Calcium and Phosphate Regulation Part 2 Flashcards
How can calcium and phosphate homeostasis be disrupted?
-dietary deficiency or excess calcium
-mutations in genes for vitamin D receptors
-elevated or decreased PTH
-insensivity of tissues to PTH
-mutation in phosphate transporter molecules
-mutations in FGF23 or regulators of FGF23
-chronic kidney disease
What is hypocalcemia?
total serum calcium concentration <8.5mg/dL in the presence of normal plasma protein concentrations or a serum ionized calcium concentration <4.4 mg/dL
What are symptoms of hypocalcemia?
-muscle cramping
-increased neuromuscular excitability
-muscle spasm
-fatigue
-cardiac dysfunction
-depression, psychosis, seizures
What is hypoparathyroidism?
undersecretion of PTH
-relatively rare
What is the most common cause of hypoparathyroidism?
autoimmune destruction of parathyroids/loss of parathyroids due to thyroidectomy
What does the loss of PTH producing tissue do?
hypocalcemia due to decreased calcium uptake in gut/kidney and decrease calcium release from bone
What is Di George syndrome?
congenital disease with complete lack of parathyroids at birth
What are the treatments for hypoparathyroidism?
calcium and calcitriol supplementation
-PTH 1-84 has now been approved in USA and Europe as treatment
What do constitutively activating mutations in CaSR do?
cause autosomal dominant hypocalcemia
What does autosomal dominant hypocalcemia do?
CaSR is hypersensitive to extracellular Ca2+ and suppresses PTH production even though Ca2+ levels are low
-decreases Ca2+ resaborption in the kidney and decreases release from bone, uptake in gut
-leads to low serum calcium
What is the treatment for autosomal dominant hypocalcemia?
calcium and calcitriol
What is pseudohypoparathyroidism?
hypocalcemia due to lack of responsiveness of target tissue to PTH
-serum PTH is high
What causes pseudohypoparathyroidism?
mutations in the G proteins important for PTH signaling
What can cause vitamin D deficiency?
dietary deficiency, lack of sunlight, and malabsorption of vitamin D
What is rickets?
vitamin D deficiency seen in growing children
-impaired bone mineralization/outward curvature of long bones
-insufficiently mineralized vertebrae/curved spine
-disorganized growth plate/growth retardation
What is osteomalacia?
vitamin D deficiency in adults
-due to low serum calcium and phosphate
What is VDDR type I?
vitamin D dependent rickets type I
-autosomal recessive
-defect in renal 25-OH-vitamin D-1 alpha-hydroxylase
-low serum Ca2+ and phosphate
-high PTH
-very low 1,25 (OH)2D3
What is VDDR type II?
vitamin D dependent rickets type II
-autosomal recessive
-defect in vitamin D receptor
-several mutations identified
-low serum Ca2+ and phosphate
-high PTH
-alopecia in some patients
-elevated 1,25(OH)2D3
What is the definition of hypercalcemia?
serum total calcium >10.5 mg/dl or ionized calcium >5.4mg/dl
What are the symptoms of hyercalcemia?
-fatigue
-electrocardiogram abnormalities
-nausea, vomiting, constipation
-anorexia
-abdominal pain
-hypercalciuria/kidney stone formation
-calcification of soft tissues
-hypercalcemic crisis
What is primary hyperparathyroidism?
-common endocrine disorder of parathyroid hyperfunction
-makes too much PTH due to formation of benign adenoma
-hypercalcemia
-low phosphate
-high bone turnover
-kidney stones
treatment for primary hyperparathyroidism?
parathyroidectomy may be recommended
What are the two inherited forms of familial primary hyperparathyroidism?
MEN 1 and MEN 2
What is MEN 1?
multiple endocrine neoplasia type I
-inactivation of tumor suppressor gene Menin
