Water Excretion pdf - Dr. Abdullah

بسم هللا الرحمن الرحيم

Water excretion

WATER EXCRETION

• Normally,

180 L

of fluid is filtered through the

glomeruli each day, while the average daily urine
volume is about

1 L

• The same load of solute can be excreted per 24

hours in a urine volume of

500 mL

with a

concentration of

1400 mosm/kg

or in a volume of

23.3 L

with a concentration of

30 mosm/kg

• These figures demonstrate two important facts:

– first, that at least

87%

of the filtered water is

reabsorbed, even when the urine volume is 23 L; and

– second, that the reabsorption of the

remainder

of the

filtered water can be

varied

without affecting total

solute excretion.

Alterations in water metabolism produced by
vasopressin in humans. In each case, the
osmotic load excreted is 700 mosm/d.

WATER EXCRETION

• Therefore, when the urine is concentrated,

water is retained in excess of solute

; and when

it is dilute, water is lost from the body in
excess of solute.

• Both facts have great importance in the

body

economy

and the regulation of the

osmolality

of the body fluids.

• A

key regulator

of water output is

vasopressin

acting

on the collecting ducts.

Aquaporins

• Research indicates that rapid diffusion of

water across cell membranes depends on

water channels

made up of proteins called

aquaporins

• Four aquaporins

—aquaporin-1, -2, -5, and -

9—have been characterized in humans.

• Most are found in the

kidneys

, though

aquaporin-9 is found in human

leukocytes

liver

lung

, and

spleen

; and aquaporin-5 is

found in human

lacrimal glands

Proximal Tubule

• Many substances are

actively transported

out of the

fluid in the proximal tubule, but fluid obtained by

micropuncture remains essentially

isosmotic

to the end

of the proximal tubule .

• Therefore, in the proximal tubule

, water moves

passively

out of the tubule along the

osmotic gradients

set up by active transport of solutes, and

isotonicity is

maintained

• Since the

ratio

of the concentration in tubular fluid to

the concentration in plasma

(TF/P)

of the

nonreabsorbable substance

inulin

2.5-3.3

at the end

of the proximal tubule, it follows that

60-70%

of the

filtered solute and

60-70%

of the filtered water have

been removed by the time the filtrate reaches this

point .

Reabsorption of various solutes in the proximal

tubule. TF/P, tubular fluid:plasma concentration

ratio.

Changes in the percentage of the filtered amount of substances

remaining in the tubular fluid along the length of the nephron in the

presence of vasopressin.

Loop of Henle

• As noted , the loops of Henle of the

juxta-medullary

nephrons

dip deeply into the medullary pyramids before

draining into the distal convoluted tubules in the cortex,

and all of the collecting ducts descend back through the

medullary pyramids to drain at the

tips of the pyramids

into

the renal pelvis.

• There is a graded increase in the osmolality of the

interstitium of the pyramids

, the osmolality at the tips of

the papillae normally being about

1200 mosm/kg of H

approximately

four times

that of plasma.

• The

descending

limb of the loop of Henle is

permeable

water, but the

ascending

limb is

impermeable

• Na

, K

, and Cl

are cotransported out of the thick segment

of the ascending limb .

Loop of Henle

• Therefore, the fluid in the

descending

limb of the

loop of Henle becomes

hypertonic

as water

moves into the hypertonic interstitium.

• In the

ascending

limb it becomes more

dilute

and when it reaches the

top it is hypotonic to

plasma

because of the movement of Na

and Cl

out of the tubular lumen.

• In passing through the loop of Henle, another

15% of the filtered water is removed

, so

approximately 20% of the filtered water enters
the distal tubule, and the

TF/P of inulin

at this

point is about

Loop of Henle

• In the

thick ascending

limb, a carrier cotransports one Na

one K

, and 2 Cl

from the tubular lumen into the tubular

cells.

• This is another example of

secondary active transport

; the

is actively transported from the cells into the

interstitium by

-K

ATPase

in the basolateral membranes

of the cells, keeping the intracellular Na

low.

• The K

diffuses back

into the tubular lumen and back into

the interstitium via

ROMK and other K

channels

• The Cl

diffuses into the interstitium via ClC-Kb channels .

• This K

recycles across the luminal and the basolateral

membrane, while there is no transport of Na

and Cl

into

the interstitium.

NaCl transport in the thick ascending limb of the loop of Henle. The

, K

2Cl

cotransporter moves these ions into the tubular cell by secondary active

transport. Na

is transported out of the cell into the interstitium by

-K

ATPase

in the basolateral membrane of the cell. Cl

exits in basolateral ClC-Kb

channels.

Barttin

, a protein in the cell membrane, is essential for normal

ClC-Kb function.

moves from the cell to the interstitium and the tubular

lumen by

ROMK

and other K

channels.

Distal Tubule

• The distal tubule, particularly its first part, is in

effect an

extension of the thick segment

of the

ascending limb.

• It is relatively

impermeable to water

, and

continued removal of the solute in excess of
solvent further dilutes the tubular fluid.

• About

of the filtered water is removed in

this segment.

Collecting Ducts

• The collecting ducts have

two portions

– a cortical portion and
– a medullary portion.

• The changes in osmolality and volume in the collecting

ducts depend on the amount of

vasopressin

acting on the

ducts.

• This

antidiuretic hormone

from the posterior pituitary

gland increases the

permeability

of the

collecting ducts

water.

• The key to the action of vasopressin on the collecting ducts

is aquaporin-2.

• The effect is mediated via the

vasopressin V

receptor,

cyclic AMP

protein kinase A

, and

a molecular motor

, one of

the dyneins .

Collecting Ducts

• In the presence of

enough vasopressin

to produce maximal

antidiuresis, water moves out of the hypotonic fluid

entering the cortical collecting ducts into the interstitium of

the cortex, and the tubular fluid becomes isotonic.

• In this fashion

, as much as

10%

of the filtered water is

removed.

• The isotonic fluid then enters the medullary collecting

ducts with a

TF/P inulin

of about

• An additional 4.7% or more of the filtrate is reabsorbed into

the hypertonic interstitium of the medulla, producing a

concentrated urine with

a TF/P

inulin of over

300

• In humans, the osmolality of urine may reach

1400

mosm/kg

of H

O, almost

five times

the osmolality of

plasma, with a total of

99.7%

of the filtered water being

reabsorbed

Collecting Ducts

• When

vasopressin

is absent, the collecting duct epithelium is

relatively impermeable to water.

• The fluid therefore

remains hypotonic

, and large amounts

flow into the renal pelvis.

• In humans, the urine osmolality may be as low as

mosm/kg

of H

• The

impermeability

of the distal portions of the nephron is

not absolute

; along with the salt that is pumped out of the

collecting duct fluid, about

of the filtered

water

reabsorbed

in the absence of vasopressin.

• However, as much as

13%

of the filtered water may be

excreted, and urine flow may reach

15 mL/min

or more.

Role of Urea

• Urea contributes to the establishment of the

osmotic gradient

in the medullary pyramids and

to the ability to form a concentrated urine in the

collecting ducts.

• Urea transport is mediated by

urea transporters

presumably by

facilitated diffusion

• The amount of urea in the

medullary interstitium

and, consequently, in the urine varies with the

amount of urea , and this in turn varies with the

dietary

intake of protein

• Therefore,

a high-protein diet

increases the

ability of the kidneys to

concentrate the

urine.

Water Diuresis

• The

water diuresis

produced by drinking large

amounts of hypotonic fluid begins about

minutes

after ingestion of a water load and

reaches its maximum in about

40 minutes

• The

act of drinking

produces a small decrease

vasopressin

secretion before the water is

absorbed, but most of the inhibition is
produced

by the decrease in plasma

osmolality

after the water is absorbed.

Water Intoxication

• During excretion of an average osmotic load, the maximal

urine flow that can be produced during a

water diuresis is

about 16 mL/min

• If water is ingested at a higher rate than this for any length

of time, swelling of the cells because of the uptake of water

from the hypotonic ECF becomes severe and, rarely, the

symptoms of water intoxication

may develop.

• Swelling of the cells in the brain causes

convulsions

and

coma

and leads eventually to

death

• Water intoxication can also occur when water intake is not

reduced after administration of

exogenous vasopressin

secretion of

endogenous vasopressin

in response to

nonosmotic stimuli such as surgical trauma.

Osmotic Diuresis

• The presence of large quantities of

unreabsorbed

solutes

in the renal tubules causes an increase in

urine volume called

osmotic diuresis

• Solutes that are not reabsorbed in the proximal

tubules exert an

appreciable osmotic

effect as the

volume of tubular fluid decreases and their
concentration rises.

• Therefore, they "

hold water in the tubules

.“

• In addition, there is a limit to the concentration

gradient against which Na

can be pumped out of

the proximal tubules.

• Normally, the movement of water out of the

proximal tubule prevents any appreciable
gradient from developing, but

concentration

in the fluid falls when water

reabsorption is decreased because of the
presence in the tubular fluid of increased
amounts of unreabsorbable solutes.

Osmotic Diuresis

• The

limiting concentration gradient

reached, and further proximal reabsorption of
Na

is prevented; more Na

remains in the

tubule, and water stays with it.

• The result is that the loop of Henle is

presented with a greatly increased volume of
isotonic fluid.

Osmotic Diuresis

• This fluid has a

decreased Na

concentration

, but

the

total amount of Na

reaching the loop per

unit time is increased.

• In the loop, reabsorption of water and Na

decreased because the

medullary hypertonicity

decreased

• The decrease is due primarily to

decreased

reabsorption of Na

, K

, and Cl

in the ascending

limb of the loop because the limiting
concentration gradient for Na

reabsorption is

reached.

•

More fluid passes

through the distal tubule,

and because of the decrease in the osmotic
gradient along the medullary pyramids,

less

water is reabsorbed

in the collecting ducts.

• The result is a marked increase in urine

volume and excretion of Na

and other

electrolytes.

Osmotic Diuresis

• Osmotic diuresis is produced by the administration of

compounds such as

mannitol

and related

polysaccharides that are

filtered

but

not reabsorbed

• It is also produced by

naturally

occurring substances

when they are present in amounts exceeding the

capacity of the tubules

to reabsorb them.

• In diabetes mellitus, for example, the

glucose

that

remains in the tubules when the filtered load exceeds
the

causes

polyuria

• Osmotic diuresis can also be produced by the infusion

of large amounts of

sodium chloride or urea.

Osmotic Diuresis

• It is important to recognize the difference between

osmotic diuresis and water diuresis.

• In

water diuresis

, the amount of water reabsorbed in

the proximal portions of the nephron

is normal

, and

the maximal urine flow that can be produced is about

16 mL/min.

• In osmotic diuresis, increased urine flow is due to

decreased water reabsorption

in the proximal tubules

and loops and very large urine flows can be produced.

• As the load of excreted solute is increased, the

concentration of the urine approaches that of plasma

in spite of maximal vasopressin secretion, because an

increasingly large fraction of the excreted urine

isotonic proximal tubular fluid

Approximate relationship between urine concentration and urine

flow in osmotic diuresis in humans. The dashed line in the lower

diagram indicates the concentration at which the urine is

isosmotic with plasma.

Relation of Urine Concentration to GFR

• The

magnitude

of the

osmotic gradient

along the

medullary pyramids is increased when the

rate of

flow

of fluid through the loops of Henle is

decreased

• A reduction in GFR such as that caused by

dehydration

produces a decrease in the volume

of fluid presented to the countercurrent

mechanism, so that the

rate of flow

in the loops

declines and the urine becomes

concentrated

• When the GFR is low, the urine can become

quite concentrated in the absence of

vasopressin.

Thank you