You Know We’re All About That Acid/Base

General approach

General approach to assessing acid/base discrepancies:

  1. Determine the primary disturbance
  2. Determine the degree of compensation
  3. Calculate the anion gap and determine the presence of a concurrent acid/base problem
    • If AGMA, then calculate the delta ratio
    • If NAGMA, then calculate the urine anion gap
  4. Consider etiologies and establish a clinical diagnosis

Key point: It’s essential to consider the clinical picture when evaluating a patient with an acid/base disorder, and balance the clinical presentation with the test results.

Determining the primary disturbance

To determine the primary acid/base disturbance, we first look at the pH followed by PCO2 (respiratory component) and HCO3 (metabolic component.)

Acidemia refers to the overall state of acid in the blood (i.e., arterial pH <7.35), whereas acidosis refers to any process that increases the concentration of hydrogen ions (e.g., AGMA or NAGMA.) The idea is similar for alkalemia and alkalosis.

Source: WikiMedia Commons
  • Metabolic acidosis = disorder that reduces the serum HCO3 concentration and the pH
  • Metabolic alkalosis = disorder that elevates the serum HCO3 concentration and the pH
  • Respiratory acidosis = disorder that elevates the arterial PCO2 and reduces the pH
  • Respiratory alkalosis = disorder that reduces the arterial PCO2 and elevates the pH

Determining the degree of compensation

The body attempts to normalize the acid/base equilibrium in response to any acid/base disorder, thus compensation depends on the primary disorder.

Primary disorderPCO2-pH relationshipPCO2-HCO3 relationship
Respiratory acidosisFor each 10 mmHg increase in PCO2, pH decreases by 0.08 (acute) or 0.03 (chronic)For each 10 mmHg increase in PCO2, HCO3 increases by 1 mEq/L (acute) or 3.5 (chronic)
Respiratory alkalosisFor each 10 mmHg decrease in PCO2, pH increases by 0.08 (acute) or 0.02 (chronic)For each 10 mmHg decrease in PCO2, HCO3 decreases by 2 mEq/L (acute) or 5 (chronic)
Metabolic acidosis“2-digit rule”: Last 2 digits of pH correspond to PCO2Winter’s formula: PCO2 = 1.5xHCO3 + 8 ± 2
Metabolic alkalosis“2-digit rule”: Last 2 digits of pH correspond to PCO2For each 10 mEq/L increase in HCO3, PCO2 increases by 6
Source: ACP Critical Care Video Shorts

If compensation is less or greater than expected, a second acid/base disorder is likely present in addition to the primary disorder (i.e., mixed disorder.)

  • If PCO2 is too low, there is an additional respiratory alkalosis; if PCO2 is too high, there is an additional respiratory acidosis
  • If HCO3 is too low, there is an additional metabolic acidosis; if HCO3 is too high, there is an additional metabolic alkalosis
  • Note that because we can’t hypoventilate and hyperventilate at the same time, we can’t simultaneously have a respiratory acidosis and respiratory alkalosis

Anion Gap & Other Calculations

Determination of the serum anion gap (AG) is primarily used in the differential diagnosis of metabolic acidosis.

Serum AG = Na – (Cl + HCO3)

  • In general, a normal AG is ~12; however, each laboratory determines its own reference range
  • It’s essential to check the AG, even with a normal pH. This will help prevent missing mixed acid/base disorders in which the pH is normal because of 2 or even 3 different ongoing processes.
  • AG should be corrected for hypoalbuminemia. In general, AG decreases by ~2.5 for every 1 g/dL decrease in albumin
    • Actual formula: Albumin-corrected AG = AG + (2.5 x [4.5 – albumin])
      • ex: if AG is 15 and albumin is 2, then the albumin-corrected AG is 21

Assuming that HCO3 is our primary buffer, then an increase in AG would correspond to a similar decrease in HCO3. This ratio is known as the delta ratio, which compares the change in AG relative to the change in HCO3. If the change in HCO3 is different than expected, then an additional acid-base disorder may be present.

Delta ratio = (measured – normal AG) / (measured – normal HCO3)

  • Delta ratio <1 suggests a concurrent acidosis (i.e., presence of NAGMA in addition to AGMA)
  • Delta ratio >2 suggests a concurrent metabolic alkalosis
  • Note that the delta ratio assumes that there is 1:1 buffering by HCO3, when in reality the blood buffering system is much more complex (i.e., also mediated by hemoglobin, albumin, phosphate, body temperature, and oxygen saturation)

Determination of the urine anion gap (UAG) is primarily used to determine the etiology of NAGMA by providing an estimate of urinary ammonium excretion (i.e., acid excretion.)

UAG = (urine Na + urine K) – urine Cl

  • Positive UAG (usually 20-90 mEq/L; low or normal ammonium excretion) suggests an intrinsic renal issue (e.g., RTA)
  • Negative UAG (usually between -20 and -50 mEq/L; increased ammonium excretion) suggests an extra-renal etiology (e.g., diarrhea)

Osmolality is a measurement of the number of moles of dissolved particles per kg of solvent (for clinical purposes, water is the solvent.) The osmolar gap is the difference in the measured osmolality and calculated osmolality.

Osmolar gap = measured Osm – calculated Osm

  • Calculated Osm = 2xNa + glc/18 + BUN/2.8
  • Normally, the measured osmolality and the calculated osmolality are similar (generally within approximately 6 mosmol/kg.) An elevated osmolar gap suggests the presence of osmotically active compounds in the bloodstream (e.g., methanol, ethylene glycol, isopropyl alcohol)

Base excess is the amount of acid needed to be added to the blood to restore it to standard conditions (i.e., arterial pH of 7.40 and PaCO2 of 40.) The reference value for standard base excess is 0 mmol/L (±2).

  • The terms “base deficit” and “base excess” are often used interchangeably, creating confusion. Recognize that in a patient with metabolic acidosis, a negative base excess (e.g., −6 mmol/L) is perhaps easier to think about as a base deficit (6 mmol/L; i.e., an excess of acid in the body binds any available base, leading to a base deficit)



We categorize metabolic acidosis into high anion gap metabolic acidosis (AGMA or HAGMA) or normal anion gap metabolic acidosis (NAGMA).

  • In acidotic states with low HCO3 values, NAGMA can exist through the buffering effect of Cl (i.e., hyperchloremic NAGMA.) In these conditions, the relative ratio of anions and cations remains intact, with the anions balanced by an increase of Cl equal to the decrease in HCO3.


  • “MUDPILES” is the classic mnemonic for common causes of AGMA:
    • Methanol / Metformin
    • Uremia
    • DKA
    • Paraldehyde / Phenformin
    • Iron / Isoniazid
    • Lactic acidosis
    • Ethylene glycol
    • Salicylates
  • AGMA occurs in AKI/CKD when GFR <15 due to retention of sulfates, phosphates, and organic acids


  • “HARDASS” is a mnemonic for common causes of NAGMA:
    • Hyperalimentation
    • Addison’s disease
    • RTA
    • Diarrhea
    • Acetazolamide
    • Spironolactone
    • Saline infusion
  • NAGMA occurs in AKI/CKD when GFR <45 due to decreased excretion of urine ammonium

Respiratory acidosis

  • Most often occurs in the presence of impaired ventilation, impaired gas exchange, and/or airway obstruction:
    • Decreased CNS drive: drugs (narcotics, sedatives), CNS structural lesions, severe metabolic or endocrinopathies
    • Neuromuscular disease: myasthenia gravis, Guillan-Barre syndrome, ALS, muscular dystrophy, polymyositis, cervical spinal cord injury, diaphragmatic fatigue
    • Chest wall / spine disease: kyphoscoliosis, ankylosing spondylitis
    • Lung disease: COPD, asthma, ARDS, end-stage ILD
    • Other: obesity


Metabolic alkalosis

  • Most often occurs as a result of gastric or renal losses:
    • Gastric losses: vomiting, NG suction
    • Renal losses: diuretics, excess mineralocorticoids, post-hypercapnic state, Bartter syndrome, Gitelman syndrome, licorice ingestion
    • Other: hypokalemia, bicarbonate administration, dehydration, chloride-depletion alkalosis (for which contraction alkalosis is a misnomer)

Respiratory alkalosis

  • Most often occurs in the presence of increased respiratory drive, hypoxemia, and/or pulmonary disease with thoracic stretch stimulation
    • CNS disease: stroke, intracerebral hemorrhage, CNS infection
    • Psychiatric: anxiety, panic attack, voluntary hyperventilation
    • Hormones/drugs: thyroid, pregnancy, stimulants, salicylates
    • Lung disease: asthma, ILD, PNA, ARDS
    • Other: PE, high altitude, liver disease

Blog post based on Med-Peds Forum talk by Julia Solomon, PGY4

Scroll to Top