Understanding Acid-Base Disturbances Gaps, Deficits and Differences

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1 Critical Care Medicine Apollo Hospitals Understanding Acid-Base Disturbances Gaps, Deficits and Differences Ramesh Venkataraman, AB(Int Med), AB (CCM) Consultant, Critical Care Medicine Apollo Hospitals Chennai

2 Understanding Acid-base Three approaches Conceptual evolution Limitations Comparison Understanding acid-base Relative diagnostic efficacy Prognostic value Conclusion

3 Acid vs. Base Bronsted-Lowry Theory (1923) Acid - a substance which donates a hydrogen ion Volatile vs. Non volatile (Carbonic vs. Noncarbonic) Base a substance which accepts the H + from the acid

4 Acid Homeostasis Carbonic Acid (Respiratory) Noncarbonic acid (Metabolic) Dissolved CO2 + H2O H2CO3 HCO3- + H+

5 Physiologic approach Henderson-Hasselbalch equation ph = 6.10+log([HCO 3- ]/0.03xPCO 2 ) 1. Acid base status determined by net H + balance 2. Blood ph determined by PaCO2 Respiratory component Bicarbonate Metabolic component Simplified into the Henderson equation 3. Uses only carbonic acid/bicarbonate buffer system [H + ] = 24 x (PCO 2 /[HCO 3- ])

6 Primary Disorder And Compensation Increased Acid Acidemia Metabolic Decreased Bicarbonate Respiratory Increased Carbonic acid (PCO2) Increased Alkali Alkalemia Metabolic Increased Bicarbonate Respiratory Decreased Carbonic acid (PCO2) Dissolved CO2 + H2O H2CO3 HCO3- + H+ PCO2 and Bicarbonate go in the same direction in case of compensation

7 Metabolic Acidosis Cations K Anions PO4 AG Prot HCO3 Cations K Anions AG PO4 Prot HCO3 Cations K Anions PO4 Prot AG HCO3 Na Cl Na Cl Na Cl Normal High AG acidosis Normal AG acidosis

8 Anion Gap - Pitfall Cations K Na Anions PO4 Prot AG HCO3 Cl AG Protein and phosphates AG determines cause of metabolic acidosis But is underestimated by hypoalbuminemia AG MUST be corrected for albumin and phosphorus Corrected AG = 2 (S.albumin) + ½ (S.Phosphorus) Normal

9 Is bicarbonate a good indicator? Metabolic derangement Change in alveolar ventilation Altered renal acidification Altered HCO3/CO2 equilibrium Change in bicarbonate Kurtz I et al: Am J Physiol Renal Physiol 294: (2008) F1009 F1031 Bicarbonate doesn t accurately reflect the degree of primary metabolic derangement

10 (Un)Physiological Approach? Plasma bicarbonate affected by changes in PaCO2 One component influences other Standard bicarbonate calculation Sustained changes in PaCO2 modify renal acidification Chronic hypercapnia increases plasma bicarbonate Failure of quantitation of buffers other than bicarbonate Isohydric principle Level of bicarbonate qualitatively reflects status of all buffers Quantifies magnitude but no insight into cause

11 Base Excess Approach Also advocates centrality of H + / HCO3 - Base excess - metabolic component Assumes 100% oxygenation, 37 o C and PCO2 40mmHg Measure of the contribution of all the ECF buffers INDEPENDENT of respiratory component Three relevant acid-base variables ph PCO2 Base Excess (BE)

12 Is SBE a good indicator? Metabolic derangement Change in alveolar ventilation Altered renal acidification Altered HCO3/CO2 equilibrium Change in SBE Kurtz I et al: Am J Physiol Renal Physiol 294: (2008) F1009 F1031 BE changes independent of metabolic derangement in chronic hypo/hypercapnia

13 Base Excess has Deficits!!!!! BE changes with changes in PCO2 invivo Increased PCO2 causes negative BE Equilibration occurs across entire extracellular fluid space (Whole blood + interstitial fluid) Extracellular or Standard BE Diluting blood threefold with its own plasma (Hb 5g/dl) At best a GUESSTIMATE Accurate ONLY when constant hemoglobin assumed Does not help identify the cause

14 (Mis)understanding acid-base The serum potassium varies with changes in ph due to exchange of K + for H + Serum K + concentration is in mmol/l (i.e ) but that H + concentration varies in nanomolar range (i.e )

15 (Mis)understanding Acid-base Vomiting causes metabolic alkalosis by loss of H + Why can t the correction be done with H 2 O to replenish the H +? Saline-induced acidosis - Dilutional acidosis Decrease in bicarbonate cannot cause hyperchloremia How does sodium bicarbonate rectify acidosis? Fernandez PC, et al. KI 1989; 36: Garella S, et al. NEJM 1973; 289: Androgue HJ, et al. JCI 1983; 71:

Stewart s definition of acid H + = OH - - Acid-Base Neutral Acidic solution H + > OH - Basic solution H + < OH - Acids when added to a solution increase H + Dissociate to

16 Stewart s definition of acid H + = OH - - Acid-Base Neutral Acidic solution H + > OH - Basic solution H + < OH - Acids when added to a solution increase H + Dissociate to yield an anion and H HA = [H + ] [A - ] Complete or partial Associate with hydroxyl ion H + concentration by itself is not a reliable measure of acidity, alkalinity or neutrality

17 Determinants of ECF acid-base [H + ] [OH - ] = K`w [H + ] [A - ] = K A [HA] [AH] [A - ] = [A TOT ] [H + ] [HCO 3- ] = K c pco 2 [H + ] [CO 3 -- ] = K 3 [HCO 3- ] [SID] + [H + ] - [HCO 3- ] - [A - ] - [CO 3 -- ] - [OH - ] = 0

18 Determinants of [H + ] Blood Plasma H 2 O A - = Ionized weak acid buffer HA = Non-ionized weak acid buffer A TOT = Total weak acid buffer A TOT = 2.43 x total protein g/dl OH - H + pco 2 A TOT SID Stewart P. Can J Physiol Pharm 1983;61:1444

19 Strong Ion Difference Mg ++ Ca ++ K + Na + Cl - Others (lactate, etc) These are the Strong Ions, so-called because they do not readily combine with other ions or lose their charge. Conversely, H + and HCO 3 - readily combine, and are called weak ions The difference between strong cations and strong anions is called Strong Ion Difference (SID) - indicates the net ionic charge of the weak anions; so it indicates the relative strength of H + and HCO3 -.

20 Physico - Chemical Approach 1. Determinant H + and HCO3 are only DEPENDENT of H+ is water dissociation 2. Water dissociation Determined by SID, variables A TOT and PCO2 Aqueous Solutions Water Dissociation Acids increase water dissociation H 2 O H + + OH -

21 Physico-chemical Approach Both H + and HCO3 - are dependent variables Bicarbonate just a gap filler between strong cations and anions Metabolic component Strong Ion Difference and A TOT Respiratory component PCO2 Six acid-base disorders SID increase and decrease alkalosis and acidosis A TOT increase and decrease acidosis and alkalosis Respiratory

22 Stewart Approach SID = 40

23 SID vs. AG AG = (Na + + K + ) (Cl - + HCO3 - ) Cations K SIDa Anions PO4 Prot AG SIDe HCO3 SIDa (40) = (Na + + K + ) Cl - SIDe = Bicarbonate + A TOT - Na Cl SIDa = SIDe Normal SIG = 0

24 SIG vs. AG acidosis Cations K SIDa Na Anions SIG AG PO4 SIDe Prot HCO3 Cl AG increased SIDa unchanged SIDe decreased SIG increased High AG or SIG acidosis

25 SID vs. Normal AG acidosis Cations K SIDa Anions PO4 Prot AG HCO3 SIDe AG unchanged SIDa decreased Na Cl SIDe decreased equally SIG = 0 Normal AG or SID acidosis

26 Strong ion theory - Weaknesses Very complex to practice SIG index of unmeasured anions after discounting for albumin and phosphates Advantage negated by correcting AG for albumin and phosphate No assessment of compensatory response Requires routine measurement of multiple other ions SIG varies with analyzer Measurement of SIDa Variable electrolytes being used in definition SIDe calculated by formula or normograms Cumbersome at bedside; SIG calculators available

27 Classification too complex Normal SIDa Decreased SIDe Increased SIG Decreased SIDe No SIG Decreased SIDa Decreased SIDa But no SIG High A TOT acidosis Low A TOT alkalosis

28 More Confusion Clinical relevance of A TOT acidosis and alkalosis? No regulation of albumin to maintain acid-base status invivo Changes in serum albumin do not correlate with changes in ph or PCO2 Stewart approach blending of diagnosis and cause Mathematically accurate but no validation on cause and effect relationship Adrogue HJ et al: Kidney Int. 2009; 76:

29 Conceptual Comparison

30 SIG vs AG 1. AG = [Na + ] [K + ] [Cl - ] [HCO - 3 ] 2. SIDa = Na + +K + -Cl - 3. SIDe = HCO A - 4. SIG = SIDa - SIDe [{Na + + K + -Cl} - -( HCO A - )] Combining above 4 equations SIG = [Na + ] [K + ] [Cl - ] [HCO - 3 ] - [A - ] SIG = AG - [A - ] where [A - ]= 2.8 (albumin g/dl)+ 0.6(phosphate mg/dl) at ph 7.4 SIG approximates AG corr

31 Diagnostic Accuracy Dubin A, et al. CCM 2007; 35:

Diagnostic and prognostic value Discordant ABG interpretation - 26 % 1 Stewart method superior in identifying patients with high lactate levels Can be rectified by incorporating albumin levels in AG

32 Diagnostic and prognostic value Discordant ABG interpretation - 26 % 1 Stewart method superior in identifying patients with high lactate levels Can be rectified by incorporating albumin levels in AG calculations No difference in quantifying complex acid-base disorders when AG corrected for albumin 2,3 Conflicting data on prognostic value of SID and SIG 1,4,5 1. Balasubramanyan N, et al. CCM 1999; 27(8): Moviat M, et al. CCM 2003; 7(3):R41 3. Lautrette A, et al. Minerva Anesthes 2013; 79(10): Cisack RJ et al. ICM 2002; 28(7): Kaplan LJ et al. SHOCK 2008; 29(6): 662

33 Conclusion Difficult to explain and understand metabolic acidbase disturbances using bicarbonate-based approaches Need to invoke complex mechanisms and hormones Physico chemical approach lends itself for easy explanation and understanding Blending of diagnosis and cause a concern More cumbersome If AG corrected for albumin, no difference between approaches in diagnostic efficacy Data conflicting on relative prognostic value of variables derived from all three approaches

34 Understanding Acid- base Final Verdict!!!

36 Physico - chemical Principles Electrical Neutrality In macroscopic aqueous solutions, the sum of all positively charged ions must equal the sum of all negatively charged ions Conservation of Mass The amount of a substance remains constant unless it is added or removed or unless it is generated or destroyed

37 Electrical Neutrality Mg ++ Ca ++ lactate PO Na + K + Cl - H + alb - CO 2 SO 4 - -, OH -, others

38 Electrical Neutrality [H + ] [OH - ] = K`w [H + ] [A - ] = K A [AH] [AH] [A - ] = [A TOT ] [H + ] [HCO 3- ] = K c pco2 [H + ] [CO -- 3 ] = K 3 [HCO 3- ] [SID] + [H + ] - [HCO 3- ] - [A - ] - [CO -- 3 ] - [OH - ] = 0 Stewart P. Can J Physiol Pharm 1983;61:1444

39 Electrical Neutrality [H + ] 4 + ([SID] + K A ) [H + ] 3 + (K A ([SID] - [A TOT ]) - K`w - K c pco 2 ) [H + ] 2 - (K A (K`w + K c pco 2 ) - K 3 K c pco 2 ) [H + ] - K A K 3 K c pco 2 = 0 Stewart P. Can J Physiol Pharm 1983;61:1444

40 A/V SBE SBE vs SID The standard base excess corresponds to the change in SID required to restore the plasma (in vivo) to ph 7.40 with pco 2 of 40 mm Hg R 2 = A/V SIDe -10 Kellum et al. J Crit Care 1997; 12: 7-12

41 Saline Acidosis SID = 40 Serum Na meq/l Total Body Na + : 140 x 42 = 5880 meq Serum Cl meq/l Total Body Cl - : 100 x 42 = 4220 meq Add 10L of 0.9% saline = /52 = meq/l Add 10L of 0.9% saline = /52 = meq/l SID = 32

42 Electrical Neutrality How does Saline cause acidosis?...by decreasing the SID and increasing water dissociation.

43 Electrical Neutrality Mg ++ Ca ++ lactate PO Na + K + alb - CO 2 H + Cl - SO 4 - -, OH -, others

44 Saline Acidosis Na + K + Mg ++ Ca ++ H + lactate PO CO alb - 2 Cl - SO 4 - -, OH -, others

45 Electrical Neutrality Mg ++ Ca ++ lactate PO Na + K + alb - CO 2 H + Cl - SO 4 - -, OH -, others

46 Further Implications How does sodium bicarbonate increase the plasma ph?...by increasing plasma Na + and thus SID

47 Sodium Bicarbonate HCO 3 - is a dependent variable. It does not have a Vd. Its concentration is set by the prevailing pco 2, SID and A TOT. NaHCO 3 increases the plasma ph by increasing the Na + and thereby the SID. This results in decreased water dissociation and increased ph.

48 More Acid-Base Questions Why do patient s with NG drainage develop alkalemia? Distinguish H + loss as HCl from H + loss as H 2 O

49 Geocentric Universe

50 Copernicus

51 Geocentric Universe HCO 3 - CO 2 Cl - H + Buffers

52 Post-Copernicus H + A - CO 2 SID ATOT HCO 3 -

53 Changing Practice Saline causes acidosis, especially in the critically ill NaHCO 3 only works by increasing the serum Na + (relative to Cl - ) Lactate is a strong acid but NaL is a salt. Lactate is acidifying; ATP hydrolysis is not. Base excess is a reliable measure of metabolic acid-base status relative to baseline The anion gap (when the corrected normal range is used) is a reliable measure of missing anions

54 Base Excess calculations Calculated the same way, in practice, as SID: Buffer Base = HCO A - HCO 3 calculated by ph & pco 2 (blood gas machine) A - calculated using ph & hemoglobin (whole blood) OR A - calculated using albumin & phos (plasma) BE = Buffer Base expected buffer base (expected if ph = 7.4 and pco 2 = 40)

55 Tight regulation to maintain this level Chemical buffering Control of PaCO 2 - alveolar ventilation Control of plasma bicarbonate Renal H + excretion Buffers Uses SOLELY the carbonic acid/bicarbonate buffer system to assess acid-base status Abundance Physiological pre-eminence Both components undergo homeostatic control

[Part II] Chemistry and Physiology

[Part II] Chemistry and Physiology [Part II] Quantitative Acid-Base Chemistry and Physiology [Chapter 10] Normal [SID] Peter Wilkes 10.1 Introduction This chapter will discuss issues surrounding the measurement and conceptualization of