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‫ا‬ ‫بسم‬‫هلل‬‫الرحمن‬‫الرحیم‬
Contents
 Overview of vitamins
 Physiology of vitamin-A
 Clinical Manifestations of
VAD
 Diagnosis
 Epidemiology and Public
Health Issues
 Treatment
 Prevention
 Hypervitaminosis-A
 Conclusion
Overview of Vitamins
 Vitamins are essential organic compounds that are
required in a very small amount( micronutrients) and
are involved in fundamental functions in the body like
Growth, Maintenance of body health and
Metabolism.
 Vitamins must be taken in the diet because our body
either cannot synthesize them at all or insufficient
amount are synthesized in the body.
vitamins
Water-
Soluble
Vit-B
Complex
Vit-C
Fat-
Soluble
ADEK
Overview of Vitamin A
 Vitamin A is a general term that refers to all
compounds which has the biologic activity of All-
trans retinol .
 Sometimes vitamin A and Retinol are used as
synonyms.
 Some authors call it Anti-Infection vitamin.
Vitamin A has two
Bioactive forms
Vit-A acid
(Retinoic
acid)
Vit-A
aldehyd
(Retinal)
Dietary Sources
of Vit-A
Preformed Vit-A
{Animal (Main)}
Retinyl(Vit-A esters)
Provitamin A
Plants
(Carotenes)
Animal Sources of Vit-A
Organic meats like Shark Liver Oil, Cod
Liver Oil and animal kidney are very
rich of vitamin A.
Other meats, Milk, Cheese and Egg
yolk contains moderate level of vitamin
A.
Plants Sources of Vit-A
Red Palm Oil(‫خرما‬ ‫)روغن‬ is the best source.
Yellow orange Vegetables like:
Pumpkin‫کدو‬
Mango ‫ام‬
Carrots
Sweet potato
Plants Sources of Vit-A…
Leafy Dark Green vegetable like:
Chard ‫چغندر‬ ‫برګ‬
Broccoli
Spinach
Ingested Retinyl esters
Retinol to be absorbed
Re-esterified in enterocytes
Retinyl esters are transported
by chylomicrons to liver
Metabolism of Vit-A…
 Retinyl esters (Retinyl palmitate) are stored
mainly in liver and partially in kidney, eyes
and testes.
 Beta Carotens undergoes a process of
cleavage in intestinal lumen and than are
absorbed in the form of carotens, in
enterocytes beta carotens are converted
into retinol.
Metabolism of Vit-A…
From liver released retinols are transported
as bounded to retinol-binding protein (RBP).
RBP makes a complex with transthyretin
(TTR).
This complex delivers retinol and thyroid
hormone to target tissues.
Metabolism of Vit-A…
In target tissue cells a Protein called
Stra6 functions as receptor for Retinol
bound to RBP.
In Target tissues retinol is esterified into
retinyl ester for storage or is oxidized
into retinoic acid and retinal in the eyes.
Metabolism of Vit-A…
Absorption of preformed vitamin A is
very efficient, about 70-90% of
preformed vitamin is absorbed in the
presence of 10g or more fat in meal.
Absorption efficiency of carotens is
about 20-25%.
Normal plasma level
Infants 20-50 micro grams retinol
Other children 30-225 micro grams
retinol
Recommended daily allowances (RDAs)
for Vitamin A
Daily requirements…
Average daily requirements
Infants: 300-400µg~1300IU
Children: 400-600µg
Adults: 750µg
Units of measuring vitamin A
Each μg RAE corresponds to
1 μg retinol,
2 μg of β-carotene in oil,
12 μg of "dietary" beta-
carotene,
One International Unit (I.U.)
0.3 mcg. of retinol
0.6 mcg. of beta-carotene
1.2 mcg. of other total
mixed carotenoids
1µg retinol=3.3 IU vitamin A
=12µg beta carotene
Physiological
Functions
Gene
regulation
Vision
Physiological Functions…
Many systemic functions of vit A are related
to its role in regulating Many genes that are
involved in fundamental biologic activities
like:
Cell division
Cell death
Cell differentiation
Physiological Functions…
 All-trans retinoic acid is the bioactive form of
vit A that acts as a ligand for specific
receptors in the cell surfaces known as
RARs,RXRs
 When Retinoic acid is bind to RAR it is
activated and then combines with RXR and
then this complex is bind to specific DNAs.
Physiological Functions…
. Through this vit A has many systemic functions like:
 Epithelial cell integrity against infections
 Immune response
 Haematopoiesis
 Skeletal growth
 Fertility (male and female)
 Embryogenesis
 Growth and development
Physiological Functions…
 Reproduction
 Embryonic and fetal development
 Bone development
Epithelial cell integrity
Epithelial cell integrity
Functions of Vitamin A:
Vision
In retina there are two types of
Photoreceptors:
Rods---------Rhodopsin------low intensity
light
Cons---------Iodopsin--------color vision
Functions of Vitamin A:
Vision…
Retinal aldehyd has the ability of
Photoisomerization (change shape
when exposed to light)
Rhodopsin has two parts
Protein-------Scotopsin----Opsin
retinal
Functions of Vitamin A…
Role in Prevention of cardiovascular
disease
Antioxidant capabilities---beta caotenes
≥5 servings/day of fruits and vegetables
Functions of Vitamin A…
 Role in Cancer prevention
Antioxidant capabilities
Lung, oral, and prostate cancers
Studies indicate that vitamin A-
containing foods are more protective
than supplements
Functions of Vitamin A…
Other Roles in
Age-related macular
degeneration
Cataracts
Acne
AML
High risk groups
 Infancy
 Childhood
 Pregnancy
 Lactation
 Urban poor
 Older adults
 Alcoholism
 Liver disease (limits
storage)
 Fat malabsorption
 Increased excretion as in
cancer & UTI
 Low protein intake resulting
in deficient carriers
VAD…
Dietary deprivation
Usually, Vitamin A Deficiency
(VAD) develops in an
environment of ecological social
and economical deprivation
VAD…
Infections:
Synergism between deficient dietary intake of
vitamin A coexists with severe infections, such
as measles, and frequent infections causing
diarrhea and respiratory diseases that can
lower intake through depressed appetite and
absorption, and deplete body stores of vitamin
A through excessive metabolism and excretion
VAD…
 The most common cause of VAD is
Malnutrition
 Impaired synthesis of RBP and TTR
 Infection
Classification of xerophthalmia
 XN Night blindness
 X1A Conjunctival Xerosis
 X1B Bitot’s spot
 X2 Corneal Xerosis
 X3A Corneal ulceration/keratomalacia (< 1/3 corneal surface)
 X3B Corneal ulceration/keratomalacia (≥ 1/3 corneal surface)
 XS Corneal scar
 XF Xerophthalmic fundus
Bitot’s Spot
These are foamy and whitish
cheese-like tissue spots that
develop around the eye ball,
causing severe dryness in
the eyes.
These spots do not affect
eye sight in the day light.
Conjunctival Xerosis
Conjunctiva
becomes dry and
non wettable.
Instead of looking
smooth shiny it
appears muddy
&wrinkled.
Keratomalacia
One of the major
cause for blindness
Cornea becomes soft
and may burst
The process is rapid
If the eye collapses
vision is lost.
Other Symptoms of VAD
 Alteration of skin and mucous membrane
 Hepatic dysfunction
 Headache
 Drowsiness
 Peeling of skin about the mouth and elsewhere
Follicular hyperkeratosis
Assessing vitamin A status
and deficiency
Two sets of indicators of VAD are commonly used for
population surveys:
1. clinically assessed eye signs.
Term xerophthalmia encompasses the clinical spectrum
of ocular manifestations of VAD, from milder stages of
night blindness and Bitot’s spots, to potentially blinding
stages of corneal xerosis, ulceration and necrosis
(keratomalacia)
1. biochemically determined concentrations of retinol in
plasma or serum
Serum retinol concentrations
 Serum retinol concentrations in a population constitutes
the second major approach to assessing vitamin
 A status in a population, with values below a cut-off of
0.70 μmol/l representing VAD , and below 0.35 μmol/l
representing severe VAD.
 A serum retinol concentration below a cutoff of 1.05
μmol/l has been proposed to reflect low vitamin.
Universal vitamin A distribution
schedule for preschool and
lactating mothers
Children 1–6 years
200,000 IU of vitamin A orally every 3–6 months.
Infants 6–11 months
100,000 IU of vitamin A orally every 3–6 months.
Lactating mothers
200,000 IU of vitamin A orally once at delivery or during
the first 8 weeks postpartum if breastfeeding or during
the first 6 weeks if not breast-feeding
Recommended Xerophthalmia
treatment schedule
6 -12 months > 1 yr
Immediately 100,000 IU 200,000 IU
Next day 100,000 IU 200,000 lU
2–4 weeks later 100,000 IU 200,000 IU
Severe Protein-Energy Malnutrition (PEM) Monthly until
PEM resolves
100,000 IU 200,000 IU
Upper Level for Vitamin A
 3000 μg retinol
 Hypervitaminosis A results from long-term
supplement use (2 – 4 x RDA)
 Toxicity
 Fatal dose (12 g)
Hypervitaminosis A
Acute Intoxication:
 Results when excessively large single doses >300,000 IU
ingested
 Infants: n/v, drowsiness or irritability w/signs of increased
ICP
 Adults: drowsiness, irritability, headache & vomiting
 Serum vitamin A values = 200-1000 IU/dl (N: 50-100
IU/dl)
drpankajyadav05@gmail.com
Toxicity of Vitamin A
Acute toxicity
short-term megadose (100 x RDA);
symptoms disappear when intake stops
GI effects
Headaches
Blurred vision
Poor muscle coordination
drpankajyadav05@gmail.com
Chronic Intoxication
 Results when >50,000 IU/day ingested for several wks
or more
 Signs & symptoms in infants:
 Early are anorexia, pruritus, irritability, tender
swollen bones w/motion limitation
 Alopecia, seborrhea, cheilosis & peeling of palms &
soles
 Hepatomegaly & hypercalcemia observed
 Craniotabes & hyperostosis of long bones
 Elevated serum vit A levels confirms diagnosis
 Reversible manifestations when vitamin A discontinued
Chronic Toxicity of Vitamin A
long-term megadose; possible permanent damage
Bone and muscle pain
Loss of appetite
Skin disorders
Headache
Dry skin
Hair loss
Increased liver size
Vomiting
drpankajyadav05@gmail.com
Toxicity of Vitamin A
Teratogenic (may occur with as little as 3 x RDA of
preformed vitamin A)
Tends to produce physical defect on developing fetus
as a result of excess vitamin A intake
Spontaneous abortion
Birth defects
drpankajyadav05@gmail.com
References
 Nelson 20th edition
 Current pediatrics 21th edition
 GHAI essential of pesiatrics
 https://www.google.com
 www.who.int/
Prepared by:
Dr.Mujeebullah Mahboob
1st year resident at FMIC, Kabul, Afghanistan
14/09/2015 01:10pm
W_mahboob@yahoo.com
0798984142

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Vitamin A deficiency,by,Dr.M.Mahboob

  • 2.
  • 3. Contents  Overview of vitamins  Physiology of vitamin-A  Clinical Manifestations of VAD  Diagnosis  Epidemiology and Public Health Issues  Treatment  Prevention  Hypervitaminosis-A  Conclusion
  • 4. Overview of Vitamins  Vitamins are essential organic compounds that are required in a very small amount( micronutrients) and are involved in fundamental functions in the body like Growth, Maintenance of body health and Metabolism.  Vitamins must be taken in the diet because our body either cannot synthesize them at all or insufficient amount are synthesized in the body.
  • 6. Overview of Vitamin A  Vitamin A is a general term that refers to all compounds which has the biologic activity of All- trans retinol .  Sometimes vitamin A and Retinol are used as synonyms.  Some authors call it Anti-Infection vitamin.
  • 7. Vitamin A has two Bioactive forms Vit-A acid (Retinoic acid) Vit-A aldehyd (Retinal)
  • 8. Dietary Sources of Vit-A Preformed Vit-A {Animal (Main)} Retinyl(Vit-A esters) Provitamin A Plants (Carotenes)
  • 9. Animal Sources of Vit-A Organic meats like Shark Liver Oil, Cod Liver Oil and animal kidney are very rich of vitamin A. Other meats, Milk, Cheese and Egg yolk contains moderate level of vitamin A.
  • 10. Plants Sources of Vit-A Red Palm Oil(‫خرما‬ ‫)روغن‬ is the best source. Yellow orange Vegetables like: Pumpkin‫کدو‬ Mango ‫ام‬ Carrots Sweet potato
  • 11. Plants Sources of Vit-A… Leafy Dark Green vegetable like: Chard ‫چغندر‬ ‫برګ‬ Broccoli Spinach
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  • 13. Ingested Retinyl esters Retinol to be absorbed Re-esterified in enterocytes Retinyl esters are transported by chylomicrons to liver
  • 14. Metabolism of Vit-A…  Retinyl esters (Retinyl palmitate) are stored mainly in liver and partially in kidney, eyes and testes.  Beta Carotens undergoes a process of cleavage in intestinal lumen and than are absorbed in the form of carotens, in enterocytes beta carotens are converted into retinol.
  • 15. Metabolism of Vit-A… From liver released retinols are transported as bounded to retinol-binding protein (RBP). RBP makes a complex with transthyretin (TTR). This complex delivers retinol and thyroid hormone to target tissues.
  • 16. Metabolism of Vit-A… In target tissue cells a Protein called Stra6 functions as receptor for Retinol bound to RBP. In Target tissues retinol is esterified into retinyl ester for storage or is oxidized into retinoic acid and retinal in the eyes.
  • 17. Metabolism of Vit-A… Absorption of preformed vitamin A is very efficient, about 70-90% of preformed vitamin is absorbed in the presence of 10g or more fat in meal. Absorption efficiency of carotens is about 20-25%.
  • 18. Normal plasma level Infants 20-50 micro grams retinol Other children 30-225 micro grams retinol
  • 19. Recommended daily allowances (RDAs) for Vitamin A
  • 20. Daily requirements… Average daily requirements Infants: 300-400µg~1300IU Children: 400-600µg Adults: 750µg
  • 21. Units of measuring vitamin A Each μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg of "dietary" beta- carotene, One International Unit (I.U.) 0.3 mcg. of retinol 0.6 mcg. of beta-carotene 1.2 mcg. of other total mixed carotenoids 1µg retinol=3.3 IU vitamin A =12µg beta carotene
  • 23. Physiological Functions… Many systemic functions of vit A are related to its role in regulating Many genes that are involved in fundamental biologic activities like: Cell division Cell death Cell differentiation
  • 24. Physiological Functions…  All-trans retinoic acid is the bioactive form of vit A that acts as a ligand for specific receptors in the cell surfaces known as RARs,RXRs  When Retinoic acid is bind to RAR it is activated and then combines with RXR and then this complex is bind to specific DNAs.
  • 25. Physiological Functions… . Through this vit A has many systemic functions like:  Epithelial cell integrity against infections  Immune response  Haematopoiesis  Skeletal growth  Fertility (male and female)  Embryogenesis  Growth and development
  • 26. Physiological Functions…  Reproduction  Embryonic and fetal development  Bone development
  • 29. Functions of Vitamin A: Vision In retina there are two types of Photoreceptors: Rods---------Rhodopsin------low intensity light Cons---------Iodopsin--------color vision
  • 30. Functions of Vitamin A: Vision… Retinal aldehyd has the ability of Photoisomerization (change shape when exposed to light) Rhodopsin has two parts Protein-------Scotopsin----Opsin retinal
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  • 32. Functions of Vitamin A… Role in Prevention of cardiovascular disease Antioxidant capabilities---beta caotenes ≥5 servings/day of fruits and vegetables
  • 33. Functions of Vitamin A…  Role in Cancer prevention Antioxidant capabilities Lung, oral, and prostate cancers Studies indicate that vitamin A- containing foods are more protective than supplements
  • 34. Functions of Vitamin A… Other Roles in Age-related macular degeneration Cataracts Acne AML
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  • 36. High risk groups  Infancy  Childhood  Pregnancy  Lactation  Urban poor  Older adults  Alcoholism  Liver disease (limits storage)  Fat malabsorption  Increased excretion as in cancer & UTI  Low protein intake resulting in deficient carriers
  • 37. VAD… Dietary deprivation Usually, Vitamin A Deficiency (VAD) develops in an environment of ecological social and economical deprivation
  • 38. VAD… Infections: Synergism between deficient dietary intake of vitamin A coexists with severe infections, such as measles, and frequent infections causing diarrhea and respiratory diseases that can lower intake through depressed appetite and absorption, and deplete body stores of vitamin A through excessive metabolism and excretion
  • 39. VAD…  The most common cause of VAD is Malnutrition  Impaired synthesis of RBP and TTR  Infection
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  • 41. Classification of xerophthalmia  XN Night blindness  X1A Conjunctival Xerosis  X1B Bitot’s spot  X2 Corneal Xerosis  X3A Corneal ulceration/keratomalacia (< 1/3 corneal surface)  X3B Corneal ulceration/keratomalacia (≥ 1/3 corneal surface)  XS Corneal scar  XF Xerophthalmic fundus
  • 42. Bitot’s Spot These are foamy and whitish cheese-like tissue spots that develop around the eye ball, causing severe dryness in the eyes. These spots do not affect eye sight in the day light.
  • 43. Conjunctival Xerosis Conjunctiva becomes dry and non wettable. Instead of looking smooth shiny it appears muddy &wrinkled.
  • 44. Keratomalacia One of the major cause for blindness Cornea becomes soft and may burst The process is rapid If the eye collapses vision is lost.
  • 45. Other Symptoms of VAD  Alteration of skin and mucous membrane  Hepatic dysfunction  Headache  Drowsiness  Peeling of skin about the mouth and elsewhere
  • 47. Assessing vitamin A status and deficiency Two sets of indicators of VAD are commonly used for population surveys: 1. clinically assessed eye signs. Term xerophthalmia encompasses the clinical spectrum of ocular manifestations of VAD, from milder stages of night blindness and Bitot’s spots, to potentially blinding stages of corneal xerosis, ulceration and necrosis (keratomalacia) 1. biochemically determined concentrations of retinol in plasma or serum
  • 48. Serum retinol concentrations  Serum retinol concentrations in a population constitutes the second major approach to assessing vitamin  A status in a population, with values below a cut-off of 0.70 μmol/l representing VAD , and below 0.35 μmol/l representing severe VAD.  A serum retinol concentration below a cutoff of 1.05 μmol/l has been proposed to reflect low vitamin.
  • 49. Universal vitamin A distribution schedule for preschool and lactating mothers Children 1–6 years 200,000 IU of vitamin A orally every 3–6 months. Infants 6–11 months 100,000 IU of vitamin A orally every 3–6 months. Lactating mothers 200,000 IU of vitamin A orally once at delivery or during the first 8 weeks postpartum if breastfeeding or during the first 6 weeks if not breast-feeding
  • 50. Recommended Xerophthalmia treatment schedule 6 -12 months > 1 yr Immediately 100,000 IU 200,000 IU Next day 100,000 IU 200,000 lU 2–4 weeks later 100,000 IU 200,000 IU Severe Protein-Energy Malnutrition (PEM) Monthly until PEM resolves 100,000 IU 200,000 IU
  • 51. Upper Level for Vitamin A  3000 μg retinol  Hypervitaminosis A results from long-term supplement use (2 – 4 x RDA)  Toxicity  Fatal dose (12 g)
  • 52. Hypervitaminosis A Acute Intoxication:  Results when excessively large single doses >300,000 IU ingested  Infants: n/v, drowsiness or irritability w/signs of increased ICP  Adults: drowsiness, irritability, headache & vomiting  Serum vitamin A values = 200-1000 IU/dl (N: 50-100 IU/dl) drpankajyadav05@gmail.com
  • 53. Toxicity of Vitamin A Acute toxicity short-term megadose (100 x RDA); symptoms disappear when intake stops GI effects Headaches Blurred vision Poor muscle coordination drpankajyadav05@gmail.com
  • 54. Chronic Intoxication  Results when >50,000 IU/day ingested for several wks or more  Signs & symptoms in infants:  Early are anorexia, pruritus, irritability, tender swollen bones w/motion limitation  Alopecia, seborrhea, cheilosis & peeling of palms & soles  Hepatomegaly & hypercalcemia observed  Craniotabes & hyperostosis of long bones  Elevated serum vit A levels confirms diagnosis  Reversible manifestations when vitamin A discontinued
  • 55. Chronic Toxicity of Vitamin A long-term megadose; possible permanent damage Bone and muscle pain Loss of appetite Skin disorders Headache Dry skin Hair loss Increased liver size Vomiting drpankajyadav05@gmail.com
  • 56. Toxicity of Vitamin A Teratogenic (may occur with as little as 3 x RDA of preformed vitamin A) Tends to produce physical defect on developing fetus as a result of excess vitamin A intake Spontaneous abortion Birth defects drpankajyadav05@gmail.com
  • 57. References  Nelson 20th edition  Current pediatrics 21th edition  GHAI essential of pesiatrics  https://www.google.com  www.who.int/
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  • 60. Prepared by: Dr.Mujeebullah Mahboob 1st year resident at FMIC, Kabul, Afghanistan 14/09/2015 01:10pm W_mahboob@yahoo.com 0798984142