Diabetes InsipidusAvorque, Maro L.Austria, JillianBaloro, Alexis Anne

Diabetes Insipidus

-a condition characterized by excessive thirst (polydipsia) and excretion of large amounts of severely diluted urine (polyuria)

-the biochemical mediator that is responsible for this disorder is the Antidiuretic hormone (ADH)/ Arginine Vasopressin

Antidiuretic Hormone (ADH)/ Arginine Vasopressin

-synthesized in the hypothalamus by the supraoptic and paraventricular nuclei-transported to the posterior pituitary gland where it is stored

Amino Acid Sequence of Vasopressin in contrast to Oxytocin

Physiological differences between the two similar hormones are due to the slight molecular structure variation.

Vasopressin Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2Oxytocin Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2.

Molecular effect on target organ

-the main effector of this organ is the kidneys -the V2 receptors are present on the collecting tubule. ADH will bind to the receptor, activating the

second messenger cAMP. cAMP will act on the aquaporins to attach to the apical membrane facilitating the movement of water through osmosis back to the portal circulation.

- Blood vessels ADH will bind to the V1 receptors. That will activate the GTP that will react to the phospholipase. That will result to the formation of IP3 and DAG. IP3 will bind to its receptor that will release Calcium. DAG will allow calcium influx because of the activation of calcium voltage gated channel, resulting to the increase calcium inside the cell that will bind to the actin and myosin that will cause vasoconstriction of blood vessels.

Signs and Symptoms of DI-Polyuria -High Plasma Osmolality-Polydipsia -Low Urine Osmolality

The hypothalamus can detect the need to secrete ADH when there is an increase on the plasma osmolarity that can be detected by the osmoreceptors located on the hypothalamus. On the other hand, the baroreceptors can detect if there is a decrease blood volume and arterial blood pressure which sends signal to the hypothalamus to release ADH.

Biochemical Defect

1. Central/Pituitary/Neurogenic DI-the most common type of DI-caused by lack of vasopressin-posterior pituitary can be destroyed by a variety of underlying disease including tumors, infections,

head injuries but, most of the cases of neurogenic DI are idiopathic

2. Nephrogenic DI-inability of the kidneys to respond to the “antidiuretic effect” of normal amounts of vasopressin-defective receptors for the Vasopressin-can be induced by drugs like Lithium

3. Gestagenic or Gestational DI-developed during pregnancy if the pituitary is slightly damaged and/or the placenta destroys the

hormone rapidly

4. Dipsogenic DI-ADH is suppressed by excessive intake of fluids-usually referred as primary polydipsia caused by an abnormality in the thirst mechanism of

hypothalamus

Diagnosis

Urine Analysis24 hour urine collection Urine Specific GravityUrine Osmolality

Water Deprivation Test- used to differentiate neurogenic DI and Nephrogenic DIAlso called “Miller-Moses”Duration: up to 7 h (until 12–14 h in primary polydipsia)

Monitoring: BW, plasma Na+, Posm, Uosm, plasma AVP Interruption if: - Loss of 3–5% of BW - Plasma Na+ >143 mEq/l

- Posm >295 mosm/kg H2O - inc Uosm to normal

Condition Urine Osmolality after water deprivation test

mOsm/kg

Urine Osmolality after Desmopressin/ Vasopressin

mOsm/kgCentral/ Neurogenic DI <300 >800

Nephrogenic DI <300 >300 (Non-Responsive)

Blood testsSerum electrolyte levels Plasma Osmolality ADH level in the blood

Pituitary studiesMRIMeasurement of circulating pituitary hormones

Management/Treatment

Neurogenic DI and Gestational DI-Desmopressin acetate (1-deamino-8-D-arginine vasopressin); a synthetic analogue of

AVP/ADH; V2 antagonist

-Desmopressin enhances water reabsorption by increasing permeability of renal collecting ducts to adenosine monophosphate and water, thereby reducing urinary output and increasing urine osmolality.

-Usually given intranasally but can be given orally or IM for comatose patientsDRUGS (Carbamazepine, Chlorpropamide,Clofibrate; pressor drugs;potentiation of desmopressin effects

Nephrogenic DI-there is still no cure for Nephrogenic DI therefore, management of symptoms is recommended

-Provision of adequate fluids-Low Sodium diet-Drugs: Hydrochlorothiazide and amiloride (inhibits sodium reabsorption in distal renal

tubules, resulting in increased excretion of water and of sodium, potassium, and hydrogen ions

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