Regulation of urine concentration Flashcards
(27 cards)
How much primary urine is produced per minute and per day under normal conditions?
1.25ml.min = 1.8L/day
What happens to the flow rate in the nephron?
Flow rate decreases along the nephron as water is reabsorbed.
What hormone regulates urine osmolality and flow?
ADH
What is another function of ADH?
Increases BP by acting on vessels.
Where is ADH synthesised?
Synthesised in the hypothalamus but released from the terminals of hypothalamic neurons in the posterior pituitary/neuropophysis and then released into the circulation.
Where does ADH act and what does it cause?
Acts on distal tubule and MCD to increase permeability of H2O by increasing AQP2 insertion on to the apical membrane. ADH stimulates thirst.
How does ADH produce its affect? What happens in the short and long term?
ADH is detected by V2 receptors on the basolateral membrane. V2 is a GPCR that activates PKA pathway.
In the short term PKA phosphorylates proteins involved in AQP2 insertion. It uses premade AQP2 for fast changes in absorption.
In the long term cAMP leads to the transcription and synthesis of AQP2 which is packaged into vesicles for storage.
What results from no ADH?
Dilute and high urine output as the duct remains less permeable.
Flow rate will be UNCHANGED as less reabsorption.
What results from maximum ADH?
Distal tubule equilibrates with the cortex and MCD equilibrates with the medulla to produce concentrated urine, due to the high osmotic gradient of the medulla. Urea permeability increases resulting in a low and concentrated urine output.
Why is the kidney’s capacity to concentrate urine reduced in a patient with selective protein starvation?
Urea is formed from N2 after protein degradation in order to remove N2 from the body. Less proteins = Less N2 = Less urea.
Out of Aldosterone and ADH which directly increases blood volume?
ADH DIRECTLY increases blood volume by increasing water permeability.
Aldosterone indirectly increases volume by increasing Na permeability through ENAC.
How does ADH affect urea?
ADH results in the insertion of UT-A1 channels when detected by V2.
What is the movement of urea?
Moves across the apical membrane via UT-A1 and into the interstitium within the MCD.
How are medullary cells adapted for survival in the highly osmotic environment?
The accumulation of organic osmolytes prevents a gradient forming across the cell and interstitium to prevent the intracellular fluid being absorbed.
Give an example of an organic osmolyte.
Sorbitol, inositol, betaine, glycerophosphorylcholine
What occurs along side protein malnutrition?
Dehydration as the urine remains dilute in malnutrition due to the lack of urea.
What is Diabetes Insipidus?
The inability to concentrate urine leading to polyuria of low omsmolality, dehydration, polydipsia, hypovolaemia.
What will results from insufficient fluid intake in a pt with diabetes insipidus?
HYPERnatraemia
What are the two types of diabetes insipidus?
Central - Loss of ADH secretion
Nephrogenic - Loss of ADH sensitivity in V2 receptors
What causes central DI?
Head injury, tumour, brain infection
How can central DI be treated?
Desmopression - ADH analogue with a long half life to increase AQP2 and urea channel insertion for reabsorption.
Can use thiazide diuretic - produce the opposite effect to normal by preventing hypernatraemia and encourages PCT absorption and increases AQP2 expression.
What causes nephrogenic DI?
Loss of receptor sensitivity due to toxicity in the kidneys, hypercalaemia or genetic mutation in V2 or AQP2.
How can nephrogenic DI be treated?
Thiazide diuretic and low salt diet.
Cannot use ADH analogue as the receptors are damaged.
What is SIADH?
Syndromes in inappropriate ADH release resulting in excess ADH
