Acidosis, Metabolic, Decreased or Normal Anion Gap

Essentials of Diagnosis

• Decreased HCO₃^– and hyperchloremia (usually) with acidemia

• Normal anion gap acidosis is mainly caused by gastrointestinal HCO₃^– loss or RTA. Urinary anion gap may help distinguish between these causes

General Considerations

• Most common causes

  • Gastrointestinal (GI) HCO₃^– loss

  • Defects in renal acidification (renal tubular acidoses)

• The urinary anion gap can differentiate between these two causes

• Table 21–12 outlines anion gap in metabolic acidosis

Renal tubular acidosis (RTA)

• Hyperchloremic acidosis with a normal anion gap and normal or near normal glomerular filtration rate, in the absence of diarrhea

• Three major types of RTA can be differentiated by the clinical setting: urinary pH, urinary anion gap, serum K⁺ level

• Type I (distal H⁺ secretion defect)

  • Characterized by selective deficiency in H⁺ secretion by alpha intercalated cells in the collecting tubule

  • Enhanced K⁺ excretion occurs probably due to less competition from H⁺ in the distal nephron transport system

  • Develops as a consequence of paraproteinemias, autoimmune disease, and drugs and toxins such as amphotericin

• Type II (proximal HCO₃^– reabsorption defect)

  • Due to a defect in the ability of the proximal tubule to reabsorb filtered HCO₃^–

  • Hypokalemia results when a patient is treated with HCO₃^– without adequate K⁺ supplementation

  • Can exist with other proximal reabsorption defects resulting in glucosuria, aminoaciduria, phosphaturia, and uricosuria (Fanconi syndrome)

  • Causes include plasma cell myeloma and nephrotoxic drugs and carbonic anhydrase inhibitors (acetazolamide)

• Type IV (hyporeninemic hypoaldosteronism)

  • Most common RTA in clinical practice

  • Due to a defect in aldosterone action that impairs distal nephron Na⁺ reabsorption and therefore K⁺ and H⁺ excretion

  • Common causes include diabetic nephropathy and tubulointerstitial renal diseases

  • In patients with these disorders, drugs such as ACE inhibitors, ARBs, spironolactone, and NSAIDs, can worsen the hyperkalemia and acidosis

• Symptoms are mainly those of the underlying disorder

• Compensatory hyperventilation is an important clinical sign and may be misinterpreted as a primary respiratory disorder

• When acidosis is severe, Kussmaul breathing (deep, regular, sighing respirations) occur

Laboratory Tests

• Blood pH, serum HCO₃^–, and PCO₂ are decreased

• Serum anion gap may be normal (hyperchloremic) or increased (normochloremic)

• Hyperkalemia may be seen

• Urinary anion gap = U_Na + U_K – U_Cl

  • Negative urinary anion gap with gastrointestinal HCO₃^– loss (diarrhea), since renal acidification remains intact and NH₄Cl excretion increases appropriately

  • Negative urinary anion gap (often) with proximal (type II) RTA, since the primary problem is impaired HCO₃^– reabsorption, leading to increased HCO₃^– excretion rather than decreased NH₄Cl excretion

  • Positive urinary anion gap with distal RTA, since ammonium excretion is impaired

Medications

• See Table 21–14

• Treatment of RTA is mainly achieved by administration of alkali (either as bicarbonate or citrate) to correct metabolic abnormalities and prevent nephrocalcinosis and chronic kidney disease

• Large amounts of oral alkali (10–15 mEq/kg/day) may be required to treat proximal RTA because most of the alkali is excreted into the urine, which exacerbates hypokalemia and a mixture of sodium and potassium salts is often required

• The addition of thiazides may reduce the amount of alkali required, but hypokalemia may develop

• Correction of type 1 distal RTA requires

  • Less alkali (1–2 mEq/kg/day) than proximal RTA

  • Potassium supplementation may be necessary

• For the treatment of type IV RTA

  • Dietary potassium restriction may be needed and potassium-retaining drugs should be withdrawn

  • Loop diuretics may be beneficial

  • Fludrocortisone may be effective in some cases without significant volume expansion

  • In some cases, oral alkali supplementation (1–2 mEq/kg/day) may be required

Complications

• The hyperkalemia can be exacerbated by drugs, including

  • Angiotensin-converting enzyme inhibitors

  • Angiotensin receptor blockers

  • Aldosterone receptor blockers, such as spironolactone

  • Nonsteroidal anti-inflammatory drugs

When to Refer

• Most clinicians will refer patients with renal tubular acidoses to a nephrologist for evaluation and possible alkali therapy

When to Admit

• Patients will require emergency department evaluation or hospital admission depending on the severity of the acidosis and underlying conditions