C H A P T E R 5 0
Introduction to the kidneys and the urinary tract
799
Calcium regulation
Calcium is important in muscle function, blood clotting,
bone formation, contraction of cell membranes and
muscle movement, and is another important cation
that is regulated by the kidneys. The absorption of
calcium from the gastrointestinal (GI) tract is regulated
by vitamin D ingested as part of the diet. The vitamin
then must be activated in the kidneys to a form that
will promote calcium absorption. Once absorbed from
the GI tract, calcium levels are maintained within a
very tight range by the activity of parathyroid hormone
(PTH) and calcitonin.
Calcium is filtered at the glomerulus and mostly
reabsorbed in the proximal convoluted tubule and
ascending loop of Henle. Fine-tuning of calcium reab-
sorption occurs in the distal convoluted tubule, where
the presence of PTH stimulates reabsorption of calcium
to increase serum calcium levels when they are low (see
Figure 50.3 and Chapter 37).
Blood pressure control
The fragile nephrons require a constant supply of
blood and are equipped with a system to ensure that
they are perfused. This mechanism, called the
renin–
angiotensin–aldosterone system
, involves a total body
reaction to decreased blood flow to the nephrons.
Whenever blood flow or oxygenation to the nephron
is decreased (due to haemorrhage, shock, heart failure or
hypotension), renin is released from the juxtaglomerular
cells. (These cells, which are positioned next to the
glomerulus, are stimulated by decreased stretch and
decreased oxygen levels.) The released renin is imme-
diately absorbed into the capillary system and enters
circulation.
The released renin activates angiotensinogen, a sub-
strate produced in the liver, which becomes angiotensin I.
Angiotensin I is then converted into angiotensin II by a
converting enzyme found in the lungs and some blood
vessels. Angiotensin II is a very powerful vasoconstric-
tor, reacting with angiotensin II–receptor sites in blood
vessels to cause vasoconstriction. This powerful vaso-
constriction raises blood pressure and should increase
blood flow to the kidneys.
Angiotensin II is converted in the adrenal gland to
angiotensin III, which stimulates the release of aldos-
terone from the adrenal gland. Aldosterone acts on
the renal tubules to retain sodium and therefore water.
This increases blood volume and further increases
blood pressure, which should increase blood flow to
the kidneys. The osmotic centre in the brain senses the
increased sodium levels and releases ADH, leading to
a further retention of water and a further increase in
blood volume and pressure, which should again increase
blood flow to the kidneys.
The renin–angiotensin–aldosterone system con-
stantly works to maintain blood flow to the kidneys.
For example, an individual rising from a lying position
experiences a drop in blood flow to the kidneys as blood
pools in the legs because of gravity. This causes a massive
release of renin and activation of this system to ensure
that blood pressure is maintained and the kidneys are
perfused. Blood loss from injury or during surgery also
activates this system to increase blood flow through the
kidneys.
Drugs that interfere with any aspect of this system
will cause a reflex response. For instance, taking a drug
such as a diuretic to decrease fluid volume can lead to
decreased blood flow to the kidneys as blood volume
drops. This in turn leads to rebound retention of fluid as
part of the effects of the renin–angiotensin–aldosterone
system (Figure 50.4).
Regulation of red blood cell production
Whenever blood flow or oxygenation to the nephron
is decreased (due to haemorrhage, shock, heart failure
or hypotension), the hormone erythropoietin is also
released from the juxtaglomerular cells. This hormone
stimulates the bone marrow to increase the production
of red blood cells, which bring oxygen to the kidneys.
Erythropoietin is the only known factor that can
regulate the rate of red blood cell production. When
↓
Blood flow
↓
Oxygenation
NEPHRON
Renin release
Activation of angiotensinogen
LUNGS
Converting enzyme (ACE)
Angiotensin I Angiotensin II
Angiotensin I
ADRENAL GLAND
Angiotensin III
↑
Aldosterone release
Retention of sodium with water
↑
Blood volume and pressure
↑
Blood flow to the kidneys
Erythropoietin
release
↑
RBC production
Powerful
vasoconstriction
↑
Blood pressure
↑
Blood flow
to the kidneys
FIGURE 50.4
The renin–angiotensin–aldosterone system for reflex
maintenance of blood pressure control.
