Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

NFS382 > Vitamin D > Flashcards

Vitamin D Flashcards

osteoporosis and bone health

1
Q

Why is osteoporosis an emerging epidemic?

A

aging population

-osteoporosis largely diagnosed during aging

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is osteoporosis?

A
  • skeletal disorder characterized by: compromised “bone strength” predisposing a person to an increased risk of fracture
  • bone strength: integration of bone density and quality
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are some common sites of fragility fracture?

A
  • hip
  • spine/vertebra
  • destruction of bone microarchitecture: decrease mineral, decrease matrix proteins

microarchitecture: bone matrix proteins and mineral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the Cortical bone? (bone structure)

A

compact/dense

  • represents about 75-80% of total bone in the body
  • consists of LAYERS of mineralized protein (mostly type I collagen)
  • found mainly on the surfaces of all bones and the shaft of long bones of the limbs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the Trabecular Bone? (bone structure)

A

spongy appearance

  • represents ~20-25% of total bone in the body
  • consists of an INTERCONNECTED system of mineralized proteins (mostly type I collagen)
  • found in relatively high conc. in the axial skeleton (vertebrae and pelvic region) and the ends of long bones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are some risk factors for osteoporosis?

A
  1. genetic: family history (PBM)
  2. small-boned
  3. no physical activity
  4. early menopause, loss of estrogen
  5. some medications: corticosteroids, anticonvulsants
  6. smoking
  7. alcohol ( >2 drinks/day)
  8. excessive caffeine
  9. other nutritional inadequacies
    ex. fluoride not essential but important for bones and teeth in terms of strength)

female more prone than males

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How to assess bone health?

A

Bone Mineral Density (BMD) by DXA: gold standard
-changes in BMD measured after many months/years: bone mass, bone quality, T-scores, area (cm2), BMC (g), BMD (g/cm2)

BMD: bch assessment of bone health
-do it every 2 years: not often use numbers to diagnose osteoporosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How to measure bone density by DXA?

A

Bone health is determined by comparing BMD with young health reference population

T-scores are calculated based on BMD (g/cm2)

Osteoporosis is a skeletal disorder characterized by: compromised bone strength predisposing a person to increased risk of fracture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does T-score for bone density indicated?

A 
T-score:
\+2.5 to -1.0: normal
-1.0 to -2.5: osteopenia
< -2.5: osteoporosis
< -2.5 with fracture: severe osteoporosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are some biochemical markers of bone turnover?

A

used as surrogate measures for changes in BMD: altered in weeks
-markers of bone formation and bone resorption

changes in bch markers of bone turnover provide a crude prediction of changes in BMD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some markers of bone formation?

A

Production of bone matrix proteins by osteoblasts detected in serum/plasma:
bone-specific alkaline phosphatase

procollagen type 1 N-terminal peopeptide

procollagen type 1 C-terminal propeptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some markers of bone resorption?

A

Breakdown of bone matrix proteins by osteoclasts:

  • deoxypyridinoline
  • pyridinoline
  • N-telopeptide

changes in bch markers of bone turnover provide a crude prediction of changes in BMD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are some facts of DRI for vitamin D?

A

DRI based on bone outcomes only

  • assume sun exposure is minimal
  • Serum vit.D level required to facilitate bone health was 50 nmol/L
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some food sources of vit.D?

A

food sources from dairy products: mandatory to be fortified with vit.D

-Milk, fortified soy, rice and almond beverages (mandatory for cow’s milk, voluntary for others)
-fortified margarine (mandatory)
-orange juice (voluntary)
fatty fish, eggs, organ meats, fish liver oils, shitake mushrooms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Units of vitamin D?

A

1 microgram vitamin D = 40 IU or 1 IU = 0.025 microgram vit.D

most supplements provide vitamin D3

vitamin D is fairly stable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is vit.D synthesize endogenously?

A

cholesterol –> 7-dehydrocholesterol in skin glands
–>move into different layers in skin
when skin exposed to direct sunlight
–>UVB cause B ring of 7-dehydrocholesterol to break apart
–>pre-vit D3
–>continue exposure
–>become actual vit.D3 (thermo-isomerization)
chages shape
–>B ring fully opened up (cholecalciferol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How is vit.D synthesize endogenously?

A
  1. ergosterol previtamin D2 (found in plant foods)
    - -irradiation–> ergocalciferol vitamin D2
  2. Cholesterol
    - -> 7-dehydrocholesterol
    - -UVB (skin)–> previtamin D2 (precalciferol)
    - -> vitamin D3 (cholecalciferol)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does endogenous synthesis of vit.D changes with the season?

A

Full-body skin exposure to UVB = 10,000 IU/day oral vitamin

Seasonal variation:
Winter:
1.5 IU vitamin D/cm2 of skin/ h

summer:
6 IU vitamin D/cm2 of skin/h

latitude: above 40N, below 40S: no vit.D syn. for 3-4 winter months
- more extreme latitudes: 6 months or more

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How is vitamin D absorbed in the small intestine (enterocytes)?

A

vit. D absorption from food/supp. does NOT require any digestion
- fat micelles diffuse through enterocytes
- mostly in duodenum and jejunum
- not all vit.D in food (50%) absorbed

once inside cell: become part of chyomicron and enter lymphatic system –>plasma
–>go to liver

vit.D from skin: does not go into lymph–>diffuse through skin and enter blood directly (via binding to vit.D binding protein (DBP))
and travels through body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How is vitamin D transport, metabolize, and stored?

A

40% vit.D in blood transported by chylomicrons
-cholecalciferol diffuses from skin into blood & picked up by vitamin D-binding protein (DBP) for transport

both metabolized to 25-OH D3 in liver
25-OH D3 secreted into blood-transported by DBP

kidneys converted to 1,25-(OH)2 D3 (calcitriol) by 1-hydroxylase

calcitriol transported in blood via DBP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the hydroxylation process for vit.D?

A

active form of vitamin D (cholecalciferol) goes to various tissues to carry out effect

22
Q

How is vitamin D regulated by 1-hydroxylase?

A

Calcium phosphorus levels: decrease levels –> 1,25(OH)2D

PTH (parathyroid hormone): increase pTH –> 1,25(OH)2D

1,25(OH)2D3 levels (calcitriol)

23
Q

What is the mechanism of action of calcitriol?

A

concentration of 1,25(OH)2D influences the enzyme’s response by binding to a vit.D response element (VDRE) on the promoter region of the 1-hydroxylase gene

  • low levels + 1-hydroxylase synthesis: upregulated gene
  • high levels calcitriol + production of other mixed function oxidases: turn off hydroxylase

once made calcitriol in kidneys: half-life 2-6 hours
(not telling vit.D status)
25-hydroxyl vit.D: half-life 2-3 weeks

24
Q

How does genomic mediate the function of calcitriol?

A

2 mech.: genomic, non-genomic
Calcitriol binds to VDR and RXR
–>binds to response element (part of promoter of gene)
–>changes in gene transcription –>changes in protein synthesis

25
Q

How does genomic and non-genomic mediated functions of calcitriol (active vit.D)?

A

involves signal transduction pathways (intracellular signalling) linked to cell membranes

  • thought to account for vit.D’s rapid response effect
    e. g. membrane response steroid binding protein (MARRS)

Non-genomic effects: thought active in intestine, parathyroid, liver, pancreatic B-cells

actions include increased Ca uptake

26
Q

What is an example of non-genomic membrane response steroid binding protein?

A

vit.D binds to receptor on surface of cell
–>signalling pathways
–>downstream effects
ex. increase calcium uptake muscle cells: exchange of calcium is important for contraction
more rapid than genomic mech.

27
Q

Function and mechanisms of action of vit.D:

What is the main function of vitamin D?

A

to maintain serum calcium homeostasis: actions to increase serum calcium

Calcitriol syn. is stimulated in response to changes in serum calcium conc. and the release of PTH
-normal serum calcium 8.5 to 10.5 mg/dL (2.12-2.62 mmol/L)

  • hypocalcemia <8.5 mg/dL
  • Calcium homeostasis: calcitriol and the intestine, kidney, and bone
28
Q

How is calcitriol homeostasis maintained starting from the intestine?

A
  1. intestinal stimulus: low blood calcium
    calcitriol helps get more calcium out of food
    (sufficient: absorb 30%, insuff. 10-15%)
  2. Signals PT gland to release PTH –> increase PTH in the blood
  3. stimulates kidneys to increase Ca2+ reabsorption
    –>increase blood Ca2+
    and stimulates renal-hydroxylase to convert 25-OH D to 1,25-(OH)2-D (calcitriol)
  4. increase blood calcitriol
  5. increase calcitriol stimualtes Ca2+ absorption in intestine by increasing calbindin D9K syn., Ca2+-ATPase exporters, and claudin protein syn., among other means
  6. increase blood Ca2+

increase PTH–>Increase calcitirol travels to bone

  • ->stimulate resorption of Ca2+ and P from bone
  • ->end result increase blood Ca2+
29
Q

How is 1,25 (OH)2D3 absorbed in the intestine?

A

primary role is to increase absorption of calcium via a number of calcitriol dependent mechanisms:
1. uptake of Calcium through calcium-dependent channels (TRPV6) at brush border membrane (BBM): calcitriol promotes syn. of TRPV6

  1. stimulation of calbindin D9K syn.: thought to be responsible for 90% of Calcium transport at BBM
    help get Ca2+ into cell and travel around cell in cytosol
  2. Extrusion of Calcium across the basolateral membrane into plasma by enhancing the synthesis of Ca2+-ATPase pumps
    pump Ca2+ out from enterocyte to blood
  3. stimulation of the production of claudins: proteins that facilitate paracellular transport
30
Q

How does intestine increase absorption of calcium via a number of calcitriol dependent mechanisms?

A
  1. calcitriol (vit.D) enters intestinal cell and binds to VDR
  2. VDR-calcitirol complex travels to nucleus
  3. binds to VDRE on DNA
  4. Calbindin mRNA enters cytosol
  5. Calbindin mRNA travels to ER for translation into protein calbindin
  6. Calbindin goes to brush border to facilitate Ca2+ absorption
  7. Calcium enters the intestinal cell by a specialized channel (calcium channel) and the transport protein calbindin
  8. calcium effluxes from intestinal cell into the blood via active transport
31
Q

How is calcium absorbed from diet?

A

the effect of vit.D nutrition (based on 25(OH)D reaches a plateau at about 80nmol/L)

overall have vit.D in form of calcitriol to help you absorb
(not like you need vit.D and calcium at the same time)

32
Q

How does kidney and vit.D work to maintain calcium homeostasis? PTH

A

Role with PTH is to increase re-absorption of calcium via a variety of mechanisms:
1. calbindin D28K synthesis

  1. TRPV5 and Ca2+-ATPase at the basolateral membrane
function in kidney to prevent kidney from re-filter 
grabs calcium and prevent calcium to be secreted into the urine

when excess calcium: protein shut off and excrete in urine

33
Q

How does bone and vit.D work together to maintain calcium homeostasis? PTH

A

Role with PTH to direct mobilization out of bone:
1. presence of PTH + calcitriol interacts with the nucleus of mature osteoblasts to induce cytokine (RANKL)

  1. RANKL then interacts w/ a RANK receptor found on the immature osteoClast precursor cell to stimulate: differentiation, production, and maturation of osteoclasts
  2. Mature osteoclasts release HCl, alkaline phosphatase, collagenase, and other hydrolytic enzymes which dissolve and catabolize bone
    - ->increase serum calcium (and P) conc.
34
Q

Function and mechanisms of action of vit.D:

What is the main function of vitamin D? decrease

A

Maintain serum calcium homeostasis: actions to decrease serum calcium
(tightly regulated)
-calcitriol NOT thought directly to be involved in decreasing serum Ca conc.: rise above normal (indirectly via PTH)

Calcitonin (produced in thyroid):
-blocks Ca2+ and P mobilization from bones by inhibiting osteoclast activity

-inhibits tubular resorption of calcium increasing urinary calcium losses

35
Q

How does calcitriol maintain Phosphorus homeostasis?

A

Calcitriol can INCREASE absorption of phosphorus by increase phosphatase

Calcitirol thought to play role in:

  • increasing brush border alkaline phosphatase which hydrolyzes phosphate ester bonds to free P enabling absorption
  • regulation of a number of carriers responsible for sodium dependent absorption at the BBM
  • promotes resorption out of bone into blood
  • enhances phosphorus resorption in the distal tubules of the kidney
36
Q

How is calcitriol (vit.D) involve in cell differentiation, proliferation, and growth?

A
  1. act on variety of tissues
  2. stimulates differentiation:
    - stem cells in bone marrow to osteoclasts
    - intestinal epithelial cells
    - pre-osteoblasts ot osteoblasts
  3. inhibits proliferation, promotes differentiation: fibroblasts, keratinocytes, lymphocytes
  4. Psoriasis: potential therapeutic effects?
    skin condition: non-diff. keratunocytes that built up
37
Q

What are some other functions of vit.D?

A
  • Myopathy notes those w/ vit.D deficiency (calcitriol?)
  • neuromuscular and immune function
  • reduction of inflammation
  • vit.D regulates BP and decreases risk of heart disease
  • vit.D deficiency linked w/ autoimmune disorders
  • may improve blood glucose levels in diabetics
38
Q

What are some nutrients that vit.D interacts with?

A

Calcium
Phosphorus
Vitamin K

39
Q

How are vit.D (Calcitriol) excreted?

A

Calcitirol is metabolized prior to excretion:
-hydroxylated –>oxidized
1,24,25(OH)3D3 –> 1,25(OH)2 24-oxoD3

side-chain cleavageL calcitroic acid

via bile –> feces

<30% in urine

40
Q

How do we assess the nutritional status of vit.D?

A

Serum 25-OH-vit.D <50 nmol/L though insufficient

-controversy about this cut off: ex. Ca. Pediatric Society:
deficient: < 25 nmol/L
Insufficient: 25-75 nmol/L
optimal: 75-225 nmol/L

major storage depots are in plasma and adipose
-in overweight/obese individuals plasma vit.D levels may be lower as greater proportion stored in adipose

41
Q

What is vit.D status dependent on?

A

skin pigment, latitude, time of year, skin exposure, sunscreen use, altitude, pollution, cloud cover

42
Q

What are some risk factors for vit.D deficiency?

A

age, dark skin pigment, clothing practices (e.g. burka), residence, obesity, malabsorption (e.g. IBD, Crohn’s, renal disease), breast-fed infants

43
Q

What are some alterations of vit.D related to aging?

A

Sunlight exposure

syn. in skin (decreased 7-dehydrocholesterol)

dietary intakes

intestine: absorption, CaBP
liver: hydroxylation

Kidney: hydroxylaiton, reabsorption

44
Q

What are some units to keep in mind when studying vit.D?

A

Serum/plasma 25(OH)D conc. units:
1 ng/mL = 2.5 nmol/L
30 ng/mL = 75 nmol/L

oral dosage units:
40 IU = 1 microgram
40,000 IU = 1000 microgram (1 mg)

45
Q

What is the prevalence of vit.D inadequacy in children and adults?

A

high prevalence of inadequacy

overall: only ~35% were at 75/higher (optimal vit.D)

young kids and older adults have most sufficient vit.D

46
Q

How does consumption of non-cow’s milk beverages affect serum vit.D levels in early childhood?

A

Drinking non-cow’s milk beverages: 4.2 nmol/L decrease in 25-OH-vit.D levels per cup consumed among children who drank cow’s milk

children who drank only non-cow’s milk were at higher risk of having 25-OH-vit.D levels below 50 nmol/L compared to children who only drank cow’s milk

47
Q

What are some facts about vit.D deficiency?

A

widespread worldwide

ex.
Rickets: children: seizures, growth retardation, bones dont mineralize

Osteomalacia: adults: prolonged elevation in PTH and bone-mineralization

Supplement breast fed infants, adults over 50, others w/ impaired vit.D absorption

48
Q

What is Rickets? vit.D deficiency

A

epiphyseal cartilage continues to grow and enlarge w/o replacement of bone matrix and minerals

effects esp. at wrists, ankles, knees, long bones, spine, pelvis, and thoracic area

49
Q

What are some toxicity of vit.D?

A

UL = 100 microgram (4000 IU)
(sun exposure 10,000 IU/d)

MOST likely of all vit. to cause toxicity
endocrine society’s clinical practice guidelines suggest higher intakes than RDA for those at risk of deficiency:
1500-2000 IU daily and
UL = 10,000 IU for adults 19-70 yo

50
Q

Is indoor tanning safe?

A

exposed to both UVA and UVB
–>damage skin can lead to cancer
user younger than 35: 59% higher risk of melanoma

NFS382 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions