5 - Osmolarity Control And Calcium And Kidney Stones

Question 1

What are disorders of water balance usually caused by?

Answer 1

Changes in plasma osmolarity, leading to an imbalance of electrolytes e.g. changes to [Na+].
N.B. Changes to [Na+] will change volume, not osmolarity.

Question 2

If water intake > water excretion how will plasma osmolarity be affected?

Answer 2

More water in the body = decrease in plasma osmolarity.

Question 3

If water intake < water excretion how will plasma osmolarity be affected?

Answer 3

Less water in the body = increase in plasma osmolarity.

Question 4

How does osmolarity differ from osmolality?

Answer 4

Osmolarity: Concentration of a solution - number of osmoles dissolved in a litre.
Osmolality: Concentration of a solution - number of osmoles dissolved in a kg of solution.

Question 5

What is a normal range for urine output?

Answer 5

1 - 1.5L a day.

Question 6

What is normal urinary osmolarity? What is it dependent on?

Answer 6

~500 - 700mOsm/L. It is dependent on the volume of osmoles we ingest in a day (600-1000mOsm/day) and therefore can range from 50-1200mOsm/L.
N.B. 1000mOsm/L could be excreted through the kidneys in 10L of 100mOsm/L or 1L of 1000mOsm/L.

Question 7

What is plasma osmolarity regulated by?

Answer 7

ADH and thirst.

Question 8

How is plasma osmolarity regulated by ADH?

Answer 8

Hypothalmic osmoreceptors sense changes in plasma osmolarity. ADH released - reducing renal water excretion - decreasing osmolarity.

Question 9

What are osmoreceptors? What are their functions?

Answer 9

Fenestrated leaky endothelium in contact with systemic circulation - sense changes in plasma osmolarity. They are located in the hypothalamus (OVLT).

Question 10

What is ADH? Where is it released from?

Answer 10

Peptide hormone (small - 9 AAs long). It is also known as arginine vasopressin (AVP). ADH induces aquaporin channels in late DCT and CD, increasing reabsorption of water. It is secreted from the posterior pituitary gland.

Question 11

Changes in plasma osmolarity will affect the secretion of ADH. What is the relationship?

Answer 11

ADH release will increase (~1%) in response to an increase in osmolarity. Decreased osmolarity inhibits ADH secretion.

Question 12

How does the body prevent ‘excessive corrections of osmolarity’ through ADH secretion?

Answer 12

Negative feedback.
Osmoreceptors sense increased osmolarity, this increases ADH secretion. Increased ADH will decrease osmolarity - inhibiting osmoreceptors.

Question 13

How is plasma osmolarity regulated by thirst?

Answer 13

Hypothalmic osmoreceptors sense changes in plasma osmolarity. Thirst centres become activated (it water intake < water excretion), the brain will mediate action through drinking behaviour - increasing water intake - decreasing osmolarity.

Question 14

What stimulates thirst? How sensitive are these mechanisms?

Answer 14

Increase in plasma osmolarity or decreases in ECF (significant but <10% changes).
Salt ingestion is an analogue to thirst.

Question 15

How will low ADH stimulation affect [H2O]?

Answer 15

Reduced aquaporin in the late DCT and CD - limited water reabsorption in both. Tubular fluid (rich in water) passes through the hyperosmotic renal pyramid (with no change in water content). Therefore [H2O] will be high and urine will be hypo-osmotic (dilute).

Question 16

How does ADH affect Aquaporin channels?

Answer 16

In the late DCT and CD, apical membranes do not have Aquaporin channels in the absence of ADH. Release of ADH allows Aquaporin 2 channels to be inserted into the apical membrane - making the cell water permeable (the basolateral membrane always has Aquaporin 3 and 4 channels).

Question 17

How are the Aquaporin 2 channels inserted into the apical membrane of late DCT and CD cells?

Answer 17

The basolateral membrane has adenylate cyclase present on it. ATP –> cAMP. This activates PKA which inserts the Aquaporin 2 channel into the apical membrane.

Question 18

How are Aquaporin 2 channels removed from the apical membrane?

Answer 18

They are retrieved by endocytosis.

Question 19

In full - how does the presence of ADH affect the nephron?

Answer 19

Glomerular capillaries: vasoconstriction (decreasing effective filtering surface area)
LOH - thick ascending limb: increases Na+, K+ and Cl- reabsorption.
Late DCT & CD: increases water reabsorption (Aquaporin 2)

Cortical CD: K+ secretion
Medullary CD: Urea reabsorption

Question 20

Do changes in blood volume and pressure effect the response to changes in osmolarity (i.e. secretion of ADH)?

Answer 20

Yes. A fall in ECV/BP will shift the set point (more ADH will be secreted at a certain osmolarity) in order to lower osmolarity values. In contrast an increase in ECV/BP will shift the set point (less ADH will be secreted at a certain osmolarity) - increasing osmolarity values - volume is more important than osmolarity.

Question 21

In circulatory collapse how will the response to changes in osmolarity change? How will this affect body fluids?

Answer 21

Massive fall in ECV/BP - shift set point to lower osmolarity values - more ADH is secreted, reducing water excretion. Will conserve H2O but will reduce osmolarity of body fluids.

Question 22

How does diabetes insipidus arise?

Answer 22

Posterior pituitary gland not producing sufficient ADH.

Acquired insensitivity of the kidney to the nephron.

Question 23

What is one of the main symptoms of diabetes insipidus? How can it be treated?

Answer 23

Polyuria. It can be managed with ADH injections or nasal sprays.

Question 24

Is there a condition that causes excess ADH secretion?

Answer 24

Syndrome of Inappropriate ADH secretion (SIADH).

Question 25

How does SIADH cause excess ADH secretion? Why might it cause clinical problems?

Answer 25

Excessive release of ADH from the posterior pituitary gland. Dilutional hyponatraemia due to increases in ECV can cause problems.