Download Vitamin A

Vitamins
Vitamins
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Essential
organic compounds
Micronutrients
Involved in growth, metabolism,
healing/health, immunity
Vitamins
• Water-soluble or fat-soluble
• Dietary reference intakes (DRI)
• Deficiency associated with malnutrition,
malabsorption from chronic disorders or
genetically inherited diseases
• Toxicity from Vitamin A & D
Vitamin A
Source
• Carotenoids from
plants, green & yellow
vegetables, yellow
fruits
• liver, fish liver oils
• dairy fat
• egg yolk
Forms
• all-trans-retinol:
alcohol form
• Pro-Vitamin
A
carotenoids (-,-,carotenes)
• Retinyl
palmitate:
storage form
• Retinal:
aldehyde
form
• Retinoic acid
Vitamin A Forms and Function
• Retinoic Acid most important vit A
metabolite
• Acts as a ligand for specific nuclear
transcription factors
• Retinoic acid gene receptors vital in
fundamental biological activities of all
cells: division, death, differentiation
• Retinal: rhodopsin in rods of the retina
Vitamin A deficiency
• Night- blindness, photophobia: absence
of retinal in rhodopsin of the retina
• Xerophthalmia  keratomalacia
• Bitot’s spots
• conjunctival xerosis
At risk for Vitamin A
deficiency
• Undernourished of mother & child
• Measles
Tx of Vitamin A deficiency
Oral dose to be given on Day 1, 2 & 2 wks later
• for age >12 months 200,000 IU
• for age 6-12 months 100,000 IU
• for age 0-5 months 50,000 IU
(unless there is definite evidence that a dose
has been given in the last month)
Tx of Xerophthalmia
• Vitamin A
5000 IU/kg BW OD PO x 5days
followed by 25000 IU IM in oil
until recovery
Prevention of Vitamin A
deficiency in High Risk Areas
Vitamin A for Mother
Vitamin A for Newborn
• 200,000 IU OD x 2
doses post-partum
• 25,000 IU x 3 doses
at 1-3 months of age
Hypervitaminosis A
• Excess over weeks or months
• Adults 50000 IU
Child 20000 IU
• Sx: headache, vomiting, anorexia, seborrhea,
oral fissures, alopecia, bone abnormalities:
hyperostosis, hepatosplenomegaly, diplopia,
irritability, stupor
• Sx resolve on withdrawal of Vit A
Hypervitaminosis A
• Congenital malformations & abortions:
0.5-1.5mg/kg oral retinoic acid for acne
or cancer, >20% incidence
• Carotenemia: yellow discoloration of
skin due to excessive intake of
carotenoids (low enzymes, liver dse,
DM or hypothyroidism)
Vitamin B Complex
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Thiamine
Riboflavin
Niacin
Vitamin B6
Folate
Vitamin B12
Biotin
Pantothenic Acid
(Choline)
(Inositol)
Thiamine (Vitamin B1)
Source
• meat (lean pork)
• legumes
• cereal
Forms/ functions
• Coenzyme thiamine
pyrophosphate
(glycolysis)
• Hexose
monophosphate shunt
• Synthesis of
acetylcholine (nerve
conduction)
Prevention of Thiamine
deficiency
• Undernourishment of mother & child
• Diseases of the gastrointestinal tract
and liver
• Increased requirement if CHO in diet is
high: TPN, Alcoholics
• Thiamine dependence: megaloblastic
anemia, maple syrup urine disease,
Leigh encephalomyelopathy
Clinical Manifestation of
Thiamine deficiency
• Fatigue, apathy, irritability, depression,
poor concentration, anorexia, nausea,
abdominal discomfort
• Peripheral neuritis (paresthesias of the
toes and feet),  DTR’s, loss of vibration
sense, leg cramps, psychic
disturbances, ptosis, atrophy of optic
nerve
• Hoarseness, aphonia
Clinical Manifestation of
Thiamine deficiency
• Muscle atrophy, tenderness of nerve
trunks, loss of deep sensation
•  ICP, meningismus, coma
• Wernicke encephalopathy:
encephalopathy, opthalmoplegia +
ataxia
• CHF death
Beriberi
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Wet
Undernourished,
pale, edema
Dyspnea
Vomiting
Tachycardia
Waxy skin
Urine albumin, casts
Dry
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Plump
Pale
Flabby
Listless
Dyspnea
Tachycardia
Hepatomegaly
Treatment of Thiamine
deficiency
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Vitamin B1 10mg OD PO (child)
Vitamin B1 50 mg OD PO (adult)
If with CHF, give IV or IM
Tx over several weeks
Clinical response to thiamine is best
confirmation of thiamine deficiency
Niacin
Source
• Meat
• Fish poultry
• Legumes
• Fortified bread and
cereal
• Tryptophan from milk
& eggs (6mg= 1mg
niacin)
Forms/ functions
• Nicotinamide,
nicotinic
acid
&
derivatives
• Coenzyme NADP, NAD
(electron transfer and
glycolysis)
At risk for Niacin deficiency
• Inadequate intake
• Regions where corn is a staple
Clinical Manifestations of
Niacin deficiency
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Anorexia
Lassitude
Weakness
Burning sensation
Numbness
Dizziness
Glossitis, GI symptoms, symmetric
dermatitis
Pellagra
• Triad: dermatitis, diarrhea and dementia
• Dermatitis symmetric, sharply
demarcated from surrounding healthy
skin, sun-exposed areas
• Scaling, crusting, vesicles, bullae
• Pellagrous glove, boot, Casal necklace
• Alternating diarrhea and constipation
• Depression, disorientation, insomnia,
delirium
Treatment of Niacin
deficiency
• Niacin 50-300mg/ day
• Niacin 100mg IV, if sever or poor
intestinal absorption
Vitamin B6 (Pyridoxine)
Source
• Meat
• Fish
• Poultry
• liver
• Fortified Cereal
Forms/ functions
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Pyrodixine
pyridoxal
Pyridoxamine
Coenzymes Pyridoxal 5phosphate, pyridoxamine
phosphate: AA metab,
aminotransferases,
decarboxylases,
racemaces, dehydratases
• Neurotransmitter
synthesis:
serotonin,
GABA, dopamine
• Synthesis of histamine,
heme, porphyrins
Functions of Pyridoxine
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Metabolism of glycogen
Conversion of tryptophan to Niacin
Synthesis of cysteine from methionine
AA active transport across cell
membranes
• Chelation of metals
• linoleic acid  arachidonic acid
• linolenic acid  docosahexaenoic acid
At risk for Pyridoxine
deficiency
• Inadequate intake
• Milling of rice, cereal removes
Pyridoxine
• Vegetarian
• Larger requirement if high protein in diet
• Inhibited by drugs:
Isoniazid,penicillamine, steroids, anticonvulsants,
• Women on oral contraceptives
• Maintenance dialysis
Clinical Manifestation of
Pyridoxine deficiency
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Irritability & Convulsions in infants
Peripheral neuritis
Dermatitis
anemia
Aggravated startle response
Cheilosis
Glossitis
Seborrheic dermatitis
infections
Vitamin B6 dependence
Syndromes
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Vit B6- dependent convulsions
Vit B6- responsive anemia
Xanthurenic aciduria
Cystathioninuria
homocystinuria
Treatment of Pyridoxine
deficiency
• Vitamin B6 100mg IM for Infantile
seizures
• Daily Vitamin B6 2-10mg IM or 10100mg PO if pyridoxine-dependent
Folate
Source
• Green vegetables
• Oranges
• Legumes, nuts
• Fortified Cereal
• liver
• yeast
Forms/ functions
• Folic
acid=
pteroylglutamic acid
• Folate coenzymes:
DNA and purine
synthesis,
AA
intercorversion,
homocysteine

methionine
Prevention of Folate
Deficiency
• Inadequate intake
• Deficiency during periods of rapid
growth or increased cellular metabolism
• (sickle cell anemia), psoriasis
• NSAIDs, anticonvulsants i.e.
diphenylhydantoin, phenobarbital,
Methotrexate
• Pregnancy,Protective for neural tube
defects (spina bifida, anencephaly)
Prevention of Folate
Deficiency
• Malabsorption (hereditary folate
malabsorption, celiac, inflammatory
bowel disease, alcoholism)
• Inborn errors of folate metabolism
• Autoantibodies against cerebral folate
receptor in the choroid plexus
Hereditary Folate
Malabsorption
• Recurrent diarrhea, failure to thrive, oral
ulcers, neurologic deterioration,
megaloblastic anemia
• At 1-3 months of age
• Poor neurologic outcome
• poor immunity
• DX: low serum folate
• Rx: Folinic acid IM or hi dose oral folinic
acid
Cerebral Folate Deficiency
• Irritability, microcephaly, developmental
delay, cerebellar ataxia, pyramidal tract
signschoreoathetosis, ballismus,
seizures
• Blindness from optic nerve atrophy
• Dx: normal serum folate, low CSF folate
• Rx: oral folinic acid
Treatment of Folate
Deficiency
• Women of child-bearing age: Folate
400mcg daily
Vitamin B12
(Cobalamin)
Source
• Muscle meats
• Eggs
• Dairy
• Tempeh, nori
• Fortified cereal
Functions of Vitamin B12
(Cobalamin)
Forms/ functions
• Cofactor
for
lipid
and
carbohydrate
metabolism
• Isomerization of methylmalonyl coenzyme A
to succinyl coenzyme A
• Maintainance of cellular folate levels; Folate
metabolism; homocysteine  methionine
• Protein biosynthesis
• Synthesis of purines and pyramides
• Methylation reactions
Prevention of Vitamin B12
deficiency
• Inadequate intake i.e. strict vegetarian
diet in a nursing Mom
• Abnormal absorption (gastric resection,
autoimmune pernicious anemia with IF
deficiency)
• Poor ileal absorption (Crohn’s, tropical
sprue, SBS)
• Competition for B12 in the gut
• IEM of Vit B12
Transcobalamin II deficiency
• Inherited defect
• Defective intestinal transport of Vitamin
B12
• Severe megaloblastic anemia, Diarrhea,
vomiting
Juvenile pernicious anemia
• Defective IF production in the stomach
• Vit B12 malabsorption
• Megaloblastic anemia, growth failure
Imerslund Syndrome
• Defective ileal absorption of Vit B12
• Normal ileal structure and function
• Megaloblastic anemia
Treatment of Cobalamin
deficiency
• Vit B12 100mcg once a month IM
• Vit B12 1000 mcg twice a week IM for
transcobalamin II deficiency
• Once in hematologic remission,
intranasal Vit B12 500mcg once weekly
• If at risk for Leber Optic atrophy, treat
with Vit B12 other than cyanocobalamin
Vitamin C
Source
• Vegetables
• Fruits esp citrus
Forms
• Dehydroascorbate:
Simple diffusion or
Active transport
• Ascorbate: plasma
transport form
Vitamin C functions
• Collagen formation: hydroxylation of lysine and
proline
• Maintains iron and copper in a reduced state for
metalloenzymes to convert
Dopamine  norepinephrine
Tryptophan  serotonin
Cholesterol  steroids
• Antioxidant
• Enhances non-heme iron absorption, transfer of iron
from transferrin to ferritin & formation of
tetrahydrofolic acid
Clinical Manifestation of
Vitamin C deficiency
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Onset of Sx 6-24 months of age
Fever
Irritability
Tachypnea
Digestive disturbances
Loss of appetite
Generalized tenderness (pseudoparalysis)
Leg edema
Femoral subperiosteal hemorrhage
Clinical Manifestation of
Vitamin C deficiency
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Scorbutic rosary
Sternal depression
Gingival swellings
Anemia
Sicca syndrome of Sjögren: xerostomia,
keratoconjunctivitis sicca, enlarged salivary
glands
• Swollen joints, arthralgia, muscle weakness
• Purpura, ecchymosis, petecchiae, perifollicular
hemorrhages
• Hyperkeratosis of hair follicles
Prevention of Vitamin C
deficiency
• Cow’s milk, evaporated milk for infants
• Picky eaters
• Increased requirement: febrile illness,
infections, diarrhea
Treatment of Vitamin C
deficiency
• 3-4 oz of orange or tomato juice daily
• Vit C 100-200mg oral or IV daily
• Rapid recovery of sx and resumption of
normal growth
• Resolution of swelling from subperiosteal
hemorrhage after several months
Vitamin D
Source
• Exposure to sunlight
• Fish oils
• Fatty fish
• Egg yolks
• Fortified formula,
milk, cereal, bread
Forms/ functions
• Skin:
7dehydrocholesterol 
Vitamin D3
• Liver: Vit D  25hydroxy vit D (25-D)
• Kidney: 25-D 1,25Dihydroxyvitamin D
Functions of Vitamin D
• 1,25-D binds to intracellular receptor  gene
expression
• Increase calcium absorption in the
intestines
• Inc. in phosphorus absorption
• Negative feedback: Inhibits PTH secretion
and 1,25-D synthesis
• Mediates bone resorption
Clinical Manifestation of
Vitamin D deficiency
• Rickets in growing children
• Osteomalacia
• Tetany and seizures from hypocalcemia
Rickets
• A disease of growing bones skeletal
deformities, short stature
• Craniotabes: softening of cranial bones
• Growth plate widening swelling of wrists
and ankles, Rachitic rosary
• Softening of the ribs  Harrison’s groove
• Failure to thrive
• Symptomatic hypocalcemia
Rickets on Xray
• Wrist PA: rachitic
changes
• Loss of
sharp/convex border
at the end of the
metaphysis: fraying,
cupping
• Thickening of the
growth plate:
decreased
calcification
Prevention of Vitamin D
deficiency
• Inadequate intake
• Inadequate cutaneous synthesis
• Breastfed baby must get sunlight or
200-400 IU Vitamin D po
• Drugs: phenobarbital, phenytoin, INH,
RIfampicin
• Congenital rickets
• Genetic
Genetic causes of Rickets
• Vitamin D-dependent rickets type 1; Rx:
Calcitriol 0.25-0.5mcg/day
• Vitamin D-dependent rickets type 2
Treatment of Vitamin D
deficiency
• Vit D + adequate Calcium and Phosphorus in
diet
• Stoss therapy: 300,000- 600,000 IU po or IM
divided into 2-4 doses in one day
• Vitamin D 2000-5000 IU OD po over 4-6 wks
• Calcitriol 0.05 mcg/kg/day
• Symptomatic hypocalcemia Ca gluconate
100mg/kg bolus or 20mg/kg Calcium Chloride
Vitamin E
Source
• Vegetable oils
• Seeds
• Nuts
• Green leafy vegetables
• margarine
Forms/ functions
• - tocopherol
• Anti-oxidant
Vitamin E
• Antioxidant
• Integral part of cell membranes
• Prevents lipid peroxidation & freeradical formation
Clinical Manifestation of
Vitamin E deficiency
• Premature infants: transfer of Vit E in
last trimester; thrombocytosis, edema,
hemolysis
• Premature formula: low PUFA, low iron,
adequate Vit E
• Fat-malabsorption: cholestatic liver
disease, short bowel syndrome
Clinical Manifestation of
Vitamin E deficiency
•  DTR’s  Severe progressive
neurologic disorder
• Cerebellar disease: limb ataxia, truncal
ataxia
• Posterior column dysfunction
• Retinal disease: visual field constriction,
blindness
Treatment of Vitamin E
deficiency
• Neonates: 25-50 units daily for 1 week
• -tocopheryl polyethylene glycol
succinate (TPGS) 20-25 U/kg/day
Vitamin K
Source
• Green leafy vegetables
• Liver
• Legumes
• Plant oils
Forms/ functions
• Vit K1-phylloquinone
• Vit K2-menaquinones
• Cofactor
for
glutamyl carboxylase
Functions of Vitamin K
• -glutamyl carboxylase: converts glutamate to carbohyglutamate
• Factors II (prothrombin), VII, IX & X
• Protein C & S deficiency, Protein Z
• Bone and vascular biology
Who are at risk for Vitamin K
deficiency
• Inadequate intake
• Decreased absorption: bile saltrequiring
Vitamin K- deficiency
bleeding (VKDB)
• Early VKDB: 1-14 days of life; poor
placental transfer, inadequate intake,
low Vit K in breastmilk, no intestinal
synthesis of Vit K2 in sterile gut
• Late VDKB: 2-12 wks; brestfed or
occult malabsorption (CF, cholestatic
liver disease)
• VDKB sec to maternal drugs: warfarin,
Pb, Phenytoin)
Clinical Manifestation of
Vitamin K deficiency
• Long-term bone health and vascular
health
• Early VKDB: GI, mucosal, cutaneous
bleeding: umbilical stump, circumcision
site
• Late VKDB: intracranial bleed frequent
• Prolonged protime
Treatment Vitamin K
deficiency
• Vit K 1mg IM/ IV
• Vit K 2.5-10mg IV/IM, rapid correction in
adolescents
• FFP for severe coagulopathy with
bleeding
• Vitamin K 1mg IM to newborn: current
practice
Vitamin Excess
• Hypervitaminosis A
• Hypervitaminosis D
Hypervitaminosis D
• hypercalcemia: emesis, anorexia,
pancreatitis, hypertension, arrhythmias,
CNC effects, polyuria, nephrolithiasis,
renal failure
• Accidental overfortification of milk,
inadvertent use as cooking oils, misuse
of Vit D supplements
Hypervitaminosis A
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Anorexia
Failure to thrive
Dry, cracking skin
Hepatosplenomegaly
Swelling and pain of long bones
Bone fragility
Increased ICP
Alopecia
Carotenemia
Fetal abnormalities