5 Renal Tubular Function 2 Flashcards
What is the key function of the thick ascending limb?
to create a hyperosmolar interstitial space in the medulla to drive water loss from the descending limb and cortical collecting duct
What is the descending limb permeable to?
water, which passes paracellularly passively
How does Na+ leave the filtrate in the ascending limb?
apical cotransporter
takes K+, Na+ and 2x Cl-
NKCC2
basolateral 3x Na+ / K+ exchanger
Why do we need a pump and not a channel to facilitate Na+ reabsorbtion in the ascending limb?
because it’s against its’ electrochemical gradient
Why does K+ reenter the filtrate after reabsorption in the ascending limb?
we have more Na+ than K+ in the filtrate, so reabsorbing Na+ and K+ 1:1 will cause us to run out of K+ in the filtrate
letting K+ out stops this from happening
What is the osmotic gradient, maintained by the ascending limb?
200 mOsm.kg-1
What does Furosemide do?
blocks the NKCC2 co-transporter in the ascending limb
causes water and sodium loss
acts as a diuretic
Why is Furosemide so useful?
it is very potent, so can be given in a wide range of doses to give effects of varying degrees
When is furosemide used?
cardiac and renal failure
types of volume overload
What is the major side-effect of furosemide, and what exacerbates this?
K+ loss (hypokalaemia), leading to cardiac dysrythmias
Digoxin coadministration
Name 3 minor side-effects of furosemide
hypovolaemia
mild metabolic alkalosis
Mg2+ and Ca2+ loss
What might people on Furosemide be told to do by their doctor?
eat a banana
or just some KCl tablets lol
How does a loop contribute to ion reabsorption?
takes it from 70% if it were a straight tube to 93%
What is the osmolality of the filtrate at different points of the loop of Henle?
285 as it enters
1200 in deep medulla
85 as it leaves
What happens to ions and water in the loop of Henle?
ions leave the ascending loop into interstitial space
water leaves descending loop into interstitial space
this hence causes osmolality change
How is Sodium reabsorbed in the distal tubule?
Na+ and Cl- cotransport
What do Thiazides do?
diuretics inhibiting Na+ and Cl- absorption on the apical membrane of the DCT
What are thiazides used as?
antihypertensives, although they’re being phased out for thiazide-like alternatives with fewer side-effects (endapomide)
What is different about Na+ reabsorption along the collecting duct?
we usually use the Na+ electrochemical gradient to drive the movement of other stuff, but here we need to separately regulate Na+
How is Na+ reabsorbed in the collecting duct?
What happens to K+?
Na+ channel, influx, Na/K ATPase on basolateral membrane
K+ efflux through ion channel on apical membrane
On the whole, what does the kidney do to K+ and Na+ levels and why?
It sees a lot of Na+ and little K+
to maintain this, the kidney has to reabsorb more Na+ and secrete more K+ to maintain whole body homeostasis
Name 2 hormone anti-diuretics
ADH
Aldosterone
How does Aldosterone work?
increases expression of epithelial sodium channel (ENAC) and sodium potassium ATPase
Name 2 pharmacological diuretics
Amiloride
Spironolactone
How does Amiloride work?
inhibits Na+ channels
How does Sprinolactone work?
inhibits receptors for aldosterone, indirectly inhibiting sodium reabsorption
What inadvertent effect does Sprinolactone cause, why might this be useful?
reduces K+ secretion, so we maintain potassium in our blood
we can hence use it with Furosemide!
What is sprinolactone used for?
heart failure (as it’s a K+ sparing diuretic)
Name 3 side-effects of Sprinolactone
inhibits other steroid receptors (androgens)
causes feminising in men (gynaecomastia)
menstrual disorders in women
What is the process of Urea cycling
reabsorbed into blood by UT-A1 transporters
this increases the osmolality in the interstitial space, facilitating water reabsorption
some then goes back into the kidney in the descending loop of Henle (UT-A2)
