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)
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