Distal Tubular Transport

Question 1

moa of lasix

Answer 1

block NKCC on ascending limb of loop

Question 2

fn of lasix

Answer 2

increased urination by blocking Na reabsorption, can cause low K and Ca by loss of K+ backleak and gradient for Ca (lost in urine)

Question 3

syndrome equivalent to lasix, manifestations

Answer 3

Bartter’s- defect in NKCC in ascending

hypokalemia, met alkalosis (more Na delivery to distal, more H+ exchange), polyuria, polydipsia/dehydration

Question 4

overall fn of early distal tubule

Answer 4

diluting segment, aldo independent NaCl reabsorption by NCC

Question 5

overall fn of late DCT/ cortical collecting duct

Answer 5

aldo dependent Na reabsorption and K secretion, ADH water reabsorption- principal cells

H+/bicarb secretion- intercalated cells

Question 6

overall fn of medullary CD

Answer 6

aldo dependent Na reabsorption (ENaC)

ADH dependent water permeability and urea (adds to gradient)

Question 7

main transporter of early distale tubule

Answer 7

NCC- dilutes tubular fluid, reabsorbs Na and Cl

Question 8

fn of late distal/CCD principal cells

Answer 8

aldo dependent Na reabsorption (ENaC) and K+ secretion (ROMK)

K+ follows electric gradient as lumen becomes negative after Na leaves

Question 9

alpha intercalated cell fn

Answer 9

H+ secretion- H+ ATPase, H/K ATPase- excreted H+ binds to buffers like NH3

bicarb reabsorption via bicarb/Cl exchanger on basolateral (bicarb reabsorbed from lumen as CO2, converted via CA)

Question 10

thiazide moa

Answer 10

inhibit NCC in DCT

Question 11

amiloride/ tramterene moa

Answer 11

inhibit ENaC at CCD/MCD

K+ sparing

Question 12

gitelman syndrome

Answer 12

loss of fn at NCC, acts like thiazide diuretic

causes hypokalemia, met alkalosis

Question 13

gordons syndrome

Answer 13

gain of fn in NCC, causes HTN, hyperkalemia, met acidosis

low renin/aldo

Question 14

liddle’s syndrome

Answer 14

gain of fn at ENaC- uncontrolled Na retention

HTN, hypokalemia, met alkalosis

Question 15

pseudohypoaldosteronism I

Answer 15

loss of fn at ENaC- hypovolemia, Na wasting, hyperkalemia, high aldo, hyponatremia

Question 16

what is syndrome of apparent mineralcorticoid excess? SAME

Answer 16

defect in 11-beta-HSD2 enzyme

excess cortisol in the body which binds to MR- appears like high aldo

HTN, hypoK, alkalosis (aldo stimulate H+ secretion), low renin, low aldo

Question 17

aldo effect on principal and intercalated

Answer 17

stimulates insertion of ENaC and ROMK in luminal membrane

H+ ATPase activity stimulated

Question 18

ANP effect on principal cells

Answer 18

inhibit aldo effects (less ENaC)

responds to atrial stretch

Question 19

ADH impact on principal cells

Answer 19

bind V2 receptor on basolateral, stimulate insertion of AQP2 on luminal side

water enters cells via AQP2, leaves thru basolateral via AQP3

Question 20

describe hormonal regulation in the MCD

Answer 20

ADH water and urea reabsorption, aldo Na reabsorption and K secretion

Question 21

macula densa role in nephron

Answer 21

sense hypovolemia via low NaCl delivery to distal, stimulate RAAS and maintains GFR (also dilates afferent)

Question 22

determinant of urine osmolality

Answer 22

ADH presence in distal tubule- high (600-1200mOsm) means ADH is there, low (100) means absent

Question 23

why does pseudohypoaldosteronism type I cause hyponatremia

Answer 23

most distal segment- loss of fn at ENaC, low volume causes ADH to reabsorb water but no Na is absorbed