Calcium—a mineral we've all grown up hearing about, whether it's being advised to drink milk for strong bones or taking calcium supplements to maintain our health. Calcium not only plays a crucial role in building bones but also influences muscle contractions, including skeletal muscles for voluntary limb movement, involuntary muscles for digestion, and our ever-beating heart muscle.
But there's more to calcium than meets the eye.
Calcium also acts as a messenger, activating enzymes and regulating various bodily functions. So significant is calcium in our biochemistry that nearly every comprehensive blood panel, whether for humans or our furry companions, includes a calcium measurement. Our bodies meticulously control blood calcium levels within a narrow range, utilizing storage sources for when more circulating calcium is needed and mechanisms to eliminate excess.
How Calcium Operates in Our Bodies
Calcium exists in different states in our bodies, depending on whether it's in use or stored. Ionized calcium circulates freely in the bloodstream, ready for various calcium-dependent bodily functions. This fraction of calcium in the blood is tightly regulated because too much or too little can be dangerous. About 50% of blood calcium exists as ionized calcium.
Bound calcium also circulates in the bloodstream, but it's not free-floating. Instead, it's carried by albumin molecules or bound to other ions. Roughly 40% of blood calcium is bound to proteins, such as albumin or complexed with other ions. When ionized calcium and bound calcium are combined, they form the total calcium value, which is typically reported in blood chemistry panels. It's essential to note that total calcium refers to calcium levels in the bloodstream, not the entire body.
Additionally, calcium is stored in bone minerals. While we often think of bones as mere scaffolding, they are, in fact, dynamic tissues that can store and release calcium as needed. Typically, there's an abundant supply of calcium, and this mobilization doesn't significantly weaken bone structure. However, excessive calcium mobilization can lead to bone depletion and weakening.
Regulating Calcium Levels
When the body requires an increase in ionized calcium levels, it can tap into several sources: bones (where calcium is stored as minerals), the intestines (where dietary calcium enters the body), and the kidneys (where excess calcium is excreted in urine). We can also regulate the amount of dietary calcium absorbed from the gastrointestinal tract. This intricate dance involves the release of two hormones: parathyroid hormone (PTH) and calcitriol (vitamin D).
Calcitriol enhances calcium absorption from the intestine, promotes calcium release from bones, and reduces calcium excretion in urine, ultimately increasing blood-ionized calcium levels. PTH also mobilizes calcium from bones and curbs renal calcium excretion, elevating blood-ionized calcium levels. Remarkably, these two hormones effectively regulate each other by mutually inhibiting their own production.
The sequence goes something like this: When blood-ionized calcium levels drop, the parathyroid glands sense this and release PTH, causing ionized calcium levels to rise. With increased PTH levels, calcitriol becomes activated, further elevating ionized calcium levels. Once sufficient calcium levels are reached, the parathyroid glands reduce PTH production, triggering a drop in PTH and calcitriol levels. As both hormones decrease, blood calcium levels start to decline, setting the stage for the cycle to begin anew.
Why Elevated Calcium Levels Are Problematic
Elevated blood calcium levels occur when bones receive an inappropriate signal to release calcium. This signal can originate from either excess parathyroid hormone (commonly seen in parathyroid gland tumors) or high levels of parathyroid hormone-related protein (PTH-rP). When calcium is drawn from bones, it leaves behind a weakened fibrous structure that can lead to fractures.
Normally, the kidneys would recognize the elevated calcium levels and attempt to excrete as much calcium as possible in the urine. However, when parathyroid hormone levels are high, the kidneys are unable to do so, leading to excessive urine production (and increased thirst). Over time, the excess calcium flowing through the kidneys can cause kidney damage, leading to kidney failure. Furthermore, elevated calcium levels can deposit in soft tissues throughout the body, causing mineralization and inflammation, resulting in pain and discomfort.
What Causes Hypercalcemia?
Given the intricate feedback system described, the list of potential causes of hypercalcemia is relatively short:
- Tumors Overproducing PTH-rP: Tumors like lymphoma, anal sac carcinoma, mammary tumors, and multiple myeloma can excessively produce PTH-rP, leading to dangerously high calcium levels.
- Parathyroid Gland Tumor: A tumor in the parathyroid glands can produce excessive parathyroid hormone, leading to hypercalcemia.
- Kidney Failure: Kidney dysfunction can disrupt the balance of calcium and phosphorus in the body, causing hypercalcemia. It's worth noting that kidney failure can both cause and result from hypercalcemia.
- Addison's Disease: Also known as hypoadrenocorticism, this condition involves a deficiency in adrenal steroid hormones and can lead to elevated calcium levels.
- Vitamin D Poisoning: Some rat poisons contain vitamin D analogs that can lead to hypercalcemia if ingested by pets.
- Fungal Disease: Certain fungal infections can cause tissue calcification, particularly in the lungs, and be associated with elevated blood calcium levels.
- Idiopathic Hypercalcemia: While rare in dogs and common in cats, idiopathic hypercalcemia occurs when no specific cause can be identified even after a comprehensive diagnostic work-up. Most cats with idiopathic hypercalcemia show no clinical signs, though some may develop calcium oxalate bladder stones.
What's the Next Step in Diagnosis?
When dealing with a patient exhibiting elevated calcium levels, it's crucial to follow these steps:
Step One: Confirm ionized calcium levels.
Total calcium is usually reported on blood panels, but ionized calcium is the active portion we're concerned about. Elevated total calcium might result from factors other than hypercalcemia, such as high blood fat levels, increased blood pH, or dehydration. If ionized calcium levels are normal, hypercalcemia is not the issue.
Step Two: Rule out obvious diseases.
Examine the patient for signs of disorders that could elevate calcium levels. A thorough examination should include checking for palpable parathyroid gland enlargement, rectal examination to exclude anal gland tumors, assessing lymph nodes for enlargement, and examining mammary glands for growths. Kidney function should also be evaluated as kidney failure can cause hypercalcemia.
Step Three: Consider an ACTH stimulation test for Addison's Disease.
This test helps determine if Addison's disease is a contributing factor to hypercalcemia. Addison's disease often presents with varied symptoms and can mimic other conditions.
Step Four: Conduct PTH and PTH-rP testing.
PTH levels can help identify a parathyroid tumor. Elevated PTH levels in the presence of high calcium are indicative of inappropriate PTH production. On the other hand, high PTH-rP levels strongly suggest cancer. Lymphoma is the primary suspect, but other tumors should also be considered.
Step Five: Initiate a tumor search.
If no obvious tumor is found, further testing is necessary to locate potential hidden tumors. This includes chest and abdominal radiographs, bone marrow aspiration (under anesthesia), abdominal ultrasound to detect hidden tumors and assess kidney health, and additional radiographs to evaluate bone quality. In some cases, multiple myeloma may be considered if specific criteria are met, including elevated monoclonal gammopathy in the blood, moth-eaten bone appearance on X-rays, abnormal proteins in urine (Bence-Jones proteins), and a high percentage of cancer cells or plasma cells in the bone marrow.
Hypercalcemia Management
Treatment strategies for hypercalcemia depend on the underlying cause:
- Dietary Therapy: Reducing dietary calcium intake can be effective in lowering blood calcium levels. Various approaches, such as lightly salting food, supplementing with fiber, or using diets designed for specific conditions like kidney insufficiency or calcium oxalate bladder stones, may help.
- Bisphosphonates: These drugs can suppress osteoclast activity (cells that dissolve bone), reducing calcium release from bones. Alendronate is a common oral veterinary product, while zoledronate is administered intravenously.
- Prednisone: Prednisone can help the kidneys excrete excess calcium, but it should be used cautiously as it can mask lymphoma, the most common cause of hypercalcemia.
- Saline Diuresis: Hospitalization with intravenous fluids can support kidney function and help manage hypercalcemia. Low doses of furosemide may also be used to remove excess calcium from the bloodstream.
Elevated calcium levels in your pet should not be taken lightly. Prompt diagnostic testing is essential to identify the cause and initiate appropriate treatment. If you have further questions or concerns about hypercalcemia or related conditions, consult your veterinarian for guidance.