Renal Transport Mechanisms

Question 1

what are the two “routes” of transportation through tubular epithelium in the nephron

Answer 1

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

Question 2

what is the transport maximum (Tm). why is it important?

Answer 2

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

Question 3

what is the biggest energy demand on kidneys

Answer 3

creating concentration gradients for Na reabsorption

Question 4

describe the coupled reabsorption of Na and HCO3

Answer 4

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

Question 5

describe the sequential use of high capacity/low affinity and low capacity/high affinity transporters

Answer 5

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

Question 6

how does osmolarity change along the PT

Answer 6

the tight junctions and cells are both permeable to water, allowing it to escape as substances are reabsorbed, holding the osmolariy relatively constant

Question 7

what is solute drag?

Answer 7

as water leaves along its concentration gradient, its flow sweeps some of its solutes along for the ride

Question 8

how does Cl concentration change along the length of the PT

Answer 8

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

Question 9

describe NaCl reabsorption via the second half of the PT

Answer 9

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

Question 10

what is nonionic diffusion

Answer 10

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

Question 11

what is the “rate limiting” part of PT reabsorption

Answer 11

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

Question 12

what is glomerulotubular balance?

Answer 12

a constant fraction of filtrate (2/3) is reabsorbed, regardless of changes in the amount of filtrate

1. Na reabsorption co transportation is limited by the availability of cotransported substances. more substances = more transport
2. when GFR changes d/t efferent tone, it creates increased filtration and decreases peritubular oncotic pressure, maximizing reabsorption
3. increased flow through the Pt is sensed via microvilli and causes increased Na reabsorption

Question 13

what affect does angiotensin 2 have on the Pt?

Answer 13

increases the Na/H exchanger

Question 14

what affect does the sympathetic nervous system have on the PT?

Answer 14

PT cells are directly innervated sympathetically and recieve feedback from low-pressure baroreceptors. low volume causes them to increase the Na/H exchanger

Question 15

what are the 2 main inhibitors of Na reabsorption in the PT?

Answer 15

ANP (hormone) and Dopamine (autocrine excretion)

Question 16

how are xenobiotics excreted?

Answer 16

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

Question 17

how are large proteins in the PT reabsorbed?

Answer 17

via receptor mediated endocytosis

Question 18

how are small proteins in the PT reabsorbed?

Answer 18

via breakdown by ectopeptidases in the brush border of the PT and reabsorbed as AAs

Question 19

is the LOH permeable to water? salt?

Answer 19

only descending is permeable to water. salt can travel through the ascending and descending limbs

Question 20

what is the main mechanism for Na reabsorption in the LOH

Answer 20

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

Question 21

how does the nephron prevent calcification

Answer 21

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

Question 22

how is the macula densa important in salt reabsorption

Answer 22

it uses the Na/K/2Cl cotransporter but reabsorbs a negligible amount.

instead, it senses overall NaCl load and gives feedback

Question 23

how is Na removed in the distal tubule?

Answer 23

Na/Cl cotransporter

Question 24

what are the 2 cell types in the CD and what do they do?

Answer 24

principle cells- solute transport

intercalated cells- acid/base regulation

Question 25

how is Na removed in the collecting duct?

Answer 25

Na moves passively b/c of the concentration gradient and the voltage gradient. its removed apically with the Na/K pump. K is removed apically

Question 26

how does aldosterone affect Na reabsorption in CD?

Answer 26

it stimulates Na reabsorption

Question 27

how does ANP affect Na reabsorption in CD?

Answer 27

it inhibits Na reabsorption

Question 28

how does ADH affect Na reabsoprtion in CD?

Answer 28

it causes aquaporin 2 to be inserted into the basolateral membrane to allow passage of h2o into the interstitium.

Question 29

which areas of the nephron are permeable to urea?

Answer 29

the Pt and thin loops of henle