Parathyroid Glands and Calcium Regulation

Question 1

what are the 6 essential physiological functions of calcium?

Answer 1

1. formation of bones and teeth
2. skeletal structural integrity
3. second messenger system activity (intracellular signaling)
4. trans-membrane potential (neural action)
5. muscle contraction (smooth, cardiac, skeletal)
6. blood coagulation (clotting)

Question 2

list and describe 2 problems with calcium regulation

Answer 2

1. hypercalcemia: high calcium levels leads to mineralization of soft tissues, PU/PD, and cardiac problems
2. hypocalcemia: low calcium levels leads to weakness (cows) or tetany (dogs) and hypotension

Question 3

describe calcium distribution in the body (total body calcium)

Answer 3

99% in bones and teeth (but only a little of this “the rapidly exchangeable pool” can be readily released)
0.9% is in soft tissue cells
0.1% in extracellular fluid (immediately available for activity)

Question 4

what are the 3 forms that calcium is distributed in in the body? (calcium fractions) which is bioactive?

Answer 4

1. 45% is free in solution as ionized Ca2+
2. 50% bound to plasma protein (albumin) as protein-bound Ca2+
3. 5% is complexed calcium, typically with PO4 and SO3

ONLY free Ca2+ is bioactive

Question 5

what is total body calcium regulated by? (2)

Answer 5

1. GI tract absorption of Ca2+
2. renal excretion

Question 6

what is the level of free ionized calcium regulated by? (2)

Answer 6

1. exchange between bone and ECF
2. renal excretion

Question 7

what are the three 3’s of regulation of calcium levels?

Answer 7

3 tissues:
1. GI tract (dietary intake and fecal excretion)
2. bone (storage and release)
3. kidney (urinary excretion)

3 processes:
1. calcium absorption (GI tract)
2. calcium resorption or deposition (bone)
3. calcium reabsorption (kidney)

3 hormones:
1. parathyroid hormone
2. active vitamin D3 (calcitriol)
3. calcitonin

Question 8

how does the parathyroid gland regulate plasma calcium?

Answer 8

decreased levels of ionized calcium increase secretion of parathyroid hormone from the parathyroid glands

Question 9

describe parathyroid hormone (hormone type, target tissues (3), and functions

Answer 9

protein hormone (acts on membrane-bound receptors on target cells)

target tissues: skeletal system (bone), kidneys, GI tract (indirectly via activation of Vitamin D3)

function: to control calcium and phosphate homeostasis by increasing blood calcium and decreasing blood phosphorous by binding to specific PTH receptors on target cells (PTH1R and PTH2R)

Question 10

describe PTH synthesis and degradation

Answer 10

constantly produced, stored in secretory vesicles and released by exocytosis in response to low extracellular calcium levels or degraded if calcium levels are fine

Question 11

how are calcium levels monitored physiologically? give 5 relevant tissues

Answer 11

specific calcium sensing receptors (CasR) enable key tissues to closely monitor blood calcium levels

CasR expressing tissues are:
1. parathyroid (principle/chief cells): secrete PTH
2. thyroid parafollicular cells (C cells): secrete calcitonin
3. intestines: determine how much calcium moves in and out of the body
4. kidneys
5. bone (determines how much calcium moves between the ECF and bone)

Question 12

describe calcium regulation of PTH secretion; does the HPA have anything to do with this?

Answer 12

high serum calcium concentration promotes CasR activation, which inhibits release of PTH

low serum calcium concentration promotes release of PTH

HPA does not have anything to do with regulation of PTH secretion!! only serum calcium levels!!

Question 13

describe PTH function in bone (main function and then 3 mechanisms)

Answer 13

main: promote release of calcium from bone (bone resorption/breakdown) by

1. release of calcium from the rapidly exchangeable pool (rapid response)
2. increases activity and survival of existing osteoclast cells
3. promotes the differentiation, proliferation, and new osteoclast cells (long term response = how chronic hypocalcemia can lead to significant bone damage over time)

Question 14

describe PTH function in the kidneys (2, plus its indirect effect on the GI tract)

Answer 14

1. increases renal reabsorption of calcium in the distal tubules
2. increases renal excretion of phosphate (reduces the phosphate that can bind calcium, increasing the amount of free calcium)
3. induces activation of vitamin D, which promotes the absorption of calcium in the GI tract

Question 15

what are the 2 sources of vitamin D? how is it both a vitamin and a hormone? is it water or lipid-soluble?

Answer 15

2 sources:
1. produced in skin from a bio-inactive precursor by UV light
2. contain in some foods

vitamin and hormone:
not a classic hormone because not produced and secreted by an endocrine gland, but not a classic vitamin because can by synthesized de novo (from the beginning) by the body

lipid-soluble; binds to a typical nuclear receptor

Question 16

is vitamin D produced in the skin or obtain from the diet active?how is vitamin D activated?

Answer 16

no! must be activated in the liver and kidney to 1,25-dihydroxyl vitamin D3

first hydroxyl group added in liver = calcidiol = STILL INACTIVE

second hydroxyl group added in the kidneys when PTH activates 1alpha- hydroxylase enzyme = calcitriol = ACTIVE

Question 17

how is 1alpha-hydroxylase regulated in the kidney?

Answer 17

stimulated by:
1. PTH
2. low plasma ionized calcium
3. low plasma ionized phosphate
4. prolactin (during lactation)

inhibited by:
1. high plasma ionized calcium (renal hydroxylation produces an inactive form of vitamin D3)
2. high plasma ionized phosphate

Question 18

what are the 2 functions of active vitamin D?

Answer 18

1. increases total body calcium by increasing GI absorption of calcium: dose-dependent, slow, long-lasting response that adjusts calcium intake from diet to match needs via changes in ratio of active/inactive vitamin D
2. increases ECF ionized calcium by enhancing response of bone to PTH (resulting in resorption of calcium from bone)

Question 19

describe calcitonin (hormone type, where produced, and functions (main function and the 3 mechanisms))

Answer 19

peptide hormone, produced by parafollicular cells (C-cells) of the thyroid

function: lower plasma calcium by:
1. inhibiting activity of osteoclasts (decrease bone resorption)
2. decreasing calcium reabsorption in kidney (increases Ca2+ excretion)
3. inhibiting GI absorption of calcium
all by binding to calcitonin receptors

exact opposite of PTH!

Question 20

how is calcitonin secretion regulation?

Answer 20

1. low serum calcium inhibits calcitonin release
2. high serum calcium promotes calcitonin release to lower plasma calcium

Question 21

describe the physiological role and clinical significance of calcitonin

Answer 21

physiological role: technically could act as a PTH antagonist, but does not usually do so; relatively small role and mostly important in bone remodeling (not very important hormone)

clinical significance: administration of exogenous calcitonin as a treatment for intractable (non-responsive to treatment) hypercalcemia

Question 22

describe hyperparathyroidism and hypoparathyroidism

Answer 22

hypoparathyroidism:
1. rare condition usually caused by autoimmune disease
2. low PTH secretion results in low plasma calcium levels (hypocalcemia)
3. low calcium disrupts neuromuscular excitability (can lead to tetany/muscle spasms)

hyperparathyroidism:
1. primary form usually due to hypersecreting parathyroid tumor
2. high PTH can result in hypercalcemia
3. can also be due indirectly to chronic renal disease or vitamin D deficiency causing hypocalcemia, which in turn then promotes HIGH PTH to compensate

Question 23

what are 3 clinical problems due to high PTH levels WITH elevated calcium?

Answer 23

1. depressed muscle and nerve excitability due to high ECF calcium
2. increased risk of fractures due to demineralization of bone
3. risk of kidney stones due to high concentration of calcium in renal filtrate

Question 24

what is seen with HIGH PTH and vitamin D defiency?

Answer 24

impairs absorption of calcium in the GI tract, which leads to resulting high PTH that causes bone demineralization, can cause rickets in children and osteomalacia (softening of bones) in adults