Hypercalcemia - causes, symptoms, diagnosis, treatment, pathology

Summary

Hypercalcemia refers to elevated calcium levels in the blood, which can lead to a range of health issues. The majority of calcium in the body is stored in bones, with small amounts in blood and cells. Disruptions in calcium regulation, such as excessive osteoclast activity or certain tumors, can cause hypercalcemia. Symptoms include muscle weakness, constipation, confusion, and kidney stones. Diagnosis involves blood tests and an electrocardiogram, with treatment focusing on lowering calcium levels through hydration, medications, and preventing bone resorption. Proper regulation of calcium is critical for cellular processes and overall body function.

Takeaways

• 😀 Hypercalcemia refers to high calcium levels in the blood, generally over 10.5 mg/dL.
• 😀 Calcium is the most abundant metal in the body, with 99% stored in bones and only 1% in extracellular and intracellular spaces.
• 😀 High levels of intracellular calcium can cause cell death, such as during apoptosis (programmed cell death).
• 😀 Calcium enters cells through ligand-gated and voltage-gated channels, and excess calcium is pumped out using ATP-dependent pumps and Na+-Ca2+ exchangers.
• 😀 Extracellular calcium is divided into free-ionized calcium (active in cellular processes), complexed calcium (inactive), and protein-bound calcium (also inactive).
• 😀 The calcium-sensing receptor in the parathyroid gland helps regulate calcium levels by controlling the release of parathyroid hormone (PTH).
• 😀 Low blood pH (acidosis) decreases calcium binding to albumin, increasing free ionized calcium levels, which can lead to symptoms of hypercalcemia.
• 😀 True hypercalcemia can result from increased osteoclastic bone resorption, parathyroid gland overgrowth, malignancies, excess vitamin D, or medications like thiazide diuretics.
• 😀 Symptoms of hypercalcemia include slower reflexes, muscle weakness, constipation, confusion, and hallucinations due to disrupted neuronal activity.
• 😀 Diagnosis of hypercalcemia involves blood tests measuring calcium levels and related substances, such as PTH, vitamin D, and albumin.
• 😀 Treatment for hypercalcemia includes hydration, loop diuretics, glucocorticoids, bisphosphonates, and calcitonin to reduce calcium levels and prevent further complications.

Q & A

What is hypercalcemia, and what are its common causes?

Hypercalcemia refers to elevated calcium levels in the blood, typically above 10.5 mg/dL. Common causes include increased osteoclastic bone resorption (bone breakdown), malignancies that secrete parathyroid hormone-related protein (PTHrP), excess vitamin D intake, and certain medications like thiazide diuretics.

How is calcium distributed in the human body?

Around 99% of calcium is stored in the bones as calcium phosphate (hydroxyapatite). The remaining 1% is divided into extracellular calcium (99%) and intracellular calcium (1%), with the majority of extracellular calcium existing as diffusible calcium and a small portion as non-diffusible calcium bound to proteins like albumin.

What are the roles of ligand-gated and voltage-gated channels in calcium regulation?

Ligand-gated channels allow calcium to enter cells and are regulated by hormones or neurotransmitters, while voltage-gated channels are primarily found in muscle and nerve cells and are controlled by changes in electrical potential. Both types help regulate intracellular calcium levels, which are vital for various cellular functions.

How does the body maintain calcium homeostasis?

Calcium homeostasis is regulated by the parathyroid hormone (PTH), which controls calcium levels by increasing calcium release from bones, reabsorption from kidneys, and absorption from the gastrointestinal tract through active vitamin D (calcitriol). The calcium-sensing receptor in parathyroid cells helps detect changes in extracellular calcium levels and adjusts PTH release accordingly.

What is the difference between free-ionized calcium and complexed calcium?

Free-ionized calcium is the biologically active form of calcium that participates in processes like muscle contraction, neuronal action potentials, and blood coagulation. Complexed calcium is bound to negatively charged molecules like oxalate and is electrically neutral, meaning it cannot participate in cellular processes like free-ionized calcium.

What causes false hypercalcemia, and how is it different from true hypercalcemia?

False hypercalcemia, or pseudohypercalcemia, occurs when there is an increase in protein-bound calcium due to conditions like high albumin levels (often caused by dehydration). This condition does not reflect an actual increase in free-ionized calcium levels, unlike true hypercalcemia, where there is an actual increase in free-ionized calcium.

How does the blood's pH affect calcium levels?

In acidosis (low pH), albumin molecules become more positively charged as they bind protons, leading to less bound calcium and more free-ionized calcium in the blood. This increase in free-ionized calcium can contribute to symptoms of hypercalcemia.

What are some of the neurological symptoms associated with hypercalcemia?

Neurological symptoms of hypercalcemia include confusion, hallucinations, and stupor. These occur because high levels of calcium affect the excitability of neurons, making them less responsive.

How does hypercalcemia affect muscle function?

High calcium levels reduce the excitability of muscle cells, leading to slower muscle contractions, muscle weakness, and constipation. This occurs because calcium ions stabilize sodium channels, making it harder for neurons to initiate depolarization.

What are some treatment options for hypercalcemia?

Treatment for hypercalcemia may include rehydration to increase urinary calcium excretion, the use of loop diuretics to prevent calcium reabsorption in the kidneys, glucocorticoids to reduce calcium absorption in the gastrointestinal tract, and medications like bisphosphonates or calcitonin to inhibit bone resorption by osteoclasts.