Lect 9: Tubular reabsorption & Secretion

Question 1

What is reabsorption?

Answer 1

it is the movement of filtered solutes and water from the tubular fluid across the epithelial cell tubule into the peritubular capillaries and the circulation

Question 2

What is secretion?

Answer 2

moving solutes from the circulation via the peritubular capillaries across the epithelial cell tubule into the tubular fluid.

Solutes can be secreted but water cannot

Question 3

Two types of renal transport, what are they?

Answer 3

Transcellular and paracellular (solutes and water moving through cell junctions)

Question 4

Transcellular Transport

can be actve or passive

Answer 4

depends on transporters facing the tubular fluid in the lumen and in the basolateral membrane facing the peritubular space and capillaries

Question 5

What is the function of the Na/K ATPase?

Answer 5

it is found only on the basolateral side of all renal epithelial cells within the nephron where it maintains the Na gradient (Na high outside, K high inside…important for creating the inside negative membrane potential)

Question 6

Secondary active transport can occur

Answer 6

in the same direction across the membrane (co-transport) or it could be transported in the opposite direction (counter-transport) depending on which solute has the greater gradient

Question 7

Passive Transcellular transport

Answer 7

channels, uniporters

Question 8

Paracellular transport

Answer 8

passive, and is driven by a transepithelial solute EC potential gradient; permeability property of the junctional resistance or leakiness between cells makes it tight o

Question 9

Movement of water from the tubular lumen across the intracellular junctions to the peritubular space occurs by

Answer 9

osmosis (because it is following the increased osmolarity) and may entrain the movement of solute by a process of “solvent drag” which contributes to transtubular solute reabsorption or secretion

Question 10

Tubular reabsorption of a solute can occur from

Answer 10

active transport (uptake) at the the lumen and passive transport at the basolateral membrane OR passive transport at the lumen and active transport at the basolateral membrane. The same is true for secretion

Question 11

Transcellular reabsorption and secretion is inhibited by drugs

Answer 11

such as diuretics and circulating metabolites.

Question 12

Which direction is reabsorption?

Answer 12

lumen to blood

Question 13

Which direction is secretion?

Answer 13

blood to lumen

Question 14

Renal Handling of Glucose: What is the equation for reabsorbed glucose?

Answer 14

Reabsorbed glucose = filtered glucose – excreted glucose
Filtered glucose: Pglu x GFR – Ugl x Vurine (rate of urine flow)
Excreted glucose is usually 0

Question 15

Glucose Titration Curve

Answer 15

looks at the effect of raising glucose conc on the filtered load, reabsorption and the excretion of glucose

Question 16

Increasing the plasma conc of glucose, what happens to the filtered load?

Answer 16

it goes up linearly.

Question 17

At 5-10mM of glucose, how much of it is in the urine?

Answer 17

None of it. It is ALL REABSORBED but as we continue to increase the glucose conc, glucose begins to appear in the urine over 15mM….because we have saturated the proximal tubule to reabsorb the glucose.

–happens in diabetes mellitus

Question 18

Glucose Clearance

Answer 18

C = U x V/ Pgl clearance is normally 0 but if you continue to incerase the plasma glucose conc then this formula becomes greater than 0.
==>Cgl/Cin will always be lower than inulin, less than 1, indicating reabsorption

Question 19

Membrane Transport mediating transcellular glucose reabsorption on the lumenal side - active uptake with passive efflux

Answer 19

Lumenal membrane: Na-glucose cotransporter mediate the accumulation of glucose inside the cell via the inwardly directed Na-electrochemical potential gradient (SGLT2).

Question 20

How is SGLT1 special?

Answer 20

the Na-glucose transport or coupling ratio is 1 to 2 to 1 resulting in net positive charge transfer with each glucose transported. Adding two Na concentrates glucose inside the cell to a much higher level

Question 21

What about transporters on the basolateral membrane?

Answer 21

passive efflux mediated by facilitated diffusion

Question 22

Phosphate Reabsorption

Answer 22

occurs in the proximal tubule and it increases with increasing filtered load. This reaches a maximum phosphate where the process of transcellular phosphate transport becomes saturated and the rate of phosphate reabsorption becomes maximal and constant.

Question 23

Phosphate reabsorption similar to glucose

Answer 23

active uptake at the apical membrane and passive efflux at the basolateral membrane

Question 24

Reabsorption of Amino Acids

Answer 24

active uptake at the apical membrane and passive efflux at the basolateral membrane

Question 25

Secretion …into the urine

Answer 25

Many blood borne solutes enter the fluid by transcellular secretion from the perutibular space to the lumen across the segments of the nephron

Question 26

Renal Handling of PAH

Answer 26

….PAH is a secreted molecule
is an example of a solute which is secreted into the tubular fluid but not reabsorbed from the tubular fluid.

The amount of PAH excreted in the urine is a function of the amount filtered as well as the amount secreted by the tubule. Comtrast the renal handling of PAH with the renal handling of glucose, which are reabsorbed but not secreted

Question 27

Formula for Secretion

Answer 27

secreted PAH = Excreted PAH – Filtered PAH

Excretion > Filtered in secretion

Question 28

PAH Clearance

Answer 28

clearance of PAH is much greater than the clearance of inulin.

At low plasma PAH conc the clearance of PAH equals RPF (renal plasma flow)

Question 29

As plasma solute conc increases and approaches the tubular secretion maximum, the cellular transport processes mediating solute secretion become saturated and plasma solute conc begins to increase.

Answer 29

you will begin to see PAH in the renal vein.
==> At increasing plasma PAH conc where secretion becomes saturated, the secretory tubular maximum for PAH is achieved and PAH secretion becomes proressively smaller fraction of the amount of PAH in the urine and PAH filtration becomes a progressively larger fraction of the amount of PAH in the urine

Question 30

How does the clearance of PAH equal the RPF?

Answer 30

At 100% of the filtered load, you have 500% secreted you have 600% remaining in the tubule and ultimately excreted in urine.

Question 31

On the BASOLATERAL side you have the

Answer 31

Na- dicarboxylate cotransporter that mediates the accumulation of dicarboxylate inside the cell driven by the inwardly directed Na gradient. this gradient becomes a driving force for PAH uptake into the cell

Question 32

An antiporter OAT 1 or OAT3 mediates

Answer 32

the exchange of intracellular ketoglutarate for extracellular PAH. The ketoglutarate to PAH transport is 1 to 1 resulting in a net NEGATIVE charge transfer out of the cell with each PAH transported. ==> This makes the organic anion antiport electronegative and sensitive to membrane potential as an additional driving force increasing concentrative PAH accumulation

Question 33

PAH uptake is an example of which type of transport

Answer 33

tertiary

Question 34

Clearance of PAH measures renal plasma flow

Answer 34

PAH going in = PAH going out (bc it is not metabolized)
==>PAH, enters via renal artery= rate of this = RPF x Ppah
==>PAH exit via renal vein: PRF x Pveinpah + Upah x V

Question 35

All of it exits via urine, not the vein

So RPFvein x Pvein PAH = 0

Answer 35

RPF x pah = Upah X V

therefore RPF = Upan x V/ Ppah = Clearance of PAH