Regulation of urine concentration

Question 1

How much primary urine is produced per minute and per day under normal conditions?

Answer 1

1.25ml.min = 1.8L/day

Question 2

What happens to the flow rate in the nephron?

Answer 2

Flow rate decreases along the nephron as water is reabsorbed.

Question 3

What hormone regulates urine osmolality and flow?

Answer 3

ADH

Question 4

What is another function of ADH?

Answer 4

Increases BP by acting on vessels.

Question 5

Where is ADH synthesised?

Answer 5

Synthesised in the hypothalamus but released from the terminals of hypothalamic neurons in the posterior pituitary/neuropophysis and then released into the circulation.

Question 6

Where does ADH act and what does it cause?

Answer 6

Acts on distal tubule and MCD to increase permeability of H2O by increasing AQP2 insertion on to the apical membrane. ADH stimulates thirst.

Question 7

How does ADH produce its affect? What happens in the short and long term?

Answer 7

ADH is detected by V2 receptors on the basolateral membrane. V2 is a GPCR that activates PKA pathway.
In the short term PKA phosphorylates proteins involved in AQP2 insertion. It uses premade AQP2 for fast changes in absorption.
In the long term cAMP leads to the transcription and synthesis of AQP2 which is packaged into vesicles for storage.

Question 8

What results from no ADH?

Answer 8

Dilute and high urine output as the duct remains less permeable.
Flow rate will be UNCHANGED as less reabsorption.

Question 9

What results from maximum ADH?

Answer 9

Distal tubule equilibrates with the cortex and MCD equilibrates with the medulla to produce concentrated urine, due to the high osmotic gradient of the medulla. Urea permeability increases resulting in a low and concentrated urine output.

Question 10

Why is the kidney’s capacity to concentrate urine reduced in a patient with selective protein starvation?

Answer 10

Urea is formed from N2 after protein degradation in order to remove N2 from the body. Less proteins = Less N2 = Less urea.

Question 11

Out of Aldosterone and ADH which directly increases blood volume?

Answer 11

ADH DIRECTLY increases blood volume by increasing water permeability.
Aldosterone indirectly increases volume by increasing Na permeability through ENAC.

Question 12

How does ADH affect urea?

Answer 12

ADH results in the insertion of UT-A1 channels when detected by V2.

Question 13

What is the movement of urea?

Answer 13

Moves across the apical membrane via UT-A1 and into the interstitium within the MCD.

Question 14

How are medullary cells adapted for survival in the highly osmotic environment?

Answer 14

The accumulation of organic osmolytes prevents a gradient forming across the cell and interstitium to prevent the intracellular fluid being absorbed.

Question 15

Give an example of an organic osmolyte.

Answer 15

Sorbitol, inositol, betaine, glycerophosphorylcholine

Question 16

What occurs along side protein malnutrition?

Answer 16

Dehydration as the urine remains dilute in malnutrition due to the lack of urea.

Question 17

What is Diabetes Insipidus?

Answer 17

The inability to concentrate urine leading to polyuria of low omsmolality, dehydration, polydipsia, hypovolaemia.

Question 18

What will results from insufficient fluid intake in a pt with diabetes insipidus?

Answer 18

HYPERnatraemia

Question 19

What are the two types of diabetes insipidus?

Answer 19

Central - Loss of ADH secretion

Nephrogenic - Loss of ADH sensitivity in V2 receptors

Question 20

What causes central DI?

Answer 20

Head injury, tumour, brain infection

Question 21

How can central DI be treated?

Answer 21

Desmopression - ADH analogue with a long half life to increase AQP2 and urea channel insertion for reabsorption.
Can use thiazide diuretic - produce the opposite effect to normal by preventing hypernatraemia and encourages PCT absorption and increases AQP2 expression.

Question 22

What causes nephrogenic DI?

Answer 22

Loss of receptor sensitivity due to toxicity in the kidneys, hypercalaemia or genetic mutation in V2 or AQP2.

Question 23

How can nephrogenic DI be treated?

Answer 23

Thiazide diuretic and low salt diet.

Cannot use ADH analogue as the receptors are damaged.

Question 24

What is SIADH?

Answer 24

Syndromes in inappropriate ADH release resulting in excess ADH

Question 25

What is the cause of SIADH?

Answer 25

Head injury

Question 26

How does a pt with SIADH present?

Answer 26

Concentrated and low volume urine with HYPOnatraemia due to the excess water retention diluting the body fluid.

Question 27

How can SIADH be treated?

Answer 27

Fluid restriction despite the stimulation of thirst
Take urea to aid the concentration mechanism - prevents as much water from being absorbed as urea will not move into the interstitium if in excess, increasing osmolality in MCD.
V2 Receptor antagonist in chronic hyponatraemia to block UT-A1 insertion so that more urea stays in the filtrate and blocks AQP2 insertion to reduce reabsorption.