1. Acid-Base Disorders Alan You, MD Combined EM/IM Residency Program
Virginia Commonwealth University Health System

3. Overview Physiologic Effects of Acid-Base Disturbances
Traditional (Schwartz-Bartter) Approach
Stewart Method
Fluid Resuscitation

4. Physiologic Effects of Acid-Base Disturbances

5. Consequences of Severe Acid-Base Disturbances
Organ System
Acidemia (pH <7.20)
Alkalemia (pH >7.60)
Cardiovascular
↓ contractility, arteriolar vasodilation ↓ MAP & CO; ↓ response to catecholamines
↑ risk of arrhythmias
Arteriolar vasoconstriction
↓ coronary blood flow ↑ risk of arrhythmias
Respiratory
Hyperventilation, ↓ resp muscle strength
Hypoventilation
Metabolic ↑K
↓ K, ICa, Mg, PO4
Neurologic
∆ MS
∆ MS, seizures

6. Traditional (Schwartz-Bartter) Approach

8. Step 1: Acidosis vs Alkalosis
Normal
??? pH
Alkalosis
Acidosis 14

9. Step 1: Acidosis vs Alkalosis
Normal
7.36 pH
7.44
Alkalosis
Acidosis 14

10. Step 2: Respiratory vs Metabolic
Primary Disorder pH
HCO3
PaCO2
Metabolic Acidosis
Respiratory Acidosis
Metabolic Alkalosis
Respiratory Alkalosis

11. Step 2: Respiratory vs Metabolic
Primary Disorder pH
HCO3
PaCO2
Metabolic Acidosis ↓
Respiratory Acidosis
Metabolic Alkalosis
Respiratory Alkalosis

12. Step 2: Respiratory vs Metabolic
Primary Disorder pH
HCO3
PaCO2
Metabolic Acidosis ↓
Respiratory Acidosis ↑
Metabolic Alkalosis
Respiratory Alkalosis

13. Step 2: Respiratory vs Metabolic
Primary Disorder pH
HCO3
PaCO2
Metabolic Acidosis ↓
Respiratory Acidosis ↑
Metabolic Alkalosis
Respiratory Alkalosis

14. Step 2: Respiratory vs Metabolic
Primary Disorder pH
HCO3
PaCO2
Metabolic Acidosis ↓
Respiratory Acidosis ↑
Metabolic Alkalosis
Respiratory Alkalosis

15. Step 3: Disorder-Specific Calculations
Anion Gap
AG = Na – (Cl + HCO3)
Expected AG = 2.5 × [albumin]

16. Step 3: Disorder-Specific Calculations
Delta-Delta
∆∆ = ∆AG / ∆HCO3
∆AG = measured AG – expected AG
= Na – (Cl + HCO3) – 2.5 × [albumin]
∆HCO3 = 24 – measured HCO3

17. Step 3: Disorder-Specific Calculations
Osmolar Gap
OG = measured osmolality – calculated osmolality
Calculated osmolality = (2 × Na) + (glu / 18) + (BUN / 2.8)

18. Step 3: Disorder-Specific Calculations
Urine Anion Gap
UAG = (UNa + UK) – UCl

19. Step 4: Compensation

20. Respiratory Disorders
Step 4: Compensation
∆ 10 pCO2
HCO3 1 2
Acute 4
Chronic
Respiratory Disorders
∆ 10 HCO3
pCO2
7.5
12.5
Metabolic Disorders

21. pCO2 = last two digits of pH
Step 4: Compensation
pCO2 = (1.5 × HCO3) + 8 ± 2
Winter’s Formula
pCO2 = last two digits of pH
Eyeball Method

22. Step 4: Compensation

23. Respiratory Disorders
Step 4: Compensation
∆ 10 pCO2 pH
0.08
Acute
0.03
Chronic
Respiratory Disorders

24. Step 5: Mixed Disorders
After adjusting for expected compensation, if the measured ________ is ________:
Too Low
Too High
pCO2
HCO3

25. 2° Respiratory Alkalosis
Step 5: Mixed Disorders
After adjusting for expected compensation, if the measured ________ is ________:
Too Low
Too High
pCO2
2° Respiratory Alkalosis
HCO3

26. Step 5: Mixed Disorders
After adjusting for expected compensation, if the measured ________ is ________:
Too Low
Too High
pCO2
2° Respiratory Alkalosis
2° Respiratory Acidosis
HCO3

27. Step 5: Mixed Disorders
After adjusting for expected compensation, if the measured ________ is ________:
Too Low
Too High
pCO2
2° Respiratory Alkalosis
2° Respiratory Acidosis
HCO3
2° Metabolic Acidosis

28. Step 5: Mixed Disorders
After adjusting for expected compensation, if the measured ________ is ________:
Too Low
Too High
pCO2
2° Respiratory Alkalosis
2° Respiratory Acidosis
HCO3
2° Metabolic Acidosis
2° Metabolic Alkalosis

29. Step 5: Mixed Disorders If the pH is normal but:
↑ pCO2 + ↑ HCO3
↓ pCO2 + ↓ HCO3
normal pCO2 + normal HCO3 + ↑ AG
normal pCO2 + normal HCO3 + normal AG

30. Step 5: Mixed Disorders If the pH is normal but:
↑ pCO2 + ↑ HCO3
respiratory acidosis + metabolic alkalosis
↓ pCO2 + ↓ HCO3
normal pCO2 + normal HCO3 + ↑ AG
normal pCO2 + normal HCO3 + normal AG

31. Step 5: Mixed Disorders If the pH is normal but:
↑ pCO2 + ↑ HCO3
respiratory acidosis + metabolic alkalosis
↓ pCO2 + ↓ HCO3
respiratory alkalosis + metabolic acidosis
normal pCO2 + normal HCO3 + ↑ AG
normal pCO2 + normal HCO3 + normal AG

32. Step 5: Mixed Disorders If the pH is normal but:
↑ pCO2 + ↑ HCO3
respiratory acidosis + metabolic alkalosis
↓ pCO2 + ↓ HCO3
respiratory alkalosis + metabolic acidosis
normal pCO2 + normal HCO3 + ↑ AG
AG metabolic acidosis + metabolic alkalosis
normal pCO2 + normal HCO3 + normal AG

33. Step 5: Mixed Disorders If the pH is normal but:
↑ pCO2 + ↑ HCO3
respiratory acidosis + metabolic alkalosis
↓ pCO2 + ↓ HCO3
respiratory alkalosis + metabolic acidosis
normal pCO2 + normal HCO3 + ↑ AG
AG metabolic acidosis + metabolic alkalosis
normal pCO2 + normal HCO3 + normal AG
no disturbance or non-AG metabolic acidosis + metabolic alkalosis

34. Step 5: Mixed Disorders ∆∆ = ∆AG / ∆HCO3
If there is an AG metabolic acidosis and:
∆∆ < 1
AG metabolic acidosis + non-AG metabolic acidosis
∆∆ > 2
AG metabolic acidosis + metabolic alkalosis
∆∆ = ∆AG / ∆HCO3

36. Metabolic Acidosis Anion Gap Metabolic Acidosis
Caused by increase in unmeasured anions such as organic acids, phosphates, and sulfates
KIL-U
Ketones
Ingestions
Lactate
Uremia (Renal Failure)
Ketones
DM, alcoholism, starvation
Ingestions
Methanol, ethylene glycol, propylene glycol, salicylates, acetaminophen
Lactate
Type A, Type B, D-lactic acidosis
Uremia
Urate, phosphate, sulfate

37. Metabolic Acidosis Anion Gap Metabolic Acidosis
Delta-Delta (∆∆) used to assess for concurrent non-AG metabolic acidosis or metabolic alkalosis
Osmolar gap (OG) used to differentiate different types of ingestions
Normal OG ≤10 AG OG
Ingestion ↑ nl
Acetaminophen, salicylates
Ethanol, methanol, ethylene glycol, propylene glycol
Isopropyl alcohol

38. Metabolic Acidosis Non-AG Metabolic Acidosis
Caused by decrease in albumin or increase in unmeasured cations
GRIPED
GI loss
RTA
Ingestion
Post-hypocapnia
Early renal failure
Dilution
GI Loss
Diarrhea, fistula
RTA
Type II, type I, type IV
Ingestion
Acetazolamide, sevelamer, cholestyramine, toluene
Post-Hypocapnia
Rapid correction of respiratory alkalosis
Early Renal Failure
Impaired generation of ammonia
Dilution
Rapid infusion of acidic fluids
Type II – Proximal
Type I – Distal
Type IV - Hypoaldo

39. Metabolic Acidosis Non-AG Metabolic Acidosis
Urine Anion Gap (UAG) used to evaluate for appropriate renal response to acidemia
Indirect assay for renal NH4 as ammonium is the primary unmeasured cation in UAG calculation
Positive UAG
Early renal failure, type I or IV RTA
Negative UAG
GI loss, type II RTA, ingestions, dilution
More NH4 means more negative
Less NH4 means more positive

40. Metabolic Alkalosis Caused by loss of H+ or gain of HCO3- by the body
Categorized as saline-responsive (UCl <20) vs saline-resistant (UCl >20)
Saline-responsive
GI loss, diuretics, post-hypercapnia
Saline-resistant
Hyperaldosteronism, severe hypokalemia, exogenous alkali

41. Respiratory Acidosis Caused by hypoventilation CNS depression
Neuromuscular disorders
Upper airway abnormalities
Lower airway abnormalities
Lung parenchyma abnormalities
Thoracic cage abnormalities

42. Respiratory Alkalosis
Caused by hyperventilation
Hypoxia-driven hyperventilation
CNS disorder
Pain/anxiety
Toxicologic
Pregnancy
Sepsis
Hepatic failure

43. Case 1
19-year-old female presenting to ED with 2 day history of nausea, vomiting, abdominal pain, and polyuria.
ABG – 7.25 / 23 / 97 / 10
Albumin – 3.6

44. Case 2 ABG – 7.50 / 20 / 92 / 15 Albumin – 4.4 Osmolality – 302
34-year-old male with no past medical history presenting to ED with a three hour history of altered mental status, vertigo, and vomiting.
ABG – 7.50 / 20 / 92 / 15
Albumin – 4.4
Osmolality – 302

45. Stewart Method

47. Stewart Method
Alternative acid-base model created by Dr. Peter A. Stewart
Also referred to as quantitative acid-base
Initially outlined in 1981 in his book, “How to Understand Acid-Base” followed by a 1983 paper, “Modern quantitative acid-base chemistry” in the Canadian Journal of Physiology and Pharmacology

48. 1. The human body must maintain electrical neutrality.
Prime Concepts
1. The human body must maintain electrical neutrality.

49. Prime Concepts
2. The elements that comprise acid-base homeostasis can divided into two categories of variables: independent and dependent.

50. Prime Concepts
3. H+ and HCO3- ions are plentiful in the human body and can be generated at will to maintain electrical neutrality.

51. Prime Concepts
4. There are only three truly independent variables in acid-base homeostasis: strong-ion difference (SID), total weak non-volatile acids (ATOT), and pCO2.

54. Traditional (Schwartz-Bartter) Approach
Input
Output pH
HCO3
Metabolic Acidosis
Metabolic Alkalosis
Respiratory Acidosis
Respiratory Alkalosis
Descriptive approach to acid-base

55. Stewart Method Input Output Status SID ATOT pCO2
Two ways to describe same thing, so there will be some ability for overlap but don’t do it.

56. Stewart Approach Variables
Independent Variables
SID
ATOT
pCO2
Dependent Variables H+
OH-
HCO3-
CO32-
HA (weak acids)
A- (weak ions)
Two ways to describe same thing, so there will be some ability for overlap but don’t do it.

57. Quantitative Model [H+] × [OH-] = K'w [H+] × [A-] = KA × [HA]
The influence of the independent variables can be predicted through 6 simultaneous equations:
[H+] × [OH-] = K'w
Water Dissociation Equilibrium
[H+] × [A-] = KA × [HA]
Weak Acid
[HA] + [A-] = [ATOT]
Conservation of Mass for “A”
[H+] × [HCO3-] = KC × pCO2
Bicarbonate Ion Formation Equilibrium
[H+] × [CO32-] = K3 × [HCO3-]
Carbonate Ion Formation Equilibrium
[SID] + [H+] – [HCO3-] – [A-] – [CO32-] – [OH-] = 0
Electrical Neutrality
Two ways to describe same thing, so there will be some ability for overlap but don’t do it.

58. Strong Ion Difference (SID)
The difference between the sums of the concentrations of the strong cations and the strong anions:
SID = Na + K + Ca2+ + Mg2+ – Cl – [other strong anions]

59. Strong Ion Difference (SID)
The difference between the sums of the concentrations of the strong cations and the strong ions:
SID = Na+ – Cl- ( – [other strong anions] )

60. Strong Ion Difference (SID)
The difference between the sums of the concentrations of the strong cations and the strong ions:
SID = Na+ – Cl- ( – [other strong anions] )
Under normal conditions, SID ≈ 40

61. Changing SID SID = Na+ – Cl- ⇒ relative excess of Na+ cations
If SID >40
⇒ relative excess of Na+ cations
⇒ body generates additional HCO3- anions to maintain electrical neutrality
⇒ pH increases and body becomes more alkalotic

62. Altering SID SID = Na+ – Cl- ⇒ relative excess of Cl- anions
If SID <40
⇒ relative excess of Cl- anions
⇒ body generates additional H+ cations to maintain electrical neutrality
⇒ pH decreases and body becomes more acidotic

63. Altering SID SID = Na+ – Cl- ( – [other strong anions] )
If SID <40
⇒ presence of other strong anions (eg. lactate, ketoacids)
⇒ body generates additional H+ cations to maintain electrical neutrality
⇒ pH decreases and body becomes more acidotic

64. Total Weak Non-Volatile Acids (ATOT)
The plasma concentration of non-volatile weak acids comprised primarily of inorganic phosphate, albumin, and other plasma proteins.
ATOT = [PiTOT] + [PrTOT] + [albumin]
Phosphate is PO4 3-, Albumin is negatively charged as well
Remember that PO43- and [albumin-] are both negatively charged ions.

65. pCO2
As in the traditional method, pCO2 combines with H2O to form H2CO3 (carbonic acid), a highly volatile acid. Therefore:
Increased pCO2 leads to increased acid formation.
Decreased pCO2 leads to decreased acid formation.
CO2 + H2O ⇄ H2CO3

66. Fluid Resuscitation

68. Fluid Resuscitation with Quantitative Acid-Base
Quantitative acid-base allows you to more easily understand how the infusion of certain fluids will affect a patient’s acid-base status
Each type of IVF has its own calculable SID
Ex. 0.9% sodium chloride
Because of dilutionary effects on albumin, the ideal SID for a fluid to not affect acid-base status when infused is actually around 24-28

69. Fluid Resuscitation with Quantitative Acid-Base
Quantitative acid-base allows you to more easily understand how the infusion of certain fluids will affect a patient’s acid-base status
Each type of IVF has its own calculable SID
Ex. 0.9% sodium chloride = 154 mEq Na mEq Cl ⇒ SID = 0
Because of dilutionary effects on albumin, the ideal SID for a fluid to not affect acid-base status when infused is actually around 24-28

70. SIDs of Various IVF IVF SID Sodium chloride 0.9% Sodium chloride 0.45%
Sodium bicarbonate
Lactated ringer’s
Normosol-R
Plasma-Lyte A
Albumin
Dextrose 5%

71. SIDs of Various IVF IVF SID Sodium chloride 0.9% Sodium chloride 0.45%
Sodium chloride 0.45%
Sodium chloride 3%
Sodium bicarbonate
892
Lactated ringer’s 28
Normosol-R 50
Plasma-Lyte A
Albumin
Dextrose 5%

72. Effects of IVF on Acid-Base
Direct infusion of strong ions
Causes direct modification of patient’s SID
Eg. Sodium chloride 0.9%, sodium bicarbonate
Direct infusion of weak ions
Causes direct modification of patient’s ATOT
Eg. Albumin, potassium phosphate
Relative dilution/concentration of plasma
Causes indirect modification of patient’s SID and ATOT
Eg. Dextrose 5%, sodium chloride 3%

74. Questions?

75. References
Grogono AW. “Stewart's Strong Ion Difference.” Available at: Accessed October 3, 2017.
Nickson C. “Strong Ion Difference.” Available at: Accessed October 3, 2017.
Sabatine MS. Pocket Medicine. Lippincott Williams & Wilkins; 2010.
Sterns RH. “Strong ions and the analysis of acid-base disturbances (Stewart approach).” Available at: Accessed October 3, 2017.
Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol. 1983;61(12):
Weingart S. “EMCrit Podcast 44 – Acid Base: Part I.” Available at: Accessed October 3, 2017.
Weingart S. “EMCrit Podcast 50 – Acid Base Part IV – Choose the Solution Based on the Problem.” Available at: Accessed October 3, 2017.
Wikipedia, the free encyclopedia. “Peter A. Stewart”. Available at: Accessed October 3, 2017.