Physiology of the Renal System IV: Osmoregulation Flashcards
What regulates the osmolality of urine?
Primarily determined by ADH (vasopressin)
Where are the neurones that detect osmolality in the brain?
3rd ventricle
What is ADH?
Also known as vasopressin is anti-diuretic hormone.
Where is ADH synthesised and released?
Synthesised in the hypothalamus
Released from the pituitary gland
What is the stimulus for ADH secretion?
Osmolality increase
decrease in osmolality shuts off ADH production
What does ADH do?
ADH increases the number of AQP2 channels expressed on the apical membrane of the collecting duct allowing for more reabsorption of water.
How does ADH regulate AQP2 on the apical membrane of the collecting duct?
ADH binds to V2 receptors.
This increases cAMP created from adenylyl cyclase.
cAMP activates PKA
Vesicles containing AQP2 are then inserted into the apical membrane.
Additionally cAMP moves to the nucleus to increase AQP2 synthesis.
How does osmolality change throughout the nephron?
PCT, osmolality remains around 285mOsm.kg-1
Down the descending loop of Henle, osmolality increases as water is moved out.
Ascending loop of Henle, DCT, collecting duct the osmolality decreases as ions are pumped out and leads to dilute urine as no ADH means little water is reabsorbed.
How does flow rate change throughout the nephron?
flow rate decreases along the nephron.
Flow rate of about 17ml/min in CD
Little water reabsorption without ADH
How does osmolality change in the nephron with maximal ADH?
Same mechanism occurs until the DCT and collecting duct.
As ADH increase AQP2 number in the collecting duct, more water can be absorbed and therefore leads to heavily concentrated urine due to the majority of water being removed.
How does flow rate change in the nephron with maximal ADH?
Same mechanism as with no ADH, until DCT and collecting duct.
Here the flow rate is reduced massively to 0.1 ml/min in CD.
What is the reason for water reabsorption in the nephron?
High osmolality in the extracellular space (driving force) and increased AQP2 via ADH leading to increased permeability.
What causes high osmolality in the extracellular space?
Urea and the action of ions being pumped out of the ascending limb of the loop of Henle.
What controls the absorption of urea?
ADH controls the UT-A1 (urea transporters) meaning that when urea reabsorption is high, reabsorption of water is also high.
How do cells survive in high osmolality?
Accumulation of a range of organic osmolytes within the cells.
These include sorbitol, inositol,glycerophosphorylcholine and betaine.
What is diabetes insipidus?
Due to a loss of ADH secretion(central) or loss in the sensitivity to ADH within the kidney (nephrogenic).
This means that people are unable to produce concentrated urine.
What issues are related with diabetes insipidus?
polyuria (lots of urine production), dehydration and hypovolaemia.
This can then lead to polydipsia (drinking too much)
What happens when fluid intake is inadequate?
They become hypernatraemic (high sodium concentration in the body)
What is the cause of central diabetes insipidus?
Head injury
Tumours
Infection
How can diabetes insipidus be treated?
Give desmopressin
(ADH analogue) which mimics the action of ADH.
What causes nephrogenic diabetes insipidus?
Toxicity (lithium)
Hypercalcaemia
Genetic due to mutations in either V2 or AQP2
How is nephrogenic diabetes insipidus treated?
Not with desmopressin
Thiazide diuretic
Low salt diet.
What is SIADH?
Syndrome of inappropriate ADH
Produces too concentrated urine and leads to people becoming hyponatraemic
What are the causes of SIADH?
Caused by head injury or other causes.
What is the treatment to SIADH?
Fluid restriction
Give urea
V2 receptor antagonists (vaptanse)
What are the symptoms of SIADH?
High ADH
How does thirst occur?
Inadequate water intake leads to increased osmolality.
Osmolality is detected in the anteroventral third ventricle (AV3V) region.
AV3V neurones project to the median preoptic area of the hypothalamus and increases thirst
What are the dominant osmolytes in circulation?
Na and Cl
What are the dominant osmolytes that are ingested?
Potassium and sodium
What is HHS?
Hyperosmolar hyperglycemic state
Occurs when glucose is higher than 33mM giving an osmolality of around 320m Osm
What can HHS cause?
seizures and other neurological signs, altered mental status.
