When the Results Say Low
Blood Calcium
Calcium is a mineral we have all heard about as we have been told to
drink our milk for adequate calcium since we were children. Women are
encouraged to supplement calcium, not just in pregnancy but virtually
throughout adulthood in hope of staving off osteoporosis. Calcium is
not only important as a component of bone; it is also involved in the
contraction of all muscle tissue from the skeletal muscles that move
our limbs voluntarily to the involuntary
muscles that move our intestinal contents to our heart muscle that
beats
regularly and tirelessly throughout life. There's more. Calcium is used
as a messenger to activate enzymes and regulate all sorts of body
functions.
Calcium is such a crucial component of our biochemistry that virtually
any
complete blood panel, whether human or veterinary, will include a
measurement of calcium. Our bodies go to tremendous lengths to regulate
our blood calcium levels within a narrow range. We need a storage
source to draw upon for when we need more circulating calcium as well
as a system to unload excess.
How Calcium is Organized in Our Bodies
Calcium exists in several states in our bodies depending on whether it
is being used or stored. Ionized calcium is circulating free in the
bloodstream and is “active” or ready to be used in one of the numerous
body functions requiring calcium. The amount of ionized calcium in the
blood is tightly regulated. Too much is dangerous. Too low is
dangerous. About 50% of blood calcium is present as ionized calcium.
Bound calcium is also circulating in the bloodstream but it is not
floating around freely. It is instead, being carried by molecules of
albumin (a blood protein whose job is to transport substances that
don't freely dissolve in blood) or complexed with other ions. About 40%
of blood calcium is bound (i.e,. carried by albumin or complexed with
another ion).
Calcium is also stored in the minerals of bone. We don’t
usually think of bone as more than just scaffolding but living bone is
a surprisingly active tissue. One of its functions is to store calcium
and when calcium is needed, it can be mobilized from the bone. Normally
there is plenty of calcium and such mobilization does not significantly
weaken the bone structure but if excess calcium is mobilized, bone can
be depleted and softened.
Adjusting Calcium Levels
When the body needs to raise blood ionized calcium levels, the sources
it may draw from are the bones (where calcium is stored as mineral),
and the intestine (where the calcium we eat enters our bodies). We can
regulate how much dietary calcium is allowed to enter from the GI
tract. We can cause our bones to relinquish stored calcium quickly or
slowly as our needs dictate.
When we want to drop the ionized calcium level, our kidneys are able to
remove circulating calcium, including it in our urine so that it can be
happily flushed away.
These processes are controlled by two hormones: parathyroid hormone
(affectionately called PTH) and calcitriol(affectionately known as
vitamin D). Calcitriol acts to enhance calcium absorption into the body
from the intestine, promote release of calcium from bone, and cause the
kidney to avoid dumping calcium. This adds up to higher blood ionized
calcium. PTH also acts to mobilize bone calcium (and phosphorus with
it) and to shut off renal calcium dumping. This also adds up to more
blood ionized calcium. (The phosphorus is attached to calcium in bone.
There is no way to release the calcium from bone without also releasing
phosphorus. To get rid of the excess phosphorus, PTH enhances the
kidney's ability to “dump” phosphorus into the urine.)
What keeps calcium from rising higher and higher? Calcitriol shuts off
PTH production in the parathyroid glands. PTH is necessary for
activation of vitamin D. Essentially these two hormones shut each other
off.
The sequence of events might be this: blood ionized calcium begins to
drop. The parathyroid glands sense this and release PTH. Ionized
calcium
begins to rise. When PTH levels are high enough, vitamin D is
activated.
Ionized calcium begins to rise more. When enough vitamin D has been
activated,
the parathyroid glands shut of PTH production. When PTH levels are low
enough, vitamin D activation ceases and calcium levels drop again.
Parathyroid Hormone (PTH) Deficiency
As noted, when blood calcium levels drop, PTH would normally bring it
back up. What happens when there isn't any PTH or there isn't enough?
Calcium stays low and vitamin D is not activated. Phosphorus levels in
blood rise as there is no PTH to enhance the kidney's ability to remove
it. Elevated phosphorus levels further suppress the system for Vitamin
D activation.
Without calcium, muscle contraction becomes abnormal and the nervous
system more excitable. Seizures (called hypocalcemic tetany) can
result. This type of seizure occurs when the calcium level drops below
6 mg/dl and in dogs (but not cats) seem to be associated with exercise.
Other symptoms include: nervousness, disorientation, drunken walk,
fever, weak pulses, excessive panting,
muscle tension, twitches and tremors. Cats tend to show more
listlessness than dogs and also tend to raise their third eyelids.
Painful muscle cramping occurs which can lead a pet to become
aggressive. If calcium levels drop to
4 mg/dl or below, death generally results.
The average age of onset is about 5 years for dogs and the most
frequently identified breeds are the toy poodle, the miniature
schnauzer, the Labrador retriever, the German shepherd dog, the
dachshund, and the entire terrier group.
How Does One Get a Parathyroid Deficiency?
There are several ways. The most common way for cats to get a
parathyroid deficiency is from damage to the parathyroid glands as the
result of surgery for hyperthyroidism. The diseased thyroid glands are
located adjacent to the tiny parathyroid glands and inadvertent removal
or damage to the parathyroids is an obvious surgical pitfall. For this
reason, surgery has largely fallen out of favor for this condition and
has largely been replaced by radiotherapy or medication. See the
Hyperthyrodism Center for details on this condition.
In dogs, cellular infiltration (of a lymphoplasmacytic type) of the
parathyroid glands is often found which suggests that immune-mediated
process of parathyroid destruction may be a common route to
hypoparathyroidism.
Another mechanism seems to involve magnesium depletion. A severe
magnesium deficiency can lead to secondary hypoparathyroidism and has
been described in dogs with protein-losing enteropathy. Magnesium is
depleted in this case by loss through the GI tract but magnesium can
also be lost via kidney disease, or dietary deficiency. Magnesium
depletion causes the body's tissues to become insensitive to PTH plus
it also suppresses PTH secretion.
Diagnosis
Diagnosis is made by blood testing and urine testing. There are many
causes of low blood calcium besides hypoparathyroidism: low albumin
levels, kidney failure, pancreatitis, antifreeze poisoning, exposure to
a phosphate enema, Low magnesium, nutritional deficiency, nursing a
litter, bone tumors and the list continues. History and physical
examination will narrow this list substantially.
A basic blood panel and urinalysis is ordered for the medical work-up
of most medical conditions. If calcium is low and phosphorus is high,
then the patient either is in kidney failure or the patient has
hypoparathyroidism. These two conditions are readily distinguished by
the other blood test results.
If for some reason it not clear which condition the patient has, a PTH
blood level will settle the question. The PTH level will be needed
anyway at this point to confirm that the patient truly has primary
hypoparathyroidism and will require lifelong treatment and monitoring
(vs. a more temporary calcium problem). PTH levels must be interpreted
in the context of the low calcium so they must be drawn before therapy
is started.
Low magnesium levels in the body cause a secondary hypoparathyroidism
so it is important to run a magnesium level at some point in the
work-up
to rule this condition out.
Treatment
If the patient is having an acute crisis from the seizures and twitches
and/or the calcium level is dangerously low, hospitalization will be
needed and calcium will be required intravenously.
After the crisis has been overcome or if the patient is stable to start
with, oral calcium and vitamin D supplementation, the basis of long
term
therapy, can be started. These two oral medications take up to 4 days
show
an effect so many patients must receive calcium in the hospital
intravenously
or under the skin during this period. Receiving injections under the
skin
is vastly less expensive than hospitalization but the occasional
patient
develops very inflamed calcium deposits under the skin.
There are three forms of Vitamin D that can be used for long-term
management of this condition: Vitamin D2 (ergocalciferol), DHT
(Dihydrotachysterol), and Vitamin D3 (Calcitriol).
Vitamin D2
Vitamin D2 is an over-the-counter vitamin D supplement readily
available where nutritional supplements are sold. It is not recommended
to treat hypoparathyroidism because when it is first delivered into the
body, it is stored in fat, not used as active vitamin D in the blood.
This means that before it can have any effect at all, the body's fat
stores must be filled to capacity with Vitamin D2. Only after the
body's fat stores are filled, will it circulate. This means many weeks
of injectable calcium before switching to oral medication. Further, if
problems occur and calcium levels get too high, it means weeks before
the fat stores deplete adequately to bring the calcium level down.
Treatment of hypoparathyroidism requires the ability to effect faster
changes in blood calcium levels than Vitamin D2 can manage.
DHT
DHT (Dihydrotachysterol) has a much faster onset of action (1-7 days)
but if there is a problem it can take 4 to 21 days to get the calcium
level lowered. Occasionally animals seem to be resistant to the pill
form of this medication so liquid seems to be best.
Calcitriol
Calcitriol is the first choice medication for managing
hypoparathyroidism. It is generally given twice a day and has its
maximum effect in 1 to 4 days. If calcium levels get too high, they
will drop in 1 to 14 days after discontinuing this medication.
Calcitriol is made in capsules for human use so a compounding
pharmacyis generally needed to make a dosing size that is appropriate
for pets.
Oral Calcium
Calcium supplements are available in most grocery stores, drug stores,
and nutrition supplementation stores. Calcium comes in several salts:
calcium gluconate, calcium lactate, calcium chloride, and calcium
carbonate. They are not all created equal so you need to know
what you are doing when you choose a calcium supplement intending to
give a specific amount of calcium. Because lactate and gluconate are
such large molecules, and calcium is so small, one needs to give a lot
more pills of calcium gluconate or lactate to match the amount of
calcium in the same number of pills of calcium chloride or calcium
carbonate. Because calcium chloride can irritate the stomach, calcium
carbonate is considered the supplement of choice. Do not change the
type of calcium supplementation you use without informing your vet so
that proper dosing calculations can be made.
In the future it may become possible to supplement the patient with
actual parathyroid hormone but as of yet that day has not arrived.
Monitoring Tests
Too much blood calcium causes kidney failure and too little causes
seizures. Blood calcium is normally tightly regulated around a normal
range and the goal in treatment is to keep the range normal (8-9
mg/dl). The stable patient with hypoparathyroidism should come in
quarterly for a calcium level to make sure no problems are occurring
and no dose adjustments are needed. If the calcium level is at an
undesirable level, dosing changes are done gradually to correct them.
Signs at home that calcium is getting too high include vomiting,
diarrhea, excess water consumption, and listlessness. If the calcium
level becomes too high the patient may require hospitalization and
fluid therapy or simply discontinuing of the medication depending on
how far out of the desired range the calcium goes.
Copyright 2005 - 2007 by the
Veterinary Information Network, Inc. All rights reserved.
This work was originally published by Veterinary Information Network,
Inc. (VIN)
and is republished with VIN's permission.
The above information is simply
informational. It's intent is not to replace the advice of a
veterinarian nor to assist you in making a diagnosis of your pet.
Please consult with your own veterinarian for confirmation of any
diagnosis. Your pets life may depend on it.
