Endocrine System: Parathyroid and Calcium

Where is calcium distributed in the body?

-bones (majority)

-in blood

How is calcium found in blood?

-bound to protein

-bound to anions

-fee ionized state

What is calcium regulatory mechanism based on?

free ionized calcium in blood

What happens to calcium in blood in acidic conditions?

increase ionized calcium concentration

What happens to calcium in blood in basic conditions?

decrease ionized calcium concentration

What are consequences of hypocalcemia?

-hyperreflexia

-spontaneous twitching

-muscle cramps

-tingling

-numbness

What are consequences of hypercalcemia?

-constipation

-polyuria

-polydipsia

-hyporeflexia

-lethargy

-coma

-death

What is the external calcium balance?

maintain calcium balance throughout the entire body

-balance between calcium intake and excretion

What is the internal calcium balance?

maintaining calcium in cellular compartments

What organs are involved in calcium homeostasis?

-bone

-kidney

-intestine

What hormones are involved in calcium homeostasis?

-parathyroid hormone

-vitamin D

-calcitonin

What secretes parathyroid hormone?

parathyroid gland

What does parathyroid hormone do?

-promote bone resorption to release Ca

-promote Ca reabsorption from renal tubule

-activate 1 alpha hydroxylase to convert vitamin D to active form

What si the role of vitamin D in calcium homeostasis?

-promote Ca absorption from the small intestine

-promote bone resorption to rlease Ca

What is the role of calcitonin?

-stimulates diposition in bone

-reduce reabsorption from renal tubule

What opposes parathyroid hormone? Which of these is stronger?

calcitonin

-parathyroid is stronger

Where is the parathyroid gland located?

posterior surface of the thyroid gland

What type of hormone is parathyroid gland?

peptide

What synthesized parathyroid hormone?

cheif cells of parathyroid

What regulates parathyroid synthesis?

-plasma calcium concentration

-extracellular hypocalcemia

-chronic hypercalcemia

-decreased extracellular magnesium

What is the effect of parathyroid hormone on organ systems?

-coordinates action of bone, intestine, and kidney to increase Ca

-adenylyl cyclase dependent mechanism of action in kidney and bone

Where are parathyroid hormone receptors in bone?

osteoblasts

How does parathyroid hormone cause calcium to be released from bone?

1) PTH binds to receptors on osteoblasts

2) RANKL is released from osteoblasts

3) RANKL binds to RANK receptor on osteoclasts

4) osteoclasts rsorb bone

What is the effect of parathyroid hormone on kidney?

-stimulates calcium reabsorption in distal tubule and collecting duct

-inhibits phosphate reabsorption

-activates renal 1 alpha hydroxylase

Why is phosphate excreted while calcium is reabsorbed?

phosphate forms complexes with calcium preventing it from binding to its desired receptors

What is the effect of parathyroid hormone on small intestine?

PTH stimulates conversion of vitamin D into active form which causes intestinal calciun absorption

What is primary hyperparathyroidism?

problem in the parathyroid gland itself leads to excess PTH

What is the most common cause of primary hyperparathyroidism?

parathyroid adenoma

What is the effect of primary hyperparathyroidism?

-excessive PTH secretion

-hypercalcemia

-excessive excretion of phosphate, cAMP, and calcium in urine

-hypophosphatemia

-increased actived levels of active vitamin D

What is the treatment for primary hyperparathyroidism?

parathyroidectomy

What is secondary hyperparathyroidism?

excessive secretion of PTH due to renal failure decreasing the amount of active vitamin D absorbing calcium from the diet

What are the effects of secondary hyperparathyroidism?

-hypocalcemia (due to lack of vit D absorbing dietary calcium)

-excessive PTH secretion

-increased bone resorption

-hyperphosphotemia due to renal dysfunction

-decreased vitamin D

-osteomalacia

What is osteomalacia?

softening of the bone due to defective remineralization caused by a lack of vitamin D

What are treatments for secondary hyperparathyroidism?

-active form of vitamin D

-phosphatebinders

-parathyroidectomy

What are phosphatebinders?

bind to phosphate before it can be absorbed in the intestines

What is hypoparathyroidism?

abnormally low PTH levels

What can cause hypoparathyroidism?

-thyroidectomy (accidental removal of part of parathyroid)

-parathyroidectomy

-autoimmune and conjenital anomalies (less common)

What is the effect of hypoparathyroidism?

-low PTH secretion

-hypocalcemia

-hyperphosphatemia

-decreased active form of vitamin D

How do you treat hypoparathryroidism?

-calcium supplements

-vitamin D supplements

-phosphatebinders

What is pseudohypoparathyroidism?

symptoms of hypoparathyroidism but the issue is not with PTH levels

What are common causes of pseudohypoparathyroidism?

-inhereted condition

-G protein coupled PTH receptor in bone and kidney are defective

What is the result of pseudohypoparathyroidism?

-hypocalcemia

-hyperphosphatiemia

-increased PTH stimulated by hypocalcemia

-reduced vitamin D

What is another name for pseudohypoparathyroidism?

Albright's Hereditary Osteodystrophy (AD)

What are the characteristic phenotypes of a person with pseudohypoparathyroidism?

-short stature

-short neck

-shortened metatarsals and metacarpals

-round face

-mild mental retardation

What is the treatment for pseudohypopararthyroidism?

-calcium supplements

-vitamin D supplements

-phostphatebinders

What is the purpose of vitamin D?

regulatory hormone for calcium and phosphate

Where do we get vitamin D?

-cholecalceferol in diet

-synthesized in the skin

What happens to the synthesize of vitamin D in the absence of 1-alpha-hydroxylase?

secondary metabolism occurs by CYP24A1

-this produces inactive form of vitamin D

What is the effect of vitamin D in the intestine?

-promote synthesis and expression of TVRP5 calcium channels

-promote synthesis of calbindin D28K (calcium binding protein)

-promote caclim absorption in intestine

-promote phosphate transporters in intestine

What is the effect of vitamin D in the kidney?

promotes calcium and phosphate reabsorption in the distal tubules

What is the effect of vitamin D on the bones?

-stimulates osteoclast activity

-bone remodeling

What causes a vitamin D deficiency?

-dietary deficiency

-congenital condition

-renal failure

-absense of hydroxylation in liver

Who is affected by osteomalacia?

adults who developed vitamin D deficiency later in life

What is the reuslt of osteomalacia?

-defective remineralization of bone

-large spaces inside bone

-joint and bone pain

-muscle weakness

-softening and bending

-easy fracture

What is rickets disease?

softening of the bone due to defective remineralization caused by a lack of vitamin D in children

Who is affected by rickets?

children

What is the result of rickets disease?

-defective remineralization of bone

-large spaces inside bone

-joint and bone pain

-muscle weakness

-softening and bending

-easy fracture

-growth failure

-skeletal deformities

What is the most common cause of hyperthyroidism?

Graves disease