Lect 9: Tubular reabsorption & Secretion Flashcards
What is reabsorption?
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
What is secretion?
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
Two types of renal transport, what are they?
Transcellular and paracellular (solutes and water moving through cell junctions)
Transcellular Transport
can be actve or passive
depends on transporters facing the tubular fluid in the lumen and in the basolateral membrane facing the peritubular space and capillaries
What is the function of the Na/K ATPase?
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)
Secondary active transport can occur
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
Passive Transcellular transport
channels, uniporters
Paracellular transport
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
Movement of water from the tubular lumen across the intracellular junctions to the peritubular space occurs by
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
Tubular reabsorption of a solute can occur from
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
Transcellular reabsorption and secretion is inhibited by drugs
such as diuretics and circulating metabolites.
Which direction is reabsorption?
lumen to blood
Which direction is secretion?
blood to lumen
Renal Handling of Glucose: What is the equation for reabsorbed glucose?
Reabsorbed glucose = filtered glucose – excreted glucose
Filtered glucose: Pglu x GFR – Ugl x Vurine (rate of urine flow)
Excreted glucose is usually 0
Glucose Titration Curve
looks at the effect of raising glucose conc on the filtered load, reabsorption and the excretion of glucose
Increasing the plasma conc of glucose, what happens to the filtered load?
it goes up linearly.
At 5-10mM of glucose, how much of it is in the urine?
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
Glucose Clearance
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
Membrane Transport mediating transcellular glucose reabsorption on the lumenal side - active uptake with passive efflux
Lumenal membrane: Na-glucose cotransporter mediate the accumulation of glucose inside the cell via the inwardly directed Na-electrochemical potential gradient (SGLT2).
How is SGLT1 special?
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
What about transporters on the basolateral membrane?
passive efflux mediated by facilitated diffusion
Phosphate Reabsorption
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.
Phosphate reabsorption similar to glucose
active uptake at the apical membrane and passive efflux at the basolateral membrane
Reabsorption of Amino Acids
active uptake at the apical membrane and passive efflux at the basolateral membrane
Secretion …into the urine
Many blood borne solutes enter the fluid by transcellular secretion from the perutibular space to the lumen across the segments of the nephron
Renal Handling of PAH
….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
Formula for Secretion
secreted PAH = Excreted PAH – Filtered PAH
Excretion > Filtered in secretion
PAH Clearance
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)
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.
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
How does the clearance of PAH equal the RPF?
At 100% of the filtered load, you have 500% secreted you have 600% remaining in the tubule and ultimately excreted in urine.
On the BASOLATERAL side you have the
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
An antiporter OAT 1 or OAT3 mediates
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
PAH uptake is an example of which type of transport
tertiary
Clearance of PAH measures renal plasma flow
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
All of it exits via urine, not the vein
So RPFvein x Pvein PAH = 0
RPF x pah = Upah X V
therefore RPF = Upan x V/ Ppah = Clearance of PAH
