Professional Documents
Culture Documents
N°55
Transport
mechanisms
in
the
kidneys
(This
is
not
a
proper
chapter
of
a
textbook;
I
don’t
know
where
to
start!)
DIFFUSION
• Net
movement
of
substances
down
an
electrochemical
gradients
• Occurs
across
the
plasma
membrane
(lipid-‐soluble)or
through
channels
(water-‐soluble)
FACILITATED
DIFFUSION
• Net
movement
of
a
substance
down
itselectrochemical
gradient
which
depends
on
interaction
of
the
substance
with
a
specific
membrane
protein
called
transporters
or
carriers
Ok
take
it
as
the
title
want
to
mention,
I’ll
write
down
some
key
features:
• Solutes
can
be
transported
through
epithelial
cells
or
between
cells,
and
here
we
divide
the
transcellular
pathway
from
the
paracellular
pathway
(do
you
remember
the
tight
junctions)
• Primary
active
transport
through
the
tubular
membrane
is
linked
to
hydrolysis
of
ATP,
here
you
have
to
remember
the
importance
of
transporting
solutes
against
an
electrochemical
gradient,
some
important
examples:
1. Na+-‐K+
ATPase
2. H+
ATPase
3. K+
ATPase
4. Ca++
ATPase
• Secondary
active
reabsorption
through
the
tubular
membrane
is
the
transport
of
two
substances
at
the
same
time:
1. Co-‐transport
(Na+/Glucose,
Na+/AA)
2. Counter-‐transport
(Na+/H+)
• Last
but
not
least
we
have
to
consider
endocytosis
and
pinocytosis
as
active
transport
pathways
N°56
Regulation
of
tubular
reabsorption
–
generalities
and
Hormonal
control
(super-‐synthesis)
1. Glomerotubular
balance:
intrinsic
ability
of
the
tubules
to
increase
their
reabsorption
rate
in
response
to
increased
tubular
load
(increased
tubular
inflow).
The
importance
of
glomerulotubular
balance
is
that
it
helps
to
prevent
overloading
of
the
distal
tubular
segments
when
GFR
increases.
2. Peritubular
capillary
and
renal
interstitial
fluid:
Changes
in
peritubular
capil-‐
lary
reabsorption
can
in
turn
influence
the
hydrostatic
and
colloid
osmotic
pressures
of
the
renal
interstitium
and,
ultimately,
reabsorption
of
water
and
solutes
from
the
renal
tubules.
3. Effects
on
arterial
pressure
on
urine
output
(natruresis/diuresis):
Even
small
increases
in
arterial
pressure
often
cause
marked
increases
in
urinary
excretion
of
sodium
and
water,
phenomena
that
are
referred
to
as
pressure
natriuresis
and
pressure
diuresis.
Hormonal
Control
(nothing
to
understand,
sorry
guys,
this
is
just
about
your
memory!)
Ok
you
would
have
thought
that
I’m
not
so
clear,
but
I
love
you
so…
…Here
you
find
some
key
features!!!
• Aldosterone:
increases
sodium
and
water
reabsorption,
stimulate
potassium
secretion,
affects
positively
on
renin-‐
angiotensin
system.
How
can
you
remember
it?
“Salt-‐retaining
hormone”
It
reduces
urine
volume
(more
k+,
less
NaCl)
• Angiotensin
II:
increases
sodium
and
water
reabsorption,
stimulate
hydrogen
ions
secretion,
in
particular:
1. Stimulate
aldosterone
secretion
-‐>
increase
sodium
reab.
2. Constricts
efferent
arterioles
-‐>
reduces
peritubular
capillary
hydrostatic
pressure
-‐>
net
filtration
increase!
• ADH:
once
again…
increase
water
reabsorption,
is
secreted
by
pituitary
gland
in
response
to
dehydration
and
a
rising
blood
osmolarity,
makes
collecting
ducts
more
permeable
to
H20
and
avoid
the
risk
of
water
loss
in
the
urine
• ANP:
decrease
sodium
and
water
reabsorption,
it
is
secreted
by
atrial
myocardium
of
heart
in
response
to
high
blood
pressure,
have
4
actions:
1. Dilates
afferent
arterioles
and
constricts
efferent
ones
(inc.
GFR)
2. Antagonizes
angiotensin
–
aldosterone
mechanism
3. Inhibits
secretion
of
ADH
by
pituitary
gland
4. Inhibits
NaCl
reabsorption
by
collecting
duct
• Paratyroid
Hormone:
increase
calcium
reabsorption,
promotes
also
Mg++
reabsorption,
and
stimulates
kidneys
to
complete
synthesis
of
calcitriol.
Also
inhibits
phosphate
reabsorption.
N°
57
Renal
Clearance
Renal
clearance
is
a
measurement
that
allows
one
to
analyze
the
activity
of
the
kidney.
It
is
a
very
peculiar
measurement
and
this
leads
to
confusion
for
students.
The
definition
for
clearance
is
the
volume
of
plasma
from
which
a
substance
is
completely
removed
by
the
kidney
in
a
given
amount
of
time
(usually
a
minute).
For
example,
the
clearance
for
urea
is
65
ml/min.
This
means
that
the
kidney
removes
all
of
the
urea
in
65
ml
of
plasma
in
one
minute.
Now,
what
is
the
actual
meaning
of
this
number?
Is
this
high?
Is
it
low?
What
significance
does
this
number
have
for
you?
(At
the
moment,
none
at
all!!)
Before
talking
about
clearance,
lets
examine
the
flow
of
plasma
in
the
kidney.
Every
minute
approximately
625
ml
of
plasma
goes
to
the
kidney.
This
is
the
renal
plasma
flow.
Some
of
the
fluid
leaves
the
kidney
in
the
plasma
while
some
leaves
the
kidney
as
urine.
There
are
only
two
ways
for
a
substance
to
end
up
in
the
urine:
either
it
is
filtered
at
the
glomerulus
and
then
not
reabsorbed
from
the
tubules,
or
the
substance
is
not
filtered
but
is
secreted
by
from
the
peritubular
capillaries
into
the
tubules.
In
either
instance,
the
substance
ends
up
in
the
collecting
duct
and
is
excreted
into
the
urine.
Of
the
625
ml/min
of
plasma
that
goes
to
the
glomerulus,
125
ml/min
are
filtered
into
Bowman's
Capsule
forming
the
filtrate
(this
is
known
as
the
glomerular
filtration
rate).
The
remaining
500
ml/min
remain
in
the
blood
and
enter
into
the
peritubular
capillaries.
Of
the
125
ml/min
filtered,
almost
all
of
the
water
in
this
fluid
is
reabsorbed
and
put
back
into
the
blood.
It
is
important
to
remember
that
the
composition
of
the
filtrate
in
Bowman's
Capsule
is
identical
to
the
composition
of
the
plasma
except
that
the
filtrate
has
no
(or
very
few)
proteins
(do
not
forget
that
this
is
not
true
for
the
urine).
This
means,
for
example,
that
the
concentration
of
glucose
in
the
filtrate
in
Bowman's
Capsule
is
the
same
as
that
in
the
plasma.
The
same
is
true
for
almost
all
of
the
other
solutes
in
the
filtrate
don't
forget
this!
Ok
Renal
clearance
is
not
so
easy
to
understand,
just
remember
that
some
substances
are:
• Completely
reabsorbed:
GLUCOSE,
normal
values
(ml/min)
=
0
• Not
reabsorbed
and
not
secreted:
INULIN,
NV
=
125
(ml/min)
you
must
underline
the
result,
in
poor
words
125
is
the
normal
filtration
rate
of
plasma,
it
is
not
reabsorbed,
not
secreted
so
its
value
will
remain
the
same
of
the
filtration
rate!
• PAH
(para-‐amino-‐hippuric
acid)
is
a
substance
that
will
be
completely
secreted…
wonder
what
is
the
normal
value??
Easy
Man!
=
625
(ml/min)
I
hope
it
has
been
useful
to
explain
it
step
by
step
and
with
some
details…
N°58/59/60
Physiology
of
proximal
tubule
and
mechanism
(Here
start
the
boring
part)
It
is
in
the
proximal
convoluted
tubule
that
we
reabsorb
most
of
the
materials
that
we
need
to
reabsorb
from
the
filtrate.
The
reabsorption
of
this
material
is
called
tubular
reabsorption.
When
we
talk
about
reabsorption,
it
is
clear
that
the
materials
we
are
taking
back
up
must
eventually
get
back
into
the
blood.
But
it
doesn't
go
directly
into
the
blood
from
the
tubules.
Instead,
it
is
taken
out
of
the
filtrate
by
the
cells
that
make
up
the
tubules
and
sent
into
the
interstitial
fluid
of
the
cortex
or
medulla.
From
there,
these
molecules
will
diffuse
into
the
blood
through
the
peritubular
capillaries.
The
peritubular
capillaries
are
more
porous
than
most
capillaries
and
also
have
very
low
blood
pressure
(because
they
are
the
second
set
of
capillaries);
therefore,
they
are
quite
good
at
allowing
material
to
diffuse
back
into
them.
Let's
now
talk
about
what,
specifically,
the
proximal
convoluted
tubule
(PCT)
does
and
how
it
does
it.
About
65
per
cent
of
the
filtered
Electrolytes
are
reabsorbed
in
the
proximal
tubule.
However,
the
tubular
membranes
are
highly
perme-‐
able
to
water,
so
that
whenever
solutes
are
reabsorbed,
water
also
diffuses
through
the
tubular
membrane
by
osmosis.
Therefore,
the
osmolarity
of
the
fluid
remains
about
the
same
as
the
glomerularfiltrate,
300
mOsm/L.
The
proximal
tubule
regulates
the
pH
of
the
filtrate
by
exchanging
hydrogen
ions
in
the
interstitium
for
bicarbonate
ions
in
the
filtrate;
furthermore,
it
is
responsible
for
secreting
organic
acids,
such
as
creatinine
and
other
bases,
into
the
filtrate.
Fluid
in
the
filtrate
entering
the
proximal
convoluted
tubule
is
reabsorbed
into
the
peritubular
capillaries.
This
is
driven
by
sodium
transport
from
the
lumen
into
the
blood
by
the
Na+/K+
ATPase
in
the
basolateral
membrane
of
the
epithelial
cells.
This
antiporter
primarily
drives
sodium
reabsorption.
This
is
the
most
important
transport
mechanism
in
the
PCT.
Well,
I’m
sorry
to
tell
ya
that
for
a
good
10
you
should
study
each
substance’s
parameter
and
mechanisms…
I’m
not
going
to
take
it
further
than
this,
in
the
proximal
convoluted
tubule
there
are
quite
the
most
important
functions
of
the
entire
nephron…
don’t
ask
me
to
write
more
than
this
please!!!
Take
care
about
foundations,
this
is
the
rule
for
me.
I’m
writing
only
what
is
written
on
the
slides,
cant
find
better
now…
Secretion
of
organic
acids
Endogenous
substances:
• Bile
acids
• cAMP
• Hydroxyindoleacetic
acid
• Oxalic
acid
• Uric
acid
Drugs
and
other
substances:
• Cephalothin
• Chlorothiazide
• Iodohippuric
acid
• Salicydic
acid
Secretions
of
organic
bases
Endogenous
substances:
• Acetylcholine
• Creatinine
• Dopamine
• Epinephrine
• Histamine
• N-‐methylnicotamide
• Norepinephrine
• Serotonin
• Thiamine
Drugs
and
other
substances:
• Amiloride
• Atropine
• Cimetidine
• Isoprotenol
• Morphine
• Neostigmine
• Procaine
• Quinine,
ratinidine,
trimethoprim
(why
should
whe
know
them?)
N°61
Physiology
of
the
Henle
loop
(much
more
interesting)
The
loop
of
Henle
is
also
called
the
nephron
loop.
You
have
seen
that
it
runs
into
the
medulla
(through
its
descending
limb)
and
then
back
out
(through
its
ascending
limb).
It
turns
out
that
the
descending
and
ascending
loop
differ
in
their
permeabilities.
Unlike
the
PCT,
the
cells
of
the
loop
of
Henle
are
not
equipped
with
tons
of
protein
channels
to
provide
passage
to
all
sorts
of
materials.
Instead,
they
are
quite
specific.
Key
features:
permeable
to
waters
in
the
descending
limb,
permeable
to
sodium
and
chloride
in
the
ascending
portion.
Therefore,
when
the
filtrate
runs
through
the
loop
of
Henle,
water
will
want
to
move
across
the
tubule.
You
can
probably
figure
that
it
will
move
out
of
the
tubule
because
you
know
we
are
not
done
with
reabsorption.
But
the
reason
that
it
moves
out
of
the
tubule
is
because
the
filtrate
is
hypotonic
to
the
interstitial
fluid,
and
WATER
ALWAYS
MOVES
FROM
HYPOTONIC
TO
HYPERTONIC.
Because
the
descending
limb
is
highly
permeable
to
water,
water
moves
by
osmosis
here.
As
described
above,
it
moves
out
of
the
tubule
and
into
the
medullary
interstitial
fluid
for
reabsorption.
It
should
be
easy
to
imagine
how
come
the
descending
limb
epithelium
doesn't
allow
the
solutes
across,
right?
The
descending
limb
epithelial
cells
just
do
not
have
the
protein
channels
on
them.
In
the
ascending
limb,
the
sodium-‐potassium
pump
is
working
like
mad
to
keep
shoving
sodium
out
into
the
medullary
interstitial
fluid.
This
is
a
large
part
of
the
reason
that
the
medullary
interstitial
fluid
has
its
solute
concentration
gradient
to
begin
with!
You
might
think
that
if
the
cells
shove
sodium
out,
that
potassium
would
be
in
low
concentration
in
the
interstitial
fluid,
but
potassium
ions
are
allowed
to
flow
out
passively
through
other
channels.
As
the
positive
ions
leave
the
ascending
limb
cells,
the
negative
ions
tend
to
follow,
and
that
is
why
your
book
mentions
that
chloride
ions
also
leave
in
the
ascending
limb.
Note
that
the
ascending
limb
is
NOT
permeable
to
water.
This
is
pretty
unusual.
Most
cells
allow
some
water
to
slip
through
at
any
time.
These
cells
are
specialized
to
prevent
it.
Even
their
tight
junctions
to
one
another
are
excessively
tight
so
that
water
won't
slip
by
between
the
cells.
Well
if
we
put
both
limbs
together
now…
The
beauty
of
the
loop
of
Henle
is
that
each
limb
reinforces
the
other.
By
allowing
sequential
reabsorption,
the
actions
within
the
loop
are
enhanced.
Everytime
fluid
goes
through
the
loop,
the
medulla
becomes
more
concentrated.
This
continually
provides
an
environment
for
the
water
to
be
drawn
out
of
the
tubule.
The
vasa
recta
enhance
this
even
more.
The
vasa
recta,
the
portion
of
the
peritubular
capillaries
that
overlies
the
loop
of
Henle,
does
not
carry
away
much
solute
from
the
medullary
interstitial
fluid.
In
fact,
it
kicks
out
most
of
the
sodium
ions
that
it
carries
before
ending
in
venules.
So,
the
actions
of
the
vasa
recta
also
work
to
preserve
the
gradient
set
up
in
the
medulla.
In
order
to
understand
how
the
nephron
works,
you
will
need
to
understand
osmosis
and
diffusion.
I
hope
that
you
go
back
to
look
up
and
review
osmosis...
One
of
the
hardest
things
to
understand
about
osmosis
is
the
fact
that
it
is
totally
passive,
yet
we
can
force
it
to
occur
in
the
kidneys.
How
is
that
possible?
No
matter
what,
water
flows
from
hypotonic
to
hypertonic.
That
cannot
change.
So,
if
we
want
to
force
water
to
flow,
we
can
force
a
change
in
solute
concentration
in
one
environment.
So,
if
we
shoved
lots
of
solute
into
one
compartment,
water
would
flow
into
that
(hypertonic)
compartment.
That
is
how
the
loop
of
Henle
operates
in
the
medulla.
N°
62
Physiology
of
the
distal
tubule
and
collecting
duct
Anatomically,
the
collecting
duct
is
not
a
part
of
the
nephron.
But
physiologically,
it
works
with
the
nephron.
The
distal
convoluted
tubule,
or
DCT,
has
a
lot
to
do.
It
carries
out
both
tubular
reabsorption
and
secretion:
• Reabsorption
of
sodium
• Reabsorption
of
water
• Secretion
of
hydrogen
ions
(for
blood
pH
omeostasis)
• Secretion
of
potassium
Both
the
DCT
and
the
collecting
duct
are
involved
in
reabsorption
of
water.
You
see,
if
they
only
reabsorb
a
tiny
bit
of
water,
then
around
97%
of
all
the
water
that
was
in
the
filtrate
is
reabsorbed.
If
they
hardly
reabsorb
any
water,
then
only
around
95%
of
all
the
water
that
was
in
the
filtrate
is
reabsorbed.
But
if
they
are
very
active
in
water
reabsorption,
then
we
can
reabsorb
99%
of
all
the
water
that
was
in
our
filtrate.
Since
our
kidneys
handle
180
liters
of
fluid
a
day,
5%
loss
versus
1%
loss
is
a
big
deal!
I
took
these
numbers
from
books,
but
5%
of
180
is
9
liters.
I
can't
believe
a
person
can
ever
urinate
9
liters
in
one
day!
Depending
on
our
condition,
we
may
want
to
reabsorb
as
much
water
as
possible
in
our
kidneys
or
urinate
as
much
water
as
possible.
If
you
are
in
an
arid
climate
and
haven't
had
much
food
or
water,
you
would
be
better
off
if
you
didn't
lose
much
water
in
your
urine.
And
if
you
are
drinking
tons
of
liquids,
you
would
be
better
off
excreting
plenty
of
water
in
your
urine.
The
only
place
where
we
regulate
our
water
reabsorption
is
in
the
DCT
and
collecting
duct.
Here,
the
permeability
of
the
epithelia
to
water
depends
on
hormonal
influence.
ADH
(from
the
posterior
pituitary)
causes
these
epithelia
to
do
a
lot
of
water
reabsorption.
N°63
Role
of
the
ADH
in
the
concentration
of
urine
Roughly
60%
of
the
mass
of
the
body
is
water,
and
despite
wide
variation
in
the
amount
of
water
taken
in
each
day,
body
water
content
remains
incredibly
stable.
Such
precise
control
of
body
water
and
solute
concentrations
is
a
function
of
several
hormones
acting
on
both
the
kidneys
and
vascular
system,
but
there
is
no
doubt
that
antidiuretic
hormone
is
a
key
player
in
this
process.
Antidiuretic
hormone,
also
known
commonly
as
arginine
vasopressin,
is
a
nine
amino
acid
peptide
secreted
from
the
posterior
pituitary.
Within
hypothalamic
neurons,
the
hormone
is
packaged
in
secretory
vesicles
with
a
carrier
protein
called
neurophysin,
and
both
are
released
upon
hormone
secretion.
The
single
most
important
effect
of
antidiuretic
hormone
is
to
conserve
body
water
by
reducing
the
loss
of
water
in
urine.
A
diuretic
is
an
agent
that
increases
the
rate
of
urine
formation.
Injection
of
small
amounts
of
antidiuretic
hormone
into
a
person
or
animal
results
in
antidiuresis
or
decreased
formation
of
urine,
and
the
hormone
was
named
for
this
effect.
Antidiuretic
hormone
binds
to
receptors
on
cells
in
the
collecting
ducts
of
the
kidney
and
promotes
reabsorption
of
water
back
into
the
circulation.
In
the
absense
of
antidiuretic
hormone,
the
collecting
ducts
are
virtually
impermiable
to
water,
and
it
flows
out
as
urine.
Continue
in
the
next
page….
…
I’m
kidding,
it’s
over!
Ok
guys,
our
little
trip
around
the
physiology
world
ends
here,
it
was
a
pleasure
for
you,
class,
to
make
this
review.
Consider
it
a
good
point
of
starting
to
make
this
kind
of
works
in
groups
for
the
next
year,
how
much
time
we
can
save
to
make
parties
and
make
Giallo
a
fool…!
By
the
way
I
hope
this
work
will
be
helpful
for
each
of
us
to
face
the
exam,
thanks
a
lot
to
my
beloved
master
class
colleague
Mr.
Giallo
for
his
help,
and
thanks
a
lot
for
the
appreciations
I
received…
Yours,
truly…
Alessandro
Motta
“May
the
force
be
with
you”