Approach to acid–base disorders in primary care

Opening Vignette

Arthur, a 70-year-old Chinese man with a history of hypertension and atopic dermatitis requiring steroids, comes to your clinic for routine follow-up. On his last visit 3 months ago, his blood pressure (BP) had been suboptimally controlled and hydrochlorothiazide (HCTZ) was added to his regimen. His BP has been in the optimal range since then. He has been feeling lethargic for the last few weeks. His medications consisted of Losartan 50 mg once daily (for the last 3 years), HCTZ 12.5 mg once daily (for the last 3 months) and prednisolone 5 mg once daily (for the last 2 years). Physical examination showed that he was alert with BP 140/80 mmHg, heart rate 70 beats per minute and respiratory rate 12 breaths per minute. His skin was scaly, thin and cracked in a few areas. Table 1 summarises his renal profile.

Table 1.

Renal profile of the patient.

Variable	Current	1 year ago
Sodium (Na+) (mmol/L)	140	140
Potassium (K+) (mmol/L)	3.6	4.1
Bicarbonate (HCO3–) (mmol/L)	30	24
Chloride (Cl–) (mmol/L)	100	105
Urea (mmol/L)	6	4

WHAT ARE ACID–BASE DISORDERS?

Acid–base disorders (ABD) are a group of conditions characterised by changes in the concentration of hydrogen ions (H⁺) or bicarbonate (HCO₃⁻) ions, which lead to changes in the arterial blood pH.[1,2,3] A definitive diagnosis is made by arterial blood gas (ABG) analysis. There are four primary ABD, namely metabolic acidosis, respiratory acidosis, metabolic alkalosis and respiratory alkalosis.

When approaching a case of ABD, the following should be noted: (a) For every primary ABD, there is usually a secondary (compensatory) response, as the body tries to normalise the pH. Hence, for a primary metabolic acidosis (where HCO₃⁻ is low), there will be a secondary (compensatory) respiratory alkalosis (as the body blows out partial pressure of carbon dioxide (pCO₂) to increase the pH). For a primary respiratory acidosis (where pCO₂ is high), there will be a secondary metabolic alkalosis (body retains HCO₃⁻); (b) There are two types of primary metabolic acidosis — high anion gap metabolic acidosis and normal anion gap acidosis.[1,2]

The anion gap (AG) is calculated by the following equation: serum Na⁺ – (HCO₃⁻ + Cl⁻). In a healthy person, AG depends mainly on the serum albumin and phosphate concentrations and is typically around 12 (although this number is fairly arbitrary). Organic acids constitute only a small fraction of AG. However, in patients with uraemia, diabetic ketoacidosis (DKA) or lactic acidosis, metabolic acidosis is associated with an increase in AG caused by the increased amount of organic acids.

HOW RELEVANT IS THIS TO MY PRACTICE?

Acid–base disorders are commonly encountered in clinical practice, and some ABD have life-threatening implications. Patients suffering from ABD present to primary care clinics with non-specific symptoms or they may be picked up from routine laboratory tests.[1,2] A missed diagnosis could result in the delay of life-saving treatment for patients such as those suffering from DKA or lactic acidosis. In primary care, doctors frequently encounter patients with underlying medical conditions who are on certain medications that predispose them to developing ABD [Box 1 and Figure 1]. Thus, primary care physicians play a crucial role not only in the early diagnosis of ABD, but also the continuing care of these patients after the initial event has been managed (usually in an acute care hospital). Proper management of any predisposing medical condition can prevent recurrence of ABD and its long-term complications. These complications include (a) osteoporosis and increased the risk of fractures; (b) increased kidney damage, which can worsen chronic kidney disease; (c) muscle loss or wasting; (d) insulin resistance and potentially, diabetes mellitus; (e) shock, (f) coma; (g) seizures; and (h) increased intracranial pressure.[4,5]

Box 1.

Predisposing medical conditions that lead to acid–base disorders.

• Diabetes mellitus

• Congestive heart failure

• Alcoholism

• Chronic liver disease

• Chronic kidney disease stage 3B and above

• Adrenal insufficiency

• Short gut syndrome

• Excessive/prolonged exercise

• Hyperaldosteronism

• Cushing’s syndrome

• Asthma/chronic obstructive pulmonary disease

• Diseases with weak respiratory muscles, e.g., neuromuscular disorder, brainstem stroke

• Severe obesity

• Panic attacks

Figure 1.

Classification of acid–based disorders and the common causes of each disorder. Cl^–: chloride, COPD: chronic obstructive pulmonary disease, H⁺: hydrogen, HAGMA: high AG metabolic acidosis, HCO₃⁻: bicarbonate, Na⁺: sodium, NAGMA: normal AG metabolic acidosis, pCO₂: partial pressure of carbon dioxide, pH: potential of hydrogen

WHAT CAN I DO IN MY PRACTICE?

History and physical examination

Patients with ABD can be asymptomatic or have non-specific symptoms such as weakness, general poor health, giddiness, nausea, vomiting, confusion and breathlessness.[6] A patient may have undiagnosed diabetes mellitus (DM) and may present with symptoms of DKA. Having good knowledge of the patient’s background medical problems will guide a primary care physician into having a high index of suspicion of ABD in such a patient.

Although most primary care clinics are not equipped with an ABG machine to confirm the diagnosis of ABD through stat investigations, a physician should still be able to make a presumptive diagnosis of primary metabolic ABD with comprehensive history taking, relevant physical examination and a renal panel with bicarbonate.[1,2,3,7] During evaluation of patients with predisposing medical conditions [Box 1] that can lead to ABD, it is important to look out for markers of severe illnesses, such as confusion, jaundice, fruity-smelling breath, tachypnoea, hypotension with tachycardia, poor oral intake and blood oxygen saturation (SpO₂) less than 94% in room air. Patients with such markers need to be referred to the accident and emergency department for urgent management.

Besides addressing the biological factors leading to the development of ABD, the psychosocial determinants of health should also be looked at to prevent recurrence.[8] Work stress, financial difficulties and family dysfunction are factors that may lead to poor adherence to medication and follow-up appointments. Poor understanding of the disease due to intellectual disability or cognitive impairment poses another challenge. These patients may need simpler management plans and caregiver involvement. Depression might lead to disinterest in one’s own health issues and forgetfulness.

There is also the possibility of intellectual insight in the management of individual medical problems not translating into emotional insight in some patients.[9] Patients might be fully aware that the prognosis of their disease is dependent on their participation in management of chronic diseases and any non-adherence can impact it. This intellectual insight is acquired from education by healthcare professionals. However, some patients lack the emotional awareness of the impact of the diagnosis on their psyche and quality of life, leading to difficulties as they try to adapt to living with chronic disease(s). Some of the issues include frustration and rebellious behaviour. Acknowledging the distress felt by these patients and managing the impact on their quality of life will improve the outcomes.

Investigation and management

A complete diagnosis of ABD is made with ABG and serum electrolytes analysis [Table 2]. The first thing to consider is the serum pH level, followed by the other results, which will determine whether the disorder is of a metabolic or respiratory nature [Table 3].

Table 2.

Laboratory readings related to acid–base calculations.

Variable	Normal range (2 SD)
Potential of hydrogen	7.35–7.45
Partial pressure of carbon dioxide (mmHg)	35–45
Bicarbonate (mmol/L)	22–26
Anion gap (mmol/L)	10–14
Sodium (mmol/L)	135–145
Chloride (mmol/L)	96–108

SD: standard deviation

Table 3.

Examples of abnormal laboratory results seen in acid–base disorders.

Serum electrolytes (mmol/L)		Evaluation steps (with relevant information)	Diagnosis	Management
Current	1 year ago
Na+: 140 K+: 4.8 HCO3–: 14 Cl–: 102 Cr: 400 Urea: 20 Glucose: 15 HbA1c: 12%	Na+: 140 K+: 4.6 HCO3–: 22 Cl–: 105 Cr: 160 Urea: 8 Glucose: 10 HbA1c: 10%	A 65-year-old with diabetes mellitus, chronic kidney disease stage 2, HTN; feels giddy and fatigue: • HCO3– is low, suggesting metabolic acidosis • AG=140–(14+102)=24=HAGMA	Two likely causes: 1. ESRF (possibly secondary to poor diabetes control) 2. Diabetic ketoacidosis Another common differential diagnosis is lactic acidosis due to shock of any nature)	Refer to A&E as both differential diagnoses carry serious complications if not treated immediately and aggressively
Na+: 142 K+: 3.5 HCO3–: 16 Cl–: 114, Cr: 170 Urea: 8	Na+: 140 K+: 3.6 HCO3–: 24 Cl–: 105 Cr: 100 Urea: 4	A 40-year-old man with HTN; has diarrhoea for 4 days and goes for annual check-up: • Low HCO3– suggests metabolic acidosis • AG=142–(16+114)=12=NAGMA	NAGMA secondary to diarrhoea Differential diagnosis: renal tubular acidosis	Refer to A&E in view of worsening of renal function by 70%
Na+: 140 HCO3–: 30 Cl–: 100 Cr: 120 Urea: 6 Glucose: 5	Na+: 141 HCO3–: 31 Cl–: 103 Cr: 110 Urea: 4 Glucose: 7	A 55-year-old woman with COPD, HTN and obesity BMI (40 kg/m2); ex-smoker who stopped smoking 10 years ago, has no breathlessness for a long time and is on routine follow-up. Medications: enalapril, Ventolin metered dose inhaler prn  • High HCO3– suggests metabolic alkalosis, primary or compensatory); there is no clear reason for primary metabolic alkalosis, but being morbidly obese, the patient likely has OHS	Primary respiratory acidosis due to OHS with compensatory metabolic alkalosis; this is not due to COPD, as the patient has no signs of severe COPD	Refer to respiratory team

AG: anion gap, A&E: accident and emergency department, BMI: body mass index, Cl^–: chloride, COPD: chronic obstructive pulmonary disease, Cr: creatinine, ESRF: endstage renal failure, HAGMA: high anion gap metabolic acidosis, HbA1c: glycosylated haemoglobin, HCO₃^–: bicarbonate, HTN: hypertension, K⁺: potassium, Na⁺: sodium, NAGMA: normal anion gap metabolic acidosis, OHS: obesity hyperventilating syndrome

The management of ABD depends on the causes. Treatment can be broadly divided into supportive and specific measures.

Supportive treatment in the primary care setting includes temporising measures, such as setting of an intravenous (IV) line and administration of a fluid bolus in a patient with lactic acidosis from septic shock, before the arrival of the ambulance. Oxygen supplementation is needed in a patient with chronic obstructive pulmonary disease (COPD) presenting with hypoxia and primary respiratory acidosis. However, in a patient with chronic hypercapnia, one should be careful about excessive supplementation due to concerns of suppressing the hypoxic drive and potentially worsening the hypercapnia. Targeting an SpO₂ of around 92% may be prudent in such cases.

Specific treatment directed at the underlying cause is usually done in the hospital setting. For example, lactic acidosis due to shock of any cause (septic, cardiogenic or hypovolaemic) requires inotropes for maintenance of BP. Fluid resuscitation is beneficial in septic and hypovolaemic shock. In addition to fluids, antibiotics and/or source control are needed in cases of septic shock.

Once patients have been discharged and are referred back to their primary care physician, it is crucial to revisit any causes that could have tipped the balancing scale and led to the decompensation of their medical conditions, contributing to the development of ABD. For example, a diabetic patient who does not adhere to treatment regime is prone to DKA, a patient who is consuming traditional medications/over-the-counter products with steroid components can develop metabolic alkalosis and a patient with advanced renal failure will have uraemic acidosis, especially if the patient has refused dialysis. In addition, a patient who smokes and has COPD/asthma should discuss smoking cessation with his/her physician.

TAKE HOME MESSAGES

1. In the primary care setting, measurement of HCO₃⁻ and calculation of AG are useful in the assessment of ABD.

2. A provisional diagnosis of ABD (especially, primary metabolic ABD) can be made by taking a thorough history and performing relevant physical examination and laboratory testing.

3. It is vital to know the common causes of primary ABD.

4. Treatment of ABD must be aimed at correction of the underlying disease process, together with supportive management.

5. Holistic management includes managing the biopsychosocial factors that led to deterioration of the underlying medical conditions causing ABD.

Closing Vignette

Arthur has elevated HCO₃⁻, which suggests metabolic alkalosis [Table 1]. He is on two medications that could cause this type of ABD, that is, prednisolone and HCTZ. However, he was on prednisolone for 2 years with normal HCO₃⁻. Hence, HCTZ is the most likely cause. There is no indication of this being a compensatory mechanism. You inform Authur that his lethargy is likely due to a chemical disorder related to HCTZ that was started recently. One week after stopping HCTZ, he no longer feels lethargic and his HCO₃⁻ returns to normal with no increase in serum Cr or K⁺. His home BP remains optimal with increment of the losartan dose as a replacement for HCTZ.

Financial support and sponsorship

Nil.

Conflicts of interest

How CH is a member of the SMJ Editorial Board and was thus not involved in the peer review and publication decisions of this article.

SMC CATEGORY 3B CME PROGRAMME

Online Quiz: https://www.sma.org.sg/cme-programme

Deadline for submission: 6 pm, 15 March 2024

Question	True	False
1. Acid–base disorders (ABDs) are a group of conditions characterised by changes in the concentrations of hydrogen ions and bicarbonate (HCO3−) ions.
2. The four primary ABDs are metabolic acidosis, respiratory acidosis, metabolic alkalosis and respiratory alkalosis.
3. In a patient with diabetic ketoacidosis (DKA), the partial pressure of carbon dioxide (pCO2) in the arterial blood gas is expected to be low.
4. Calculation of the anion gap (AG) can help distinguish between metabolic acidosis caused by lactic acidosis and diarrhoea.
5. In healthy people, albumin is the main component of AG.
6. Some common medications that can cause primary metabolic ABD are diuretics, corticosteroids, spironolactone and acetazolamide.
7. In a chronic obstructive pulmonary disease patient with primary respiratory acidosis, serum HCO3− is expected to be high.
8. Complications of ABD include osteoporosis, muscle wasting, seizures and insulin resistance.
9. Patients with ABD will always present with symptoms.
10. Some of the symptoms that patients with ABD might present with include weakness, general poor health, giddiness, nausea and breathlessness.
11. A complete diagnosis of ABD is made with an arterial blood gas and serum electrolytes.
12. A person who suffers from metabolic acidosis is expected to have elevated serum HCO3− and reduced pCO2.
13. Some of the predisposing medical conditions that can increase the risk of developing an ABD include congestive heart failure, alcoholism, adrenal insufficiency, short gut syndrome , panic attacks and severe obesity.
14. Some of the psychosocial factors that may lead to development of ABD are financial difficulties, family dysfunction, cognitive impairment and depression.
15. The normal range of bicarbonate is 22–26 mmol/L.
16. The normal range of pH is 7.25–7.45.
17. The causes of high AG metabolic acidosis include diarrhoea, adrenal insufficiency and renal tubular acidosis.
18. Severe vomiting can cause a metabolic acidosis through hydrogen ion loss.
19. Large infusions of normal saline can cause a normal anion gap acidosis.
20. Primary hyperaldosteronism (Conn’s syndrome) can cause primary metabolic alkalosis.