Conditions · Metabolism (biochemistry)
Normal anion gap (hyperchloraemic) metabolic acidosis !
Bicarbonate is lost through the gut or kidney and chloride rises; the most common cause is diarrhoea.
Updated 2026-11-01
Structures involved
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In biochemistry
In physiology
- Water and electrolyte absorption and how diarrhea happens
- Metabolic acidosis, the anion gap and compensation
- Proximal tubule transport
- Renal handling of H⁺ and bicarbonate
- IV fluids: tonicity and where they go
What it is
A metabolic acidosis from bicarbonate loss or failure of the kidney to excrete acid, with high chloride and a normal anion gap.
Who gets it
Acute diarrhoea, very common in Latin American children, is its main cause; in hospital it is common after resuscitation with large volumes of saline. Renal tubular acidoses are less common.
Causes
- Gut loss of bicarbonate: diarrhoea, pancreatic or biliary fistulas, high-output ileostomy, urinary diversion into bowel (ureterosigmoidostomy)
- Distal (type 1), proximal (type 2) or hypoaldosteronism (type 4) renal tubular acidosis
- Drugs: acetazolamide, topiramate, amiloride and spironolactone (type 4)
- Excess 0.9 % saline (dilutional hyperchloraemic acidosis)
- Recovery phase of diabetic ketoacidosis
Risk factors
- Acute diarrhoea in infants and children
- Resuscitation with large volumes of saline
- Autoimmune disease (Sjögren) and tubulotoxic drugs
- Diabetes with hyporeninaemic hypoaldosteronism
Pathophysiology
When bicarbonate is lost in stool or urine, or the tubule cannot excrete H⁺, HCO₃⁻ falls and the kidney retains chloride to keep neutrality: the anion gap does not change. In distal RTA H⁺ secretion fails in the collecting duct, urine cannot be acidified and there is hypokalaemia, nephrocalcinosis and stones; in proximal RTA HCO₃⁻ is lost through a low reabsorption threshold, often with Fanconi syndrome; in type 4 lack of aldosterone or of response to it causes hyperkalaemia, which suppresses ammonium production. The urine anion gap (Na⁺ + K⁺ − Cl⁻) estimates urine ammonium: negative when the kidney responds (diarrhoea), positive when it cannot excrete acid (RTA).
Classification
- Extrarenal (gut): negative urine anion gap
- Renal: RTA type 1 (distal), type 2 (proximal), type 4 (hyperkalaemic); positive urine gap
- Dilutional or chloride-driven (saline)
Symptoms and signs
- Often only those of the cause (diarrhoea, dehydration)
- Fast, deep breathing if severe
- Muscle weakness from hypokalaemia (diarrhoea, RTA 1 and 2)
- Poor growth and rickets in children with RTA
- Kidney stones (distal RTA)
Diagnosis
- Clinical
- History of diarrhoea, stomas, drugs or autoimmune disease; signs of dehydration.
- Tests
- Gases and electrolytes with high chloride and normal (albumin-corrected) anion gap, potassium, urine anion gap, urine pH, glycosuria and phosphaturia with normal blood glucose (Fanconi), aldosterone and renin in type 4.
- Imaging
- Renal ultrasound for nephrocalcinosis or stones in distal RTA.
Treatment
- Medical
- Rehydrate and replace bicarbonate or its precursors (citrate) in gut losses
- Medical
- Continuous oral alkali in RTA types 1 and 2, with potassium when needed
- Medical
- In type 4: correct hyperkalaemia, stop causative drugs and, when indicated, give a mineralocorticoid
- Follow-up
- Prefer balanced solutions over saline in large resuscitations and monitor chloride and gases
Complications
- Severe hypokalaemia and paralysis
- Nephrocalcinosis and stones
- Rickets and poor growth
- Bone loss
Prognosis
Good in treated diarrhoea; chronic RTAs need lifelong treatment and monitoring of growth and kidneys.
Prevention
- Early oral rehydration salts in childhood diarrhoea
- Sensible use of saline
- Electrolyte monitoring with drugs that affect the tubule
Test yourself
Think of the answer, then tap the question to see it.
What is the most common cause of normal anion gap acidosis?
Diarrhoea, through gut loss of bicarbonate.
What is the urine anion gap used for?
It estimates urine ammonium: negative when the kidney excretes acid (diarrhoea), positive when it cannot (renal tubular acidosis).
Which RTA comes with hyperkalaemia?
Type 4, from lack of or resistance to aldosterone, common in diabetes.
Why is distal RTA linked to kidney stones?
Persistently alkaline urine, low urine citrate and hypercalciuria favour calcium phosphate precipitation.
Related conditions
- High anion gap metabolic acidosis
- Hypokalaemia
- Hyperkalaemia
- Acute (viral) gastroenteritis
- Chronic kidney disease
- Adrenal insufficiency
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Metabolic acidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Distal renal tubular acidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Proximal renal tubular acidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Chloride Blood Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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