Acid-Base Physiology

Case 2 : A sick diabetic patient

Clinical Details

A 19 year old pregnant insulin dependent diabetic patient was admitted with a history of polyuria and thirst. She now felt ill and presented to hospital. There was a history of poor compliance with medical therapy.

She was afebrile. Chest was clear. Circulation was adequate. Perioral herpes was present. Urinalysis: 2+ ketones, 4+ glucose. Biochemistry on admission: Na+ 136, K+ 4.8, Cl- 101, 'total CO2' 10, glucose 19.0, urea 8.1 and creatinine 0.09 (all biochem results in mmol/l). Arterial blood gases were collected on arrival:

Arterial Blood Gases

pH 7.26

pCO2 16 mmHg

pO2 128 mmHg

HCO3 7.1 mmol/l


First: Initial clinical assessment

The diagnosis is obvious on history: the patient has a severe diabetic ketoacidosis.

If the diagnosis is so obvious on the history then why do we need to bother with the systematic approach?

Because the 3 step systematic approach has several advantages:-

In this case then, the patient has a diabetic ketoacidosis. Our clinical knowledge leads us to the need to consider other acid-base disorders that can occur in such patients. In particular:

Second: The acid-base diagnosis

Proceeding systematically:

  1. pH: The acidaemia indicates the presence of an acidosis
  2. Pattern: The low bicarbonate & the low pCO2 are typical of a metabolic acidosis
  3. Clues: The hyperglycaemia, glycosuria & ketonuria indicate the presence of a diabetic ketoacidosis. The anion gap is elevated (at 25) supporting a diagnosis of a high anion gap disorder. There is no evidence of renal failure. The delta ratio is (25-12)/(24-7) = 0.76 and the chloride level is normal (as is [Na+])
  4. Compensation: The appropriate rule to assess compensation for a metabolic acidosis is the 'one & a half plus 8' rule (rule 5). The expected pCO2 is (1.5 x 7.1 + 8) = 18.5mmHg. The actual pCO2 is only 2 mmHg different so there is no evidence of a co-existing respiratory acid-base disorder. Sufficient time (12-24 hours) has passed so compensation would be expected to have reached its maximum value. Note that this 'maximal compensation' is rarely if ever enough to return the pH completely to normal
  5. Formulation: A severe metabolic acidosis (diabetic ketoacidosis) is present. There is no evidence of any other acid-base disorder. The delta ratio is not low enough nor the chloride level high enough to indicate a definite hyperchloraemic acidosis but this commonly develops during treatment. A lactic acidosis component cannot be totally excluded as no lactate result has been recorded but the fact that the urine test for ketones was reactive argues against a major component of lactic acidosis
  6. Confirmation: A lactate level would be useful but this unfortunately is often not done in such cases

Finally: the Clinical Diagnosis

Diabetic ketoacidosis due to poor compliance with diabetic treatment.


This case history is of a patient with a high anion gap metabolic acidosis. The overview of causes in the table below is what a clinician should have a mental picture of as she/he approaches the differential diagnosis of a high anion gap acidosis.

Diabetic ketoacidosis is the commonest severe acid-base disorder that presents to hospital so you should be particularly familiar with this diagnosis.

Overview of Classification of Causes of a Metabolic Acidosis

Principle: Metabolic Acidosis is classified into 2 major groups based on whether the Anion Gap is normal or elevated (see Section 5.2.2)

First Group: High anion gap metabolic acidosis (HAGMA)

- Ketoacidosis

- Lactic acidosis

- Acidosis of renal failure

- Acidosis due to toxins

Second Group: Normal anion gap (or hyperchloraemic) metabolic acidosis (NAGMA)

- Renal causes of loss of HCO3 (eg renal tubular acidosis)

- GIT causes of loss of HCO3

- Other causes

General Approach

The approach will be to follow the following steps:

A high anion gap alerts to the presence of an underlying HAGMA.

This is particularly useful in patients with the combination of a HAGMA & a metabolic alkalosis

So the diagnosis so far is that a HAGMA is present. Now determine the cause among the following 4 groups:


In this case, the patient recovered with management but compliance with diabetic therapy continued to be poor. An intrauterine foetal death occurred four months after this admission.

This patient had had several previous admissions with diabetic ketoacidosis. Results on presentation five months prior to the admission discussed in the example were:

Arterial Blood Gases

pH 6.93

pCO2 10 mmHg

pO2 138 mmHg

HCO3 2 mmol/l

Other biochemistry: Na 140, K 4.3, Cl 111, glucose 24.8, urea 4.6 mmol/l.

What is your analysis in this case? Try your hand at the following questions:

Question 1: The delta ratio here is about 0.68 - What does this indicate in this case?

Question 2: Is respiratory compensation appropriate or is there a mixed disorder present?