Diabetes Insipidus

Question 1

What stimulates the release of arginine vasopressin (AVP)?

Answer 1

Increase in plasma osmolality
- osmoreceptors
- magnocellular neurons can be directly stimulated

Question 2

What decreases AVP release?

Answer 2

• baroreceptors in the atrium and pulmonary venous system (via vagus and glossopharyngeal nerves) –> a decrease in blood volume and
• natriuretic peptide (its release is also stimulated by AVP, negative feedback)

Question 3

What’s the MOA of water conservation of AVP?

Answer 3

relocation of aquaporin from basolateral to apical membrane (binds to V2 receptors)
- this leads to increased permeability to water (resorption) and the the collecting duct

Question 4

What else (other than water conservation) can happen when AVP binds to V2 receptors?

Answer 4

Release: von Willebrand factor, tissue plasminogen activator, atrial natriuretic peptide
- also stimulates synthesis of nitric oxide
- increase circulating concentration of coagulation factor VIII

Question 5

What does AVP binding to V1a receptor lead to?

Answer 5

vasoconstriction
glycogenolysis
platelet activation

Question 6

What does AVP binding to V1b receptor lead to?

Answer 6

In Pituitary: acts synergistically for CRH to stimulate release of ACTH
In other tissues: increase catecholamine and insulin
AVP is an important neurotransmitter and chemical mediator in the brain

Question 7

What’s the cause for central diabetes insipidus?

Answer 7

Complete or partial deficiency in AVP
Due to structural defects within the hypothalamus, posterior pituitary, or both
Dogs: mostly due to neoplasia
Cats: mostly due to trauma
In dogs that had hypophysectomy due to Cushings, CDI may prolong and some may need supplementation. This is not as common in cats with hypophysectomy.
Other causes: idiopathic, infection, inflammation, cyst, could be congenital (noted in one Afghan litter)

Question 8

What’s the cause of nephrogenic diabetes insipidus?

Answer 8

Primary nephrogenic diabetes insipidus = rare, was noted in a litter of male Huskies. Not reported in cats
Secondary nephrogenic diabetes insipidus: hyperadrenocorticism, hyponatremia, pyelonephritis, pyometra, hypercalcemia, liver disease

Question 9

What are some clinical features of diabetes insipidus?

Answer 9

PU/PD. Patient drinks a large quantity of water.
- nocturia, urinary overflow incontinence
- neurological abnormalities
- withholding water = dehydration, watch for salt toxicity
- may have concurrent endocrinopathies, such as hyperadrenocorticism, and hypothyroidism. Hypoadrenocorticism is less common
- low urea may be present due to renal medullary washout
- USG = hyposthenuria! Isosthenuria more with partial CDI
- need to rule out UTI

Question 10

How is diabetes insipidus diagnosed?

Answer 10

1. Water deprivation test
   - 3 phases
   - Phase 1: gradual decrease in water intake
   - Phase 2: withhold water. Ends when patient loses 3-5% of bodyweight or USG >1.025. If USG > 1.025 = primary polydipsia
   - Phase 3: Give desmopressin. If USG >1.015 then it’s a central DI. No response = nephrogenic DI
2. Desmopressin Test
   - if it works, then it’s CDI. PP or NDI will not work
3. Hypertonic saline infusion
   - a decrease in AVP = CDI; normal or exaggerated AVP response w/out concurrent change in USG = NDI; normal AVP response w/ appropriate change in USG = PP.

Question 11

What’s the treatment for diabetes insipidus?

Answer 11

1. DDAVP (Desmporessin) - works for CDI
   - potent V2 receptor agonist, but doesn’t cause hyponatremia or excessive volume expansion
2. Thiazide diuretics for NDI

Question 12

What’s the prognosis for diabetes insipidus?

Answer 12

Depends on the underlying cause for the CID - neoplastic: not so good; trauma or idiopathic: can be well managed for many years