Lecture 22 3/8/24 Flashcards by Danika Boltz

Where is the majority of calcium in the body located?

within the bone as hydroxyapatite

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Where is the majority of calcium located when it is NOT in the bone?

sequestered in the plasma membrane and ER of cells

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What are the characteristics of phosphorus in the body?

-85% located in bone
-15% in soft tissue
-majority of free fraction is in serum, not bound to proteins

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How does bone play a role in calcium regulation?

-Ca source during low calcemia
-Ca storage during high calcemia
-collagen fibrils have “hole zones” to nest CaPO4 crystals

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When does precipitation of calcium phosphate occur?

When Ca x PO4- exceeds the solubility

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What are the characteristics of bones as dynamic structures?

-bone mass grows until maturity
-old bone is permanently reabsorbed and replaced by new bone

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How does calcium turnover differ between children and adults?

-100% of Ca is turned over in children each year
-20% of Ca is turned over in adults each year

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When do cells express RANKL in order to communicate with RANK on osteoclasts?

after stimulation via PTH

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What is Osteoprotegerin (OPG)?

molecule secreted by osteoblasts that protects the skeleton from excessive bone resorption

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How does OPG work?

binds to RANKL and prevents it from interacting with RANK when PTH levels are low

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What are the steps of bone resorption by osteoclasts?

-podosomes and associated proteins create a sealed chamber
-acid secretion by protein pump dissolves mineral complex
-acid proteases break down collagen
-erosion of bone produces cavities
-Ca, PO4, and HyP released into ECF and blood

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What are the steps of bone formation by osteoblasts?

-lay down collagen and ALK phosphatase on osteoclast cavities
-ALKP hydrolyzes PO4 to increase local amounts and cause CaPO4 precipitation
-bone mineralization
-osteoblasts bury in collagen, become osteocytes

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What are the four main processes involved in bone remodeling?

-activation
-resorption
-reversal
-formation

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Which hormones are involved in increasing blood calcium?

-PTH
-calcitriol

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Which hormone is involved in decreasing blood calcium?

calcitonin

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What are the characteristics of PTH?

-from parathyroid gland
-leads to bone breakdown

What are the characteristics of calcitriol?

-from kidney tubule
-leads to bone breakdown

What are the characteristics of calcitonin?

-from C cell of thyroid gland
-stops bone breakdown
-Ca back into bone

Why can PTH not be given orally?

it is a polypeptide that will be deactivated by gastric acidity and intestinal bacteria

What are the objectives of PTH?

-break the bone matrix
-dissolve salts
-move Ca into blood

What does PTH stimulate osteoclasts to release?

-collagenase
-hydroxylase
-PO4-ase
-H+ pump
-carbonic anhydrase
-citrate
-lactate
-hyaluronate

What is the function of collagenase, hydroxylase, and PO4-ase?

break down of collagen, Ca, and PO4

What is the function of H+ pump, carbonic anhydrase, citrate, and lactate?

create acidic environment

What is the function of hyaluronate?

modulate osteoblast adhesion

Why must osteoclasts be activated by osteoblasts?

osteoclasts do not have PTH receptors, but osteoblasts do

Why is there an increased risk of osteoporosis during menopause?

-estrogen increases synthesis of OPG -estrogen levels decrease during menopause

How does hypercalcemia impact the kidneys?

-decreased reabsorption of P in proximal tubules (phosphaturia) -reabsorption of Ca in distal tubules -conversion of calcidiol to calcitriol to increase intestinal reabsorption of Ca and P

How is vitamin D3 produced?

the action of ultraviolet light on a sterol precursor within the skin

What does calcitriol stimulate?

-osteoclasts -Ca absorption by kidney -Ca and P uptake in the intestine

What is the function of vitamin D?

causes retention of mineral ions to ensure mineralization of bone matrix

What is the function of PTH?

maintain proper ratio of calcium to phosphorus in ECF

What is calcium-binding protein/calbindin?

vitamin D-dependent protein that directly impacts the absorptive capacity of the intestine for calcium

What are the characteristics of calcitonin?

-only Ca lowering hormone -receptors present in bone and kidney -directly inhibits osteoclasts -decreases differentiation of stem cells in osteoclasts -increases kidney excretion of Ca and P -secreted in response to blood Ca above set-point

How does Ca above or below the set point impact feedback regulation?

below set-point: secretion of PTH above set-point: secretion of calcitonin

What are the cellular functions of phosphate?

-handling/storage of energy -second signaling (phosphorylation) -building important structures

What are the characteristics of PTHrP?

-not strictly a calcium-regulating hormone -widely produced -numerous functions in fetus and adult

What is the main function of PTHrP in the fetus?

calcium-regulating hormone

What are the functions of PTHrP in adults?

-mainly a paracrine cellular regulator -may play a role in the transport of calcium into milk

Why is it important that PTHrP is 70% similar to PTH?

-PTHrP often associated with humoral hypercalcemia of malignancy -PTHrP can stimulate PTH receptors on bone and kidney cells -results in PTHrP functioning similarly to PTH in patients with HHM, causing hypercalcemia