RENAL - Case of the Week - Diabetes Insipidus

Question 1

Where is ADH synthesised and what happens to it following synthesis?

Answer 1

• Magnocellular neurons in SON and PCN of hypothalamus
• Transported down axons of neurons to posterior pituitary gland and stored in vesicles

Question 2

What can trigger ADH release?

Answer 2

• Increased plasma osmolality - detected by hypothalamus osmoreceptors
• Decreased blood volume or pressure - detected by baroreceptors
• Stress, pain and certain medications

Question 3

What is the target organs and receptors for ADH?

Answer 3

• Kidneys - specifically DCT and collecting ducts
• Binds to V2 receptors on basolateral membrane of cells in collecting duct

Question 4

Describe the exact mechanism of action of ADH.

Answer 4

• Activates GPCR pathway - increase in cAMP levels within cells
• Triggers insertion of aquaporin-2 water channels into apical membrane of collecting duct cells

Question 5

What are the direct effects of aquaporin insertion?

Answer 5

• Collecting ducts become more permeable to water
• Increased reabsorption of water back into bloodstream
• Urine becomes concentrated and reduced water loss

Question 6

What are the wider effects of ADH on the body?

Answer 6

• Maintains fluid balance and prevents dehydration - regulation of plasma osmolality
• Vasoconstrictive properties - blood pressure raised via arteriole constriction

Question 7

Describe how ADH is regulated.

Answer 7

• Negative feedback - osmoreceptors reduce stimulation of ADH release once plasma osmolality returns to normal
• Alcohol consumption can inhibit ADH release - increased urine output and potential dehydration

Question 8

Name two areas that when damaged can lead to diabetes insipidus.

Answer 8

• Hypothalamus
• Posterior pituitary

Question 9

IN FLUID DEPRIVATION TESTS

What might suggest neurogenic diabetes insipidus and why?

Answer 9

• Low urine osmolality that normalises following desmopressin administration
• Caused by lack of ADH production - osmolality normalised since desmopressin is synthetic ADH

Question 10

IN FLUID DEPRIVATION TESTS

What might suggest nephrogenic diabetes insipidus and why?

Answer 10

• Urine osmolality remains low regardless of desmopressin
• Kidneys won’t respond to synthetic or endogenous ADH

Question 11

IN FLUID DEPRIVATION TESTS

What might suggest primary polydypsia and why?

Answer 11

• Urine osmolality remains high after both fluid deprivation and desmopressin administration
• Vasopressin axis is intact

Question 12

In fluid deprivation tests, what happens if you get partial diabetes insipidus or polydypsia?

Answer 12

Cannot make a clear diagnosis
- Further investigations needed

Question 13

IN FLUID DEPRIVATION TESTS

What might suggest central diabetes insipidus and why?

Answer 13

• Patient lacks ADH.
• Kidneys are still capable of responding to ADH.
• Initially, the urine osmolality remains low as it continues to be diluted by the excessive water lost in the urine.
• After desmopressin is given, the kidneys respond by reabsorbing water and concentrating the urine. The urine osmolality will be high.

Question 14

SEE DISEASES TABLE FOR MORE INFO ABOUT DIABETES INSIPIDUS

Answer 14

SEE DISEASES TABLE FOR MORE INFO ABOUT DIABETES INSIPIDUS

Question 15

What would happen if a normal person with functional ADH did the water deprivation test?

Answer 15

Raised plasma osmolality - stimulates ADH secretion and therefore urine becomes concentrated so its osmolality is raised

Question 16

What is a risk that comes with using desmopressin?

Answer 16

Water retention leading to hyponatremia
- Synthetic ADH not as suppressible as ADH upon falls in plasma osmolality

Question 17

How might thiazide diuretics help in diabetes insipidus?

Answer 17

Initial diuresis it causes prompts a hypovolaemia that results in increased sodium and water reabsorption