1. The proximal tubule reabsorbs most of the filtered sodium, glucose, and amino acids via active transport mechanisms. Water follows osmotically. 2. The loop of Henle plays a key role in urine concentration. The thin descending limb is water permeable while the thin ascending limb reabsorbs NaCl passively. The thick ascending limb actively transports NaCl but is impermeable to water, creating the osmotic gradient. 3. Later segments fine tune urine composition. The distal tubule and collecting duct reabsorb sodium, chloride and water under hormonal control like ADH, with the collecting duct permeability to water regulating final urine concentration.

1. Physiology of the
Proximal Tubule
••••••••••••••••••••••••••••••••
Dr. Ramadan Saad
Tubular functions

2. Mechanisms of Urine Formation
• Urine formation and
adjustment of blood
composition involves three
major processes
–Glomerular filtration
–Tubular reabsorption
–Secretion
2

3. oThe Proximal tubule receives the
ultrafiltrate from the glomerulus.
oThe proximal tubule is an epithelium
consisting of a single layer of cells.
oThe membrane surface in contact with
the luminal compartment (apical
membrane) has microvilli (brush
border), and the surface in contact with
the interstitium (basolateralmembrane)
oTransport can be divided into active
(transcellular) and passive
(paracellular) transport.
o65% Na+, Cl-, and H20 reabsorbed
across the proximal convoluted
tubule into the vascular system.
o 100% Glucose, protein and
Amino Acids
o 60% Sodium, Cl, and H2O.
o 80% PH, HCO3, K.
o 60% Ca.
o 50% of Filtered Urea.

4. Na reabsorption
 At basolateral side:
 It pumps 3 Na+ actively
out of the cell into the
interstitium, and at the
same time carries 2 K+
into the cell.
 As a result of this there
is:
-  intracellular Na+
concentration.
 At luminal membrane
there will therefore be
passive diffusion of Na+ into
the cell along both
concentration gradients.
This diffusion is facilitated
by a protein carrier.
o Active transport of solutes in
the proximal tubule leads to
an intraluminal fluid that is
hypo-osmotic compared
with the blood.
o The proximal tubule has a
very high osmotic water
permeability due to the
presence of aquaporin in its
apical and basolateral
membranes.
o The high permeability allows
for the rapid movement of
water and the nearly iso-
osmotic reabsorption of
the glomerular filtrate.
Transport of Water

5. Glucose Transport
o Early in the proximal tubule, there is
a sodium-glucose cotransporter
(SGLT2) that transports one sodium
ion and one glucose molecule.
o As the proximal tubule intracellular
glucose concentration rises, glucose
diffuses out through the basolateral
membrane by means of a facilitative
transporter (GLUT2).
o This process is saturable.
o This is the basis for the osmotic
diuresis found in the diabetic patient
when the serum glucose
concentration is elevated and
exceeds the transport maximum for
glucose.
Tubular maximum for
glucose (TmG)
• The maximum amount of
glucose (in mg ) that can be
reabsorbed per min.
• It equals the sum of TmG of all
nephrons.
• Value; 300 mg/min in ♀, 375
mg/ min in ♂.
Renal Threshold for
Glucose
• Is approximately 180 mg/dl
• When the blood glucose level
exceeds about180 mg/dL (8.9-
10 mmol/L), the proximal tubule
becomes overwhelmed and
begins to excrete glucose in the
urine.

6. Glucosereabsorption
Glucosuria
Presence of glucose in
urine
1. Diabetes mellitus
oblood glucose level > renal threshold.
2. Renal glucosuria
oIt is caused by the defect in the glucose
transport mechanism.
3. Phlorhizin
oA plant glucoside which competes with
glucose for the carrier and results in
glucosuria (phloridzin diabetes).

7. Bicarbonate Transport
oSodium-hydrogen exchanger exchanges one
hydrogen ion for each sodium ion that enters
the cell and is the first step in the
reabsorption of bicarbonate.
oOnce the hydrogen ion enters the lumen of
the tubule, it combines with a bicarbonate ion
to form carbonic acid,
oIn the presence of carbonic anhydrase, the
carbonic acid is converted to carbon dioxide
(CO2) and water, which then enter the cell.
oIntracellular carbonic anhydrase then
catalyzes the recombining of the CO2 and
water into carbonic acid.
oThe bicarbonate then exits the cell via the
basolaterally located carrier.

8. Phosphate Transport
o Under normal conditions, about 85% of the filtered phosphate is reabsorbed
by the proximal tubule by means of the sodium-phosphate cotransporter
(NaPi2)
o Parathyroid hormone (PTH) promotes renal excretion of phosphate.
o It stimulates endocytosis of the NaPi2 cotransporters from the apical
membrane of the proximal tubule cells.

9. Secretion in the Proximal Tubules
oA number of organic molecules are actively secreted in the proximal
tubule.
o The mechanism of secretion is similar to that of reabsorption, except
that the transporters for uptake are located in the basolateral
membrane.
o The principal molecules that are secreted include
Hydrogen secretion for acid/base regulation.
Ammonia secretion for acid/base regulation.
PAH.
Creatinine.
Uric acid.
Penicillin.

10. Metabolic Functions of PCT
o Ammoniagenesis
o If the body has accumulated acid, it must generate new bicarbonate.
o It does so by generating ammonia, which is then secreted into the lumen of the tubule for eventual excretion in the
form of ammonium chloride.
o Under conditions of acidosis, the kidney can more than double its production of ammonia so that the body can
repair the base deficit that has accumulated.

11. Metabolic Functions
oGluconeogenesis
oThe proximal tubule has all the enzymes for gluconeogenesis.
oThe rate of glucose production by the kidney is second only to
that by the liver.
oVitamin D Synthesis
oThe proximal tubule is the site in the kidney for the 1α-
hydroxylase enzyme in the synthetic pathway for vitamin D
activation.
oThis enzyme is primarily under the control of PTH.

12. Physiology of the
Loop of Henle
and distal renal
Tubules
••••••••••••••••••••••••••••••••
Ramadan Saad

14. Loop of Henle
Thin Descending
15% of H2O reabsorbed.
H2O
Na+Cl-
Thin Ascending
Passive reabsorption of
Na+, K+, Cl-.
Impermeable to H2O.
Thick Ascending
25% of Na+, K+, Cl-
reabsorbed.
Impermeable to H2O.
Called = Diluting segment.

15. Loop of Henle
oWater reabsorption occurs exclusively in the thin descending
limb of Henle via AQP1 water channels. (Aquaporins).
o Reabsorption of NaCl occurs in both thin and thick ascending
limb of Henle.
o In thin ascending limb NaCl is reabsorbed passively. However,
in thick ascending limb NaCl is reabsorbed actively.
oAscending limb is impermeable to water.
oReabsorption of Ca++ and HCO3- occurs also in Loop of Henle.

16. Thick ascending limb of Henle
Furosemid
e
Voltage
Impermeable
to water
- Impermeable to water
- High reabsorptive power for solutes: It actively reabsorbs 25% of filtered
- Na+, K+, & Cl- (by 1 Na+, 2 Cl-, 1 K+ cotransport) to medullary interstitium.
 Osmolality of tubular fluid  gradually as it reaches DCT (becomes hypoosmotic). It is called the
diluting segment.

17. Early Distal Tubule
o Also impermeable to water (like TAL)
o Continues the dilution of urine; the “cortical diluting segment”
o Reabsorption of Na/Cl (cotransporter)
o Inhibited by Thiazide diuretics
Impermeable
to water
Thiazide
s

18. Late Distal Tubule/Collecting Duct: fine tuning
o Principal cells--reabsorb Na, H2O, and secrete K+
o Impermeable to water, except in presence of ADH (Vasopressin)
o ADH causes water channels to relocate to apical cell membrane (AQUAPORIN 2)
o Aldosterone causes an increase in Na absorption and increases K secretion
permeability to water
depends on ADH
Amilorid
e

19. Medullary Collecting Duct
• Reabsorbs < 10% of filtered Na+ and water
• Final site for processing of urine
Functional characteristics:
1. Permeability to water is controlled by ADH level
-  ADH →  water reabsorption.
2. Permeable to urea
- Urea is reabsorbed into the medullary interstitium
where it help increase the osmolality of the
interstitium and therefore help to concentrate urine.

21. Hormonal regulation:
(Antidiuretics actions)
oAng II: stimulates NaCl and water
reabsorption.
oAldosterone: stimulates NaCl
reabsorption in the loop of Henle, DT
and CD. Also stimulates K secretion.
oADH: Is the most important regulator of
water reabsorption in the kidney. It
increases water reabsorption across
the CD and has little effect on NaCl
excretion. (Concentrating urine)
o Atrial Natriuretic Peptide (ANP):
stimulate urinary NaCl and water
excretion. Also they inhibit function and
secretion of ADH hormone.
o Dopamine: It inhibits NaCl and water
reabsorption.
oClinically elevated Blood
pressure increase urine
output how?
Hormonal regulation:
(diuretics actions)
Hormonal regulation of renal tubules

22. 22
Na+ handling along the nephron

23. 23
K+ handling along the nephron

24. HANDLING OF CERTAIN IMPORTANT SOLUTES BY RENAL
TUBULES
Calcium:
 67% are reabsorbed in PCT.
 25-30%% are reabsorbed in the loop of Henle.
 5-10% are reabsorbed in DCT & CD. PTH stimulates Ca2+ reabsorption from
DCT.
Urea
 50% are reabsorbed in PCT.
 5-10% are reabsorbed in medullary CD. ADH stimulates urea reabsorption.

25. Amino acid and protein handling
oAmino acid; Secondary
active transport coupled
with sodium
oProteins; By Pinocytosis
oBoth of them 100%
reabsorbed in PCT

26. 300
300
300
300
300
300
1200
Low permeability to solutes
High permeability to water
H2O
H2O
1200 1200 1200
Thin descending
limb of the loop
of Henle

27. 300
300
300
300
300
300
1200
permeable to solutes
H2O
H2O
Thin ascending
limb of the loop
of Henle
low permeability to H2O
NaCl
Urea

28. 300
300
300
300
300
300
1200
1200 1200 1200
Na+
K+
2 Cl-
Na+
K+
2
Cl-
150
Thick Ascending
limb of the loop
of Henle (TAL)
Diluting segment
impermeable to H2O
Special carriers co-transport
ions from tubule to interstitium
Na+
K+
2
Cl-
Na+
K+
2 Cl-

29. 300
300
300
300
300
1200
1200 1200 1200
Na+
K+
2 Cl-
Na+
K+
2
Cl-
150
Distal Tubule
Na+
K+
2
Cl-
Na+
K+
2 Cl-
Impermeable to H2O
Special carriers
co-transport
ions from tubule
to interstitium
60
Na Cl Na Cl

30. 300
300
300
300
300
1200
1200 1200 1200
Na+
K+
2 Cl-
Na+
K+
2
Cl-
150
Na+
K+
2
Cl-
Na+
K+
2 Cl-
60
Na Cl Na Cl
Cortical
Collecting Duct
1200
H2O
H2O
H2O
H2O
Medullary
Collecting Duct
Variable permeability
to H2O
Regulated by
Antidiuretic Hormone
(ADH)

31. Summary;
1- PCT = Active transport of sodium, glucose
and amino acids occur; water follows
passively.
2-DLH=Passively permeable to water; no
solute exchange.
3-Thin ALH= Passively permeable to NaCl;
impermeable to water.
4-Thick ALH=
Active transport of sodium occur;
impermeable to water and called the diluting
segment.
4-ThickALH= Where Furosemide diuretic
inhibits 1Na-1K-2Cl symporter
5 and 6-DCT and CD= Are passively
permeable to water under ADH stimulation.
.

32. References
o Human physiology by Lauralee Sherwood, 8th edition
o Text Book Of Physiology by Guyton & Hall, 13th edition
o Review of Medical Physiology by Ganong. 24th edition