Parathyroid and Calcium Regulation

Question 1

describe the calcium distribution in the body.

Answer 1

99% is in the skeleton, 1% is in the ECF and muscles, ).1% (1 g) in the plasma and half is ionized

Question 2

what form of Ca is regulated in the body? why can high albumin levels give a false positive for hypercalcemia?

Answer 2

ionized Ca

because albumin binds Ca and total calcium measurement will include this

Question 3

what does acidemia do to calcium homeostasis?

Answer 3

albumin releases Ca- hypercalcemia (reverse for alkalemia)

Question 4

what are the symptoms of high calcium?

Answer 4

fatigue, headache, muscle weakness, reduced neural responses, bradycardia, short QT interval and polyuria

Question 5

what are the symptoms of low calcium?

Answer 5

learning retardation, tetany, increased hypersensitivity of neurons, long QT interval and weak bone development

Question 6

describe familial hypercalcemic hypocalcuria

Answer 6

the normal Ca set point is higher with no symptoms. appear to be hypercalcemic

Question 7

what causes hypocalcemia and hypercalcemia?

Answer 7

hypo- primary and secondary causes (lactation, malabsorption and poor diet)
hyper- hyperparathyroidism

Question 8

what three organ systems control calcium homeostasis?

Answer 8

digestive system, kidneys and the skeleton

Question 9

how much of dietary calcium is absorbed?

Answer 9

20%

Question 10

when are bones remodeled?

Answer 10

throughout lifetime- even on a normal day

Question 11

what is the role of bone in calcium homeostasis?

Answer 11

to buffer calcium intakes and losses

Question 12

what are the short term and long term effects of low dietary calcium?

Answer 12

short term- kidney reabsorption increases

long term- bones demineralize

Question 13

what does calcitonin do?

Answer 13

it is produced by the thyroid gland in early development to prevent bone resorption

Question 14

how does phosphate buffer calcium concentration?

Answer 14

by binding calcium and reducing the ionized calcium level or releasing it to increase it

Question 15

what is the main target organ of PTH? what is the effect?

Answer 15

the kidney- stimulates resorption of calcium in the distal tubule and increases the excretion of phosphate at the proximal tubule
increases activation of Vit D to calcitriol

Question 16

what is the second target of PTH? what does it do?

Answer 16

bone
acts on osteoblasts> secrete paracrine agents to activate osteoclasts to resorb bone
releases Ca and Phosphate

Question 17

what stimulates the release of PTH by chief cells?

Answer 17

reduction of calcium in extracellular fluids and plasma by calcium receptor

Question 18

describe the calcium receptor action in PTH chief cells.

Answer 18

g coupled receptor with Ca involved intracellular cascade that controls release and synthesis of PTH

Question 19

how does PTH stimulate increased phosphate release in the kidney? why does this occur?

Answer 19

decreases resorption from the proximal tubule

occurs because both calcium and phosphate are released from bone- phosphate is kept at normal level

Question 20

when is the concentration of active Vit D increased? what are the two main target tissues?

Answer 20

with decreased plasma calcium

bone and intestines

Question 21

what is vit D effect in the intestine?

Answer 21

increases transport of calcium and phosphate from the lumen into the plasma

Question 22

what is vit D effect in the bone?

Answer 22

acts on osteoblast receptors> signal maturation and activation of osteoclasts to resorb bone

Question 23

what is vitamin D’s effect in the kidney?

Answer 23

assists in the transport of calcium during reabsorption in the distal tubules

Question 24

what is vitamin D’s effect on the parathyroid?

Answer 24

reduces the production of PTH (negative feedback)

Question 25

what is the primary source of vitamin D precursors?

Answer 25

cholesterol derivatives in the skin> converted to cholicalciferol with UV exposure (vit D3)

Question 26

describe the subsequent processing of cholicalciferol?

Answer 26

liver: converted to 25 OH D3 (calcidiol) kidney: converted to 1,25 dihydroxy D3 (calcitriol)- enhanced by PTH

Question 27

where is vitamin D stored?

Answer 27

as calcidiol in the liver

Question 28

what is measured to assess vitamin D status?

Answer 28

serum calcidiol

Question 29

how does vitamin D increase intestinal calcium absorption?

Answer 29

increases calbindin levels to sequester the Ca inside the cell (transporter)

Question 30

what causes rickets? what is the result?

Answer 30

deficiency of vitamin D, calcium or phosphorus during early development poor bone mineralization causing bowed long bones and large growth plates

Question 31

what is osteomalacia?

Answer 31

lack of bone mineralization in adults leading to poor quality bone formation during remodeling

Question 32

what is the implication of elevated calcium and elevated PTH? describe the urine calcium levels

Answer 32

hyperparathyroidism | urine calcium is high because of the high Ca levels- even though PTH stimulates resorption

Question 33

what is a marker for bone turnover?

Answer 33

alkaline phosphatase

Question 34

what could cause hypercalcemia with low PTH levels? how does this occur? what could be another cause?

Answer 34

humoral hypercalcemia of malignancy PTH-rp (related peptide) is secreted by tumor cells that activate the PTH receptors hyperalbuminemia (in this case albumin would be normal)

Question 35

what would cause secondary hyperparathyroidism?

Answer 35

hypocalcemia from low vitamin D, renal failure or diet

Question 36

what causes pseudohypoparathyroidism?

Answer 36

genetic defect in the PTH receptor g protein in the kidney

Question 37

what is the effect of chronic kidney failure on phosphate?

Answer 37

hyperphosphatemia

Question 38

describe phosphorus values in the blood

Answer 38

2.5-4.5 mg/dl in the blood (inorganic portion) 10-20% is protein bound not rigidly maintained

Question 39

what do osteoblasts do?

Answer 39

synthesize collagen precursors to polymerize outside the cell (osteoid) that mineralizes signaling in bone to osteoclasts

Question 40

what is a measure of the state of health of the skeleton?

Answer 40

the thickness of the not yet mineralized collagen

Question 41

what cells sense mechanical loading and coordinate a response to it?

Answer 41

osteocytes

Question 42

what is the mineral component of bone? how much of the bone is it by weight?

Answer 42

hydroxylapatite | 65% of bone by weight

Question 43

what factors moderate the remodeling rate of bone?

Answer 43

plasma calcium levels, injury, immobilization, metabolic changes and hormones

Question 44

what part of the skeleton has a high remodeling rate and why?

Answer 44

vertebrae because they are made of trabecular bone | cortical bone is more stable

Question 45

what do osteoclasts do?

Answer 45

dissolve bone by secreting acidic molecules and proteases to degrade collagen (do not proliferate)

Question 46

what is RANK-L?

Answer 46

a cytokine from osteoblasts that bind to receptors on the osteoclast precursors (RANK)

Question 47

what causes binding of RANK in bone?

Answer 47

stimulated by endocrine factors (PTH and calcitriol) and growth factors (some paracrine)

Question 48

what is OPG?

Answer 48

a soluble substance secreted by osteoblasts binds RANK receptors and inhibits differentiation of osteoclasts (analogs treat osteoperosis)

Question 49

what does estrogen, glucocorticoids and mechanical loading do to bone remodeling and calcium?

Answer 49

estrogen- reduces resportion glucocorticoids- inhibits intestinal Ca absorption (excess can cause osteoperosis) Mechanical loading- promotes bone deposition and maintenance

Question 50

what is sclerostin and how does it relate to mechanical loading of bone?

Answer 50

it is a molecule that inhibits bone formation when bone loading is weak. its expression is reduced by osteocytes with mechanical loading

Question 51

what is the definition of osteoperosis? osteopenia?

Answer 51

loss of bone mass associated with fracture | bone loss not enough to be in danger of fracture

Question 52

what bone loss occurss first?

Answer 52

trabecular bone is lost first with some cortical loss as well (becomre more porous and thinner)

Question 53

what are the treatments for osteoperosis?

Answer 53

replacing nutrients, loading exercise or drugs to reduce osteoclasts or stimulate osteoblasts