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1. Biochemistry of Kidney
LESSON 3

2. Loop of Henle
• Cells of the loop of Henle and the distal regions of the
nephron are thinner they are no less important in
reabsorption and secretion.

3. • The descending limb of the loop is permeable to water but not
to solutes, thus when the tubular fluid reaches the bend in the
loop it has a higher osmolality than when it left the PCT.

4. • The ascending limb is thicker than the
descending limb, reflecting its role in further
reabsorption of solutes, for example sodium
chloride, potassium, calcium and magnesium.

5. The loop of Henle functions basically in regulating the salt (electrolyte)
concentration in urine.
Let us see the anatomy of the loop first – it consists of three parts – the
descending thin segment, the ascending thin segment and the thick ascending
segment.

6. In the thick ascending loop Na+ and Cl- reabsorption is accomplished
by a Na+, K+, Cl- symporter. The thick ascending limb has a high
reabsorptive capacity and is responsible for reabsorbing 25% of the
filtered load of Na+.

7. • The descending part of the thin segment is highly permeable to
water and moderately permeable to most solutes. About 20% of
the filtered water is reabsorbed in the descending limb, because,
the ascending limb (both thin and thick parts) are impermeable to
water – a characteristic which is important for concentrating urine.
• Because the thick segment of the ascending limb is virtually
impermeable to water, most of the water delivered to this segment
remains in the tubule, diluting the urine, as most of the solutes are
reabsorbed. This feature is important in allowing the kidneys to
dilute or concentrate urine under different conditions.

9. • And when there is a water deficit in the
body, the kidney forms a concentrated
urine by continuing excrete solutes while
increasing water reabsorption and
decreasing the volume of urine formed.

11. • So, what ultimately happens is that, of the urine
filtered through the nephron, most of it is
reabsorbed (water as well as solutes) by the
proximal tubule and the loop of Henle.
• When urine reaches the distal tubule, urine is
essentially diluted.
• The final concentration of the urine formed
depends on the condition of the body, and the
distal tubules, accordingly dilute or concentrate
urine.

13. Distal tubule and collecting duct

15. The distal tubule and collecting duct
• The volume of fluid entering the distal tubule is
only about 90% of the original filtered load and is
approximately isotonic with respect to plasma.
• It is the distal nephron that controls the fine
tuning of the chemical composition of the blood
by reabsorbing, for example, more or less sodium
(under the influence of aldosterone), water
(controlled by ADH, in the collecting duct),
calcium (via parathyroid hormone, PTH).

16. • The DCT is also very important in achieving
subtle pH regulation.
• A number of substances, for example some
drugs and urate (uric acid) are secreted
directly into the lumen of the distal tubule

18. “Osmolality” refers to the concentration of dissolved particles of chemicals and minerals --
such as sodium and other electrolytes -- in your serum. Higher osmolality means more
particles in your serum. Lower osmolality means they're more diluted.

19. Sodium reabsorption
Much less than 10% of the filtered load of NaCl
reaches the distal nephron. Regulation of Na
uptake, occurring mainly in the principal cells of
the cortical collecting tubule, is controlled by
the steroid hormone aldosterone.
The net effect of aldosterone is the reclamation
of NaCl and potassium excretion in to the
luminal fluid.

20. • Like all steroids, aldosterone enters the target cell and
combines with cytosolic mineralocorticoid receptor.
• Such receptors are not entirely specific for aldosterone and
will also bind cortisol, the principal glucocorticoid hormone.
• The receptors are ‘protected’ from cortisol activation by 11 β
hydroxysteroid dehydrogenase which converts cortisol into
cortisone, a steroid which does not engage the aldosterone
receptor and so does not influence sodium and potassium
transport.

23. Two cell types in the cortical collecting duct.
A, The principal cells mediate sodium (Na+) reabsorption energized
by the basolateral Na+, K+ pump. Entry from the lumen is through
the epithelial Na+ channel (ENaC), which renders the lumen
negatively charged (–mv). This transepithelial voltage stimulates
secretion of potassium (K+) through K+ channels. Reabsorbable
anions such as chloride (Cl–) lessen the luminal negativity and
decrease K+ secretion. Bicarbonate (HCO3
–) has an effect to increase
K+ secretion. High flow rates increase net K+ secretion by preventing
development of high lumen K+ concentrations. The effects of the
renin-angiotensin-aldosterone axis are shown: increased
mineralocorticoid receptor (MR) activation increases ENaC, the Na+,
K+ pump, and K+ channels, thereby increasing Na+ reabsorption and
K+ secretion. Cortisol would also increase MR activity, but it is
inactivated by the enzyme, 11β-hydroxysteroid dehydrogenase (11β-
HSD).
AI = angiotensin I; AII = angiotensin II; ACE = angiotensin-converting
enzyme; mv, millivolts.

26. B, Intercalated cells are carbonic anhydrase–rich
cells that secrete acid and reabsorb HCO3
–. The H+
ATPase secretes H+ in a way favored by the
negatively charged lumen in conjunction with the
aldosterone-stimulated effect on Na+
reabsorption in neighboring principal cells. The
K+, H+-ATPase is an electroneutral pump. The
K+/H+ exchanger, reabsorbing K+, is important in
states of K+ depletion when urinary K+ is
decreased.
ADP = adenosine diphosphate; ATP = adenosine
triphosphate."