Tubular Function 2 pdf - Dr. Abdullah

بسم هللا الرحمن الرحيم

Tubular function 2

Additional Examples of

Secondary Active Transport

• Like glucose reabsorption,

amino acid

reabsorption is

most marked in the early portion of the

proximal

convoluted

tubule.

• Absorption in this location resembles absorption in the

intestine .

• The main carriers in the luminal membrane

cotransport Na

whereas the carriers in the

basolateral membranes are not Na

-dependent.

• Na

is pumped out of the cells by

-K

ATPase

and

the amino acids leave by

passive or facilitated

diffusion

to the interstitial fluid.

Additional Examples of

Secondary Active Transport

• Some Cl

is reabsorbed with Na

and K

in the

thick ascending limb of the loop of Henle .

• In addition,

two members

of a family of Cl

channels have been identified in the kidney.

• The family is characterized by

transmembrane domains

, and members of it

are also found in muscle and other tissues.

Tubuloglomerular Feedback &

Glomerulotubular Balance

• Signals from the renal tubules feed back to affect

glomerular filtration.

• As the

rate of flow

through the ascending limb of the loop

of Henle and first part of the distal tubule increases,

glomerular filtration in the same nephron decreases, and,

conversely, a

decrease in flow

increases the GFR .

• This process, which is called

tubuloglomerular feedback

tends to maintain the constancy of the load delivered to

the distal tubule .

• The sensor for the response appears to be the

macula

densa

, and GFR is adjusted by constriction or dilation of the

afferent arteriole

• Constriction may be mediated by

thromboxane A

Tubuloglomerular Feedback &

Glomerulotubular Balance

• Conversely

, an increase in GFR causes an increase in the

reabsorption of solutes, and consequently of water,

primarily in the proximal tubule, so that in general the

percentage of the solute reabsorbed is held constant.

• This process is called

glomerulotubular balance

, and it is

particularly prominent for Na

• The change in Na

reabsorption occurs within seconds

after a change in filtration, so it seems unlikely that an

extrarenal humoral factor is involved.

• One factor is the

oncotic pressure

in the peritubular

capillaries.

• When the GFR is high, there is a relatively large increase in

the oncotic pressure of the plasma by the time it reaches

the

efferent arterioles and their capillary branches

. This

increases the reabsorption of Na

from the tubule.

REGULATION OF NA

& CL

EXCRETION

• Na

is filtered in large amounts, but it is actively

transported out of all portions of the tubule

except the

thin loop of Henle.

• Normally,

96%

to well over

99%

of the filtered

is reabsorbed.

• Most of the

is reabsorbed with Cl

, but some

is reabsorbed in the processes by which one Na

ion enters the bloodstream

for each H

ion

secreted by the tubules, and in the distal tubules

a small amount is actively reabsorbed in

association with the

secretion of K

Regulation of Na

Excretion

• Because Na

is the

most abundant

cation in ECF

and because Na

salts account for over

90%

the

osmotically active

solute in the plasma and

interstitial fluid, the amount of Na

in the body

a prime determinant of the ECF volume.

• Through the operation of the regulatory

mechanisms, the amount of Na

excreted

adjusted to

equal

the amount

ingested

over a

wide range of dietary intakes, and the individual

stays in Na

balance.

• Thus,

urinary Na

output ranges from

less than 1

meq/d

on a low-salt diet to

400 meq/d

or more

when the dietary Na

intake is high.

Regulation of Na

Excretion

• In addition, there is a

natriuresis

when saline is

infused intravenously and a

decrease in Na

excretion

when ECF volume is reduced.

• Variations in Na

excretion are effected by changes

in the

amount filtered

and the

amount reabsorbed

the tubules.

• The factors affecting the GFR, including

tubuloglomerular feedback

• Factors affecting Na

reabsorption include the

circulating level of

aldosterone

and

other

adrenocortical hormones, the circulating level of

ANP

and other

natriuretic

hormones, the amount of

angiotensin II

and

PGE

in the kidneys, and the rate

of tubular secretion of H

and K

Effects of Adrenocortical Steroids

• Adrenal mineralocorticoids such as aldosterone

increase tubular

reabsorption of Na

in association

with

secretion of K

and H

and also

reabsorption

with Cl

• When these hormones are injected into

adrenalectomized animals, there is a latent period of

10-30 minutes before their effects on Na

reabsorption

become manifest, because of the time required for the

steroids to

alter protein synthesis via their action on

DNA.

• The mineralocorticoids

act

primarily on the

cortical

collecting ducts.

• As noted , they act on

P cells

to increase the number

of active

ENaCs

in the apical membranes of these cells .

Renal P cell. Na

enters via the ENaCs in the apical membrane and is

pumped into the interstitial fluid by Na

-K

ATPases in the basolateral

membrane. Aldosterone activates the genome to produce sgk and

other proteins, and the number of active ENaCs is increased

Effects of Adrenocortical Steroids

• In

Liddle's syndrome

, mutations in the

genes that code for the

β subunit

and less

commonly the

γ subunit

of the

ENaCs

cause

them to become

constitutively active

in the

kidney.

• This leads to

retention

and

hypertension

Other Humoral Effects

• Reduction of

dietary

intake of

salt

increases

aldosterone secretion , producing marked but slowly

developing decreases in Na

excretion.

• A variety of other humoral factors affect Na

reabsorption.

• PGE

causes

a natriuresis

, possibly by inhibiting Na

-K

ATPase .

•

Endothelin

and

IL-1

cause natriuresis, probably by

increasing the formation of

PGE

• ANP

and related molecules increase intracellular

cGMP,

and this inhibits transport via the

ENaCs

• Inhibition of

-K

ATPase

by the other natriuretic

hormone, also increases Na

excretion.

•

Angiotensin II increases reabsorption

of Na

and HCO

by an action on the proximal tubules.

Other Humoral Effects

• There is an appreciable amount of

angiotensin-converting

enzyme

in the kidneys, and the kidneys convert of the

circulating angiotensin I reaching them to angiotensin II. In

addition,

angiotensin I is generated in the kidneys.

• Prolonged exposure to high levels of circulating

mineralocorticoids does not cause edema

in otherwise

normal individuals

because eventually the kidneys

escape from the effects of the steroids.

• This

escape phenomenon

, which may be due to increased

secretion of

ANP

• It appears to be reduced or absent in

nephrosis, cirrhosis,

and heart failure,

and patients with these diseases continue

to retain Na

and become edematous when exposed to

high levels of mineralocorticoids.

REGULATION OF K

EXCRETION

• Much of the filtered K

is removed from the tubular

fluid by

active reabsorption

in the

proximal

tubules ,

and K

is then

secreted

into the fluid by the

dista

tubular cells.

• The

rate of K

secretion

is proportionate to the

rate of

flow

of the tubular fluid through the distal portions of

the nephron, because with rapid flow there is less

opportunity for the tubular K

concentration to rise to

a value that stops further secretion.

• In the absence of complicating factors,

the amount

secreted

is approximately

equal to the K

intake

, and K

balance is maintained.

• In the distal tubules

, Na

is generally reabsorbed and

is secreted

•

REGULATION OF K

EXCRETION

• There is no rigid

one-for-one

exchange, and

much of the

movement of K

is passive

• However, there is electrical coupling in the

sense that

intracellular migration of Na

tends

to lower the potential difference across the
tubular cell, and this favors movement of K

into the tubular lumen.

• Since

is also reabsorbed in association

with

secretion, there is competition for the

in the tubular fluid.

REGULATION OF K

EXCRETION

• K

excretion is decreased

when the amount of

reaching the distal tubule is

small

, and it is also

decreased when

secretion

increased

• When

total body K

is high

, H

secretion is inhibited,

apparently because of intracellular alkalosis; K

secretion and excretion are therefore facilitated.

• Conversely

, the cells are acidic in

depletion

, and K

secretion declines.

• Apparently the K

secretory mechanism is capable of

adaptation

," because the amount of K

excreted

gradually increases when a constant large dose of a
potassium salt is administered for a prolonged period.

Hypokalemia

•

Hypokalemia

is common and can be severe.

• In addition to its occurrence when there is

excessive loss in the urine

, it is occasionally

seen in patients with excess loss in

diarrheic

stools

, in patients in whom K

shifted

into

cells by

insulin

β-adrenergic agonists

, and in

patients with a prolonged

low intake of K

• Hyperkalemia

is a more dangerous condition

because of its effects on the heart , but

rarely occurs unless

renal function is

depressed.

Renal handling of various plasma constituents in a

normal adult human on an average diet

THANK

YOU