Combined Metabolic Acid-Base Balance Disorders

Summary:

Combined acid-base balance disorders are caused by a combination of several simple disorders. Examples of com-mon combinations:

• Vomiting (loss of chlorides → metabolic alkalosis) + fasting (accumulation of ketone bodies → metabolic acidosis)

• Diabetic ketoacidosis + dehydration (poor tissue perfusion → lactate formation → metabolic acidosis)

• Salicylate intoxication (organic acid → metabolic acidosis + respiratory centre irritation by salicylate → respiratory alkalosis)

• Respiratory insufficiency with hypercapnia (e.g. respiratory acidosis in COPD - Chronic obstructive pulmo-nary disease) is also connected with hypoxia and lactic acidosis

The treatment for combined disorders focuses on removing the cause (all of the causes if there are more than one);

the target laboratory parameter is pH (not BE).

If two or more simple disorders are present at the same time, the condition is referred to as a combined (mixed) acid-base balance disorder. The disorders either develop independently of each other, or one disorder conditions the

other, which, however, never develops in order to compensate the former.

The disorders may counteract one another (a combination of acidosis and alkalosis), so the resulting pH does not deviate much from the norm and blood pH and other ABB parameters may even be in the physiological range. In other cases, both disorders shift the pH value in the same direction and potentiate each other. The paragraphs below descri-be some examples of combined disorders.

15.2.1. Combination of Counteracting Disorders

15.2.1.1. Combined MAc and MAl

The patient vomits and develops hypochloraemic MAl. Since the patient is not taking in any food, another disorder, metabolic ketoacidosis, gradually develops as a result of fasting. One disorder may cancel out the other, so acid-base assays do not show any pathological deviation. In such instance it is very important to examine the basic ion concent-ration in the serum (Figure 16.1).

The first column represents anions in healthy individual’s serum. The second column shows changes caused only by the loss of chlorides through vomiting. In the third column accumulating ketone bodies (included within unmeasured anions) will cause a decrease in HCO₃^- concentration to the normal level. The necessity to consider patient history and the clinical presentation of the disease is beyond dispute.

Another example of a MAc and MAl combination is a patient with uraemia (renal MAc) who vomits repeatedly (hypochloraemic MAl is developing).

Figure 15.7. The development of a combined acid-base balance disorder with concurrent vomiting and fasting as shown by serum anions; figures show ion concentration in mmol/l. Lost chlorides are replaced with hydrogen carbonates during vomiting (and there will be no change in the anion gap). An increase in ketone bodies (organic acids) during fas-ting leads to a rise in unmeasured anions (and the anion gap) – refer to the preparation for the relevant calculations.

15.2.1.2. Combined MAc and RAl

In salicylate intoxication, the presence of relatively strong salicylic acid in the blood will induce MAc at first. As soon as the acid crosses the blood-brain barrier, RAl will develop as a result of respiratory centre irritation.

15.2.2. Combination of Disorders Acting in the Same Direction

15.2.2.1. Combination of Two Different MAcs

Example: A decompensated diabetic with ketoacidosis and hyperglycaemia; this will cause osmotic diuresis with polyuria and dehydration. Hypovolaemia will lead to tissue hypoxia and another MAc (this time lactic MAc) will deve-lop.

15.2.2.2. Combined RAc and MAc

A typical example is the situation occurring in a patient with severe global respiratory insufficiency or even with cardiac and respiratory arrest. Carbon dioxide accumulates in the body (RAc) and tissues demanding oxygen produce a large amount of lactate (MAc). The result is a dramatic decrease in the internal environment pH.

Additional examples of the RAc and MAc combination, developing from a compensated simple disorder, are shown in the diagram in Figure 15.8.

Patient A is a diabetic with acute developing metabolic ketoacidosis (Position A₁). As the disorder has lasted for some time, it is compensated by hyperventilation, at first partially (A₂), later in full (A₃). Subsequently, the condition was complicated by respiratory muscle fatigue, which not only prevented pulmonary compensation, but also led to the development of respiratory acidosis (A₄).

The second patient B suffers from respiratory acidosis, at first acute (B₁), later partially (B₂) and fully compensated (B₃) by renal function. Extensive pneumonia has led to further worsening of gas exchange in the lungs with a further increase in hypercapnia and hypoxaemia, resulting in hypoxic lactic MAc (B₄).

Figure 15.8. The development of a combined disorder from the primary simple compensated disorder (see text for de-tails); a = acute, s = stabilized.

15.2.3. Combination of Multiple Disorders

Perhaps the best example of the whole range of potential disorders is a patient with severe hepatic disease. The following acid-base disorders may occur in such patient:

• Lactic MAc as a result of impaired lactate elimination in the liver;

• Metabolic alkalosis in hypoalbuminaemia (a decrease in the anion column is compensated by a rise in hydrogen carbonate concentration); decreased oncotic pressure due to hypoalbuminaemia may lead to reduced blood stream with overproduction of renin and subsequently aldosterone, which supports the development of MAl;

• Respiratory alkalosis is the result of respiratory centre irritation by accumulating toxic substances;

• If the hepatic failure is complicated by hepato-renal syndrome, renal MAc will develop;

• Additional disorders may be induced by pharmacotherapy with diuretics (e.g. hypochloraemic metabolic alkalosis due to furosemide administration);

• Alcoholic ketoacidosis also exists – this occurs mainly in alcoholics or following a one-time ingestion of a large amount of ethanol. It is caused by a combination of fasting (increased elimination of fatty acids and formation of ketone bodies), dehydration from vomiting (reduced excretion of ketone bodies through the kidneys), and the metabolic effects of ethanol (mainly an increase in the NADH + H⁺/NAD⁺ ratio and the resulting decrease in gluconeogenesis and production of ketone bodies with prevalent β-hydroxybutyrate – undetectable by urine dip sticks).

15.2.4. Summary of Mixed Acid-Base Disorder Diagnostics

A simplified procedure that offers the fastest diagnosis of acid-base disorder is as follows:

1. Clinical approach – detailed patient history and physical examination often provide sufficient informati-on for correct diagnosis. For example, informatiinformati-on about vomiting, diarrhoea, polyuria, exposure to toxic noxa, alcoholism, use of diuretics, concomitant diseases or Kussmaul breathing, acetone breath or signs of cardiac failure can lead us to a correct diagnosis very fast.

2. Compensation (diagnostic) diagram – see Figures 2 and 3. A good tool since it allows us to easily identify the development of a disorder over time (compensation, correction), to differentiate the respiratory and metabolic components and to estimate therapeutic doses. The diagram does not work when used for mixed disorders (counteracting disorders in particular), nor does it allow the cause of the disorder to be revealed and the zone of compensated MAl is too broad (due to the limitation of hypoventilation com-pensation by hypoxia).

3. Auxiliary calculations – based on the model of electroneutrality. Corrected chloride concentration and the anion gap (or unmeasured anions for greater precision) are particularly useful. The corrected chloride con-centration helps reveal any effect of the change of chlorides on the acid-base balance, the anion gap helps in the case of increased production of acids (mainly in poisonings – methanol, ethylene glycol, ethanol, salicylates, less in lactic acidosis and ketoacidosis – the clinical picture is quite characteristic here).

15.2.5. Notes on Acid-Base Disorder Treatment

Treatment for acid-base disorders should always be based on patient history and the clinical presentation of the di-sease. The objective is to remove or mitigate the root cause of the disease (vomiting in hypochloraemic MAl, tissue oxy-genation disorders in lactic MAc, bronchopneumonia in RAc, diabetic decompensation in diabetic ketoacidosis, etc.).

If acidifying or alkalizing solutions are administered to treat for metabolic acid-base disorders, the aim is to reach the target pH; this is 7.2 in acidoses and 7.4 in alkaloses. Adjusting the BE value to zero is not advisable and will not normalize pH, which should be the ultimate goal of the treatment.

Care should be taken during infusion correction of metabolic acid-base disorders, in particular compensated acido-ses or mixed disturbances with acidosis and alkalosis. Most disorders will resolve spontaneously if the underlying cause is eliminated. In any case, persistence of compensatory mechanisms following elimination of the cause of disorder has to be taken into account in compensated disorders. The same certainly holds true for compensated respiratory disorders, where renal compensation persists even for several days. The principle of concurrent treatment for both disorders must be adhered to in mixed disorders so that the other one does not become prevalent. Figure 3 shows several examples of inappropriate approach.

Figure 15.9. Examples of inappropriate treatment for compensated and combined acid-base balance disorders, leading to dangerous alkalaemia.

Patient A is a diabetic in ketoacidosis (A₁), which is gradually compensated by hyperventilation (A₂, A₃). If the pri-mary disorder, MAc, is eliminated by insulin administration, persisting hyperventilation will induce severe alkalaemia in the patient, albeit with BE = 0 (A₄).

Patient B has chronic respiratory acidosis fully compensated by renal function (B₁). If normocapnia is reached in the patient by controlled ventilation, persisting renal compensation of the respiratory disorder will once again induce alkalaemia (B₂).

Position C₁ represents a patient with hypochloraemic MAl (vomiting) combined with metabolic ketoacidosis (fasting). If only MAc is eliminated, for example by glucose infusion, this would lead to a shift back to the alkalaemia region (C₂). Therefore, both disorders must be treated at the same time in combined disorders, i.e. to supply missing chlorides in the form of an isotonic NaCl solution infusion, for example, in addition to glucose.

In all cases mentioned above, the patients were at risk of alkalaemia, with all its adverse effects such as:

• Hypokalaemia;

• Decrease in ionized calcium and magnesium concentration with proneness to tetany;

• Oxyhaemoglobin dissociation curve shift to the left with decreased release of oxygen from the bond to haemoglobin;

• Increased toxicity of some drugs such as digoxin.

CHAPTER 16