Urine Concentration and Dilution

Question 1

List the osmolalities of filtrate along the length of the nephron, and the approximate range of urine osmolality.

Answer 1

• Proximal tubule: 285 mOsm kg^-1.
• Descending limb: 285 mOsm kg^-1.
• Bottom of Loop of Henle: 1200 mOsm kg^-1.
• Ascending limb: 90 mOsm kg^-1.
• Cortical collecting duct: 90-285 mOsm kg^-1 (depends on water reabsorption).
• Medullary collecting duct: 60-1400 mOsm kg^-1.

Question 2

List the flow rates of filtrate along the length of the nephron.

Answer 2

• Proximal tubule: 125 ml min^-1.
• Descending limb: 45 ml min^-1.
• Ascending limb: 25 ml min^-1.
• Cortical collecting duct: 6 ml min^-1.
• Medullary collecting duct: 1.25 ml min^-1.

Question 3

Which molecule is the primary determinant of urine osmolality and flow?

Answer 3

ADH.

Question 4

Where is ADH synthesised and released?

Answer 4

• Synthesised in the hypothalamus.

- Released from the hypothalamic neurones in the posterior pituitary.

Question 5

What is the effect of ADH on the cellular level?

Answer 5

ADH increases expression of AQP2 on the apical membrane of epithelial cells of the collecting duct.

Question 6

Describe the cellular pathway of ADH.

Answer 6

1 - ADH binds to the V2 receptor on the basolateral surface of the epithelial cell.

2 - This stimulates the Gs pathway:

3 - Gs activates adenylyl cyclase, which converts ATP into cAMP.

4 - cAMP acts at the nucleus to increase AQP2 and UT-A1 synthesis.

5 - cAMP activates PKA, which leads to the insertion of AQP2 and UT-A1 vesicles into the apical membrane.

Question 7

List the effects of ADH on the osmolality of the filtrate along the length of the nephron.

Answer 7

• The osmolality at the bottom of the loop of Henle is increased.
• The osmolality at the collecting duct is increased.

Question 8

List the effects of ADH on the flow of the filtrate along the length of the nephron.

Answer 8

The flow at the collecting duct is decreased.

Question 9

Why does the kidney have a lower capacity to concentrate urine in the presence of protein starvation?

Answer 9

• Urea is a product of nitrogen (and therefore protein) metabolism, so will be low in the presence of protein starvation.
• Urea has a role in concentrating the osmolality in the renal medulla as it diffuses out of the collecting duct via UT-A1.

Question 10

How do cells of the renal medulla survive in the highly osmolar environment?

Answer 10

By accumulating a range of organic osmolytes within the cells such as:

1 - Sorbitol.

2 - Inositol.

3 - Glycerophosphorylcholine.

4 - Betaine.

Question 11

Define diabetes insipidus.

Answer 11

A condition where ADH action is decreased, meaning urine cannot be concentrated and water cannot be reabsorbed.

Question 12

What is the difference between central diabetes insipidus and nephrogenic diabetes insipidus?

Answer 12

• Central diabetes insipidus refers to a loss of ADH secretion.
• Nephrogenic diabetes insipidus refers to a decrease in ADH sensitivity (often due to a problem with the V2 receptors).

Question 13

List 6 signs and symptoms of diabetes insipidus.

Answer 13

1 - Polyuria.

2 - Dehydration.

3 - Hypovolaemia.

4 - Polydipsia.

5 - Low urine osmolality.

6 - Hypernatraemia.

Question 14

List 3 causes of central diabetes insipidus.

Answer 14

1 - Head injury.

2 - Tumours.

3 - Infection.

Question 15

How is central diabetes insipidus treated?

Answer 15

By administering desmopressin (an ADH analogue).

Question 16

List 3 causes of nephrogenic diabetes insipidus.

Answer 16

1 - Toxicity e.g. by lithium.

2 - Hypercalcaemia.

3 - Genetic, e.g. due to mutations in V2 or AQP2.

Question 17

List 2 ways to treat nephrogenic diabetes insipidus.

Answer 17

1 - Administer thiazide diuretics (paradoxical use but it works somehow).

2 - Low salt diet.

Question 18

Why might a low salt diet improve the symptoms of diabetes insipidus?

Answer 18

Because fewer salts in the filtrate will result in a lower volume of the filtrate, as less water will be retained.

Question 19

What is Syndrome in Inappropriate ADH (SIADH)?

Answer 19

Symptoms related to inappropriately high ADH, commonly caused by head injury.

Question 20

List 3 signs of SIADH.

Answer 20

1 - Hyponatraemia.

2 - High urine osmolality.

3 - Hypertension (due to hypervolaemia).

Question 21

List 2 treatments for SIADH.

Answer 21

1 - Fluid restriction.

2 - Give urea.

Question 22

What is an aquaretic?

Answer 22

A class of drug that is used to promote aquaresis: the excretion of water without electrolyte loss.

Question 23

Give an example of an aquaretic.

Describe the mechanism of action for this drug.

What is this drug used to treat?

Answer 23

• Tolvaptan.
• Acts on the late portion of the distal tubule and the collecting duct to block ADH action.
• Used to treat SIADH and, more broadly, chronic hyponatraemia.