1. Renal Physiology
Transport of solutes
Dr. Sara Reza
Quaid-e-Azam Medical College

2. Functions of the Kidney:
Maintaining balance
• Regulation of body fluid volume and
osmolality
• Regulation of electrolyte balance
• Regulation of acid-base balance
• Excretion of waste products (urea,
ammonia, drugs, toxins)
• Production and secretion of
hormones
• Regulation of blood pressure

3. The Kidney and the Nephron
A. Renal Vein
B. Renal Artery
C. Ureter
D. Medulla
E. Renal Pelvis
F. Cortex
1. Ascending loop of
Henle
2. Descending loop of
Henle
3. Peritubular
capillaries
4. Proximal tubule
5. Glomerulus
6. Distal tubule

4. Overview of nephron function
From http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookEXCRET.html

5. Membrane Transport
• Passive diffusion
 Facilitated diffusion
 Osmosis
• Active transport
 Primary active transport
 Secondary active transport
 Co-transport
 Counter transport

6. Passive Diffusion
• When two aqueous compartments
containing unequal concentrations of a
soluble compound or ions are separated
by a permeable membrane the solute
moves by simple diffusion from the region
of higher concentration, through the
membrane, to the region of lower
concentration, until the two compartments
have equal solute concentration.

8. The diffusion velocity of a pure phospholipid
membrane will depend on:
• concentration gradient,
• hydrophobicity,
• size,
• charge, if the molecule has a net charge

9. Facilitated Diffusion
• Facilitated diffusion of ions takes place
through proteins, or assemblies of
proteins, embedded in the plasma
membrane. These transmembrane
proteins form a water-filled channel
through which the ion can pass down its
concentration gradient

10. • Proteins act as carriers or pores permit
flux of substances that cannot diffuse
directly through the membrane.
• Movement is still passive (like diffusion),
from high concentration to low.
• Occurs across cell membranes only.
• Related substances can compete for the
same carrier or pore.
• Maximum rate of transport (fully saturated)
is called Tm, the transport maximum.

12. Osmosis
• Diffusion of water down its concentration
gradient is called osmosis.

14. Active Transport
• When cell membrane moves molecules or
ions uphill against concentration gradients
or uphill against an electrical or pressure
gradient, requiring energy, the process is
called Active transport.
• Types
1.Primary active transport
2.Secondary active transport

15. Primary active transport
• Energy is derived directly from ATP
• Best example is sodium potassium pump
• Sodium potassium pump
• Pumps Na ion outside and at the same
time pumps K ion inside the cell to
maintain Na K concentration across the
cell membrane

16. • The carrier protein of Na-k pump
-has three receptor sites for binding Na
ions that protrude inside the cell
-has two receptor sites for K ions on the
outside
-inside portion also has ATPase activity
• When two K ion bind on outside of carrier
protein and the Na ion on inside, the
ATPase function becomes activated
• Cleaves ATP
• Liberate energy that cause conformational
change in carrier molecule
• Extruding three Na to outside and two K to
inside.

18. Secondary active transport
• Indirect active transport uses the downhill
flow of an ion to pump some other
molecule or ion against its gradient. The
driving ion is usually sodium (Na+) with its
gradient established by the Na+/K+
ATPase.
• Types
• co-transport
• counter transport

19. Cotransport (Symport)
• When Na ions are transported out of the
cells by primary active transport a large
concentration gradient of Na develops
• This represent store house of energy
because excess Na always attempt to
diffuse inside cell
• Under appropriate conditions the diffusion
energy of Na can pull other substance
along with Na through cell membrane
• This phenomenon is called co transport
• E.g. Na co transport of glucose

21. Counter Transport (Antiport)
• Na ions again attempt to diffuse to interior
of cells because of their concentration
gradient
• This time the substances must be
transported to the outside
• Once both have bound a conformational
change occurs, energy is released by the
Na ions moving to interior causes other
substance to move to exterior
• E.g. Na counter transport of Ca and H

23. Proximal convoluted tubule
• Role: Initial adjustment of tubular fluid by
reabsorption (main mechanism) and by
secretion
Reabsorption: Transport from
tubular lumen to peritubular capillary
blood
Secretion: Transport from
peritubular capillary blood into the
tubular lumen

24. • Substances actively reabsorbed (mainly
transcellular)
 Sodium ion about 70% (60-80%,
including passive component)
 Chloride ion about 70% (60-80%,
including passive component)
 Glucose complete
 Amino acids complete
 Inorganic phosphate complete
 Plasma proteins complete (only
small amount filtered)

26. • Passive Reabsorption: due to concentrating
effect of active reabsorption followed by
water reabsorption plus solvent drag
 Sodium ion
 Chloride ion
 Bicarbonate ion variable (depends in
part on H+ secretion)
 Potassium ion most or all
 Urea about 40% (because of low
permeability)
 Water about 70% (60-80%) (due to
osmotic effect of particle reabsorption)

27. Mechanism:
• Active particle reabsorption (particularly
Na+) creates a small osmotic gradient
between the luminal fluid and the spaces
between tubule cells on the interstitial
surface.
• The osmotic gradient causes water to be
reabsorbed because the proximal tubule is
very permeable to water.
• The water reabsorption concentrates the
remaining dissolved substances (including
Na+), and, if they are readily
permeable, the resulting concentration
gradient leads to their reabsorption at
about the same rate as water.

28. Note: The above mechanism maintains proximal tubule fluid approximately iso-
osmotic with plasma
Note: About two-thirds of the water and filtered particles are reabsorbed in the
proximal tubule. If the GFR is reduced, reabsorption is reduced in proprotion; if
GFR increases, reabsorption increases in proportion. This is termed
Glomerular-Tubular Balance.

29. • Active Secretion
1. Mechanism: cotransport with Na+ ion
reabsorption
2. Substances secreted, e.g.
 Exogenous
Para-aminohippurate (PAH)
Iodinated dyes (e.g., Diodrast)
Certain pharmacological agents (e.g.
penicillin, note effect of probenecid)
 Endogenous
Hydrogen ion (Na+ antiport)

30. • No Transport
1. Not actively transported and tubule
impermeable to diffusion
Inulin (exogenous indicator)
Creatinine (endogenous protein
metabolism product)

31. Reabsorption in Proximal Nephron

32. Secretion of Hydrogen and Potassium

33. Apical Transporters Function
Na/glucose CT Na uptake, glucose uptake
Na/Pi CT Na uptake, Pi uptake
Na amino acid CT Na uptake, amino acid uptake
Na/lactate CT Na uptake, lactate uptake
Na/H exchanner Na uptake, H extrusion
Cl/base exchanger Cl uptake

34. Loop of Henle
• Concentrates and dilutes urine
• Descending limb is permeable only to
water
• Ascending limb is impermeable to
water and acts as an active NaCl pump
• 30% of the filtered sodium is
reabsorbed using a luminal Na-K-2Cl-
cotransport mechanism
• Furosemide inhibits the Na-K-2Cl
cotransporter and leads to a massive
natriuresis and loss of potassium,
calcium and magnesium.

35. Reabsorption in Loop of Henle

36. Reabsorption in Loop of Henle

37. Apical transporter Function
Na, 2 Cl, K CT Na uptake, Cl uptake, K uptake
Na/H exchanger Na uptake, H extrusion
K channels K extrusion (recycling)

38. Distal convoluted Tubule
• Reabsorbs water, NaCl, and bicarbonate
• About 10% of the filtered sodium is
reabsorbed in the distal tubule
• Maintains acid base balance by
secreting hydrogen ions
• Site of ADH (Anti-diuretic hormone) and
aldosterone mechanisms of action (ADH
influences water re-absorption and
aldosterone influences sodium re-
absorption)
• Thiazides inhibit the sodium
reabsorption in the distal tubule and lead
to a mild diuresis without loss of calcium

39. Secretion of Hydrogen and Potassium

40. Apical transporters Function
NaCl CT Na uptake, Cl uptake

41. Collecting duct
• The permeability of the collecting ducts
for water lead to a concentration of the
urine up to the fivefold osmolarity of the
plasma
• The permeability of the collecting ducts
is regulated with ADH (antidiuretic
hormone, Vasopressin). ADH causes
the incorporation of additional water
channels (aquaporins) into the luminal
membrane
• ADH can control 10% of the primary
urine volume, thus can regulate the
diuresis between 1–20 l/d.

42. • Additional sodium reabsorption takes
place in the collecting ducts via luminal
sodium channels.
• The energy for the sodium reabsorption
derives from the basolateral sodium-
potassium pump.
• Aldosterone regulates the sodium and
water reabsorption and potassium
secretion via expression of the sodium
channels and the basolateral sodium-
potassium pump.
• The luminal sodium channels can be
inhibited by amiloride, a potassium-sparing
diuretic

43. Apical transporters Function
Na channel (ENaC) Na uptake

44. THANK YOU