Lecure 3 Flashcards
what is osmolality and how is it measured?
Is the measure of how concentrated a solution is ( [X]*n- mOSmol/kgH20). Measure the concentration of solute and multiply by the number of particles it dissociates into e.g. NaCl - 100mmol x 2= 200 m osmol/kgH20. About 90% dissociate so the number is smaller with an osmolitor.
Where is urine concentrated and by what mechanism?
In the loop of Henle and the collecting duc by counter current manipulation. 15% of loop of Henles are juxtamedullary= go deep into the medulla which is important for concentrating urine
What are the permeabilities of water in the loop of Henle?
Water moves out of the descending limb but not the ascending limb which is only permeable to NaCl. In the inner medulla, water only moves out in the presence of vasopressin
What is the transverse and vertical gradient hypothesis?
There is a transverse gradient (290 d and 90 a) and a vertical gradient (1400 where the tubes meet and 290 D) in osmolality between the sections of the loop of Henle
Explain the transverse and vertical gradient
As you go down the descending limb, osmolality increases as a result to water moving out of the tube causing an increase in concentration. The osmolality then decreases going up the A limb due to NaCl moving out which causes the filtrate to become less concentrated. Vasopressin handles NaCl to drive water reabsorption and also drives water reabsorption in the collecting duct through AQ2
What are the features of the descending limb and give an example of KO mouse for one of those features?
Is basically NaCl impermeable (although some seep through). Is very water permeable- water is reabsorbed through AQ1. KO Aq1= mice have trouble concentrating urine. Can be seen by immunostaining
What are the features of the thin ascending limb?
NaCl and urea permeable (passive mechanisms). Water impermeable- not very well understood as it is difficult to dissect out
What are the features of the cells in the thick ascending limb?
Have NKCC2 on the apical side (require all 4 ions to bind) and ROMK to allow K+ to go back out as there isn’t enough in the urine. Has CLCK, ROMK and Na/K ATPase on the basolateral side.
What is Barter’s syndrome?
Is a salt wasting disease due to mutations in the channels of the thick ascending limb (can’t reabsorb NaCl). Causes polyuria, hypotension, hypokalaemia (failure to reabsorb K+), hypercalciuria and nephrocalcinosis and metabolic alkalosis.
What are the properties of the cortical and outermedullary collecting duct principle cell?
ENac, ROMK and AQ2 on the apical side. AQP3 and 4, Na+/K+ ATPase and Kir2.3 on the basolateral side. Vasopressin causes shuttling of AQP2 to the apical membrane- failure to do so causes diabetes insipidus
Explain the importance of urea in water reabsorption
50% of interstitial osmolality is driven by NaCl and the other 50 is driven by urea. The outer medullary part of the collecting duct (early) has low urea permeability. As water leaves, the urine becomes more concentrated and causes an increase in driving force for urea to leave. In the presence of vasopressin, the inner medullary part of the collecting tube becomes permeable to urea which causes a high influx of urea which adds to the driving force of water reabsorption.
What are the features of the inner medullary collecting duct and what experiments can be done to observe the importance of urea handling?
Have UT-A1 on apical side and UT-A3 on the basolateral side- urea moves along its concentration gradient. Can do a double KO- compare dehydrated to free access to water mice= urine osmolality remains the same. In WT it increases therefore urea is very important.
What is the Vasa recta?
Specialised blood supply in the kidney that leads to the efferent arteriole. It goes up then down like the loop of Henle to prevent wash out as a lot of energy is spent to move NaCl move into the ISF. UTB is a urea transporter on red blood cells that aid movement of urea out of the blood once it reaches the top to allow water to move out. Patients with UTB mutation have problems concentrating urine
