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

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

Physiologic Effects of Acid-Base Disturbances

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

Traditional (Schwartz-Bartter) Approach

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

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

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

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

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

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

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

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

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

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

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

Step 4: Compensation

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

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

Step 4: Compensation

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Stewart Method

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

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

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

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

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.

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

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.

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.

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.

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]

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] )

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

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

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

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

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.

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

Fluid Resuscitation

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

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 + 154 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

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%

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%

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%

Questions?

References Grogono AW. “Stewart's Strong Ion Difference.” Available at: https://www.acid-base.com/strongion.php. Accessed October 3, 2017. Nickson C. “Strong Ion Difference.” Available at: https://lifeinthefastlane.com/ccc/strong-ion-difference/. 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: https://www.uptodate.com/contents/strong-ions-and-the-analysis-of-acid-base-disturbances-stewart-approach. Accessed October 3, 2017. Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol. 1983;61(12):1444-61. Weingart S. “EMCrit Podcast 44 – Acid Base: Part I.” Available at: https://emcrit.org/emcrit/acid-base-i. Accessed October 3, 2017. Weingart S. “EMCrit Podcast 50 – Acid Base Part IV – Choose the Solution Based on the Problem.” Available at: https://emcrit.org/emcrit/acid-base-4-use-of-fluids. Accessed October 3, 2017. Wikipedia, the free encyclopedia. “Peter A. Stewart”. Available at: https://en.wikipedia.org/wiki/Peter_A._Stewart. Accessed October 3, 2017.