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Step 2 CK · Internal Medicine · Nephrology

Acid-Base Disorders (Clinical)

A repeatable system that exposes mixed disorders

Nephrology·Fluids, Electrolytes & Acid-Base·4 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy
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A fixed system for every gas

Why a system. Mixed disorders hide behind a normal-looking pH; only a fixed sequence exposes them. Normal values are pH 7.35–7.45, HCO₃⁻ 22–26 mEq/L, and PaCO₂ 35–45 mmHg.

  1. pHAcidemia (<7.35) or alkalemia (>7.45).
  2. Primary disorderHCO₃⁻ change = metabolic; PaCO₂ change = respiratory.
  3. CompensationIs it appropriate, or is a second disorder present?
  4. Anion gapNa − (Cl + HCO₃⁻), corrected for albumin.
  5. Delta gapUnmasks a second metabolic disorder.
  6. ReconcileMatch the numbers to the clinical picture.
Systematic ABG interpretation

Anion gap. Anion gap = Na − (Cl + HCO₃⁻); normal is 8–12 mEq/L. Albumin is the main unmeasured anion, so add 2.5 to the measured gap for every 1 g/dL that albumin is below 4; otherwise a gap acidosis hides in sick, hypoalbuminemic patients.

Compensation and mixed disorders

Winter formula. In metabolic acidosis the expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2. A measured PaCO₂ above the range means a superimposed respiratory acidosis; below it, a superimposed respiratory alkalosis. Example: HCO₃⁻ 12 predicts PaCO₂ about 26, so a measured 34 reveals inadequate ventilation.

Expected compensation
Primary disorderPrimary changeExpected compensation
Metabolic acidosis↓ HCO₃⁻PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2
Metabolic alkalosis↑ HCO₃⁻PaCO₂ rises ~0.7 per 1 mEq/L rise in HCO₃⁻
Respiratory acidosis↑ PaCO₂HCO₃⁻ rises ~1 per 10 mmHg (acute), ~3.5–4 per 10 (chronic)
Respiratory alkalosis↓ PaCO₂HCO₃⁻ falls ~2 per 10 mmHg (acute), ~4–5 per 10 (chronic)
Compensation never fully normalizes the pH; overshoot or undershoot defines a mixed disorder.

Delta ratio. Rise in anion gap divided by fall in HCO₃⁻, or (AG − 12) / (24 − HCO₃⁻):

  • About 1–2: pure high-gap acidosis
  • Less than 1: HCO₃⁻ fell more than the gap explains, so a normal-gap acidosis coexists
  • Greater than 2: HCO₃⁻ is higher than expected, so a metabolic alkalosis (or chronic respiratory acidosis) coexists, as in the vomiting DKA patient

High anion gap acidosis

MUDPILES. Unmeasured anions consume bicarbonate. Lactate and ketones (diabetic, alcoholic, starvation) are the most common causes.

MUDPILES and their clues
CauseClueKey management
MethanolVisual loss; high osmolal gapFomepizole, ± dialysis
UremiaAdvanced kidney failureDialysis if refractory
DKAHyperglycemia, β-hydroxybutyrateFluids, insulin, potassium; close the gap
Propylene glycolHigh-dose lorazepam infusionsStop the infusion
Iron / isoniazidGI bleeding (iron); seizures (isoniazid)Deferoxamine; pyridoxine
Lactic acidosisType A: shock, sepsis, hypoxia; type B: drugs such as metformin, linezolidTreat the underlying cause
Ethylene glycolCalcium oxalate crystals, AKI; high osmolal gapFomepizole, ± dialysis
SalicylatesTinnitus, tachypnea, hyperthermiaUrine alkalinization; dialysis if severe

DKA. The gap comes from β-hydroxybutyrate. Treat with fluids, insulin, and potassium, and titrate to closing the gap, not just to lowering glucose. Hold insulin until potassium is at least 3.3 mEq/L.

Salicylate toxicity produces two primary disorders at once: respiratory alkalosis from medullary stimulation plus a high-gap metabolic acidosis from uncoupled oxidative phosphorylation, so the pH may be near normal. Give sodium bicarbonate to alkalinize the urine, which traps ionized salicylate in the tubule and boosts clearance (ion trapping); dialyze for severe toxicity (altered mental status, pulmonary edema, kidney failure).

If a salicylate-poisoned patient must be intubated, keep the minute ventilation high; losing the compensatory hyperventilation deepens acidemia and drives salicylate into the brain.

Normal anion gap acidosis and RTA

Lost bicarbonate, retained chloride. Normal-gap (hyperchloremic) acidosis comes from bicarbonate loss: diarrhea, renal tubular acidosis, carbonic anhydrase inhibitors (acetazolamide), ureteral diversion, and early kidney disease. The urine anion gap separates GI causes (negative) from renal causes (positive).

  • Type 1 (distal): cannot secrete H⁺; urine pH >5.5, hypokalemia, calcium phosphate stones.
  • Type 2 (proximal): wastes HCO₃⁻; hypokalemia; part of Fanconi syndrome.
  • Type 4 (hypoaldosteronism): the only hyperkalemic RTA, with urine pH <5.5; classically hyporeninemic hypoaldosteronism in diabetics.

Metabolic alkalosis and respiratory disorders

Metabolic alkalosis by urine chloride
FeatureChloride-responsiveChloride-resistant
Urine Cl<20 mEq/L>20 mEq/L
CausesVomiting, NG suction, diuretics after they wear offHyperaldosteronism, Cushing syndrome (hypertensive); Bartter or Gitelman (normotensive)
TreatmentNormal saline, plus potassiumSaline will not fix it; treat the cause
Vomiting loses H⁺ and Cl⁻; while a diuretic is still acting, urine Cl is high despite a saline-responsive state.

Respiratory acidosis is hypoventilation: COPD, opioids and sedatives, neuromuscular disease (Guillain-Barré, myasthenia gravis), and obesity hypoventilation. Treat the ventilation problem (noninvasive ventilation, intubation, naloxone for opioids).

Respiratory alkalosis is hyperventilation: anxiety or pain, pulmonary embolism, high altitude, pregnancy, sepsis, and salicylates.