[Music]
today we're going to talk about calcium
metabolism from an endocrinologist
perspective let's start with some
revision of calcium homeostasis and bone
physiology serum calcium levels are
tightly regulated on a moment-to-moment
basis by the actions of vitamin D and
parathyroid hormone the amount of
calcium that is albumin bound can be
affected by hydration and nutritional
status when the albumin levels decrease
the total serum calcium levels may
appear low and this is known as pseudo
hypocalcemia when the albumin levels
increase total serum calcium levels will
appear elevated and this is known as
pseudo hypercalcemia
in both cases by checking an ionized
calcium level you will gain you will see
a normal level indicating that there are
normal circulating free levels of
calcium the causes of pseudo
hypercalcemia include conditions that
increase protein states within the body
multiple myeloma where there is an
elevation of monoclonal immunoglobulins
hyper albumin emia for new from numerous
causes Waldenstrom's macroglobulinemia
which is a hematologic disorder and
thrombocytosis where there is an
elevation of platelets the sources of
vitamin D which is a fat soluble vitamin
include de novo production in the skin
from sunlight in the food that we eat
and also from taking vitamin supplements
there are two forms of vitamin D
supplementation vitamin d2 also known as
agar Calcifer all which has a longer
half-life and vitamin d3 or
cholecalciferol which has tighter
bonding to vitamin D receptors it also
has a greater potency than vitamin d2
it's also identical to the vitamin D
that naturally occurs in humans after
ultraviolet light exposure vitamin d3
and d2 must be hydroxylated twice before
becoming active the first occurs in the
liver and converts vitamin D to 25
hydroxy vitamin D otherwise known as Cal
C dial
second occurs primarily in the kidney
and forms the physiologically active 125
dihydroxy in vitamin d otherwise known
as kalsi trial because 25 hydroxy
vitamin D has a relatively long
half-life of several weeks it is the
best indicator of the whole body stores
of vitamin D active vitamin D acts on
three organ systems to achieve and
maintain normal serum calcium bone
intestine and kidney PTH is secreted to
increase the calcium in the blood in
response to even the slightest degree of
hypocalcemia PTH acts on the kidney to
increase production of active vitamin D
to promote calcium resorption in the
distal convoluted tubule and the loop of
Henle PTH acts on bone to activate
calcium and release it into the
bloodstream the clinical features of
hypercalcemia occur when serum calcium
levels are above the normal range
usually greater than ten point five
milligrams per deciliter most patients
are asymptomatic and hypercalcemia may
be noted incidentally on lab tests
obtained for other reasons symptoms may
occur with any degree of hypocalcemia
but there are much more common when
calcium levels exceed 12 milligrams per
deciliter there is a really good way to
remember the clinical findings and
symptoms that occur in hypercalcemia
stones refers to calcium levels being
elevated causing kidney stones abdominal
groans are a feature of hypercalcemia in
that patients tend to present with
nonspecific abdominal pain bones a
reminder that because of act elevated
levels of PTH the bones of the primary
source of calcium break down that enters
into the bloodstream to cause
hypercalcemia
and finally the presence of elevated
calcium as it increases causes mood
disturbances and ultimately other
central nervous system effects the
classic symptoms are usually based on
the severity of calcium
so starting at a calcium level of around
11 milligrams per deciliter one notices
the classical features of polyuria
polydipsia nocturia which is increased
urination at night and the presence of
kidney stones as the calcium levels
increase above 11 patients may manifest
anorexia nausea abdominal pain
constipation they may also be effects on
the kidneys the creatinine may arise
because elevations of calcium cause what
we know as a calcio rhesus or an
increased diuresis of water that the
body loses causing a pre renal state and
hence arise in creatinine levels this
can also be followed with some mild
mental status changes and then finally
as the calcium increases above 12
patients present with profound mental
status changes they may be up tended and
kidney injury due to profound
dehydration may be a manifestation one
will also note an increase in creatinine
level at this stage the causes of
hypercalcemia can be divided into
parathyroid mediated and non parathyroid
mediated parathyroid mediated causes are
typically those caused by elevations in
parathyroid hormone primary
hyperparathyroidism usually caused by an
adenoma or increased hyperplasia of the
parathyroid gland is the most common
cause
parathyroid cancers although very very
rare may cause it and tertiary
hyperparathyroidism which is a rare
condition that occurs in patients with
chronic kidney failure and then finally
the even rarer familial hypocalcemic
hypercalcemia which will we'll discuss
later
moving on to non parathyroid mediated
causes of hypercalcemia hypercalcemia of
malignancy otherwise known as humoral
hypercalcemia is a condition where an
abnormal parathyroid hormone is secreted
causing elevations of calcium and
usually from bone sources that are
related to tumors this is usually a
paraneoplastic manifestation another
malignant manifestation
hypercalcemia are those tumors that
metastasize to bone and cause bone
destruction these can cause calcium
release into the bloodstream and are
mainly because of Ostia lysis of bone
another common cause of non paratha
remediated hypercalcemia is vitamin D
toxicity these are individuals who take
excessive levels of vitamin D causing
increased calcium absorption and
hypercalcemia it is also seen but to a
rarer degree with high levels of vitamin
A granulomatous diseases like
sarcoidosis and TB also cause
hypercalcemia but these are usually
mediated through a vitamin D mechanisms
that we'll talk about later
rarer conditions like milk alkali
syndrome thyrotoxicosis and prolonged
immobilization can also cause elevations
of serum calcium
[Music]
you