Outline the physiological consequences of hyperosmolar diabetic

ketoacidosis

HYPEROSMOLAR: plasma osmolality > 295mosmol/kgH20

Diabetic ketoacidosis arises from an absolute insulin deficiency such that cellular
glucose uptake is limited and hepatic ketogenesis is unsuppressed. It leads to
- increased ketone bodies in the plasma (acetoacetate, acetone, beta-hydroxy
butyrate)
- Acidaemia (pH <7.35)
- Hyperosmolality (where osmolality = [glucose] +[urea] + 2[Na +]

There is a concomitant rise in stress hormones (glucagon, cortisol,

catecholamines) which further exacerbates ketogenesis

Net effect is a state of severely deranged metabolism with acidosis and

dehydration potentially leading to acute kidney injury
and systemic shock

Consequences:

HYPEROSMOLALITY
- sensed by paraventricular and supraoptic nuclei of the posterior
hypothalamus
o Stimulates ADH release from posterior pituitary
 ADH acts at V2 receptors in the cortical collecting ducts to
increase H2O reabsorption .
 ADH also increases urea reabsorption in attempt to maintain
medullary tonicity gradient
o Stimulates thirst

HYPERGLYCAEMIA (normal BSL 4-7mmol/L)

- arises secondary to decreased cellular uptake of glucose, and increased
gluconeogenesis (which is usually suppressed by insulin)
- leads to
o osmotic diuresis
 Glucose load overwhelms transport mechanism for tubular
reabsorption
 Increased osmolality of tubular fluid
 Loss of H2O > solutes
 Leads to dehydration and further hyperosmolality
 Washes away medullary interstitial gradient with
inability to concentrate urine and further dehydration

KETOACIDOSIS
- Metabolic consequences
 o Hyperkalaemia (H+ moves into cells in exchange for K+)
 Conduction abnormalities, arrhythmias
 Stimulates aldosterone release
- Hyperchloraemia (especially if N/S administered)
 Large amounts of ketones secreted in exchange for increased
chloride reabsorption/retention
o Increased free calcium
 Consequences of hypercalcaemia
 Hypertension, nausea and vomiting, anorexia,
polyuria/polydipsia
 Worsened dehydration and renal failure
- Respiratory consequences
o Increased MV secondary to stimulation of central chemoreceptors in
ventral medulla
 Increased WOB
 Hypocarbia
o R shift of OHDC (depending on degree of respiratory correction)
- CVS consequences
o Myocardial depression
o Vasodilatation (both direct effects of acidaemia)
o Along with hypovolaemia can lead to hypotension/shock
o SNS stimulation likely counteract this
- GIT consequences
o Nausea/vomiting
 Worsens dehydration and acid base disturbance

Nb Other acid-base disorders may be present, having arisen as a cause or

consequence of the DKA
- Lactic acidosis due to hypoperfusion and anaerobic metabolism
o This may mask detection of ketosis as beta hydroxybutyrate tends to
predominate (POC test looks for acetoacetate/acetone)
- Renal tubular acidosis