Renal Chapter 6: Basic Renal Processes for Na+, Cl-, Water Flashcards

1
Q

Describe transport of water.

A

water follows osmoles

some regions low water permeability limits amount of water following osmoles

(no pumps for water)

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2
Q

Describe what Na, Cl, and water have in common.

A

all freely filterable at the renal corpsule

all undergo considerable reabsorption, usually more than 99% but normally no tubular secretion. (most renal ATP energy expended is used for this task

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3
Q

Describe the major tubular mechanisms for reabsorption of sodium.

A

mainly an active, transcellular process driven mostly by Na-K- adenosine triphosphatase (Na-K-ATPase)

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4
Q

Describe the major tubular mechanism for reabsorption of chloride.

A

reabsorption of chloride is both passive (paracellular diffusion) and active (transcellular), but it is directly or indirectly coupled with the reabsorption of sodium, thus explaining why the reabsorption of the 2 ions usually occurs in parallel.

(when describing the reabsorption of sodium, a parallel reabsorption of chloride is usually implied.

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5
Q

Describe reabsorption of water.

A

reabsorption of water is by osmosis and is secondary to reabsorption of solutes, particularly sodium and substances whose reabsorption is dependent on sodium reabsorption (mostly chloride)

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6
Q

Where is sodium mostly reabsorbed, in what percentages, how much is usually excreted?

A

in individual w average salt intake, PT reabsorbs 65% of filtered sodium, the thin and thick ascending limbs of Henle’s loop 25% and distal convoluted tubule and collecting duct- system the remaining 10% so that final urine contains less than 1% of total filtered sodium

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7
Q

In all nephron segments, what is the essential event for active transcellular sodium reabsorption?

A

primary active transport of sodium from cell to interstitial fluid by the Na-K-ATPase pumps in the basolateral membrane

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8
Q

What is the importance of the Na/K pumps in basolateral membrane?

A

pumps keep the intracellular sodium concentration lower than in the surrounding media. Because the inside of the cell is negatively charged with respect to the lumen, luminal sodium ions enter the cell passively down their electrochemical gradient.

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9
Q

How is sodium and chloride percentages and locations of reabsorption related?

A

bc chloride reabsorption is dependent on sodium… tubular locations and percentages of filtered chloride reabsorbed are similar to those of sodium

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10
Q

What is absolute constraint of electroneutrality?

A

any finite volume of fluid reabsorbed must contain equal amounts of anion and cation equivalents

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11
Q

One L of normal filtrate contains 140mEq of sodium. Describe its anion concentration.

If 65% of the filtered sodium is reabsorbed in the proximal
tubule, how much chloride is reabsorbed?

A

must contain
about 140 mEq of anions, mainly chloride (110 mEq) and bicarbonate (24 mEq)

0.65 x 140=91mEq reabsorbed in PT. so some combination of 91mEq of chloride and bicarbonate must also be reabsorbed to accomnay sodium…

we know that about 90% of filtered bicarb is reabsorbed in PT

(.90x24= 22) 91-22 =69mEq of chloride that must be reabsorbed in the PT

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12
Q

What is the critical transport step for chloride? Why?

Describe the chloride transport process. Where are pumps necessary and why?

A

critical step is from lumen to cell.

the chloride transport process in the luminal membrane must achieve a high enough intracellular chloride conc. to cause downhill chloride movement out of the cell across the BL membrane…(of course, the movement of Cl across basolateral membrane is also prompted by negative potential within the cell)

so luminal membrane chloride transporters serve same purpose as BL membrane Na-K-ATPase pumps do for Na. (they move Cl uphill from lumen to cell against its electrochemical gradient)

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13
Q

Describe the major transporters on the apical lumen/basolateral sides of PT.

A

See Figure 6-1 p 90 or printout

According to the luminal membrane depicted in Figure 6–1, the major routes are
(1) paracellular absorption and (2) a complicated parallel set of Na-H and Cl-base
antiporters (described later). These mechanisms are dependent on sodium movement
across the membrane and are, therefore, linked to sodium reabsorption.

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14
Q

How does the kidney regulate how much water is excreted based upon hydration status? Where does this regulation of water reabsorption take place?

A

regardless of hydration state, collective actions of renal tubular segments before cortical collecting tubule reabsorb more solute than water…

this leaves large volume of dilute tubular fluid (approx 110 mOsm/kg H2O) entered the limited segment of the cortical collecting tubule.

if individual is overhydrated most of this water will be excreted w limited further reabsorption

if dehydrated, vast majority of the dilute water is reabsorbed.. leaving low volume of concentrated final urine

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15
Q

Where does water reabsorption occur and in what percentages?

A

always occurs in the proximal tubule (65% of filtered water), descending limb of Henle’s loop (10%) and collecting duct system (where fractional reabsorption is the most variable)

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16
Q

Sodium and water reabsorption occur in the proximal tubule to the same extent; however, their reabsorption in Henle’s loop differs. Explain how.

A

both are also reabsorbed in Henle’s loop, but not in equal proportions.

The part of the loop involved in water reabsorption is different from that for sodium
reabsorption, and the fraction of sodium reabsorbed by the loop as a whole is always greater than that of water (ie, the loop overall is a site where salt is reabsorbed and excess water is left in the lumen of the nephron: “separating salt from
water”).

sodium reabsorption, but not water reabsorption, occurs in the distal convoluted tubule.

both occur in the collecting-duct system, but
the percentages of sodium and water reabsorbed in the collecting-duct system vary
enormously depending on a number of factors

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17
Q

What are some routes by which water can move down an osmotic gradient?

A

simple net diffusion through the lipid bilayer

through aquaporins in plasma membrane of tubular cells

through tight junctions between cells

amt of water that moves for a given osmotic gradient and its route dep. on the water permeability of different cellular components

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18
Q

Which areas are more/less permeable to water?

A

basolateral membrane of all renal cells are quite permeable to water due to presence of protein aquaporins that act as water pores (so cystolic osmolality is always close to that of the surrounding interstitium. It is the luminal membrane and tight junctions where most variability lies

(1) The luminal
membranes of the proximal tubule and descending thin limb of Henle’s loop
always have a high water permeability

(2) the luminal membrane of the ascending limbs of Henle’s loop (both thin and thick; recall from Chapter 1 that only long
loops have ascending thin limbs) and the luminal membranes of distal convoluted tubule are always relatively water impermeable, as are the tight junctions;

(3) the water permeability of the luminal membrane of the collecting-duct system
is intrinsically low but can be regulated so that its water permeability increases
substantially.

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19
Q

What is obligatory water loss?

Is it fixed?

A

the sum of urea, sulfate, phosphate, and other waste products, and a small number of nonwaste ions excreted each day normally averages approx 600mOsm/day. Therefore, the minimal volume of water in which this mass of solute can be dissolved is roughly 600mmol/1400mOsm/L =0.43L/day

(The human kidney can
produce a maximal urinary concentration of 1400 mOsm/kg in extreme dehydration)

-not fixed volume, changes. for ex: during increased tissue catabolism, as during fasting or trauma, releases excess solute and so increases obligatory water loss

p 92

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20
Q

What happens in the early portion (the proximal convoluted tubule)?

A

large fraction of filtered sodium enters the cell across the luminal membrane via an antiport with protons

(these protons which are supplied by CO2 and water cause the secondary active reabsorption of filtered bicarbonate)

so bicarb is a major anion reabsorbed w sodium, and the luminal bicarb conc. decreases markedly

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21
Q

How does most chloride reabsorption in the PT occur? paracellular or transcellular?

Describe its conc. along the early PT.

A

paracellular diffusion

conc. of chloride in BC is basically same as plasma (about 110mEq/L)

along the early PT however, the reabsorption of water, driven by the osmotic gradient created by the reabsorption of sodium plus its co-transported solutes and bicarb, causes the chloride conc. in the tubular lumen to increase somewhat above that in the peritubular capillaries.

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22
Q

Describe chloride conc. as fluid flows through the middle and late proximal tubule.

A

conc. gradient, maintained by continued reabsorption of water, provides the driving force for paracellular chloride reabsorption by diffusion

in the late PT, it uses parallel Na-H and Cl-base antiporters. Chloride transport into the cell is powered by the downhill antiport of organic bases which are continuously generated in the cell by dissociation of their respective acids into a proton and base

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23
Q

Explain diagram 6-2 on p 94.

A

p 94/notes

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24
Q

Describe what happens to protons generated within the cell by dissociation of acids.

Will the pH of lumen change?

A

They are actively transported into the lumen by Na-H antiporters. In the lumen the protons and organic bases recombine to form the acid, which is a neutral molecule. This nonpolar neutral acid then diffuses across the luminal membrane back into the cell where the entire process is repeated

most of the protons are not acidifying the lumen but are simply combining with the base and moving back into the cells

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25
Q

Describe result of parallel Na-H and Cl-base antiporters.

A

same as if Cl and Na were co-transported into cell together

Na in, Cl in.

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26
Q

What powers the luminal Na-H transporter?

A

the Na-K-ATPase in the basolateral membrane

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27
Q

Describe water reabsorption in the proximal tubule.

A

PT has high permeability to water

this mean that v small differences in osmolality (less than 1mOsm/L) will suffice to drive the reabsorption of v large quantities of water (normally about 65% of filtered water)

the osmolality difference is created by reabsorption of solute

The osmolality of the freshly filtered tubular
fluid at the very beginning of the proximal tubule is, of course, essentially the
same as that of plasma and interstitial fluid. Then, as solute is reabsorbed from
the proximal tubule, the movement of this solute out of the lumen lowers luminal osmolality (ie, raises water concentration) compared with interstitial fluid. It also raises interstitial fluid osmolality (only a bit bc high perfusion through peritubular capillaries keeps it close to plasma value)

28
Q

How does water diffuse from lumen to interstitial fluid? Then what?

A

Osmotic gradient from lumen to interstitial fluid causes osmosis of water from the lumen across the plasma membranes via aquaporins and tight junctions into the interstitial fluid. The Starling forces across the peritubular capillaries in the interstitium favor reabsorption and so water and solutes then move into peritubular capillaries and are returned to general circulation

29
Q

Given the tremendous amount of sodium reabsorbed, how can the luminal sodium concentration and osmolality not progressively decrease along the proximal tubule?

A

iso-osmotic volume reabsorption

Whereas 65%
of the mass of filtered sodium and total solute has been reabsorbed by the end of the proximal tubule, so has virtually the same percentage of filtered water. This is because the water permeability of the proximal tubule is so great that passive water
reabsorption always keeps pace with total solute reabsorption. Therefore, the
concentrations of sodium and total solute (osmolality), as opposed to their masses, remain virtually unchanged during fluid passage through the proximal tubule

30
Q

What is osmotic diuresis and what causes it?

Explain its effects relating to water/Na reabsorption.

A

when tight coupling between proximal sodium and water reabsorption is disrupted

diuresis= increased urine flow
osmotic diuresis= situation in which increased urine flow is due to an abnormally high amount of any substance in the glomerular filtrate that is reabsorbed incompletely or not at all by PT
-when water reabsorption begins in this segment, the conc. of any unreabsorbed solute rises and its osmotic presence retards further reabsorption of water here…failure of water to follow sodium causes the sodium conc. in PT lumen to fall slightly below that in the interstitial fluid.

(this created conc. difference that will result in a net passive diffusion of sodium across epithelium back into the lumen through leaky tight junctions.. PT is a leaky epithelium

31
Q

Describe Henle’s loop.

A

reabsorbs more Na and Cl than water… (25% solutes, 10% water)

descending limb does not reabsorb sodium or chloride but is quite permeable to water and reabsorbs it

ascending limbs (both thin and thick) reabsorb sodium and chloride but little water (bc they are quite impermeable to water)

ascending limb is “diluting segment” …reabsorbs more solute than water, leaving fluid to enter the distal convoluted tubule as hypo-osmotic (more dilute) as compared w plasma.

32
Q

What are the mechanisms of sodium and chloride reabsorption by the ascending limbs?

Describe water reabsorption in the descending limb.

A

these are mainly passive in the thin ascending limb and active in the thick ascending limb (Na-K-2Cl symporter and Na-H antiporter, also sodium reabsorption (about 50% by paracellular diffusion) p 97)

water reabsorption in the descending limb concentrates luminal sodium and creates a favorable gradient for passive sodium reabsorption (reabsorbs water and not NaCl)

33
Q

What is the main target for loop diauretics like furosemide and bumetanide?

A

the Na-K-2Cl symporter (NKCC)

34
Q

What is the point on the nephron where salt is separated from water?

A

TAL bc they reasborb salt but not water

35
Q

Why doesn’t luminal potassium limit sodium and chloride reabsorption through Na-K-2Cl symporters? (There is far less K in lumen than sodium and the Na-K-2Cl requires equal amounts of K and Na to be transported- it seems the lumen would be depleted of K before v much Na was reabsorbed?)

A

the luminal membrane has large number of K channels that allow much of the K transported into the cell on the Na-K-2Cl symporter to leak back

36
Q

What is the major transport pathway for reabsorption of Na and Cl in the distal tubule?

A

Na-Cl symporter

37
Q

What type of cells are associated with reabsorption of sodium and water in the collecting ducts?

Describe how Na, Cl, and water are reabsorbed here.

A

See Figure 6-5 p 99.

principal cells (make up about 70% of cells in CCD) 
they also play a major role in maintaining potassium homeostasis. they reabsorb sodium. (the luminal entry step is via epithelial sodium channels) 

Na reabsorption is through apical sodium channels whose activity is controlled by aldosterone

chloride reabsorption is passive via paracellular pathway

water reabsorption is via aquaporins (controlled by ADH)

38
Q

Describe water reabsorption in the tubular segments beyond the loop of Henle.

A

water permeability of the distal convoluted tubule is always very low and unchanging (similar to ascending limbs of Henle)

(so the already hypo-osmotic fluid entering the distal convoluted tubule from TAL becomes even more hypo-osmotic)

so both ascending loops and distal convoluted tubule both act as diluting segments and further separate salt from water

39
Q

Describe the water permeability of the collecting duct system.

A

both cortical and medullary portions are subject to physiological control by circulating ADH.

40
Q

What is water diuresis? When is the last tubular segment to reabsorb large amounts of water?

A

large excretion of a large volume of very hypo-osmotic (dilute) urine

(when most water entering medullary collecting duct is not reabsorbed and flows onto ureter)

last tubular segment to reabsorb large amounts of water- descending limb of Henle’s loop

41
Q

Describe ADH; its mechanism, where it acts, its effect.

A

ADH acts in the collecting ducts on the principal cells, the same cells that reabsorb sodium (and secrete K)

renal receptors for ADH are in BL membrane of principal cells

binding of ADH by its receptors results in the activation of adenylate cyclase which catalyzes the intracellular production of cyclic adenosine monophosphate. this second mesanger then induces migration of intracellular vesicles to and their fusion w the luminal membrane

ADH can constrict arterioles and thus increase arterial bp, but its major renal effect is anti-diuresis

The vesicles contain an isoform
of a water channel protein, aquaporin 2, through which water can move, so the luminal
membrane becomes highly permeable to water. In the absence of ADH, the
aquaporins are withdrawn from the luminal membrane by endocytosis

42
Q

Between the luminal membrane and the basolateral membrane of renal epithelial cells, which is rate-limiting?

A

water permeability of the basolateral membranes of renal epithelial cells
is always high because of the constitutive presence of other aquaporin isoforms;
thus, the permeability of the luminal membrane is rate limiting

43
Q

Describe the osmotic value of the medullary interstitium (how it changes/varies and when).

A

gradient of osmolaity from nearly iso-osmotic value at corticomedullary border to max of greater than 1000mOsm/kg at the papilla. This peak value is not rigidly fixed; it is a variable that changes dep. on conditions.

It is highest during periods of water deprivation and dehydration, when urinary
excretion is lowest, and is “washed out” to only about half of that during excess
hydration and urinary excretion is high

44
Q

What are the main components of the system that develop the medullary osmotic gradient?

A

main components of the system that develops the medullary osmotic gradient are

(1) active NaCl transport by the thick ascending limb (the reabsorption of Na and Cl by TAL)

(2) the unusual arrangement
of blood vessels and nephron segments in the medulla, with descending components in close apposition to ascending components; and

(3) the recycling of urea between the medullary collecting ducts and the deep portions of the loops of
Henle

45
Q

What happens if loop diauretics block the Na-K-2Cl symporter?

A

then transport in the TAL is inhibited and lumen is not diluted and the interstitium is not concentrated and the urine becomes iso-osmotic

46
Q

Describe the portions of the TAL in the cortex. How does reabsorbed solute affect system?

How does this differ from the medulla?

A

reabsorbed solute simply mixes w material reabsorbed by the nearby proximal convoluted tubules.. Bc the cortex contains abundant peritubular capillaries and high blood flow, the reabsorbed material immediately moves into the vasculature and returns to general circulation

in medulla rebabsorbed solute is not immediately removed; it accumulates. degree of accumulation is a function of the vasa recta, their permeability properties and the volume of blood flowing within them

47
Q

Describe the vasa recta vessels peremability and how it differs in ascending v descending.

A

blood enters and leaves the outer medulla through
parallel bundles of descending and ascending vasa recta. These vessels are permeable
to sodium and they take up most of the sodium that is being transported
by the thick ascending limbs into the interstitium of the outer medulla

The ascending
vasa recta return sodium to the general circulation, but the descending vessels distribute it down into the inner medulla, where it diffuses out across the
endothelia of the vasa recta and the interbundle capillaries that they feed, thereby
raising the sodium content (and osmolality) throughout the medulla

48
Q

Describe countercurrent exchange between ascending and descending vessels in vasa recta.

A

The process of crossing between ascending and descending vessels is
called countercurrent exchange

The walls of the ascending vasa recta are fenestrated, allowing rapid and thorough equilibration of water and small solutes between plasma and interstitium. As the total sodium content of the medulla
rises, blood in the ascending vessels takes on an increasingly higher sodium concentration, while blood entering the medulla always has a normal sodium concentration (about 140 mEq/L). Accordingly, some of the medullary sodium begins
to re-circulate, diffusing out of ascending vessels and reentering nearby descending
vessels

49
Q

What are the two sources by which sodium enters the descending vasa recta?

A

re-circulated sodium from ascending vasa recta and new sodium from TAL

50
Q

What happens to water in the medulla?

A

must be constant otherwise the medulla would undergo significant swelling or shrinking

endothelial cells of descending vasa recta, although not as leaky as fenestrated epithelium of ascending vasa recta, contain aquaporins, allowing water to be drawn osmotically into the medullary interstitium by the high salt content

This loss of water from descending vasa recta decreases
the plasma volume of blood penetrating deeper into the medulla and raises
its osmolality, thereby reducing the tendency to dilute the inner medullary interstitium.
Water leaving descending vessels diffuses across to nearby ascending vasa
recta and is removed from the medulla. Just as there is countercurrent exchange of
solute between descending and ascending vessels, there is countercurrent exchange
of water. In descending vessels water leaves and solute enters, while in ascending
vessels water enters and solute leaves

51
Q

Where else does water enter the medullary interstitium?

A

Water also enters the medullary interstitium by reabsorption from thin descending limbs and from
medullary collecting ducts. As there is no water secretion by the tubules, all water
entering the medullary interstitium from tubules and descending vasa recta must
leave the medulla via ascending vasa recta

p 105 GOOD DIAGRAM

52
Q

What happens if blood flow in vasa recta is very high?

A

then water from iso-osmotic plasma entering the medulla in descending vasa recta dilutes the hyperosmotic interstitium.

53
Q

Peak osmolality in renal papilla is over 1000mOsm/kg. How much of this is accounted for by sodium chloride/urea?

A

urea is about half … (500-600mOsm/kg)

54
Q

Describe urea.

Where/when is it reabsorbed/transported? What is the effect of this?

A

freely filtered
half reabsorbed in proximal tubule
secreted in the loop of Henle (thin regions) driven by the high urea concentration in the medullay interstitium (this restores amount of tubular urea back to filtered load)

from end of thin limbs to inner medullary collecting ducts, little urea transport occurs, so whatever urea arrives at the TAL is still there at the start of the inner medullary collecting ducts.

Because the vast majority of water has been reabsorbed before the inner medullary collecting ducts (by the cortical and outer medullary collecting ducts), the luminal urea concentration has risen up to 50 times its plasma value (ie, 500 mmol/L or more).
In the inner medullary collecting ducts, some urea is reabsorbed via specialized
urea uniporters and the rest (typically about half the filtered load) is excreted.

55
Q

What drives urea secretion in thin limbs?

A

bc blood flow in inner medullary collecting ducts (?) is low, the reabsorbed urea accumulates and raises the interstitial concentration close to that in lumen …

p 105

56
Q

Under conditions of high ADH one might expect that there would be even more water reabsorbed from the medullary collecting ducts than with low ADH and this water would dilute the interstitium and abolish the osmotic gradient. Why isn’t this the case?

A

Water does enter the medullary interstitium from medullary
collecting ducts aided by the actions of ADH, but so little water remains in the tubule after passage through the cortex that the amount remaining to be reabsorbed is quite small. Also, as described earlier, water enters from descending thin
limbs of the loops of Henle and from descending vasa recta.

Although there is a
tendency for all of this water to dilute the interstitium, there is also a continuing deposition of new solute by the thick ascending limb. The competing tendencies to dilute the interstitium with water and to concentrate the interstitium with salt reach a balance in which osmolality is high. It is this balance that sets the upper
limit on medullary osmolality.

57
Q

During diuresis when ADH is low and body is excreting large amounts of water, more water is reabsorbed in the medulla than during antidiuresis when ADH is high and the body is conserving water. Why?

A

during diuresis there is little cortical water reabsorption, so the amount of medullary water reabsorption is greatly exceeded by the amount not reabsorbed (excreted)

See diagram p 108)

58
Q

A man ingests 12 g of sodium/day. His nonrenal loss (gastrointestinal tract and
sweat) is 0.4 g/day. In the steady state, what amount of sodium chloride is excreted
daily in the urine?

A

11.6 g/day

59
Q

Mannitol is a substance sometimes infused to reduce cerebral edema. It is handled
by the kidneys similarly to inulin. What effect would a large mannitol infusion have
on sodium excretion?
A. No effect
B. Increase sodium excretion
C. Reduce sodium excretion

A

The answer is B. Mannitol is freely filtered and neither secreted nor reabsorbed.
It acts as an excess osmole in the same way that glucose does
when its filtered load exceeds the Tm for reabsorption. Sodium excretion
will increase and for the same reasons as when there is excess glucose.

60
Q

Would complete inhibition of active sodium and chloride transport by the thick
ascending limb of Henle’s loop eliminate the ability to excrete a concentrated
urine or a dilute urine?

A

The answer is both. The luminal fluid and the medullary interstitium would both become isosmotic, and so would the final urine.

61
Q

Increasing the passive permeability of the thick ascending limb of Henle’s loop to sodium and chloride would reduce the maximal concentrating ability of the kidney.
True or false?

A

The answer is true. Allowing back-leak of chloride would reduce the paracellular reabsorption of sodium, and thus reduce the overall reabsorption
of both sodium and chloride and prevent concentrating the
medullary interstitium.

62
Q

Active reabsorption of sodium and chloride by the descending thin limb of Henle’s
loop is a component of the countercurrent multiplier system. True or false?

A

The answer is false. There is no reabsorption of sodium or chloride by the descending thin limb of Henle’s loop.

63
Q

In conditions of maximum levels of ADH, there is net bulk flow of fluid from medullary
interstitium into the vasa recta. True or false?

A

The answer is true. There is always net reabsorption of both sodium and water in the medulla from long loops of Henle and medullary collecting
ducts. Under the influence of ADH, the reabsorption of water in the inner medullary collecting ducts is further stimulated. This solute and water must be removed from the medullary interstitium.

64
Q

In conditions of minimum levels of ADH, there is net bulk flow of fluid from medullary
interstitium into the vasa recta. True or false?

A

The answer is true. As with maximum levels of ADH, there is always net reabsorption of sodium and water in the medulla. With minimum levels of ADH, there is still net reabsorption of water in the inner medullary
(not cortical) collecting ducts. As described in the text, with low
levels of ADH (and hence little reabsorption in the cortex), the gradient for water reabsorption in the inner medulla is quite large, and there is always some finite water permeability in this region.

65
Q

A drug is given that blocks all sodium channels and transporters in the luminal
membrane all along the tubule but does not act on the Na-K-ATPase pumps in the
basolateral membrane. What happens to sodium reabsorption?

A

It ceases completely. Even though the active step is not altered by the drug,
there will be no sodium entering the cell to be acted on by the pumps.

66
Q
The osmolality in the renal papilla in a healthy young person with excellent renal
function who is not taking any medications is always 1200 mOsm/kg or more. True
or false?
A

The answer is false. The medullary osmolality reaches its highest value only during extreme dehydration. The normal value is somewhat below
the maximum, and fluctuates throughout the day in response to dietary input.