Metabolic alkalosis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Bicarbonate rises when hydrogen and chloride are lost from the stomach or kidney, alkali is added, or a chronically hypercapnic patient rapidly loses carbon dioxide while renal bicarbonate remains. Healthy kidneys can excrete excess bicarbonate, so persistent alkalosis usually needs a maintenance factor: volume and chloride depletion, low potassium, mineralocorticoid activity or impaired filtration.

Alkalemia increases albumin binding of calcium, shifts potassium into cells and reduces cerebral blood flow. Symptoms include light-headedness, paraesthesia, cramps, tetany, weakness, confusion, seizure and atrial or ventricular arrhythmia. Hypoventilatory compensation is limited by oxygenation; a striking carbon dioxide rise may therefore represent additional respiratory failure rather than appropriate adaptation.

Urine chloride links mechanism to treatment. A low value suggests remote vomiting, resolved diuretic effect or chloride depletion likely to respond to chloride and volume. A persistently higher value suggests active diuretic, severe potassium depletion, mineralocorticoid excess or inherited tubulopathy. Current diuretics, recent saline and advanced CKD complicate the thresholds, so serial context is essential.

Key points

Metabolic alkalosis is a primary bicarbonate increase; respiratory compensation raises carbon dioxide, but a value outside the expected range reveals an additional respiratory disorder.
Generation and maintenance are separate: vomiting may initiate acid and chloride loss, while low effective volume, chloride depletion, hypokalaemia and reduced GFR prevent renal bicarbonate excretion.
A spot urine chloride obtained before treatment helps divide chloride-responsive disease from continuing diuretic or mineralocorticoid-driven chloride-resistant disease, but timing matters.
Vomiting and nasogastric suction, loop or thiazide diuretics, post-hypercapnic physiology, alkali with renal impairment and mineralocorticoid excess are leading causes.
Alkalemia lowers ionised calcium and promotes intracellular potassium shift, so paraesthesia, cramps, tetany and arrhythmia may occur even when total calcium looks normal.
For true chloride-depletion alkalosis, isotonic sodium chloride and potassium chloride can restore renal bicarbonate excretion, but they may be unsafe in oedematous heart or renal failure.
Correct magnesium and potassium actively because potassium depletion increases renal bicarbonate generation and sustains alkalosis through multiple tubular mechanisms.
Acetazolamide, potassium-sparing therapy, acid infusion or dialysis are specialist options for selected resistant or volume-overloaded cases, not routine first-line answers.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Gastric acid and chloride loss

Vomiting or gastric drainage removes hydrogen and chloride, while volume depletion and aldosterone activity maintain renal bicarbonate retention.

Renal chloride and potassium loss

Loop or thiazide diuretics, inherited tubulopathies and severe potassium depletion increase distal hydrogen loss and sustain alkalosis.

Mineralocorticoid excess

Aldosterone or similar activity promotes sodium retention with renal potassium and hydrogen secretion, often alongside hypertension.

Alkali load or post-hypercapnia

Bicarbonate administration or rapid correction of chronic respiratory acidosis leaves excess bicarbonate that kidneys may not immediately excrete.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Hydrogen or chloride is lost
Gastric or renal losses raise bicarbonate relative to chloride and reduce extracellular volume as the process continues.
2
Kidneys retain bicarbonate
Volume depletion, chloride scarcity, low potassium, mineralocorticoid action or impaired filtration prevent normal excretion of the excess buffer.
3
Ionised calcium and potassium fall
Alkalaemia increases calcium binding and shifts potassium into cells, producing paraesthesia, cramps, weakness and electrical instability.
4
Ventilation compensates incompletely
Hypoventilation raises carbon dioxide but is limited by oxygenation, so a striking rise suggests additional respiratory failure.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Neuromuscular alkalemiaRed flag

Perioral tingling, carpopedal spasm, cramps, hyperreflexia, confusion or seizure can result from reduced ionised calcium and altered neuronal excitability.

Arrhythmic combinationRed flag

Palpitations, syncope, ectopy or QT-related ventricular arrhythmia is more likely with concurrent potassium and magnesium depletion or digoxin treatment.

Chloride-depletion history

Persistent vomiting, nasogastric drainage, high-output gastric fistula or remote diuretic exposure with postural symptoms supports volume- and chloride-responsive disease.

Mineralocorticoid phenotype

Hypertension, potassium wasting and metabolic alkalosis without volume depletion suggests aldosterone or cortisol mineralocorticoid effect and needs controlled endocrine testing.

Post-hypercapnic state

Rapid correction of chronic carbon dioxide retention after ventilation can leave renal bicarbonate temporarily high, especially when chloride and potassium are depleted.

Mixed ventilatory failureRed flag

Drowsiness, hypoxia or a carbon dioxide rise beyond expected compensation indicates superimposed respiratory acidosis and requires urgent respiratory support assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Venous or arterial blood gasFirst step
Why
Confirm alkalemia, primary bicarbonate elevation and the adequacy of respiratory compensation.
Interpretation and limitations
A near-normal pH can conceal mixed disease; use arterial sampling when oxygenation and precise carbon dioxide are needed for ventilatory decisions.
02
Serum sodium, chloride, potassium and magnesium
Why
Identify the chloride and potassium deficits that maintain alkalosis and determine replacement safety.
Interpretation and limitations
Low chloride and potassium support depletion but are not mechanism-specific; severe magnesium loss promotes ongoing renal potassium wasting and arrhythmia.
03
Ionised calcium
Why
Explain tetany, paraesthesia or seizure that appears disproportionate to total calcium.
Interpretation and limitations
Alkalemia increases protein binding and lowers the ionised fraction; treat severe manifestations while correcting the primary alkalosis and magnesium.
04
Spot urine chloride before treatment
Why
Separate likely chloride-responsive depletion from active renal chloride wasting or mineralocorticoid effect.
Interpretation and limitations
A low result supports saline-responsive physiology, while a higher result suggests continuing diuretic, mineralocorticoid or tubulopathy; recent drugs and fluids alter interpretation.
05
Renal function and fluid-status assessment
Why
Determine whether chloride and volume can be given safely and whether low filtration maintains bicarbonate.
Interpretation and limitations
Acute kidney injury can prevent bicarbonate excretion, while heart failure may produce low effective arterial volume despite oedema and make saline hazardous.
06
Medication, feed and loss chart
Why
Find loop or thiazide diuretics, alkali, antacids, steroids, licorice, vomiting and nasogastric suction.
Interpretation and limitations
Relate the last active dose or loss to urine chloride; a remote diuretic may have a low urine chloride whereas a current dose maintains renal chloride wasting.
07
Renin and aldosterone pathway when indicated
Why
Investigate hypertensive chloride-resistant alkalosis after acute correction.
Interpretation and limitations
Correct potassium and manage interfering medicines through an endocrine protocol before sampling, because diuretics and RAAS drugs can invalidate the ratio.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Chronic respiratory acidosis

Renal bicarbonate retention compensates for longstanding high carbon dioxide; blood-gas relationships and respiratory history identify the primary disorder.

Vomiting or remote diuretic effect

A low urine chloride in the correct context supports chloride-responsive depletion after gastric loss or a diuretic that has worn off.

Active diuretic or tubulopathy

Persistently higher urine chloride with renal salt loss suggests ongoing diuretic action or an inherited tubular disorder.

Primary mineralocorticoid excess

Hypertension, renal potassium loss and a chloride-resistant pattern suggest aldosterone-driven disease rather than simple volume depletion.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ConfirmDefine primary and mixed alkalosisFirst stepBicarbonate or base excess is high, pH is alkalemic or symptoms suggest altered ionised calcium.

1Check pH, bicarbonate and carbon dioxide together, compare with expected compensation and identify an additional respiratory acidosis or alkalosis rather than assuming a single process.
2Measure chloride, potassium, magnesium, ionised calcium and renal function, review blood pressure, volume state, ventilation and all gastrointestinal and medicine losses.
3Obtain urine chloride before saline or the next diuretic dose when feasible, then classify the likely maintenance mechanism and urgency.

02ChlorideCorrect depletion-responsive alkalosisHistory, examination and low urine chloride support gastric or remote diuretic chloride loss with reduced effective volume.

1Stop or reduce vomiting, nasogastric suction and causal diuretics where clinically safe, giving antiemetic or acid-suppression treatment appropriate to the underlying disease.
2Replace intravascular volume and chloride with 0.9% sodium chloride under NICE fluid reassessment, adding separately prescribed potassium chloride through the approved safety pathway.
3Recheck gas, urine output, chloride, potassium, magnesium and lungs during treatment, stopping or adapting fluids when renal excretion resumes or overload appears.

03ResistantTreat ongoing renal alkali maintenanceUrine chloride remains high, hypertension is present or saline cannot be given because the patient is oedematous.

1Confirm current diuretics and exclude recent saline, then assess blood pressure, renal function, cortisol or aldosterone clues and inherited tubulopathy context.
2Correct potassium and magnesium, redesign necessary diuretic therapy and treat mineralocorticoid disease through endocrine or renal guidance rather than repeated saline challenges.
3For volume-overloaded or severe persistent alkalosis, obtain specialist advice on acetazolamide, potassium-sparing treatment or renal replacement, with close acid–base surveillance.

04EscalateManage severe alkalemiaEscalationNeurological, cardiac or ventilatory instability accompanies marked alkalemia or standard cause correction is failing.

1Use ABCDE, ECG and ionised calcium, correct dangerous potassium and magnesium deficits and address seizure or arrhythmia in a monitored critical-care environment.
2Identify ongoing alkali administration, gastric loss, diuretic effect, post-hypercapnia and renal failure, and stop the active generator while supporting oxygenation and ventilation.
3Discuss specialist bicarbonate-removal or acidifying strategies and dialysis; do not improvise hydrochloric or ammonium chloride therapy outside expert critical-care protocols.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Restores effective volume and chloride so kidneys can excrete retained bicarbonate in chloride-responsive alkalosis.

Intravenous 0.9% sodium chloride

Prescribe through the NICE five-R fluid framework in staged volumes with reassessment, using the patient’s deficit, pressure, urine output, heart failure and renal function rather than a fixed metabolic-alkalosis total.

It is ineffective or harmful in active mineralocorticoid excess and may worsen oedematous heart or kidney failure. Monitor lungs, sodium, chloride, pressure and balance and stop when the physiological endpoint is reached.

Corrects potassium and chloride depletion that maintains renal bicarbonate retention and increases neuromuscular and cardiac toxicity.

Potassium chloride replacement

Choose oral or approved ready-diluted intravenous potassium chloride from the current measured deficit, symptoms, renal function and local chart, with repeat potassium before further dosing and monitored infusion for high-risk treatment.

Never give intravenous concentrate directly or add it casually to a bag. Check magnesium, renal output and ECG risk; overshoot can occur when vomiting stops, diuretics are withheld or kidney function changes.

Promotes renal bicarbonate excretion when chloride-rich volume cannot be given or the maintenance setting specifically supports carbonic-anhydrase inhibition.

Acetazolamide in selected resistant alkalosis

If a specialist identifies a suitable volume-overloaded or post-hypercapnic indication, use the current BNF, SmPC and local critical-care dose adjusted for renal function; there is no universal ward regimen for metabolic alkalosis.

Can worsen potassium depletion, cause metabolic acidosis and accumulate in renal impairment, and is inappropriate with severe hepatic disease or sulfonamide-related contraindication. Monitor gas and electrolytes and preserve the underlying ventilatory plan.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Cardiac arrhythmia

Alkalaemia combined with potassium and magnesium depletion destabilises myocardial repolarisation and increases atrial and ventricular arrhythmia risk.

Neurological irritability

Reduced ionised calcium and cerebral blood flow can cause paraesthesia, cramps, tetany, confusion and, in marked alkalosis, seizure.

Respiratory compromise

Compensatory hypoventilation can worsen hypoxaemia, while coexisting respiratory disease limits compensation and may cause combined ventilatory failure.

Persistent treatment resistance

Without restoring chloride, potassium or volume and stopping the driver, bicarbonate remains elevated despite superficial fluid correction.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat gas, chloride and bicarbonate after each meaningful intervention, ensuring pH improvement is not masking a new respiratory acidosis or overcorrection.
Trend potassium and magnesium closely during diuretic adjustment and replacement; arrhythmic risk may persist even after bicarbonate begins to fall.
Use continuous ECG for severe alkalemia, important hypokalaemia, digoxin exposure or ventricular ectopy and repeat ionised calcium when tetany or seizure continues.
Record nasogastric, vomit, stoma and urine losses and the timing of every diuretic and alkali dose, since ongoing generation determines whether chloride replacement can succeed.
Assess daily weight, lungs, oedema, pressure and urine output during saline treatment; a rising chloride is not a reason to ignore emerging congestion.
After acute correction, repeat blood pressure, potassium and bicarbonate off interfering treatment before endocrine testing or diagnosing a chronic renal tubular disorder.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Persistence needs a kidney explanation

Acid loss generates alkalosis, but low chloride, potassium, effective volume or GFR usually explains why filtered bicarbonate is not excreted.

Urine chloride is time-sensitive

Active diuretic raises urine chloride, whereas the same patient sampled after its effect fades may look chloride depleted and responsive.

Total calcium can reassure falsely

A high pH increases albumin binding and lowers ionised calcium, producing tetany even when adjusted total calcium remains within range.

Potassium sustains bicarbonate

Potassium depletion increases hydrogen secretion, ammoniagenesis and intracellular acidosis, making direct potassium treatment part of alkalosis correction.

Oedema can hide effective depletion

Heart failure may activate aldosterone despite total fluid excess, creating chloride-resistant physiology that worsens with indiscriminate saline.

Post-hypercapnia has a lag

Kidneys retain bicarbonate during chronic respiratory acidosis; rapid ventilatory carbon dioxide correction reveals alkalosis until renal adaptation catches up.

11Common pitfallsFrequent interpretation and management errors.

01
Calling a high bicarbonate metabolic alkalosis without checking whether it is appropriate renal compensation for chronic respiratory acidosis.
02
Giving repeated saline to an oedematous patient with active mineralocorticoid or diuretic-driven alkalosis and worsening pulmonary congestion.
03
Interpreting urine chloride after several saline bags or a fresh loop-diuretic dose as though it represented the original untreated mechanism.
04
Correcting chloride but overlooking profound magnesium and potassium loss that continues the alkalosis and ventricular electrical risk.
05
Using acetazolamide reflexively without accounting for renal impairment, hepatic disease, potassium depletion and the possibility of overshoot acidosis.
06
Treating a bicarbonate number while ongoing vomiting, nasogastric suction, alkali administration or ventilator change keeps generating the disorder.