Biochemistry of Renal Functions

• Most renal functions are the sums of the activities of thousands of

nephrons.

• The number of nephrons varies among species, with larger species

having more of them.

• Example: Cat has about 190,000, Dog has 430,000 and Cow has about
4 million per kidney.
• A simple view of nephron function can be summarised as follows:
Perfusion of glomerular capillaries with blood under pressure results in the passage of
filtrate through the capillary wall into Bowman’s space.

Filtrate then passes through the tubular system of each nephron and is modified in
composition during its passage.

Modification occurs primarily by reabsorption of lumen contents by tubular cells for

return to the body.

In addition, important secretory functions are performed by tubule cells, whereby
materials are transported from interstitium to the tubule lumen for excretion.

The end result of these tubular activities is a marked reduction in the volume of filtrate
and a modification of its character.
a. Kidneys perform filtration of macromolecules:

Filtration barrier prevents macromolecules and cells from entering filtrate.

This indicates that the size and shape of molecules influence their filtration.

Filtration is also influenced by electrical charges.

Negatively charged sialoproteins are components of all three layers of the

capillary wall.

These negative charges facilitate the passage of cationic macromolecules

and impede passage of anionic macromolecules through the filter.

The size, shape and presence of negative charges on albumin prevent from
its passage through the glomerular capillary wall.
b. Tubular Modification of filtrate:
The renal tubules modify glomerular filtrate to achieve body homeostasis for
water and most electrolytes.

Large quantities of filtrate (65-80%) are reabsorbed in the proximal tubules.

As the reduced volume of filtrate moves the more distal portion of nephrons,
further reabsorption takes place.

Secretion of certain endogenous materials such as protons, potassium, organic

anions as well as exogenous materials such as certain drugs, toxins from tubular
cells into tubular lumen also is important in renal excretory functions.
c. Conservation of nutrients:

i. Glucose:
 Glucose (Mw: 180 Da) passes freely through the glomerular filtration barrier and
attains the same concentration in filtrate as in plasma.

At the normal blood level of glucose, reabsorption of filtered glucose is nearly
complete within 20% of the proximal tubule.

At the luminal membrane, glucose reabsorption takes place by secondary active
transport mechanism.
ii. Amino acids:
 In nearly all species, more than 99% of amino acids is reabsorbed by specific
mechanism by the tubules.

An exception is the domestic cat, which normally has 1 to 1.8 gm/litre of a
sulphur containing amino acid (Felinine) in its urine.

The bulk of amino acid reabsorption occurs in the early portions of the proximal
tubule.
iii. Other Metabolites:
Some metabolites such as citrate, α- ketoglutarate and succinate might be
excreted in urine.

Urine of dogs and cats contain fat as normal component because of exocytosis of
fat from tubular cells into lumen.
d. Role of kidneys in electrolyte homeostasis:
The kidneys play a significant role in maintaining the concentration of
many plasma electrolytes within narrow limits.
These electrolytes include sodium, potassium, calcium, chloride and
magnesium.

i. Sodium homeostasis:
A large quantities of sodium is filtered daily and most is reabsorbed in the
proximal tubules by passive transport process.
Additional sodium is reabsorbed in ascending limb of Henle.
Further reabsorption of sodium occurs in the more distal portions (Distal
tubule, collecting duct) of the nephron.
ii. Potassium homeostasis:
 Nearly 70% of filtered potassium is reabsorbed in the first two-thirds of the proximal
tubule.

The major nephron sites for potassium homeostasis are the terminal distal tubule and
the cortical collecting duct.

Potassium is secreted from cells into the tubular lumen at these sites by passive
mechanism.

Cattle normally excrete a much larger percentage of the filtered load of potassium than
do carnivores because of higher dietary potassium intake.
iii. Chloride:
Chloride is reabsorbed in concert with sodium by sodium depedent
mechanism.
Sodium independent mechanism also exists for chloride reabsorption.

iv. Calcium:
Plasma ionised calcium easily pass through glomerulus but protein bound
calcium is retained in blood.
In the tubule, calcium is reabsorbed roughly in parallel to sodium in the
proximal tubule
v. Magnesium :
Proximal tubule reabsorption of magnesium is only 20-30% of the
amount filtered.
The major site of reabsorption under normal condition is the thick
ascending limb of henle.
About 10% of filtered magnesium is normally reabsorbed more
distally.
e. Role of kidneys is acid base balance:
Kidneys help in acid base balance by :
Conservation and generation of bicarbonate
Secretion of hydrogen ions
Excretion of hydrogen ions in the form of ammonium ions and
titratable acidity.
f. Role of kidneys in water balance:
All mammals and birds have some ability to concentrate urine.

Animals also have ability to excrete hypotonic urine so that excess body
water can be excreted without solute depletion.
In the proximal tubule, 60-80% of filtrate is reabsorbed secondary to solute
reabsorption.
In the descending limb, loop of Henle and in the proximal portion of the
distal tubule, further reabsorption occurs so that only about 9% of filtrate
remains as fluid that enters the terminal portion of distal tubule and
collecting duct.
 Urine volume is determined by the amount of this 9% that is
reabsorbed.
In times of body water deficit, nearly all of 9% is reabsorbed and
urine voided is very low in volume and high in solute concentration.
In times of body water excess, little of the 9% is reabsorbed, so that
urine volume is high and solute concentration is low.
The reabsorption of water at collecting tubules takes place by
antidiuretic hormone(ADH).
g. Renal Metabolism:
The kidneys use primarily free fatty acids, lactate, glutamine, glucose
and citrate.
During starvation, kidney produces glucose via gluconeogenesis.
Kidneys also secrete erythropoietin, Renin.
Alanine and serine are released by kidneys. Both amino acids are
utilised by liver for gluconeogenesis.