Case study – Hypercalcemia
A 20-year-old female college student presented in the emergency room with hypercalcemia and kidney failure. She notes the onset of polyuria and nocturia 6 to 8 months earlier. She reported an onset of headache, constipation, urinary tract infection, and fatigue approximately 6 weeks earlier. She admitted to some nausea and vomiting. Yesterday she visited her father who commented that she seemed dazed and confused. Her father brought her to the emergency room. Past medical history reveals recurrent nephrolithiasis (kidney stones). She does not smoke or drink alcohol. She denies the use of any other medications or over–the-counter supplements. On examination, she appears in no acute distress. Blood pressure is 130/80 mm Hg; pulse 70 per minute; respiratory rate 12 per minute; body temperature 37o C. Heart rate is regular, no murmurs detected. The examination of her neck reveals the presence of a palpable mass. Neurological examination shows mild depression and some cognitive dysfunction. Routine laboratory studies are normal except for serum Ca2+ levels of 17 mg/dl (normal 9-11mg/dl). You suspect carcinoma of the parathyroid gland and order further studies.
Note: If the patient does have carcinoma of the parathyroid gland it would cause increased secretion of parathyroid hormone.
1. Define the terms indicated in bold.
Hypercalcemia: Excess calcium in the blood
Polyuria: Excessive urination
Nocturia: Excessive urination during the night
Carcinoma: A malignant tumor that originates from epithelial cells.
Definitions paraphrased from the MedlinePlus Medical Dictionary online.
2. Describe the composition of the extracellular matrix (ECM) of bone.
The ECM of bone is primarily composed of calcium, phosphate, collagen fibers, and proteoglycans.
3. What is the source of the minerals in the ECM of bone?
Minerals of the bone are absorbed from the blood and stored in the form of calcium phosphate, also called hydroxyapatite. The original source of calcium is from the diet.
4. What characteristic of bone is due to the mineral component?
The minerals of the bone provide rigidity.
5. What is an osteoclast and what is its function?
An osteoclast is a specialized macrophage cell associated with bone. Osteoclasts'
primary function is to resorb bone and increase calcium levels in the bloodstream. It does this by releasing enzymes and acids that break down the bone matrix to cause the release of calcium into the bloodstream (Clark, 2005, p. 91).
6. Parathyroid glands secrete parathyroid hormone (PTH). Describe the role of PTH in calcium homeostasis.
PTH is released into the bloodstream when calcium levels are low. PTH activates osteoclasts formation and increases the release of acid and enzymes to resorb bone and release calcium (Clark, 2005, p. 246). In addition, PTH increases the production of activated vitamin D, which increases the absorption of dietary calcium by the intestines (Scanlon & Sanders, 2011, p. 251).
7. Is the homeostatic regulation of serum Ca2+ levels achieved through a negative or positive feedback mechanism? Explain your reasoning.
Homeostatic regulation of calcium is a negative feedback loop. When calcium levels drop, PTH levels increase resulting in the release of calcium from the bone. This is a negative feedback loop. If it were a positive feedback loop, then when calcium levels drop, the “feedback” would cause calcium levels to drop further.
8. How does an excessive level of PTH result in increased serum Ca2+?
Excessive levels of PTH cause increased osteoclast activity resulting in bone reabsorption into the bloodstream, as well as activation of vitamin D by the kidney and increased uptake of calcium from the intestine.
9. What is the role of vitamin D in calcium absorption?
Vitamin D acts on the intestine to increase active calcium absorption.
10. Why is the patient exhibiting neurological symptoms?
Calcium ions play a critical role in signal transduction in the brain.
11. X-ray studies showed subperiosteal bone resorption of the distal phalanges. What does this mean in common language?
Calcium is being lost from the bones in the fingertips.
12. Given what you know about the periosteum why is this finding not surprising?
The periosteum surrounds the bones so it is not surprising that the bone resorption would be under the periosteum or “sub-periosteal”. Also, osteoclasts are located just under the periosteum.
13. Several medications used to decrease blood Ca2+ levels prevent osteoclast attachment to the bone matrix (bisphosphonates). How does this lower serum Ca2+ levels?
Physical contact between the osteoclast and the bone stimulates acid release and calcium release into the bloodstream. If attachment is prevented, calcium cannot be released into the serum in this way (Teitlebaum, 2000).
Hypercalcemia, Polyuria, Nocturia, Carcinoma, (n.d.). In MedlinePlus Medical Dictionary online.
Clark, R.K. (2005). Anatomy and physiology: Understanding the human body. Sudbury, MA: Jones and Bartlett Publishers.
Scanlon V.C. & Sanders T. (2011). Essentials of anatomy and physiology. Philadelphia, PA: F.A. Davis Company.
Teitelbaum, S.L. (2000). Science, 289 (5484), 1505-1508. Bone resorption by osteoclasts. DOI:10.1126/science.289.5484.1504