disorders of Calcium Flashcards
Calcium distribution
- Bones and Teeth (~ 99%). 2. Intracellular Compartment (~ 1%). 3. Extracellular Fluids (< 1%) -Ionized Calcium - 48%, Protein Bound Calcium - 44%
serum Ca limits
10.5mg/dl is upper limit and 8.5mg/dl is lower limit. At 9.0mg/dl Ca raising mechanisms are initiated. At 10.0mg/dl Ca lowering mechanisms are initiated
PTH effects
Increases Serum Ca: increases bone resorption, increases Ca absorption from intestines, decreases Ca excretion by kidneys, increases Vit D production by kidneys and increases phosphate excretion by kidneys
compare Vitamin D from skin vs diet
Skin: D3 cholecaldiferol. Diet: D2 ergocalciferol or D3 cholecalciferol
Vitamin D effects
Increases Serum Ca: Increases bone resorption, increases Ca absorption from intestines and increases phosphate absorption
Calcitonin effects
Decreases Serum Ca: decreases bone resporption
List hypercalcemic disorders with elevated PTH
primary hyperparathyroidism, familial hypocalciuric hypercalcemia
Classifications of primary hyperparathyroidism
Adenoma (85%), hyperplasia (15%), carcinoma (<1%)
Clinical features of primary hyperparathyroidism
> 50% are asymptomatic. Skeletal dz, kidney dz, GI dz, psychiatric dz, arthritis, muscle weakness, band keratopathy, hypertension, anemia
Hyperparathyroidism imaging
Brown tumor- osteoclastoma. Osteitis fibrosa cystica (bones appear large and hollow). Chondrocalcinosis
Hyperparathyroidism physical exam findings
Band keratopathy of the eyes.
Primary hyperparathyroidism diagnosis
Increased serum Ca, decreased serum phosphate, increased serum PTH
Causes of primary hyperparathyroidism
sporadic (90%), famial (10%)- familial HPT, MENI, MENIIA
Components and cause of MENI
Pituitary tuors, pancreatic islet tumors and parathyroid hyperplasia. Caused by germline mutation of Menin gene
Components and cause of MENIIA
medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia. Caused by germline mutation of Ret gene (GDNF receptor)
Treatment of primary hyperparathyroidism
- surgery. 2. Calcimimetic drugs (cinacalcet). 3. anti-resorptive bone drug (bisphosphanate, denosumab)
When is surgery recommended for primary hyperparathyroidism
Serum Calcium > 1 mg/dl Above Normal, Creatinine Clearance < 60 ml/min, BMD T-Score < -2.5 or Fragility Fracture, Kidney Stones, Age < 50 Years
Management of mild asymptomatic primary hyperparathyroidism
Ca and Vit D supplements. Measure Serum Ca and creatinine every 6-12 month. Measure bone density every 1-2 years
Secondary hyperparathyroidism
decreased calcium, increased phosphorus and/or decreased Vitamin D lead to increased PTH.
What is hypercalcemia of malignancy
Elevated Ca and decreased PTH in the setting of cancer
List mediators of hypercalcemia of malignancy
PTH related peptide, TGFBeta, TNF, Interleukin1 or 6, RANK-L, DKK-1, Vitamin D
Diagnosis of hypercalcemia of malignancy
elevated serum Ca, decreased serum PTH, elevated PTH-RP or other mediator
Treatment of hypercalcemia of malignancy
- Promote Urine Calcium Excretion- Saline Infusion. 2. Inhibit Bone Resorption- IV Bisphosphonates, Denosumab, Calcitonin, Plicamycin. 3. Remove Calcium- Dialysis
What is familial hypocalciuric hypercalcemia
Mutations lead to increased PTH secretion and decreased Ca excretion. This causes increased serum Ca. Urine Ca/ Creatinine clearance ratio is <0.01
familial hypocalciuric hypercalcemia treatment
None needed. Avoid surgery
Causes of hypocalcemia
- decreased PTH: hypoparathyroidism. 2. Vit D deficiency. 3. hypomagnesemia. 4. renal or liver failure. 5. acute pancreatitis. 6. hypoproteinemia
Clinical features of hypocalcemia
Paresthesias, Muscle Cramps, Muscle Weakness, Chvostek’s Sign (tapping facial nerve at masseter causes contraction of muscles of face) , Trousseau’s Sign (occlusion of brachial artery induces spasm of muscles of hand and forearm)
Causes of Vitamin D deficiency
- Poor intake or sunlight. 2. Renal dz. 3. hypoparathyroidism. 4. Congenital 1-alpha hydroxylase deficiency (Vit D dependent rickets type 1). 5. congenital Vit D receptor deficiency (Vit D dependent rickets type 2)
Vit D deficiency labs
Decreased serum Ca, decreased Phosphate, increased alkaline phosphatase, increased PTH, decreased Vit D, decreased urine Ca
Signs of Vit D deficiency
osteomalacia-pseudofracture (milkmans fracture or loosers line)
Hypoparathyroidism labs
decreased Ca, increased phosphate, decreased PTH
hypoparathyroidism treatment
Ca supplements, Calcitriol, thiazide diuretics
Pseudohypoparathyroidism
Inactivating mutation of the Gs alpha subunit or other downstream PTH response element
Pseudohypoparathyroidism signs
albrights hereditary osteodystrophy (short 4th and 5th metacarpals)
Pseudohypoparathyroidism labs
decreased serum Ca, increased serum phosphate, increased serum PTH
Pseudohypoparathyroidism treatment
calcium, calcitriol, thiazide diuretics
