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Nutr 3330 > Midterm 2 (Lec 8) > Flashcards

Midterm 2 (Lec 8) Flashcards

1
Q

Vitamin D

A

Fat soluble - aka calciferol

2 forms;
- vitamin d3: cholecalciferol ( animal foods and from sun
- vitamin d2: ergocalciferol ( plant foods, converted to d3 for food fortification

Both forms are biologically inert and must be converted to other forms to be activated

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2
Q

Vitamin D activation

A

Vitamin D3 (cholecalciferol) must undergo two hydroxylations for activation :
- LIVER: vitamin D to 25OH-D3 (calcidiol) by 25-hydroxylase
- KIDNEY: 25(OH)D3 to 1,25(OH)2-D3 (calcitriol) by 1-alpha-hydroxylase

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3
Q

Vitamin D synthesis

A

Adequate sun exposure can eliminate dietary need yet still considered essential since sun exposure is not always available

Vitamin D synthesis decreased by:
- clothing
- sunscreen
- smoke/pollution
- age
- latitude

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4
Q

Vitamin D synthesis (sun)

A

Cholesterol -> sunlight -> vitamin D3
- occurs in our skin

Reasons for dietary vitamin D:
10-2

Distance from equator

Seasonal variation

UV photons get absorbed by ozone

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5
Q

Vitamin D absorption and transport

A

Absorption involved incorporation into chylomicrons (because it’s a fat soluble vitamin)

Transported bound to a protein - DBP (vitamin D binding protein) *needs binding protein since its fat soluble

Converted to active form in the kidney

Can be stored in the liver, other tissues as well especially adipose (vitamin D produced in sunny seasons can be stored for winter)

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6
Q

Vitamin D overall metabolic role

A

Maintains calcium and phosphorus homeostasis
- ensure that calcium and phosphorus are available in the blood that bathes the bones (bone health)
- acts as a STEROID HORMONE
- vitamin D endocrine system

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7
Q

Vitamin D as a steroid hormone

A

Specific cells in target organs with nuclear vitamin D receptor (VDR)
1. 1,25(OH)2-D3 travels to specific cell
2. Enters cell and binds to nuclear VDR
3. Binds to the actual DNA
4. Alters transcription rate of mRNA which code for synthesis of specific proteins - altering proteins to be able to bind vitamin D

Main target organs are intestine and bone
Other targets:
- brain and nervous systems
- pancrease, reproductive organs
- muscle, cartilage
- cancer cells

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8
Q

Vitamin D and calcium homeostasis

A

Tight regulation of calcium (and phosphorus) important for:
- bone growth
- maintenance of bone density
- nervous system
- blood clotting (remember vitamin K)

Complex system that involves
- vitamin D (steroid hormone role)
- parathyroid hormone (PTH)

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9
Q

Parathyroid hormone (PTH)

A

Peptide hormone produce by parathyroid glands

Key role in calcium homeostasis - also regulates phosphorus (same role as vitamin D)

Parathyroid gland contains a protein that acts as a SENSOR of blood calcium
- sensor protein will detect decreased blood calcium and increase PTH synthesis

“PTH synthesis tiggers increase of calcitrol formation in kidney - vitamin D cannot perform until PTH increases”

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10
Q

PTH effects

A
  • Goal is to restore normal blood calcium and maintain phosphorus homeostasis
  • Negative feedback loop created
  • Primary target organs are kidney and bone

KIDNEY:
A) stimulates activation of vitamin D
- stimulates 1-alpha-hydroxylase
- 25OH-D3 -> 1,25(OH)2-D3 (calcitrol)
B) increases calcium reabsorprion
- decrease urinary calcium
- increase blood calcium
C) decreases phosphate reabsorption
- prevents hyperphosphatemia: which can inhibit conversion of vitamin D to its active form (calcitrol)
- when calcium is removed from bone, P is as well so we need t to keep P in check
- increases urinary phosphate

BONE
A) increases osteoclast activity
- increases bone resorption (bone breakdown)
- calcium and phosphorus are released
- increased blood calcium and phosphorus

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11
Q

Calcitrol 1,25(OH)2-D3

A

Goal is to restore normal blood calcium
Production in the kidney is stumbled by PTH
Acts on intestine and bone

1) INTESTINE
A) stimulates calcium absorption
- also need magnesium
- increase blood calcium
B) stimulates phosphorus absorption
- increases blood phosphorus

  1. BONW
    A) increases osteoclast activity
    - increases bone resorption (breakdown)
    - calcium and phosphorus are released
    - increase in blood calcium and phosphorus
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12
Q

Review of PTH and vitamin D

A

Both act to restore calcium homeostasis

PTH acts on kidney and bone
- kidney: stimulates 1-alpha-hydroxylase
- kidney: increases calcium reabsorption, decreases phosphorus reabsorption
- bone: increases osteoclast activity

1,25(OH)2D3 acts on intestine and bone
- intestine: increases calcium and phosphorus absorption
- bone: increases osteoclast activity, increases resorption, takes calcium out of bone

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13
Q

Hyperparathyroidism

A

Primary hyperparathyroidism
- direct problem with parathyroid glands
- non cancerous growth , cancer

Secondary hyperparathyroidism
- due to another condition that causes low blood calcium that then increases PTH (too much)
- could be conditions of calcium deficiency or vitamin D deficiency or chronic kidney failure

Week and poorly mineralized bones

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14
Q

Secondary hyperparathyroidism

A

One of the most common complications of chronic kidney disease

Kidney can’t activate vitamin D - chronic low blood calcium

Increased PTH, doesn’t work on kidney properly, can’t help to reabsorption calcium, decreased calcium reabsorption

Can’t excrete phosphate in kidney or decrease reabsorption - excess blood phosphate

Can cause bone disease due to bone turnover increasing osteoclast activity

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15
Q

How does vitamin D facilitate calcium absorption

A

Increasing calbindin synthesis

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16
Q

Calcium

A

Most abundant mineral in body - 99% in bones

Passive absorption
- doesn’t depend on vitamin D
- concentration dependent

Active transport absorption
- depends on vitamin D
- requires a transporter and energy
- requires a calbindin (calcium binding protein)

17
Q

Calbindin

A

Free calcium is very toxic to inside of cells - need to move calcium across cell

Need to have calcium BOUND - calbindin binds calcium and acts as a shuttle for calcium through the cell

Facilitates calcium absorption across intestinal cell, also needs magnesium

Vitamin D increases calbindin synthesis

18
Q

Factors affecting calcium absorption

A

ENHANCE absorption
- vitamin D: presence of calbindin (transport of calcium across intestinal cell)
- stomach acid
- supplements best absorbed with a meal
- optimal ratio of calcium to phosphorus

INHIBIT absorption
- vitamin D deficiency
- lack of stomach acid
- excess phosphorus
- high fiber diet
- phytic acid (storage form of phosphate - tends to be in high fiber foods)
- oxalate

19
Q

Calcium metabolic role

A

Bone health (major role)
- bone tissue gains and loses minerals
- goal is to balance this
- teeth similar, fluoride acts as stabilizer

Regulator of cellular processes (minor role)
- muscle contraction, blood clotting
- nerve impulse transmission
- second messenger

20
Q

Calcium as a second messenger

A

Signal transduction

Intracellular messenger of hormone action

Peptide hormone action
- hormone binds to receptor (first message)
- now need to transducer the signal inside the cell
- involves G proteins that need to be activated
- CALMODULIN is an intracellular protein (calcium receptor) that binds calcium allowing for activation of intracellular proteins and enzymes

21
Q

CALMODULIN

A

Intracellular protein/ calcium receptor aka calcium dependent regulatory protein

Found in all cells - binds intracellular calcium

Allows for signal transduction to occur

Activates proteins and enzymes

Key in mechanism of section of numerous peptide hormones

Slide 32

22
Q

Vitamin D food sources

A

Found naturally in very few foods - hard to get requirement through diet only

Fish, egg yolk, mushrooms

Fortified foods

23
Q

Vitamin D and Calcium

A

With vitamin D deficiency:
- production of calbindin is decreased
- calcium absorption is decreased
- thus vitamin D and calcium are related

Specific syndromes related to vitamin D and calcium deficiencies:
- rickets (children)
- osteamalacia and osteoporosis (adults)

24
Q

Rickets

A

Classic severe vitamin D deficiency disease in children
- Involves calcium- low blood calcium
- Still occurs in children world wide

Impaired mineralization of growing bones
- lumps on ribs due to unformed bone
- growth retardation, skeletal abnormalities
- bowlegs, knock needs, spine curvature, protruding belly

Muscle weakness and nervousness
- tetany (calcium involved in muscle contraction)

Factors that contribute towards rickets:
- poor diet
- low UV exposure (pollution, season, sunscreen, tall buildings)

25
Q

Osteamalacia

A

Severe vitamin D deficiency; adult form of rickets
- also involved calcium: low blood calcium
- relatively rare
- could occur in women with: low calcium intake and low sun exposure, multiple pregnancies and lactation

remember bone is in a constant state of turnover
new bone matrix is laid down but NOT mineralized properly (defect in the mineralization of bone matrix)
- amount is not affected
- composition is affected

Softening of bones : bending of spine, bowing of legs

26
Q

Osteoporosis

A

Disease related to calcium deficiency

Amount of bone - opposite of osteomalacia (no change in composition of bone, instead loss of overall amount of bone)
- reduced bone density

Increased susceptibility to fracture especially at wrist spine and hip

27
Q

Types of bone

A

Bone made of 2 compartments :

  1. CORTICAL
    - 80% of skeleton
    - dense bone tissue, shafts of long bone, other hard shell of flat bones
    - calcium loss is slow
  2. TRABECULAR
    - inner structural matrix
    - at ends of long bones, inside cortical shell of flat bones
    - loses calcium readily, calcium loss is faster
28
Q

Type 1 osteoporosis

A

Rapid bone loss

Due to rapid loss of estrogen in women following menopause and decrease of testosterone in men with old age (50 to 70 years old)

More common in women “and than type 2” - called post menopausal osteoporosis

Primarily trabecular bone - wrist and spine fractures

29
Q

Type 2 osteoporosis

A

Slower bone loss - > 70 years old

Due to aging factors
- reduced calcium absorption
- increases risk of falling
- increased bone mineral loss

Both trabecular and cortical bone

Hip fractures

30
Q

Vitamin D status

A

Measurement of blood 25OH-D3 (calcidiol)
- > or equal to 50 nmol/L is sufficient amount

A biomarker of vitamin D exposure (from food supplements and sun exposure)

31
Q

Vitamin D concern in older adults

A

Reduced dietary intake

Low use of supplements

Less time outside

Less cutaneous synthesis due to thinning of skin

32
Q

Vitamin D and calcium toxicity

A

HYPERVITAMINOSIS D
- results in enhanced calcium absorption

Symptoms
- hypercalcemia
- loss of appetite, anorexia
- fatigue, irritability
- headache
- calcinosis

No documented cases due to excess sun: process is self limiting

CALCINOSIS
- deposition of calcium in soft tissues
- blood vessels
- heart, kidney, lungs
- kidney stones
- tissue around joints

33
Q

Vitamin D and non skeletal health outcomes

A

Very active area of research
- cancers, CVD
- diabetes, immunity

Multiple sclerosis
- substantial evidence to support a role for vitamin D
- lower rates of MS closer to the equator and in people who get more sun exposure/ have higher vitamin D status

34
Q

Vitamin D and Covid 19

A

Active area of research

Lower rates of Covid 19 closer to equator

Inverse associations of Covid with 25(OH)D3

Similar risk factors for Covid and vitamin D deficiency
- may relate to vitamin D’s role as a hormonal modulator of immune cells which all have vitamin D receptors

Nutr 3330 (21 decks)

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