Renal Transport Mechanisms Flashcards
what are the two “routes” of transportation through tubular epithelium in the nephron
transcellular- requires a polarization of cells via segregating specific transporters to the apical and basolateral membranes. this creates a 2-step process where a solute uses one type of transporter to move into the cell and a different transporter to move out of the cell, usually one of which requires energy
paracellular- passive diffusion between cells with permeability and selectivity determined by tight junctions
what is the transport maximum (Tm). why is it important?
the maximum rate of reabsorption via the paracellular pathway.
it can be used to regulate normal concentrations of solutes by not allowing futhurr reabsorption when solute levels are already at the upper end of normal
what is the biggest energy demand on kidneys
creating concentration gradients for Na reabsorption
describe the coupled reabsorption of Na and HCO3
in the proximal tubule, H ions are pumped out of the cells via a Na/H exchanger (intracellular Na is low b/c of Na/K pumps on the apical surface). the H ions combine with HCO3 to form H2CO3, which is converted by carbonic anhydrase at the cell surface to H20 and CO2, which are then taken into the cell. H2CO3 is reformed intracellularly by carbonic anhydrase, which spontaneously dissociates to H and HCO3. Na and HCO3 are transported to the blood along with Na by a cotransporter. this system is entirely dependent on carbonic anhydrase activity
describe the sequential use of high capacity/low affinity and low capacity/high affinity transporters
Na is reabsorbed in the PT by a variety of co-transporters. transporters are put in series with increasing Na:Substrate ratios to ensure that all nutrients are reabsorbed within the Pt
how does osmolarity change along the PT
the tight junctions and cells are both permeable to water, allowing it to escape as substances are reabsorbed, holding the osmolariy relatively constant
what is solute drag?
as water leaves along its concentration gradient, its flow sweeps some of its solutes along for the ride
how does Cl concentration change along the length of the PT
because Na is being selectively reabsorbed, eventually the Cl concentration builds. This causes it to diffuse through the paracellular pathway out into the interstitium, which leaves a relatively positively charged lumen, which further promotes cation reabsorption
describe NaCl reabsorption via the second half of the PT
it begins with the Na/H exchanger on the apical surface, which puts 1 Na intracellularly for one H extracellularly. this H binds to an anion in the lumen and they are moved into the cell, where they dissociate. The anion moves into the cell using an A-/Cl- exchanger, such that a Cl- enters the cell and is removed basally by a K/Cl symporter
what is nonionic diffusion
the movment of a lipid soluble weak acid or base in their undissociated form. If there is a pH gradient causing dissociation, it can cause net movement
what is the “rate limiting” part of PT reabsorption
movement of fluid from the interstiitum to the peritubular capillary
thus, the oncotoic and hydrostatic pressures have a significant effect on reabsorption in the capillaries
what is glomerulotubular balance?
a constant fraction of filtrate (2/3) is reabsorbed, regardless of changes in the amount of filtrate
- Na reabsorption co transportation is limited by the availability of cotransported substances. more substances = more transport
- when GFR changes d/t efferent tone, it creates increased filtration and decreases peritubular oncotic pressure, maximizing reabsorption
- increased flow through the Pt is sensed via microvilli and causes increased Na reabsorption
what affect does angiotensin 2 have on the Pt?
increases the Na/H exchanger
what affect does the sympathetic nervous system have on the PT?
PT cells are directly innervated sympathetically and recieve feedback from low-pressure baroreceptors. low volume causes them to increase the Na/H exchanger
what are the 2 main inhibitors of Na reabsorption in the PT?
ANP (hormone) and Dopamine (autocrine excretion)
how are xenobiotics excreted?
they bind to high affinity receptors on the basolateral membrane and are excreted into the PT lumen. this process is effecient and nearly matches RBF
how are large proteins in the PT reabsorbed?
via receptor mediated endocytosis
how are small proteins in the PT reabsorbed?
via breakdown by ectopeptidases in the brush border of the PT and reabsorbed as AAs
is the LOH permeable to water? salt?
only descending is permeable to water. salt can travel through the ascending and descending limbs
what is the main mechanism for Na reabsorption in the LOH
Na/K/2Cl cotransporter. The K is in much lower concentration inside the lumen, so it must be recycled for continued use of the transporter. this creates a positive voltage inside the lumen
how does the nephron prevent calcification
divalent cations are transported paracellularly via the leaky tight junctions and the increased positive voltage inside the lumen d/t the cotransporter. There are receptors that sense extracellular Ca basolaterally, and if it becomes activated, it inhibits apical K channels, inhibiting the Na/K/2Cl cotransporter
how is the macula densa important in salt reabsorption
it uses the Na/K/2Cl cotransporter but reabsorbs a negligible amount.
instead, it senses overall NaCl load and gives feedback
how is Na removed in the distal tubule?
Na/Cl cotransporter
what are the 2 cell types in the CD and what do they do?
principle cells- solute transport
intercalated cells- acid/base regulation
