By Wendy C. Brooks, DVM, DipABVP
Educational Director, VeterinaryPartner.com
When the Results say low Blood Calcium
Photo courtesy of Morguefile
Calcium is a mineral we have all heard about as we have been told to drink milk for adequate calcium since we were children. Women are encouraged to take calcium supplements, 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 including the skeletal muscles that move our limbs voluntarily, the involuntary muscles that move our intestinal contents from one end to the other, and our heart muscle that beats regularly and tirelessly throughout life.
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 the 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 percent of blood calcium is ionized calcium.
Bound calcium is also circulating in the bloodstream but it is not floating around freely. It is being carried by molecules of albumin (a blood protein whose job is to transport substances that don't freely dissolve in blood) or it is complexed with other ions. About 40 percent of blood calcium is bound (i.e. carried by albumin or complexed with another ion). Ionized calcium and bound calcium added together are called total calcium. This value is reported on most blood chemistry panels. Total calcium refers to the total calcium in the bloodstream, not the total calcium in the body.
Calcium is also stored in the minerals of bone. We do not 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.
Photo courtesy of Morguefile
When we want to drop the ionized calcium level, our kidneys are able to remove circulating calcium, placing 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 off PTH production.
When PTH levels are low enough, vitamin D activation ceases and calcium levels drop again.
There are a number of conditions that can interfere with the above system. Vitamin D deficiency, kidney disease, too many puppies nursing for a small mother dog. We will review the classic causes in a moment but first, the symptoms.
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 (1.50 mmol/L) and in dogs (but not cats) and seems to be associated with exercise during the hypocalcemia state. 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 (1.00 mmol/L) or below, death generally results.
How Might a Pet Come to Have Hypocalcemia?
When a small mother dog attempts to nurse too large a litter, she can find herself depleted in calcium. She will show the typical symptoms as described and the diagnosis is usually pretty clear as the patient is a female dog nursing a litter. Blood tests will confirm the diagnosis; treatment involves an injection of calcium followed by oral calcium supplements. It should be noted that attempting to prevent this condition with oral calcium supplements frequently backfires as it suppresses the mother dog's natural ability to mobilize calcium by fooling her body into thinking there is plenty. If there really isn't plenty, she will not be hormonally prepared to liberate more.
Chronic Renal Failure
When the kidneys become too damaged to respond to the hormones described above, calcium can end up either high or now depending on a number of factors. There is tendency towards high phosphorus levels in this situation and proper management will depend on keeping the phosphorus levels under control. Basic blood and urine testing will reveal the state of the kidneys and lead to a proper treatment plan. For more information on renal calcium/phosphorus imbalance, click here.
The pancreas produces the enzymes we use to digest our food. There are numerous safeguards to prevent these enzymes from digesting our own bodies but when the pancreas gets inflamed, this is exactly what happens. When this condition presents acutely, the patient has fairly sudden onset of extreme nausea, diarrhea and pain. As body fats are digested, the triglycerides that are released bind blood calcium driving ionized calcium levels down. Hypocalcemia can result. For more information on pancreatitis, click here.
Using a human phosphate-based enema to relieve constipation, adds a huge amount of phosphate to the patient's system. The phosphate binds circulating calcium and can lead to a calcium crisis especially in a small patient. Such products cannot safely be used in pets so it is important not to attempt to treat constipation without veterinary guidance.
Antifreeze (ethylene glycol) poisoning leads to an almost untreatable acute kidney failure. Part of the syndrome can include low blood calcium.
Parathyroid Hormone (PTH) Deficiency - Not Common but still a Classic Disease
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 reduce it. Elevated phosphorus levels further suppress the system for Vitamin D activation.
The average age of onset for PTH deficiency is about 5 years for dogs and the most requently identified breeds are the toy poodle, the miniature schnauzer, the Labrador retriever, the German shepherd dog, the dachshund, and the entire terrier group.
Diagnosis of Hypocalcemia
Diagnosis is made by testing blood and urine. 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 (especially the infamous "all meat diet"), nursing a litter, and the list continues. A 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 is not clear which condition the patient has, a PTH blood level will settle the question. If the PTH level is low, then 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.
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 given 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 four
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 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 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. It will only circulate after the body's fat stores are filled. This means needing many weeks of injectable calcium before switching to oral medication. Further, if problems occur and calcium levels get too high, it means many 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 (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 is the first choice medication for managing hypoparathyroidism. It is generally given twice a day and has its maximum effect in one to four 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 pharmacy is generally needed to make a dosing size that is appropriate for pets.
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're doing when you choose a calcium supplement and intending to give a specific amount of calcium. Because lactate and gluconate are such large molecules, and calcium is so small, you need 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 that day has not arrived.
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 or 2.0-2.25 mmol/L). 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.