Can arterial pH be low in a patient with Hyperosmolar Hyperglycemic State (HHS) when ketones are absent?

Can pH Be Low in HHS When Ketones Are Absent?

Yes, arterial pH can be low in HHS even when ketones are absent, though the diagnostic criteria specify pH >7.30 as typical for HHS. 1

Understanding the pH Threshold in HHS

The American Diabetes Association's diagnostic criteria clearly establish that HHS is characterized by:

• Arterial pH >7.30 (not <7.30 as in DKA) 1
• Serum bicarbonate ≥15 mEq/L 1
• Small or minimal ketones (not absent, but minimal) 1
• Effective serum osmolality ≥320 mOsm/kg 1

The Joint British Diabetes Societies similarly defines HHS with pH >7.3 and bicarbonate ≥15 mmol/L, with ketonaemia ≤3.0 mmol/L (not necessarily absent). 2

When pH Can Be Lower in HHS

While HHS by definition has pH >7.30, several clinical scenarios can cause a lower pH even with minimal ketones:

Lactic Acidosis Superimposed on HHS

• Severe dehydration and hypoperfusion in HHS can lead to concurrent lactic acidosis, lowering pH independent of ketone production 1
• The profound volume depletion (100-220 ml/kg fluid losses) creates conditions for tissue hypoperfusion 2

Mixed DKA/HHS Presentations

• Increasingly recognized overlap syndromes occur where patients have features of both conditions 2
• These patients may have pH <7.30 with variable ketone levels 2

Other Causes of Metabolic Acidosis

• Uremia from acute kidney injury (common in HHS due to severe dehydration) 1
• Concurrent sepsis or other acute illness (infection is the most common precipitant) 3, 2

Critical Diagnostic Pitfall

The anion gap is "variable" in HHS, not consistently elevated like in DKA (>10-12 mEq/L). 1, 4 If you see:

• pH <7.30
• Minimal/absent ketones
• Elevated anion gap >12 mEq/L

You must consider alternative causes of high anion gap metabolic acidosis beyond simple HHS, including lactic acidosis, uremia, or a mixed DKA/HHS picture. 1, 4

Practical Clinical Approach

When encountering hyperglycemia with low pH but minimal ketones:

1. Calculate effective osmolality: 2[Na] + glucose/18 1, 2

   • If ≥320 mOsm/kg, consider HHS with superimposed acidosis 1, 2

2. Measure lactate to identify lactic acidosis as contributor to low pH 1

3. Check renal function (BUN/creatinine) for uremic contribution 1, 2

4. Assess for sepsis/infection as the precipitant (most common trigger) 3, 2

5. Consider mixed DKA/HHS if ketones are present but not profoundly elevated 2

The key distinction: Pure HHS should not have pH <7.30 by definition, so a lower pH with minimal ketones mandates investigation for concurrent pathology causing the additional acidosis. 1, 2