Lect 10: Proximal Tubule Flashcards Preview

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The PT receives the ultrafiltrate from the BS. How does it maintain ECF solute and fluid volume?

it maintains homeostasis by a process of separating solute and water from the plasma (filtration) and returning solute and water to the plasma (reabsorption).


Each segment of the nephron may be considered for its constitutive and regulatory function with regard to the renal handling of solutes and water.

CONSTITUITVE function (not regulatory-regardless of changes in ion homeostasis) occurs with little regulation and mediates a lesser renal response to changes in solute or water balance. The regulatory function of the different segments of the nephron mediates the renal response to changes in solute or water balance.


The PT is the nephron segment mediating

REABSORPTION of 67% both filtered water and salt and put back into circulation.


The PT fluid reabsorption occurs isosmotically, without a change in NaCl conc in the 33% of the tubular fluid remaining in the PT

The 33% had the same conc as the plasma conc. So there is equal proportion of water and solute in the PT.


The PT is a "leaky" epithelium meaning

that its resistance to water reabsorption is very low. A small difference in peritubular osmolarity relative to tubular osmolarity is enough to cause a drive this isosmotic fluid reabsorption from the tubular into the peritubular (BLOOD SIDE) out to renal vein


After the solutes are filtered in the glomerulus, the job of the PT is to reabsorp and return all of this back into

the blood via transcellular and pericelluar transport.


If the filtered load is more than the saturable load in the PT

it will appear in the urine....because there is no other way to reabsorb any of the solutes/glucose. This also means that the presence of glucose in the tubular lumen will raise the osmolarity pf the tubular fluid. By doing this you oppose the ability of the downstream segments to reabsorp fluids. This is why the pt. becomes dehydrated. Bc you can't reabsorb water in excess of solutes as well as you could if the solute wasn't there.


The PT mediates the SECRETION of organic anions (drugs, metabolites, diuretics) from the peri- capillaries to the lumenal fluid

where they remain until they are excreted into the urine.


The PT is also the nephron segment mediating the secretion of organic cations (drugs, metabolites) from

the peri- to the lumenal fluid where they remain and are excreted in the urine.


Solute conc from beginning to end

at the beginning the TF/P ratio is 1


Changes for Inulin: an increase in TF/P

Inulin is freely filtered at the glomerulus and is neither reabsorbed from nor secreted into the tubular fluid. It is pretty much trapped in the tubular fluid. An increase in TF/P for inulin indicates an increased conc of inulin in the TF resulting from the reabsorption of water from the tubular fluid. WATER IS LEAVING but inulin cannot leave


Changes for Na

A TF/P close to 1 for Na indicates the equivalent reabsorption of Na and water from the proximal tubular fluid resulting in a constant Na conc in the tubular fluid. 67% of the filtered Na and water is reabsorbed in the PT, the Na conc does not change and remains constant. Na conc in glomerular filtrate is 145


Changes for Cl-

The incerase in TF/P reflects the preferential reabsorption of HCO3 (transcellular) rather than Cl-- in the early PT.


Changes for HCO3, a.a and glucose--

The decrease in TF/P for HC03, amino acids and glucose indicates reabsorption from the tubular fluid, which contributes, as osmotic equivalents to driving the reabsorption of water


The change in transepithelial voltage from --3mV at the beginning of the PT to +3mV "downstream" results from the exit of more positive cationic charged solutes in first 25% of the PT

So there is more negative anionic charge left back. The slight excess of positive charge remaining in the TF in the form of cations creates the lumen positive transepithelial voltage difference measured across the tubule cell layer.


The change in the transepithelial voltage from --3mV to +3mV results from the net efflux and reabsorption of more positively charged, cationic solutes in the first 25% of the PT

and the net efflux anf reabsorption of more negatively charged, anionic solutes downstream in the remaining 75% of the PT. The slight excess of negative or positive charge in the tubular fluid in the form of anions or cations creates the lumen positive transepithelial voltage difference in the first 25% of the PT and creates the lumen net negative transepithelial voltage difference downstream in the remaining 75%


The conc HCO3, a.a. and glucose falls because

the PT is extracting them out of the tubular fluid and putting them back into the circulation


Paracellular and Trancellular

Paracellular: Na and Cl travels between cells through tight junctions

Transcellular: uptake across the lumenal membrane and efflux across the basal membrane or the lateral membrane


Na and Cl Reabsorption

The major driving force for Na uptake is the difference in electrochem potential. More Na is outside the cell than inside (15mM inside compared to 145mM outside) (due to Na/K pump)
Bc Na is positively charged all that negative charge inside is another driving force
3. There is a backleak: --3mV is the driving force that pulls Na that has been reabsorbed. 33% of the Na absorbed transcellularly back leaks into the TF paracellular


Transporters in the early PT

the Na/Glucose co-transporter transfers these two into the cell. Resulting in a a lumen negative charge (which is what drives the paracellular backleak of Na into the lumen of early PT. Co-transport creates the lumen neg voltage difference


Cl- transport occurs both betw cells (paracellular and transcelular) in the

EARLY and LATE PT. It is mediated by uptake of apical membrane and efflux at the basal & lateral membrane in the LATE PT.


What is responsible for paracellular Cl-- transport?

paracellular transport in the early convoluted PT (and late prox straight tubule) is driven by a lumen negative transepithelial voltage difference. it drives by repulsion (negitve lumen repels negative ions). Negative due to preferential HCO3- reabsorption in the early PT, lumenal Cl- conc is elevated above plasma Cl- conc in the late PT and an outward transepithelial Cl- conc gradient exists driving passive paracellular efflux of lumenal Cl-. The paracellular efflux of Cl- creates a lumen potential diffusion potential, which in turn drives paracellular efflux of Na in the late PT


Transcellular transport of Cl-

happens mainly in the late PT.
The active uptake of Cl- across the PT apical membrane occurs by Cl solute antiport driven by an outwardly directed anion conc gradient. The passive efflux of intracellular C--across the basolateral membrane is mediated by a Cl- channel and by a KCl symporter


Water Reabsorption

Most of the glomerular filtrate is returned to the circulation at the PT where reabsorption of tubular fluid occurs w/o a change in osmolarity.


The primary driving force for paracellar and transcellular water reabsorption is

the small osmotic gradient resulting from active solute reabsorption across the PT. This PT is very leaky and permits lots of water movement in response to small changes in the gradient. - aquaporins allow transcellular - ABSORPTION > filtration


How is paracellular movement of water happening?

it is driven by active Na-dependent increase in osmolarity in the lateral space entrains or sweeps Na and Cl within the flow in the direction of the peritubular capillary by a process of "solvent drag"


Role of PT in acid base balance (1)

Reabsorb and return most of the filtered HC03 to the circulation maintaining ECF HCO3 conc constant (24mL)


Role of PT in acid base balance (2)

Secretes H+ protons generated from acid metabolism, production of organic acids such as lactic acid and from intestinal bicarb loss, which may decrease THE BICRB conc in the plasma. Losing bicarb upsets the balance of acid-base so that extra proton that remain can also be secreted by the PT


Role of PT in acid base balance (3)

The process of secreting H generates "new" bicarb, which replaces HCO3 lost in buffering organic and inorganic acid. (When HCO3 buffers the H+ generated it becomes H2CO3 (it gets "lost") and needs to be replaced. If we lost HCO3 in the urine we would become acidotic and die. HCO3 conc has to be around 24mM


HCO3 reabsorption

On the lumenal side, there is a carbonic anhydrase enzyme which dehydrates HCO3 into OH and CO2. CO2 is extremely diffusible. OH combines with H to form HOH (water). The CO2 and H2O recombine intracellular to form HCO3 which moves out of the cell via a Na/HCO3 transporter. The Na/bicarb transporter (3HCO3: 2Na) has a --2 charge which serves as a driving force to push Na and HCO3 out of the cell against their conc difference