Renal Chapter 4: Basic Transport Mechanisms Flashcards Preview

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Draw/explain the 4 step process of salt/water transport in renal system.

Step 1: active extrusion of sodium via Na-K/ATPase from the cell to the interstitium
(creates low concentration of sodium within the cell so sodium moves downhill from lumen to the cell interior via ariety of symporters, antiporters and channels. This separation of charge (excess Na on interstitial side) promotes Step 2 (in step 1 any substance that enters the epithelial cells with sodium across the apical membrane must exit across the basolateral membrane)

Step 2: movement of anions through anion-specific transcellular and paracellular pathways to balance positive charge (accumulation of sodium and anions in the interstitial space produces an osmotic gradient from lumen to interstitum that promotes water movement (Step 3)

Step 4: accumulation of salt and water in interstitum promotes bult flow of solute and water into PT capillaries drive by Starling forces


How does glucose cross apical and basolateral membranes?

crosses apical membrane via the Na/glucose symporter and exits BL membrane via a GLUT uniporter


What happens in the tight junctions between lumen and interstitium as luminal concentration of solute rises (as water follows sodium and its anions across epithelium)?

What happens if 2/3 of water is removed, how much will nontransported solute change?

non-transported solute will increase in concentration to 3x its original value

As the luminal concentration rises, this generates a concentration gradient across the tight junctions between the lumen and the interstitium. If the tight junctions are permeable to the substance in question
(“leaky”), the substance will diffuse from the lumen to the interstitium. This is precisely what happens to many solutes (eg, urea, potassium, chloride, calcium, and magnesium) in the PT.


How does transepithelial voltage play a role in the proximal tubule?

early in PT lumen is slightly negative relative to the interstitium, whereas later it is slightly positive.

This voltage enhances paracellular anion reabsorption early and reduces it later.


Describe the re-absorption process of glucose. (Which mechanisms does it use, which does it never use?)

One substance that
does not get reabsorbed by the paracellular route is glucose.

First, it is transported
by the transcellular route. Second, the tight junctions are not permeable to saccharides.
Thus, it cannot diffuse no matter how large the concentration gradient might be.


What is Tm?

What happens if it is reached?

upper limits to the speed with which any given solute can be re-absorbed from tubular lumen to capillary blood

if limits reached then more than usual amount of solute is not reabsorbed (left in lumen to be passed on to next nephron segment)


Describe the types of Tm systems.

When/why is Tm reached?

tubular maximum-limited or gradient-limited

upper limit is reached bc transporters moving the substance become saturated; any further increase in solute concentration does not increase the rate at which substance binds to the transporter and thereafter moves through the membrane.


Why do gradient limited systems reach an upper limit?

What is the difference between an upper rate for Tm limited system and gradient-limited system?

gradient limited reach upper limit bc the tight junctions are leaky and any significant lowering of luminal concentration relative to interstitium results in a leak back into the lumen as fast as the substance is transported out

(the epithelium has a significant passive permeability to the substance, usually through the tight junctions, such that the establishment of a large concentration gradient between the interstitium and lumen results
in a large passive back-leak.

upper rate for Tm limited system is a property of the transporter
upper rate of gradient-limited system is a property of the permeability of the epithelial monolayer regardless of the maximal rate of transport protein


Explain Tm limited systems using glucose as an example.

Glucose is present
in plasma at a concentration of about 5 mmol/L (90 mg/dL) and is freely filtered. It is reabsorbed by the transcellular route. Glucose enters the epithelial
cells across the apical membrane via a symporter with sodium (a member of the SGLT protein family) and exits across the basolateral membrane into the interstitium via a uniporter (a GLUT protein family member). Normally, all the filtered
glucose is reabsorbed in the proximal tubule, with none remaining in the lumen
to be passed on to the loop of Henle. However, if the filtered load of glucose is abnormally high, the SGLT proteins’ upper limit for reabsorption is reached. That upper limit is the tubular maximum, or Tm, for glucose. It is the maximum rate at which the substance (glucose in this case) can be reabsorbed regardless of the luminal concentration.

Any increase in filtered load above the Tm, which for glucose represents a pathological situation, results in glucose being passed to loop of Henle


Describe how gradient-limited systems relate to sodium.

If a epithelium was very leaky would its gradient limit be lower or higher?

in PT the tight junctions are quite permeable to Na. Any significant lowering of the concentration in the lumen as sodium is reabsorbed results in a large passive flux from the interstitium back into the lumen. Sodium is freely filtered and present in the luminal fluid at a concentration of about 140 mEq/L, the same as in plasma. As sodium is transported into the interstitium,
the interstitial concentration begins to rise and the luminal concentration falls.
The rise in interstitial concentration not only drives a flux of sodium into the peritubular
capillaries, but also back through the tight junctions into the lumen

Most of the sodium moves into the blood, accomplishing the goal of reabsorption, but
some does leak back into the lumen. When the concentration of sodium reaches a
sufficiently low level in the lumen, the concentration gradient between the interstitium
and the lumen drives sodium back across the tight junctions as fast as it can be transported through the transcellular pathway from lumen to interstitium.
At this point, transport through paracellular and transcellular pathways is large,
but net transport is zero: The system has established the largest gradient possible,
its gradient limit.

The leakier the epithelium, the lower is the gradient limit

In normal conditions the reabsorption of sodium is accompanied by a proportional
reabsorption of water, so that the luminal sodium concentration actually falls very little, ie, it does not reach its limiting gradient


How would mannitol affect the reabsorption of Na and water?

if there is an unusually large amount of poorly reabsorbed solute in the lumen (eg, infused mannitol), this restrains reabsorption of water because nonreabsorbed osmoles remain in the lumen. In turn, less
water accompanies reabsorbed sodium. Then as sodium is reabsorbed, its luminal
sodium concentration falls and reaches the gradient limit. This reduces the amount
of sodium that is reabsorbed and leads to an osmotic diuresis


Can substances in Tm or gradient-limited systems be reabsorbed completely?

solutes handled by Tm systems may, if the filtered load is below the Tm, be reabsorbed essentially completely, whereas solutes handled by gradient-limited systems are never reabsorbed completely, ie, a substantial amount always remains in the tubule to be passed on to the next nephron segment.


Flux of a solute out of a cell, whether via a uniporter, symporter, or an ATPase, is
always a process of active transport (primary or secondary). True or false?

The answer is false. Flux by a uniporter is always passive, down the electrochemical
gradient. Flux by a symporter may be active depending on
direction. Flux via an ATPase is always active. (Theoretically, it could pump downhill, but this does not normally occur.)


Reabsorption in the proximal tubule is described as being iso-osmotic, leaving the
luminal fluid isosmotic with plasma. Yet we already know from earlier chapters
that the excreted urine usually is quite different osmotically from the surrounding
interstitium. Why is the final urine not always iso-osmotic?

Most regions of the nephron have tight junctions that are far less leaky than those found in the proximal tubule, and most apical membranes are far less permeable to water. As a result, it is possible to sustain much
larger osmotic gradients across the epithelium in tubular regions beyond the proximal tubule. Reabsorption beyond the proximal tubule is generally not iso-osmotic.


In the proximal tubule, the tubular epithelium is far less permeable to small solutes
than is the endothelium of the surrounding peritubular capillaries. True or false?

The answer is true. The tubular epithelium is quite permeable to many (but not all small solutes), but the peritubular endothelium is even more permeable.


Low plasma oncotic pressure inhibits volume reabsorption from tubular lumen to
interstitium. Because this is plasma oncotic pressure, how can it affect transepithelial

Failure to move fluid from the interstitium to peritubular capillary as a result of low plasma oncotic pressure quickly leads to a backup of fluid
in the interstitial space. Since the interstitial space contains a small fraction of total volume of the kidneys, only a small increase in fluid volume
is required to generate a rise in hydrostatic pressure. Once interstitial pressure rises significantly, this drives an increasing back-leak.


Even though values of osmolality and osmolarity differ numerically, any 2 solutions
of equal osmolarity will have equal osmolality. True or false?

The answer is false. Not all solutes are alike osmotically. Proteins, eg, exert far more osmotic effect mole for mole than do saccharides. In addition,
saccharides exert a somewhat higher osmotic effect than simple
salts. In this text, we sometimes simplify things by using osmolarity, when technically we should use osmolality. In most cases, this does not introduce a large error.


Given the high volume of fluid normally moving from interstitium to blood in the
renal cortex, how can secreted substances move from blood to epithelium? Are they not going the wrong way?

Despite the volume flow, most solutes are close to diffusional equilibrium between plasma and interstitium. If the interstitium starts to become depleted of a substance as a result of secretion, net diffusion from
the plasma will soon replenish it.


The Tm for glucose is set at what level?
A. Close to the normal filtered load
B. Well above the normal filtered load
C. Well below the normal filtered load

The answer is B. Normally, all the filtered glucose is reabsorbed, meaning that the filtered load does not saturate the transporter capacity. If either A or C was true, there would be at least some glucose in the urine.


Define channel “gating,” and state whether changing interstitial osmolality is a
way of gating channels.

Gating is a process that changes the probability that a channel is open. Changes in interstitial osmolality are not known to gate channels directly. However, if a change in interstitial osmolality causes a cell to swell or shrink, the resulting change in mechanical stretch of mechanosensitive channels could gate them (this is thought to be how hypothalamic cells detect changes in plasma osmolality).