Metabolic Acidosis

See also: Lactic acidosis

Metabolic acidosis is defined as an arterial blood pH <7.35 with plasma bicarbonate <22 mmol/l. In a pure metabolic acidosis there will be a normal arterial pCO₂, but the condition may co-exist with respiratory acidosis/alkalosis that complicates the picture. There is a relative excess of total body acid that cannot be dealt with by the body's normal buffering systems. It is not a diagnosis, rather a metabolic derangement that indicates underlying disease(s) as a cause. Determination of the underlying cause is the key to correcting the acidosis and administering appropriate therapy.¹

It is relatively common, particularly among acutely unwell/critical care patients. There are no reliable figures for its overall incidence or prevalence in the population at large.

There are many causes. They can be classified according to their pathophysiological origin, as below. The table is not exhaustive but lists those that are most common or clinically important to detect.

History

There are no specific symptoms of metabolic acidosis as such. Those that occur are due to the effects of the metabolic derangement on the body, or may give clues to the underlying cause.² Patients may notice a subjective sensation of dyspnoea caused by stimulation of the respiratory centre in an attempt to 'blow off' CO₂ and increase blood pH. Nausea, vomiting and anorexia are frequently present, particularly in children. Metabolic acidosis occurring in children is more likely due to an inborn error of metabolism.

The following points should be covered in the history in an attempt to identify the underlying cause:

• Family history of any similar episodes of illness (may indicate inborn error of metabolism).
• Family or personal history of diabetes.
• Symptoms of undiagnosed diabetes, eg polyuria, polydipsia or weight loss.
• Symptoms of renal failure such as nocturia, polyuria, oliguria, pruritus and anorexia.
• Recent history of urinary problems such as nephrolithiasis may indicate renal tubular acidosis.
• Recent history of severe or prolonged diarrhoea.
• Recent nutritional status.
• Alcohol intake.
• Any history of deliberate or accidental ingestion of potentially toxic materials or medicines.
• Occupational/DIY exposure to fumes or solvents.
• Visual disturbances such as dimming, photophobia, scotomata or blindness may indicate methanol poisoning. Blurred vision may occur with salicylate poisoning.
• Tinnitus or vertigo may occur with salicylate poisoning.
• Ask about any chest pain, palpitations, dyspnoea or oedema indicating possible cardiovascular causes for lactic acidosis.
• Recent history of confusion, headache or visual changes may indicate poisoning, particularly with methanol or ethylene glycol.

Examination

• Lethargy, stupor and progression to a state of coma may occur, particularly in cases of poisoning. An intoxicated-appearing patient who has no smell of alcoholic drink on their breath may have ingested ethylene glycol.
• Check vital signs as hypotension may occur due to myocardial suppression in severe acidaemia.
• In undiagnosed renal failure there may be dryness of mouth, eyes and skin, scratch marks on skin, pallor, drowsiness and fetor.
• To detect diabetic ketoacidosis look for evidence of dehydration and smell the patient's breath to detect the presence of ketones (which give off a musty/fruity odour akin to pear-drops or nail-polish remover).
• Look for signs of congestive cardiac failure that may be caused by the acidosis itself, or suggest lactic acidosis as a cause, due to generalised hypoperfusion.
• Listen for a pericardial rub which may indicate acute renal failure as the cause.
• Tachypnoea is likely to be present.
• The presence of tachypnoea without any history of pre-existing cardiorespiratory disease to account for it should strongly suggest metabolic acidosis as the cause of the illness.
• Kussmaul's respiration may be noted where there is deep, slowly rhythmic breathing that increases the minute tidal volume.
• Children with chronic metabolic acidosis may suffer growth retardation and show signs of rickets.
• Neurological examination may reveal cranial nerve palsies in the case of ethylene glycol poisoning.
• Retinal oedema may be noted on fundoscopy in cases of methanol ingestion.

The combination of clinical features of illness and arterial blood gas/plasma bicarbonate results indicate the presence of a metabolic acidosis. Determination of its underlying cause, as outlined in the investigation section below, is crucial to try and optimally treat and correct the acidosis. As such there is no differential diagnosis, rather a list of possible underlying causes to be refuted/confirmed as its cause. See the table above for a list of potential causes.

The first indication of an acidotic problem may be the presence of a low serum bicarbonate on routine U&E testing. This in itself is not enough to confirm an acidosis. The presence of metabolic compensation of respiratory alkalosis, or a lab error could account for a low plasma bicarbonate. Arterial blood gases must be checked to determine the arterial blood pH and confirm the dimunition of bicarbonate. pH and pCO₂ values must be interpreted carefully and a judgement made as to whether this is a pure metabolic acidosis or a mixed acid-base disorder. The base excess or base deficit is usually given as a part of the ABG result and allows a determination of the overall severity of the acidosis, particularly where respiratory compensation complicates the picture.

U&Es help to determine the cause of the acidosis by allowing the calculation of the anion gap as below:

Further general investigations

• Elevation of urea and creatinine will indicate that renal failure is the likely cause.
• Hyperkalaemia often accompanies a normal-anion-gap acidosis, and some cases of acute renal failure.
• Potassium may be elevated in diabetic ketoacidosis but usually minimally so for the degree of acidosis.
• Plasma and urinary glucose and ketones need to be checked to look for evidence of diabetic ketoacidosis.
• Alcoholic ketoacidosis will show evidence of ketone formation without grossly elevating plasma glucose in most cases. A random alcohol level or expired breath alcometer reading may help to make the diagnosis, along with details from the history.
• FBC should be checked but is usually non-specific and unhelpful, except in the case of severe anaemia, where it is likely that lactic acidosis is the cause, or grossly elevated WCC indicating sepsis or haematological neoplasm.
• LFTs should be checked to look for evidence of chronic liver disease, indicating alcohol abuse as a likely aetiology.
• Send any appropriate samples for culture, particularly blood and urine if sepsis leading to lactic acidosis is possible.
• ECG helps to detect arrythmias.
• Consider CXR to look for evidence of infection/cardiac failure or ingested iron/other radio-opaque toxins.

Investigations for specific causes

• Osmolar gap. This is measured minus calculated plasma osmolarity, where osmolarity is calculated using the formula below:
  

  Plasma Osmolarity = 2([Na mmol/l] + [K mmol/l]) + [Urea mmol/l] + [glucose mmol/l]

  Where the osmolar gap is elevated, it indicates the presence of plasma solute which is not being measured by the lab. Its normal range is 10–15 mmol/l. It is elevated by methanol or ethylene glycol ingestion.
• Plasma lactate, where lactic acidosis is a potential cause. Values >2 mmol/l indicate hyperlactataemia and >5 mmol/l indicate definite lactic acidosis.
• Plasma salicylate levels. Levels >40–50 mg/dl indicate salicylate toxicity. >100 mg/dl indicates severe toxicity.
• Iron levels if there is a supicion of deliberate or accidental overdose. Levels >300mg/dl are considered toxic. An abdominal x-ray may be of use if there is suspected ingestion of iron tablets.
• Urine microscopy may show the presence of needle-shaped oxalate crystals which is indicative of ethylene glycol toxicity. Usually urine pH will be <5.0–5.5. Alkaline urine in the face of acidosis is usually caused by Type 1 renal tubular acidosis or salicylate poisoning.

General measures

• Put patient in resuscitation area, or transfer to high dependency area as soon as feasible.
• Put patient on ECG monitor, SaO₂ monitor and BP monitor.
• Give oxygen to patients with low SaO₂ levels.
• In patients who are clinically unwell and have deteriorating SaO₂ levels, consider intubation and assisted ventilation, after taking senior A&E/medical/anaesthetic advice.
• Get large-bore IV access (central venous line may be needed).
• Consider catheterisation to monitor urine output and obtain urine for analysis.
• If there is any possibility of drug or toxin ingestion give initial therapies such as activated charcoal/chelating agents/emetics, dependent on the specific compound ingested and latest local guidelines for poisoning.
• If there is evidence of gross dehydration then commence infusion of crystalloid, usually 1 litre of normal saline over the first hour, while investigations/therapy are commenced.
• If patient is markedly hypotensive consider rapid infusion of colloid.
• Take care with fluid infusion if there is reason to suspect impaired cardiac function, or in frail, older patients.
• Liaise with local or national toxicology/poisoning services if there has been ingestion of a potentially dangerous substance.
• Obtain all possible information about any ingested materials; ask relatives/friends to get hold of packaging/medicine bottles which may give useful initial advice on management following ingestion, or help toxicology services to advise appropriately.
• If unknown tablets have been ingested, use a pictorial tablet guide to try and identify what has been taken.
• Obtain specialist input (usually on-call general-medical team initially) as soon as possible.

Correction of acidosis

This may be achieved through the use of sodium bicarbonate infusion. It is not of definite proven usefulness in adults or children.^3,4 The main problem is that bicarbonate generates CO₂ that may worsen acidosis if there is insufficient respiratory compensation. The sodium load can also have undesirable metabolic effects. Use of bicarbonate may be considered where pH is very low at 7.1–7.2 to reduce the imminent danger of fatal cardiac arrythmia. Other therapies such as carbicarb can neutralise blood without generating CO₂, but are of unproven clinical efficacy as yet (see article on lactic acidosis for further details). Acidosis may also be corrected by haemodialysis. Any decision to use specific anti-acidosis strategies should be taken by senior medical/critical-care/renal physicians in the context of the patient's clinical condition, biochemistry results and the underlying cause of the acidosis.

Specific therapy for the underlying cause

This is the most important and efficient way to correct the acidosis and improve the patient's outlook. Toxicological/general medicine/renal medicine expertise should be engaged to offer specific therapy for the identified underlying problem. It is beyond the scope of this article to discuss specific treatments for all of the potential causes of metabolic acidoses. See other articles on the diagnoses in question, or consult the internet section below.

The major problem is suppression of myocardial contractility and unresposiveness to catecholamines caused by the acidaemic state. This may lead to a vicious cycle of hypoperfusion, worsening lactic acidosis and further cardiac suppression, causing multi-organ failure. If pH is <7.1–7.2 then cardiac arrythmias are likely.

This is largely dependent upon the underlying cause and severity of the illness in a given patient. There is no doubt that metabolic acidosis can be life-threatening and carries a significant mortality and morbidity. Appropriate initial management and ongoing expert input will improve the outlook for individual patients.