4: Basic Transport Mechanisms

Question 1

Explain the main difference between tubular transport between the cortex and medulla

in regards to barriers and interstitial composition compared to plasma

Answer 1

cortex: peritubular capillaries are abundent and fenestrated –> water and small solutes flow easily and passively from the interstitium into the capillaries
* cortical transport between blood and tubules relies on tubular epithelium rather than vascular endothelium
* cortical interstitium is similar to plasma composition

Medulla: less blood flow and less fenestration
* medullary transport between blood and tubules relies on both vascular and tubular properties
* medullary interstitium is different to the plasma composition

Question 2

What route for tubular epithelial crossing is more commong, paracellular or transcellular?

Answer 2

transcellular

Question 3

What are the two steps for transcellular tubular transport?

Answer 3

across the apical membrane from the tubular lumen and across the basolateral membrane into the interstitium (absorption)

reversed for secretion

Question 4

List 6 mechanism of cellular transmembrane transport

tubular

Answer 4

• Diffusion
• Uniporter
• Symporter
• Antiporter
• Ion channel
• Primary active transport

Question 5

What determines the degree to which different substances can pass through the paracellular route in the tubule?

Answer 5

tight junction proteins - members of the claudin family

Question 6

Compare the paracellular selectivity of the proximal tubule versus the thick ascending loop of Henle

Answer 6

Proximal tubule - permeable to small ions, e.g., Na, K, and water, urea
Thick ascending loop of Henle - permeable to Na, K, NOT water or urea

Question 7

can glucose move paracellular in the tubule?

Answer 7

no

Question 8

What are the driving forces of diffusion?

Answer 8

• concentration gradient
• electrical potential gradient

Question 9

Describe the structure of a cell membrane channel?

Answer 9

small pores - proteins with a “hole” through the inside of the protein

Question 9

What do you call channels that allow diffusion of water?

Answer 9

aquaporins

Question 10

After a transmembrane channel opens, what drives the movement of substances past the cell membrane?

Answer 10

the electrochemical gradient (i.e., concentration gradient and electrical potential gradient)
movement then is passive - no external energy required

Question 11

What are the 4 different mechanisms regulating the permeability of cellular membrane channels?

Answer 11

1. gated channels
2. phosphorylation sites (either locks it shut or allows it to be gated)
3. movement of channels into intracellular vesicles
4. genomic expression of channels alters number of channels up or down

Question 12

Give different examples of mechanisms of channel gating

Answer 12

• ligand-gated channels: reversible binding of small molecules as part of signaling cascades
• voltage-gated channels: changes in membrane potential
• stetch-gated channels: mechanical distortion of channel

Question 13

What is the typical life span of a transmembrane channel or transporter?

Answer 13

a few hours

Question 14

Compare the speed and magnitude at which transmembrane channels versus transporters transport solutes

Answer 14

• channels can very quickly move large amounts of solutes
• transporters have a lower rate of transport because of solutes binding strongly to the transport protein and because the protein needs to undergo a cycle of conformational changes

Question 15

How are transmembrane transporters regulated?

Answer 15

• phosphorylation
• sequestration into intracellular vesicles
• changes in genomic expression (determines density)

Question 16

What does facilitated diffusion in the context of uniporters mean?

Answer 16

rather than allowing direct diffusion (e.g., through the hole of a channel), uniporter undergoes configuration flip, making the solute move through the protein itself and be transported to the other side

Question 17

What kind of transporters are GLUT and where in the kidneys are they located?

Answer 17

uniporter
proximal tubule epithelial cells –> on the basolateral membrane
i.e., movement of glucose from the cytosol to the interstitiumn

Question 18

What are the two types of multiporters?

Answer 18

Symporter - also called cotransporter
Antiporter - also called exchanger

Question 19

What are SGLT transporters?

Answer 19

Sodum Glucose transporters
symporter –> move glucose and one or two Na+ into the cell

Question 20

Explain the secondary active transport by symporters and antiporters

Answer 20

one of the solutes will move up its electrochemical gradient and acquires the energy to do so by the other solute moving down its electrochemical gradient

stoichiometry explains the balance of energy available by movement of solutes down its electrochemical gradient

Question 21

What is the NBCe transporter?

Answer 21

electrogenic sodium-bicarbonate co-transporter
* moves three bicarbonate ions and one sodium ion out of the cell
* bicarbonate moves down and sodium up its electrochemical gradient

Question 22

What is the stoichiometry of Na-K-ATPase?

Answer 22

moves three Na out and two K in for each ATP molecule hydrolyzes

Question 23

Name 3 examples of primary active transporters

Answer 23

• Na-K-ATPase
• H-ATPase
• Ca-ATPase

Question 24

What are the MDR proteins?

Answer 24

multidrug resistance proteins
class of primary active transporters&raquo_space; move therapeutic drugs out of the cell

Question 25

Explain how tubular cells take up and degrade proteins or how they transport proteins intact

Answer 25

receptor-mediated endocytosis –> protein is bound on the apical surface of tubular epithelial cells –> patch of membrane is internalized as a vesicle –> protein is being degraded into its amino acids –> AAs are released across the basolateral membrane

transcytosis –> protein is taken up by a vesicle but transported intact to the other side

Question 26

what is osmolarity versus osmolality?

Answer 26

osmolarity - mOsm/L
osmolality - mOsm/kg

Question 27

Define osmotic pressure and how do you calculate it?

Answer 27

osmotic pressure is the pressure that theoretically would have to be applied to a solution on one side of a barrier to prevent the movement of water into it by osmosis of pure water from the other side

van’t Hoff equation give the osmotic pressure

osmotic pressure = gas constant x absolute temperature x osmolality

usually osmolality x 19.3 in mm Hg

Question 28

Explain how semipermeable membranes are crucial for water movement by osmosis

Answer 28

only if a membrane is semipermeable can it establish a solute/osmole concentration gradient –> dragging water by osmosis

Question 29

where in the kidneys is absorption iso-osmotic or not iso-osmotic and what does that mean?

Answer 29

in the proximal tubules absorption is isoosmotic –> osmoles/solutes are absorbed proportionately to water

beyond the proximal tubules absorption is not isoosmotic –> water and solute reabsorption are not proportional

Question 30

the difference in osmolality over a semipermeable membrane of 1 mOsm/kg is equal to how much mm Hg in hydrostatic pressure?

Answer 30

19.3 mm Hg

Question 31

What achieves polarization of tubular epithelial membranes

Answer 31

different proteins (channels and transporters) on each side of the cells (apical versus basolateral membrane)

Question 32

Explain these steps

Answer 32

1. Na-K-ATPase moves Na out of the tubular cells on the basolateral membrane –> Na cc in the cell drops
2. Na moves down its concentration gradient into the cell - most of these go via the sodium-proton antiporter (NHE3 isoform)
3. Anion will follow Na to preserve electroneutrality - mostly Cl- and HCO3-
4. Water will move down its osmotic gradient/concentration gradient through aquaporin channels and the tight junctions which are permeable to water –> towards interstitium
5. Due to water movement into the interstitium the hydrostatic pressure will rise here - concurrently the peritubular capillaries will have a higher oncotic pressure because glomerular filtration made their protein cc increase –> Starling’s forces will allow net movement of water from interstitium into capillaries

capillary hydrostatic pressure about 15-20 mm Hg
capillary oncotic pressure rises above 30 mm Hg here

Question 33

Explain how solutes other than Na and the accompaning anions move from the proximal tubular space to the capillaries

Answer 33

when 2/3 of Na and water are removed –> every other solute not removed increases in concentration by 3 fold

will establish a concentration gradient of this solute between the tubular space and the interstitium (same as plasma due to high peritubular blood flow in the cortex)

the solute can then move following its concentration gradient IF the pericellular tight-functions are permeable enough for the solute in question

e.g., urea, K, Ca, Mg can move
glucose cannot pass tight-junctions

Question 34

What makes a solute’s reabsorption in the tubules gradient-limited?

Answer 34

gradient-limited system:
tight-junctions between tubular cells are permeable to the solute

if there is “too much” solute moved from the tubular space to the interstitium, i.e., concentration in the interstitium rises above the tubular space, the solute will “leak” back
- tubular reabsorption will be limited by this gradient

in the case of sodium, the tubules can still reabsorb a large amount becasue water is being absorbed concurrently –> keeping the Na cc lower than if only Na was absorbed alone

Question 35

What makes a solutes reabsorption in the tubules Tm-limited (tubular maximum limited)

Answer 35

means that the tight junctions between cells are not permeable to the solute –> the concentration gradient between interstitium and tubular space will not generate back-flow

the absorption will be limited by the densite of the designated transporter or channel allowing the solute to move

e.g., glucose

Question 36

Why does osmotic diuresis increase renal Na loss?

Answer 36

Na’s reabsorption is the proximal tubules is gradient-limited, i.e., tight-junctions between cells let it diffuse freely

if there is a high amount of osmoles (e.g., mannitol or glucose) in the tubular space, water cannot move with the sodium to the same extent –> the interstitial Na cc will actually rise above the tubular and Na will leak back from the interstitium to the tubular space