Acid-base terms and definitions
Term Definition
Acid
  • An acid is a substance that can release a hydrogen ion (H+)
  • In water, an acid dissociates reversibly into a H+ and its conjugate base (written as A-): HA ⇌ H+ + A-
  • The more an acid is present in the dissociated form at equilibrium (H+ + A-), the stronger the acid
Base
  • A base is a substance that can accept a hydrogen ion (H+)
  • In the formula HA ⇌ H+ + A-, A- is a base because it can accept H+
Buffer
  • A buffer is a chemical that minimizes the change in pH when an acid or base is added to a solution
  • The main buffer in the human body is carbonic acid (H2CO3)
  • Carbonic acid buffers blood through the following reaction:
    • H+ + HCO3- ⇌ H2CO3 ⇌ H2O + CO2
Anions and cations
  • Anions are atoms or groups of atoms that carry a negative charge. The main anions in human blood are chloride (Cl-) and bicarbonate (HCO3-).
  • Cations are atoms or groups of atoms that carry a positive charge. The main cation in human blood is sodium (Na+).
  • In blood, the concentration of cations and anions must always balance in order to maintain electroneutrality
pH
  • pH is a measure of free hydrogen ions (H+) in a solution
  • pH is calculated in the following manner: pH = log10(1/[H+])
  • Because pH is inversely related to H+, the pH decreases as the concentration of H+ increases
  • pH is measured on an arterial blood gas
  • The normal pH of arterial blood is 7.35 - 7.45
PaCO2
(pCO2,PCO2)
  • PaCO2 is the partial pressure of CO2 in arterial blood
  • Partial pressure is defined as the amount of pressure an individual gas contributes to the overall pressure of a mixture of gases
  • In arterial blood, CO2 normally exerts a partial pressure of 38 - 42 mmHg
  • The PaCO2 in arterial blood is identical to the PaCO2 in alveolar air
  • PaCO2 is measured by drawing an arterial blood gas
  • The normal PaCO2 in arterial blood is 38 - 42 mmHg
PaO2
(pO2,PO2)
  • PaO2 is the partial pressure of oxygen in arterial blood
  • Partial pressure is defined as the amount of pressure an individual gas contributes to the overall pressure of a mixture of gases
  • PaO2 is measured by drawing an arterial blood gas
  • The normal PaO2 of arterial blood is 75 - 100 mmHg
HCO3-
(arterial)
  • HCO3- is the concentration of arterial bicarbonate. Because HCO3- has a negative charge, it is a anion
  • The carbon dioxide value reported on a venous blood draw is also equivalent to the bicarbonate concentration (see carbon dioxide below)
  • HCO3- is measured indirectly on an arterial blood gas
  • The normal concentration of bicarbonate is 22 - 26 mEq/L (mmol/L)
Carbon dioxide (CO2)
(venous)
  • Carbon dioxide is the amount of dissolved carbon dioxide in venous blood
  • Carbon dioxide dissolved in venous blood is almost entirely in the form of bicarbonate
    (H2O + CO2 ⇌ H2CO3 ⇌ H+ + HCO3-). Because of this, the carbon dioxide value is considered equivalent to the venous bicarbonate (HCO3-) value.
  • Carbon dioxide (CO2) is reported on a standard basic metabolic profile
  • The normal value for carbon dioxide is 18 - 30 mEq/L













Acid-base disorder compensation
Primary disorder Compensation
Metabolic acidosis Respiratory compensation (decrease in PaCO2):
  • Compensated PaCO2 is decreased by 1.3 mmHg for each 1 mEq/L decrease in HCO3-
  • Begins within minutes and is maximal at 12 - 24 hours
Metabolic alkalosis Respiratory compensation (increase in PaCO2):
  • Compensated PaCO2 is increased by 0.7 mmHg for each 1 mEq/L increase in HCO3-
  • Begins within minutes and is maximal at 12 - 24 hours
Respiratory acidosis Renal compensation (increase in HCO3-):
  • Acute:
    • Compensated HCO3- is increased by 1 mEq/L for each PaCO2 increase of 10 mmHg above 40 mmHg
  • Chronic (full compensation occurs in 2 - 5 days):
    • Compensated HCO3- is increased by 4 - 5 mEq/L for each PaCO2 increase of 10 mmHg above 40 mmHg
Respiratory alkalosis Renal compensation (decrease in HCO3-):
  • Acute:
    • Compensated HCO3- is decreased by 2 mEq/L for each PaCO2 decrease of 10 mmHg below 40 mmHg
  • Chronic (full compensation occurs in 2 - 5 days):
    • Compensated HCO3- is decreased by 4 - 5 mEq/L for each PaCO2 decrease of 10 mmHg below 40 mmHg




Alveolar-arterial gradient under certain conditions
Condition A-a gradient Cause/Comment
Diffusion impairment Increase
  • Occurs when there is impairment of oxygen diffusing across alveolar-capillary membrane
  • Causes include pulmonary edema, pulmonary fibrosis
Ventilation-perfusion mismatch Increase
  • Occurs when areas of the lung do not receive normal ventilation and/or normal perfusion
  • Causes include pulmonary embolism, airway obstruction, and pneumonia
Physiologic shunt Increase
  • Occurs when blood is shunted from the venous circulation to the arterial circulation
  • Causes include cardiac right-to-left shunt, alveolar shunt, etc.
Generalized hypoventilation Normal
  • Occurs when there is a decrease in overall respiration
  • Causes include emphysema, head injury, drug overdose, comatose patient
Reduced oxygen content of blood Normal
  • Occurs when the oxygen-carrying capacity of the blood is reduced
  • Causes include anemia and carbon monoxide poisoning






















Practical approach to acid-base disorders
Step 1 - obtain appropriate lab values

  • In order to assess acid-base disorders, the following lab values are necessary:
    • Arterial blood gas (ABG) - pH value, PaCO2, PaO2, HCO3-
    • Comprehensive metabolic profile - Sodium (Na+), Chloride (Cl-), Carbon dioxide (CO2), Albumin
Step 2 - determine if the primary disorder is an acidosis or alkalosis

  • pH < 7.35 - primary disorder is an acidosis
  • pH > 7.45 - primary disorder is an alkalosis
Step 3 - determine the source of the primary disorder

  • Acidosis (pH < 7.35)
    • If the PaCO2 is > 42 mmHg, then the primary disorder is a respiratory acidosis
    • If the HCO3- is < 22 mEq/L, then the primary disorder is a metabolic acidosis
  • Alkalosis (pH > 7.45)
    • If the PaCO2 is < 38 mmHg, then the primary disorder is a respiratory alkalosis
    • If the HCO3- is > 26 mEq/L, then the primary disorder is a metabolic alkalosis

  • Compensation - respiratory/metabolic compensation may or may not be present depending on the length of the disorder. See compensation above for more.
Step 4 - calculate the anion gap

  • Anion gap
    • Anion gap = Na+ - [Cl- + HCO3-] where HCO3- is represented by venous carbon dioxide
    • If serum albumin is < 4 grams/dl, then the anion gap should be corrected:
      • Corrected anion gap (hypoalbuminemia) = (4 - serum albumin concentration) X 2.5 + calculated anion gap
    • See anion gap for a review of the anion gap

  • If the anion gap is ≥ 20, then a metabolic acidosis is either the primary or coprimary disorder regardless of the bicarbonate or pH value
    • The reasoning behind this is that the body will not generate an anion gap ≥ 20 even in the face of chronic alkalosis

  • If the primary disorder is a metabolic acidosis:
Step 5 - look for a mixed acid-base disorder

  • Calculate the excess anion gap and add it to the bicarbonate value:
    • Excess anion gap (EAG) = Calculated anion gap - 12
    • Bicarbonate value = venous carbon dioxide measurement

  • If EAG + bicarbonate > normal serum bicarbonate (30 mEq/L) then extra bicarbonate has been added to the serum and a metabolic alkalosis is also present
  • If EAG + bicarbonate < normal serum bicarbonate (23 mEq/L) then a normal anion gap metabolic acidosis is also present






Acetazolamide for prevention of acute mountain sickness
Dosing:
  • 250 mg two to three times a day starting 24 - 48 hours before ascent and continued for 48 hours while at high altitude or longer if necessary
Dosage form:
  • 125 and 250 mg tablet
  • Cost for 30 tablets is < $50
Contraindications/precautions:
  • Sulfonamide allergy - acetazolamide is a sulfonamide derivative
  • Hyponatremia - may worsen
  • Hypokalemia - may worsen
  • Significant kidney disease - may worsen acidosis
  • Metabolic acidosis - may worsen
  • Cirrhosis - may exacerbate hepatic encephalopathy
Common side effects:
  • Paresthesia (numbness and tingling) of the fingers and toes - up to 90%
  • Increased urination - up to 55%
  • Nausea and tiredness - up to 20%
  • Taste perversion, especially carbonated beverages - up to 14%