RENAL TRANSPORT

MECHANISMS
Renal Physiology 4
09/19/2012
Charles J. Foulks, M.D.

GFR 125 ml/min (180L/day)

(about 1% is excreted)

Filtration, reabsoption, and excretion rates of substances by the

kidneys

Glucose

Filtered

Reabsorbed

Excreted

Reabsorbed

(meq/24h)

(meq/24h)

(meq/24h)

(%)

(g/day)

Bicarbonate (meq/day)

180
4,320

180

4,318

100
2

> 99.9

Sodium

(meq/day) 25,560

25,410

150

99.4

Chloride

(meq/day) 19,440

19,260

180

99.1

Water

(l/day)

169

167.5

1.5

99.1

Urea

(g/day)

48

24

24

50

Creatinine

(g/day)

1.8

1.8

Two pathways of the absorption:

Transcellular
Pathway

Lumen
Cells

Paracellular
transport
Plasma

Mechanism of Transport
1. Primary Active Transport
2. Secondary Active Transport
3. Pinocytosis
4. Passive Transport

Primary active reabsorption

1- Na+ diffuse across basolateral memb by
Na+ -K+ pump
2- Na+ diffuses across luminal memb into
the cell according to electro chemical
gradient established by Na+ -K+ pump
3- Na+, water & other substances are
reabsorbed into peritubular capillaries

Primary Active Transport

Secondary active reabsorption

Co transport
2 substances bind to a specific carrier
protein
E.g. Na+ diffuses down electrochemical
gradient & glucose is transported against
its chemical gradient in luminal border
No direct energy from ATP but it depends
on energy of primary active Na+ - K+ pump

Passive reabsorption
It occurs secondary to solute reabsorption
Chloride
-follows Na reabsorption
-PCT& DCT
Water
By osmosis to interstitium through
paracellular route
Bicarbonate
formed inside the cell from carbonic
acids by the help of carbonic anhyderase
Urea
Reabsorped secondary to water
reabsorption

Passive Transport Diffusion

Pinocytosis:
Some parts of the tubule,
especially the proximal tubule,
reabsorb large molecules such
as proteins by pinocytosis.

Transportation of Sodium, Water and

Chloride
Sodium,
water
and
chloride
reabsorption in proximal tubule
Proximal tubule, including the proximal
convoluted
tubule
and
thick
descending segment of the loop
Proximal reabsorption is ISOMOTIC.
The PT is the Arnold Schwarzennger of
the kidney.

Tubular secretion
Transport of substances from peritubular
capillaries to tubular lumen
Primary active secretion
-For H+
-In late distal & collecting tubules
-H+ -ATPase pump at luminal memb
Secondary active secretion
-H+ in PCT (counter-transport)
-K+, urate in distal tubules

Reabsorption & secretion along

different parts of the nephtron
The proximal convoluted tubule PCT
Reabsorption of

65% of Na+ ( 1ry active)

65 % of K+ (2ry active), water, urea & Cl- (passive)

100% of glucose & amino acids ( 2ry active)

90% Ca

Po4 , Mg+, nitrate, sulfate

Bicarbonate
formed inside the cell from carbonic acids by
the help
of carbonic anhyderase to give HCO3&H2
HCO3 is reabsorbed &H2 is secreted

Secretion

H2 (2ry active counter transport - antiport)

Ammonia
formed inside the tubular cells
acts as H2 acceptor

Waste products & drugs

Reabsorb about 65 percent of the filtered sodium, chloride,

bicarbonate, and
potassium and essentially al the filtered glucose and amino
acids.

Sodium, water and chloride reabsorption

in proximal tubule
The sodium-potassium ATPase: major force
reabsorption of sodium, chloride and water

for

In the first half of the proximal tubule, sodium is

reabsorbed by co-transport along with glucose, amino
acids, and other solutes.
In the second half of the proximal tubule, sodium
reabsorbed mainly with chloride ions.

Sodium, water and chloride

reabsorption in proximal tubule
The second half of the proximal tubule has a relatively
high concentration of chloride (around 140mEq/L)
compared with the early proximal tubule (about 105
mEq/L)
In the second half of the proximal tubule, the higher
chloride concentration favors the diffusion of this ion
from the tubule lumen through the intercellular
junctions into the renal interstitial fluid.
Early PT reabsorbs bicarbonate which is gone by late
PT.

Na+ absorption

Na+ absorbed by active

transport mechanisms, NOT
by TM mechanism.
Basolateral ATPases establish
a gradient across the tubule
wall.
Proximal tubule is very
permeable to Na+, so ions
flow down gradient, across
membranes.
Microvilli create large surface
area for absorption.
Electrical gradient created
also draws Cl- across.
H2O follows Na+ due to
osmotic force.
Means fluid left in tubule is
concentrated.

(2) Sodium and water transport in the

loop of Henle
The loop of Henle consists of three functionally
distinct segments:
the thin descending segment,
the thin ascending segment,
and the thick ascending segment.

TDLH
High permeable to water
and moderately permeable
to most solutes
but has few mitochondria
and little or no active
reabsorption.
TALH
Reabsorbs about 25% of
the
filtered
loads
of
sodium,
chloride,
and
potassium, as well as large
amounts
of
calcium,
bicarbonate,
and
magnesium.
This segment also secretes
hydrogen ions into the
tubule

Mechanism of sodium, chloride, and potassium

transport in the thick ascending loop of Henle

K+ handling

K+ is major cation in cells and

balance is essential for life.
Small change from 4 to 5.5
mmoles/l = hyperkalaemia =
ventric. fibrillation = death.
To 3.5 mmoles/l =
hyperpolarise = arrhythmias
and paralysis = death.
Reabsorb K+ at proximal
tubule.
Changes in K+ excretion due
to changes in K+ secretion in
distal tubule
Medullary trapping of K+
helps to maximise K+
excretion when K+ intake is
high.

K+ handling

K+ reabsorption along
the proximal tubule is
largely passive and
follows the movement of
Na+ and fluid (in
collecting tubules, may
also rely active
transport).

K+ secretion occurs in
cortical collecting tubule
(principal cells), and
relies upon active
transport of K+ across
basolateral membrane
and passive exit across
apical membrane into
tubular fluid.

Modulation of K+ secretion
Luminal factors
Stimulators

Inhibitors

Flow rate

[K+]

[Na+]

[Cl-]

[Cl-]

[Ca2+]

[HCO3-]

Ba2+

-ve luminal voltage

Amiloride

Selected Diuretics
Peritubular Factors
Stimulators

Inhibitors

K+ intake

pH

[K+]

Adrenaline

pH
Aldosterone

2. Glucose Reabsorption
Glucose is reabsorbed along with Na+ in the
early portion of the proximal tubule.
Glucose is typical of substances removed
from the urine by secondary active transport.
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 (PG) times the GFR up to the
transport maximum (TmG);
But when the TmG is exceed, the amount of
glucose in the urine rises
The TmG is about 375 mg/min in men and 300
mg/min in women.

GLUCOSE REABSORPTION HAS A

TUBULAR MAXIMUM
Glucose
Reabsorbed
mg/min

Filtered

Excreted

Reabsorbed

Renal threshold (300mg/100 ml)

Plasma Concentration of Glucose

The renal threshold for glucose is the

plasma level at which the glucose first
appears in the urine.
One would predict that the renal
threshold would be about 300 mg/dl ie,
375 mg/min (TmG) divided by 125
mL/min (GFR).
However, the actual renal threshold is
about 200 mg/dL of arterial plasma,
which corresponds to a venous level of
about 180 mg/dL.

Top: Relationship
between the plasma
level (P) and
excretion (UV) of
glucose and inulin

Bottom:
Relationship
between the plasma
glucose level (PG)
and amount of
glucose reabsorbed

Glucose handling

Glucose
absorption also
relies upon the
Na+ gradient.
Most reabsorbed
in proximal
tubule.
At apical
membrane,
needs
Na+/glucose
cotransporter
(SGLT)
Crosses
basolateral
membrane via
glucose
transporters
(GLUTs), which
do not rely upon
+

Amino acid handling

Preserve as much of these essential nutrients as possible.

Can be absorbed by GI tract, products of protein catabolism,
or de novo synthesis of nonessential amino acids.
TM values lower than that of glucose, so can excrete excess in
urine.
Amino acid transporters rely upon Na+ gradient at apical
membrane, but a couple of exceptions dont.
Exit across basolateral membrane via diffusion , but again,
some exceptions rely on Na+.

1. Reabsorption is a 2-step process: lumen to interstitium,

and interstitium to peritubular capillary.
2. Flux from lumen to interstitium can be transcellular,
using separate transport steps in the apical and
basolateral membranes, or paracellular,
around the cells through tight junctions.
3. Channels and transporters promote the transmembrane
flux of solutes that cannot permeate lipid bilayers.
4. Osmotic gradients drive a volume flux across
membranes and epithelia.

5. Osmotic pressure and osmolality mean the same thing and represent
the power of dissolved solute to drive an osmotic flux of water.
6. For convenience, osmolality is approximated by the easier concept of
osmolarity.
7. Water and solutes, which are reabsorbed from lumen to interstitium,
then move from interstitium to peritubular capillaries by bulk flow,
driven by Starling forces.
8. The reabsorption of water and almost all solutes is linked, directly or
indirectly, to the active reabsorption of sodium.
9. All reabsorptive processes have a limit on how fast they can occur,
either because the transporters saturate (Tm systems) or because the
substance leaks back into the lumen (gradient-limited systems)