Acid Base Disorders: Key Core Concepts

Thomas DuBose M.D., MACP, FASN

ASN Board Review Course

Online Resource Material

2014

Speaker Disclosure

I, Thomas DuBose, M.D., have no financial relationships or affiliations with industry to disclose.

Basic Concepts of Acid-Base Balance

• Henderson-Hasselbach Equation:

pHa = 6.1 + log10 (HCO3-/PaCO2 X 0.0301)

• pH maintained between 7.35 & 7.45 and pHi 7.0-7.3. Fine tuned regulation occurs in face of continuous production of acid metabolites and is accomplished by intracellular and extracellular buffers in conjunction with respiratory and renal regulatory mechanisms.

Primary Disturbance and Compensatory Responses

pH pCO2 HCO3-

Metabolic acidosis 2o 1o

Metabolic alkalosis 2o 1o

Respiratory acidosis 1o 2o

Respiratory alkalosis 1o 2o

Compensatory Responses for Simple Acid-Base Disorders*

*DuBose TD, Acidosis and Alkalosis, in HPIM ED 19, Chapt 66, 2014

(Winter Equation)

Derivation of Winter Equation

A Simpler Approach to Predict Respiratory Compensation in Metabolic

Acidosis and Metabolic Alkalosis

• In range of serum bicarbonate of 10-40 mEq/L

Add 15 to patient’s [HCO3-] to predict PCO2

Examples:

HCO3- Predicted PCO2

15 30

35 50 • Compare predicted and measured values

Types of Acid-Base Disturbances 1. Simple

Respiratory

acidosis

alkalosis

Metabolic

acidosis

alkalosis

2. Mixed

Mixed Acid-Base Disturbances

• Definition

– Combination of two or more of the 4 simple disturbances

• Examples

– Mixed respiratory-metabolic disorders

– Mixed metabolic disorders

Key Board Review Point: Step-wise evaluation of acid-base disorders

1. Always analyze acid-base disturbance with both ABG and Venous Electrolyte Panel (BMP)

2. Verify accuracy

Compare calculated [HCO3-] on arterial blood gas with

measured [HCO3-] on electrolyte panel

3. Calculate anion gap; but correct for deviation of Palb from normal (4.0 Gm/dL)

4. Calculate predicted respiratory or metabolic compensation

5. Know Causes of HAG and NAG acidosis

6. Compare Δ HCO3- with D AG

7. Compare D Na+ with D Cl-

8. Calculate Serum Osmolar Gap when cause of HAG not known or toxic alcohol ingestion suspected

The Anion Gap

AG = Na+ − (Cl- + HCO3-)

Normal Value 6 -12 mEq/L

Represents unmeasured anions present in serum including anionic proteins, phosphate, sulfate, and organic anions. Major assumption is that ECFV is “normal” or that Hct and Palb are “normal”. If not must correct AG for deviation of Palb from normal value of 4.0 Gm/dL.

Anatomy of the Anion Gap

Na+

140

Cl-

105

HCO3 25

PO4/SO4 2

Organic acid 4

Protein 16

Mg 2

Ca 5

K 5

These cations = 12 These anions = 22

Anion gap is Unmeasured

anions - Unmeasured

cations or

22-12 = 10

Anion gap is calculated as Na -

(Cl + HCO3) or

140-130 = 10

Cations Anions

mEq/L

Correction of the AG for PAlb

For each 1 Gm/dL DECREASE in albumin below 4.0mEq/L the reported AG will be factitiously reduced by 2.5mEq/L

For each 1 Gm/dL INCREASE in albumin above 4.0mEq/L the reporteded AG will be factitiously increased by 2.5mEq/L

Example: if PAlb is 2 and AG is 15, to correct AG add 2.5 X 2 = 5 to 15

Corrected AG = 20 mEq/L

Illustration of Method

• Na 140, K 4.9, Cl 106, HCO3 14, BUN 23, Cr 1.1, Alb 4.0

• pH 7.39, PaCO2 24, PaO2 90, HCO3 13

• Apply the step-wise approach to answer next question:

Question: What is the precise acid-base diagnosis in the previous

example? 1. Metabolic acidosis with

overcompensation

2. High anion gap metabolic acidosis

3. Mixed metabolic acidosis + respiratory alkalosis

4. Mixed metabolic acidosis + respiratory acidosis

Stepwise solution for diagnosis

• Measured and calculated HCO3 similar

• AG = 20, defines presence of a high anion gap acidosis

• What is predicted respiratory compensation in this case?: – Winter equation: 1.5 X 14 + 8 = 29

– 29 ≠ 24

• Therefore, correct answer? – (next slide)

Correct Answer, # 3

1. Metabolic acidosis with overcompensation

2. High anion gap metabolic acidosis

3. Mixed metabolic acidosis – respiratory alkalosis

4. Mixed metabolic acidosis – respiratory acidosis

Example of stepwise approach using D values (step 6)

• A patient is admitted with a history of vomiting for 2 days and orthostatic hypotension. PMH of CKD secondary to DM, baseline Cr 3.

• Laboratory: Na 140, K 3.7, Cl 95, HCO3- 25,

BUN 80, Cr 7.9, glucose 130, pH 7.40, PaCO2 39, PO2 92, Albumin 4.0

• Consider the AG, and the DHCO3 vs. DAG

Using D values

• AG = 20, DAG = 10

• DHCO3 = 0

• Therefore, DAG > DHCO3, defines a mixed high anion gap metabolic acidosis plus metabolic alkalosis

Mixed Metabolic Acidosis-Alkalosis

Electrolyte Values (mEq/L)

Serum

Electrolytes

Normal

High Gap

MA

MA and

MA

(Vomiting)

Sodium 140 140 140

Chloride 105 105 95

Bicarbonate 25 15 25

Anion gap 10 20 20

DAG +10 +10

DC- -10 0

Step 5: Causes of High Anion Gap Acidosis

• Ketoacidosis

– Diabetic ketoacidosis

– Alcoholic ketoacidosis

– Starvation ketoacidosis

• Lactic Acidosis

– L-Lactic acidosis

Type A

Type B

– D-Lactic acidosis

Causes of High Anion Gap Acidosis - continued

• Renal Failure

– Acute and Chronic

• Toxins

– Ethylene glycol – High Osmolar Gap

– Methyl alcohol – High Osmolar Gap

– Propylene glycol – High Osmolar Gap

– Salicylates – high salicylate level

– Pyroglutamic acid or 5- oxoprolene (glutathione depletion)

Gold Mark: Modern Mnemonic for Anion Gap Acidosis

GOLD MARK Glycols (ethylene and propylene) Oxoproline L-lactate D-lactate Methanol Aspirin Renal failure Ketoacidosis

Mehta, AN, Emmett,JB and Emmett, M. The Lancet, 2008; 372: 892

Useful Ancillary Tests in the Diagnosis of High AG Metabolic Acidosis

• Serum and urine ketones

• Serum creatinine

• Serum L-lactate (consider D-lactate)

• Serum osmolality to calculate osmolar gap

• Serum toxic alcohols

• Pyroglutamic acid (5-oxoproline)

• Urine microscopy for crystals

Osmolar Gap in Diagnosis of Toxin-Induced Anion Gap Acidosis

Compare measured and calculated osmolality

Gaposm = Posmdet - Posm

cal Posm

cal = 2Na+ + BUN/2.8 + Glu/18

Key Point: Gaposm > 10 mOsm/kg. in setting of possible toxin ingestion suggests methyl alcohol, ethylene glycol, or propylene glycol intoxication

UNDERSTANDING NON-GAP METABOLIC ACIDOSIS

Overview of Renal Pathophysiology

Distinguishing Renal from Non-Renal Forms

Role of the Kidney in the Defense Against Metabolic Acidosis

Role of the Kidney in Regulation of Acid-Base Balance: 2 Components

• Reclamation of Filtered Bicarbonate –Proximal Tubule

–Distal Nephron

• Regeneration of ECF [HCO3-]

consumed by net acid production –Ammonia production and excretion

increases with dietary acid load

Definition of Non-Gap Acidosis

• Low Bicarbonate, low pH

• Normal Anion Gap (~8-10 mEq/L)

– Note Albumin – correct to 4 Gm/dL

• Compensatory decrease in PCO2

– Predicting Respiratory Compensation:

• Winter Equation: PCO2 = 1.5 (HCO3-) + 8 ± 2

• Add 15 to Patient’s [HCO3-]

• Example:

Clinical Examples: NAG Acidosis Electrolyte Values ( mEq/L)

Serum

Electrolytes

Normal

NAG - MA

NAG - MA

+ High

AG - MA

S o dium 1 4 0 1 4 0 1 4 0

Chlo r ide 1 05 1 1 5 1 1 5

Bicarbonate 25 15 5

Ani o n gap 10 10 20

AG 0 +10

C - 10 - 20

Causes of Non-Gap Acidoses (step 5) Diarrhea or other GI losses of alkali (e.g., tube drainage) Ureteral diversion (e.g., ileal loop,

ureterosigmoidostomy) Posttreatment of ketoacidosis (dilutional) Progressive chronic kidney disease Toluene ingestion (excretion of hippurate) Drugs

Carbonic anhydrase inhibitors: acetazolamide, topiramate, sulfamyalon Amphotericin B CaCl2, MgSO4, Cholestyramine Acid loads (NH4Cl, acidic amino acids -TPN, sulfur) For Hyperkalemia: amiloride, triamterenene, spironolactone, TMP

Post - hypocapnic state RTA’s – proximal, classical distal, mixed, type 4

Mnemonic for Non-Gap Acidosis

• HAARDUPS

– Hyperalimentation

– Acetazolamide or any CA Inhibitor

– Amphotericin B

– RTA

– Diarrhea

– Ureterosigmoidostomy

– Post hypocapneic state, pancreatic fistula

– Sulfamyalon

Types of Renal Acidoses • Hypokalemic Forms

– Proximal RTA (Type 2)

– Classical Distal RTA (Type 1)

• Hyperkalemic Forms – Aldosterone Deficiency or Resistance (Type 4)

– Non-mineralocorticoid Voltage Defect

• Normokalemic – RTA of CKD 2-4

– Uremic Acidosis

Distinction between Non-Renal and Renal Origin of NAG Acidosis; Use

of the Urine Anion Gap: Pathophysiological Response of

Kidney to Acidosis

Renal Origin vs. Non Renal Origin

• Estimate Urine Ammonium (spot urine lytes)

–Urine Anion Gap is Surrogate for UAm

–UAG = [UNa + UK] -UCl

• Interpretation:

–Negative Value: Non-Renal Origin (Ammonium Adequate)

–Positive Value: Renal Origin (Ammonium Low)

Clinical Recognition of Renal Response To Non-Gap Metabolic Acidosis

• Non-Renal – Increase in NH4

+ Excretion (kidney response appropriate) • Negative Urine Anion Gap • Acid urine pH (<5.5) - exceptions

• Renal – Inability to increase NH4

+ Excretion (inappropriate kidney response) • Positive Urine Anion Gap • Urine pH typically > 5.5 but more variable in

Type 4

Tests useful in the Differential Diagnosis of NAG Metabolic Acidosis

• Serum potassium

• Serum creatinine

• Urine electrolytes

– TTKG or FEK

– FEHCO3-

• Urine osmolality and urine osmolar gap

• Urine pH

Mixed High Anion Gap and Normal Anion Gap Metabolic Acidosis in a Patient with Severe

Diarrhea Electrolyte Values (mEq/L)

Serum

Electrolytes

Normal

NAG-MA

NAG-MA

+ High

AG-MA

Sodium 140 140 140

Chloride 105 115 115

Bicarbonate 25 15 5

Anion gap 10 10 20

DAG 0 +10

DC- -10 -20

Adverse Consequences Severe Acidemia

• Cardiovascular – Impaired contractility, vasodilatation,

venoconstriction, decreased C.O., sensitization to arrhythmias, decreased responsiveness to pressors.

• Respiratory –Hyperventilation, respiratory muscle fatigue,

dyspnea

• Metabolic – Insulin resistance, inhibition of anaerobic glycolysis,

protein degradation, decreased ATP synthesis, hyperkalemia.

Complications of Bicarbonate Therapy • Overshoot alkalosis: –Exogenously administered NaHCO3 must be

added to endogenously produced by metabolism of ketones, lactate, etc.

• Increase in lactate generation • Volume expansion with ARF or ESRD • Increased CO2 production • Hypocalcemia • Cardiac depression

When to Give NaHCO3 • In ESRD, CKD stage 2-4 keep HCO3>22 to avoid osteopenia,

hypercalciuria, natriuresis, sarcopenia, and to help slow progression of CKD.

• In DKA, almost never; extreme acidosis? (pH<6.9), never for children? – Treat the underlying cause with regular insulin + i.v. fluid

replacement

• In L-lactic acid acidosis, pH < 7 – Treat the underlying cause – Give no more NaHCO3 than needed to increase pH to 7.1 – Consequence of NaHCO3 in lactic acidosis: increase in lactate

production

Summary: Solving Acid-base Problems • If metabolic acidosis:

– For Non-gap Acidoses • Distinguish renal from non-renal forms

• Calculate urine anion gap and/or urine osmolar gap and note urine pH

– For High AG Acidoses • Know causes of high anion gap metabolic acidosis

• If toxin suspected: calculate Osmolar Gap

• If hypokalemia:

– Calculate TTKG or FE K+ to determine if K loss of renal origin • If metabolic alkalosis:

– Look at urine [Cl-] and separate into two categories: Cl responsive and Cl unresponsive