Fat Soluble Vitamins DLA Flashcards
Describe vitamin A
- Collectively called retinoids
- Retinol – transport and storage form
- 11-cis retinal is required for vision
- Retinol and retinal can be easily interconverted
- Retinoic acid cannot be converted to retinol or retinal
- Retinoic acid – epithelial growth and differentiation. It has steroid hormone like effects
Describe the absorption and transport of vitamin A
- Diet contains retinol esters and beta-carotene
- Absorption requires bile salts. Beta-carotene is converted to retinol
- Esterification and secretion in chylomicrons as retinol esters taken up by the liver where it is stored
- Plasma retinol binding protein (transthyretin) transports vitamin A to extra hepatic tissues
- Tissues contains cellular retinol binding that carries retinol into the cell
What are the sources of vitamin A?
Dietary Sources
• Liver, kidney, butter and cream products; egg yolk
• Yellow vegetables and fruits (Dietary provitamin form: β-carotene)
What are the functions of vitamin A?
Functions
-Vision – 11 cis retinal is a component of rhodopsin (visual pigment). Visual cycle requires the isomerization reaction between cis and trans-retinal.
- Maintenance of specialized epithelia, especially mucus secreting cells (retinoic acid)
- Growth (retinoic acid)
- Reproduction (retinol)
What is the role of 11-cis retinal?
- All trans-retinol is isomerized in the retina to 11-cis retinol
- 11-cis retinol is oxidized to 11-cis retinal
- 11-cis retinal enters the rod cell where it combines with opsin to form rhodopsin (visual pigment)
- Absorption of a photon of light catalyzes the isomerization of 11-cis-retinal to all-trans-retinal triggering a cascade of events.
- Leading to the generation of an electrical signal to the optic nerve which is interpreted as vision
What is the mechanism of action pf retinoic acid in epithelial cells?
- Retinol enters the target cell and is oxidized to retinoic acid in the cytosol
- From the cytosol, the retinoic acid moves into the nucleus with the help of cellular retinoid binding proteins.
- Retinoic acid binds to nuclear receptors forming an activated receptor complex (acts like a transcriptional regulator)
- Retinoic acid-receptor complex binds to chromatin activating the transcription of specific genes (keratin)
Similar to mechanism of action of a steroid hormone
Describe the risk factors of vitamin A deficiency
Riskfactors:
– Dietary deficiency is the commonest cause – fat free diets; lack of dietary sources
– Fad diets: Teen Eats Chicken Nuggets for 15 Years, Nothing Else
– Malabsorption of fats (cystic fibrosis, obstructive jaundice)
What are the signs and symptoms of vitamin A deficiency?
Signs and symptoms
- Night blindness – earliest symptom; inability to see in dim light; Regeneration of rhodopsin is delayed
- Xerophthalmia – dryness of the conjunctiva and cornea.
- Bitot spots
- Keratomalacia – corneal erosion and ulceration
- Increased risk of pulmonary infections
- Immune deficiency – weakened innate immunity
What does deficiencies in retinoids lead to?
Deficiencies of dietary retinoids leads to night blindness, less fertility, slowed growth and skin problems.
Retinoic acid is used to treat severe acne and psoriasis
What are the clinical uses of retinoids?
- Retinol or β-carotene: Treatment of dietary deficiency
- β-carotene is a lipid soluble antioxidant (along with vitamin E)
- Retinoic acid is used in the treatment of acne, especially topical treatment
- The all-trans retinoic acid is used in the treatment of acute promyelocytic leukemia
What is hypervitaminosis A?
• Dry and pruritic (itchy) skin – skin peeling
• Central nervous system – raised intracranial pressure – headaches
– may mimic brain tumors – Benign intracranial hypertension
- Enlarged liver and altered liver function tests
- http://www.theguardian.com/science/antarctica-live/2013/dec/04/douglas-mawson-antarctic-trek
• Vitamin A in Pregnancy – spontaneous abortions and congenital
malformations in the fetus. (vitamin A is a teratogen)
– Vitamin A supplements (greater than the 10,000 IU) should be avoided in pregnant wome
What is vitamin D(Calciferol)?
- Group of sterols that have a hormone like function
- Ergocalciferol (vitamin D2) – found in plants
- Cholecalciferol (vitamin D3) – Found in animal sources
- The precursor for cholecalciferol (vitamin D3) synthesis in the skin is 7-dehydrocholesterol (intermediate in cholesterol synthesis)
- Adequate exposure to sunlight can prevent vitamin D deficiency
What are the factors affecting the formation of vitamin D in the skin?
• Increased melanin pigment reduces its formation • Time of exposure and latitude • Amount of exposed skin/ sunscreen reduces formation • Winter months and latitude
How is 1,5 DHCC inactivated?
Action of 24-hydroxylase
And forms 1,24,25-hydroxycholecalciferol (inactive calcitriol)
What is The mechanism of action of 1,25-dihydroxycholecalciferol?
- 1,25 Dihydroxycholecalciferol (Calcitriol) binds to intracellular receptor proteins in target cells (intestinal mucosal cells)
- 1,25-DHCC receptor complex interacts with DNA (hormone response element) in the nucleus of target cells (intestine)
- Can either selectively stimulate gene expression or repress gene expression – Increases synthesis of
calbindins (similar to mechanism of action of steroid hormones, thyroid hormone, retinoic acid)
What is the impact of vitamin D on serum calcium?
- Ontheintestine–stimulatesintestinalabsorptionof calcium and phosphate by increased synthesis of a specific calcium binding protein (calbindin)
- On the bone – stimulates the mobilization of calcium and phosphate from the bone in the presence of parathormone (when the serum calcium level is low)
- On the kidneys–inhibits calcium excretion by stimulating parathyroid dependent calcium reabsorption
How does vitamin D impact serum phosphate?
- Vitamin D increases serum phosphate by increasing its absorption from the intestine
- In the presence of vitamin D, serum calcium and phosphate are elevated – Increases the tendency to form bone mineral (Vitamin D facilitates mineralization, when serum calcium and phosphate are adequate)
• In vitamin D deficiency, reduced absorption of calcium reduces serum calcium level – stimulates secretion of PTH, which in turn causes
demineralization of bone. Remember, PTH also increases excretion of phosphate in kidney
• Patients with vitamin D deficiency have low serum calcium and low serum phosphate levels and decreased bone mineralization
What are the risk factors of vitamin D deficiency?
Risk factors:
• Inadequate exposure to sunlight (common during winter; in elderly)
- Nutritional deficiency – decreased intake/ fat malabsorption/ exclusively breast fed infants
- Chronic renal disease, chronic liver disease results in decreased hydroxylation of vitamin D
What are the characteristics rickets?
Decreased calcium absorption from the diet → Decreased serum calcium →↑Parathyroid hormone release → ↑demineralization of bone**
Demineralization of bone – soft pliable bones
Characteristic bow-leg deformity
Overgrowth at costochondral junction – rachitic rosary
Pigeon chest deformity
Frontal bossing, delayed closure of fontanelle
Delayed teething in infants
Describe the lab findings of rickets
Lab findings
• Elevated Serum alkaline phosphatase (ALP)
• Low serum calcium levels
• Low serum phosphate levels
Rickets. Anteroposterior radiograph of the wrist and hand in a 3-year-old child with nutritional rickets. The child had been put on a strict diet without dairy products. Note the widening, cupping, and fraying of the distal radius (arrowhead) and ulna metaphyses with an associated increase in the thickness of the growth plate (arrow). These changes are the consequence of disordered endochondral growth.
(B) Normal. Radiograph of the hand of a healthy 3-year-old child, without ricke
What are the characteristics of osteomalacia?
- Osteomalacia: Vitamin D deficiency in an adult
- Bones are de-mineralized and are susceptible to fracture; May present as non-specific bone pain
- Osteomalacia can be secondary to reduced exposure to sunlight, dietary deficiency, renal disease or liver disease
What are the lab findings of osteomalacia?
Lab findings
– Serum alkaline phosphatase activity is elevated
– Serum calcium and phosphate levels are low
• Subclinical vitamin D deficiency is common in the population (Teens, young adults and elderly); In teens and young adults vitamin D deficiency affects the attainment of peak bone mass
What are the mutations in the calcitriol receptor?
Inherited condition where calcitriol is unable to bind to its receptor in the intestinal mucosal cells (receptor mutation results in reduced binding of calcitriol)
- As a result, these children have high levels of calcitriol (loss of feedback inhibition)
- Serum calcium and phosphate levels are low but 1,25-hydroxyvitamin D levels are high
- Compare to vitamin D deficient rickets, which has low serum calcium and phosphate and low levels of 25-hydroxyvitamin D
Describe hypervitaminosis D
- Hypervitaminosis D is characterized by hypercalcemia (high serum calcium levels) – Due to increased calcium absorption from the diet
- Vitamin D also increases phosphate absorption.
• Increase in serum calcium and phosphate results in an
increased tendency for ectopic (soft tissues) mineralization
• Prolonged hypervitaminosis D (prescription medications) can lead to calcification in soft tissues like kidney
