Lecture 19 - Osmoregulation

Question 1

What is regulation of urine osmolality primarily determined by?

Answer 1

ADH (vasopressin)

Question 2

State the sections though the base of the brain (right side)

Answer 2

• PVN - Paraventricular nucleus
• SON - Supraoptic nucleus
• OT - optic tract
• INF - Infundibulum
• 3V - 3rd ventricle

Question 3

What is ADH and its role?

Answer 3

• Synthesised in the hypothalamus
• Also known as arginine vasopressin (AVP) or just vasopressin
• Released from the terminals of the hypothalamic neurons found within the posterior pituitary.
• Acts in the distal tubules and collecting duct to increase water permeability by increasing AQP2.

Question 4

Explain the role of urea?

Answer 4

• 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 kidney has a lower capacity to concentrate urine.
• The urea transporter UT-A1 is also regulated by ADH, in a similar way as for AQP2.

Question 5

Describe cell survival in the medulla

Answer 5

Cells in the medulla routinely see 1200mOsm.kg^-1 so to survive they have one key adaptation: accumulation of a range of organic osmolytes within the cells.

Question 6

What causes diabetes insipidous?

Answer 6

• Due to a loss of ADH secretion or a loss in the sensitivity of the kidney to ADH often because of a problem with the V2 receptors.
• This means that they are unable to produce concentrated urine, leading to polyuria, dehydration and hypovolemia. This them causes polydipsia.
• if fluid intake is inadequate they become hyponatremic.

Question 7

What are the causes of central diabetes insipidus and what is its management?

Answer 7

• Causes: head injury, tumours, infection

- management: Give desmopressin (ADH analogue), paradoxical use of thiazide diuretics.

Question 8

What are the causes of nephrogenic diabetes insipidous and its treatment?

Answer 8

• Causes: toxicity, hypercalcaemia, genetics

- Treatment: not with desmopressin, thiazide diuretic, low salt diet.

Question 9

What is SIADH?

Answer 9

• Sydromes in inappropriate ADH
• Commonly caused by head injury
• Produces concentrated urine
• Become hyponatremic
• treatments: Fluid restriction, give urea

Question 10

How does ADH cause thirst?

Answer 10

• inadequate water intake causes an increase in osmolality of the plasma.
• As for the regulation of ADH release, osmolality is detected in the anteroventral third ventricle region.
• AV3V neurons project to the median prep-tic area of the hypothalamus, which increases thirst.

Question 11

Why are not all dietary osmolytes equal?

Answer 11

• The dominant osmolytes in the circulation are Na+ and Cl- bu they aren’t the dominant osmolytes ingested. Much larger quantities of carbohydrates, fat and proteins are consumed than the mass of: potassium (3.5g) and sodium (2.4g).
• Excluding fat, all these intakes reach the circulation from the gut in a water soluble form and therefore contributes osmolytes which can affect osmolality

Question 12

What is Hyperosmolar hyperglycemic state (HHS)?

Answer 12

• In diabetes mellitus, the glucose concentration can get so high that it becomes a large contributor to osmolality.
• Gives strong thirst drive, which if insufficient leads to cellular dehydration and if sufficient to lower glucose leads to hyponatraemia.
• Causes altered mental status, seizures and other neurological signs. Also increases blood viscosity and clotting risk.