Diabetes Insipidus.

Valmiki K. Seecheran | Year V MBBS StudentUniversity of the West Indies, Cave Hill Campus.Dr. Krishnamurthy |PICU | Senior Pediatric Clerkship.

April 24th 2014.

History.

• ‘Diabainein’(Greek) which means, go through/ siphon. – 16th century the word precipitated into ‘Diabetes’.

• ‘Insipidus’ comes from the French word ‘insipide’ which thereby means tasteless. – This is because D.I has no glycosuria ( excretion of

glucose into urine).

Objectives.

• To understand signs and symptoms.• To understand the work-up investigations.• To understand the pathophysiology.• To understand the various types of D.I.• To understand management and treatment.

Introduction | DI.

• Characterized by:– Excessive thirst.– Excretion of large amounts of severely diluted urine.– Reduction of fluid intake has no effect on the concentration

of urine.

• Various types of DI:– Most common type is Central DI.

• Deficiency of Arginine Vasopressin (ADH).

– 2nd type is Nephrogenic DI.• Kidneys insensitive to ADH.

Signs & Symptoms.

• Excessive urination and thirst.• Interferes with appetite, eating, weight gain

and growth.• Dehydration and hypokalaemia.

Work up.

• 24 hour urine collection.• Serum electrolytes and glucose.• Plasma and Urine Osmolality.• Plasma ADH levels.• Anticipatory results– Hypernatremia .– Urinalysis shows dilute urine with low specific

gravity.– Urine osmolarity levels are low.

Work up.

• Fluid deprivation test. (Miller-Moses test)– Excessive intake of fluid (primary polydipsia).

• Urine osmolality should increase and stabilize at above 280 Osm/kg with fluid restriction, while a stabilization at a lower level indicates DI.

– Defect in ADH production.• Desmopressin stimulation. Patient consumes water only when thirsty,

this can lead to sudden fluid accumulation. • If the Desmopressin reduces urine output and increases urine

osmolarity, ADH production was deficient.• MRI + testing of other hormones of pituitary.

– Defect in kidney’s response to ADH.• Renal pathology.

Physiology.

• Hypothalamus. – regulation of urine production. Also produces

ADH in supra-optic and para-ventricular nuclei. – In addition, sensation of thirst is regulated in the

ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex.

• ADH is transported to posterior lobe of pituitary gland.

Physiology.

• ADH increases water permeability in collecting ducts and distal convoluted tubules.

• Aquaporin (2)• ADH binds to G-protein coupled receptors increasing cyclic

AMP and couples with protein kinase A stimulating translocation of aquaporin in distal convoluted tubules and distal tubules.

• The transcribed channels allow water into collecting duct cells.

• Increase in permeability for reabsorption increases concentration of urine.

Pathophysiology.

• Neurogenic/central DI. – Lack of vasopressin production in brain.– Vasopressin acts to increase intravascular volume and

decrease urine output.– Low ADH causes increase urine production and volume

depletion. • 25% of cases are idiopathic.• 20% of cases are benign suprasellar tumours. • 17% of cases are due to trauma.• 10% of cases are due to neurosurgery.

Pathophysiology.• Nephrogenic .

– Lack of Aquaporin channels in the distal collecting duct (decreased surface expression and transcription).

– As a result, kidney is insensitive to vasopressin.• Major causes

– Hereditary.• AVPR2 – malfunction of vasopressin receptor.• AQP2 – malfunction of aquaporin.

– Osmotic.• Hypokalaemia.• Renal cystic disease.

– Acquired.• Lithium toxicity.• Hypercalcemia.

Classification.

• Neurogenic.• Nephrogenic.• Dipsogenic*– Defect in thirst mechanism. Results in increased

fluid intake that suppresses vasopressin secretion and increases urine output.

• Gestational*– Women produce vasopressinase in the placenta

which breaks down ADH.

Treatment.• Nephrogenic.

– Treat underlying medical aetiology and replace free water deficit.– Hydrochlorothiazide – create mild hypervolemia to encourage salt and

water uptake in proximal tubule. Combined with amiloride to prevent hypokalaemia.

– Thiazide diuretic will decrease DCT reabsorption of sodium and water. Subsequently decreases plasma volume and thus lowers GFR and hence augments absorption of sodium and water in proximal nephron. Less fluid reaches the distal nephron so overall fluid conservation is obtained.

• Central DI.– Desmopressin.

• Intranasal.• Oral tablets.

Thank you.