Metabolic Alkalosis

Also known as: Alkalaemia

Metabolic alkalosis is a primary rise in serum bicarbonate producing a rise in pH, compensated by hypoventilation with a rise in PaCO₂.

It is among the commonest acid-base disturbances in hospital inpatients, largely because vomiting, nasogastric drainage and diuretics are so common.

Two distinct processes are always involved, and separating them clarifies management.

A generation step creates the alkalosis ; loss of gastric acid, diuretic use, mineralocorticoid excess, or bicarbonate administration.
A maintenance step prevents the kidney from excreting the excess bicarbonate, and is usually chloride depletion, volume depletion, hypokalaemia, or mineralocorticoid excess. Since a healthy kidney can excrete bicarbonate readily, an alkalosis that persists always implies a maintenance factor, and treating that factor is what resolves it.

Causes are classified by urine chloride into saline-responsive and saline-resistant, which is the practical division that determines treatment.

Blood gas showing raised pH and raised bicarbonate, with compensatory hypoventilation raising PaCO₂ by roughly 0.7 mmHg per 1 mmol/L rise in bicarbonate. Compensation is limited by hypoxaemia, so PaCO₂ rarely exceeds about 55 mmHg
Urine chloride is the essential discriminating test:
- Below 20 mmol/L ; saline-responsive: vomiting, nasogastric aspiration, prior diuretic use, post-hypercapnic alkalosis, villous adenoma, congenital chloride diarrhoea
- Above 20 mmol/L ; saline-resistant: current diuretics, primary hyperaldosteronism, Cushing's syndrome, Liddle syndrome, Bartter and Gitelman syndromes, severe hypokalaemia, licorice ingestion
Blood pressure further subdivides the saline-resistant group: hypertension points to mineralocorticoid excess, while normotension points to Bartter or Gitelman syndrome, diuretic use, or surreptitious vomiting
Potassium and magnesium, which are almost always low and which perpetuate the alkalosis
Consider surreptitious vomiting or diuretic misuse where no cause is apparent, particularly with a normal blood pressure and a puzzling picture
Aldosterone and renin where mineralocorticoid excess is suspected

Saline-responsive:

0.9% saline to restore volume and chloride, which allows renal bicarbonate excretion
Potassium chloride, which is essentially always required; the alkalosis will not resolve while hypokalaemia persists, since potassium depletion drives hydrogen ion into cells and promotes renal bicarbonate reabsorption
Magnesium replacement, without which potassium cannot be corrected
Treat the source: antiemetics, reduce or replace nasogastric losses, manage gastric outlet obstruction, and review diuretic dosing
Proton pump inhibitors reduce gastric acid loss in patients on continuous nasogastric drainage, which is a simple and effective preventive measure

Saline-resistant:

Saline is ineffective and may cause harm through volume overload
Acetazolamide promotes bicarbonate excretion, and is particularly useful in diuretic-associated alkalosis in heart failure, where a saline load is undesirable
Potassium-sparing diuretics (spironolactone, amiloride) where ongoing diuresis is needed
Treat mineralocorticoid excess specifically: spironolactone or surgical management for primary hyperaldosteronism, and appropriate treatment for Cushing's syndrome
Correct severe potassium depletion, which can itself sustain the alkalosis

Severe alkalosis (pH above approximately 7.55) risks arrhythmia, seizures, reduced cerebral perfusion and tetany from reduced ionised calcium; hydrochloric acid infusion via central access or haemodialysis are options in extremis and warrant critical care involvement.

Referral: nephrology for saline-resistant alkalosis and suspected tubular disorders; endocrinology for mineralocorticoid excess.

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Hypercalcaemia

Also known as: Hypercalcemia, High calcium

Hypercalcaemia is a raised corrected serum calcium, graded broadly as mild (up to about 3.0 mmol/L), moderate (3.0–3.4 mmol/L) and severe (≥3.4 mmol/L, or any level with significant symptoms).

Because roughly 40% of calcium is albumin-bound, the corrected value must be used, or hypercalcaemia will be missed in hypoalbuminaemic patients and over-diagnosed in others.

Primary hyperparathyroidism and malignancy together account for around 90% of cases, and the distinction is usually straightforward: primary hyperparathyroidism tends to be chronic, mild and asymptomatic in an outpatient, while malignancy-associated hypercalcaemia is usually higher, symptomatic and of shorter history.

Other causes include granulomatous disease (sarcoidosis, tuberculosis), vitamin D toxicity, thiazides, lithium, thyrotoxicosis, immobilisation, milk-alkali syndrome and familial hypocalciuric hypercalcaemia.

The classic summary of "bones, stones, abdominal groans and psychic moans" remains a useful memory aid.

Renal: polyuria and polydipsia (nephrogenic diabetes insipidus), nephrolithiasis, nephrocalcinosis, and acute kidney injury from volume depletion
Gastrointestinal: anorexia, nausea, vomiting, constipation, abdominal pain, peptic ulceration and pancreatitis
Neuropsychiatric: fatigue, poor concentration, depression, confusion, and in severe hypercalcaemia drowsiness, stupor and coma
Musculoskeletal: bone pain, proximal muscle weakness, and in longstanding hyperparathyroidism osteitis fibrosa cystica
Cardiac: shortened QT interval, bradycardia, and arrhythmia in severe cases, with increased digoxin sensitivity

Volume depletion is central to the pathophysiology and drives a vicious cycle: hypercalcaemia causes polyuria and vomiting, which cause dehydration, which reduces renal calcium excretion, which raises calcium further. Breaking that cycle with fluid is the first therapeutic priority.

Corrected calcium, repeated to confirm, alongside albumin. Ionised calcium is preferable where available and where the correction is unreliable, as in critical illness or acid-base disturbance
PTH is the single most useful discriminating test: an inappropriately normal or raised PTH indicates primary (or tertiary) hyperparathyroidism, while a suppressed PTH points to a non-parathyroid cause, principally malignancy
If PTH is suppressed: PTHrP (humoral hypercalcaemia of malignancy), vitamin D metabolites (raised 1,25-dihydroxyvitamin D suggests granulomatous disease or lymphoma), myeloma screen, and imaging directed by the clinical picture
Renal function, phosphate, magnesium, alkaline phosphatase
ECG for QT shortening
24-hour urinary calcium and the calcium-creatinine clearance ratio to identify familial hypocalciuric hypercalcaemia, an important benign mimic in which parathyroidectomy is inappropriate and which is otherwise easily mistaken for mild primary hyperparathyroidism
Review medications, particularly thiazides, lithium, calcium and vitamin D supplements

Differentials: as above, with the practical task usually being to separate parathyroid-driven from non-parathyroid causes and then to identify the specific underlying disease.

Severe or symptomatic hypercalcaemia:

Intravenous isotonic saline is the first and most important step, typically several litres over the first 24 hours, correcting volume depletion and promoting calciuresis. This alone often produces a substantial fall
Loop diuretics are no longer recommended routinely and should be used only once the patient is genuinely volume replete and where fluid overload is a concern; giving furosemide to a dehydrated hypercalcaemic patient worsens the problem
Intravenous bisphosphonate (zoledronic acid or pamidronate) for malignancy-associated hypercalcaemia, with the important caveat that the effect takes 2–4 days, so it does not substitute for fluid in the acute phase. Dose adjustment is needed in renal impairment
Calcitonin works within hours and is useful as a bridge while awaiting bisphosphonate effect, though tachyphylaxis limits it to a few days
Denosumab is an option in bisphosphonate-refractory hypercalcaemia or significant renal impairment
Corticosteroids are effective specifically in granulomatous disease, lymphoma and vitamin D toxicity, where the mechanism is excess 1,25-dihydroxyvitamin D
Haemodialysis for severe hypercalcaemia with renal failure or where the patient is unable to tolerate fluid loading
Stop contributing drugs and mobilise the patient where possible

Underlying cause:

Primary hyperparathyroidism: parathyroidectomy where criteria are met; cinacalcet where surgery is not appropriate
Malignancy: treat the underlying disease, recognising that hypercalcaemia of malignancy carries a poor prognosis and that discussion of goals of care is often appropriate alongside treatment

Referral: endocrinology for parathyroid disease; oncology or palliative care for malignancy-associated hypercalcaemia; nephrology for dialysis or severe renal impairment.

Metabolic Alkalosis

Overview

Diagnosis

Management

Overview

Clinical Features

Diagnosis

Management