Differentials

Common

GI loss of bicarbonate

History

diarrhea, GI drainage and fistulas, surgical urinary diversion of bowel, intake of chloride-containing anion-exchange resins such as calcium chloride or magnesium chloride

Exam

diagnosis is usually based on historical versus physical findings

1st investigation
  • serum anion gap:

    <12 mEq/L

Other investigations
  • urine anion gap:

    low (<0 mEq/L)

Renal loss of bicarbonate - renal tubular acidosis type 1 and 2

History

family history, autoimmune disease (Sjogren syndrome, systemic lupus erythematosus, rheumatoid arthritis), amyloidosis, multiple myeloma, urinary obstruction, medication history (lithium, amphotericin B, ifosfamide, carbonic anhydrase inhibitors), osteomalacia, or rickets

Exam

diagnosis is usually based on historical versus physical findings

1st investigation
  • serum anion gap:

    <12 mEq/L

Other investigations
  • urine anion gap:

    high (> 0 mEq/L)

  • urinary pH:

    type 1 >5.3; type 2 <5.3

  • serum potassium:

    low

Renal tubular acidosis type 4

History

diabetes, hypoaldosteronism, medication history (amiloride, spironolactone, trimethoprim, cyclosporine)

Exam

diagnosis is usually based on historical versus physical findings

1st investigation
  • serum anion gap:

    <12 mEq/L

Other investigations
  • urine anion gap:

    high (>0 mEq/L)

  • urinary pH:

    low

  • serum potassium:

    high

  • plasma aldosterone:

    low in primary adrenal failure and secondary renal causes

  • plasma renin:

    high in primary adrenal failure and low in secondary renal causes

Diabetic ketoacidosis

History

patients with type 1 diabetes, particularly in the setting of concomitant illness such as infection or myocardial infarction; can occur rarely in patients with type 2 diabetes; history of taking fluoroquinolone antibiotics, atypical antipsychotics, corticosteroids, some beta-blockers, thiazide and thiazide-like diuretics, protease inhibitors, calcineurin inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors (licensed to treat type 2 diabetes mellitus)

Exam

confused, drowsy, vomiting, smell of ketones on breath

1st investigation
  • serum anion gap:

    >12 mEq/L

Other investigations
  • serum and urinary ketones:

    elevated (measurable)

  • serum and urinary glucose:

    elevated

  • serum lactate:

    elevated

Alcohol ketoacidosis

History

chronic alcohol consumption; malnutrition; nausea, vomiting, abdominal pain

Exam

confused, drowsy, smell of ketones on breath; peripheral signs of chronic liver disease (spider nevi, leukonychia, palmar erythema, bruising, jaundice, scratch marks); hepatomegaly

1st investigation
  • serum anion gap:

    >12 mEq/L

Other investigations
  • urinary ketones:

    usually present

    More
  • ethanol level:

    low or absent

  • serum and urinary glucose:

    low or normal

  • serum lactate:

    elevated but insufficient to explain acidosis

Ingestion of toxic substances

History

history of ingestion: ethanol, methanol (ethanol substitute), ethylene glycol (constituent of automobile antifreeze), propylene glycol (diluent in many intravenous medications such as lorazepam)

Exam

confused, drowsy

1st investigation
  • serum osmolar gap:

    normally <10 mOsm/L

  • serum anion gap:

    >12 mEq/L

Other investigations
  • serum toxicology screen (ethanol, methanol, ethylene glycol, propylene glycol):

    positive

  • serum lactate:

    elevated

Acetaminophen ingestion (5-oxoproline toxicity)

History

history of chronic ingestion of acetaminophen or acetaminophen overdose; associated comorbidities such as malnutrition and chronic kidney disease

Exam

confused, drowsy

1st investigation
  • serum anion gap:

    >12 mEq/L

Other investigations
  • serum and urinary acetaminophen:

    positive (not necessarily in the toxic range)

  • serum lactate:

    elevated

  • mass spectrography for 5-oxoproline:

    positive

    More

Salicylate intoxication

History

therapeutic aspirin use or deliberate overdose

Exam

confusion, tinnitus, hyperventilation, pulmonary edema

1st investigation
  • serum anion gap:

    >12 mEq/L

Other investigations
  • salicylate level:

    >300 micrograms/mL

Lactic acidosis

History

history of possible underlying cause: tissue hypoperfusion, diabetes, medication (e.g., metformin, paraldehyde, antiretroviral therapy), genetic defects (e.g., MELAS syndrome [mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes])

Exam

may have physical findings relating to underlying cause

1st investigation
  • serum anion gap:

    >12 mEq/L

Other investigations
  • serum lactate:

    elevated

Acute renal failure

History

may be asymptomatic; symptoms include anorexia, fatigue, itch, nausea, vomiting, and shortness of breath (SOB)

Exam

asterixis, pericardial or pleural rub, peripheral edema, pulmonary rales, urine output <400 mL/day

1st investigation
  • serum anion gap:

    >12 mEq/L

  • renal function tests:

    elevated creatine and BUN, variable potassium concentration

    More
Other investigations

    Chronic renal failure

    History

    history of renal impairment; usually asymptomatic

    Exam

    may have physical findings relating to underlying cause; itch, peripheral edema, pulmonary rales if fluid overload present

    1st investigation
    • serum anion gap:

      >12 mEq/L

    • renal function tests:

      elevated creatinine and BUN, variable potassium concentration

    Other investigations

      Uncommon

      Addition of acid

      History

      total parenteral nutrition, ingestion of elemental sulfur, addition of hydrogen chloride (e.g., congeners such as ammonium chloride); patients who have received rapid administration of fluids not containing HCO3 will have a dilutional acidosis

      Exam

      diagnosis is usually based on historical versus physical findings

      1st investigation
      • serum anion gap:

        <12 mEq/L

      Other investigations
      • urine anion gap:

        low (<0 mEq/L)

      Use of this content is subject to our disclaimer