Acid-Base Balance: Part II. Pathophysiology J. McNAMARA, L. I. G. WORTHLEY Department of Critical Care Medicine, Flinders Medical Centre, Adelaide, SOUTH AUSTRALIA ABSTRACT Objective: To review the normal human acid-base physiology and the pathophysiology and manage- ment of acid-base disturbances in a two-part presentation. Data sources: Articles and published peer-review abstracts and a review of studies reported from 1990 to 2000 and identified through a MEDLINE search of the English language literature on acid-base balance. Summary of review: Acid-base disorders are usually classified as metabolic (non-respiratory) or respiratory, depending on whether the primary change occurs in the plasma bicarbonate or the carbonic acid (i.e. carbon dioxide) concentrations, respectively. Respiratory or renal compensatory changes usually occur to minimise the effect of the primary disturbance. A metabolic acidosis arises from an abnormal - process that generates non-carbonic acid or an abnormal loss of HCO3 and may be identified by an increase or normal anion gap, respectively. The arterial blood gas usually reveals a pH < 7.36, PCO2 < 35 - mmHg and ‘calculated’ HCO3 < 18 mmol/L. In general, a high anion gap acidosis is managed by treating the disorder generating the acid (thereby ceasing the acid production) and enhancing the clearance of the - acid anion (e.g. by metabolism or excretion) thereby regenerating the HCO3 reduced by buffering. - A metabolic alkalosis arises from an abnormal process generating excess HCO3 . The arterial blood - gas usually reveals a pH > 7.44, PCO2 > 45 mmHg and ‘calculated’ HCO3 > 32 mmol/L. As the kidney - has a large capacity to excrete HCO3 , management usually requires treatment of the processes that are generating as well maintaining the alkalosis. Respiratory acidosis and alkalosis are usually caused by a primary disorder of carbon-dioxide excretion, and correction of the pH disorder only occurs with correction of the primary disease process. Conclusions: In man, acid-base disturbances are usually classified as either metabolic or respiratory. Correction of the underlying disorder is often all that is required to allow the body to metabolise or excrete - the acid or alkali and return the buffer pair (HCO3 and PCO2) to normal. (Critical Care and Resuscitation 2001; 3: 188-201) Key words: Acid-base balance, metabolic acidosis, metabolic alkalosis, anion gap, strong ion difference, renal tubular acidosis Classification of an acid-base defect physiological response to the primary disturbance and is The primary defect in an acid-base disorder is by definition not designated as an acidosis or an usually defined by its initiating process (e.g. lactic alkalosis.1 The responses are described as secondary or acidosis, ketoacidosis or renal tubular acidosis). A compensatory responses and may be broadly quantified, broader classification, however, divides them into for example: metabolic or respiratory, with the latter relating to - Chronic respiratory acidosis with partial renal changes in arterial blood carbonic acid (i.e. carbon compensation, dioxide) only. - Lactic acidosis with respiratory compensation, or A compensatory response describes the secondary - Metabolic alkalosis without respiratory compensation Correspondence to: Dr. L. I. G. Worthley, Department of Critical Care Medicine, Flinders Medical Centre, Bedford Park, South Australia 5042 (e-mail: [email protected]) 188 Critical Care and Resuscitation 2001; 3: 188-201 J. McNAMARA, ET AL - Biochemical description of an acid-base defect 1. The arterial blood pH, pCO2 and HCO3 . These Three arterial blood values are necessary to describe values are used to detect the major acid-base defect, an acid-base defect: the likely compensatory response and the presence of 1. pH or H+ nmol/L, i.e. a measure of the acidity or a mixed disorder. alkalinity, 2. The anion gap. This is used to detect a high anion 2. PaCO2 (mmHg or kPa), i.e. a measure of the gap metabolic acidosis (e.g. keto-acidosis or lactic respiratory component, and acidosis) and a mixed metabolic acidosis. For - - 3. HCO3 (mmol/L), i.e. a measure of the metabolic example, if the decrease in HCO3 is greater than the component. increase in anion gap, then both a high anion and - Although pH and PaCO2 may be measured directly, normal anion gap (i.e. HCO3 losing) metabolic - there is no direct method to measure the plasma HCO3 acidosis may coexist, whereas if the decrease in - - concentration. Also HCO3 concentrations may vary with HCO3 is less than the increase in the anion gap, the changes in PaCO2. patient may have both a high anion gap metabolic To separate the respiratory from the non-respiratory acidosis and a metabolic alkalosis. - HCO3 components, derived indices of standard 3. An acid base diagram. This may be used as an aid to bicarbonate (i.e. the plasma bicarbonate concentration in the diagnostic process.5 However, diagrams are not fully oxygenated blood which has been equilibrated to a mandatory, as various ‘rules of thumb’ are easily 6 PCO2 of 40 mmHg at 37°C), buffer base (i.e. the sum of used at the bedside to facilitate the diagnosis. For the concentrations of all the buffer anions in the blood, example: which includes haemoglobin, bicarbonate, protein, and a. A primary metabolic acidosis is associated with a phosphate), “strong ion difference” (similar to plasma compensatory decrease in PaCO2, the numerical buffer base which is the sum of the concentrations of all value of which (in mmHg) is usually within + 5 the buffer anions in the blood, excluding haemoglobin), mmHg of the number denoted by the two digits base excess or deficit (i.e. the titratable base or acid, in after the decimal point of the pH value, down to a mmol/L, needed to titrate blood in vitro to a pH of 7.4, pH of 7.15 - 7.10 (i.e. the PaCO2 usually goes no 2 at a PCO2 of 40 mmHg and temperature of 37°C), and lower than 10 mmHg, even with a profound standard base excess (or in vivo base excess where metabolic acidosis).7 correction factors, e.g. 0.3 x the Hb value, are used to Also in a primary metabolic acidosis as the - approximate the buffering effect of the extracellular calculated HCO3 halves, the pH decreases by fluid),3 have been proposed. approximately 0.1. Although many believe that from all of the above b. A primary metabolic alkalosis may be associated derived indices, standard base excess reflects the with a compensatory increase in PaCO2, the metabolic component of an acid-base disorder most numerical value of which (in mmHg) is usually accurately, the correction does not differentiate a up to the number denoted by the two digits after metabolic alkalosis or acidosis from a compensatory the decimal point of the pH value, until the pH 3 renal response. value reaches 7.55 - 7.60 (i.e. the PaCO2 usually For clinical purposes, in addition to the history and goes no higher than 60 mmHg, even with a - physical examination, the HCO3 concentration calculat- profound metabolic alkalosis). However, ed from the Henderson equation (i.e. the ‘actual’ or compensatory changes in PaCO2 are not immed- ‘calculated’ bicarbonate), with the PaCO2 and pH, are iate (c.f. metabolic acidosis) and usually do not 2,4 all that are required to interpret the acid-base disorder. occur in the presence of hypoxia. c. In a primary acute respiratory acidosis the calcul- - Diagnosis of an acid-base defect ated HCO3 value rises 1 mmol/L for each 10 + - Here one seeks to define the primary attack upon H mmHg (1.3 kPa) rise in PaCO2, up to a HCO3 homeostasis, the duration and severity of the pH defect value of 30 mmol/L. and assess the body’s compensatory response. Clinical Also in a primary respiratory acidosis the pH features (e.g. Kussmaul breathing, tachypnoea, cyano- decreases by approximately 0.1 for each 20 sis, tracheal ‘tug’, hypotension, shock, ketotic breath) mmHg increase in the PaCO2. and biochemical data (e.g. arterial blood gas analysis, d. In a primary respiratory alkalosis (both acute and - anion gap, renal and hepatic plasma ‘profiles’ and chronic) the calculated HCO3 decreases 2.5 urinary electrolytes) should all be taken into account. mmol/L for each 10 mmHg (1.3 kPa) reduction - The acid-base defects, however, are usually identified in PaCO2, down to a HCO3 value of 18 mmol/L. from: 189 J. McNAMARA, ET AL Critical Care and Resuscitation 2001; 3: 188-201 Also, in a primary respiratory alkalosis the pH Table 1. Aetiology of metabolic acidosis increases by approximately 0.1 for each 10 mmHg decrease in PaCO2. Accumulation of acid (anion gap > 16 mEq/L) e. In chronic respiratory acidosis (due to renal Disorder Acid - compensation) the calculated HCO3 increases by Ketoacidosis β-hydroxybutyrate, acetoacetate 4 mmol/L for each 10 mmHg (1.3 kPa) rise in Lactic acidosis D or L-lactate - PaCO2, up to a HCO3 value of 36 mmol/L. Methanol Formate, lactate Also in chronic respiratory acidosis the pH Renal failure Sulphate, phosphate decreases by approximately 0.05 for each 20 Salicylic acid Salicylate, lactate, keto-acids mmHg increase in PaCO2. Paraldehyde Lactate, acetate Formaldehyde Formate CLINICAL ACID-BASE DISORDERS Ethylene glycol Glycolate, oxalate, lactate Toluene Hippuric acid Metabolic (nonrespiratory) acidosis Paracetamol Lactate, pyroglutamate This arises from an abnormal process generating Intravenous - excess non-carbonic acid or an abnormal loss of HCO3 , Fructose Lactate which may be identified by an increased anion gap (the Sorbitol Lactate 8 anion in question approximating the ‘gap’ increase ) or Ethanol Lactate normal anion gap, respectively (Table 1). Characterist- Xylitol Lactate ically, the arterial blood gas analysis reveals a pH < 7.36 Accumulation of HCl (anion gap < 16 mEq/L) + (H > 44 nmol/L), PCO2 < 35 mmHg (4.7 kPa), and Releasing HCl with metabolism - calculated HCO3 < 18 mmol/L.