PTH, Regulation of Calcium and Phosphate Flashcards Preview

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Flashcards in PTH, Regulation of Calcium and Phosphate Deck (47):

What are sources of vitamin D?

Photoisomeriztion of provitamin D in the skin to vitamin D3(cholecalciferol). Intestinal absorption from fortified milk, fatty fish, cod-liver oil, lesser extent eggs. Liver stores Vitamin D, excess stored in adipose tissue


What is 1,25-dihydroxycholecalciferol (calcitriol)?

Formed in the proximal tubules (kidney). Most active form of vitamin D. This step stimulated by parathyroid hormone


How do the parathyroids respond to hypocalcemia?

increased PTH increases the activity of alpha-1-hydroxylase in the kidney resulting in increased levels of calcitriol


What regulates renal enzyme alpha-1-hydroxylase?

PTH (reduces the gene activity allowing for more calcitriol to be synthesized if calcium is low), low serum level of phosphate, and plasma calcitriol concentration


What are the functions of calcitriol?

Primarily promotes enterocyte differentiation and promote intestinal absorption of Ca2+. Also stimulates phosphate absorption, direct suppression of PTH, and allows PTH-induced osteoclast activation


What are the effects of vitamin D deficiency?

reduced absorption of Ca2+ & phophorus. Hypocalcemia causes secondary hyperparthyroidism. This can lead to phosphaturia, demineralization of bones, osteomalacia (adults)/osteoporisis; rickets/(children).


What are etiologies of vitamin D deficiency?

Glucocorticoids inhibit intestinal vitamin D absorption. Winter months/housebound status. Chronic renal disease. GI disease or malabsorption. Liver failure. Drugs : phenytoin, phenobarbital, carbamazepine, isoniazid and rifampin


What causes vitamin D toxicity?

Excessive vitamin D supplementation


What are signs and symptoms of vitamin D toxicity?

Hypercalcemia, hypercalciuria, polyuria, polydipsia, confusion, anorexia, vomiting, muscle weakness & bone demineralization


Where is the majority of calcium in your body?

99% remains in bone as hydroxyapatite which serves as a calcium reservoir.


What are the functions of calcium?

Contraction of cardiac, skeletal and smooth muscle, transmission of nerve signals, and effects clotting cascade.


What is the function of osteoblasts and osteoclasts?

Osteoblasts-continually deposit bone even in adults. Osteoclasts- continually absorb bone and are found in the bone matrix


Describe the remodeling cycle

Resorption: Osteoclasts remove mineral and matrix on trabecular & cortical bone. Reversal: Mononuclear cells lay down a glycoprotein-rich matrix so the new osteoblasts can adhere. Formation: Waves of osteoblasts lay down bone until the resorbed bone is completely replaced


What is the effect of PTH on bone?

When secreted intermittently stimulates bone formation. When secreted continually it stimulates bone resorption by increasing the number of osteoclasts. After several months of increased PTH there is more bone resorption and weakened bone w/ large cavities filled w/ osteoclasts


What is osteomalacia and osteopenia?

Osteomalacia: poor bone calcification
Osteopenia: diminished organic bone matrix


What is the importance of the embryological migration of the parathyroid glands?

Extra parathyroid glands or aberrant locations are not uncommon especially along the path of embryologic migration


What is the function of the parathyroid hormone?

main player in controlling CA2+ & phosphate homeostasis in the body. feeds back to stimulate conversion of 25-hydroxycholecalciferol in the kidney to 1,25-dihydroxycholecaleciferol (calcitriol


How is PTH regulated?

Ca2+ controls the secretion of PTH. Parathyroid cells have a calcium-sensing receptor (CaR).
CaR is also expressed in the kidney


Describe how adequate levels of calcium effect calcium feedback

Adequate/elevated Ca2+ levels block PTH from activating 25-hydroxycholecalcetriol, blocks leaching Ca2+ from bones, and maintain balanced renal absorption of Ca2+ and phosphate


What is the effect of calcitriol activity on parathyroids?

Parathyroids contain vitamin D receptors. Calcitriol binds to the receptors: Inhibits PTH synthesis and inhibits parathyroid-cell proliferation. Hyperphosphatemia also stimulates PTH secretion


What is the PTH-related protein (PTHrP)?

Secreted by nonmetastatic solid tumors and some patients w/ non-Hodgkin lymphoma. cause secondary hyperparathyroidism. Increases bone resorption and distal tubule Ca2+ reabsorption.
Does not increase Ca2+ absorption from the intestines


What is calcitonin?

secreted by the thyroid gland—parafollicular cells. Stimulated by high Ca2+ levels to Decreases plasma Ca2+ by decreasing absorptive activities osteoclasts and decreasing formation of new osteoclasts


What are etiologies of primary hyperparathyroidism?

parathyroid adenoma, hyperplasia, parathyroid carcinoma


What is the presentation of parathyroid carcinoma?

rare and occurs btw 44-54yrs. Moderate Ca2+ concentration: 14.6-15.9. Can present w/neck mass, bone disease, or renal disease


What is treatment of parathyroid cancer?

surgery. if not surgically treatable manage hypercalcemia


What is the presentation of primary hyperparathyroidism?

hypercalciemia, decreased bone mineral density, increased risk of vertebral fracturs, HTN, LV hypertrophy/diastolic dysfxn


What are etiologies of secondary hyperparathyroidism?

multiple myeloma, lung, kidney, esophagus, head & neck, breast, skin and bladder cancers are some of the more common. chronic or advanced renal disease.


What are etiologies of hypercalcemia?

primary hyperparathyroidism, solid tumors and leukemias, milk-alkali syndrome, meds


What is milk-alkali syndrome?

High intake of milk or calcium carbonate. Metabolic alkalosis stimulates Ca2+ reabsorption


What are medications that can cause hypercalcemia?

Lithium (increased secretion PTH)‏, thiazide diuretics (lower urinary Ca2+ excretion)


What is pseudohypercalcemia?

Elevation in total Ca2+, but not ionized caused by thyrotoxicosis, adrenal insufficiency, tumors of the pancreas


What are the manifestations of hypercalcemia?

“bones, stones, abdominal pain and psychic groans.” bone pain and muscle weakness, nephrolithiasis, constipation, nausea, anorexia,
anxiety, depression and cognitive dysfunction, arrhythmias


What are symptoms of hypercalcemia?

polydipsia and polyuria, bradycardia, shortened QT, arrhythmias, muscle weakness, renal insufficiency


What are lab tests for hyperparathyroidism?

serum calcium: 8.2-10.2 mg/dL. ionized calcium: 1.15-1.35 mg/dL. serum phosphate: 2.5-4.5 mg/dL. need to know albumin from CMP because Can be artificially increased by elevated albumin or decreased if albumin is decreased


How are lab results interprated for hyperparathyroidism?

Confirm elevated Ca2+ with two readings with albumin. Phosphate usually slightly decreased. ALP may be slightly increased. R/O thyroid dsyfxn. Check PTH level (INTACT) and if need PTHrP


What should you check if PTH or PTHrP are low or normal?

Measure Vitamin D metabolites. If those are normal check for vitamin A deficiency. If uncertain can check 24 hr urinary calcium excretion


What are normal PTH and appropriate steps to take with this result?

normal 10-50 pg/mL. get serum creatinine, bone specific alkaline phosphate. vitamin D metabolites—suppressed in hypercalcemia; normal < 42 pg/mL. PTHrP: increased in hypercalcemia due to malignancy; levels > 1.5 pmol/L


What is the management of asymptomatic patients with hypercalcemia?

Avoid meds that can make hypercalcemia worse, Low calcium diet: < 800-1000 mg/day, physical activity, Adequate hydration, Adequate vitamin D: 400-600 IU/daily


What medications are used to treat patients with hypercalcemia?

Bisphosphonates: Pamidronate (Aredia) & Zoledronate (Zometa)—renal problems and jaw necrosis. Calcimimetic: (cinacalcet) used in pts w/parathyroid carcinoma or w/secondary hyperparathyroidism. Dialysis is last resort


What is the treatment for a hypercalcemic crisis?

Infuse 250-500 mL/hr of saline to rehydrate. Give IV synthetic calcitionin. Give IV bisphosphonates


What are symptoms of hypocalcemia?

mild: parethesias/hyperventilation, myalgias, muscle cramps, fatigue, hyperirritability, anxiety. Severe: Tetany/laryngospasm, Seizures, Papilledema, Myopathy, Hypotension, Prolonged QT interval on EKG


What are the etiologies of hypocalcemia?

hypoparathyroidism, hypovitaminosis D, hyperphosphatemia usually to secondary renal failure


What are expected lab results of hypocalcemia?

Decreased serum Ca2+ , Increased serum phosphate, 1,25(OH)2D levels can be low, Usually high PTH levels


What are treatment options of hypocalcemia?

Vitamin D supplement + Calcium, Can add thiazide diuretic, Calcitriol can be given as increases levels more rapidly


What are etiologies of hyperphosphatemia?

tissue breakdown, Lactic acidosis/ketoacidosis, Exogenous phosphate intake, Renal failure, Hypoparathyroidism, Vitamin D toxicity


What is treatment for hyperphosphatemia?

Acute: Saline infusion to increase phosphate excretion, but can lower Ca2+ more
Hemodialysis Chronic: Low phosphate diet—900mg a day.


What are signs and symptoms of hypersphatemia?

parasthesias, irritability, can progress to seizures & coma, CHF, proximal myopathy, dysphagia, ileus, if severe can get rhabdomyolysis