L07-Urine concentration and dilution Flashcards
What is the main regulator or urine osmolality and flow?
ADH (vasopressin)
Where is it synthesised and released?
synthesised in the hypothalamus and released from the posterior pituitary.
Where does it act and what effect does it have?
It acts on distal tubule and collecting duct to increase water permeability by increasing AQP2
By what mechanism does ADH upregulate AQP2 channels?
binding to its receptor activates adenyl cyclase that increases the intracellular cAMP levels. this causes increased transcription of AQP2 proteins from the nucleus and also causes more AQP2 to be released from vesicles.
What effect does ADH have on the urea transporter?
ADH also increases transcription and release of UT-A1 which causes increased urea absorption that with it brings more water.
How do cells in the medulla survive such high osmolalitites around them?
One technique is the accumulation of organic osmolytes within the cells.
What are the two types of diabetes insipidus?
Central diabetes insipidus - lack of production of ADH
Nephrogenic diabetes insipidus - a problem with the V2 receptors detecting ADH binding.
What are the symptoms of diabetes insipidus?
they are unable to concentrate urine resulting in polyuria and dehydration. This then causes polydipsia (drinking too much)
What are the causes and treatment for central diabetes insipidus?
The typical causes are head injury, tumour or infection.
they are treated with ADH analogues or can be paradoxially treated with thiazide diuretics as these encourage AQP2 upregulation and help prevent hypernatraemia caused by the indipidus.
What are the causes and treatments of nephrogenic diabetes inspidus?
The causes are hypercalcaemia, toxicity or genetic mutations of the V2 receptors.
They are treated with thiazide diuretics and low salt diet.
What is SIADH and what are its treatments?
It is syndromes of inappropriate ADH and is commonly caused by head injury. Cause concentrated urine and patients become hyponatraemic. Treated with fluid restriction and urea.