Tubular Function pdf - Dr. Abdullah

بسم هللا الرحمن الرحيم

Tubular function

TUBULAR FUNCTION

General Considerations

• The amount of any substance (X) that is filtered is the product of

the

GFR

and the

plasma level of the substance

• The tubular cells may add more of the substance to the filtrate

(

tubular secretion

), may remove some or all of the substance from

the filtrate (

tubular reabsorption

), or may do both.

• The amount of the substance excreted per unit time (U

V.) equals

the amount

filtered plus

the

net amount transferred

by the

tubules.

• This latter quantity is conveniently indicated by the symbol T

• The

clearance

of the substance

equals

the GFR if there is no net

tubular secretion or reabsorption,

exceeds

the GFR if there is net

tubular secretion, and is

less than

the GFR if there is net tubular

reabsorption.

Tubular function

Mechanisms of Tubular

Reabsorption & Secretion

• Small proteins

and some

peptide

hormones are

reabsorbed in the

proximal

tubules by

endocytosis

• Other substances are secreted or reabsorbed in the

tubules by

passive diffusion

between cells and through

cells by

facilitated diffusion

down chemical or

electrical gradients or

active transport

against such

gradients .

• Movement is by way of

ion channels

exchangers

cotransporters

, and

pumps

•

Mutations

of individual

genes

for many of them cause

specific syndromes such ,

Bartter's

syndrome, and

Liddle's

syndrome, and a large number of mutations

have been described.

Mechanism for Na

reabsorption in the proximal tubule. Solid lines indicate active transport;

dashed lines indicate cotransport; and the dotted line indicates passive diffusion.
Note that Na

moves from the lumen into the cells by cotransport and that Na

and H

diffuse into the tubular lumen at the intercellular tight junctions.

Mechanisms of Tubular

Reabsorption & Secretion

• It is

important to note

that the

pumps

and

other units

in the

luminal membrane are different from those in the basolateral

membrane.

• It is this

different distri-bution

that makes possible net movement

of solutes across the epithelia.

• Like transport systems elsewhere, renal active transport systems

have a maximal rate, or

transport maximum (Tm),

at which they

can transport a particular solute.

• Thus, the

amount

of a particular solute

transported

proportionate to the amount present up to the Tm for the solute

but at higher concentrations

, the transport mechanism is saturated

and there is no appreciable increment in the amount transported.

• However, the Tms for

some systems are high

, and it is difficult to

saturate them

Mechanisms of Tubular
Reabsorption & Secretion

• It should also be noted that the tubular epithelium, like

that of the small intestine and gallbladder, is a

leaky

epithelium

in that the tight junctions between cells

permit

the passage

of some water and electrolytes.

• The

degree

to which leakage by this

paracellular pathway

contributes

to the

net flux

of fluid and solute

into and out

of the tubules is controversial since it is difficult to

measure, but current evidence seems to suggest that it is a

significant factor.

• One indication of this is that

paracellin-1

, a protein

localized to tight junctions, is related to Mg

reabsorption,

and a loss-of-function mutation of its gene causes

severe

and Ca

loss in the urine.

Mechanism for Na

reabsorption in the proximal tubule. Solid lines indicate active transport;

dashed lines indicate cotransport; and the dotted line indicates passive diffusion.
Note that Na

moves from the lumen into the cells by cotransport and that Na

and H

diffuse into the tubular lumen at the intercellular tight junctions.

Renal handling of various plasma constituents
in a normal adult human on an average diet.

Reabsorption

• The

reabsorption

and Cl

plays a major role in body electrolyte

and water metabolism .

•

In addition, Na

transport is

coupled

to the movement of

, other

electrolytes

glucose

amino acids

organic acids

phosphate

, and other

substances across the tubule walls.

• The principal

cotransporters

and

exchangers

in the various parts of the

nephron are shown in table.

•

In the

proximal

tubules, the

thick

portion of the ascending limb of the

loop of Henle, the

distal

tubules, and the

collecting ducts

, Na

moves

cotransport or exchange

from the tubular lumen into the tubular

epithelial cells down its

concentration and electrical

gradients and is

actively pumped

from these cells into the interstitial space.

• Thus, Na

is actively transported out of all parts of the renal tubule

except the thin portions of the loop of Henle.

• Na

is pumped into the interstitium by

-K

ATPase

• It extrudes

three Na

in exchange for

two K

that are pumped into the

cell.

Transport proteins involved in the movement of Na

and Cl

across

the apical membranes of renal tubular

cells

Reabsorption

• The tubular cells are connected by

tight junctions

at their luminal edges,

but there is space between the cells along the rest of their lateral borders.

•

Much of the Na

is actively transported into these extensions of the

interstitial space, the

lateral intercellular spaces

•

Proximal tubular reabsorbate is,

slightly hypertonic

and water moves

passively along the

osmotic gradient

created by its absorption into tubular

epithelial cells.

•

It is now known that the

apical membranes of proximal tubule cells

contain water channels

which aid the movement of water .

•

From the cells,

the water moves into the lateral intercellular spaces

• The rate at which

solutes and water move into the capillaries

from the

lateral intercellular spaces and the rest of the interstitium is determined

by the

Starling forces

determining movement across the walls of all

capillaries, ie, the

hydrostatic and osmotic

pressures in the interstitium

and the capillaries .

•

and H

leak back

to the tubular lumen via the

intercellular

junctions

, especially when the lateral intercellular spaces are distended.

Glucose Reabsorption

• Glucose

amino acids

, and

bicarbonate

are reabsorbed

along with Na

in the early portion of the

proximal tubule

• Farther along the tubule,

is reabsorbed with Cl

• Glucose is typical of substances removed from the urine by

secondary active transport

• It is filtered at a rate of approximately 100 mg/min .
• Essentially

all of the glucose is reabsorbed

, and no more

than a few milligrams appear in the urine per 24 hours.

• The amount

reabsorbed

is proportionate to the amount

filtered

and hence to the plasma glucose level (P

) times

the GFR

up to

the transport maximum (Tm

); but when the

is exceeded, the amount of glucose in the urine rises .

• The Tm

is about 375 mg/min in men and 300 mg/min in

women.

Top: Relation between the plasma level (P) and excretion (UV.) of
glucose and inulin. Bottom: Relation between the plasma
glucose level (P

) and amount of glucose reabsorbed (T

)

Glucose Reabsorption

• The

renal threshold

for glucose is the plasma

level at which the glucose first appears in the
urine in more than the normal minute amounts.

• However, the actual renal threshold is about 200

mg/dL of arterial plasma, which corresponds to a
venous level of about 180 mg/dL .

Glucose Transport

Mechanism

• Glucose reabsorption in the kidneys is similar to

glucose reabsorption in the intestine .

• Glucose and Na

bind to the common carrier

SGLT 2

the luminal membrane , and

glucose is carried into the

cell as Na

moves down its electrical and chemical

gradient.

•

The Na

is then pumped out of the cell into the lateral

intercellular spaces, and the glucose is transported by

GLUT 2

into the interstitial fluid.

• Thus, glucose transport in the kidneys as well as in the

intestine is an example of

secondary active transport

Glucose Transport
Mechanism

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