Pathophysiology
Clinical meaning
Hyperosmolar hyperglycemic state (HHS) is a life-threatening hyperglycemic emergency characterized by severe hyperglycemia (glucose >600 mg/dL, often >1000), profound dehydration (average 8-12 L fluid deficit), hyperosmolarity (serum osmolality >320 mOsm/kg), and altered mental status โ WITHOUT significant ketoacidosis (pH >7.3, bicarbonate >18, absent or mild ketonemia). HHS occurs primarily in type 2 diabetes where residual insulin secretion is sufficient to prevent lipolysis and ketogenesis but insufficient to control hepatic gluconeogenesis and peripheral glucose uptake. The pathogenesis involves a precipitating stressor (infection is the #1 trigger โ pneumonia, UTI, sepsis; also MI, stroke, medications such as corticosteroids and thiazides) causing counter-regulatory hormone release (glucagon, cortisol, catecholamines, growth hormone) that drives hepatic glucose output. Profound hyperglycemia creates an osmotic gradient that pulls water from cells into the extracellular space, causing severe intracellular dehydration and then overwhelming renal glucose reabsorption capacity, producing massive osmotic diuresis with electrolyte losses. The free water loss exceeds sodium loss, creating hyperosmolarity. Neurological dysfunction (confusion, lethargy, seizures, coma) directly correlates with the degree of hyperosmolarity rather than glucose level. Key distinguishing features from DKA: HHS has MORE severe...