tubular function Flashcards by Marissa Bobay

the proximal tubule (PT) is the _____ segment of the nephron; is called _____

longest

“workhorse” of the nephron

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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)

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loop of Henle (LoH) function & key role

continues obligatory salt & water reabsorption

key role in creating medullary osmotic gradient

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thin descending limb of LoH is _____ to water, _____ to solutes

permeable to water (via AQP1)

impermeable to solute (ex. NaCl/salt)

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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

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thick ascending limb transporters (both apical & basolateral)

apical:
NKCC
ROMK (K+ channel)
NHE

basolateral:
Na+/K+ ATPase

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NKCC regulation (in TALH)

inhibited by loop diuretics

activity increased by ADH/AVP

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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

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how does TALH dilute the fluid if it can’t remove water?

it removes salt

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both TALH & early distal tubule are _____ segments

diluting

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early distal tubule is _____ to water, _____ to salt

impermeable to water

permeable to salt (via NCC)

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what are the transporters in early distal tubule (both apical & basolateral)

apical:
NCC

basolateral:
Na+/K+ ATPase
Cl- channel

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what is NCC, what is it inihibited by

NaCl Co-transporter in apical membrane of early distal tubule

inhibited by thiazide diuretics

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2 functions of thiazide diuretics in early distal tubule

inhibit NCC

indirectly stimulate Ca2+ reabsorption

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what is the collecting system comprised of

late distal tubule & cortical collecting tubule (CCT)

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CCT and OMCD are comprised of _____ epithelium (with _____ & _____ cells)

heterogeneous epithelium

with principal cells & intercalated cells

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what cell type is in the IMCD (and what epithelium)

a cell type analogous to principal cells

homogenous epithelium

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in the collecting system: function of principal cells

electrolyte & water balance

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in the collecting system: function of intercalated calls

acid/base balance

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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

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what type of transport does the PCT use to reabsorb / secrete things

transepithelial transport

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water reabsorption in the PCT is _____

iso-osmotic

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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

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transporters that do reabsorption at basolateral membrane in proximal tubule

Na+/K+ ATPase

GLUT2

AQP1

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"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

K+ wasting diuretics

in pt with low K+, which transporter would be upregulated, & at which cell is this located & what transporter is NOT upregulated for this

upregulate H+/K+ ATPase in alpha intercalated cells in CCT (NOT upregulating NKCC for hypokalemia)