Tubular Resorption and Secretion Flashcards
define resorption. why is it regulated?
movement of solutes and water from tubular fluid into the peritubular capillaries
regulated to maintain homeostatic balance with variable consumption
define secretion.
movements of solutes from peritubular capillaries into the tubular fluid
what is the ratio of organic and inorganic solute concentration in the plasma and the ultrafiltrate?
they are the same
what happens to most of the solutes and water in the tubular fluid?
they are reabsorbed and returned to circulation
what is the main mechanism of solute resorption?
primary active transport or coupling to energy stored in transmembrane ion concentrations
what is the main mechanism of water resorption?
passive
driven by the osmolarity gradient formed by solute resorption
describe paracellular transport
movement of solute and water through junctions of contiguous cell
what is transcellular transport dependent upon?
the coordinate function of solute specific transporters in the apical and basolateral membranes
transcellular transport mechanisms have what two specificities?
solute specificity and segment specificity
where in the renal epithelial cell is the Na/K pump located? what is its function?
in the basolateral membrane of all renal epithelial cells
creates concentration gradient of Na and K
what causes the inside negative membrane potential difference of renal epithelial cells?
K channel mediated high K conductance in either the lumen and/or basolateral membrane
describe primary active transport.
transports solutes against their concentration gradient by coupling to ATP hydrolysis
what are counter transporters?
ransporters that mediate transporter in either direction across the membrane depending on which of the coupled solutes has the larger gradient
what type of transport mechanism is involved in paracellular transport? what does it depend on?
passive
depends on tightness or solute specific resistance through the cell junctions
what methods of water and solute transport occurs across the intercellular junctions?
water- osmosis
solute- solvent drag
what are three methods of solute entry into the renal epithelial cell?
diffusion, cotransport and counter transport
tubular reabsorption of a solute may result from what two pathways?
1) active uptake at luminal menbrane and passive trasport at basolateral
2) passive uptake and active efflux at basolateral
tubular secretion of a solute may result from what two pathways?
1) active uptake at BL membrane and passive efflux into lumen
2) passive uptake a BL and active efflux at luminal membrane
describe the kinetics of transcellular resorption and secretion.
they are saturable
T max is achieved at a defined, solute specific plasma and/or tubular fluid solute concentrations
what inhibits transcellular resorption?
drugs and circulating metabolites
reabsorbed glucose can be determined by subtraction of what two numbers? what equation is used for this?
filtered glucose-excreted glucose
P glu x GFR - (U glu x V urine)
describe the renal handling of glucose.
it is filtered and reabsorbed, but not secreted.
reabsorbed only in the proximal tubule
what is the T max of glucose resorption? at physiologic concentration, what happens to the filtered glucose?
400 mg/min
it is all reabsorbed at physiological concentration
what happens to glucose not reabsorbed in the proximal tubule?
it is lost in the urine because other segments do not have the ability to transport it
when does clearance of glucose begin? what is it normally?
normally it is zero
begins to increase at plasma levels of 200mg/dL
what is the role of kidney in maintaining glucose homeostasis?
return glucose to circulation unless plasma levels are excessively high
describe glucose transport at the lumenal membrane of the PT.
Na/glucose cotransporter concentrates glucose inside the cell (driven by Na gradient)
2Na for every glucose transported- electrogenic
describe glucose transport at the basolateral membrane.
passive efflux mediated by facilitated diffusion
how does the amount of phosphate filtered into the ultrafiltrate compare to the total extracellular pool?
it is more than ten times the total
what happens to resorption of phosphates with increasing filtered load?
reabsorption increases and becomes constant when transcellular transport is saturated
at physiological phosphate concentrations, how is it handled by the kidney?
it is virtually all reabsorbed and a small amount is excreted.
where is phosphate reabsorbed in the nephron? how much remains in the urine?
most is absorbed in the proximal tubule and a small amount is absorbed in the distal convoluted tubule
10% is excreted
describe phosphate transport at the lumenal membrane of the proximal tubule.
Na/PO4 cotransporters driven by Na gradient- results in net positive transfer because 2-3 Na absorbed for every PO4 absorbed as HPO4 2-.
how does increasing tubular fluid acidity inhibit PO4 transport?
dibasic PO4 (HPO4 2-) is titrated to monobasic (H2PO4-) in an acidic solution. dibasic transport is therefore decreased
describe phosphate transport at the basolateral membrane of the proximal tubule.
passive efflux mediated by facilitated diffusion
where do circulating levels of amino acids come from?
GI absorption, protein catabolism and de novo synthesis
describe the renal handling of amino acids.
AA are filtered at the glomerulus and are completely reabsorbed by AA specific transcellular transport (mostly in the proximal tubule)
describe AA transport at the luminal and basolateral membrane.
Na/AA symport at the lumenal membrane and passive efflux at the basolateral membrane
what is the cause of aminoaciduria?
saturation of AA transport because of AA levels above a threshold concentration
either plasma AA is excessively high or there is a tubule defect in AA resorption
how do solutes from the blood enter the tubular fluid if they are not filtered out?
they are transcellularly secreted from the peritubular space to the tubular lumen
what solutes are secreted into the tubular fluid?
foreign solutes (drugs or toxins), those metabolized by the kidney and liver for excretion or those regulated in the blood (H+ and K+)
describe the renal handling of p-Aminohippuric acid (PAH)
PAH is freely filtered into the ultrafiltrate and then secreted into the tubular fluid but not reabsorbed
at low circulating PAH concentrations, how much is cleared from renal circulation?
all of it is excreted as urine
<10 mg/dL
describe the kinetics of PAH secretion into the renal tubule
it is saturable- when concentration in the plasma is increased above a certain point it is no longer all secreted into the tubule and some remains in circulation
what is the equation for secreted PAH?
secreted= excreted-filtered
= U PAH x V urine - (P PAH x GFR)
what is the PAH clearance compared to inulin?
C PAH/ C inulin > 1
where is most of the PAH secreted?
in the proximal tubule
describe transport of PAH in the proximal tubule basolateral membrane.
Na/ dicarboxlate (ketoglutarate) cotransporter mediated accumulation of dicarboxylate by Na gradient
organic anion antiporter exchanges ketoglutarate for extracellular PAH (1:1)
how is PAH transport affected by membrane potential?
because dicarboxylate/PAH exchange is electrogenic with net transfer of a negative charge out of the cell per cycle, it is influenced by the potential already present
describe proximal tubular PAH transport in the lumenal membrane.
efflux of PAH is passively and mediated by facilitated diffusion or it may be actively mediated by anion gradient driven antiport
what is an equation that can be used for the rate of PAH entry into the kidney?
RPF artery x P PAH
the rate at which PAH enters the kidney is the renal artery plasma flow rate multiplied by the plasma PAH concentration
what is an equation for PAH exit from the kidney?
RPF vein x P vein PAH + (U PAH x V urine)
sum of the amount of PAH exiting in the renal vein and in the urine
when the plasma levels of PAH are sufficiently low the rate of PAH entering the kidney equals what?
the rate of PAH leaving the kidney in the urine
how are PAH measurements used to determine renal plasma flow?
RPF= (U PAH x V urine)/ P PAH
it is equal to the clearance of PAH
how does PAH clearance compare to inulin clearance? what inferences does that make about renal function?
PAH is 4.5 fold the clearance of inulin (meausures GFR)
RPF is 4.5 fold greater than the GFR
what two forms is salicylate filtered in?
weak acid form (HA) and conjugate base form (A-)
describe the renal handling of salicylate.
salicylate is both secreted and reabsorbed
describe secretion of salicylate into the tubular fluid.
there is active basolateral transport and passive luminal transport of the conjugate base form across the proximal tubule
how is PAH and Salicylate transport similar?
uses the same active and passive transporters mediating transcellular secretion
describe resorption of salicylate out of the tubular fluid. how is it changed by tubular fluid pH and flow rates?
occurs by passive process of nonionic diffusion across the distal nephron (passive with no transporters)
decreases with increased tubular fluid pH and flow rates
increasees with decreasing tubular fluid pH and flow rates
where does resorption of salicylate occur? in what form is it transported?
occurs in the distal nephron where tubular fluid is more acidic
transported in the acidic form of the buffer. this form is increased with decreased pH
what drives diffusion of protonated salicylate across the basolateral membrane in resorption?
the difference in pH across the basolateral membrane where pH is lower in the cell creating a concentration gradient of protonated salicylate driving efflux into the peritubular space and capillaries
how does tubular fluid pH influence clearance of salicylate?
with decreased pH in the tubular fluid, the clearance of salicylate is decreased because more is reabsorbed
with increased pH, clearance is increased because less is reabsorbed
how can clearance of anionic drugs be related to salicylate clearance? how can this be related to drug overdose?
have similar renal handling.
upon overdose, IV infusion of bicarbonate at high enough concentration to saturate PT reabsorption will increase the pH of tubular fluid
promotes higher clearance of the anionic drug
