Flashcards in Renal Chapter 4: Basic Transport Mechanisms Deck (50)
Basic process of moving substances between blood and tubular lumen require solutes and water to cross what?
2 cell layers: tubular epithelium and vascular endothelium plus region of interstitial fluid between then
in cortex where fluxes of filtered substances are huge, vascular endothelium (peritubular capillaries) is fenestrated ...fenestrae and loose underlying basement membrane offer virtually no resistance to the passive movement of water and small solutes
What are two consequences of the fact that fenestrae and loose underlying basement membrane offer virtually no resistance to the passive movement of water and small solutes in cortex?
(Are events governed more by vascular or tubular epithelium)
overall transport is governed by events in tubular epithelium rather than vascular endothelium
cortical interstitium, which is the medium faced by the basolateral membranes of tubular epithelia, has an osmolality and concentration of small solutes close to those in plasma
(interstitial composition changes when plasma composition changes)
How is transport different in medulla? (What determines properties of overall transport and what is medullary interstitium like in comparison to plasma?)
blood flow and transport events are lower...
only some regions of vasculature are fenestrated
so overall transport depends on properties of vascular endothelium and tubular epithelium
medullary interstitium is NOT plasma-like in its composition
What is the paracellular route (crossing which epithelium)?
crossing tubular epithelium...
substance goes around the cells (through matrix of tight junctions that link epithelial cell to neighbor)
What is transcellular route?
crossing tubular epithelium
substance goes through the cells
2 step process: across apical membrane facing tubular lumen and across basolateral membrane facing interstitium
Describe movement by diffusion.
frenzied random movement of free molecules in solution
Net diffusion occurs across barrier (more molecules moving one direction than the other) if there is a driving force (concentration gradient) and barrier is permeable
applies to all substances crossing endothelial barrier lining peritubular capillaries, and most substances taking paracellular route around tubular epithelium, some substances taking transcellular route through membranes
What can directly diffuse across the lipid bilayer?
lipid soluble substances like blood gases or steroids
What are channels?
Provide a few examples.
Describe how they open.
Is movement passive or active?
small pores (proteins with a "channel" or pathway through interior of a protein) that permit, depending on structure, water or specific solutes to diffuse through them
aquaporins- permeable to water
open and close so that permeability of a membrane containing lots of channels is proportional to the probability of being open
movement is passive (no external energy req.)
What is the inherent energy driving diffusion?
concentration gradient or electrochemical gradient
gradients of voltage and concentration
When might channels be gated?
(channels permeability is regulated by environmental factors and signaling cascades)
if gated- prob. of channel being open is increased or decreased
Describe some types of gating channels.
How might some of these channels change expression?
reversible binding of small molecules that are components of signaling cascades (ligand-gated)
changes in membrane potential (voltage gated)
mechanical distortion (stretch-gated)
phosphorylation sites- P either locks shut or allows it to be gated by a mechanism above
some channels can move back and forth between surface membrane and intracellular vescicles, thereby regulating how many existing channels are actually functioning as permeability pathways
genomic expression of channels is regulated so total number is altered up or down.
How do channels and transporters differ in regards to rate of transport?
channels move large amounts of materials across membranes in short period of time
transporters have much lower rate of transport bc transported solutes bind much more strongly to transport protein
(protein also much undergo a more elaborate cycle of conformational change to move the solute from one side of membrane to the other)
Describe the mechanisms by which a transporters can be regulated.
changes in phosphorylation of transporter (turning its activity on/off), sequestration into vesicles, changes in genomic expression
What is the difference between a channel and uniporter?
Provide an example of a molecule that uses this type of transporter.
permit movement of single solute species through membrane
channel is a tiny hole, uniporter requires solute to bind to a site that is alternatively available to one side and then the other side of membrane
uniporter- facilitated diffusion (driven by concentration gradients but transported material moves through uniporter protein rather than membrane)
GLUCOSE -uses members of GLUT family of proteins in proximal tubule epithelial cells (move glucose from cytosol across basolateral membrane into interstitium)
Describe symporters and antiporters.
Provide a few examples of each
move 2 or more solute species in the same direction (symporters or cotransport) or in opposite direction across membrane (antiporters or exchange/counter transport)
symporters- 1 or 2 Na and glucose together into cells (SGLT protein family), Na K and Cl all into cell
antiporters- (Na in, proton out (sodium hydrogen exchangers -NHE protein family)
Cl in one direction and bicarbonate in other direction
Describe energy in diffusion, uniporter, antiport/symport
diffusion and uniport- energy inherent in electrocheical gradient
symport/antiport- need ENERGY (one solute moves down its concentration gradient provides the energy to move 1 or more other solute up its electrochemical gradient)
-use secondary active transport
Describe active/secondary active transport.
active transport is whenever a solute moves up electrochemical gradient
but secondary active bc does not hydrolyze ATP ...energy comes indirectly from transport of another solute rather than directly from chemical reaction
(Na often used by symporter or antiporter to provide energy) ...energetics of sodium always favor entrance ...if cell permeable to Na then it will always enter not leave the cell.
(stoichiometry..energy available from gradient multiplied by number of molecules that move per transport cycle)
Describe primary active transporter. Give an example.
membrane proteins that are capable of moving 1 or more solutes up their electrochemical gradients using the energy obtained from hydrolysis of ATP
all transporters that use this are ATPases (structure is both that of enzyme that splits ATP and a transporter that has binding sites that alternatively are open to one side and then other side of membrane)
Na/K pump (3 Na out, 2 K in)
Describe receptor-mediated endocytosis.
solute, usually protein, binds to a site on apical surface of an epithelial cell, then a patch of membrane with the solute bound to it is internalized as a vesicle in the cytoplasm
subsequent processes then degrade the protein into its constituent amino acids, which are transported across the basolateral membrane and into the blood
(apical surface to lumen, basolateral surface to basement membrane-interstitial space-blood)
What is transcytosis? When is it important in kidney?
immunoglobins, endocytosis can occur at either apical or basolateral membranes, then endocytic vesicles remain intact and are transported to the opposite cellular membrane where they undergo exocytosis to release the protein intact
important in host defense and in the prevention of urinary tract infections
How will solutes dissolved in water change concentration of water and its diffusion?
reduce concentration of water and therefore reduce tendency of water to diffuse out of a solution
Describe osmosis and osmolality.
When solutions of a different solute concentration are separated by a barrier, water will move from more dilute solution to more concentrated solution (from where water is more concentrated to where it is less concentrated)
osmolality- ability of solutes to lower concentration of water (function of concentration and type of solute- protein better than sugar, sugar better than ion at lowering concentration of water) = osmotic pressure,
units osmoles/kg water
Given a cell membrane or epithelial layer in which solutions on the 2 sides have different osmolalities, where will water move?
water will move by osmosis toward the side with higher osmolality
"water follows the osmoles"
When is osmolality/osmotic pressure effective in driving osmosis?
Give example of when it won't be effective in influencing movement.
only when barrier is less permeable to solutes than water
in fenestrated endothelial barriers of GC and peritubular capillaries, most of solutes are as permeable through the fenestrae as water and do not influence water movement ...large plasma proteins are NOT permeable and therefore do influence water movement
What does most of transport in kidney consist of?
Define iso-osmotic, what areas are iso-osmotic?
reabsorption (most of the 180L of water and several pounds of salt filtered each day into Bowman's space are reabsorbed..along w other substances
much is iso-osmotic- water and solutes reabsorbed in equal proportions (filtration in glomerulus is iso-osmotic... all solutes except large plasma proteins move from plasma into filtrate in same proportion as water )
-PT- iso-osmotic mostly, later portions of nephron..NOT iso-osmotic which is important for regulation of solute and water balance
How does tubular hydrostatic pressure affect reabsorption?
its several mmHg higher than interstitial hydrostatic pressure which favors reabsorption
(small influence normally)
It requires a hydrostatic
pressure gradient of 19.3 mm Hg to act as a driving force equivalent to
an osmotic gradient of 1 mOsm/kg, and the hydrostatic pressure difference is
usually not more than 5–8 mm Hg.
What might happen if liver disease prevents normal production of serum albumin?
results in low plasma oncotic pressure... absorption of fluid from the cortical interstitium can be slowed, causing a backup of fluid that inhibits
fluid movement from tubular lumen to interstitium. Ultimately, this can lead to increased excretion of water and electrolytes from the body.
What happens between capillary plasma and cortical interstitial fluid as blood flows through peritubular capillaries?
there is a rapid diffusion of
individual molecules back and forth between capillary plasma and cortical interstitial
fluid. The total volume of interstitial space is only 4% of the total cortical
volume, and the vascular volume is a little higher. Given the very high renal blood
flow, the solute concentrations in the interstitial fluid are essentially clamped to
those in the blood perfusing the cortex. The cortical interstitium remains quite
plasma-like (minus the proteins) in its composition, even though large amounts of
solute continuously cross through the interstitium from tubule to blood.
Between the following pressures, which favor and which oppose uptake?
-hydraulic pressure in pertitubular capillaries of 20mmHg
-oncotic pressure in pertitubular capillaries of 33mmHg
-interstitial hydraulic pressure of 3mmHg
-interstital oncotic pressure of 6mmHg
What is net pressure for uptake?
Figure 4-1 (p. 66)
interstitial hydraulic pressure
oncotic pressure in peritubular capillaries
hydraulic pressure in peritubular capillaries
interstitial oncotic pressure
net pressure for uptake (1-2) = 10mmHg