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The Meaning of Acidosis? 
Dave Story 
MBBS, MD, BMedSci, FANZCA 
Professor and Chair of Anaesthesia 
Head of Anaesthesia, Perioperative and Pain Medicine Unit (APPMU) 
Melbourne Medical School 
The University of Melbourne
Conflict of Interest 
I think I have no conflict of interest associated with this 
presentation
The OED 
Acid: from “acidus”, Latin: “sour” 1625 
Boswell: “Rather an acid expression 
of countenance”
Definitions of acid 
Like other definitions “sour” is still used today 
in parallel with other acid definitions 
Depends on context
Strong ion acidosis- Stewart 
Bicarbonate and hydrogen ions dependent factors 
H+ / HCO3 
CO2 
Bicarbonate is a marker not a mechanism 
Base-excess is a marker 
Sirker et al. Anaesthesia, 2002 
Miller’s Anesthesia 
SID 
Weak acids 
Kw + Ka
Definitions of acid 
Faraday, 1830s 
English electrochemist, 
-metal ions (sodium): base forming 
-ions like chloride: acid forming
Definitions of acid 
Arrhenius, 1870s 
Swedish Chemist 
• Electrolytic theory for ions 
(Almost failed PhD but later Nobel Prize) 
• First suggested CO2 greenhouse effect 
General acid definition: 
Substance that increases [H+] 
when added to a solution
The next step 
Naunyn, 1890s 
German Diabetes physician 
Combined Arrhenius definition of acid 
with Faraday’s ideas: 
plasma acid-base status partly determined by electrolytes 
-particularly sodium and chloride
Henderson and Hasselbalch 
Henderson, 1908 
Boston Physician 
H+ = Ka X [H2CO3] 
[NaHCO3] 
Henderson, Am J Phys, 1908 
Hasselbalch, 1916 
Danish gentleman farmer and chemist 
pH = pKa + log [HCO-] 
3 
 pCO2 
Astrup and Severinghaus, 
The history of blood gasses, acids and bases. 1986
Van Slyke 
US Clinical Chemist 
1910 -1960s 
“... the roles played…anions other than bicarbonate, and by 
the cations, in determining the acid-base balance and the 
bicarbonate content of the blood.” 
Peters and Van Slyke, 
Quantitative Clinical Chemistry 1935
Bicarbonate and carbon dioxide 
Henderson and Hasselbalch (before 1920) knew challenge: 
To assess effects of disease on bicarbonate, 
must account for effects on carbon dioxide: 
Isolate non-respiratory effects
The rise of bicarbonate 
The Modern Way in 1950s 
Calculate bicarbonate using Henderson-Hasselbalch equation: 
Measure pH, pCO2 + know constants 
pH = pKa + log [HCO3 
-] 
 pCO2 
Carbonic acid true Bronstead-Lowry acid 
Describe plasma pH ([H+]) with two measurable variables 
Simple maths (B.C. - before calculators) 
CO2 and bicarbonate = meaning of life, the universe, and everything 
Christensen, Am J Med 1957
Intensive Care born 1952
Bicarbonate and carbon dioxide (again) 
Siggaard-Andersen, Denmark, 1960s onward 
Base Excess = amount of acid (mmol/l) added 
to return blood to pH 7.40 after equilibration 
with pCO2 of 40 mmHg at 37oC 
Quantify change in non-respiratory component 
www.osa.suite.dk
But… 
Schwarz and Relman, NEJM 1963 
Boston Physicians 
Found flaws in (original) base-excess: ABE 
CO2 and bicarb “rules-of-thumb” 
and 
“The Great Trans-Atlantic Acid-Base Debate” 
Bunker, Anesthesiology, 1965
Then we have… 
Siggaard-Andersen (fights back) 
-Altered the “buffering” component 
“Standard base-excess” 
-Gained support form Severinghaus (US) 
Severinghaus, Am J Respir Crit Care 
Med, 1998
Peter Stewart 1921-1993 
Canadian physiologist working in USA 
Stewart. Can J Physiol Pharmacol 1983 
Acid base chemistry: 
“…piecemeal, qualitative, confusing…” 
Returned to Arrhenius, Naunyn, Van Slyke 
QUANTITATIVE 
Used principles of chemistry: 
electroneutrality 
conservation of mass 
dissociation of electrolytes
Strong ion acidosis- Stewart 
Bicarbonate and hydrogen ions dependent factors 
H+ / HCO3 
CO2 
Bicarbonate is a marker not a mechanism 
Base-excess is a marker 
Sirker et al. Anaesthesia, 2002 
Miller’s Anesthesia 
SID 
Weak acids 
Kw + Ka
The Gamblegram 
Gamble , 1950s 
- chloride = acid 
- Gamblegram 
- important aid to Stewart 
Gamble, 
Chemical Anatomy, Physiology 
and Pathology of Extracellular Fluid 1954 
Watson: www.ppn.med.sc.edu/watson/Acidbase/
Fencl 
Boston based Physician 
Originally suggested dividing 
base-excess into effects of: 
• Sodium 
• Chloride 
• Albumin 
• Unmeasured ions 
Gilfix J Crit Care 1993
Figge 
Boston Physician 
-quantified the base-excess effect of albumin 
Complex version 
Albumin effect (mmol/L) = (0.123pH- 0.631) X [42-albumin (g/l)]. 
Simple version: 
Albumin effect (meq/L) = 0.25 X (42-Albumin) 
Figge, Crit Care Med 1998 
Value for anion gap increasingly understood 
(even by Boston Physicians) 
Fencl-Stewart = Figge-Fencl 
www.acid-base.org
Kellum and the SIG 
(NOT) Boston physician 
Strong ion gap: 
Sum of all measured strong ions, 
and weak anions albumin, phosphate, bicarbonate 
“anion-gap” on steroids 
Kellum J Crit Care 1995 
Net unmeasured ions 
Lloyd, Crit Care Resus, 2005
Then I came along… 
1. SBE = overall metabolic effect 
2. Principal SID = Na – Cl (simplify Fencl), 140 – 102 = 38 (35) 
3. Principal Weak acid = albumin (use simple Figge), 
4. Rest = other ions 
SBE = NaCl efffect + Albumin Effect + Other ion effect 
For bedside use, not for the OCD 
Not a Boston Physician
Simplify
In 2014 add lactate… 
Plasma lactate now routinely measured 
SBE = 
NaCl Effect + Albumin Effect + Lactate Ion Effect + Other Ions 
Lactate is a strong anion so effect on SBE = negative [lactate] 
Median Reference Range = 1 mmol/L (ie when SBE = 0) 
SBE effect = 1 – lactate, mmol/L 
Eg Lactate ion effect of lactate of 4 mmol/L = - 3 mmol/L 
Story, Anesthesia and Analgesia, 2006
SBE = NaCl + Albumin + Lactate + OI 
78 yr old female with AAA post op 
Na = 142, Cl = 110, Albumin = 26, Lactate = 6, 
SBE = - 8 mmol/L 
NaCl effect = 142 - 110 - 38 = - 6 mmol/l 
Albumin effect = 0.25 x (42-26) = 0.25 x (16) = 4 mmol/l 
Lactate effect = 1 - 6 mmol/L = -5 mmol/L 
Other ions = SBE – NaCl effect – Albumin – Lactate 
OI = -8 – (-6) - 4 – (-5) 
= - 1 mmol/L
How will clinical acid-base evolve? 
• Readily understood 
• Clinically useful 
• Quantifiable 
• Identifiable 
• Modifiable 
Try different approaches in 
YOUR clinical practice! 
But, in my view…
Rules-of-thumb 
The Neanderthals
Base-excess 
The “sapiens” 
way forward
But can the US cope?
…and add Stewart! 
Thank you !!

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The Meaning of Acidosis by Story

  • 1. The Meaning of Acidosis? Dave Story MBBS, MD, BMedSci, FANZCA Professor and Chair of Anaesthesia Head of Anaesthesia, Perioperative and Pain Medicine Unit (APPMU) Melbourne Medical School The University of Melbourne
  • 2. Conflict of Interest I think I have no conflict of interest associated with this presentation
  • 3. The OED Acid: from “acidus”, Latin: “sour” 1625 Boswell: “Rather an acid expression of countenance”
  • 4. Definitions of acid Like other definitions “sour” is still used today in parallel with other acid definitions Depends on context
  • 5. Strong ion acidosis- Stewart Bicarbonate and hydrogen ions dependent factors H+ / HCO3 CO2 Bicarbonate is a marker not a mechanism Base-excess is a marker Sirker et al. Anaesthesia, 2002 Miller’s Anesthesia SID Weak acids Kw + Ka
  • 6. Definitions of acid Faraday, 1830s English electrochemist, -metal ions (sodium): base forming -ions like chloride: acid forming
  • 7. Definitions of acid Arrhenius, 1870s Swedish Chemist • Electrolytic theory for ions (Almost failed PhD but later Nobel Prize) • First suggested CO2 greenhouse effect General acid definition: Substance that increases [H+] when added to a solution
  • 8. The next step Naunyn, 1890s German Diabetes physician Combined Arrhenius definition of acid with Faraday’s ideas: plasma acid-base status partly determined by electrolytes -particularly sodium and chloride
  • 9. Henderson and Hasselbalch Henderson, 1908 Boston Physician H+ = Ka X [H2CO3] [NaHCO3] Henderson, Am J Phys, 1908 Hasselbalch, 1916 Danish gentleman farmer and chemist pH = pKa + log [HCO-] 3  pCO2 Astrup and Severinghaus, The history of blood gasses, acids and bases. 1986
  • 10. Van Slyke US Clinical Chemist 1910 -1960s “... the roles played…anions other than bicarbonate, and by the cations, in determining the acid-base balance and the bicarbonate content of the blood.” Peters and Van Slyke, Quantitative Clinical Chemistry 1935
  • 11. Bicarbonate and carbon dioxide Henderson and Hasselbalch (before 1920) knew challenge: To assess effects of disease on bicarbonate, must account for effects on carbon dioxide: Isolate non-respiratory effects
  • 12. The rise of bicarbonate The Modern Way in 1950s Calculate bicarbonate using Henderson-Hasselbalch equation: Measure pH, pCO2 + know constants pH = pKa + log [HCO3 -]  pCO2 Carbonic acid true Bronstead-Lowry acid Describe plasma pH ([H+]) with two measurable variables Simple maths (B.C. - before calculators) CO2 and bicarbonate = meaning of life, the universe, and everything Christensen, Am J Med 1957
  • 14. Bicarbonate and carbon dioxide (again) Siggaard-Andersen, Denmark, 1960s onward Base Excess = amount of acid (mmol/l) added to return blood to pH 7.40 after equilibration with pCO2 of 40 mmHg at 37oC Quantify change in non-respiratory component www.osa.suite.dk
  • 15. But… Schwarz and Relman, NEJM 1963 Boston Physicians Found flaws in (original) base-excess: ABE CO2 and bicarb “rules-of-thumb” and “The Great Trans-Atlantic Acid-Base Debate” Bunker, Anesthesiology, 1965
  • 16. Then we have… Siggaard-Andersen (fights back) -Altered the “buffering” component “Standard base-excess” -Gained support form Severinghaus (US) Severinghaus, Am J Respir Crit Care Med, 1998
  • 17. Peter Stewart 1921-1993 Canadian physiologist working in USA Stewart. Can J Physiol Pharmacol 1983 Acid base chemistry: “…piecemeal, qualitative, confusing…” Returned to Arrhenius, Naunyn, Van Slyke QUANTITATIVE Used principles of chemistry: electroneutrality conservation of mass dissociation of electrolytes
  • 18. Strong ion acidosis- Stewart Bicarbonate and hydrogen ions dependent factors H+ / HCO3 CO2 Bicarbonate is a marker not a mechanism Base-excess is a marker Sirker et al. Anaesthesia, 2002 Miller’s Anesthesia SID Weak acids Kw + Ka
  • 19. The Gamblegram Gamble , 1950s - chloride = acid - Gamblegram - important aid to Stewart Gamble, Chemical Anatomy, Physiology and Pathology of Extracellular Fluid 1954 Watson: www.ppn.med.sc.edu/watson/Acidbase/
  • 20. Fencl Boston based Physician Originally suggested dividing base-excess into effects of: • Sodium • Chloride • Albumin • Unmeasured ions Gilfix J Crit Care 1993
  • 21. Figge Boston Physician -quantified the base-excess effect of albumin Complex version Albumin effect (mmol/L) = (0.123pH- 0.631) X [42-albumin (g/l)]. Simple version: Albumin effect (meq/L) = 0.25 X (42-Albumin) Figge, Crit Care Med 1998 Value for anion gap increasingly understood (even by Boston Physicians) Fencl-Stewart = Figge-Fencl www.acid-base.org
  • 22. Kellum and the SIG (NOT) Boston physician Strong ion gap: Sum of all measured strong ions, and weak anions albumin, phosphate, bicarbonate “anion-gap” on steroids Kellum J Crit Care 1995 Net unmeasured ions Lloyd, Crit Care Resus, 2005
  • 23. Then I came along… 1. SBE = overall metabolic effect 2. Principal SID = Na – Cl (simplify Fencl), 140 – 102 = 38 (35) 3. Principal Weak acid = albumin (use simple Figge), 4. Rest = other ions SBE = NaCl efffect + Albumin Effect + Other ion effect For bedside use, not for the OCD Not a Boston Physician
  • 25. In 2014 add lactate… Plasma lactate now routinely measured SBE = NaCl Effect + Albumin Effect + Lactate Ion Effect + Other Ions Lactate is a strong anion so effect on SBE = negative [lactate] Median Reference Range = 1 mmol/L (ie when SBE = 0) SBE effect = 1 – lactate, mmol/L Eg Lactate ion effect of lactate of 4 mmol/L = - 3 mmol/L Story, Anesthesia and Analgesia, 2006
  • 26. SBE = NaCl + Albumin + Lactate + OI 78 yr old female with AAA post op Na = 142, Cl = 110, Albumin = 26, Lactate = 6, SBE = - 8 mmol/L NaCl effect = 142 - 110 - 38 = - 6 mmol/l Albumin effect = 0.25 x (42-26) = 0.25 x (16) = 4 mmol/l Lactate effect = 1 - 6 mmol/L = -5 mmol/L Other ions = SBE – NaCl effect – Albumin – Lactate OI = -8 – (-6) - 4 – (-5) = - 1 mmol/L
  • 27. How will clinical acid-base evolve? • Readily understood • Clinically useful • Quantifiable • Identifiable • Modifiable Try different approaches in YOUR clinical practice! But, in my view…
  • 30. But can the US cope?
  • 31. …and add Stewart! Thank you !!