Parathyroid and Calcium Regulation Flashcards
describe the calcium distribution in the body.
99% is in the skeleton, 1% is in the ECF and muscles, ).1% (1 g) in the plasma and half is ionized
what form of Ca is regulated in the body? why can high albumin levels give a false positive for hypercalcemia?
ionized Ca
because albumin binds Ca and total calcium measurement will include this
what does acidemia do to calcium homeostasis?
albumin releases Ca- hypercalcemia (reverse for alkalemia)
what are the symptoms of high calcium?
fatigue, headache, muscle weakness, reduced neural responses, bradycardia, short QT interval and polyuria
what are the symptoms of low calcium?
learning retardation, tetany, increased hypersensitivity of neurons, long QT interval and weak bone development
describe familial hypercalcemic hypocalcuria
the normal Ca set point is higher with no symptoms. appear to be hypercalcemic
what causes hypocalcemia and hypercalcemia?
hypo- primary and secondary causes (lactation, malabsorption and poor diet)
hyper- hyperparathyroidism
what three organ systems control calcium homeostasis?
digestive system, kidneys and the skeleton
how much of dietary calcium is absorbed?
20%
when are bones remodeled?
throughout lifetime- even on a normal day
what is the role of bone in calcium homeostasis?
to buffer calcium intakes and losses
what are the short term and long term effects of low dietary calcium?
short term- kidney reabsorption increases
long term- bones demineralize
what does calcitonin do?
it is produced by the thyroid gland in early development to prevent bone resorption
how does phosphate buffer calcium concentration?
by binding calcium and reducing the ionized calcium level or releasing it to increase it
what is the main target organ of PTH? what is the effect?
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
what is the second target of PTH? what does it do?
bone
acts on osteoblasts> secrete paracrine agents to activate osteoclasts to resorb bone
releases Ca and Phosphate
what stimulates the release of PTH by chief cells?
reduction of calcium in extracellular fluids and plasma by calcium receptor
describe the calcium receptor action in PTH chief cells.
g coupled receptor with Ca involved intracellular cascade that controls release and synthesis of PTH
how does PTH stimulate increased phosphate release in the kidney? why does this occur?
decreases resorption from the proximal tubule
occurs because both calcium and phosphate are released from bone- phosphate is kept at normal level
when is the concentration of active Vit D increased? what are the two main target tissues?
with decreased plasma calcium
bone and intestines
what is vit D effect in the intestine?
increases transport of calcium and phosphate from the lumen into the plasma
what is vit D effect in the bone?
acts on osteoblast receptors> signal maturation and activation of osteoclasts to resorb bone
what is vitamin D’s effect in the kidney?
assists in the transport of calcium during reabsorption in the distal tubules
what is vitamin D’s effect on the parathyroid?
reduces the production of PTH (negative feedback)
what is the primary source of vitamin D precursors?
cholesterol derivatives in the skin> converted to cholicalciferol with UV exposure (vit D3)
describe the subsequent processing of cholicalciferol?
liver: converted to 25 OH D3 (calcidiol)
kidney: converted to 1,25 dihydroxy D3 (calcitriol)- enhanced by PTH
where is vitamin D stored?
as calcidiol in the liver
what is measured to assess vitamin D status?
serum calcidiol
how does vitamin D increase intestinal calcium absorption?
increases calbindin levels to sequester the Ca inside the cell (transporter)
what causes rickets? what is the result?
deficiency of vitamin D, calcium or phosphorus during early development
poor bone mineralization causing bowed long bones and large growth plates
what is osteomalacia?
lack of bone mineralization in adults leading to poor quality bone formation during remodeling
what is the implication of elevated calcium and elevated PTH? describe the urine calcium levels
hyperparathyroidism
urine calcium is high because of the high Ca levels- even though PTH stimulates resorption
what is a marker for bone turnover?
alkaline phosphatase
what could cause hypercalcemia with low PTH levels? how does this occur? what could be another cause?
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)
what would cause secondary hyperparathyroidism?
hypocalcemia from low vitamin D, renal failure or diet
what causes pseudohypoparathyroidism?
genetic defect in the PTH receptor g protein in the kidney
what is the effect of chronic kidney failure on phosphate?
hyperphosphatemia
describe phosphorus values in the blood
2.5-4.5 mg/dl in the blood (inorganic portion)
10-20% is protein bound
not rigidly maintained
what do osteoblasts do?
synthesize collagen precursors to polymerize outside the cell (osteoid) that mineralizes
signaling in bone to osteoclasts
what is a measure of the state of health of the skeleton?
the thickness of the not yet mineralized collagen
what cells sense mechanical loading and coordinate a response to it?
osteocytes
what is the mineral component of bone? how much of the bone is it by weight?
hydroxylapatite
65% of bone by weight
what factors moderate the remodeling rate of bone?
plasma calcium levels, injury, immobilization, metabolic changes and hormones
what part of the skeleton has a high remodeling rate and why?
vertebrae because they are made of trabecular bone
cortical bone is more stable
what do osteoclasts do?
dissolve bone by secreting acidic molecules and proteases to degrade collagen (do not proliferate)
what is RANK-L?
a cytokine from osteoblasts that bind to receptors on the osteoclast precursors (RANK)
what causes binding of RANK in bone?
stimulated by endocrine factors (PTH and calcitriol) and growth factors (some paracrine)
what is OPG?
a soluble substance secreted by osteoblasts binds RANK receptors and inhibits differentiation of osteoclasts
(analogs treat osteoperosis)
what does estrogen, glucocorticoids and mechanical loading do to bone remodeling and calcium?
estrogen- reduces resportion
glucocorticoids- inhibits intestinal Ca absorption (excess can cause osteoperosis)
Mechanical loading- promotes bone deposition and maintenance
what is sclerostin and how does it relate to mechanical loading of bone?
it is a molecule that inhibits bone formation when bone loading is weak. its expression is reduced by osteocytes with mechanical loading
what is the definition of osteoperosis? osteopenia?
loss of bone mass associated with fracture
bone loss not enough to be in danger of fracture
what bone loss occurss first?
trabecular bone is lost first with some cortical loss as well (becomre more porous and thinner)
what are the treatments for osteoperosis?
replacing nutrients, loading exercise or drugs to reduce osteoclasts or stimulate osteoblasts
