4: Basic Transport Mechanisms Flashcards
Explain the main difference between tubular transport between the cortex and medulla
in regards to barriers and interstitial composition compared to plasma
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
What route for tubular epithelial crossing is more commong, paracellular or transcellular?
transcellular
What are the two steps for transcellular tubular transport?
across the apical membrane from the tubular lumen and across the basolateral membrane into the interstitium (absorption)
reversed for secretion
List 6 mechanism of cellular transmembrane transport
tubular
- Diffusion
- Uniporter
- Symporter
- Antiporter
- Ion channel
- Primary active transport
What determines the degree to which different substances can pass through the paracellular route in the tubule?
tight junction proteins - members of the claudin family
Compare the paracellular selectivity of the proximal tubule versus the thick ascending loop of Henle
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
can glucose move paracellular in the tubule?
no
What are the driving forces of diffusion?
- concentration gradient
- electrical potential gradient
Describe the structure of a cell membrane channel?
small pores - proteins with a “hole” through the inside of the protein
What do you call channels that allow diffusion of water?
aquaporins
After a transmembrane channel opens, what drives the movement of substances past the cell membrane?
the electrochemical gradient (i.e., concentration gradient and electrical potential gradient)
movement then is passive - no external energy required
What are the 4 different mechanisms regulating the permeability of cellular membrane channels?
- gated channels
- phosphorylation sites (either locks it shut or allows it to be gated)
- movement of channels into intracellular vesicles
- genomic expression of channels alters number of channels up or down
Give different examples of mechanisms of channel gating
- 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
What is the typical life span of a transmembrane channel or transporter?
a few hours
Compare the speed and magnitude at which transmembrane channels versus transporters transport solutes
- 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
How are transmembrane transporters regulated?
- phosphorylation
- sequestration into intracellular vesicles
- changes in genomic expression (determines density)
What does facilitated diffusion in the context of uniporters mean?
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
What kind of transporters are GLUT and where in the kidneys are they located?
uniporter
proximal tubule epithelial cells –> on the basolateral membrane
i.e., movement of glucose from the cytosol to the interstitiumn
What are the two types of multiporters?
Symporter - also called cotransporter
Antiporter - also called exchanger
What are SGLT transporters?
Sodum Glucose transporters
symporter –> move glucose and one or two Na+ into the cell
Explain the secondary active transport by symporters and antiporters
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
What is the NBCe transporter?
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
What is the stoichiometry of Na-K-ATPase?
moves three Na out and two K in for each ATP molecule hydrolyzes
Name 3 examples of primary active transporters
- Na-K-ATPase
- H-ATPase
- Ca-ATPase
What are the MDR proteins?
multidrug resistance proteins
class of primary active transporters»_space; move therapeutic drugs out of the cell
Explain how tubular cells take up and degrade proteins or how they transport proteins intact
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
what is osmolarity versus osmolality?
osmolarity - mOsm/L
osmolality - mOsm/kg
Define osmotic pressure and how do you calculate it?
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
Explain how semipermeable membranes are crucial for water movement by osmosis
only if a membrane is semipermeable can it establish a solute/osmole concentration gradient –> dragging water by osmosis
where in the kidneys is absorption iso-osmotic or not iso-osmotic and what does that mean?
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
the difference in osmolality over a semipermeable membrane of 1 mOsm/kg is equal to how much mm Hg in hydrostatic pressure?
19.3 mm Hg
What achieves polarization of tubular epithelial membranes
different proteins (channels and transporters) on each side of the cells (apical versus basolateral membrane)
Explain these steps
- Na-K-ATPase moves Na out of the tubular cells on the basolateral membrane –> Na cc in the cell drops
- Na moves down its concentration gradient into the cell - most of these go via the sodium-proton antiporter (NHE3 isoform)
- Anion will follow Na to preserve electroneutrality - mostly Cl- and HCO3-
- Water will move down its osmotic gradient/concentration gradient through aquaporin channels and the tight junctions which are permeable to water –> towards interstitium
- 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
Explain how solutes other than Na and the accompaning anions move from the proximal tubular space to the capillaries
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
What makes a solute’s reabsorption in the tubules gradient-limited?
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
What makes a solutes reabsorption in the tubules Tm-limited (tubular maximum limited)
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
Why does osmotic diuresis increase renal Na loss?
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
