Vitamin D and Calcium

Question 1

3 sites of extracellular fluid interface for calcium exchange

Answer 1

• the intestine
• bone
• renal tubule (kidney)

Question 2

extracellular fluid interface for calcium exchange is mainly regulated by…

Answer 2

vitamin D and parathyroid hormone, but also calcitonin

Question 3

only ___ of total body Ca is in extracellular fluid - mostly in ___

Answer 3

1%, bone

Question 4

what is the regulatory role of calcium in cellular function?

Answer 4

excitation/contraction in the heart muscles, synapse function, platelet aggregation, coagulation, and hormone secretion by exocytosis

Question 5

why is tight regulation of intracellular calcium necessary?

Answer 5

bcuz there is typically a 10,000 fold lower concentration of calcium inside the cell compared to outside. this regulation is maintained by ATP-dependent calcium pumps and the Na+/Ca2+ exchanger

Question 6

how do cells allow calcium back inside after its expulsion?

Answer 6

by rapid flow through calcium channels (receptor or voltage controlled) or by releasing internal stores from the endoplasmic reticulum or mito, often through IP3 signaling

Question 7

what are some processes that rely on calcium as a second messenger?

Answer 7

cell division, muscle contraction, cell movement, membrane trafficking, and secretion

Question 8

what are the consequences of parathyroid gland removal?

Answer 8

leads to severe hypocalcemia, tetany (involuntary muscle contraction) and potentially death due to role of parathy hormone in calcium regulation

Question 9

how does space flight-induced loss of gravity affect calcitonin production and bone health?

Answer 9

induces loss of parafollicular cells, resulting in decreased calcitonin production and bone loss.

• calcitonin can be used to treat lytic paget’s dz, hypercalcemia and osteoporosis

Question 10

what are implications of vitamin D receptors in various tissues beyond bone, kidney and intestine?

Answer 10

are present in immune, testis and breast cells, implications in cancer prevention. also crucial for hormone synthesis and secretion, and regulating genes via a nuclear receptor

Question 11

mature osteoclast

Answer 11

bone resorption cell moves to bone surface and secretes acid and enzymes to break down
bone in bone remodeling cycle; inhibited by calcitonin; mature cell does not divide; has receptor for calcitonin but
NOT for vit D or PTH

Question 12

osteoblast

Answer 12

bone forming cell;
secretes bone matrix; has
receptors for PTH and Vit. D

Question 13

macrophages

Answer 13

are “mops” of immune system, but also critical role in bone remodeling

Question 14

how much of the adult skeleton is replaced approx every 10 years?

Answer 14

about 10% is remodeled if physical or biochemical signals prompt it

Question 15

what are the steps involved in bone remodeling?

Answer 15

A) Resting bone surface
B) Osteoclasts dig a hole by releasing acid and enzymes
C) Macrophages clean up the area
D) Osteoblasts are recruited to the site
E) Osteoblasts secrete bone matrix
F-G) Calcification and Mineralization occur, resulting in the formation of crystals of hydroxyapatite and collagen.

Question 16

how long does the bone remodeling process take and what are the conseqences of an imbalanced remodeling cycle?

Answer 16

approx 6 months, bone loss may occur over time - due to low calcium, medications, fractures, hormone imbalances or aging

Question 17

vitamin D made in…

Answer 17

combo of skin, liver and kidney

Question 18

calcitonin made in…

Answer 18

parafollicular cells in thyroid gland (C cells)

Question 19

parathyroid hormone made in..

Answer 19

parathyroid cells of parathyroid gland

Question 20

what is the role of vitamin D in bone and teeth formation?

Answer 20

essential for formation by maintaining blood levels of Ca ions and phosphate ions

Question 21

besides its role in bone health, what other important effects does vitamin D have?

Answer 21

cell differentiation and development

Question 22

what are the different forms of vitamin D?

Answer 22

fat soluble vitamins - D1, D2, D3. calcitriol is the active vitamin D hormone - one of forms of D3

Question 23

why is vitamin D considered more than just a vitamin?

Answer 23

bcuz we primarily produce it (90%) in skin when exposed to UV light from a metabolite of cholesterol. obtain 10% from diet

Question 24

what is calcitriol?

Answer 24

active form of vitamin D hormone, one of forms of vitamin D3

Question 25

how does sun exposure affect vitamin D synthesis?

Answer 25

exposure of reasonable intensity for ten to fifteen minutes at least two times per week to the face, arms, hands, or back without sunscreen can promote Vitamin D synthesis in the skin. However, factors such as season, geographic latitude, time of day, cloud cover, smog, clothing, and sunscreen usage can influence UV ray exposure and Vitamin D synthesis.

Question 26

why is sunlight exposure during certain months insufficient for vitamin D synthesis in northern latitudes?

Answer 26

from nov-feb is insufficient due to lower sun angles and reduced UVB.

Question 27

why are vitamin D drops recommended for babies?

Answer 27

they may not receive sufficient sunlgiht exposure - can be toxic at high doses especially in ppl with kidney problems or hypercalcemia

Question 28

what wavelength require for vit d?

Answer 28

295nm of UVB (cannot make indoors)

Question 29

explain vitamin d structure

Answer 29

related to steroids and not a vitamin in this context because uses same type of high affinity nuclear receptor to affect transcription as steroids, and levels regulated (as compared to a vitamin that is typically from diet and is a cofactor for some protein or enzyme to assist in its function)

Question 30

explain vitamin d receptors

Answer 30

Vit D receptors in bone, kidney and gut, but also others like immune cells, testis and breast; important implications for cancer (vitamin D signals antiproliferation)

Question 31

explain vitamin D regulation

Answer 31

concentration vit D is upregulated by low phosphate, low calcium ions, low vit D and high parathyroid hormone. If high vit D, feedback inhibits own vit D receptor transcription and upregulates hydroxylase that will break down vit D. Note that vit D is NOT a protein so does not have decreased expression but rather faster breakdown and reduced receptor to receive signal

Question 32

how are vitamin D3 and D2 transported in the body?

Answer 32

by specific vitamin D transport proteins to the liver, where the cytochrome P450 oxidase enzyme acts on them

Question 33

where can vitamin D precursor be stored until needed? what controls its activation?

Answer 33

in liver and fat until needed. main control for its activation occurs at kidneys, where low levels of phosphate, calcium ions and vitamon D, w high levels of parathyroid hormone, favor the production of 1,25-dihydroxyvitamin D (calcitriol). This conversion is catalyzed by cytochrome P450 enzymes and is the rate-limiting step for synthesis.

Question 34

what enzyme involved in deactivating vitamin D in liver and kidney?

Answer 34

hydroxylase enzyme

Question 35

what is active form of vitamin D hormone?

Answer 35

is calcitriol, also known as 1,25-dihydroxyvitamin D3 or simply 1,25(OH)2D.

Question 36

how is vitamin D transported to kidney for further conversion?

Answer 36

by non-specific globulin transport protein, where another cytochrome P450 oxidase enzyme converts it

Question 37

what is the general action of the vitamin D receptor (VDR)?

Answer 37

forms a heterodimer with the retinoic X receptor (RXR) on the vitamin D response element on DNA, affecting transcription and the production of proteins for cell diff, developennt, and maintaining normal blood levels of ca ions and phosphate

Question 38

what are some specific examples of the effects of the VDR activation?

Answer 38

- Increases calcium channels in the intestine, facilitating calcium absorption into cells. - Increases the expression of calcium-binding protein (calbindin), which transports calcium within the cytosol of cells. - Increases the expression of Vitamin D receptor in many cell types. - In bone cells, increases the production of osteocalcin, a protein involved in bone formation. - Decreases the synthesis of parathyroid hormone in parathyroid cells.

Question 39

what determines the specific transcripts affected by vitamin D receptor?

Answer 39

depend on the cell type in which the VDR is expressed

Question 40

what transcriptional changes occur due to vitamin D activity?

Answer 40

increases the transcription of ca channels, calcium binding protein, VDR, and osteocalcin (essen protein for bone formation)

Question 41

how does vitamin D affect parathyroid hormone synthesis?

Answer 41

decreases it, which helps to keep ca and phosphate in bone

Question 42

what cellular differentiation processes are influenced by vitamin D

Answer 42

differentiation of hematopoietic cells, epidermal cells, hair follicle cells, osteoblasts (bone-forming cells), and osteoclasts (bone-resorbing cells)

Question 43

how does vit d influence the balance between osteoblasts and osteoclasts?

Answer 43

both vit D and PTH increase expression of RANKL on osteoblasts, which stimulates formation and activation of osteoclasts - maintaining balance critical for bone remodeling and bone health

Question 44

parathyroid hormone

Answer 44

is a peptide hormone (regulation by transcription, proteolytic processing and vesicular secretion); made in parathyroid cells of parathyroid gland

Question 45

kidney calcium

Answer 45

PTH uses a GPCR where Gαq → PLC → IP3 + DAG that signals Ca 2+ channels to open and uptake from urinary tract and increase plasma Ca 2+

Question 46

bone calcium

Answer 46

stimulates osteoclasts (indirectly) causing bone resorption such that bone releases Ca 2+

Question 47

intestine calcium

Answer 47

increases absorption of calcium indirectly via upregulation of active vitamin D; no PTH receptor in intestine but increases vit D activation in kidney thus increasing body’s calcium uptake from food

Question 48

how is PTH secretion regulated by extracellular calcium levels?

Answer 48

is very sensitive to it, an increase in ion flux into the cell inhibits PTH synthesis and release form secretory granules

Question 49

what receptor mediates the sensitivity of parathyroid cells to EC calcium levels?

Answer 49

calcium ion sensor receptor (CaR). is a GPCR that activates the aq pathway and phospholipase C, leading to production of IP3 and DAG, resulting in increase intracellular ca levels - increase ca inhibits PTH transcription and secretion

Question 50

what role does intracellular magnesium play in PTH secretion?

Answer 50

serves as a secretion signal after stimulation in parathy cells

Question 51

as ca increases...

Answer 51

PTH decreases

Question 52

what are the calcitonin effects?

Answer 52

- lowers ca2+ in blood - inhibits ca2+ reaborption in kidneys - inhibits ca2+ absorption by the intestines - promotes deposition of ca2 into bones

Question 53

what are therapeutic uses of calcitonin in humans?

Answer 53

used for pagets dz, hypercalcemia, and osteoporosis

Question 54

how does calcitonin exert its main effect on calcium levels in the blood?

Answer 54

inhibits osteoclasts, thereby lowering blood calcium levels

Question 55

what is the mechanisms of action of calcitonin?

Answer 55

binds to GPCRs on osteoclasts and kidney tubules, activating Gas pathway, which leads to increase in cAMP levels. - this inhibits osteoclast activity and reduces calcium absorption from the gut, lowering blood ca levels

Question 56

how is calcitonin secretion regulated?

Answer 56

secretion from parafollicular cells (thyroid C cells) is regulated by CaR - increased ca levels leads to calcitonin secretion

Question 57

how is PTH secretion stimulated and whats it main role?

Answer 57

by low blood ca levels. main role to ensure ca levels in plasma are maintained

Question 58

what are the effects of PTH on calcium levels?

Answer 58

enhances ca absorption from food int he gut and urine in kidneys to increase plasma ca levels

Question 59

what is role of calcitonin regulation and how is its secretion stimulated?

Answer 59

secreted by thyroid gland C cells, stimualted by high levels of plasma ca. acts to keep ca in the bone by inhibiting osteoclast activity - preventing hypercalcemia and excessive bone loss

Question 60

what are the roles of bone, intestine and kidney in ca regulation?

Answer 60

- Bone acts as a reservoir and buffer for calcium and phosphate. - Intestine: Vitamin D increases calcium absorption from the intestine, while calcitonin inhibits calcium absorption indirectly. PTH enhances calcium absorption by activating Vitamin D. - Kidney: The kidney conserves calcium and phosphate from urine. Low phosphate, low calcium, and high parathyroid hormone favor the production of 1,25-dihydroxyvitamin D (calcitriol), which enhances calcium absorption. Additionally, hydroxylase deactivates PTH.