>They try to offer explanations for such “extreme” phenomena in human physiology and disease </li></ul><ul><li>Include the “standard” model formulas as special cases </li></ul><ul><li>Grounded on physical chemistry and equilibrium thermodynamic analysis of uni- and multi-compartmental fluidic systems </li></ul><ul><ul><li>Can J Physiol Pharmacol 61:1444-1481 1983 </li></ul></ul><ul><ul><li>J Appl Physiol 86:326-334, 1999 </li></ul></ul><ul><ul><li>J Appl Physiol 95:2333-2344, 2003 </li></ul></ul>
  13. 13. Physico-chemical basis of “new” acid basis models <ul><li>In any physiologic solution, that is at thermodynamic equilibrium the following laws simultaneously apply to all acid/base pairs: </li></ul><ul><li>Conservation of mass </li></ul><ul><li>Conservation of charge </li></ul><ul><li>Law of mass action </li></ul>
  14. 14. Acid – base pairs in a physiologic solution <ul><li>Water Dissociation Equilibrium </li></ul><ul><li>Electrical Neutrality Equation </li></ul><ul><li>Weak acid (albumin, phosphate, sulfate etc) dissociation equilibrium </li></ul><ul><li>Conservation of mass for weak acids </li></ul><ul><li>Bicarbonate ion formation equilibrium (“standard” model) </li></ul><ul><li>Carbonate ion formation equilibrium </li></ul>
  15. 15. Acid – base pairs in a physiologic solution
  16. 16. The “modified” Henderson Hasselbach equation <ul><li>Accounting for all these systems simultaneously leads to a modified HH equation: </li></ul>K α : dissociation constant for weak acids A tot : total concentration of weak acids SID + : Strong Ion difference = [ Na + ] + [ K + ] – [ Cl - ] – [ lactate ] = [HCO 3 - ]+[A - ]
  17. 17. What does this all mean? <ul><li>The bicarbonate acid base system (“standard” HH) is a marker of acid base status (“CXR – pneumonia” concept) </li></ul><ul><li>The three main “independent” variables that control the pH are: </li></ul><ul><li>PCO 2 : controlled by the lungs </li></ul><ul><li>A tot : controlled by the liver </li></ul><ul><li>SID: kidney, intestine and tissue </li></ul>
  18. 18. What does this all mean?
  19. 19. Dependent v.s. Independent variables in the Stewart model <ul><li>The designation of certain variables as independent while others (pH) are dependent is a controversial aspect of the theory </li></ul><ul><li>The theory was developed years before the first epithelial H + transporter was cloned/identified i.e. biological systems do handle protons directly … </li></ul>
  20. 20. Dependent v.s. Independent variables II <ul><li>Equilibrium approaches cannot be used to infer causality relations without a model of the system as exists far from equilibrium (ion transport) </li></ul><ul><li>However equilibrium models render constraints that any quantitative description of the system should obey </li></ul><ul><li>The modified HH is thus a more general version of the Henderson Hasselbach and include the “6-pack” rule of acid base disorders of the “standard” model </li></ul>
  21. 21. Thinking about fluids and RRT in the ICU <ul><li>Even fluids that do not have any CO 2 will have an effect in the pH of body fluids according to the new theory </li></ul><ul><li>After infusion, the fluid administered will equilibrate with plasma, ECF and finally ECF </li></ul><ul><li>In the new “equilibrium” state, the SID and A tot of the ECF will change towards the ones of the infused fluid </li></ul>
  22. 22. Acid – Base Analysis within the “new” paradigm I
  23. 23. Acid – Base Analysis within the “new” paradigm II
  24. 24. Clinical Use of the Stewart Model <ul><li>Formulas are more complicated than the standard acid-base approach </li></ul><ul><li>Calculation of the Strong Ion Difference may be accomplished by the formula: </li></ul>Detection of gap acidosis is done by the Strong Ion Gap:
  25. 25. Thinking about fluids in the ICU <ul><li>It is the SID value of NS, not the dilution of plasma bicarbonate that causes the “dilutional” acidosis of massive rescuscitation, CPB * </li></ul><ul><li>Paradoxically, sodium bicarbonate will have an alkalizing effect only if ventilation is not limited (infusion of “high” SID fluid) </li></ul><ul><li>If ventilation is limited, CO2 will rise, and pH will fall after sodium bicarbonate infusion** </li></ul>* Anesth Analg 2003;96:919-922 ** Am. J. Respir. Crit. Care Med., 2000; 161 ( 4 ): 1149-1153 J Nephrol. 2005 18(3):303-7
  26. 26. Acid – Base and Chloride Transport I <ul><li>The “independent” variable of SID may explain the following basic science observations: </li></ul><ul><li>Excretion of any organic anion will decrease SID (Na + will accompany the anion) </li></ul><ul><li>NH4 + excretion will increase SID (Cl - will accompany the cation but Na + will stay behind) </li></ul><ul><li>Glimpses of the non-equilibrium model for acid base control might be re-constructed from clinical disorders of ion transport(-ers) </li></ul>
  27. 27. Acid – Base and Chloride Transport II <ul><li>A hypochloremic metabolic alkalosis is characteristic of the following disorders: </li></ul><ul><li>Cystic Fibrosis : due to mutations of CTFR (a chloride channel) </li></ul><ul><li>Bartter syndrome: due to mutations of ROMK (potassium channel) /NKCC2 (sodium chloride transporter) /CLCNKB (chloride channel) </li></ul><ul><li>Alkalosis is due to : </li></ul><ul><li>“ volume contraction” (standard model) </li></ul><ul><li>elevated SID (Stewart model) </li></ul>
  28. 28. Internet Resources <ul><li>UPMC’s Department of Critical Care pHorum (references and excel based calculator of SIG/SID, modified HH): </li></ul><ul><li>http://www.ccm.upmc.edu/education/resources/phorum.html </li></ul><ul><li>The full text of Stewart’s 1983 book is available on the web for free: http://www.acidbase.org/ </li></ul><ul><li>A “colorful” introduction at the Anesthetist: http://www.anaesthetist.com/icu/elec/index.htm </li></ul>

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