Transcript 5&6Tubular reabsorption& Secretion2015-05

TUBULAR REABSORPTION &
SECRETION
Dr. Eman El Eter
Juxtamedullary nephrons vs Cortical nephrons
Urine Formation Preview
Introduction
Urinary excretion =
Glomerular
Filtration –Tubular
reabsorption +
Tubular secretion.
Tubular secretion means:
the net movement of solutes
from peritubular
capillaries into the tubules.
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Introduction, cont…..
What are the routes through which a substance
enter the tubules?
1- Glomerular filtration.
2- Secretion from the peritubular
capillaries which occurs in two
steps:
a. simple diffusion of the
substance from peritubular
capillaries into renal inerstitium.
b. movement across the tubular
epithelium into the lumen through
active or passive transport.
Mechanisms of tubular transport:

Active transport:
ii.
Primary active transport: e.g. Na-K-pump, H+-pump
Secondary active transport : e.g. Na-K-2Cl co-transport,
glucose-sodium co-transport, amino acid-sodium co-transport.
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Passive transport:
i.
ii.
Simple diffusion e.g. Cl, HCO3-, urea.
Facilitated diffusion glucose at the basal border.
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Osmosis.
i.
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Thus the molecules moves through ion channels,
transporters, pumps & exchangers.
Pinocytosis/ exocytosis.
Primary Active transport
Carrier, direct source of
Energy ATP, against
electrochemical gradient
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Examples:
Sodium potassium
ATPase,
Hydrogen ATPase,
Hydrogen potassium
ATPase, and
Calcium ATPase.
High
conc
Na transport through PCT
Secondary active transport
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One of the substances (e.g., sodium)
diffuses down its electrochemical
gradient,the energy released is used to
drive another substance (e.g. glucose)
against its electrochemical gradient.
Both bind to one carrier protein to be
transported together.
Thus, secondary active transport does not
require energy directly from ATP.
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The direct source of the energy is that
liberated by the simultaneous facilitated
diffusion of another transported
substance down its own electrochemical
gradient.
The electrochemical gradient for Na is
maintained by Na/K pump..
Secondary active transport, cont……
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Na-K-2Cl
transport
In thick ascending
limb of Henle
“loop” diuretics
as furosemide,
inhibits the action
of the sodium 2chloride,
potassium
cotransporter.
Simple diffusion
Reabsorption of
Chloride, Urea, and
Other Solutes by
Passive Diffusion
Negative ions such as
chloride are transported
along with sodium
because of electrical
potentials.
Urea:
Inner modulary
collecting
duct, passive urea
reabsorption is
facilitated by specific
urea transporters
Osmosis
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Transport of solutes out of the tubules by either
primary or secondary active transport, makes their
concentration inside the cells to decrease while
increase in the renal interstitium. This creates a
concentration difference that causes osmosis of water
in the same direction that the solutes are transported,
from the tubular lumen to the renal interstitium.
Water reabsorption is mainly coupled to sodium.
Permeability differs through the nephron.
Route: Paracellular via tight junctions
Effect of ADH (Distal & collecting tubules).
Transport through PCT
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Criteria of PCT:
Highly metabolic cells, rich in mitochondria.
Transporter proteins & channels.
Wide surface area of brush border, basolateral
membrane
Renal tubular reabsorption through PCT
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Solute reaborption in the proximal tubule is isosmotic (water
follows solute somatically and tubular fluid osmolality remains
similar to that of plasma= equal amount of solute and water
are reabsorbed).
65%-70% of water and sodium reabsorption occurs in the
proximal tubule
 90% of bicarbonate, calcium, K+
 100% of glucose & amino acids.
 Secretion: organic acids and bases such as bile salts,
oxalate, urate, and catecholamines, certain drugs, such as
penicillin and salicylates,
Proximal tubules: coarse adjustment.
Distal tubules: fine adjustment (hormonal control).
Reabsorption through PCT
Loop of Henle
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Responsible for producing a concentrated urine by
forming a concentration gradient within the medulla
of kidney.
When ADH is present, water is reabsorbed and
urine is concentrated.
Counter-current multiplier.
Absorption through loop of Henle:
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Descending limb: is water permeable and allow absorption
of 25% of filtered H2O. It is impermeable to Na-CL.
Thin ascending limb: is impermeable to H2O, but permeable
to Na-Cl, where they are absorbed passively in this part .
Thick ascending limb: is impermeable to H2O.
Na-K-2Cl co-transport occur in this part.
By the end of ascending limb of loop, the tubular fluid
becomes hypo-osmolar to plasma.
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Na+-2Cl-K+ co transport:
Thick ascending limb of Henle
Distal convoluted tubule and collecting
ducts
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What happens here depends on hormonal control:
Aldosterone affects Na+ and K+
ADH – facultative water reabsorption
Parathyroid hormone – increases Ca++ reabsorption.
Fine adjustment of tubular filtrate takes place here
according to body needs.
The first portion of DCT forms part of JGA, that provides
feedback control of GFR and RBF of the same nephron.
The next early portion has the same characteristics as
ascending limb of Henle that is impermeable to water but
absorbs solutes. So it is called the diluting segment & the
osmotic pressure of the fluid ~ 100 mOsm/L.
DCT
Late distal tubule& collecting tubules
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Have similar functional characteristics.
Composed of two types of cells:
a. Principal cells: absorb Na+& H2O and secrete
K+
b. Intercalated cells: absorb K+ & secrete H+
Impermeable to Urea.
water permeability under ADH
Secretion of K+ and reabsorption of Na+
controlled by aldosterone.
Cell types of the nephron
Medullary collecting ducts
Reabsorb <10% of sodium & H2O.
 Final site for processing urine and so determine final
urine output of H2O & solutes
 Characteristics:
- Under ADH control.
-Highly permeable to urea.
-Secretes H+ against conc gradient (role in acid-base
balance).

Medullary collecting ducts
urea
Na+, K+, H+
urea
Distal convoluted tubule and collecting ducts
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Tubular secretion to get rid of substances:
K+, H+, urea, ammonia, creatinine and
certain drugs
 Secretion of H+ helps maintain blood pH
(can also reabsorb bicarb and generate
new bicarb)
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Na+ absorption
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Na & Cl reabsorption plays a
major role in body electrolyte
and water metabolism.
Na+ transport is also coupled to
the movement of H+, K+,
glucose, amino acids.
Na+ absorption occurs by many
mechanisms depending on the
part of nephron:
1- active transport mechanism:
E.g. Collecting tubules & ducts.
2- Passive at the thin ascending
limb
3- Co-transport: thick ascending
i.e. Active all through except thin
ascending limb.
From tubular
lumen into
tubular cells
Na+ moves
by;
Exchanger
Co-transport.
It helps
reabsorption
of nutrients
Na+ is pumped
into the
interstitium by
Na+-K+ ATPAse
Glucose handling
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Glucose absorption
also relies upon the
Na+ gradient. It is
absorbed by Naglucose cotransport.
Most reabsorbed in
proximal tubule.
At apical
membrane, needs
Na+/glucose
cotransporter
(SGLT)
Crosses basolateral
membrane via
glucose
transporters
(GLUT’s), which do
not rely upon Na+.
Glucose transport, cont…..
Tubular transport maximum for glucose
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Essentially all glucose is
reabsorbed
Tmg = 375 mg/min in
men and 300 mg/min in
women.
The renal threshold for
glucose= 180 mg/dl
Handling of glucose is
limited by saturation of
the transport mechanism
i.e. carriers.
Glucose titration curve
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Ideal curve occurs if Tmg in
all tubules is identical and
if glucose was removed
from all tubules .
Actual curve is rounded
(dashed line) and deviates
from the ideal curve. This
deviation is called splay.
The magnitude of the splay
is inversely proportionate
to the avidity with which the
transport mechanism binds
the substance it transports.
Water reabsorption
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PCT: 65% of filtered
water reabsorbed.
Descending loop of
Henle:20-25% .
Ascending limb= zero
water reabsorbed.
Distal tubules &
collecting tubules: under
ADH control
Regulation of tubular reabsorption
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There must be a balance
between tubular
reapsorption and glomerular
filtration.
This is controlled by local ,
nervous & hormonal
mechanisms.
Do you think that water and
solutes are dependently
regulated?
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1.Glomerulotubular
balance; prevents
overloading of distal parts
when GFR increases.
2. Peritubular capillary
reabsorption is regulated
by hydrostatic and colloidal
pressures through the
capillaries.
3. ABP: if increased it
reduces tubular
reapsorption:
autoregulation.
Regulation of tubular reabsorption, cont……
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4-Tubuloglomerular
feedback:
What is its
physiological
importance?
Regulation of tubular reabsorption, cont……
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4. Hormonal:
- Aldosterone: Na+
Reabsorption, K+&H+ secretion
-Ang II.: (+)Aldosterone
ADH (+) H2O2 reabsorption
ANP: (+)Na+ excretion &
diuresis
Parathyroid hormone:
Increases calcium reabsorption
& decreases phosphate
reabsorption.
Nervous: Sympathetic:
-Increases Na+
reabsorption.
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Mechanism of aldosterone action
Secondary active
secretion
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This transport is mediated by a
specific protein in the brush
border of the luminal
membrane.
As sodium is carried to the
interior of the cell, hydrogen
ions are forced outward in the
opposite direction into the
tubular lumen.
The Na+ electrochemical gradient is utilized by the
exchanger to extrude H+ from the cell with a 1
Na+ : 1 H+ coupling; Na+-H+ counter transport
Proximal tubules
K+ handling
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K+ is the major cation in
cells and its balance is
essential for life.
Small change from 4 to
5.5 mmoles/L =
hyperkalaemia
K+ is reabsorbed at
proximal tubule.
Changes in K+ excretion
due to changes in K+
secretion in distal tubule
+
K
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handling
K+ reabsorption along the
proximal tubule is largely
passive and follows the
movement of Na+ and
fluid.
K+ secretion occurs in
cortical collecting tubule
(principal cells), and relies
upon active transport
across basolateral
membrane and passive
exit across apical
membrane into tubular
fluid.
Reabsorption of bicarbonate
Summary of events that occurs in the nephron: