tubular function Flashcards
the proximal tubule (PT) is the _____ segment of the nephron; is called _____
longest
“workhorse” of the nephron
proximal tubule (PT) function
obligatory salt & water reabsorption
-reabsorbs most filtered H2O, Na+, Cl-, K+, HCO3-, Ca2+, PO4, SO4 (via NHE3, AQP1)
-reabsorbs ALL filtered organic nutrients like glucose, AAs, vitamins (via SGLT2, SGLT1, GLUT2)
-secretes H+ & reabsorbs HCO3- (via NHE3)
-secretes organic ions & ammonia (NH3)
loop of Henle (LoH) function & key role
continues obligatory salt & water reabsorption
key role in creating medullary osmotic gradient
thin descending limb of LoH is _____ to water, _____ to solutes
permeable to water (via AQP1)
impermeable to solute (ex. NaCl/salt)
thin ascending limb of LoH is _____ to water, _____ to salt, _____ to urea
impermeable to water
permeable to NaCl/salt (passive in tALH, active in TALH)
permeable to urea in tALH
thick ascending limb transporters (both apical & basolateral)
apical:
NKCC
ROMK (K+ channel)
NHE
basolateral:
Na+/K+ ATPase
NKCC regulation (in TALH)
inhibited by loop diuretics
activity increased by ADH/AVP
how does paracellular transport occur in TALH, how can this be inhibited
Ca2+, Mg2+ reabsorption
indirectly inhibited by loop diuretics- bc Ca2+, Mg2+ can be seen in pt’s urine
how does TALH dilute the fluid if it can’t remove water?
it removes salt
both TALH & early distal tubule are _____ segments
diluting
early distal tubule is _____ to water, _____ to salt
impermeable to water
permeable to salt (via NCC)
what are the transporters in early distal tubule (both apical & basolateral)
apical:
NCC
basolateral:
Na+/K+ ATPase
Cl- channel
what is NCC, what is it inihibited by
NaCl Co-transporter in apical membrane of early distal tubule
inhibited by thiazide diuretics
2 functions of thiazide diuretics in early distal tubule
inhibit NCC
indirectly stimulate Ca2+ reabsorption
what is the collecting system comprised of
late distal tubule & cortical collecting tubule (CCT)
CCT and OMCD are comprised of _____ epithelium (with _____ & _____ cells)
heterogeneous epithelium
with principal cells & intercalated cells
what cell type is in the IMCD (and what epithelium)
a cell type analogous to principal cells
homogenous epithelium
in the collecting system: function of principal cells
electrolyte & water balance
in the collecting system: function of intercalated calls
acid/base balance
both late distal tubule & cortical collecting duct (CCT) are _____ to water, & function in _____
variably permeable to water
hormonal fine tuning of Na+, K+, and water balance
what type of transport does the PCT use to reabsorb / secrete things
transepithelial transport
water reabsorption in the PCT is _____
iso-osmotic
transporters that do reabsorption at apical membrane in proximal tubule
NHE (Na+/H+ exchanger; does 2/3rd of Na+ reabsorption in PT)
SGLT2 (Na+/glucose coupled transporter), SGLT1
AQP1
transporters that do reabsorption at basolateral membrane in proximal tubule
Na+/K+ ATPase
GLUT2
AQP1
“where salt goes, _____”
water flows
transporters for glucose reabsorption in both membranes
apical:
SGLT2
basolateral:
Na+/K+ ATPase
GLUT2
what is hyperaminoacidurias
increased renal excretion of AAs
what can cause hyperaminoacidurias
increased [AAs in plasma]
genetic defects in AA transporters in the kidney
(ex. cystinuria, Hartnup disease)
what breaks down oligopeptides (how are they filtered)
brush border peptidases
break down oligopeptides into individual AAs & di/tripeptides -> then they’re transported into the cell
how are larger polypeptides & proteins filtered into the cell
via receptor-mediated endocytosis
what is the water permeability like along the proximal tubule & thin descending limb; why is this important
very high water permeability (AQP1 is the water channel)
higher water permeability = lower gradient needed to induce reabsorption
what is the trend of the TF/P ratio of inulin
PAH’s TF/P ratio starts at 1.0 at the beginning of PT
->
rises to a TF/P ratio greater than inulin’s (bc inulin is just filtered and not filtered AND secreted like PAH)
ions secreted by the PT (proximal tubule) that are diuretics
(usually on apical membrane)
creatinine (both)
amiloride (cation)
(anions:)
acetazolamide
chlorothiazide
furosemide
PAH
penicillin G
what does OAT and OCT stand for
organic anion transporter
organic cation transporter
what is happening at Tmax
transporter density limits maximum transport rate
the tubular fluid that enters the loop of Henle is _____ to plasma
iso-osmotic
TF/P ratio _____ as fluid flows through descending LoH, bc _____
increases
water is reabsorbed without solute
TF/P ratio _____ as fluid flows through ascending LoH, bc _____
decreases
solutes are reabsorbed without water
what happens to Ca2+ at the early distal tubule
it’s reabsorbed transcellularly across the epithelium
Ca2+ transporters at the early distal tubule (at both membranes)
apical:
NCC
ECaC/TRPV5
basolateral:
Na+/K+ ATPase
NCX
Ca2+ ATPase
Cl- channel
principal cell
-is what % of cells in CCT
-its apical transporters
-its basolateral transporters
is 70% of cells (majority)
apical:
ENaC (reabsorbs Na+ from TF)
ROMK (secretes K+ into TF)
AQP2
basolateral:
Na+/K+ ATPase
K+ leak channel
AQP 3/4
alpha intercalated cell
-secretes what
-apical transporters
-basolateral transporters
acid / H+ into TF
apical:
H+ ATPase
H+/K+ ATPase (HKA)
basolateral:
Cl-/HCO3- exchanger (AE1)
Cl- channel
beta intercalated cell
-secretes what
-apical transporter
-basolateral transporters
base / bicarbonate (HCO3-) into TF
apical:
Cl-/HCO3- exchanger (Pendrin)
basolateral:
H+ ATPase
Cl- channel
ENaC, ROMK are regulated by what
aldosterone
what phenomenon happens between ENaC & ROMK, what does this mean
they became electrically coupled
a change in one, affects a change in the other as well
(ex. increasing Na+ absorption, also increases K+ secretion)
5 major classes of diuretics
1) acetazolamide (carbonic anhydrase inhibitors)
2) osmotic diuretics
3) loop diuretic
4) thiazides-type diuretics
5) potassium-sparing diuretics
acetazolamide (carbonic anhydrase inhibitors) location & function
in PCT
inhibits proton formation
->
inhibits NHE bc no H+ to pump out -> so no Na+ comes in
define diuretic
drugs that cause an increase in urinary water exretion
osmotic diuretics location & function
in PCT & tDLH
increases filtered load of glucose
->
overwhelms SGLT transporters
->
all glucose cannot be reabsorbed
->
more osmotically active solutes retained in fluid = less water is reabsorbed (more water stays in fluid)
loop diuretic location & function
in TALH
inhibit NKCC activity
thiazides-type diuretics location & function
in early distal tubule
inhibit NCC activity
potassium-sparing diuretics location & function
in cortico- & outermedullary collecting duct
either block ENaC
or
inhibit aldosterone receptor
draw this table
what are the most permeable segments of the nephron under all conditions, and how much water do they reabsorb
proximal tubule
&
tDLH
reabsorb 90% of water by end of tDLH
why do proximal tubule & tDLH have high water permeability
bc of expression of AQP1 on both apical & basolateral membranes
AQP1 is not under hormonal control or responsive to ADH & has constant high permeability under all conditions
what is required to be present to have high rates of water flux
presence of AQP
if the urine is > 300 mOsm, it is bc _____
the ECF of the medulla has been more concentrated than normal
low ADH = _____ medullary osmotic gradient, collecting tubule is _____, and _____ is excreted
smaller medullary osmotic gradient
->
collecting tubule is still diluting
->
high volume, dilute urine is excreted
high ADH = _____ medullary osmotic gradient, collecting tubule has _____, tubular fluid _____, and _____ is excreted
maximized medullary osmotic gradient
->
high permeability to water
->
tubular fluid goes into equilibrium w ISF
->
low volume, concentrated urine is excreted
we require an increasing medullary osmotic gradient in order to produce _____
urine that is more concentrated than 300 mOsm (isoosmotic to plasma)
how is the medullary osmotic gradient produced
how is the medullary osmotic gradient maintained
