Acid-base disturbances & anion gap

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Acid-base status
Respiratory acidosis
Metabolic acidosis
Kussmaul breathing

Acid-base status

Acid-base status is typically assessed using arterial blood gases. normal values are shown below:

Table 1: Normal arterial blood gas values

Test	Normal range
pH	7.35-7.45
pO₂	11-14 kPa
pCO₂	4.5-6 kPa
Bicarbonate [HCO₃-]	24-30 mmol/l
Base excess	-2 to +2 mmol/l
Lactate	<2 mmol/L

Table 2: Signs and symptoms of acidosis and alkalosis

System	Acidosis	Alkalosis
Cardiovascular	hypotension peripheral vasodilatation hyperkalaemia (arrhythmia/ECG changes)	tachycardia hypokalaemia (arrhythmia/ECG changes)
Respiratory	metabolic acidosis hypoventilation respiratory acidosis Kussmaul's	metabolic alkalosis hyperventilation respiratory alkalosis hypoventilation
Neurological	lethargy drowsiness confusion headache coma	lethargy drowsiness confusion tetany temor seizures hyper-relexia peripheral tingling/numbness
Gastrointestinal	Nausea Vomiting Abdominal pain	Nausea Vomiting Abdominal pain

Disturbances
Acid-base disturbances may be classed as respiratory or metabolic in origin:

Respiratory origin where the disturbance is primarily of CO₂ exchange
Metabolic origin where the disturbance is due to bicarbonate

A number of compensatory mechanisms exist to minimise pH disturbances. Metabolic buffering primarily involving bicarbonate, alteration in ventilation to alter pCO₂ and renal excretion of acid. The relationship between acid (H⁺ ions), bicarbonate (HCO₃- ) and carbon dioxide (CO₂) can be shown by the equation below:

H⁺ + HCO₃- ‡Œ H₂CO₃ ‡Œ CO₂ + H₂O

Respiratory acidosis

Respiratory acidosis refers to acidosis (pH less than 7.35) due to a respiratory cause. In practice this means the lungs are failing to remove carbon dioxide (CO₂). The reason a rise in CO₂ results in acidosis is because it combines with water then dissociates into bicarbonate and hydrogen ions. The increase in hydrogen ions is what causes acidosis.

Causes:

COPD
decompensation in other respiratory conditions e.g. life-threatening asthma / pulmonary oedema
sedative drugs causing hypoventilation e.g. benzodiazepine and opiate overdose

Respiratory Alkalosis
Respiratory alkalosis occurs when the CO₂ level drops. This is most often due to increased ventilation rate and 'blowing off' CO₂.
Causes:

hyperventilation
pulmonary embolism
salicylate poisoning*
CNS disorders: stroke, subarachnoid haemorrhage, encephalitis
altitude
pregnancy

*salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis

Metabolic acidosis

In metabolic acidosis, there is either excessive production of acid (H⁺) or loss of bicarbonate which leads to an overall increase in H⁺ and lowering of the pH.

In metabolic acidosis there is a low bicarbonate level as bicarbonate is consumed buffering the increased acid. There are a wide range of potential causes.

In metabolic acidosis breathing first becomes rapid and shallow. As acidosis worsens the breathing pattern gradually becomes deep, labored and gasping which is known as

Kussmaul breathing

Causes:
Commonly causes classified according to the anion gap. The anion gap is the difference between the major measured cations and anions in plasma. It can be calculated using the equation below:

(Na⁺ + K⁺) - (Cl^- + HCO₃^-)

A normal anion gap is in the range 9-14 mmol/l.

Low albumin may cause a low anion gap. Some labs may provide a corrected ion gap in patients with hypoalbuminaemia.

Normal anion gap (hyperchloremic) metabolic acidosis causes remembered using mnemonic HARDUPS:

H: H⁺ secretion failure from the kidneys i.e. renal tubular acidosis types 1 &4
A: Acetazolamide use (diamoxµ)
R: Renal tubular acidosis (type 2) with loss of HCO₃- from the kidneys
D: Diarrhoea, loss of lower GI secretions including HCO₃-
U: Ureteropelvic fistula with loss of HCO₃- in secretions
P: Post-hypocapnia
S: Spironolactone

Raised anion gap metabolic acidosis causes remembered using mnemonic MUDPILERS:

M: Methanol
U: Uremia (chronic kidney failure)
D: Diabetic ketoacidosis
P: Paracetamol, Propylene glycol
I: Infection, Iron, Isoniazid (which can cause lactic acidosis in overdose), Inborn errors of metabolism
L: Lactic acidosis due to shock, hypoxia or drugs such as metformin
E: Ethylene glycol, ethanol*
R: Rhabdomyolysis
S: Salicylates (aspirin)

*Ethanol causes lactic acidosis and can produce ketones.

Metabolic alkalosis
May be caused by a loss of hydrogen ions or a gain of bicarbonate. It is due mainly to problems of the kidney or the gastrointestinal tract.

Causes

vomiting / aspiration (e.g. peptic ulcer leading to pyloric stenosis, nasogastric suction)
diuretics
liquorice, carbenoxolone
hypokalaemia
primary hyperaldosteronism
Cushing's syndrome
Bartter's syndrome
congenital adrenal hyperplasia

Mechanism of metabolic alkalosis

activation of renin-angiotensin II-aldosterone (RAA) system is a key factor
aldosterone causes reabsorption of Na⁺ in exchange for H+ in the distal convoluted tubule
ECF depletion (vomiting, diuretics) → Na⁺ and Cl- loss → activation of RAA system → raised aldosterone levels
in hypokalaemia, K⁺ shift from cells → ECF, alkalosis is caused by shift of H+ into cells to maintain neutrality