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Today we're gonna talk about calcium metabolism
from an endocrinologist perspective.
00:06
Let's talk with some revision of calcium
homeostasis in bone physiology.
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Serum calcium levels are tightly
regulated on a moment to moment basis
by the actions of vitamin D
and parathyroid hormone.
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The amount of calcium that is albumin-bound can
be affected by hydration and nutritional status.
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When the albumin levels decrease, the
total serum calcium levels may appear low
and this is known as
pseudohypocalcemia.
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When the albumin levels increase, total
serum calcium levels will appear elevated
and this is known as
pseudohypercalcemia.
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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.
00:55
The causes of pseudohypercalcemia include conditions
that increase protein states within the body,
multiple myeloma where there is an
elevation of monoclonal immunoglobulins,
hyperalbuminemia from
numerous causes,
Waldenstrom macroglobulinemia
which is a hematologic disorder,
and thrombocytosis where there
is an elevation of platelets.
01:19
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.
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There are 2 forms of
vitamin D supplementation.
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Vitamin D2, also know as ergocalciferol,
which has a longer half-life
and vitamin D3 or cholecalciferol, which has
tighter bonding to vitamin D receptors.
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It also has a greater
potency than vitamin D2.
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It's also identical to the vitamin D that naturally
occurs in humans after ultraviolet light exposure.
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Vitamin D3 and D2 must be hydroxylated
twice before becoming active.
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The first occurs in the liver and converts vitamin D
to 25-hydroxy vitamin D, otherwise known as calcidiol.
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The second occurs primarily in the kidney
and forms the physiologically active
1,25 dihydroxyvitamin D,
otherwise known as calcitriol.
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Because 25-hydroxyvitamin D has a
relatively long half-life of several weeks,
it is the best indicator of the
whole body stores of vitamin D.
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Active vitamin D acts on three organ systems to
achieve and maintain normal serum calcium:
bone, intestine and kidney.
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PTH is secreted to increase the calcium in the blood in
response to even the slightest degree of hypocalcemia.
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PTH acts on the kidney to increase production of
active vitamin D to promote calcium resorption
in the distal convuluted
tubule and the loop of Henle.
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PTH acts on bone to activate calcium
and release it into the blood stream.
03:05
The clinical features of hypercalcemia
occur when serum calcium levels
are above the normal range
usually greater than 10.5 mg/dL.
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Most patients are asymptomatic and hypercalcemia may be
noted incidentally on lab tests obtained for other reasons.
03:25
Symptoms may occur with any
degree of hypercalcemia
but they are much more common when
calcium levels exceed 12 mg/dL.
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There's a really good way to remember the clinical
findings in symptoms that occur in hypercalcemia.
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Stones refers to calcium levels being
elevated causing kidney stones.
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Abdominal groans are feature of hypercalcemia and that
patients tend to present with nonspecific abdominal pain.
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Bones are reminded that because of elevated levels of PTH,
the bones are the primary source of calcium breakdown
that enters into the blood
stream to cause hypercalcemia.
04:07
And finally, the presence of
elevated calcium as it increases
causes mood disturbances and ultimately
other central nervous system effects.
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The classic symptoms are usually based
on the severity of calcium rise.
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So starting at the calcium
level of around 11 mg/dL,
one notices the classical
features of polyuria, polydipsia,
nocturia which is increased urination at
night and the presence of kidney stones.
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As the calcium levels
increase above 11,
patients may manifest anorexia,
nausea, abdominal pain, constipation.
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There may also be
effects on the kidneys.
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The creatinine may rise because elevations
of calcium cause what we know as calciuresis
or an increased diuresis of water that
the body loses causing a prerenal state
and hence a rise in
creatinine levels.
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This can also be followed with
some mild mental status changes.
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And then finally, as the calcium increases above 12,
patients present with profound mental status changes.
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They may be obtunded and kidney injury due to
profound dehydration may be a manifestation.
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One will also note an increase in
creatinine level at this stage.
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The causes of hypercalcemia can be divided into
parathyroid mediated and non parathyroid mediated.
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Parathyroid mediated causes are typically those
caused by elevations in parathyroid hormone.
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Primary hyperparthyroidism
usually caused by an adenoma
or increased hyperplasia of the parathyroid
gland is the most common cause.
05:50
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.
06:01
And then finally, the even rarer familial hypocalciuric
hypercalcemia which we will discuss later.
06:09
Moving on to non-parathyroid
mediated causes of hypercalcemia,
Hypocalcemia 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.
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This is usually a
paraneoplastic manifestation.
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Another malignant manifestation
of hypercalcemia
are those tumors that metastasize
to bone and cause bone destruction.
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These can cause calcium release into the bloodstream
and mainly because of osteolysis of bone.
06:47
Another common cause of non-parathyroid
mediated hypercalcemia is vitamin D toxicity.
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These are individuals who take
excessive levels of vitamin D,
causing increased calcium
absorption and hypercalcemia.
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It is also seen but to a rarer degree
with high levels of vitamin A.
07:08
Granulomatous diseases like sarcoidosis
and TB also cause hypercalcemia
but these are usually mediated through vitamin
D mechanisms that we'll talk about later.
07:20
Rarer conditions like milk alkali syndrome,
thyrotoxicosis and prolonged immobilization
can also cause elevations
of serum calcium.