Renal Physiology II - Wall Flashcards
Normal GFR is about what?
120 mL/min
Normal RPF is about what?
600 mL/min
What is the filtration fraction?
Fraction of RPF that becomes GFR; normally about 20%
What is renal clearance formula?
C = (UV)/P where V=UFR
What are some ways the autoregulatory response can be disturbed?
ATII inhibition (ACE inhibitors)
NSAIDs that prevent vasodilatory prostaglandins
Inc CO2 leading to inc RPF and perfusion pressure
What does the kidney do during volume expansion?
Decrease in FF, shut off renin and AT II production, augmenting delivery to distal nephron
Where are Na/K ATPases found?
Basolateral side; never luminal side
Describe the capacity and resistance of the proximal convoluted tubule
High capacity and low resistance
Describe the capacity and resistance of the distal tubule
Low capacity and high resistance; built NOT for bulk reabsorption but maintenance of gradients
Which substances are reabsorbed via coupled symport?
Cl-, glucose, AA, lactate…phosphate
Where are aquaporins expressed in the tubule?
Proximal tubule and thin descending limb
What is the major difference between carriers and channels?
Channels are not saturable; carriers are
What protein makes up tight junctions?
Claudins
What is the biggest energy expenditure in the kidney?
Maintaining the Na/K ATPase
What mechanisms does the kidney have to save energy since it has to use so much ATP for the ATPase?
Couple transport to sodium
Where does the proximal convoluted tubule reside in the kidney?
Entirely in cortex
What is filtered load formula?
GFR x plasma concentration
What is reabsorbed in the proximal tubule up to the macula densa?
~50% of NaCL and H20
~90% of NaHCO3
100% of nutrients like glucose & AAs
Where are many drugs secreted into the nephron?
Proximal tubule
What is glomerulotubular balance (GTB)?
Matching how much of the solute is reabsorbed with how much is filtered
When the GFR increases, how does the proximal tubule compensate?
Reabsorbs higher amount of filtrate but same PERCENTAGE
What is the transport maximum
The maximum amount of a substance that can be reabsorbed or secreted
In which parts of the tubule is the Na-K ATPase found?
All parts; it is responsible for maintaining the negative cell interior and creating a sodium concentration gradient (electro and chemical gradient)
What happens to glucose filtration/excretion/reabsorption in the kidneys in diabetes?
Reabsorb glucose until the Na/glu transporter is saturated (Tm = maxed out reabsorption); if blood glucose goes up more, then it will start to be excreted into the urine and disrupts
tubule function along the way
threshold= glucose starts to be excreted
Describe how bicarbonate is reabsorbed in the proximal tubule
1) Na+/H+ antiporter spits out H+ which combines with bicarbonate
2) CA in microvilli converts into CO2 and H2O which moves through AQ-1 into cell
3) IC Ca converts them back to HCO3- and H+, which recycles
4) HCO3- leaves cell on basolateral side through specific Na/HCO3 cotransporter, which is electrogenic (3HCO3 out, 1Na+ in) and makes - charge on interstitium
What drives reabsorption of cations like Ca++ and Mg2+ in the proximal tubule?
HCO3-out/1Na+ in creates negative interstitium which attracts cations
What drug inhibits CA?
acetazolamide
Acetazolamide MOA
CA inhibitor that inhibits NaHCO3 reabsorption leading to inc excretion of NaHCO3 and water
What is reabsorbed in the thin descending limb?
Water and urea which follows it, and NO Na because no Na channels
What is reabsorbed in the thin ascending limb?
Na+ reabsorbed passively, impermeable to water
What is significant about the hairpin turn?
After the turn, the nephron is water impermeable (and also urea)
Is sodium reabsorbed in the thick ascending limb?
Yes
Is water reabsorbed in the thick ascending limb?
No
What is the purpose of reabsorbing Na in the thick ascending limb and how is it done?
Active transport; critical for maintaining hypertonic medulla needed to concentrate urine
What is the unique transporter in the thick ascending limb and what does it need to function?
Na/K/2Cl - needs all of that to work
on luminal side
Explain potassium recycling in the thick ascending limb
Need Na/K/2Cl transporter to reabsorb ions but K is in low concentration at this point, so the cell has a potassium channel that leaks K out in order for it to come back in with Na and Cl
K recycling also gives lumen a positive charge which promotes paracellular Na,Ca,Mg reabsorption
Explain the fate of the ions in the Na/K/2Cl transporter in the thick ascending limb
K is recycled; Na is pumped out into interstitium by ATPase; Cl exits cell via Cl channels
Furosemide MOA
Loop diuretic that blocks Na/K/2CL transporter in thick ascending limb
By inhibiting this transporter it also inhibits Na,Ca,Mg paracellular reabsorption resulting in urinary excretion
What is Bartter’s syndrome?
Mutation in Na/K/2Cl- transporter in thick ascending limb that causes diuretic effect similar to furosemide
What is found at the end of the cortical thick ascending limb?
Macula densa
How does the macula densa sense solute delivery?
[Cl-]
What does the macula densa do when it senses too much delivery?
Constrict afferent vessel
If renal perfusion pressure drops, how does the macula densa balance with the autoregulatory response?
MD causes vasodilation of afferent arteriole to increase GFR which was being maintained by autoregulatory response
How can the afferent arteriole directly influence low flow?
Renin secretion
Where is the distal convoluted tubule located?
Entirely in renal cortex
What happens in the distal convoluted tubule?
Some NaCl reabsorption; no H20 or water resorbed; MAJOR Ca ReabsorptioN!
What does PTH in the nephron?
Acts at distal convoluted tubule on the Ca2+-dependent protein on apical side to promote Ca2+ reabsorption
What is the unique transporter in the distal convoluted tubule?
Electroneutral Na+/Cl- cotransporter on luminal side
Are loop diuretics or thiazide diuretics more potent and why?
Loop diuretics; thiazide diuretics act at the DCT where minimal NaCl is absorbed, whereas loop diuretics act on the Na/K/2Cl- transporter in the loop where about 25% of sodium is reabsorbed
What do thiazide diuretics do to calcium levels?
Decrease Ca excretion because Ca/Na transporter on basolateral side is more active at pumping in sodium when the Na/Cl transporter (which imports Na) is inhibited
What is Gittleman’s syndrome?
Mutation in Na/Cl cotransporter in distal convoluted tubule
Which diuretic would be best for someone with calcium-based kidney stones?
Thiazide diuretics which actually promote calcium reabsorption
What are the two types of cells in the collecting duct and what are their functions
Principal cells - NaCl & H20 reabsorption, K secretion
Intercalated cells - acid-base maintenance
Where in the nephron does aldosterone have its action?
Collecting duct, where it conserves salt and stimulate K secretion
What do alpha intercalated cells do?
Secrete H+ via ATPase
What do beta intercalated cells do?
Secrete HCO3- via Cl/HCO3 exchanger
Where is potassium homeostasis primarily controlled?
Collecting duct
Which part of the nephron is responsible for calcium regulation?
Distal convoluted tubule
Explain Na and K movement in the collecting duct
Dilute tubular fluid doesn’t have much Na, but gradient still exists because of negative cell interior thanks to ATPase. So Na moves through CHANNEL into cell.
As a result, the fluid is now more negative, promoting K+ secretion.
What does aldosterone do in the collecting duct?
Binds mineralocorticoid receptor to activate transcription of Na/K ATPase on basolateral and Na & K channels in luminal side
So, it augments sodium reabsorption and potassium secretion in the collecting duct
How does the kidney conserve Na+ in low salt diets?
To conserve Na, aldosterone is released to act on CT; but it also enhances proximal reabsorption of Na so less gets to distal nephron. Less negative charge generated from Na reabsorption there, meaning drive for K secretion is lower.
Explain the effect of high salt diet on the kidney
Aldosterone inactive due to volume expansion; less Na is reabsorbed due to less lumen negativity in CD. So fewer K+ channels are in the apical membrane in order to keep it from being wasted.
In general, which diuretics will cause potassium wasting and sodium balance?
Those that act before the collecting duct, because they cause more Na+ to reach the CD resulting in more potential for K to leave
Loops
Thiazides
Osmotics
CA inhibitors
They lead to negative sodium balance which causes aldosterone activation and thus enhanced sodium reabsorption; then the more negative lumen keeps more K+
Which diuretics do not cause potassium wasting and why?
Any diuretic that acts at the collecting duct because it does not cause increased Na reabsorption. Lead to decreased K secretion
Spironolactone
Amiloride
Triamterene
How can the collecting duct conserve water?
AQP2 is waiting around in the cytoplasm and is vasopressin sensitive; when plasma osmolality due to water restriction goes up, vasopressin/ADH is released which binds basolateral V2 receptor. A GPCR/cAMP cascade inserts AQP2 into luminal membrane
Which aquaporins are constitutively expressed in the CT and where/why?
3 and 4, in the basolateral membrane to return reabsorbed water into circulation
How does the CD tubular fluid compare to the renal cortex interstitium in terms of osmolarity?
Tubular fluid much more dilute
Is most water reabsorbed in the cortical or medullary collecting duct?
Cortical
What does vasopressin do to alter urea movement in the nephron?
ADH inserts urea channels in inner medullary CD in order to pack more urea into interstitial fluid; water is conserved because it follows urea.
Water is reabsorbed from CD until the osmolarity of the tubular fluid equals the interstitium
Name the major sites of Na reabsorption and the approximate amount reabsorbed there.
Proximal tubule ~50%
Loop of Henle ~40%
Distal tubule ~8%
Collecting tubule ~2%
