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Biochemistry: Yr1 > Vitamin D, deficiency and calcium metabolism > Flashcards

Vitamin D, deficiency and calcium metabolism Flashcards

1
Q

What are the 3 main sources of vitamin D?

A

Supplements, dietary sources, skin

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2
Q

Which 2 sources contain vitamin D3?

A

Skin, supplements

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3
Q

What is the other name for vitamin D3?

A

Cholecalciferol

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4
Q

How is cholecalciferol/vitamin D3 synthesised in the skin?

A

UV light from sunlight acts on 7-dehydrocholestrol in skin and converts it into cholecalciferol

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5
Q

Why is adequate sun exposure important in providing vitamin D?

A

Sun exposure allows UV light to convert 7-dehydrocholestrol in skin into cholecalciferol/D3

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6
Q

Give 5 examples of food sources of vitamin D?

A

Oily fish, eggs, meat, fortified cereals, fortified spreads

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7
Q

What type of vitamin D is derived from plant sources?

A

D2/ergocalciferol

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8
Q

Give an example of a plant source of vitamin D?

A

Mushroom

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9
Q

What is the other name for vitamin D2?

A

Ergocalciferol

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10
Q

Do vitamin D supplements contain ergocalciferol/D2 or cholecalciferol/D3?

A

Supplements contain D2 or D3

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11
Q

Why are vitamins D2 and D3 both referred to as vitamin D?

A

D2 and D3 undergo same metabolic changes and perform same physiological actions

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12
Q

What is the main storage form of vitamin D?

A

Calcidiol

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13
Q

Why is calcidiol ideal as a storage form of vitamin D?

A

Calcidiol has a long half-life

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14
Q

What are the 2 other names for calcidiol?

A

Calcifediol

25-hydroxyvitamin D

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15
Q

Where is calcidiol formed in the body, and what enzyme catalyses the reaction?

A

Vitamin D is hydroxylated by 25-hydroxylase to 25-hydroxyvitamin D/calcidiol in the liver

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16
Q

What kind of tissue is calcidiol/25-hydroxyvitamin D usually stored in?

A

Adipose tissue

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17
Q

How is 25OHD converted to calcitriol, and what enzyme catalyses this reaction?

A

1-alpha hydroxylase converts calcidiol into calcitriol/1,25-dihydroxyvitamin D

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18
Q

What is the active hormone form of vitamin D?

A

Calcitriol/1,25-dihydroxyvitamin D

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19
Q

Where in body is calcidiol converted into calcitriol as part of vitamin D’s endocrine function?

A

Kidney

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20
Q

Where in body is calcidiol converted into calcitriol as part of vitamin D’s autoparacrine function?

A

Distant sites eg. placenta

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21
Q

Why is calcitriol ideal as the active form of vitamin D?

A

Calcitriol has a short half-life

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22
Q

What are the main 4 hormones involved in calcium and phosphate metabolism?

A

Calcitriol

Calcitonin (CT)

Parathyroid hormone (PTH)

Fibroblast growth factor 23 (Fgf23)

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23
Q

How does PTH affect serum calcium and phosphate levels in calcium and phosphate metabolism?

A

PTH causes serum calcium levels to increase

PTH causes serum phosphate levels to decrease

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24
Q

What are the 3 effects of PTH in calcium and phosphate metabolism?

A

PTH increases calcium reabsorption in kidneys

PTH increases phosphate filtration in kidneys

PTH increases 1-alpha hydroxylase to activate vitamin D (increases calcitriol)

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25
Q

What cells synthesise PTH, and where are these cells located?

A

PTH synthesised by chief cells of parathyroid gland, which is located on posterior surface of thyroid gland

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26
Q

How does calcitriol affect serum calcium and phosphate levels in calcium and phosphate metabolism?

A

Calcitriol increases serum calcium and phosphate levels

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27
Q

What are the 2 effects of calcitriol in calcium and phosphate metabolism?

A

Increases intestinal absorption of calcium

Increases phosphate reabsorption in kidneys

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28
Q

What inhibits calcitriol synthesis?

A

Calcitriol inhibits its own synthesis

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29
Q

How does calcitriol interact with PTH?

A

Calcitriol regulates how much PTH is secreted from PTH glands

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30
Q

How does calcitonin (CT) affect serum calcium and phosphate levels in calcium and phosphate metabolism?

A

Decreases serum calcium and phosphate levels

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31
Q

What are the 2 effects of CT in calcium and phosphate metabolism?

A

Inhibits calcium and phosphate reabsorption in kidneys

Inhibits intestinal absorption of calcium

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32
Q

How is secretion of CT stimulated, and what cells is CT secreted from?

A

Calcium Sensing receptors (CaSr) on parafollicular cells of thyroid gland detect serum calcium increase, so secrete CT

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33
Q

Give 4 places in which there are CaSr?

A

Brain, kidneys, osteoclasts, parafollicular cells in thyroid

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34
Q

How does Fgf23 affect serum calcium and phosphate levels in calcium and phosphate metabolism?

A

Increases serum calcium

Decreases serum phosphate

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35
Q

What is the effect of fgf23 in calcium and phosphate metabolism?

A

Increases phosphate filtration in kidney

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36
Q

In plasma, what are the 2 chemical states that calcium is found in?

A

50% albumin-bound calcium

50% ionised calcium

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37
Q

What is the total amount of plasma calcium?

A

2.2-2.6mmol/L

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38
Q

What amount of calcium is in bone?

A

1Kg

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39
Q

What percentage of calcium in bone is stored in hydroxyapatite?

A

99%

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40
Q

How does hydroxyapatite act as a reservoir for serum calcium?

A

When serum calcium decreases, bone is resorbed to break down hydroxyapatite and release calcium into blood

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41
Q

Give 5 uses of calcium?

A

Neurotransmission
Cellular growth
Hormone action
Enzyme function
Reproduction

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42
Q

What percentage of calcium is supplied by the source dairy products?

A

43%

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43
Q

What percentage of calcium is supplied by sources cereal, cereal products?

A

30%

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44
Q

Give 3 examples of calcium sources?

A

Dairy products, cereals. green leafy vegetables

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45
Q

What 3 factors affect calcium RNI?

A

Age, gender, conditions

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46
Q

Give 5 causes of calcium deficiency?

A

Low dietary intake

GI disorders with intestinal malabsorption

Phytate and phosphate binding

Post-menopausal oestrogen decrease

Vitamin D deficiency

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47
Q

How can vitamin D deficiency cause calcium deficiency?

A

Lack of vitamin D means that less calcium is absorbed from small intestine into blood, also less resorption of bone

48
Q

Give 4 factors that affect intestinal absorption of calcium?

A

Bioavailability: amount of nutrient that has active effect compared to total ingested amount
Higher the bioavailability, better the intestinal absorption

Age, vitamin D status, calcitriol

49
Q

Rank milk, spinach, beans from highest calcium bioavailability to lowest calcium bioavailability?

A

Milk
beans
spinach

50
Q

What is the percentage range of ingested calcium that is absorbed by small intestine, and what4 factors affect the percentage absorption?

A

15-85%

Intake, life stage, active absorption, physiological state

51
Q

How do phytate and phosphate binding cause calcium deficiency?

A

Phytate/phytic acid binds to calcium which prevents it from being absorbed

Phosphate binds to calcium, so there is less free calcium in the bloodstream

52
Q

How can menopause cause calcium deficiency?

A

Post-menopausal women have decreased oestrogen, this results in less stimulation of intestinal absorption of calcium, enhanced osteoclast resorption so bone turnover occurs at faster rate, so calcium is used too quickly

53
Q

Give 3 ways that calcium deficiency can be prevented?

A

Calcium supplements

promoting calcium foods

Osteoporosis medication contains 1000 mg/d calcium

54
Q

What is the level of albumin-adjusted calcium in hypocalcaemia?

A

Less than 2.2mmol/L

55
Q

Give 4 symptoms of hypocalcaemia?

A

Paranesthesia: numbness and tingling

Muscle spasms and tetany (involuntary muscle contractions)

Coma

Cardiac abnormalities eg. hypertension, arrythmia, failure

56
Q

In hypocalcemia, what are the 3 signs that show muscle spasms and tetany?

A

Chvostek’s sign: facial muscles twitch after you touch individual’s cheek, in front of their ear

Trousseau’s sign: involuntary contraction of hand and wrist muscles after compressing upper arm with bp cuff

Seizures and fits

57
Q

What is the albumin adjusted calcium level in hypercalcaemia?

A

Over 2.6 mmol/L

58
Q

Give 6 symptoms of hypercalcaemia?

A

Nausea

Peptic ulcers

Constipation

Mental disturbance (such as depression)

Renal problems eg. failure, renal stones, polyuria (excessive urination)

Soft tissue calcification

59
Q

During what 2 life stages does bone mass and strength increase?

A

Childhood growth, puberty

60
Q

At what age is peak bone mass reached?

A

30

61
Q

What 2 life stages cause peak bone mass and strength to decrease?

A

Menopause, ageing

62
Q

Before puberty, why is there a greater risk of childhood fractures?

A

Bone mass and strength is still low, which can cause rickets and lead to fractures

63
Q

After menopause and ageing, why is there a greater risk of fragility fractures?

A

Greater risk of developing osteoporosis and osteomalacia, which result in fragility fractures

64
Q

What percentage of an individual’s peak bone mass is influenced by genetics?

A

60-80%

65
Q

What percentage of an individual’s peak bone mass is influenced by modifiable factors?

A

20-40%

66
Q

Give 7 examples of modifiable factors that influence an individual’s peak bone mass?

A

Nutrition of vitamin d and calcium
Vitamin d status
Sun exposure
Hormonal status
Exercise and muscle strength
Growth rate
Body composition

67
Q

What 4 factors can disrupt bone metabolism and affect peak bone mass?

A

Medication, smoking, medical conditions, renal function

68
Q

Give examples of risk groups of vitamin D deficiency?

A

More common in people with darker skin tones

More common in people who have concealed dress style

Little UVB exposure

Obese individuals

Adolescents, as they have high calcium use due to growing bones

Frail, elderly people

Exclusively breastfed babies

Renal disease, GI disorders, severe liver disease

ICU patients

Individuals with TB, HIV, cystic fibrosis

69
Q

What 4 types of pain do both adults and children feel when they have vitamin D deficiency?

A

Joint pain, bone pain, muscle pain, hyperalgesia (feel excessive, severe pain in situations where the pain is normal)

70
Q

How does myopathy caused by vitamin D deficiency affect adults and children in 2 ways?

A

Myopathy is more common in extremities and pelvic region, which causes difficulty rising from sitting/squatting position and a waddling gait

71
Q

Do adults and children both have increased risk of fragility fractures with vitamin D deficiency?

A

Yes

72
Q

What is a fragility fracture?

A

Fracture resulting from low energy trauma caused by falling from standing height or less

73
Q

How can Bone Mineral Density (BMD) be measured, and how does it define osteoporosis?

A

DEXA scan, if T-score is -2.5 SD or below then bone is osteoporotic

74
Q

When the bone is osteoporotic, what is the extent of fracture risk shown by DEXA scan, and where are these fractures most likely to occur?

A

Severe fracture risk in hip, wrist, vertebrae

75
Q

What are 3 symptoms of vitamin deficiency only seen in children?

A

Hypercalcaemic fits

Bone deformities, especially pelvic

Cardiac problems

76
Q

How is vitamin D status investigated?

A

Level of 25OHD is measured

77
Q

How is 25OHD an integrated marker of vitamin D status in the body?

A

25OHD concentration reflects balance of vitamin D supply and how much vitamin D is being used from the supply

78
Q

Why is 25OHD a good marker of vitamin D status?

A

It has a long half-life of several weeks

79
Q

How is 25OHD used to diagnose rickets and osteomalacia?

A

Individual’s 25OHD level is compared against vitamin D threshold, if it below the threshold then individual has rickets/osteomalacia due to vitamin D deficiency

80
Q

What is the vitamin D threshold definition?

A

Level of 25OHD above which osteomalacia and rickets aren’t seen

81
Q

What 25OHD level defines vitamin D deficiency, according to NICE and Royal Osteoporosis Society guidelines?

A

25(OH)D < 25 nmol/L

82
Q

What 25OHD level defines vitamin D insufficiency, according to NICE and Royal Osteoporosis Society guidelines?

A

25(OH)D of 25–50 nmol/L

inadequate level for some people

83
Q

What 25OHD level defines vitamin D sufficiency, according to NICE and Royal Osteoporosis Society guidelines?

A

25(OH)D > 50 nmol/L

Sufficient for almost whole population

84
Q

In the UK, what percentage of patients are vitamin D deficient when first hospitalised?

A

50%

85
Q

In the UK, what percentage of people in the whole population are vitamin D deficient?

A

20%

86
Q

At what time of the year is most vitamin D supplied from skin synthesis by UV light?

A

Summer, in other seasons there are different primary sources of vitamin D as there is less exposure to sunlight

87
Q

What percentage of vitamin D is supplied by fortified cereals?

A

21%

88
Q

What percentage of vitamin D is supplied by oily fish, eggs, meat, fortified spreads?

A

17%

89
Q

How can intake of sources cause vitamin D deficiency?

A

Low sunlight exposure activates less skin synthesis

Low consumption of food sources

90
Q

How can neonatal vitamin D deficiency occur, and what are 3 risks?

A

Maternal vitamin D status is low, which decreases neonatal vitamin D reserves

Risks of impaired foetal growth, infantile eczema, rickets

91
Q

How can newborn vitamin D deficiency occur?

A

Newborn babies that are exclusively breastfed with no other supplements for a long period of time more likely to become deficient, as breast milk contains low levels of vitamin D

92
Q

Why is plain cow milk an inadequate vitamin D source for children?

A

Non-fortified cow milk contains low levels of vitamin D

93
Q

What is the vitamin D RNI for children aged 0-12 months?

A

8.5-10 micrograms (340-400 IU)

94
Q

What is the vitamin D RNI for children aged over 12 months?

A

10 micrograms (400 IU)

95
Q

How can GI disorders with intestinal/fat malabsorption cause vitamin D deficiency?

A

Vitamin D is fat-soluble and is transported within fat/organic solvent, so if small intestine can’t absorb fat then vitamin D won’t enter bloodstream

96
Q

How can obesity cause vitamin D deficiency?

A

Vitamin D accumulates in excess adipose tissue and isn’t readily transported in blood

97
Q

Can high loss/use of vitamin D lead to deficiency?

A

Yes, if more vitamin D isn’t ingested at same rate as use/loss

98
Q

Give 2 examples of how to prevent vitamin D deficiency?

A

More sunlight exposure

Supplementation so that individual reaches their RNI dose

99
Q

Who should take vitamin D supplements in winter?

A

Everyone

100
Q

When should children aged 0-4 take vitamin D supplements in the year?

A

Throughout whole year

101
Q

How can neonatal vitamin D deficiency be prevented?

A

Pregnant women take vitamin D supplements

102
Q

How can menopause cause vitamin D deficiency, and how can this be prevented in post-menopausal women (usually aged 65 and over)?

A

Decreased oestrogen level causes reduced intestinal absorption of vitamin D, so deficiency can be prevented by taking vitamin D tablets

103
Q

To correct vitamin D deficiency, what order are supplements given in?

A

Initial high loading dose is given and split into daily/weekly doses over a few weeks, then maintenance therapy dose is given daily

104
Q

How is vitamin D deficiency corrected in children?

A

loading dose is age-dependent and split then given daily/weekly over 8-12 weeks, maintenance therapy dose is 400-600 IU daily

105
Q

How is vitamin D deficiency corrected in adults?

A

loading dose is 300,000 IU and split then given daily/weekly over 6-10 weeks (avoiding giving 60,000 IU or over at once). Maintenance therapy dose is 800-2000 IU daily

106
Q

What 5 factors need to be monitored to check if vitamin D deficiency has been corrected?

A

bone profile

25(OH)D level if symptoms continue

X-ray

PTH

underlying causes

107
Q

What percentage of men and women over 50 have osteoporosis in UK?

A

50% women

20% men

108
Q

Approximately how many people in the UK have osteoporosis?

A

3 million

109
Q

Over the next 30 years, what will the percentage increase of osteoporotic individuals be in Europe/US and LMICs?

A

50% in Europe/US

100% in LMICs (low and middle income countries)

110
Q

How much does it cost to treat osteoporosis per year in the UK?

A

£1.7 billion

111
Q

Since fractures in elderly people are multifactorial, what 2 factors need to be considered when treating fractures?

A

Bone strength

Muscle strength

112
Q

When considering bone strength in treatment of an elderly fracture, what 4 conditions need to be prevented/treated?

A

bone loss

secondary hyperparathyroidism

osteomalacia

bone pain

113
Q

When considering muscle strength in treatment of an elderly fracture, what 3 conditions need to be prevented/treated?

A

Fall prevention & improvement of balance

Skeletal muscle mass and strength positively related to bone density

muscle pain

114
Q

Why are sufficient calcium and vitamin D intakes important co-therapies when on osteoporosis medication?

A

RCTs have shown that vitamin D supplements have reduced fall risk

115
Q

What is the function of PTH in calcium and bone metabolism?

A

Stimulates osteoclast proliferation and resorption, so increases calcium in blood

116
Q

What is the function of CT in calcium and bone metabolism?

A

Stimulates osteoclast contraction, which decreases their mobility so that that bone resorption is inhibited

117
Q

What is the function of calcitriol in calcium and bone formation?

A

Aids PTH and stimulates osteoclast resorption

Biochemistry: Yr1 (7 decks)

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