Acid-Base. Beyond the Basics.

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1 Acid-Base Beyond the Basics

2 Acid-Base: Why should we care? Metabolic Acidosis Osmolar Gap Lactic Acidosis Delta Gap Albumin Correction Pseudo Respiratory Alkalosis Sodium Bicarbonate Alpha-stat Vs ph-stat Trans-Atlantic Divide Boston Rules Copenhagen Rules Stewart s Strong Ion Theory

3 ph Box Jellyfish or Canary?

4 Consequences of Severe Metabolic Acidosis Cardiovascular Respiratory Metabolic Haematological Contractility & CO RR & Dyspnea Insulin Resistance Right shift of Hb O2 curve Incidence of Arrhythmia Respiratory Muscle Fatigue Inhibition of Glycolysis Clotting Factor Function Pulmonary Vascular Resistance Reduced ATP Production Hepatic and Renal Blood Flow Hyperkalaemia Centralisation of blood volume Cerebral Cerebral Blood Flow Coma

5 Normal Anion Gap vs Raised Anion Gap prognosis

6 Normal Anion Gap vs Raised Anion Gap prognosis Kyle J Gunnerson1, Melissa Saul2, Shui He3 and John A Kellum, Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Critical Care 2006, 10:R22 (doi: /cc3987) 60 Hospital Mortality % Lactate (n=239) SIG (n=204) Chloride (n=105) None (n=303) Observational, cohort study of 815 patients admitted to the ICUs of 4 Pittsburgh Hospitals

7 Metabolic Acidosis

8 Metabolic Acidosis Normal Anion Gap Anion Gap

9 Metabolic Acidosis Normal Anion Gap Anion Gap Loss of high SID fluid Gastrointestinal diarrhoea iliostomy uretosigmoidostomy Addition of low SID fluid Normal Saline Renal acetazolamide renal Tubular Acidosis hyperparathyriodism hypoaldersteronism

10 Metabolic Acidosis Normal Anion Gap Anion Gap Loss of high SID fluid Gastrointestinal diarrhoea iliostomy uretosigmoidostomy Renal acetazolamide renal Tubular Acidosis hyperparathyriodism hypoaldersteronism Addition of low SID fluid Normal Saline Lactic Acidosis Ketoacids Renal Failure Poisons salicilate methanol ethanol Glycol

11 Metabolic Acidosis Anion Gap Lactic Acidosis Ketoacids Renal Failure Poisons salicilate methanol ethanol Glycol

12 Metabolic Acidosis Anion Gap Normal Osmolar Gap Lactic Acidosis Osmolar Gap methanol ethanol Glycol Ketoacids Renal Failure Poisons salicilate

13 Osmolar Gap Poisonings Methanol drowsiness, confusion & ataxia nausea, vomiting & abdominal pain blurred vision or changes in colour perception hypotension and cardiac arrest permanent blindness seizures, coma & death Ethelene Glycol drowsiness, confusion & ataxia nausea, vomiting & abdominal pain hypertension ARDS acute tubular necrosis and renal failure - probably due to calcium oxalate deposition

14 Raised Osmolar Gap Acidosis Ethanol Alcohol Dehydrogenase Acetaldehyde CO2 + O2

15 Raised Osmolar Gap Acidosis Methanol Ethanol Ethylene Glycol Alcohol Dehydrogenase Formaldehyde Acetaldehyde Glycolaldehyde Formic Acid CO2 + O2 Glycolic Acid Oxalic Acid

16 Treatment 100% Ethanol infusion - BSL in children Fomepizole - occupies alcohol dehydrogenase without the side effects

17 Osmolar Gap Osmolar Gap = Calculated Osmolarity - Measured Osmolarity Normal less than 10 osmolarity osmolality osmole = osmoles of solute per litre of solution - Calculated = osmoles of solute per kilogram of solvent - Measured = an Avagadro s number of particles (6.022 x 1023) in solution

18 Measuring Osmolality Colligative properties depend only on the ratio of the number of particles of solute to solvent in the solution, not the identity of the solute vapour pressure depression freezing point depression boiling point elevation osmotic pressure

19 Measuring Osmolality Colligative properties depend only on the ratio of the number of particles of solute to solvent in the solution, not the identity of the solute vapour pressure depression freezing point depression boiling point elevation osmotic pressure

20 Measuring Osmolality Colligative properties depend only on the ratio of the number of particles of solute to solvent in the solution, not the identity of the solute vapour pressure depression freezing point depression boiling point elevation osmotic pressure An osmole is the amount of a substance that yields, in ideal solution, that number of particles (Avogadro s number) that would depress the freezing point of the solvent by 1.86K

21 Calculating Osmolarity (properly) φ = osmotic coefficient - accounts for the degree of non-ideality of the solution. n = number of particles into which the molecule dissociates C = molar concentration of the solute i = represents the identity of a particular solute

22 Estimating Osmolarity Osmolarity = Cations + Anions + non-ionized Solutes

23 Estimating Osmolarity Osmolarity = 2 Cations + Anions + non-ionized Solutes

24 Estimating Osmolarity Osmolarity = 2 Cations + Anions + non-ionized Solutes Na K Ca Mg

25 Estimating Osmolarity Osmolarity = 2 Cations + Anions + non-ionized Solutes Na K Ca Mg

26 Estimating Osmolarity Osmolarity = 2 Cations + Anions + non-ionized Solutes Na K Ca Mg glucose urea lipids

27 Estimating Osmolarity Osmolarity = 2 Cations + Anions + non-ionized Solutes Na K Ca Mg glucose urea lipids

28 Estimating Osmolarity Osmolarity = 2 Cations + Anions + non-ionized Solutes Na Osmolarity = 2 Na + glucose + urea K Ca Mg glucose urea lipids

29 Estimating Osmolarity Osmolarity = 2 Cations + Anions + non-ionized Solutes Na Osmolarity = 2 Na + glucose + urea K Ca Mg glucose urea lipids Osmolar Gap = Calculated Osmolarity - Measured Osmolarity

30 Using the Osmolar Gap

31 Using the Osmolar Gap Time course Osmolar Gap Acidosis

32 Using the Osmolar Gap Time course Osmolar Gap Acidosis Ethanol Cloaking 2 Na + Glucose + Urea + Ethanol

33 Using the Osmolar Gap Time course Osmolar Gap Acidosis Ethanol Cloaking 2 Na + Glucose + Urea + Ethanol Units Divide mg/dl by 4.6 to find mmol/l eg. An ethanol level of 0.05% is 50mg/dl, 50 / 4.6 = 10.9 mmols/l

34 Metabolic Acidosis Normal Anion Gap Anion Gap Loss of high SID fluid Gastrointestinal diarrhoea iliostomy uretosigmoidostomy Renal acetazolamide renal Tubular Acidosis hyperparathyriodism hypoaldersteronism Addition of low SID fluid Normal Saline Lactic Acidosis Ketoacids Renal Failure Poisons Salicilate Methanol Ethanol Glycol

35 Metabolic Acidosis Normal Anion Gap Anion Gap Loss of high SID fluid Gastrointestinal diarrhoea iliostomy uretosigmoidostomy Renal acetazolamide renal Tubular Acidosis hyperparathyriodism hypoaldersteronism Addition of low SID fluid Normal Saline Lactic Acidosis Ketoacids Renal Failure Poisons Salicilate Methanol Ethanol Glycol

Lactic Acidosis Type A - increased production Tissue hypoxia β2 stimulation insulin deficiency Type B - decreased metabolism insulin deficiency

36 Lactic Acidosis Type A - increased production Tissue hypoxia β2 stimulation insulin deficiency Type B - decreased metabolism insulin deficiency malignancies rare enzyme defects Propofol Infusion Syndrome Metformin D-lactate - bowel fermentation Short gut gram-positive anaerobes, such as Lactobacilli

37 Glucose TAG H + Glycolysis Lactate Pyruvate FFA Lipolysis Fatty acyl CoA Acetyl CoA Oxaloacetate Citrate - Hydroxybuterate Malate TCA cycle -Ketogluterate Fumerate Succinate NAD + ADP H + NADH etc ATP O2 H2O

38 Anions of the Raised Gap Lactic acidosis is so called for historical reasons A significant number of hypoxic patients have a near normal lactate Corrected anion gap or SID are better indicators of severity of tissue hypoxia DKA is not just about the ketoacids

39 Metabolic Acidosis Normal Anion Gap Anion Gap Loss of high SID fluid Gastrointestinal diarrhoea iliostomy uretosigmoidostomy Renal acetazolamide renal Tubular Acidosis hyperparathyriodism hypoaldersteronism Addition of low SID fluid Normal Saline Lactic Acidosis Ketoacids Renal Failure Poisons Salicilate Methanol Ethanol Glycol

40 Metabolic Acidosis Normal Anion Gap Anion Gap Negative Urinary anion Gap Gastrointestinal diarrhoea iliostomy uretosigmoidostomy Positive Urinary anion Gap Renal acetazolamide renal Tubular Acidosis hyperparathyriodism hypoaldersteronism

41 Urinary Anion Gap Urinary Anion Gap = Na + K - Cl Gastrointestinal Renal Compensated by increased renal excretion of NH4 NAG renal acidosis is due to deduced relative NH4 excretion + + Urinary anion gap (-ve) Urinary anion gap (+ve)

42 Delta Ratio Delta ratio = Increase in anion gap Decrease in bicarbonate Delta ratio greater than 2 strongly suggests a normal anion gap acidosis hiding behind a raised anion gap acidosis

43 Venous Blood Gases Good means of investigating Acid-Base balance Simple correction factors unless in circulatory failure

44 Venous Blood Gases Good means of investigating Acid-Base balance Pseudo-Respiratory Alkalosis Simple correction factors unless in circulatory failure

45 45 year old female nurse with nephrotic syndrome is brought to ED intoxicated ph 7.44 PCO2 34 HCO3 21 BE 0? Na 138 K 4 Cl 106 Albumin 13 Glucose 5.2 Urea 14.3 Osmolality ( 50 / 4.6 ) = 10.9 (2 * 138) = Anion Gap = 15 BAL 0.05 Osmolality 320 Corrected Anion Gap (42-13) = (27/3) = 24

46 45 year old female nurse with nephrotic syndrome is brought to ED intoxicated ph 7.44 PCO2 34 HCO3 21 Osmolality ( 50 / 4.6 ) = 10.9 (2 * 138) = Anion Gap = 15 Albumin Reduction (42-13) = 27 Corrected Anion Gap 15 + (27/3) = 24 Raised Anion Gap Metabolic Acidosis Osmolality ( 50 / 4.6 ) = 10.9 (2 * 138) = Anion Gap = 15 BE 0 Na 138 K 4 Cl 106 Albumin 13 Glucose 5.2 Urea 14.3 BAL 0.05 Osmolality 320 Corrected Anion Gap (42-13) = (27/3) = 24

47 Sodium Bicarbonate Undesirable Effects hypernatraemia & hyperosmolality volume overload hypokalaemia left shift of the HbO2 dissociation curve Increased lactate production CSF acidosis hypercapnia

48 Sodium Bicarbonate Undesirable Effects hypernatraemia & hyperosmolality volume overload hypokalaemia left shift of the HbO2 dissociation curve Increased lactate production CSF acidosis hypercapnia Animal models suggest overall harm from giving bicarb during CPR

49 Sodium Bicarbonate Undesirable Effects hypernatraemia & hyperosmolality volume overload hypokalaemia left shift of the HbO2 dissociation curve Increased lactate production CSF acidosis hypercapnia Legitimate Uses urine alkalisation life threatening hyperkalaemia Animal models suggest overall harm from giving bicarb during CPR

50 Sodium Bicarbonate Undesirable Effects hypernatraemia & hyperosmolality volume overload hypokalaemia left shift of the HbO2 dissociation curve Increased lactate production CSF acidosis hypercapnia Legitimate Uses urine alkalisation life threatening hyperkalaemia Animal models suggest overall harm from giving bicarb during CPR Never give bicarb to a patient that can t blow off excess CO2

51 Key Points ph derangement is a canary - treat the cause Correct AG for albumin or use the SIG Remember the osmols Consider a urinary anion gap for normal anion gap acidosis Beware of arterial gasses in circulatory failure

52 Alpha-stat Vs ph-stat

53 Mention the rules The Great Trans-Atlantic Acid-Base Debate Boston (Schwarts and Relman) Vs Copenhagen (Astrup and Siggaard-Anderson)

54 Mention the rules The Great Trans-Atlantic Acid-Base Debate Boston (Schwarts and Relman) Vs Copenhagen (Astrup and Siggaard-Anderson) When will BE or Bicarb differ?

Peter Stewart (1921-1993) Intensely annoyed by bicarbonate Rather than just focus on a single indicator at the

55 Peter Stewart ( ) Intensely annoyed by bicarbonate Rather than just focus on a single indicator at the centre of acid base he went in search of quantitative picture of the whole Grand unifying theory of physiological acid-base

56 Strong Ions Na + Weak Ions - HCO3 K + CO3 2- Mg 2+ - HPO4 Ca 2+ Protein Cl - SO4 2- Lactate

57 Strong Ion Difference + Na A - HCO2-142 meq K + 2+ Ca 2+ Mg Cl - Cations Anions Gamblegram 1st principal - electrical neutrality

58 Strong Ion Difference + Na A - HCO2 - K + 2+ Ca Cl - 2+ Mg Gamblegram 1st principal - electrical neutrality

59 Strong Ion Difference + Na A - HCO2 - K + 2+ Ca Cl - 2+ Mg

60 Strong Ion Difference + Na Anion Gap (10 meq) A - Unidentified anions - HCO2 - Lactate - K + 2+ Ca 2+ Mg Cl -

61 Strong Ion Difference Unidentified anions - + Na Anion Gap (10 meq) A - HCO2 - Lactate - A - HCO2 - K + 2+ Ca Cl - Cl - 2+ Mg

62 Strong Ion Difference + Na Anion Gap (10 meq) A - Unidentified anions - HCO2 - Lactate - A - HCO2 - Strong Ion Difference (40 meq) K + 2+ Ca Cl - Cl - 2+ Mg

63 The Variables Independent Dependent Constants + PCO2 H (ph) Water dissociation (Kw) Strong ion difference (SID) OH Weak acid dissociation Ka - Total weak acid (ATot) CO3 CO2 Solubility (SCO2) 2- HCO2 - - HCO2 equilibria K1 & K3 Dissociated weak acid (A ) - Undissociated weak acid (HA)

64 The Variables H + CO3 2- OH - HCO3 - HA A - Second principal dependant and independent

65 The Variables PCO2 H + CO3 2- OH - HCO3 - HA A - Second principal dependant and independent

66 The Variables PCO2 H + CO3 2- OH - HCO3 - HA A - Second principal dependant and independent Strong ion difference (SID)

67 The Variables PCO2 Total weak acid (ATot) H + CO3 2- OH - HCO3 - HA A - Second principal dependant and independent Strong ion difference (SID)

68 The Variables PCO2 Total weak acid (ATot) ph A - HCO3 - Strong ion difference (SID)

69 Stewart s Equations Third principal unified by ph

70 Stewart s Equations Water Dissociation Equilibrium 1 + H. OH = Kw Third principal unified by ph

71 Stewart s Equations Water Dissociation Equilibrium 1 + H. OH = Kw 2 Electrical Neutrality Equation 2- SID + H = HCO3 + CO3 + A + OH Third principal unified by ph

72 Stewart s Equations Water Dissociation Equilibrium 1 + H. OH = Kw 2 Electrical Neutrality Equation 2- SID + H = HCO3 + CO3 + A + OH Weak Acid Dissociation Equilibrium H. A = Ka. HA Third principal unified by ph

73 Stewart s Equations Water Dissociation Equilibrium 1 + H. OH = Kw 2 Electrical Neutrality Equation 2- SID + H = HCO3 + CO3 + A + OH Weak Acid Dissociation Equilibrium H. A = Ka. HA Conservation of Mass for A ATot = H + A Third principal unified by ph

74 Stewart s Equations Water Dissociation Equilibrium 1 + H. OH = Kw 2 Electrical Neutrality Equation 2- SID + H = HCO3 + CO3 + A + OH Weak Acid Dissociation Equilibrium H. A = Ka. HA Conservation of Mass for A ATot = H + A 5 Bicarbonate Ion Formation Equilibrium + - H. HCO3 = K1. S. PCO2 Third principal unified by ph

75 Stewart s Equations Water Dissociation Equilibrium 1 + H. OH = Kw 2 Electrical Neutrality Equation 2- SID + H = HCO3 + CO3 + A + OH Weak Acid Dissociation Equilibrium H. A = Ka. HA Conservation of Mass for A ATot = H + A 5 Bicarbonate Ion Formation Equilibrium + - H. HCO3 = K1. S. PCO2 Third principal unified by ph Carbonate Ion Formation Equilibrium H. CO3 = K3. HCO3

76 Stewart s Equations Water Dissociation Equilibrium 1 + H. OH = Kw 2 Electrical Neutrality Equation 2- SID + H = HCO3 + CO3 + A + OH Weak Acid Dissociation Equilibrium H. A = Ka. HA Conservation of Mass for A ATot = H + A 5 Bicarbonate Ion Formation Equilibrium + - H. HCO3 = K1. S. PCO2 Carbonate Ion Formation Equilibrium H. CO3 = K3. HCO3

77 Stewart s Equations Stewart s Equation ph = pki + log SID - Ka. (ATot / Ka) ph S. PCO2

78 Stewart s Equations Stewart s Equation ph = pki + log SID - Ka. (ATot / Ka) ph S. PCO2

79 Stewart s Equations Stewart s Equation ph = pki + log SID - Ka. (ATot / Ka) ph S. PCO2 HCO3 = SID - Ka. (ATot / Ka) ph

80 Stewart s Equations Stewart s Equation ph = pki + log SID - Ka. (ATot / Ka) ph S. PCO2 HCO3 = SID - Ka. (ATot / Ka) ph Henderson Hasselbach Equation ph = pki + Log { } HCO3 SCO2. PCO2

81 A New Clinical Approach PCO2 Total weak acid (ATot) ph A - HCO3 - Strong ion difference (SID)

82 A New Clinical Approach PCO2 Total weak acid (ATot) ph Strong ion difference (SID)

83 A New Clinical Approach PCO2 Total weak acid (ATot) ph Strong ion difference (SID)

84 A New Clinical Approach PCO2 Total weak acid (ATot) ph Strong ion difference (SID)

85 A New Clinical Approach PCO2 Total weak acid (ATot) ph Strong ion difference (SID)

86 A New Clinical Approach PCO2 Total weak acid (ATot) ph Strong ion difference (SID)

87 A New Clinical Approach PCO2 Total weak acid (ATot) ph Strong ion difference (SID) To analyse SID use the SIG

88 A New Clinical Approach PCO2 Total weak acid (ATot) ph Strong ion difference (SID) To analyse SID use the SIG

89 Strong Ion Gap

90 Strong Ion Gap + Na Effective Strong Ion Difference (SIDe) A - HCO2 - Apparent Strong Ion Difference (SIDa) K + Unidentified anions - 2+ Ca Cl - Lactate - 2+ Mg

91 Strong Ion Gap + Na Effective Strong Ion Difference (SIDe) A - HCO2 - Apparent Strong Ion Difference (SIDa) K + Unidentified anions - 2+ Ca Cl - Lactate - 2+ Mg Figge

92 + Na Effective Strong Ion Difference (SIDe) A - HCO2 - Apparent Strong Ion Difference (SIDa) K + Unidentified anions - 2+ Ca Cl - Lactate - 2+ Mg Apparent Strong Ion Difference SIDa = Na + K + Mg + Ca - Cl - Lactate Figge

93 + Na Effective Strong Ion Difference (SIDe) A - HCO2 - Apparent Strong Ion Difference (SIDa) K + Unidentified anions - 2+ Ca Cl - Lactate - 2+ Mg Apparent Strong Ion Difference SIDa = Na + K + Mg + Ca - Cl - Lactate Effective Strong Ion Difference SIDe = ( E10. PCO2 / 10 ) + ( Albumin ph ) + ( PO4. ( ph ) Figge

94 + Na Effective Strong Ion Difference (SIDe) A - HCO2 - Apparent Strong Ion Difference (SIDa) K + Unidentified anions - 2+ Ca Cl - Lactate - 2+ Mg Apparent Strong Ion Difference SIDa = Na + K + Mg + Ca - Cl - Lactate Effective Strong Ion Difference SIDe = ( E10. PCO2 / 10 ) + ( Albumin ph ) + ( PO4. ( ph ) Strong Ion Gap Figge SIG = SIDa - SIDa (Normal = 8 meq)

95 Predictive Power

96 Predictive Power Kaplan et al. Yale, USA Trauma requiring vascular surgery n = 282, 218 survivors 64 mortalities Compared as predictor of mortality Strong Ion Gap Corrected Anion Gap Lactate Standard Base Excess

97 Predictive Power Kaplan et al. Yale, USA Trauma requiring vascular surgery n = 282, 218 survivors 64 mortalities Compared as predictor of mortality Strong Ion Gap Corrected Anion Gap Lactate Standard Base Excess

98 Predictive Power

99 Anions of the Raised Gap Lactic acidosis is so called for historical reasons A significant number of hypoxic patients have a near normal lactate Corrected anion gap or SID are better indicators of severity of tissue hypoxia DKA is not just about the ketoacids

100 Stewart vs Tradition Moviat et al. Nijmegen, The Netherlands n = 50 Consecutive ICU patients with SBE < 5 Very close agreement between albumin corrected anion gap and strong ion gap SIG is calculated from 9 measured values each with it s own measurement error. AG is calculated from 4.

101 Stewart vs Tradition Moviat et al. Nijmegen, The Netherlands n = 50 Consecutive ICU patients with SBE < 5 Very close agreement between albumin corrected anion gap and strong ion gap SIG is calculated from 9 measured values each with it s own measurement error. AG is calculated from 4.

102 Welcome to the 21st Century

103 Welcome to the 21st Century

104 Questions

105 Key Points ph derangement is a canary - treat the cause Check the AG even if there is no apparent acid-base disturbance Correct AG for albumin or use the SIG Remember the osmols Consider a urinary anion gap for normal anion gap acidosis Beware of arterial gasses in circulatory failure Never give bicarb to a patient that can t blow off excess CO2

Understanding Acid-Base Disturbances Gaps, Deficits and Differences

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