Control of Plasma Osmolarity

Question 1

What is the osmolality of body fluids in comparison to intracellular osmolality and which is the exception?

Answer 1

Most bodily fluids are isotonic to cells Osmolality. The exception is urine. If water intake is less than water excretion then osmolality will increase and vice versa this is because we change the amount of water we excrete but not the number of osmoles of solute.

Question 2

Where are osmoreceptors found?

Answer 2

Osmoreceptors are found in the hypothalamus, in the organum vasculosum of the lamina terminalis (OVLT). OVLT is anterior and ventral to the third ventricle.

Question 3

How do osmoreceptors detect changes in osmolality?

Answer 3

Fenestrated leaky endothelium are exposed directly to systemic circulation on the plasma side of BBB. It senses changes in plasma osmolarity and signals secondary responses which are mediated via two pathways leading to concentration of urine and the feeling of thirst.

Question 4

Where are cells of the supraoptic nucelus found?

Answer 4

Cells of the supraoptic nucleus lie close to the OVLT with input from baroreceptors.

Question 5

How does the hypothalamus respond to high osmolality?

Answer 5

Under conditions of predominant loss of water osmoreceptors in the hypothalamus increase release of ADH from posterior pituitary. ADH then inhibits excretion of water in the kidneys. Low Osmolarity inhibits ADH secretion this creates a negative feedback loop.

Question 6

What happens when the blood volume or pressure changes?

Answer 6

When the blood volume or pressure changes there is a change in the set point for ADH so that the Osmolarity may change. This is to prevent circulatory collapse because volume is more important than Osmolarity.

Question 7

When does thirst behavior occur, what else does it stimulate and when does it stop?

Answer 7

This occurs when there are large deficits in water (or salt) that is only partially compensated for by ADH in the kidneys. It is stimulated by an increase in fluid Osmolarity but also by reduced ECF volume. Salt ingestion acts like thirst in that it prevents water loss. Thirst stops when sufficient fluid has been consumed but before GI tract has absorbed as this would take too long and we’d potentially overshoot. Salt intake is stimulated by a natural appetite for it.

Question 8

Describe ADH and how it works

Answer 8

Produced by neurosecretory cells in the hypothalamus but secreted form the posterior pituitary gland. Peptide that is 9 amino acids long and is also known as Arginine Vasopressin, Vasopressin and Argipressin.

ADH increases the permeability of the collecting duct to water and urea. Low plasma ADH = diuresis and high plasma ADH = anti-diuresis.

Question 9

What is central diabetes insipidus?

Answer 9

This is when plasma ADH levels are too low. This occurs due to damage to the brain, tumour, sarcoidosis or tuberculosis, aneurysms, some forms of encephalitis or meningitis and rare disease of langerhans cell histiocytosis.

Question 10

What is nephrogenic diabetes insipidus?

Answer 10

Is from an acquired insensitivity of the kidneys to ADH.

In both these cases water is inadequately reabsorbed from the collecting duct so a large volume of urine is produced. Managed clinically by ADH injections or nasal sprays.

Question 11

What is SIADH?

Answer 11

Syndrome of inappropriate antidiuretic hormone secretion. Characterised by excessive release of ADH form the PP gland or another source. This results in large retention of water and so a dilution of all the solutes. Specifically, this causes hyponatremia.

Question 12

What symptoms are there of hyponatraemia?

Answer 12

Symptoms of hyponatremia include nausea and vomiting, headache, confusion, lethargy, fatigue, appetite loss, restlessness and irritability, muscle weakness, spasms, cramps, seizures and decreased consciousness or coma.

Question 13

What are aquaporin channels?

Answer 13

Many different types found all over the body it is effectively a hole in the membrane that only allows water through.

Question 14

Where are the different aquaporin channels found?

Answer 14

AQP1 is found on both the apical and basolateral membrane of the PCT and descending limb of the loop of Henle. AQP2, AQP3 and AQP4 are all found in the latter DCT and collecting duct with AQP3 and AQP4 on the basolateral side and AQP2 on the apical side.

Question 15

How does low ADH effect aquaporin channels?

Answer 15

No ADH stimulation means no AQP2 on apical membrane of the latter DCT and collecting ducts. Ths limits water reuptake in the latter DCT and in the collecting duct. Tubal fluid rich in water passes through the hyperosmotic renal pyramid with no change in water content. Loss of large amounts of hypo-osmotic (dilute) urine. This is diuresis.

Question 16

How does high ADH effect aquaporin channels?

Answer 16

ADH is stimulated causing the addition of AQP2 channels to the apical membrane allowing the resorption of water from the collecting duct. When the ADH secretion decreases the AP2 channels are retrieved from the membrane via endocytosis

Question 17

What importance does the thick ascending limb play in medullary counter current mechanism.

Answer 17

Thick ascending limb is crucial is this as it is impermeable to water so removes solute without removing water and so increases Osmolarity of the interstitium whilst Osmolarity decreases within the filtrate. (if you were to block NaK2Cl channel with a loop diuretic the medullary interstitium becomes isosmotic and large amounts of dilute urine is produced).

Question 18

What importance does the descending limb play in medullary counter current mechanism.

Answer 18

Descending limb of LH is highly permeable to water due to AQP-1 water channels which are always open. Descending limb is not permeable to Na+ therefore Na remains in the descending limb of LH and its concentration (Osmolarity) increases. Maximum Osmolarity is at the tip of the LH which is 1200mOsm/kg.

Question 19

How does the movement of ions in the ascending and descending limbs limbs of loop of henle cause a large vertical osmotic gradient?

Answer 19

The NaCl transporters in the think ascending limb of the LH can produce an osmotic gradient of 200mOsm/kg. Meanwhile the thin descending limb of the LH removes water, concentrating the filtrate. As the filtrate moves down the descending limb it becomes more and more concentrated, but as it rises back up the ascending limb it becomes more and more dilute. This is matched in the interstitium because of the capabilities of the NaCl pump causing the medullary concentration gradient.

Question 20

What is counter current multiplication?

Answer 20

The increased concentration in the interstitium created by the loop of Henle is known as counter current multiplication and is produced by the loop of Henle.

Question 21

What role does the vasa recta of juxtamedullary nephrons play in the medullary counter current mechanism?

Answer 21

The counter current flow of the vasa recta maintains this osmotic gradient. The concentration gradient of the interstitum in the medulla would soon dissipate if not for the vasa recta. The vasa recta moves in a counter current flow to the loops of henle so that the descending part of the vasa recta takes on Na and Cl and looses water to the interstitum as it passes down the ascending limb of the loops of henle. At the hairpin it has the same concentration gradient as the Interstitium. As it rises back up parallel to the descending Loop of Henle it looses it’s Na and Cl back to the interstitium and takes on the water lost by the descending limb. The vasa recta acts as a counter current exchanger.

Question 22

Does the vasa recta have any capacity for active transport?

Answer 22

Vasa recta has no capacity for active transport.

Question 23

What is the purpose of the medullary gradient created by the counter current mechanism?

Answer 23

To allow water to be reabsorbed from the collecting ducts of the juxtamedullary nephrons and so concentrate the urine.

Question 24

How does urea assist the concentrating of urine?

Answer 24

Under the influecne of ADH Urea can leave the medullary areas of the collecting duct (via aquaproin channels) and bring water with it into the interstitium. From here it is the excreted agains into the ascending limb of the loop of Henle and so is recycled.