Metabolic acidosis

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

Metabolic acidosis develops when acid production or administration exceeds buffering and excretion, bicarbonate is lost, or the kidneys fail to excrete daily acid. Hydrogen ions reduce bicarbonate and stimulate ventilation. The circulation may deteriorate through impaired myocardial contractility, vasodilation and catecholamine resistance, while potassium shifts extracellularly even when total-body potassium is depleted.

The anion gap separates accumulation of unmeasured acids from chloride replacing lost bicarbonate. It is a framework, not a diagnosis: lactate and ketones should be measured directly, and mixed high-gap plus normal-gap disease is common. Comparing the rise in gap with the fall in bicarbonate can reveal an additional normal-gap acidosis or metabolic alkalosis, but biological and laboratory variation make bedside context essential.

Respiratory compensation is finite. Deep rapid breathing is an adaptive response to DKA, lactate or salicylate and may fail through fatigue, sedation, lung disease or an unsafe ventilator setting. Intubation in severe metabolic acidosis is high risk because even brief apnoea raises carbon dioxide sharply; experienced airway and critical-care planning is essential. Poisoning, DKA and renal replacement each require their live cause-specific protocols.

Key points

Confirm the primary process from pH, bicarbonate and carbon dioxide: metabolic acidosis lowers bicarbonate, while appropriate respiratory compensation lowers carbon dioxide rather than normalising pH completely.
Calculate anion gap as sodium minus chloride plus bicarbonate using values from the same sample; a raised gap signals unmeasured anions but a normal gap does not mean mild disease.
Low albumin lowers the expected anion gap, so correct or interpret the gap for albumin in critical illness before dismissing lactate, ketones, renal acids or toxins.
Common high-gap causes are lactic acidosis, ketoacidosis, advanced renal failure and toxic ingestion; common normal-gap causes are diarrhoea, renal tubular acidosis, saline chloride load and carbonic-anhydrase inhibition.
Compare measured carbon dioxide with expected respiratory compensation; a higher value indicates superimposed respiratory acidosis and impending ventilatory failure, while a lower value indicates additional respiratory alkalosis.
A venous gas is usually sufficient for pH and bicarbonate trends, but arterial sampling is required when accurate oxygenation or a precise arterial carbon dioxide assessment changes respiratory management.
Treat the mechanism—restore perfusion, control sepsis, give the DKA pathway, reverse toxin exposure, stop gastrointestinal loss or arrange dialysis—rather than treating pH as an isolated target.
Intravenous sodium bicarbonate is not routine for every low pH; use it for a defined indication under senior guidance because sodium load, carbon dioxide generation, hypocalcaemia and overshoot can harm.

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

Unmeasured acid accumulation

Lactate, ketones, uraemic acids and toxin metabolites consume bicarbonate and usually widen the anion gap in susceptible patients.

Bicarbonate loss

Diarrhoea, gastrointestinal drainage and renal tubular disorders lower bicarbonate while chloride rises, producing a normal-gap acidosis.

Reduced renal acid excretion

Acute or chronic kidney failure limits hydrogen-ion excretion and bicarbonate regeneration, allowing daily acid load to accumulate.

Iatrogenic chloride or acid load

Large chloride-rich fluid administration and selected medicines can add a normal-gap component to another metabolic illness.

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

1
Bicarbonate concentration falls
Added hydrogen ions are buffered or bicarbonate is lost directly, reducing the principal extracellular buffer and lowering pH.
2
Ventilation increases
Chemoreceptor stimulation produces deep rapid breathing to lower carbon dioxide and partially restore the bicarbonate-to-carbon-dioxide ratio.
3
Potassium shifts outward
Acidaemia and insulin deficiency can move potassium extracellularly even when renal or gastrointestinal losses have depleted total-body stores.
4
Cardiovascular compensation fails
Severe pH reduction impairs myocardial contractility, vasomotor response and catecholamine effectiveness, worsening shock and tissue acid production.

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

Compensatory hyperventilationRed flag

Deep rapid breathing reflects respiratory carbon dioxide clearance; slowing respiration, exhaustion or reduced consciousness during severe acidosis signals impending decompensation.

Shock and lactateRed flag

Hypotension, mottling, delayed refill, oliguria and altered mentation suggest impaired perfusion, but sepsis-associated lactate can rise before overt pressure collapse.

Ketotic patternRed flag

Polyuria, dehydration, vomiting, abdominal pain and acetone breath with ketonaemia indicates diabetic, alcoholic or starvation ketoacidosis requiring contextual separation.

Toxic mixed disorderRed flag

Tinnitus, vomiting, tachypnoea, fever, confusion or unexplained mixed respiratory alkalosis and high-gap acidosis raises salicylate poisoning and needs urgent toxicology advice.

Bicarbonate loss

High-output diarrhoea, ileostomy, fistula or urinary diversion can produce profound normal-gap acidosis with dehydration and potassium depletion.

Renal tubular phenotype

Persistent normal-gap acidosis without gastrointestinal loss, with characteristic potassium and urine findings, suggests renal tubular acidosis and merits renal or endocrine investigation.

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 acidemia, quantify bicarbonate and carbon dioxide and identify respiratory compensation or a mixed disorder.
Interpretation and limitations
Use venous pH for most metabolic trends; choose arterial sampling for oxygenation or precise ventilation decisions, and compare carbon dioxide with the expected compensatory range.
02
Electrolytes and calculated anion gap
Why
Classify unmeasured-acid accumulation versus chloride-associated bicarbonate loss.
Interpretation and limitations
Calculate from simultaneous sodium, chloride and bicarbonate and account for albumin; repeat as treatment can reveal a residual hyperchloraemic component after lactate or ketones clear.
03
Lactate with perfusion assessment
Why
Identify a common high-gap acid and monitor response to resuscitation and cause control.
Interpretation and limitations
Interpret trend with circulation, liver clearance, beta-agonists, seizure and medicines; a falling value is reassuring only if the patient’s physiology also improves.
04
Blood ketones and glucose
Why
Detect diabetic or euglycaemic DKA and distinguish other ketotic states.
Interpretation and limitations
Significant ketonaemia with acidosis invokes the dedicated DKA pathway even when glucose is modest; alcohol and starvation require thiamine and nutritional context.
05
Renal profile, urinalysis and urine studies
Why
Find excretory failure, potassium risk and a possible renal tubular bicarbonate or acidification defect.
Interpretation and limitations
Acute kidney injury may be cause and consequence; urine pH and ammonium surrogates are specialist tools affected by infection, volume and current alkali.
06
Osmolality and toxicology-directed tests
Why
Support investigation of toxic alcohol, salicylate, metformin or other poisoning when history or gap is unexplained.
Interpretation and limitations
An osmolal gap can be absent late and is not an exclusion test; obtain timed drug concentrations and antidote or dialysis advice from NPIS and specialists.
07
Albumin and delta assessment
Why
Avoid missing a high gap and look for an additional metabolic process.
Interpretation and limitations
Correcting for low albumin can expose concealed unmeasured anions; a bicarbonate fall disproportionate to gap rise suggests concurrent normal-gap acidosis, while a smaller fall suggests alkalosis.

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

Respiratory alkalosis

Low carbon dioxide can lower bicarbonate through compensation; blood-gas direction and expected compensation distinguish it from primary metabolic acid gain.

Diabetic ketoacidosis

Raised ketones, diabetes and osmotic symptoms identify a high-gap insulin-deficient process requiring its dedicated treatment pathway.

Lactic acidosis

Shock, sepsis, seizure or ischaemia with raised lactate indicates production or clearance failure rather than bicarbonate loss.

Renal tubular acidosis

Persistent normal-gap acidosis with inappropriate urinary acid handling and characteristic potassium behaviour suggests a tubular defect.

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

01ReadInterpret acid–base in sequenceFirst stepA gas shows low pH, low bicarbonate or an unexpected carbon dioxide concentration.

1Confirm sampling context, pH and primary bicarbonate reduction, then compare carbon dioxide with expected compensation to identify respiratory failure or additional respiratory alkalosis.
2Calculate an albumin-aware anion gap from the matching chemistry sample and measure lactate, ketones and renal indices directly rather than relying on a mnemonic alone.
3Use delta comparison and clinical history to identify combined high-gap, chloride-associated and alkalotic processes, documenting uncertainty and the next test.

02ResuscitateReverse tissue acid generationAcidosis accompanies shock, hypoxia, sepsis, seizure or another perfusion emergency.

1Use ABCDE, oxygen and ventilation as indicated, obtain cultures and early antimicrobials for sepsis and give balanced resuscitation through NICE fluid principles with repeated response assessment.
2Control bleeding, hypoxia, seizure, arrhythmia and source of infection, and stop medicines that worsen perfusion or lactate when clinically appropriate.
3Trend lactate, pH, pressure, urine output and mental state; persistent acidemia despite restored macro-circulation requires reassessment for hidden shock, toxin, mesenteric or limb ischaemia and renal failure.

03TargetApply the cause-specific protocolA high-gap or normal-gap mechanism is identified after initial stabilisation.

1Treat DKA with fixed-rate insulin, fluids and potassium; give thiamine and controlled glucose in alcohol-related ketosis; replace gastrointestinal losses and address renal tubular causes with specialist input.
2For suspected poisoning, contact NPIS urgently and follow antidote, alkalinisation, airway and dialysis advice specific to the agent rather than extrapolating from generic acidosis care.
3Consult renal services for severe refractory acidemia, oliguric kidney failure, toxin clearance or dangerous fluid and electrolyte constraints that may require renal replacement therapy.

04BufferUse bicarbonate selectivelySevere acidosis persists and a defined clinical indication for alkali is being considered.

1DefinitiveFirst optimise ventilation, circulation, oxygenation and definitive cause treatment, checking ionised calcium, sodium, potassium and fluid tolerance.
2Discuss bicarbonate with critical care, renal or toxicology specialists, choosing dose from base deficit and the relevant protocol rather than treating every low pH identically.
3Monitor gas, electrolytes, carbon dioxide, volume and neurological status during administration and stop for alkalosis, hypernatraemia, worsening hypocalcaemia or overload.

Key medicines and prescribing safety1 treatment · regimens, roles and cautions

Provides alkali in selected bicarbonate-loss, poisoning, renal or profound acidemia scenarios while definitive cause treatment and adequate ventilation are secured.

Intravenous sodium bicarbonate

For a defined severe metabolic acidosis indication, calculate and titrate the amount to the clinical base deficit using the current BNF, product and cause-specific protocol under senior critical-care, renal or toxicology supervision.

Not routine for DKA or lactic acidosis solely to normalise pH. It adds sodium and volume, generates carbon dioxide, lowers ionised calcium and potassium and can overshoot into alkalosis; inadequate ventilation may worsen intracellular or cerebral acidosis.

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

Circulatory collapse

Severe acidaemia depresses cardiac function and vascular responsiveness, amplifying hypotension, tissue hypoperfusion and further acid generation.

Potassium-related arrhythmia

Extracellular potassium shifts and impaired renal excretion can destabilise cardiac conduction even when whole-body potassium is low.

Respiratory fatigue

Sustained compensatory ventilation imposes a high work of breathing that may fail with sedation, lung disease or muscle exhaustion.

Hazardous airway management

Loss of compensatory ventilation during intubation can raise carbon dioxide abruptly and worsen acidaemia, requiring experienced critical-care planning.

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

Repeat gas and electrolytes according to severity and intervention, using the direction of pH, bicarbonate and carbon dioxide together rather than following base excess alone.
Trend lactate and ketones at disease-specific intervals and require clinical perfusion or DKA improvement to accompany biochemical clearance.
Use continuous ECG for severe acidemia, hyperkalaemia, hypocalcaemia or arrhythmia, and recheck potassium frequently as insulin, pH and renal function change distribution.
Track pressure, capillary refill, mental state, temperature, respiratory effort and urine output; slowing compensatory ventilation may precede a catastrophic pH fall.
During bicarbonate, monitor sodium, ionised calcium, potassium, carbon dioxide and fluid balance for predictable treatment toxicity.
After recovery, repeat bicarbonate and renal function off acute fluids or supplements to identify persistent CKD, renal tubular disease or medicine-associated acidosis.

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

Normal pH can hide two disorders

A high-gap acidosis plus respiratory alkalosis or metabolic alkalosis may produce a near-normal pH despite serious underlying physiology.

Albumin hides the gap

Albumin is a major unmeasured anion; severe hypoalbuminaemia lowers the baseline gap and can conceal clinically important lactate or ketones.

Chloride can replace the gap

As ketoanions are metabolised or lost in urine during DKA treatment, bicarbonate recovery may lag and a normal-gap hyperchloraemic acidosis can remain.

Compensation is diagnostically active

A carbon dioxide higher than expected is not simply poor compensation; it identifies a second respiratory acidosis and urgent ventilatory vulnerability.

Potassium may be deceptive

Acidemia can raise serum potassium despite substantial total-body depletion, particularly in DKA, so treatment can uncover severe hypokalaemia quickly.

Base is not definitive therapy

Buffering a lactate result without restoring oxygen delivery and treating the cause can improve a number while shock and acid production continue.

11Common pitfallsFrequent interpretation and management errors.

01
Calling every low bicarbonate metabolic acidosis without checking pH and carbon dioxide for chronic respiratory alkalosis or a mixed disorder.
02
Using an uncorrected normal anion gap to exclude lactate or ketoacidosis in a critically ill patient with very low albumin.
03
Sedating or intubating a profoundly compensating patient without a plan to match minute ventilation and avoid an abrupt carbon dioxide rise.
04
Giving sodium bicarbonate reflexively for sepsis-associated lactic acidosis while delaying perfusion assessment, antibiotics and source control.
05
Assuming a negative early osmolal gap excludes toxic alcohol exposure and failing to obtain urgent specialist toxicology advice.
06
Stopping investigation when pH normalises even though bicarbonate, anion gap and carbon dioxide reveal two opposing dangerous processes.