PTH, Regulation of Calcium and Phosphate

Question 1

What are sources of vitamin D?

Answer 1

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

Question 2

What is 1,25-dihydroxycholecalciferol (calcitriol)?

Answer 2

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

Question 3

How do the parathyroids respond to hypocalcemia?

Answer 3

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

Question 4

What regulates renal enzyme alpha-1-hydroxylase?

Answer 4

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

Question 5

What are the functions of calcitriol?

Answer 5

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

Question 6

What are the effects of vitamin D deficiency?

Answer 6

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

Question 7

What are etiologies of vitamin D deficiency?

Answer 7

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

Question 8

What causes vitamin D toxicity?

Answer 8

Excessive vitamin D supplementation

Question 9

What are signs and symptoms of vitamin D toxicity?

Answer 9

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

Question 10

Where is the majority of calcium in your body?

Answer 10

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

Question 11

What are the functions of calcium?

Answer 11

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

Question 12

What is the function of osteoblasts and osteoclasts?

Answer 12

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

Question 13

Describe the remodeling cycle

Answer 13

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

Question 14

What is the effect of PTH on bone?

Answer 14

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

Question 15

What is osteomalacia and osteopenia?

Answer 15

Osteomalacia: poor bone calcification
Osteopenia: diminished organic bone matrix

Question 16

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

Answer 16

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

Question 17

What is the function of the parathyroid hormone?

Answer 17

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

Question 18

How is PTH regulated?

Answer 18

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

Question 19

Describe how adequate levels of calcium effect calcium feedback

Answer 19

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

Question 20

What is the effect of calcitriol activity on parathyroids?

Answer 20

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

Question 21

What is the PTH-related protein (PTHrP)?

Answer 21

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

Question 22

What is calcitonin?

Answer 22

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

Question 23

What are etiologies of primary hyperparathyroidism?

Answer 23

parathyroid adenoma, hyperplasia, parathyroid carcinoma

Question 24

What is the presentation of parathyroid carcinoma?

Answer 24

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

Question 25

What is treatment of parathyroid cancer?

Answer 25

surgery. if not surgically treatable manage hypercalcemia

Question 26

What is the presentation of primary hyperparathyroidism?

Answer 26

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

Question 27

What are etiologies of secondary hyperparathyroidism?

Answer 27

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

Question 28

What are etiologies of hypercalcemia?

Answer 28

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

Question 29

What is milk-alkali syndrome?

Answer 29

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

Question 30

What are medications that can cause hypercalcemia?

Answer 30

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

Question 31

What is pseudohypercalcemia?

Answer 31

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

Question 32

What are the manifestations of hypercalcemia?

Answer 32

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

Question 33

What are symptoms of hypercalcemia?

Answer 33

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

Question 34

What are lab tests for hyperparathyroidism?

Answer 34

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

Question 35

How are lab results interprated for hyperparathyroidism?

Answer 35

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

Question 36

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

Answer 36

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

Question 37

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

Answer 37

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

Question 38

What is the management of asymptomatic patients with hypercalcemia?

Answer 38

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

Question 39

What medications are used to treat patients with hypercalcemia?

Answer 39

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

Question 40

What is the treatment for a hypercalcemic crisis?

Answer 40

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

Question 41

What are symptoms of hypocalcemia?

Answer 41

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

Question 42

What are the etiologies of hypocalcemia?

Answer 42

hypoparathyroidism, hypovitaminosis D, hyperphosphatemia usually to secondary renal failure

Question 43

What are expected lab results of hypocalcemia?

Answer 43

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

Question 44

What are treatment options of hypocalcemia?

Answer 44

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

Question 45

What are etiologies of hyperphosphatemia?

Answer 45

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

Question 46

What is treatment for hyperphosphatemia?

Answer 46

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

Question 47

What are signs and symptoms of hypersphatemia?

Answer 47

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