Acid-Base Disorders

Abstract

Acid-base disorders can either be metabolic (primary change in HCO₃) or respiratory (primary change in PaCO₂).

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FormalPara Key Points

• Acid-base disorders can either be metabolic (primary change in HCO₃) or respiratory (primary change in PaCO₂).

• Every primary acid-base disorder results in a compensatory response. Use rules of thumb to differentiate single from mixed disorders.

• Metabolic acidosis can be partitioned using the Fencl-Stewart equation into strong ion difference, albumin and unmeasured anions.

• A corrected anion gap is useful in determining the cause of metabolic acidosis.

• The underlying cause of the acid-base disorder needs to be identified and treated.

Introduction

Life is a struggle....sin, not against money power, not against malicious animal magnetism, but against hydrogen... – H.L. Mencken

Disorders of acid-base balance are very common in acutely ill patients, and accurate diagnosis of the acid-base disorder and appropriate management may be lifesaving. A systematic approach to the diagnosis and treatment of these disorders is therefore essential. An arterial blood gas (ABG) is required to identify the acid-base disorder and to document its severity. This is best performed by collecting the blood in an anticoagulant-lined syringe designed for this purpose and analysing immediately on an analyser placed at point of care. In the absence of a point-of-care device, the sample should be placed in ice and hand carried to the central laboratory as quickly as possible. Transport of ABG samples through pneumatic tube systems is not recommended as such transport can potentially alter blood gas values.

The ‘Normal’ Arterial Blood Gas [1] (Table 12.1)

Table 12.1 Normal and clinically acceptable arterial blood gas (ABG) values

The statistical ‘normal’ is derived from healthy populations. However, clinically relevant abnormal values are those beyond which there is a derangement of function and therapy is mandatory.

The Stepwise Approach to Interpreting Arterial Blood Gas [1]

Step 1: Assess Oxygenation

• First look at the absolute value of PaO₂.

  • Treat hypoxia if <60 mmHg – oxygen therapy.

  • Reduce FiO₂ if >100 mmHg.

• Then assess PaO₂/FiO₂ (P/F) ratio or A-a gradient.

  • For example, FiO₂ 21 %, i.e. 0.21, PaO₂ 84 mmHg, P/F ratio = 84/0.21 = 400

  • P/F ratio gives an indication of the degree of severity of lung pathology.

  • Normal P/F ratio 400–500. Acceptable >300.

Step 2: Identify the Primary Problem

The PaCO₂ and HCO₃ impact the pH and determine the acid-base status of the patient. The PaCO₂ is determined by the respiratory system, and the HCO₃ is regulated by the kidney, liver, gut and muscle, collectively referred to as the metabolic system. Therefore, broadly four acid-base disorders are possible (see Table 12.2).

Table 12.2 Primary acid-base disorders

Look at pH, PaCO₂ and HCO₃ for values outside acceptable range.

If the pH is abnormal, the direction in which it has moved indicates the nature of the primary disorder. For example, if the pH is 7.10, the primary disorder is definitely an acidosis. We can then look at the PaCO₂ and the HCO₃ to see if the acidosis is respiratory or metabolic.

If the pH is normal with an abnormal PaCO₂, then two possibilities exist. Either it is a mixed state, where there are two primary opposing acid-base disorders, one respiratory and one metabolic, or there is a fully compensated respiratory acid-base disturbance.

Remember, an abnormal PaCO₂ or HCO₃ indicates an acid-base disturbance even when the pH is near normal or normal.

Additionally an anion gap >20 usually points to a metabolic acidosis irrespective of the actual values of the PaCO₂ or HCO₃.

Step 3: Assess Adequacy of the Compensatory Response – Single (Simple) and Mixed Disorders

The body aims to keep the extracellular pH tightly regulated. Hence, every primary acid-base disorder initiates a compensatory response (see Table 12.3).

Table 12.3 Compensatory acid-base disorders

It can be observed that the compensatory change moves in the same direction as the primary change. For example, an increase in PaCO₂ leads to a compensatory increase in HCO₃, and a decrease in PaCO₂ leads to a compensatory decrease in HCO₃.

The diagnosis of a single acid-base disorder implies both the initial process and the appropriate compensatory mechanisms. Inappropriateness (excess or inadequate) of the expected compensatory response indicates a mixed disorder. This can be diagnosed for clinical purposes by using a few bedside rules:

• 1. Metabolic disorders.

  In a primary metabolic acidosis, the correct compensatory change is a drop in PaCO₂ due to hyperventilation. The numerical value of the reduced PaCO₂ should be within + or – 5 mmHg of the number formed by the two digits after the decimal point of the pH value down to 7.10. The PaCO₂ usually goes no lower than 10 mmHg even with a profound metabolic acidosis [2]. For example, in a primary metabolic acidosis with a pH of 7.20, the expected normally compensated PaCO₂ value will be 20 ±5 (i.e. 15–25 mmHg). If the PaCO₂ is within this range (e.g. 20 mmHg), the diagnosis is an appropriately compensated metabolic acidosis. On the other hand, if the PaCO₂ is higher than this expected range (e.g. 30 mmHg), then the diagnosis is mixed metabolic and respiratory acidosis, and if it is lower than this expected range (e.g. 10 mmHg), then the diagnosis is mixed metabolic acidosis and respiratory alkalosis. Similarly, in a primary metabolic alkalosis, the appropriate value of the elevated PaCO₂ is within ±5 mmHg of the number formed by the two digits after the decimal point of the pH value up to 7.60.

  However, these calculations of appropriate compensation as given above should be applied to spontaneously breathing patients and not to those who are mechanically ventilated because in such patients, ventilator settings determine the PaCO₂.

• 2. Respiratory disorders.

  In primary respiratory disorders, the initial change is in the PaCO₂ with a compensatory change in HCO₃. The degree of change in HCO₃ depends on both the PaCO₂ and also on whether the process is acute or chronic. The differentiation between acute and chronic respiratory disorders is based on the presence of an abnormal pH. If the change in PaCO₂ is associated with a pH <7.30 or >7.50, the disorder is acute, while in a chronic process, the compensatory process brings the pH to the lower limit of the clinically acceptable range (7.30–7.50). Table 12.4 shows the thumb rule of 1, 4; 2, 5 to calculate appropriate HCO₃ response in respiratory disorders.

  Table 12.4 Appropriate HCO₃ values in respiratory disorders

  The rise in PaCO₂ is calculated from a normal value of 40 mmHg.

  As an example, in acute respiratory acidosis, if the CO₂ is 100 mmHg, the rise in CO₂ is (100 minus 40) = 60. Since the expected rise is 1 mEq/L of HCO₃ for every 10 mmHg rise in CO₂, in this situation, the expected HCO₃ rise is 6. The expected HCO₃ is thus 6 mEq/L above the normal range of 24–28. The new expected range for HCO₃ will therefore be 30–34. If the actual HCO₃ is out of this range, there is a second process affecting it. If the actual HCO₃ is higher than 34, there is an associated metabolic alkalosis and, if less than 30, an associated metabolic acidosis.

• 3. Compensatory changes tend to return the pH to near normal.

  Compensatory mechanisms do not necessarily correct the pH to the middle of the acceptable range as the drive for correction reduces as the acceptable levels are reached. These mechanisms often only bring it to the lower limit of the acceptable range. Compensatory mechanisms never overcorrect. Hence, in a chronic respiratory acidosis, for example, the HCO₃ will compensatorily rise and move the pH to between 7.30 and 7.35. It will not move it to 7.40 and will definitely not create an alkalosis by pushing it to 7.50, unless there is a superimposed secondary or mixed acid-base disorder.

Step 4: In a Metabolic Process, Use Story’s Modification of the Fencl-Stewart Equation to Identify the Contributing Factors

The previous steps help to diagnose most forms of metabolic acid-base disorders but may miss derangements caused by abnormal chloride or albumin levels. The Fencl-Stewart approach which was suggested to overcome this issue [1, 3] is able to identify other contributors to the metabolic acid-base balance.

The Fencl-Stewart approach to acid-base disorders uses five equations of varying complexity to estimate the base excess effects of the important components: the strong ion difference (sodium and chloride), the total weak acid concentration (albumin) and unmeasured ions. Although this approach is straightforward, most people would need a calculator to use the equations.

D.A. Story simplified these equations into one, making it usable at the bedside [4].

In this approach, the base excess (which represents the metabolic component of the acid-base dysfunction) is partitioned into three domains:

• (a) Acidosis/alkalosis caused by the difference between serum Na and chloride (the strong ion difference or SID).

• (b) Acidosis/alkalosis caused by the changes in levels of albumin.

• (c) Acidosis/alkalosis caused by the unmeasured anions (UMA) such as keto acids, phosphate etc. Lactate used to be considered in this category but is now measured by most ABG machines.

$$ \begin{array}{l}\mathrm{BASE}\ \mathrm{EXCESS}=\left[\left(\mathrm{N}\mathrm{a}-\mathrm{C}\mathrm{l}\right)-38\right]+\left[2.5\left(4.2-\mathrm{serum}\ \mathrm{a}\mathrm{l}\mathrm{bumin}\right)\right]+\\ {}\left[2-\mathrm{lactate}\right]+\left[\mathrm{minus}\ \mathrm{U}\mathrm{M}\mathrm{A}\right]\end{array} $$

The normal SID (Na – Cl) is 38.

The albumin in this equation is measured as gm/dl.

The UMA represents unmeasured anions. Examples are keto acids and fixed acids in renal failure and sepsis. The algebraic signs must be correctly entered for the above equation to be mathematically correct.

A low Na – Cl difference results in an acidosis and vice versa.

A low albumin level results in a metabolic alkalosis and vice versa.

If the base excess value is not fully explained by its components, there is an unmeasured anion contributing to the process.

This process of teasing out the contributing components of the metabolic acidosis is very useful in the management of critically ill patients who often have many processes affecting the metabolic acid-base balance. For example, a patient with severe metabolic acidosis will often have a bit of SID acidosis, lactic acidosis, hypoalbuminaemic alkalosis and acidosis due to unmeasured anions. Therefore, if the predominant contributor is SID, the best treatment is an infusion of sodium bicarbonate, but if it is UMA, then haemodialysis may probably be the best option.

Causes and Treatment of Acid-Base Disorders

Now that a diagnosis has been made, the cause of the acid-base disorder must be pinpointed and appropriate therapy started as soon as possible since both acidaemia and alkalaemia have adverse physiological effects as listed in Table 12.5.

Table 12.5 Physiological effects of acidaemia and alkalaemia

Respiratory Acidosis

This results from a reduction in minute ventilation.

Causes

This could be central (affectations of the respiratory centre) or peripheral (chest wall and muscles or lung parenchyma).

Central

• Sedative and narcotic drugs

• CNS injury or infection

• Brainstem infarctions

Peripheral (see Table 12.6)

Table 12.6 Peripheral causes of respiratory acidosis

Treatment

Treat the underlying cause. Mechanical ventilation – invasive or non-invasive may be required.

Respiratory Alkalosis

This results from an increase in minute ventilation.

Causes

This could be central (affectations of the respiratory centre) or peripheral (lung parenchyma) (Table 12.7).

Table 12.7 Causes of respiratory alkalosis

Treatment

Treat the underlying cause.

Metabolic Acidosis

In addition to using the Fencl-Stewart equation, an anion gap is useful in trying to identify the cause of metabolic acidosis.

The anion gap exists because not all electrolytes are measured. The quantity of unmeasured cations is much less than unmeasured anions. The difference between these two is called the anion gap. In practice, it is calculated as:

$$ \mathrm{Anion}\ \mathrm{gap}=\left[\mathrm{N}\mathrm{a}+\mathrm{K}\right]-\left[{\mathrm{HCO}}_3+\mathrm{C}\mathrm{l}\right] $$

The normal value is 16 ± 4 mEq/L. If potassium is not included while calculating anion gap, then the normal value is 12 ± 4 mEq/L. Since the normal value of the anion gap decreases with hypoalbuminaemia, it is useful to correct the anion gap for the albumin level.

The corrected anion gap = calculated anion gap + 2.5 (4.0 – albumin). The albumin in this equation is measured as gm/dl.

Once the anion gap is calculated, it is easy to consider causes of metabolic acidosis as those causing an increased anion gap and those presenting with a normal anion gap.

Causes of High Anion Gap Metabolic Acidosis

High anion gap metabolic acidosis is usually caused by conditions where there is an accumulation of acids with a strong anion, and these can be remembered with the mnemonic ‘MUDPILES’.

M methanol; U uraemia; D diabetic ketoacidosis; P propylene glycol; I infection, sepsis; L lactic acidosis; E ethylene glycol, ethanol; S salicylates

Lactic Acidosis

Lactic acidosis is very common in acutely ill patients. It can result from an overproduction of lactate or a reduction in excretion. Common reasons for this are:

• 1. Impaired oxygen delivery to tissues: This can happen during shock, when abnormal global haemodynamics cause inadequate perfusion of all tissues, leading to anaerobic metabolism and production of lactic acid. It can also happen when tissue microcirculation is abnormal in the presence of normal global haemodynamics or when there is impaired blood flow to any one region or organ as can be seen in limb or bowel gangrene.

• 2. Mitochondrial dysfunction: This can be seen in sepsis and also as a result of use of drugs such as metformin and nucleoside reverse transcriptase inhibitors.

• 3. Pyruvate dehydrogenase deficiency: This is seen in severe sepsis and thiamine deficiency.

Causes of Normal Anion Gap Metabolic Acidosis

Normal anion gap metabolic acidosis results from conditions which reduce the strong ion difference in the extracellular fluid (Table 12.8).

Dilutional acidosis: Large volumes of intravenous fluids produce a metabolic acidosis when the SID of the infused fluids is less than the SID of extracellular fluid. This is typically seen with saline infusions as the SID of saline is 0 (Na 154 mEq/L, Cl 154 mEq/L). This tends to lower the extracellular SID and cause an acidosis.

High urinary SID: In various forms of congenital and drug-induced renal tubular acidosis, urinary SID is high even though extracellular SID is low. This happens because of defects in the proximal or distal renal tubule which impair chloride excretion resulting in hyperchloraemia and a low SID acidosis.

Loss of high SID enteric fluids: Small intestinal, pancreatic and biliary secretions have low chloride content and a high SID. Conditions such as certain diarrheal illnesses result in increased losses of such fluids resulting in a narrowing of extracellular SID.

High chloride intake: Total parenteral nutrition and ammonium chloride administration can sometimes result in this.

Table 12.8 Causes of normal anion gap acidosis

Delta Anion Gap/Delta Bicarbonate

The anion gap allows differentiation of high and normal gap acidosis. However, it is possible for a high anion gap acidosis to coexist with a normal anion gap acidosis. The delta/delta concept allows the diagnosis of this situation.

The concept behind delta/delta is based on the assumption that for every increase in anion gap of 1 mmol/L above normal (12 mmol), serum HCO₃- will drop by an equal amount, that is, the change in anion gap should be equal to change in HCO₃. Therefore, in a pure high anion gap acidosis, delta anion gap = delta HCO₃.

When the delta HCO₃ > delta anion gap, it is because a normal anion gap acidosis is present along with the high anion gap acidosis, leading to an additional drop in bicarbonate.

Treatment

In a high anion gap acidosis, there is an accumulation of a strong acid, and treatment is directed first at stopping the production of more acid, e.g. insulin therapy in ketoacidosis, haemodynamic optimisation in shock, and secondly at hastening the removal of the acid, e.g. dialysis. The underlying cause of the acid accumulation needs to be treated.

If the problem is due to a high chloride with a normal sodium (low extracellular SID), the therapy is to use chloride-free IV fluids and to give sodium without the chloride ion, e.g. in the form of sodium acetate or sodium bicarbonate or sodium lactate.

Administration of Buffers

Except for normal anion gap acidosis, the use of NaHCO₃ is not recommended for pH > 7.15. In diabetic ketoacidosis, this threshold is lowered to a pH of <7.0.

The aim of administering the NaHCO₃ is to increase the SID. Therefore, the active ingredient is Na, not HCO₃. In fact the bicarbonate ion combines with hydrogen ion and is converted to carbon dioxide and water. This potential to increase PaCO₂ levels is the reason why it should not be administered as boluses but as a continuous infusion.

NaHCO₃ can also adversely result in paradoxical intracellular acidosis, hypernatraemia, hyperosmolarity, hypocalcaemia and decreased oxygen delivery.

Metabolic Alkalosis

Metabolic alkalosis is less common than acidosis.

Causes

Metabolic alkalosis occurs by four main mechanisms (Table 12.9):

• Low urinary SID: Loop and thiazide diuretics among other causes result in a tubular loss of chloride resulting in a low urinary SID and therefore a high extracellular SID leading to alkalosis.

• Enteric losses of low SID fluid: Gastric secretions have no sodium, only chloride. Loss of this low SID fluid by vomiting or nasogastric aspiration results in a high SID metabolic alkalosis.

• Gain of high SID fluid: Administration of large quantities of NaHCO₃ or sodium citrate (in transfusions) will also raise the SID and create an alkalosis.

• Volume depletion: This has the opposite effect on extracellular SID as dilution. While dilution narrows SID, dehydration widens it.

For another diagnostic approach, see [4].

Table 12.9 Causes of metabolic alkalosis

Treatment

The underlying cause needs to be treated while also attempting to reduce the extracellular SID. This may include:

• 1. Repletion of ECF volume: Saline or similar low SID fluids need to be administered. Almost all metabolic alkalosis responds to this if enough saline can be given. In hypoalbuminaemic patients, albumin administration accelerates normalisation of the pH as it repletes volume and additionally removes the alkalosis due to low albumin levels (see the Fencl-Stewart equation above).

• 2. Replacement of potassium as chloride salt: While alkalosis produces hypokalaemia that may need replacement therapy, the more important reason to do this is to replace chloride.

• 3. Acetazolamide therapy: Acetazolamide increases proximal tubular chloride reabsorption and increases urinary SID, decreasing extracellular SID.

• 4. Administration of chloride-containing solutions: Ammonium chloride or lysine or arginine hydrochloride has occasionally been used.