FNH Final, High Yield

what are the 4 hormones that regulate the bone micronutrients?

1. PTH

2. Calcitriol

3. FGF23

4. Calcitonin

how and where is PTH secreted? what triggers it?

secreted by the parathyroid glands in response to primarily low blood calcium detected by CaSR (calcium-sensing receptor)

*high Ca → CaSR activated → PTH secretion inhibited

*low Ca → CaSR inactive → PTH secretion increases

what does increased PTH secretion do?

increases serum calcium

1. by decreasing bone calcium (bone resorption)

2. by increasing renal calcium resorption (but flushes/excretes out phosphate to do this)

3. indirectly increasing intestinal calcium absorption by increasing activation of 1a-hydroxlase that converts calcidiol to calcitriol in the kidneys

what are the three proteins that calcitriol activates and increases the formation of?

(in terms of calcium homeostasis)

TRPV6 (at the brush border membrane), Calbindin (transport protein in enterocyte and kidney), Ca2+ ATPase (for ATPase pump at basolateral membrane)

what does increased Calcitriol secretion do?

increases serum calcium

1. by decreasing bone calcium (resorption)

2. increases renal reabsorption (calbindin)

3. increases intestinal absorption (via activating 3 proteins)

increases phosphate absorption

increases magnesium absorption (minor)

how does vitamin D go from its storage form to its active form and what are the different forms called?

vitamin D2 (cholecalciferol) /D3 (egrocalciferol) → calcidiol or 25-OH D (by 25-hydroxylase in the liver) → calcitriol or 1,25-OH2D (in the kidney; by 1a-hydroxylase which is stimulated by PTH and low phosphae and inhbited by FGF23)

*calcitriol activation in the liver is regulated through the activation or inhibition of 1a-hydroxylase

*calcidiol produced automatically based on supply)

how is vitamin synthesized in the skin?

vitamin D3 (cholecalciferol) made in the skin from 7-dehydrocholesterol when exposed to UVB sunlight

what is needed for bone mineralization

adequate supply of Ca and P - vitamin D helps with this

what is FGF23? what does it do?

Fibroblast Growth Factor 23 → bone-derived hormone, high phosphate regulator

• produced in osteocytes and osteoblasts in bone

• release triggered by high serum phosphate, high calcitriol high PTH

• increases renal phosphate excretion

• supresses calcitriol production

what is Calcitonin, where is secreted from, what triggers its secretion and what does it do?

Calcitonin is a thyroid‑derived hormone that lowers blood calcium.

• opposite of PTH but much weaker and less essential to adults

• triggered by high blood calcium

• inhibits osteoclasts which decreases bone resorption

• increases renal calcium excretion

what is gamma-carboxylation?

Conversion of Glu (Glutamic acid) residues into (Gla) gamma carboxyglutamate residues via the addition of a carbonyl group (carboxylation) ; vitamin K dependent; creates Gla proteins; allows for calcium binding (blood clotting/ bone mineralization)

what are Gla proteins?

Proteins that have undergone gamma-carboxylation; allows calcium to bind; clotting factors; mineralization; MGP - prevent calcification of blood vessels and other soft tissues

forms of calcium in food and supplements

food: insoluble calcium salts

supplements : calcium carbonate, calcium citrate, other salts

digestion of calcium

insoluble calcium salts to free Ca2+ by HCl in stomach

3 absorption of calcium

1. active transport (TRPV6, Calbindin, Ca2+ ATPase pump)

2. passive transport - dose dependent

3. calcium absorption by colon (from fermented fibers)

why does bioavailability of calcium decrease with age

estrogen activates 3 absorption proteins also gastric acidity decreases with age

what food sources enhance calcium bioavailability (improves solubility)

1. food and protein

2. lactose and alcohol sugar

what are inhibitors of calcium bioavailability

1. oxalic acid and phytic acid (creates insoluble complexes)

2. magnesium and zinc (compete for absorption)

3. fiber

where in the kidney is calcium increasingly reabsorbed via PTH?

distal tubule

what increases urinary excretion of calcium

caffeine, Na (sodium)

what regulates high calcium

calcitonin

what is the difference between PTH and Calcitonin in the kidney in terms of phosphate and calcium effects

PTH → increases calcium but releases phosphate to make room for it (together in blood they can bind and be disruptive)

Calcitonin → decreases both by excreting both (can not pick and choose, just lowers minerals in general)

out of bone, serum and intracellular levels what is tightly regulated and would not really decrease with low intake of calcium

serum and intracellular (taken from bone)

what inhibits absorption of phosphate when intake is high

calcium (binding creating unabsorbable complexes)

what is the difference between osteoporosis and osteomalacia

1. osteoporosis - bond volume and density lost via imbalance of osteoclasts and osteoblast activity - mopre hormonally caused (estrogen)

2. osteomalacia - normal bone formation, impaired mineralization - more common with deficiencies of calcium and phosphate (needed for bone structure)

what are the implications of excess calcium

hypermalacia, kidney stone risks, inhibits Fe, Mg and P absorption

causes of excess calcium

high dose supplements and hyperthyroidism

implications of calcium deficiency

1. rickets in children

2. osteomalacia

3. osteoporosis

• excitability problems (neuromuscular problems, spasms, tetany)