Urine Concentration and Dilution

Question 1

What is the normal osmolality of tissues?

Answer 1

285mOsm/kg

Question 2

What is the maximum osmolality of the renal medulla?

Answer 2

1400mOsm/kg

Question 3

What is a normal GFR?

Answer 3

125ml/min

Question 4

What is the primary determinant of urine osmolality and flow?

Answer 4

ADH

Question 5

Where is ADH synthesised?
Where is it released?
Where does it act?

Answer 5

• synthesised in the hypothalamus
• released from the terminals of the hypothalamic neurones found within the posterior pituitary
• acts in the distal tubule and collecting to increase water permeability by increasing AQP2

Question 6

Describe the short term and long term cellular pathways relegating AQP2 on the apical membrane/

Answer 6

Bind of ADH to V2 receptor (Gs)
Adenylyl cyclase: ATP --> cAMP
Short term
- PKA
- instertion of vesicles contains AQP2
Long term
- nucleus, +ve transcription, AQP2 synthesis

Question 7

Describe the osmolality of the tubules and resulting urine when ADH is not present.

Answer 7

The distal tubule and collecting duct are impermeable to water as no AQP2
Osmolality of urine does not equilibrate with that of cortc
Urine is very dilute

Question 8

Describe the osmolality of the tubules and resulting urine when ADH is present.

Answer 8

Maximum water resporption through AQP2
Loop of Henle osmolality = 1400mOsm/kg
Urine equilibrates with extracellular space
Concentrated urine

Question 9

How is urea involved in the concentration of urine? When might this change?

Answer 9

• Urea has a role in maintaining osmolality in the renal medulla
• In the presence of selective protein starvation, urea production is low, and so the kindness has a lower capacity to concentrate urne. Starvation makes dehydration worse!
• the urea transporter UT-A1 is also regulated by ADH, in a similar way as for AQP2

Question 10

How do cells survive in the renal medulla?

Answer 10

One key adaptation is the accumulation of a range of organic osmolytes within the cells. These include sorbitol, inositol, glycerophosphorylcholine and betaine

Question 11

What is diabetes insipidus?

Answer 11

Loss of ADH secretion or loss in sensitivity to ADH, often because of a problem with the V2 receptors (nephrohenic diabetes insidious)
This mean that they are unable to produce concentrated urine, leading to polyuria, dehydration and hypovolaemia. This then causes polydipsia
If fluid intake it adequate, they become hypernatraemic

Question 12

Central diabetes insipidus:

• causes
• managemente

Answer 12

Causes
- head injury, tumours, infection at base of brain
Management
- give ADH analogue e.g. desmopressin (longer half life than ADH)
- paradoxical use of thiazide diuretics
- treat cause

Question 13

Nephrogenic Diabetes Insipidus

• Causes
• Treatment

Answer 13

Causes
- toxicity (e.g. lithium)
- hypercalcaemia
- genetic, due to mutation in either V2 or AQP2
Treatment
NOT with desmopressin (insensitive)
Thiazide diuretic
Low salt diet (protect against hypernatraemia)

Question 14

What is SIADH?
Symptoms
Treatments

Answer 14

Sundromes in inappropriate ADH
Symptoms are related to inappropriately high ADH, commonly caused by brain injury (other rarer causes)
Produce concentrated urine
Treatments
- fluid restriction
- give urea (increase plasma osmolality, urea acts as osmotic diuretic)

Question 15

What is an emerging therapy?

Answer 15

new class of V2 receptor antagonists (vaptans) to treat chronic hypernatraemia