RENAL TUBULAR TRANSPORT

Widayanti,dr., M.Kes
OUTLINE
• Tubular Reabsorption :
-Na reabsorption
- Glucose & amino acid reabsorption
- Tubular maximum
- PO43- & Ca 2+ reabsorption
- Cl-, H2O & urea reabsorption

• Tubular secretion :
- Hidrogen ion secretion
- Potassium ion secretion
- Organic ion secretion

• Urine excretion :
- Countercurrent multiplication
- Countercurrent exchange
TUBULAR REABSORPTION
• Tubular reabsorption is a highly selective
process.
• The quantity reabsorbed of each substance
is the amount required to maintain the
proper composition & volume of the
internal fluid environment.
• The tubules have a high reabsorptive
capacity for substances needed by the body
& little/no reabsorptive capacity for
substances of no value
• As H2O & other valuable constituents
are reabsorbed, the waste products
remaining in the tubular fluid become
highly concentrated

• The tubules typically reabsorb :

- 99% of the filtered H2O
- 100% of the filtered sugar
- 99.5 % of the filtered salt
 TRANSEPITHELIAL TRANSPORT
• Tubular reabsorption involves transepithelial
transport

• The tubule wall is one cell thick & is in close

proximity to a surrounding peritubular
capillary

• Adjacent tubular cells do not come into

contact with each other except where they
are joined by thight junctions at the lateral
edges near their luminal membranes

• Interstitial fluid lies in the gaps between

adjacent cells (lateral spaces) and between
the tubules & capillaries
• The basolateral membrane faces the
interstitial fluid at the base & lateral
edges of the cell

• The tight junctions largely prevent

substances from moving between the
cells, so materials must pass through
the cells to leave the tubular lumen &
gain entry to the blood
TRANSEPITHELIAL TRANSPORT
STEPS OF TRANSEPITHELIAL TRANSPORT

1. It leave the tubular fluid by crossing the

luminal membrane of the tubular cell

2. It pass through the cytosol from one side

of the tubular cell to the other

3. It cross the basolateral membrane of the

tubular cell to enter the interstitial fluid

4. It difusse through the interstitial fluid

5. It penetrate the capillary wall to enter

the blood plasma by ultrafiltration that is
mediated by hydrostatic & colloid
osmotic forces
PASSIVE vs ACTIVE REABSORPTION
The two type of tubular reabsorption depend
on whether local energy expenditure is
needed for reabsorbing substances :
1. Passive reabsorption
No energy is spent for the substance’s
net movement

2. Active reabsorption
If any one of the steps in the
transepithelial transport of a substance
requires energy
Net movement of the substances occurs
against an electrochemical gradient
(glucose, amino acid, Na+, PO43-)
ACTIVE REABSORPTION
1.primary active transport
Transport that is coupled directly to an
energy source, such as the hydrolysis
of ATP (sodium-potassium ATPase
pump)

2.secondary active transport

Transport that is coupled indirectly to
an energy source, such as that due to
an ion gradient (reabsorption of
glucose)
SODIUM REABSORPTION
• 80% of the total energy spent by
kidneys is used for Na+ transport
• Na + is reabsorbed throughout most of
the tubule with exception of the
descending limb of the loop of Henle

• Of the Na + filtered, 99.5% is normally

reabsorbed :
-67% in the proximal tubule
-25% in the loop of Henle
-8% in the distal & collecting tubules
• Sodium reabsoption in the proximal
tubule plays a pivotal role in reabsorbing
glucose, amino acids, H2O, Cl- & urea

• Sodium reabsorption in the ascending

limb of the loop of Henle, along with Cl-
reabsorption

• Sodium reabsorption in the distal &

collecting tubules is linked in part to K +
secretion & H + secretion
• Na + reabsorption involves the energy-
dependent Na + -K + ATPase carrier located in
the tubular cell’s basolateral membrane

• As this basolateral pump transports Na + out of

the tubular cell into the lateral space, it keeps
the intracellular Na + concentration low

• Because the intracellular Na + is kept low, a

concentration gradient is established that
favors the passive movement of Na + from its
higher concentration in the tubular lumen
across the luminal border into the tubular cell

• Sodium continues diffuse down a concentration

gradient from its high concentration in the
lateral space into the interstitial fluid & finally
into peritubular capillary blood
• In the proximal tubule & loop of Henle, a
constant persentage of the filtered Na + is
reabsorbed regardless of the Na + load (total
amount of Na + in the body fluids)

• In the distal part of the tubule, the

reabsorption of the filtered Na + is subject to
hormonal control

• Na + & Cl- account for more than 90% of the

ECF’s osmotic activity

• When Na + load is above normal & ECF’s

activity is increased, the extra Na + holds
extra H2O, expanding the ECF volume
RENIN ANGIOTENSIN ALDOSTERONE SYSTEM
• Granular cells of juxtaglomerular
apparatus secrete renin in response to ↓
NaCl/ECF volume/blood pressure

• Renin activate angiotensinogen

angiotensin I angiotensin II stimulate
secretion of aldosterone

• Aldosterone increase Na+ reabsorption by

the distal & collecting tubules by
promoting the insertion of :
-additional Na+ channels into the luminal
membranes
-additional Na+-K+ ATPase carriers into
the basolateral membranes
ATRIAL NATRIURETIC PEPTIDE
• ANP is released from the atria when the
heart is mechanically stretched by an
expansion of the circulating plasma
(ECF volume is increased)

• ANP promotes natriuresis & diuresis by

increasing the GFR through dilatation of
the afferent arterioles

• ANP inhibits renin & aldosterone

secretion
GLUCOSE & AMINO ACID REABSORPTION
Glucose & amino acids are completely
reabsorbed back into the blood by
special cotransport carriers with energy
& Na + dependent mechanisms located
in the proximal tubule
 TUBULAR MAXIMUM
• All actively reabsorbed substances bind with
plasma membrane carriers that transfer them
across the membrane against a concentration
gradient

• Each carrier is present in limited number &

specific for each substance

• The maximum reabsorption rate (tubular

maximum) is reached when all the carriers
specific for a particular substance are fully
occupied/saturated, so they cannot handle any
additional passengers at that time

• With the exception of Na + , all actively

reabsorbed substances have a tubular
maximum
 RENAL THRESHOLD
• Renal threshold is the plasma concentration
at which the Tm of a particular substance is
reached & substance first starts appearing
in urine

• Renal threshold for glucose is 300 mg/100 ml

• When plasma glucose concentration

exceeds the renal threshold in diabetes
mellitus, glucose appear in urine
PHOSPHATE & CALCIUM REABSORPTION
• Transport carriers for these electrolytes
are located in the proximal tubule
• Renal thresholds of phosphate & calcium
equal their normal plasma concentration
• Parathyroid hormone can alter the renal
threshold for phosphate & calcium
CHLORIDE REABSORPTION
• The amount of Cl- reabsorbed is
determined by the rate of active Na +
reabsorption
WATER REABSORPTION
• Water is passively reabsorbed throughout
the length of the tubule as H2O
osmotically follows Na +

• Of the H2O filtered, 65% is passively

reabsorbed by the end of the proximal
tubule, 15% from loop of Henle regardless
of the H2O load in the body

• Remaining 20% are reabsorbed in the

distal & collecting tubules under direct
hormonal control, depending on the
body’s state of hydration
• H2O passes through aquaporins/ water
channels
• The water channels in the proximal tubule
are always open
• The main driving force for H2O reabsorption
in proximal tubule is a compartment of
hypertonicity in the lateral spaces
• The accumulation of fluid in the lateral
spaces results in a build up of hydrostatic
pressure, which flushes H2O out of the
lateral spaces into interstitial fluid
• Return of filtered H2O to the plasma is
enhanced by the plasma colloid osmotic
pressure in the peritubular capillary
WATER REABSORPTION
UREA REABSORPTION
• Urea is a waste product from the
breakdown of protein

• In the proximal tubule, 40-50% urea is

reabsorbed passively

• In the inner medullary collecting duct,

passive urea reabsorption is facilitated
by urea transporter that is activated by
ADH
RECIRCULATION OF UREA
TUBULAR SECRETION

• Transepithelial transport of selected

substances from peritubular capillary
into the tubular lumen

• It is supplemental mechanism that

hastens elimination of hydrogen ion,
potassium ion, organic anion & cation
from the body
HYDROGEN ION SECRETION
• Hydrogen ion is important in regulating
acid-base balance in the body
• It can be secreted by the proximal,
distal & collecting tubules, depending
on the acidity of the body fluids
• When the body fluids are too acidic, H+
secretion increases
POTASSIUM ION SECRETION

• Potassium is actively reabsorbed in the

proximal tubule & actively secreted in
the distal & collecting tubules

• K + reabsorbed in a constant fashion,

whereas it secretion is variable

• During K + depletion, K + secretion is

reduced to a minimum
• Potassium ion secretion is coupled to Na +
reabsorption by the energy-dependent
basolateral Na + -K + pump that transports
K + from the lateral space into the tubular
cells

• The resulting of high intracellular K +

concentration favors net movement of K +
from the cells into the tubular lumen

• By keeping the interstitial fluid

concentration of K + low, the basolateral
pump encourages passive movement of K +
out of the peritubular capillary plasma
into the interstitial fluid
• Aldosterone stimulates K + secretion
while simultaneously enhancing these
cells reabsoption of Na +

• The basolateral pump in distal portions

of the nephron can secrete either K +
or H + in exchange for reabsorbed Na +

• Normally the kidneys secrete a

preponderance of K + , but when the
body fluids are too acidic, H +
secretion is increased
REABSORPTION IN LOOP OF HENLE
VASOPRESSIN-CONTROLLED IN FINAL
TUBULAR SEGMENT
• 20% of the filtered H2O remains in the
lumen to enter the distal & collecting
tubules for variable reabsorption that is
under hormonal control, depending on the
body’s state of hydration

• For H2O reabsorption, 2 criteria must be

met :
1.an osmotic gradient must exist across
the tubule
2.The tubular segment must be permeable
to H2O
• The distal & collecting tubules are
impermeable to H2O except in the
presence of vasopressin which increases
their permeability to H2O

• Vasopressin secretion is stimulated by a

H2O deficit when ECF is too concentrated
• The channels in the distal parts of the nephron
are regulated by vasopressin
Concentrated Urine
The basic requirements for forming a
concentrated urine are :
(1) a high level of ADH, which increases
the permeability of the distal tubules
and collecting ducts to water

(2) a high osmolarity of the renal

medullary interstitial fluid, which
provides the osmotic gradient
necessary for water reabsorption
OSMOLARITY OF THE RENAL
MEDULLARY INTERSTITIAL FLUID
• The process involves the operation of
the countercurrent mechanism.

• Countercurrent mechanism depends on

the special anatomical arrangement of :
- the loops of Henle and the vasa recta
- the collecting ducts, which carry urine
through the hyperosmotic renal
medulla
• The osmolarity of interstitial fluid in
almost all parts of the body is about
300 mOsm/L, which is similar to the
plasma osmolarity.

• The osmolarity of the interstitial fluid

in the medulla of the kidney is much
higher, increasing progressively to
about 1200 to 1400 mOsm/L in the
pelvic tip of the medulla.
The major factors that contribute to the build up of
solute concentration into the renal medulla are :
1. Active transport of sodium ions and co-
transport of potassium, chloride, and
other ions out of the thick portion of the
ascending limb of the loop of Henle into
the medullary interstitium
2. Active transport of ions from the
collecting ducts into the medullary
interstitium
3. Facilitated diffusion of large amounts of
urea from the inner medullary collecting
ducts into the medullary interstitium
4. Diffusion of only small amounts of water
from the medullary tubules into the
medullary interstitium,
VERTICAL OSMOTIC GRADIENT IN RENAL
MEDULLA
• The medulla has a constantly
maintained vertical osmotic gradient
that is fundamental in concentrating
urine in the collecting ducts
• The gradient is set up by a process
called countercurrent multiplication,
that occurs in the long Loop of Henle

• Filtrate enters the loop at 300

milliosmols/liter, the isotonic
concentration in the body, and exits at
100 mosm/liter, but along the way, a
process sets up the 300 to 1200 gradient
in the medulla of the kidney

• The descending loop is permeable to

water, but not NaCl, the ascending loop
is permeable to NaCl but not to water
COUNTERCURRENT MULTIPLICATION
• Once the incremental medullary gradient
is established, it stays constant because
of the continuous flow of fluid

• Benefit of countercurrent multiplication :

It establishes a vertical osmotic gradient
in the medullary interstitial fluid that
used by the collecting ducts to
concentrate urine
COUNTERCURRENT EXCHANGE
• Countercurrent exchange is the passive
exchange of solutes & H2O between the 2
limbs of the vasa recta & the interstitial
fluid to conserves the medullary vertical
osmotic gradient
• Because capillaries are freely permeable to
NaCl & H2O, the blood would progressively
pick up salt & lose H2O through passive
fluxes as it flows through the depths of the
medulla
• This dilemma is avoided by the hairpin
construction of the vasa recta which looping
back through the concentration gradient in
reverse
COUNTERCURRENT EXCHANGE