128: Calcium & Mineral Depositon Disorders Flashcards
What are the three hormones that control calcium concentration in the serum?
- Parathyroid hormone (PTH)
- Calcitonin
- 1,25-dihydroxyvitamin D3 (1,25(OH2)D3)
What is the function of Parathyroid hormone (PTH)?
- Increases calcium concentration in the serum
- Increases renal tubular reabsorption of calcium
- Increases renal clearance of phosphate
- Stimulates osteoclastic bone resorption by mobilizing calcium from bone
What is the role of calcitonin in calcium regulation?
- Lowers serum calcium concentration
- Inhibits osteoclast activity, leading to decreased calcium release from bones
How does 1,25-dihydroxyvitamin D3 (1,25(OH2)D3) affect calcium levels?
- Increases plasma calcium concentration
- Stimulates active transport of calcium across the intestine
- Mobilizes calcium from bones, requiring the presence of PTH for this effect
What is calcification and how does it relate to cutaneous tissues?
- Calcification is the deposition of insoluble calcium salts.
- When it occurs in cutaneous tissues, it is known as calcinosis cutis.
- It commonly occurs secondary to local tissue alteration or preexisting calcification.
What is ossification and how does it differ from calcification?
- Ossification is the formation of true bony tissue by deposition of calcium and phosphorus in a proteinaceous matrix as hydroxyapatite crystals.
- Unlike calcification, ossification involves the creation of bone tissue, which may occur without underlying tissue abnormalities.
What are the major classifications of cutaneous calcification?
Classification | Description |
|—————-|————-|
| Dystrophic | Most common; occurs due to local tissue injury; calcium and phosphate metabolism and serum levels are normal.
| Metastatic | Occurs due to elevated serum calcium levels, affecting multiple tissues.
What are the results of calcium salt deposition in tissues?
Calcium salts deposit in the dermis, subcutaneous tissue, or vascular endothelium when local calcium concentration exceeds its solubility in the tissue.
What are the categories of calcium deposition disorders?
Dystrophic, metastatic, idiopathic, and iatrogenic.
What is the primary function of calcium in the body?
Calcium is key to skeletal muscle and myocardial contraction, neurotransmission, and blood coagulation.
What hormones control ionic calcium concentration in the serum?
Parathyroid hormone (PTH), calcitonin, and 1,25-dihydroxyvitamin D3 (1,25(OH2)D3).
What is the effect of parathyroid hormone (PTH) on calcium levels?
PTH increases calcium concentration by mobilizing calcium from bones and increasing renal tubular reabsorption of calcium.
What is the role of calcitonin in calcium regulation?
Calcitonin lowers serum calcium concentration by inhibiting osteoclast activity.
How is vitamin D3 activated in the body?
Vitamin D3 is hydroxylated in the liver and then in the kidney to become biologically active.
What is calcification and how does it occur in tissues?
Calcification is the deposition of insoluble calcium salts, often occurring secondary to local tissue alteration or preexisting calcification.
What is ossification?
Ossification is the formation of true bony tissue by deposition of calcium and phosphorus in a proteinaceous matrix as hydroxyapatite crystals.
What are the major classifications of cutaneous calcification?
Dystrophic and metastatic calcification are the major classifications, with dystrophic being the most common due to local tissue injury.
Explain the role of parathyroid hormone (PTH) in calcium regulation.
PTH increases calcium concentration by enhancing renal tubular reabsorption of calcium, increasing renal clearance of phosphate, and stimulating 1α-hydroxylase activity to increase 1,25(OH)2D3 levels, which boosts intestinal calcium absorption. It also mobilizes calcium from bones by stimulating osteoblasts to release factors that activate osteoclasts.
What is the role of vitamin D3 in calcium homeostasis?
Vitamin D3 increases plasma calcium concentration by stimulating active calcium transport across the intestine and mobilizing calcium from bones. It also regulates growth and differentiation of the skin through the vitamin D receptor (VDR).
What is the difference between calcification and ossification?
Calcification refers to the accumulation of calcium salts in body tissue, which can occur in various conditions, while ossification is the process of bone formation, where cartilage is replaced by bone tissue. Calcification can occur in soft tissues, whereas ossification specifically pertains to bone.
What is the most common type of calcification?
The most common type of calcification is dystrophic calcification, which occurs in damaged or necrotic tissues, regardless of serum calcium levels.
What type of calcification is associated with an underlying defect in calcium and/or phosphate metabolism?
Metastatic calcification is associated with an underlying defect in calcium and/or phosphate metabolism, leading to abnormal deposition of calcium salts in normal tissues.
What type of calcification is related to local tissue injury?
Dystrophic calcification is related to local tissue injury, occurring in areas of tissue damage or necrosis, regardless of serum calcium levels.
What type of calcification has no identifiable tissue abnormality?
Idiopathic calcification occurs without identifiable tissue abnormalities, despite abnormal calcium and/or phosphate metabolism.
What type of calcification has normal serum and phosphate metabolism but abnormalities in collagen?
Iatrogenic calcification can occur with normal serum and phosphate metabolism but may involve abnormalities in collagen, often due to medical interventions or treatments.
What is dystrophic calcification?
Calcification that occurs in damaged or necrotic tissue, often associated with underlying defects in calcium and/or phosphate metabolism.
What are the common cutaneous lesions associated with scleroderma and CREST syndrome?
Nodules and plaques develop in skin, subcutaneous tissue, muscle, or tendons, primarily in the upper extremities.
What is the treatment for calcinosis cutis in scleroderma?
There is no standard treatment, but a diet low in calcium and phosphate along with aluminum hydroxide may help.
What is the most common type of calcification?
Dystrophic calcification.
What type of calcification is associated with local tissue injury?
Metastatic calcification.
What type of calcification occurs with an underlying defect in calcium and/or phosphate metabolism?
Idiopathic calcification.
What type of calcification has no identifiable tissue abnormality?
Iatrogenic calcification.
What is the significance of serum fetuin-A levels in pseudoxanthoma elasticum?
Patients have significantly reduced serum fetuin-A levels, which may allow increased calcification of elastic fibers.
Describe the pathogenesis of dystrophic calcification and its common causes.
Dystrophic calcification occurs due to local tissue injury, where calcium and phosphate metabolism and serum levels are normal. Local tissue abnormalities, such as in collagen, elastin, or subcutaneous fat, may trigger calcification. Internal organs remain unaffected.
What are the clinical features and treatment options for calcinosis cutis in CREST syndrome?
Calcinosis cutis in CREST syndrome presents as nodules and plaques in the skin, subcutaneous tissue, muscle, or tendons, most commonly in the upper extremities. Enlarged calcifications may ulcerate and exude chalky material. Treatment includes a low-calcium and phosphate diet, aluminum hydroxide, disodium etidronate, diltiazem, and surgical removal of calcium deposits.
What is the difference between calcification and ossification?
Calcification is the deposition of insoluble calcium salts, while ossification is the formation of true bony tissue by depositing calcium and phosphorus in a proteinaceous matrix as hydroxyapatite crystals.
What are the treatment options for calcinosis cutis in dermatomyositis?
Treatment includes aggressive early management of juvenile dermatomyositis, which reduces calcinosis occurrence. Calcinosis may improve spontaneously, but treatment is generally difficult.
What are the clinical features of calcinosis universalis in dermatomyositis?
Calcinosis universalis involves extensive calcium deposition along fascial planes, skin, and muscle, forming an ‘exoskeleton.’ It is associated with significant morbidity and mortality.
What are the clinical features of subcutaneous fat necrosis of the newborn?
Subcutaneous fat necrosis of the newborn presents as erythematous nodules and plaques over the cheeks, back, buttocks, and extremities. Lesions may calcify and clear spontaneously.
What are the clinical features of pancreatic panniculitis?
Pancreatic panniculitis occurs in patients with pancreatitis or pancreatic adenocarcinoma. It presents as erythematous nodules caused by calcium soap formation from fatty acids.
A patient presents with nodules and plaques in the skin, subcutaneous tissue, and tendons, along with esophageal dysfunction and telangiectasia. What condition might this indicate?
This presentation is indicative of CREST syndrome (Calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia).
A young patient develops erythematous nodules over the cheeks and buttocks, which later calcify. What condition could this be?
This could be subcutaneous fat necrosis of the newborn, which occurs in the first few weeks of life and may lead to calcification.
A patient with juvenile dermatomyositis develops calcinosis universalis. What does this condition involve?
Calcinosis universalis involves extensive calcium deposition along fascial planes, skin, and muscle, forming an ‘exoskeleton’ and is associated with significant morbidity and mortality.
A patient with scleroderma develops nodules and plaques in the upper extremities that ulcerate and exude chalky material. What is the recommended treatment?
Treatment options include a diet low in calcium and phosphate, aluminum hydroxide, disodium etidronate, diltiazem, and surgical removal of calcium deposits.
A patient with CREST syndrome develops calcinosis cutis. What is the most common site of deposition?
The most common site of deposition is the upper extremities, such as fingers and wrists.
A patient with juvenile dermatomyositis develops calcinosis on the elbows and knees. What is the recommended approach to reduce its occurrence?
Aggressive early treatment of juvenile dermatomyositis is associated with a decrease in the occurrence of dystrophic calcification.
What is the relationship between chronic renal failure and metastatic calcification?
Chronic renal failure leads to decreased clearance of phosphate, resulting in hyperphosphatemia. This condition impairs the production of 1,25(OH2)D3, decreasing calcium absorption and leading to hypocalcemia. The hypocalcemia stimulates increased PTH production, causing bone resorption and mobilization of calcium and phosphate into the serum, which can result in marked hyperphosphatemia. If the solubility product of calcium and phosphate is exceeded, metastatic calcification occurs, leading to either benign nodular calcification or calciphylaxis.
What are the clinical features of calciphylaxis?
Calciphylaxis is characterized by:
1. Progressive vascular calcification
2. Soft tissue necrosis
3. Ischemic necrosis of the skin
4. Presentation: Firm, extremely painful, reticulated violaceous plaques associated with soft tissue necrosis and ulceration.
5. Common sites: Lower extremities are most frequent.
6. Mortality rate: Approximately 80%, usually due to gangrene and sepsis.
What are the key features of benign nodular calcification?
Benign nodular calcification features include:
- Occurs at periarticular sites
- Size and number correlate with the degree of hyperphosphatemia
- Usually asymptomatic except for mass effect
- Disappears with normalization of calcium and phosphate levels
- May require surgical removal if interfering with function
- Reported following subcutaneous administration of LMW heparin in renal transplant patients, resolving after cessation of nadoparin.
What are the common cutaneous neoplasms associated with calcification and ossification?
Common cutaneous neoplasms associated with calcification and ossification include:
| Neoplasm | Calcification (%) | Ossification (%) |
|———-|——————|——————|
| Pilomatricomas | 75% | 15-20% |
| Desmoplastic malignant melanoma | Rare | Rare |
| Atypical fibroxanthoma | Rare | Rare |
| Hemangioma | Rare | Rare |
| Neuilemmoma | Rare | Rare |
| Trichoepithelioma | Rare | Rare |
| Seborrheic keratosis | Rare | Rare |
| Mixed tumors (chondroid syringomas) | Rare | Rare |
What is metastatic calcification and what conditions can lead to it?
Metastatic calcification occurs when the solubility product of calcium and phosphate is exceeded, often due to chronic renal failure, leading to hyperphosphatemia and secondary hyperparathyroidism.
What are the characteristics of benign nodular calcification?
Benign nodular calcification occurs at periarticular sites, correlates with hyperphosphatemia, is usually asymptomatic, and may require surgical removal if it interferes with function.
What is calciphyaxis and in which patients does it occur?
Calciphyaxis is a life-threatening disorder characterized by vascular calcification and soft tissue necrosis, occurring almost exclusively in patients with chronic renal failure and prolonged secondary hyperparathyroidism.
What are the common cutaneous neoplasms associated with calcification?
Common cutaneous neoplasms include pilomatricomas, which show calcification and ossification, and other tumors like pilar cysts and seborrheic keratosis.
What role does the APC gene play in pilomatricomas?
Mutations in the APC gene or β-catenin gene are associated with pilomatricomas, which are the most common cutaneous neoplasms with calcification and ossification.
What are the potential infectious agents that can cause dystrophic calcification?
Infectious agents such as Onchocerca volvulus and Taenia solium can cause enough damage to lead to dystrophic calcification.
What is the significance of hyperphosphatemia in chronic renal failure?
Hyperphosphatemia results from decreased clearance of phosphate in chronic renal failure, leading to increased PTH production and subsequent complications like metastatic calcification.
What are the clinical features of pseudoxanthoma elasticum?
Pseudoxanthoma elasticum is characterized by progressive calcification of elastin fibers in the skin, Bruch’s membranes of the retina, and the cardiovascular system. Patients often have reduced serum fetuin-A levels, an anti-mineralization protein.
