Unit 7 - Tubular Reabsorption and Secretion

Question 1

what are 2 methods of renal epithelial transport?

Answer 1

1. transcellular - occurring by uptake into and efflux from cell in either reabsorptive or secretory direction
2. paracellular - occurring by movement of solute and water through junctions of contiguous cell in either reabsorptive or secretory direction

Question 2

what is transcellular transport dependent on?

Answer 2

coordinate function of solute-specific transporters in apical membrane facing tubular fluid in lumen and in basolateral membrane facing peritubular space and peritubular capillaries
-solute-specific and nephron segment-specific transport mechanisms mediate water and solute transport in different segments of nephron

Question 3

where is Na/K-ATPase restricted to in kidneys?

Answer 3

basolateral membrane of all renal epithelial cells in all segments of nephron

• maintains steady state concentration difference across luminal and basolateral membrane
• presence and function of K+ channel-mediated, high K+ conductance in either luminal and/or basolateral membrane of renal epithelial cells maintains a steady state, inside negative membrane potential difference

Question 4

is trancellular transport active or passive?

Answer 4

both

• primary active transport
• secondary active transport (co-transporters, counter-transporters)
• passive diffusion
• passive facilitated diffusion

Question 5

what are co-transporters VS counter-transporters?

Answer 5

co: symporters that couple transport in same direction
- driving solute of most is the inwardly directed extracellular to intracellular transmembrane Na+ electrochemical potential gradient

counter: antiport/exchangers that couple transport in opposite direction across membrane
- mediate transport in either direction, depending on which of the coupled solutes has the largest electrochemical potential gradient

Question 6

is paracellular transport active or passive? what affects this?

Answer 6

passive only, and driven by transepithelial solute electrochemical potential gradient

• depends on “tightness” or solute-specific resistance to transport through intercellular junctions
• ability of epithelia to maintain transepithelial voltage difference or osmotic gradient is determined by cell-to-cell junctional resistance (“leakiness”) of epithelium to solute and water transport across junction

Question 7

what is solvent drag involved in?

Answer 7

paracellular transport; entrains movement of a solute when osmosis occurs
-contributes to transtubular solute reabsorption or secretion

Question 8

what does tubular reabsorption of a solute result from?

Answer 8

1. active uptake at luminal membrane, and passive efflux at basolateral membrane
2. passive uptake at luminal membrane, and active efflux at basolateral membrane

Question 9

what does tubular secretion of a solute result from?

Answer 9

1. active uptake at basolateral membrane and passive efflux at luminal membrane
2. passive uptake at basolateral membrane and active efflux at luminal membrane

Question 10

what is transcellular reabsorption/secretion inhibited by?

Answer 10

• saturated (has max rate Tmax); achieved at defined, solute-specific plasma and/or tubular fluid solute concentrations
• drugs

Question 11

renal handling of glucose by nephron

Answer 11

filtration and reabsorption, but not secretion

-proximal tubule is only segment where glucose reabsorption occurs, so any glucose still in urine here will be excreted

Question 12

clearance of glucose in terms of glucose in blood

Answer 12

circulating levels kept from 75 to 170 mg/dL

• freely filtered from plasma at glomerulus, and at normal levels, all of it is reabsorbed by proximal tubule (clearance = 0)
• clearance begins to increase at plasma levels 200 mg/dL (threshold plasma concentration where glucose appears in urine)

Question 13

what is Tm?

Answer 13

tubular reabsorptive maximum defining max solute reabsorptive rate or capacity for tubular solute reabsorption
-as plasma solute concentration increases and approaches Tm, the cell membrane transport mechanisms mediating transcellular solute reabsorption become saturated and solute appears in urine

Question 14

what are membrane transport mechanisms mediating transcellular glucose reabsorption in nephron?

Answer 14

in proximal tubule only

• early luminal membrane: Na+/glucose SGLT2 cotransporter
• early basolateral membrane: facilitated diffusion GLUT2
• late luminal membrane: 2 Na+/glucose SGLT1 cotransporter (allows more concentrated glucose accumulation)
• late basolateral membrane: facilitated diffusion GLUT1

Question 15

renal handling of PO4

Answer 15

filtered load of monobasic and dibasic phosphate is ~250 mmol/day (more than 10x total extracellular pool)

• reabsorption occurs in proximal tubule, where 90% of filtered load is returned to circulation
• proximal tubular phosphate reabsorption increases with increasing filtered load of phosphate, and approaches tubular max of phosphate reabsorption where transcellular phosphate transport becomes saturated, and rate of phosphate reabsorption becomes max and constant

Question 16

what are membrane transport mechanisms mediating transcellular phosphate reabsorption in nephron?

Answer 16

proximal tubule

• luminal side
• -active 3 Na+/HPO4– cotransport inside driven by Na gradient (Na-Pi-IIa)
• -active 2 Na+/H2PO4- cotransport (results in net positive charge transfer = electrogenic positive and sensitive to membrane potential as additional driving force increases concentrative, intracellular PO4 accumulation)
• basolateral side
• -passive efflux of intracellular PO4 mediated by possibly facilitated diffusion

Question 17

renal handling of AA

Answer 17

freely filtered at glomerulus and >98% reabsorbed across proximal tubule by AA-specific, transcellular transport mech mediating active uptake at luminal membrane (Na-symport) and passive efflux at basolateral membrane (facilitated diffusion)

Question 18

clearance of AA by kidney

Answer 18

essentially zero at normal circulating levels of AA
-kidney returns filtered AA to circulation, except when plasma AA are excessively high or when tubule defect in AA reabsorption exists, causing hyperaminoaciduria

Question 19

what are some “blood-born” solutes secreted from peritubular space to tubular lumen?

Answer 19

organic and inorganic:

• foreign to body (ingested drugs or toxins)
• metabolized by kidney for excretion by kidney
• metabolized by liver (glucuronidation, sulfation, carboxylation) for excretion by kidney
• regulated in blood (H+ and K+ concentration)

Question 20

renal handling of p-aminohippuric acid (PAH)

Answer 20

exogenous, monovalent organic anion freely filtered at glomerulus

• solute is secreted into tubular fluid, but NOT reabsorbed, so amount of PAH excreted in urine is function of filtered load and secreted from tubule
• at low circulating concentrations, PAH is so effectively secreted that clearance from renal circulation is complete, and no PAH exits kidney in renal vein
• when PAH increases, secretion of PAH is saturated, and it appears in renal vein

Question 21

what are membrane transport mechanisms mediating transcellular PAH secretion in nephron?

Answer 21

late proximal tubule

• basolateral
• -NaDC3: 3 Na+/dicarboxylate cotransport accumulates DC– inside cell driven by inwardly directed Na+
• -OAT1/3: antiport of PAH- inside for DC– outside (makes electrogenic negative and sensitive to membrane potential as driving force)
• luminal
• -passive facilitated diffusion
• -active anion/PAH- antiport driven by anion gradient

Question 22

how does renal clearance of PAH measure renal plasma flow

Answer 22

rate of plasma PAH entry into kidney in renal artery is equal to rate of solute exit from kidney in urine and renal vein

• if healthy, where all PAH entering peritubular capillaries is secreted into tubular fluid, none should exit via renal vein, so:
• -RPF x Ppah = Upah x V, so
• -RPF = clearance of PAH = (Upah x V)/Ppah

Question 23

renal handling of salicylate

Answer 23

circulates in plasma and is filtered in its neutral weak acid (HA) form and conjugate base (A-) form

• secretion: active (basolateral) and passive (luminal) transport of A- across proximal tubule
• -PAH and salicylates are substrates of same transproters mediating transcellular secretion
• reabsorption: passive process of nonionic diffusion across distal nephron (pH of tubular fluid is lowest)
• -decreases with increased tubular fluid pH and flow rates (increased clearance)
• -increases with decreasing tubular fluid pH and flow rates (decreased clearance)