Hyperosmolar Hyperglycaemic State (HHS) Pathophysiology Explained

Kia ora team, This video provides a clear, step-by-step breakdown of the pathophysiology of Hyperosmolar Hyperglycemic State (HHS), a serious complication of Type 2 diabetes mellitus. We walk through how insulin resistance and relative insulin deficiency—often triggered by stressors like infection or myocardial infarction—lead to severe hyperglycaemia, osmotic diuresis, and profound dehydration. You’ll also learn why, unlike diabetic ketoacidosis (DKA), patients with HHS do not develop significant ketosis or metabolic acidosis, and how preserved insulin activity allows the Krebs cycle to continue functioning. Key concepts covered: Relative insulin deficiency in Type 2 diabetes Role of stress hormones in hyperglycaemia Gluconeogenesis and glycogenolysis Osmotic diuresis and severe dehydration Hyperosmolar state and neurological symptoms Why ketosis and acidosis do NOT occur in HHS Happy studying team. Hyperosmolar Hyperglycemic State (HHS) -A patient with Type 2 diabetes mellitus has insulin resistance and/or reduced insulin production -They experience a triggering event (eg. infection, MI, illness) -This increases stress hormones (glucagon, cortisol, epinephrine) -Which increases insulin demand -There is a relative insulin deficiency due to insulin resistance and/or impaired insulin secretion -Some insulin is present, but not enough to control blood glucose -Some insulin allows limited glucose uptake into cells -Cells are not completely starved of energy (unlike DKA) -However, excess glucose remains in the blood → severe hyperglycaemia -Gluconeogenesis is stimulated because there is a relative insulin deficiency -So glucose uptake into cells is reduced -The cells perceive a state of relative starvation -(even though blood glucose is high) -This triggers the release of counter-regulatory hormones (glucagon, cortisol, epinephrine) -Which stimulate the liver to increase gluconeogenesis -Glycogenolysis also occurs -This further increases blood glucose levels -When blood glucose is very high, glucose spills into urine (glucosuria) -This causes osmotic diuresis -Which leads to large fluid loss (polyuria) -This results in severe dehydration -And increased serum osmolarity (hyperosmolar state) -Water shifts out of cells (including brain cells) -Leading to neurological symptoms (confusion, seizures, coma) -Some insulin is still present -Therefore lipolysis is reduced (but not completely absent) -Insulin inhibits the breakdown of fat -So there is no significant ketone production -Fat requires carbohydrate for complete metabolism -(“fat burns in a carbohydrate flame”) -Since some glucose can still enter cells, -there is enough carbohydrate available to generate pyruvate -Pyruvate is converted to oxaloacetate -Which allows the Krebs cycle to function normally -This means acetyl-CoA from fat metabolism can enter the Krebs cycle -instead of being converted into ketones -Therefore ketone production is prevented -And no metabolic acidosis occurs (unlike DKA)