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Renal Physiology- Tubular function

Prof Kate Denton
Kate.Denton@monash.edu
Textbooks:
VANDERS HUMAN PHYSIOLOGY
Chapter 14, Section A, pages 490-496

TEXTBOOK OF MEDICAL PHYSIOLOGY
Guyton & Hall, -- Chapters 25-29
Processes involved in urine formation
1.Glomerular filtration
2.Tubular secretion
3.Tubular reabsorption

It is the balance between all components that
determines the volume and composition of
the urine excreted
Urine production = filtration + secretion-reabsorption
Tubular function
secretion & reabsorption
Student objectives
Explain the difference between passive and active
transport processes across the tubular epithelium
Define the transport maximum for reabsorption
Describe the reabsorption of sodium in the
different sections of the nephron
Describe the reabsorption of water in the different
sections of the nephron
Urine Formation
Urine
Made up of 95% water
Other major component is urea
Other nitrogenous wastes include uric acid and
creatinine
Also contains Na, K, phosphate and small amount
of Ca, Mg and bicarbonate
Reabsorption
Quantitatively large
Plasma volume ~3L
GFR 125ml/min or 180L/day
! without tubular reabsorption " whole plasma volume &
essential solutes excreted within 30min
Selective
some substances almost completely reabsorbed
many ions highly reabsorbed
Waste products poorly reabsorbed
Secretion
Transport processes similar to
tubular reabsorption but in
reverse direction

Important for
Disposing of substances not in
filtrate such as drugs (penicillin)
Eliminating undesirable substances
that have been reabsorbed by
passive processes such as urea
Ridding body of excessive K+
Controlling blood pH
2
Tubular reabsorption
A trans-epithelial process
paracellular (through tight junctions)
Transcellular
To reach the blood, transported substances travel through
three membranes:
Luminal, basolateral and endothelium of peritubular capillary

May be passive (no ATP required) simple diffusion,
channel mediated, carrier mediated, osmosis (water)
Or active primary or secondary
The tubular epithelial cell
The luminal surface of the plasma membrane of the tubule
cell faces the filtrate,
whereas the basolateral surface is in close proximity to the
peritubular capillary.
Reabsorption
For substances to be reabsorbed they must be transported:
1. Across tubular epithelial
membranes into renal interstitial
fluid
Transcellular: through cells
Paracellular: between cells

2. Across peritubular capillary
membrane into blood
Bulk flow: mediated by hydrostatic
& oncotic Pressures
Peritubular
Capillary
Tubular
Cells Lumen
Interstitial
fluid
Paracellular
Transcellular
Bulk
Flow
Tight
Junctions
Reabsorption
Passive
None of the membrane
transport steps requires ATP
Solutes move down
electrochemical gradient
Simple diffusion
Facilitated diffusion
Channel Mediated
Carrier Mediated
Solvent drag
Active
At least one of the steps is
driven by ATP (directly or
indirectly)
Primary active transport
Secondary active transport
Pinocytosis (small proteins)
Peritubular
Capillary
Tubular
Cells Lumen
Interstitial
fluid
Solutes
Passive
(diffusion)
Active ATP
H
2
O Osmosis
Tight
Junctions
Na
+

K
+

ATP
ADP + Pi
K
+
Peritubular
Capillary
Tubular
Cells Lumen
Tight
Junctions
Na
+

Active Transport
Primary Active Transport
Transport is coupled directly
to an energy source such as
the hydrolysis of ATP
Na+ Reabsorption
Basolateral membranes of
tubular cells has extensive Na-
K-ATPase
Hydolyses ATP & uses energy
to transport Na+ out of cell into
interstitium & K+ from
interstitium to inside cell
Low intracellular vs tubular [Na
+] , 12 vs 140mEq/L
Net negative charge
PASSIVE diffusion of Na+ into
cell by carrier-mediated
facilitated diffusion
Na
+

K
+

ATP
ADP + Pi
Peritubular
Capillary
Tubular
Cells Lumen
Tight
Junctions
Na
+

Glucose
Na
+

H
+
Antiporters symporters
Active Transport
Secondary Active Transport
2 or more substances interact with a
carrier protein & are co-transported
together
As one of the substances diffuses
down its electrochemical gradient,
the energy released drives another
substance against its
electrochemical gradient

Glucose Reabsorption
Energy required to transport
substances against their transport
gradient come from the Na
+
-K
+
-
ATPase pump
Other examples include amino acids,
lactate, vitamins, and most cations
In general the transport systems for
the various solutes are quite specific
Co-transported substances move by
diffusion through the basolateral
membrane into peritubular capillaries
3
Guyton & Hall, Textbook of Medical Physiology, 2000
Transport Maximum (Tm)
For most substances that are
actively reabsorbed (or
secreted) there is a limit to the
rate the solute can be
transported
Transport Maximum (Tm; mg/min)
Due to saturation of available
carrier proteins
Excess excreted in urine
eg Glucose Transport
Tm 320mg/min
Normal filtered load: 125mg/min
no glucose in urine
Uncontrolled diabetes mellitis
filtered load: >320mg/min
glucose in urine
The mechanisms for reabsorption of sodium and
water are different in each segment of the tubule.
The reabsorption of sodium is mainly an active process. Most renal
energy utilisation goes to accomplishing this enormous task.
The reabsorption of water is by diffusion (osmosis) and is secondary to
the reabsorption of sodium
Percent of filtered load reabsorbed (%)
Tubular segment Sodium Water
Proximal tubule 65 65
Descending limb of Henle - 10
Ascending limb of Henle 25 -
Distal convoluted tubule 5 -
Collecting duct 4 -5 5 (water loading)
>24 (dehydration)
Specialized histology of the tubular cells
Proximal Tubules
Distal Tubules
Loop of Henle &
Collecting Duct
4
Reabsorption & Secretion
along different parts of the nephron
PROXIMAL TUBULE
High capacity for ACTIVE & PASSIVE
reabsorption
~65% H2O & Na+; 50% Cl-; 90% HCO3-;
>90% K+
Nearly all glucose, lactose, amino acids
Specialisations
Large numbers of mitochondria
Extensive brush border loaded with protein carrier molecules
Intercellular and basal channels
Rapid transport of Na+ and other substances
Water permeable
Reabsorption & Secretion
Proximal tubule
Taken from kidney physiology, Schnermann & Sayegh, 1998
LUMEN INTERSTITIUM
Na, K-ATPase pump
Na
+
glucose
amino acids
K
+
H
+
Na
+
Na
+
Na
+
Sodium reabsorption
Proximal tubule
Na,K-ATPase pumps in the
basolateral membranes
transport sodium from the
cell into the interstitium
Sodium is co-transported
with organic nutrients and
counter-transported with
hydrogen ions in to the
proximal tubular cells
Water follows the sodium
since the proximal tubule is
highly permeable to water
300 mOsm
1200 mOsm
300 mOsm
Reabsorption & Secretion
along different parts of the nephron
LOOP OF HENLE
3 distinct sections
Tubular fluid that enters the loop of Henle: Iso-
osmotic
More sodium (25% of the filtered load) than water
(10%) is reabsorbed by the loop of Henle
Thin Descending Limb
thin epithelial cells, no brush border, few
mitochondria
highly permeable to water
H2O reabsorbed due to medullary interstitial
concentration gradient
10% of filtered water reabsorbed
no active Na+ reabsorption
simple diffusion of some solutes (eg Urea & Na+)
Lumen Thick AL Interstitium
ATP
Na+
K+
Na+
2Cl
-

K
+

300 mOsm
1200 mOsm
LOOP OF HENLE
Ascending Limb
virtually impermeable to water
reabsorbs 25% of filtered NaCl &
K+, Ca2+ , HCO3-
almost exclusively in thick limb

Thin limb low reabsorptive
capacity
Thick limb
Na+-K+-ATPase in basolateral
membranes
movement of Na+ across luminal
membrane
1Na+, 2Cl-, 1K+ cotransporter
ATP
Na
+

K
+

Principle Cell
Intercalated Cell
Aldosterone
R
R ADH
H2O
channel
molecules
H2O
Na+
protein
carriers
Na+
LATE DISTAL TUBULE & COLLECTING DUCT
Reabsorption in this region is
dependent on the bodys needs
and is regulated by hormones
The fluid in the lumen at the end of
the distal tubule is hypo-osmotic (ie
dilute urine).
Na+
energy supplied by Na+-K+-ATPase
reabsorbed with Cl- symporter
only 3% of the filtered Na+ remains
to reabsorbed here
dependent on [Aldosterone]
H2O
normally impermeable
dependent on antidiuretic hormone
(ADH; vasopressin)
when ADH present water moves out
of tubules by osmosis
5
LUMEN INTERSTITIUM
H
+
Na
+
Principal cell
intercalated cells
Na
+
K
+
Cl
-

HCO
3
-
Reabsorption
late distal tubule & collecting duct
Two types of cells in the
collecting ducts
Intercalated cells
Principal cells
The water permeability of the
collecting duct can be very
low or very high depending
on the levels of ADH
High levels of ADH leads to
reabsorption of water and the
formation of concentrated urine
Medullary Interstitial Osmotic Gradient
If ADH is present:
High osmolarity will draw
H
2
O out of the tubule
through channels
"Concentrated urine

No ADH present:
H
2
O not reabsorbed
"Dilute urine
The mechanism involved in the
production of gradient is complex
& controversial

C
o
r
t
e
x

M
e
d
u
l
l
a

300 mOsm
1200 mOsm
150 mOsm
H
2
O
NaCl
H
2
O
Relative water permeability in different
segments of the nephron
Taken from kidney physiology, Schnermann & Sayegh, 1998
Types of nephrons
cortical and superficial
Urine concentration and the maintenance of body
fluid solute concentration
Kangaroo Rat
Desert dweller
Constant state of H
2
O deprivation
Excretion of little H
2
O in urine
Urine osmolarity:
-6,000-8000mOsm
All nephrons juxtamedullary (make
most concentrated urine, important
role in formation of medullary solute
gradient).
Beaver
Short-loop cortical nephrons
No countercurrent system
Cannot concentrate urine
Cant excrete less
Forced to drink more H
2
O
Must remain in or near aqueous
environment
Urinary concentrating
counter current system
6
Summary: sodium reabsorption
Sodium is the most abundant cation in filtrate
Filtered and reabsorbed NOT secreted
Generally 99.5% is reabsorbed
Overall, transport is active and primarily transcellular
Occurs at different rates in different parts of tubule
Luminal transport
may be passive via diffusion or facilitated diffusion (epithelial sodium
channels, co-transporters)
Basolateral transport
active via Na/K ATPases
The active basolateral pumping causes an electrochemical gradient
favouring passive entry at luminal side.
Sodium reabsorption provides the means and energy for many other ions
and water to be reabsorbed
Diffusion into peritubular capillary (bulk flow)
Can be very finely regulated (aldosterone)
Proximal
tubules - 64%
- gradient
Loop of Henle 28%
-Descending - impermeable
- Ascending- Active transport
Distal tubule
&
Collecting
Duct 7%
- Fine control
-aldosterone
Excreted 1%
Where is sodium reabsorbed?
Summary: Water reabsorption
Over 99% of filtered water is reabsorbed
Filtered and reabsorbed NOT secreted
H2O is freely filtered into the tubules
Occurs at different rates in different parts of the tubule
Osmosis driven by Na gradient (Obligatory)
Sets up gradient allowing many other solutes (eg cations, fatty acids) to follow concentration
gradient.
Most of the H2O is reabsorbed in the proximal tubule
Descending limb of the loop of Henle highly permeable to H2O
Thin and thick ascending limb of the loop of Henle impermeable to H2O
H2O permeability of the distal tubule and collecting ducts is variable
Occurs through channels called aquaporins
Distal tubule
&
Collecting
Duct 9%
Fine control ADH
(Anti-diuretic hormone)
Loop of Henle 25%
Descending- osmosis
Ascending- impermeable
Proximal
tubules - 67%
Osmosis
Excreted <1%
Where is water reabsorbed?
Revision questions
Be able to describe active and passive
reabsorption across the tubule.
Use examples
Where is sodium reabsorbed along the tubule?
What is the mechanism for sodium transport on the baso-
lateral membrane of the tubular cells?
Where is water reabsorbed along the tubule?
What is the name of the process that enables water to move
through the tubular cell?
Is the urine in the distal tubule dilute or concentrated?