Tubular Reabsorption and Secretion

Question 1

reabsorption

Answer 1

• the movement of filtered solutes and water from the tubular fluid across the epithelial cell tubule into the peritubular capillaries and into the circulation
• regulated to maintain the homeostatic balance matching solute and water excretion to a variable solute and water consumption

Question 2

secretion

Answer 2

• movement of solutes from the circulation via the peri-tubular capillaries across the epithelial cell tubule into the tubular fluid
• another mechanism in addition to filtration by which solutes may be added to the tubular fluid and excreted in urine

Question 3

renal handling of solutes not excreted by the kidney

Answer 3

excreted= filtered+ secreted- reabsorbed

Question 4

general considerations

Answer 4

• concentration of filtered organic and inorganic solutes is the same in plasma and tubular ultrafiltrate. as solutes and water in the tubular fluid advance through the nephron, most water and solutes are reabsorbed and returned to circulation. urine is formed by the solutes and water not reabsorbed and by solutes secreted into tubular fluid
• most solute transport from lumen to peri-tubular space across the tubular epithelium is active and driven by energy released from ATP hydrolysis or secondary active transport
• some solute transport from lumen to peri-tubular space is passive and not driven by ATP hydrolysis
• water transport from lumen to peri-tubular space across the tubular epithelium is passive and occurs by osmosis, driven by the difference in osm in the tubular lumen and peritubular spce
• where osm high, water low, water moves down concentration gradient

Question 5

osmolarity

Answer 5

• solutes go to peritubular space and increase water concentration in tubular space and decrease it in the peri-tubular space
• water then follows

Question 6

renal epithelial transport

Answer 6

transport of solutes is:

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

Question 7

transcellular transport

Answer 7

• dependent on the coordinate function of solute specific transporters in the apical membrane facing the tubular fluid in the lumen and in the basolateral membrane facing the peritubular space and caps
• solute specific and nephron segment specific transport mechanisms mediate water and solute transport in different segments of the nephron
• Na/K pump is restricted to basolateral membrane of all renal epithelial cells in all segments of the nephrons. it maintains a steady state concentration difference- Na less in and K greater in, Na more out and K less out
• K channel, high K conductance in either luminal or basolateral membrane maintains the steady state, inside negative membrane potential difference

Question 8

transcellular transport 2

Answer 8

• lumenal and basolateral solute transport mechanisms are defined as active or passive depending on their ability to transport solutes in a direction across the cell membrane against a solute electrochemical gradient
• active transport mechanisms mediate inward or outward solute transport across the cell membrane in a direction against solute gradient and require energy
• primary active transport mechanisms capture and transduce the energy of ATP hydrolysis to the energy stored in the formation of a solute electrochemical potential gradient

Question 9

secondary active transport

Answer 9

-transduce energy stored in the electrochemical potential gradient of one solute into another solute

Question 10

co-transporters

Answer 10

• symporters
• couple driving and driven solute in same direction across membrane
• driving solute usually inwardly directed extracellular to intracellular transmembrane Na gradient
• Na down concentration gradient and brings something with it against the something’s concentration gradient

Question 11

counter transporters

Answer 11

• anti-porters
• driving and driven in opposite direction
• mediate transport in either direction across the membrane depending on which of the coupled solutes has larger gradient

Question 12

passive transport

Answer 12

• mediate solute transport across the cell membrane down a solute electrochemical potential gradient in either inward or outward direction and do not require coupling to a source of energy
• facilitated or not
• channels/pores

Question 13

paracellular transport

Answer 13

• passive and driven by a transepithelial solute electrochemical potential gradient
• depends on tightness or solute specific resistance to transport through intracellular junctions
• the ability of epithelia to maintain a trans-epithelial voltage difference or an osmotic gradient is determined by the cell to cell junctional resistance or leakiness of the epithelium to solute and water transport across the junction
• movement of water from the tubular lumen across the intercellular junctions to the peritubular space occurs by osmosis and may entrain the movement of solute by a process of solvent drag, which contributes to transtubular solute reabsorption or secretion

Question 14

functional properties of transcellular transepithelial transport

Answer 14

• coordinate function of solut specific active and passive transporters in series, in opposing membranes mediates bi directional transcellular transepithelial transfer of solutes between the tubular fluid and the peritubular space
• reabsorption and secretion is saturable and a maximum rate is achieved at defined, solute specific, plasma and/or tubular fluid solute concentrations
• transcellular reabsorption and secretion is inhibitable by drugs and circulating metabolites

Question 15

tubular reabsorption of a solute may result from

Answer 15

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

Question 16

tubular secretion can result from

Answer 16

1. active transport uptake at the basolateral membrane and passive efflux at the lumenal membrane
2. passive uptake at the basolateral membrane and active efflux at the lumenal membrane

Question 17

reabsorbed glucose

Answer 17

-filtered glucose- excreted glucose

Question 18

excreted glucose

Answer 18

filtered glucose-reabsorbed glucose

Question 19

reabsorbed glucose

Answer 19

Pglu x GFR- Uglu x Vurine

Question 20

renal handling of glucose

Answer 20

• filtration and reabsorption but not secretion
• amt of glucose in urine is a function of amt filtered and amt absorbed
• absorbed in the proximal tubule

Question 21

glucose reabsorption

Answer 21

• circulates between 75- 170 mg/ dl
• freely filtered from plasm at glomerulus
• at normal levels all is reabsorbed at proximal tubule
• clearance of glucose is zero at normal but begins to increase around levels of 200 mg/dl-threshold plasma concentration

Question 22

Tm

Answer 22

• tubular reabsorptive maximum
• maximum solute reabsorptive rate or capacity for tubular solute reabsorption
• as plasma solute concentration approaches Tm, the transport mechanisms get saturated and solute begins to appear in urine

Question 23

membrane transport mechanisms for glucose

Answer 23

lumenal membrane:

• Na-glu cotransporters mediate concentrative accumulation of glucose inside the cell driven by inwardly directed Na current
• ratio is 1:2:1, resulting in net positive charge transfer with each glucose transported; electrogenic and sensitive to membrane potential as an additional DF to increase glucose concentration

basolateral membrane:
passive efflux of intracellular glucose mediated by facilitated diffusion (uniporter)

Question 24

excreted PO4

Answer 24

-filtered - reabsorbed

Question 25

reabsorbed PO4

Answer 25

filtered- excreted

PO4 x GFR- Upo4 x V urine

Question 26

filtered load of phosphate

Answer 26

• 250 mMole/day, more than 10x the extracellular pool
• reabsorption in proximal tubule, 90% of filtered load returned to circulation
• reabsorption increases with increasing filtered load of phosphate and approaches a tubular maximum of phosphate reabsorption where the process of transcellular transport becomes saturated and rate of reabsorption is maximal and constant

Question 27

renal handling of PO4

Answer 27

• linear relationships for filtered and excreted
• Tm is maximum amt reabsorbed
• at normal levels, almost all reabsorbed

Question 28

transcellular phosphate mechanisms

Answer 28

Lumenal membrane:

• Na/PO4 co transporters
• 2:3:1- net positive transfer with each PO4 transported
• sensitive to membrane potential as an additional DF
• titration of dibasic to monobasic by increasing tubular fluid acidity inhibits PO4 transport by decreasing the concentration of dibasic PO4 and the transport of dibasic PO4

basolateral membrane:
-passive efflux

Question 29

renal handling of amino acids

Answer 29

-circulating levels of aa arise from GI absorption, protein catabolism and de novo synthesis
-filtered at glomerulus and completely reabsorbed across proximal tubule by AA specific, transceullular transport mechanisms mediating
-active uptake at the luminal membrane (Na-symport) and passive efflux at basolateral membrane (facilitated diffusion)
-saturable above Tm, then above are excreted in urine
-

Question 30

secretion 2

Answer 30

• blood borne solutes enter tubular fluid by transcellular secretion from peritubular space to the tubular lumen across various segments of the nephron
• foreign to the body- toxins/drugs
• metabolized by kidney for excretion by kidney
• metabolized by the liver (glucuronidation, sulfation) for excretion by kidney
• regulated in blood

Question 31

renal handling of PAH

Answer 31

• secreted =excreted- filtered
• excreted= filtered+ secreted
• secreted = Upah x V urine - Ppah x GFR
• secreted into tubule
• amt of PAH excreted is a function of amy filtered and amt secreted

Question 32

renal handling of PAH 2

Answer 32

• exogenous, monovalent organic ion
• freely filtered
• at low circulating levels, so effectively secreted by the proximal tubule that its clearance form the renal circulation is complete and no PAH exits the kidney in the renal vein
• Tm is tubular secretion maximum, defines max rate
• as plasma concentration of PAH increase, Tm for PAH achieved, transport mechs become saturated and PAH appears in renal vein
• PAH secretion becomes a smaller fraction of the PAH in the urine, the PAH filtration becomes larger fraction of amt in urine

Question 33

PAH transcellular transport mechanisms

Answer 33

basolateral membrane:

• Na/ dicarboxylate co transporter mediates accumulation of ketoglutarate inside the cell
• and organic anion antiporter mediates concentrative exchange of intracellular ketoglutarate for extracellular PAH
• 1:1, but divalent for monovalent, so net negative charge out of cell, which is another DF to get PAH in

lumenal membrane:

• efflux of PAH by facilitated diffusion
• or actively by anion gradient driven antiport

Question 34

excretion of PAH measures renal plasma flow

Answer 34

• rate of plasma solute entry into the kidney in the renal artery is equal to the rate of solute exit from the kidney into the urine and renal veins
• rate PAH entering kidney=rate PAH leaving
• RPF x Ppah= RPFvein x Pvein PAH + U pah x V urine

when all is excreted, RPF x Ppah= Upah x V, RPF= Upah x V / Ppah**

rate of PAH entering = RPF x P pah

Question 35

renal handling of salicylate

Answer 35

-circulates in plasma and is filtered in its neutral weak acid for and conjugate base form

Question 36

secretion of salicylate

Answer 36

• active basolateral and passive luminal transport of the conjugate base across proximal tubule
• PAH and salicylate are substrates of the same active basolateral and passive luminal transporters

Question 37

reabsorption of salicylate

Answer 37

• occurs primarily by the passive process of non-ionic diffusion across the distal nephron
• decreases with increased tubular fluid pH and flow rates
• increases with decreasing tubular fluid pH and flow rates

Question 38

pH and salicylate

Answer 38

-when pH is high, there is secretion, at low pH there is reabsorption