Approach to
Acid Base Disorders

Tharaniya Vallipuram¹
Published online: July 5, 2022

¹McGill University, Montreal, QC, Canada
Corresponding Author: Tharaniya Vallipuram, email tharaniya.vallipuram@mail.mcgill.ca
DOI: 10.26443/mjm.v20i2.885

Question

A 23-year-old male is brought to the Emergency Department by his mother. She reports that he has been acting strangely and is unable to answer her questions coherently. She adds that this all started after he was found sitting in the corner of the bathroom with his hands covering his ears, next to an empty bottle and blood-tinged vomit on the floor. On the way to the hospital, the patient reported nausea and severe abdominal pain. His mother notes that she has been feeling worried about her son given that he lost his job during the COVID-19 pandemic and has been severely depressed for several weeks.

You observe the following on examination:

General appearance: Diaphoretic

Neurologic: Not responding coherently to questions, complains of ringing in his ear

GI: Had another blood-tinged episode of vomiting, abdomen soft but has mild diffuse tenderness

Which of the following is the most likely cause of the patient's condition and blood gas findings?

1. Salicylate intoxication
2. Opioid overdose
3. Diabetic ketoacidosis (DKA)
4. Alcohol overdose
5. Acetaminophen intoxication

Answer

A. The patient in this case is mostly likely experiencing salicylate toxicity (A). Salicylate toxicity is characterized by a mixed acid-base disturbance presentation, in which the patient exhibits respiratory alkalosis (salicylate directly stimulates the cerebral respiratory drive, leading to ↑ respiratory drive and consequent ↓ in CO₂) and anion gap metabolic acidosis (due to ↑ lactic acid, ketoacids and salicylic acid) (2,12). Respiratory alkalosis can be identified with ↑ pH > 7.45 and ↓ PaCO₂ < 32-35. Metabolic acidosis can be identified by an anion gap of 40 (Anion Gap = Na - [Cl + HCO₃]; N: 10-12) indicating the presence of unbuffered acids. Early clinical features of salicylate toxicity include tinnitus (ringing of the ears) and irritation of the GI tract which can lead to nausea, vomiting and abdominal pain and tachypnea (2). Later signs include agitation, delirium and seizures (2,12).

Initial approach

Normal serum pH is tightly controlled within a range of 7.38-7.46 (1) (Note: These values can vary between institutions; many books will use 7.35 as the lower limit). Maintenance within this range is essential for normal protein and enzymatic activity. Alterations of the serum pH can lead to disruption of cellular functions required for survival. Metabolism in the body produces large amounts of volatile and non-volatile acids. Volatile acids include CO₂ derived from the breakdown of carbohydrates and fats, which can bind with water to form carbonic acid. CO₂ levels are controlled by alveolar ventilation. Non-volatile acids are derived from a few sources, including protein metabolism. These acids are eliminated in a 2-step process: 1) Acids combine with buffers such as extracellular bicarbonate (HCO₃^-), intracellular phosphate (HPO₄^2-) and carbonate in bones and 2) Kidneys excrete surplus of H⁺ and reabsorbs HCO₃^3-.

Using these concepts, it is possible to approach acid-base disturbances using a step wise approach. This article will explore the approach that can be used to determine whether a patient is presenting with a simple or mixed acid-base disturbance.

Stepwise Approach to Acid-Base Disorders

Step 1: Establish the primary diagnosis (4,5)

• Look at the pH and determine whether there is an acidemia or alkalemia present:
• Acidemia: pH < 7.35 (~7.38 per MCC) (1)
• Alkalemia: pH > 7.45

• Look at the PaCO2 and determine if the disturbance is respiratory or metabolic:
• If PaCO₂ moves in the opposite direction of pH → Respiratory Process
• If PaCO₂ moves in the saME direction as pH → MEtabolic Process

Step 2: Assess the degree of compensation (4,5)

Use the ratios listed in Table 1 to determine whether there is adequate compensation. If there is insufficient compensation, there is a greater chance that more than one acid-base disorder is present.

Step 3: Measure the following values (especially important in metabolic acidosis) (4,5)

The Anion gap. Normally, anions are present in our bodies and act as buffers for the cations that are present; mainly Na⁺. These anions include proteins, circulating phosphates and sulphates, and albumin. It is important to note that some anions, such as pathological proteins, cannot be measured by routine labs (6). When an excess of acids are present due to any pathologic condition, a gap forms between the number of acids present and the number of anions available to buffer them. In other words, an insufficient number of anions are present to act as buffers.

• The formula for the anion gap is (AG= [Na⁺]- ([Cl^-] + [HCO₃^-]).
• The normal value for the anion gap is 12 mEq/L (4,5,6).

If the anion gap is elevated, the osmolal gap must be calculated to determine if the underlying cause of elevated acid levels can be attributed to excess alcohol present in the body. The exact alcohols will be specified later in this article.

• The formula for the osmolal gap is (Measured Osmolality on lab) - (Calculated Osmolality).
• The formula for the calculated osmolality = 2[Na⁺] + [Glucose] + [Urea].
• The normal value for osmolal gap is <10 (4).

If the anion gap is elevated, the Delta anion gap/delta HCO3- ratio can be calculated to compare the change in anion gap to the change in [HCO₃^-]. An increase in acid content, reflected by a high anion gap, will cause the [HCO₃^-] to decrease as it will act as a buffer for the excess acids. Therefore, the increase in acid levels is normally proportional to the decrease in [HCO₃^-], rendering the delta anion gap/delta HCO₃^- ratio to be usually 1:1 or between 1 to 2 (4,7).

• The formula used to calculate delta anion gap/delta HCO₃^- is

• If the ratio <1, this implies that there is a greater loss in HCO₃^- than expected via compensation. Therefore, a concurrent non-anion gap metabolic acidosis process is present (4). For instance, a patient presenting with DKA and profuse diarrhea will exhibit a ratio <1.
• If the ratio is >2, this implies that [HCO₃^-] value has not decreased as expected, and there is a concurrent metabolic alkalosis or an elevated HCO₃^- at baseline as a result of chronic respiratory acidosis (4,7). For instance, this can be seen in a patient presenting with DKA and profuse vomiting of acidic gastric content.

Step 4: Establish the final diagnosis & determine underlying causes

While Table 2 is not an exhaustive list, it highlights some of the key causes for these disturbances.

Beyond the Initial approach

Metabolic Acidosis

Metabolic acidosis is more complex than the other acid-base disturbances because it is further subdivided into two categories: 1) High anion gap metabolic acidosis (AGMA) and 2) Non-anion gap metabolic acidosis (NAGMA). As explained earlier, the increase in the anion gap occurs due to the presence of excess acids. Many etiologies can account for this increase in acid content, and these etiologies can be remembered using the commonly used acronym "MUDPILES" (see Table 2). The following text expands on these etiologies.

Methanol, Propylene, Ethylene glycol intoxication
Ingested toxic alcohols such as methanol, propylene glycol and ethylene glycol are metabolized into organic acids that have significant side effects on the body, which can include causing metabolic acidosis (9).

Uremia (reflecting renal failure)
In renal failure, a reduction in normal phosphate secretion increases hydrogen retention. (10) This process is further aggravated by impaired excretion of other substances such as organic anions and sulphates (8).

Diabetic ketoacidosis
Ketoacidosis is a metabolic state in which there is a lack of glucose or an inability to use the glucose present, causing the body to break down fatty acids for fuel production (11). This forms a high amount of ketone bodies, particularly acetone, acetoacetate, and beta-hydroxybutyric acid. This is commonly seen in: 1) diabetic ketoacidosis, 2) starvation and 3)excessive alcohol ingestion (8,9,11).

Lactic acidosis
Lactic acidosis commonly occurs as a result of hypoperfusion to the tissues. This decrease in perfusion can be due to various causes, such as systemic hypotension secondary to shock (9).

Salicylate overdose
Lastly, salicylate overdose is characterized by a mixed acid-base disturbance presentation. The patient will have respiratory alkalosis because salicylates directly stimulate the cerebral respiratory drive, resulting in increased respiratory drive and consequent decrease in CO₂. There will also be an anion gap metabolic acidosis due to cumulative accumulation of lactic acid, ketoacids and salicylic acid (12).

References

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