Transcript Vitamins - Home - Children's Hospital of Michigan

Vitamins
Usha Sethuraman, MD
Emergency Medicine
Children’s Hospital of Michigan
Case 1

A 2 year old boy is brought by the mother to your office
for a routine visit. She is worried that he is not walking
yet. He was born at 30 weeks gestation and was
exclusively breast fed until 10 months of age and has
been a poor feeder since then. On exam he is short with
bow legs and has frontal bossing and no teeth. His
height and weight are less than the 5th percentile. You
confirm your clinical diagnosis with appropriate labs and
start treatment. Mom is upset and wants to know the
cause.
Case 2

A 5 year old girl is brought to your office with the
complaint that “something is wrong with her eyes;
maybe he needs glasses”. The child was adopted from
an underdeveloped country at 4years of age and since
arrival has been noticed to squint a lot and bump into
objects in the evening hours.On exam he has a
triangular silvery plaque in the scleral area of both eyes
and his vision appears normal. You send him to an
ophthalmologist who makes the diagnosis and
recommends the appropriate treatment.
Case 3

A 2year old boy is brought to your office with the history
of refusing to move his legs. He has had no fever, no
trauma and has been fussy for past week. On exam he
is irritable and refuses to stand. He screams when you
touch his legs. You send him for x-rays suspecting a
fracture. You get the news the next day from the
radiologist. You start appropriate treatment and on follow
up in 2 months he is a smiling normal child.
Background




Vitamins are organic compounds that are
required in small amounts for normal
cellular metabolisms that are important for
the growth of the organisms.
Discovered by Hopkins in 1907
Named by Funk in 1911
Classified by McCollum into fat and water
soluble
Classification



Fat soluble vitamins include A,E,D and K
Water soluble vitamins include B and C
Vitamins are accessory food factors that
are essential for metabolic reactions and
form coenzymes
Vitamin A




Derived from pigments called carotenoids
In nature these are called provitamins A
Includes 4 compounds
The first three are hydrocarbons and the
fourth is a ßcarotene
Vitamin A - Properties




Vitamin A and it’s provitamins are water
insoluble and fat soluble
They are destroyed by light exposure and
oxidation
Protected by the presence of vitamin E
Destroyed by dehydration but not by
canning or freezing
Absorption and distribution




Exists as esters of retinol in animal
products and as ß-carotene in vegetables
Esters are hydrolysed in the intestinal
lumen and absorbed as retinol but later
converted to retinal
The esters are stored in the liver
When needed they are hydrolysed to
retinol and transported by ABP
Absorption and metabolism




Normal plasma has 18-60μ of vitamin A in
100ml
Levels are maintained by release from
liver
Very small amounts are excreted normally
Mineral oils increases excretion
Food sources and Requirement




Mainly animal sources
Liver oils of fish, egg yolk, butter, milk
Carotenes are found in green and yellow
vegetables
Children and infants require 300μg per
day
Functions of Vitamin A




Related to 3 main retinoids; retinol, retinal,
and retinoic acid
Retinol is important for growth and
integrity of epithelial cells
Retinal is important for physiology of
vision
Retinoic acid is essential for synthesis of
glycoproteins
Causes of deficiency




Inadequate absorption as in celiac disease
Chronic mineral oil consumption
Poor intake of fat and protein
Hepatic disease
Deficiency manifestations


Skin: dry and scaly – follicular
hyperkeratosis
Common on the thigh and extensor
surfaces
Clinical manifestations



Mucus membranes: atrophy resulting in
keratinization
Resembles epidermis
Common in lacrimal glands, GI tract,
respiratory tract and genitourinary tract
Hyperkeratosis follicularis
Deficiency manifestations




Eyes: keratinization of the conjunctiva
results in xerophthalmia
Bitot’s spots may occur
When the cornea is involved, vision is
impaired
Severe cases result in keratomalacia and
blindness
Bitot’s spots
Bitot’s spots
xerophthalmia
Keratomalacia
Deficiency manifestation



Wald’s cycle is a constant splitting and
resynthesis of vitamin A containing
pigment in the retina
Deficiency results in delay in resynthesis
Causes night blindness or nyctalopia
Deficiency manifestations



Bones : defective endochondral formation
Decreased osteoblastic activity
Cancellous bones
Effects of excess






Drowsiness
Painful joints
Periosteal thickening of long bones
Increased intracranial pressure
Loss of hair
carotenemia
Treatment


Oral vitamin A 1500μg/day for 5days
Then 7500μ//day parenterally until
recovery
Vitamin D






Precursors are called Provitamins-D
2 important provitamins:
Ergosterol (provitamin D2)
7dehyrdrocholesterol (provitamin D3)
D2 occurs in fungi and yeast
D3 occurs in animals
Absorption and metabolism


Irradiation by ultraviolet rays converts
ergosterol into the active ergocalciferol
(vitamin D2 )
7dehydrocholesterol is converted to
cholecalciferol (vitamin D3 )
Properties



Vitamin D is fat soluble
Resistant to oxidation and heat
Readily absorbed from small intestine
Absorption and metabolism



Carried in the chylomicrons to liver
Hydroxylated by 25 hydroxylase to
25hydroxycholecalciferol
Further hydroxylated in renal tubules by
1hydroxylase to 1,25
dihydroxycholecalciferol which acts as a
harmone
Sources and requirement



Vitamin D fortified milk
Margarine, fish liver oil, egg yolk
Infants and children require 200-400
IU/day
Functions




Regulates calcium and phophorus
metabolisms
Releases calcium from bones and
increases absorption from intestines
Hypocalcemia causes parathormone
release
Parathormone increases levels of 1,25
(OH)2 D3
Functions



Hypophosphatemia directly causes
formation of 1,25(OH)2 D3
This increases absorption of phosphate
from the intestines
Promotes endochondral growth of long
bones
Functions


Mineralization of zone of provisional
calcification (antirachitic action)
Deficiency results in defect in these areas
but with continued cartilage growth
Deficiency - causes




Exclusively breast fed infants with no
sunlight exposure or supplementation
Dark skinned babies
Rapid growth as in low birth weight infants
and adolescents
Congenital rickets can occur when
maternal stores of D are low
Deficiency - causes






Celiac disease
Pancreatitis
Steatorrhea
Cystic fibrosis
Anticonvulsants
steroids
Clinical manifestations of
deficiency



Results in rickets in children and
osteomalacia in adults
Infants show seizures, hypotonia, failure to
thrive, widened sutures, frontal bossing,
craniotabes
Older children show pot belly, delayed
milestones, delayed dentition, bowlegs,
kyphosis, pelvic abnormalities
Clinical manifestations of
deficiency


Rachitic rosary can occur
Harrison’s groove is a depression along
lower border of chest
Rickets – knock knees
Rickets - wrists
Rickety rosary
Rickets - ankles
Harrison groove
Frontal bossing of rickets
Diagnosis





Lowered serum calcium and phosphorus
Elevated alkaline phosphorus
Urinary cyclic AMP is elevated
Decreased 25 hydroxy D3
Generalized aminoaciduria occurs
Diagnosis of rickets




Xrays of the wrist and knees are best
Widened distal ends with cupping and
fraying
Uncalcified larger metaphysis and
osteopenia
A zone of preparatory calcification
separated from the distal end by a zone of
decreased calcification suggests healing
Rickets xray
Rickets - wrists
Rickets - shoulder
Rickets
Vitamin D resistant rickets





Also known as familial hypophosphatemia
Defect in the proximal reabsorption of
phosphates
Defect in the conversion of 25 (OH)2D3 to
1,25(OH)2 D3
X linked dominant inheritance
Bowing of legs appear but all else is
absent
Vitamin D resistant rickets





Near normal calcium levels
Lowered phosphorus levels
Elevated alkaline phosphate
Large urinary losses of phosphates
No evidence of secondary
hyperparathyroidism
Vitamin D dependant rickets




Due to reduced activity of 1 α hydroxylase
Decreased calcium, phosphorus
Elevated alkaline phosphatase
Levels of 1,25 (OH)2 D3 are low
Renal rickets


Due to phosphaturia of uremia
Secondary hyperparathyroidism results in
renal osteodystrophy
Treatment




Calcium and phosphorus levels are
corrected
Daily oral vitamin D 150-300 μg (500010000 IU)
Single dose of 10,000μg can be given
parenterally
Increase in phosphate occurs in 4 days
with xray evidence of healing in 1-2 weeks
Treatment

Vitamin D dependant and resistant rickets
are treated with high amounts of
phosphates and 1,25 (OH)2 D3
Prevention



AAP recommendation (April 2003,
Pediatrics)
“all infants including those who are
exclusively breast fed should have a
minimum vitamin D intake of at least 200
IU beginning in the first 2 months and
continued through adolescence”
Higher bone density in women
supplemented with vitamin D in infancy
Prevention - tips



Breast milk contains less than 25 IU/L of
vitamin D
Formula has a minimum of 400 IU/L
If an infant is ingesting at least 500ml of
formula he or she will receive the
recommended intake of 200 IU/day
Prognosis



Very good provided treatment is initiated
early
Early treatment prevents developmental
delay
Orthopedic intervention may be required
Treatment of rickets
Excess effects




Hypotonia, anorexia
Polydipsia, polyuria, dehydration
Hypertension, corneal clouding
Xrays show calcifications and
osteoporosis
Vitamin E



Group of compounds called tocopherols
Possess antioxidation properties
particularly of fats
This is facilitated by presence of ascorbic
acid
Properties




Esters are fat soluble
Susceptible to oxidation leading to loss of
vitamin activity
Protect the less susceptible compounds
by breaking up the chain of oxidation
reactions
Heat stable
Food sources




Lettuce and green vegetables
Vegetable oils
Milk
eggs
Requirement and functions





0.7mg/g of fat seems to be adequate
Inhibits oxidation of LDL cholesterol
Acts on immunomodulation
Inhibits platelet acitivity
Involved in biosynthesis of coenzyme Q
that is important in electron transport
Deficiency - causes





Malabsorption
Abetalipoproteinemia
Short bowel syndrome
Cholestatic disease
Very low birth weight infants
Deficiency








Muscle weakness
Loss of position sense
Hemolytic anemia
Double vision
Reduced reflexes
Constriction of visual fields
Sterility in animals
Arteriosclerosis?
Vitamin K





Substances with vitamin K activity are
naphthoquinones
Absorbed mainly from the jejunum
Bile salts are necessary for this
Storage is unknown
Excreted in feces
Sources




Green leafy vegetables
Cabbage
Tomatoes
Intestinal flora
Function



Essential for synthesis of prothrombin
Coagulation factors II, IV, IX and X are
vitamin K dependant
Plays a role in mitochondrial oxidative
phosphorylation
Deficiency - causes



Intestinal flora produces adequate
amounts
Hence dietary deficiency is rare
Newborns are deficient because of lower
intestinal flora content, inadequate bile
flow, intestinal hypermotility
Deficiency - causes



Prolonged oral antibiotics
Biliary obstruction, sprue, chronic diarrhea
Hepatocellular damage
Clinical features of deficiency




Uncontrollable bleeding in newborns
Exaggerated in preterms who present
between 2nd and 7th day with bleeding
Hemorrhage is more common with breast
fed infants
Maternal drugs like phenytoin cause early
bleeding
Clinical findings


Bleeding from intracranial, GI, nasal,
circumcision site
Reports of late bleeding occuring several
weeks later
Diagnosis




Prolonged PT and PTT
Normal platelet count
Normal bleeding time
Normal plasma fibrinogen levels
Treatment


All newborns should get 1mg of vitamin K
AAP recommendation is all newborns
should get parenteral vitamin K to prevent
delayed bleeding
Water soluble vitamins B complex








Include:
B1 (Thiamine)
B2 (Riboflavin)
Niacin (P-P factor of Goldberger)
Pyridoxine (B6 )
Pantothenic acid
Biotin, folic acid, and B12
Lipoic acid and inositol
Thiamine (B1 )




Water soluble
Destroyed by heat
Synthesis is limited in man
Children require 0.3mg-0.9mg/day
Sources






Breast milk and cow’s milk
Vegetables
Rice polishings
Meat
Legumes
Wheat germ
Functions



TPP functions as a coenzyme in
decarboxylation and transketolation of αketoacids
Helps in synthesis of fats from CHO
Required for synthesis of acetylcholine
Deficiency







Results in beriberi
Irritability, fatigue
Decreased tendon reflexes
Peripheral neuritis
Loss of vibration sense
Congestive cardiac failure
Hoarseness of voice and ataxia
Deficiency


Edema present in wet beriberi but absent
in dry beriberi
Wernicke’s encephalopathy: mental
changes, eye changes, cerebral bleeds
Diagnosis and treatment



Clinical response to thiamine is best
Treat mother and baby that is breast fed
50mg/day for an adult and 10mg/day for
an infant
Riboflavin




Forms 2 phosphorylated derivatives
Serve as coenzymes in oxidation –
reduction reactions and for hydrogen
transfers
Is necessary for normal metabolism of
tryptophan and oxidation of fatty acids
For retinal pigment
Sources





Eggs
Milk
Cheese
Liver
Leafy vegetables
Requirement and deficiency







0.5-1.0mg/day is required
Deficiency results in :
Cheilosis, glossitis
Keratitis, photophobia
Anemia
Seborrheic dermatitis
A urine level of < 30μg/day is abnormal
Cheilosis
Treatment

3-10 mg/day of oral riboflavin
Niacin





Forms NAD and NADPH important in
glycolysis and electron transport
End product of metabolic pathway of
tryptophan
Daily requirement is 5-13 NE
Liver and poultry are good sources
Milk and eggs are antipellagra
Deficiency
Pellagra results
 Diarrhea, dementia, dermatitis
 Skin changes resemble sunburn
 Seen in face, neck, dorsal forearms
 Diagnosis is mainly clinical
 Treat with 50-300mg of niacin
 Supplement with other vitamins

Pellagra
Pellagra
Pyridoxine (vitamin B6 )




Found in yeast, rice polishings and cereal
Serves as coenzyme in metabolism and
transfer of aminoacids
Synthesis in man is limited
Hence dietary sources are important
Deficiency and treatment




Seizures, peripheral neuritis, dermatitis,
microcytic anemia
Large amounts of xanthurenic acid in urine
following administration of tryptophan
confirms diagnosis
Administration of 100mg of pyridoxine
intramuscularly in child with seizures
In B6 dependant children 10-100mg of
pyridoxine orally
Vitamin B12





Humans cannot make B12
Microorganisms in animals make B12
The vitamin combines with intrinsic factor
in the stomach
The complex is then absorbed in the
terminal ileum
Bound to transcobolamin it enters cell
Functions




Involved in DNA synthesis and methyl
group transfer
Involved in synthesis of protein in the
microsomal system
Important for normal maintenance of
hemopoiesis
Hence also called erythrocyte maturation
factor
Requirement and food sources




Daily requirement is 2-4 mcg
Content of foods is low
Only animal sources contain vitamin
Liver, kidney, eggs, meat and milk
Deficiency - causes





Occurs in pure vegetarians
Resection of terminal ileum or stomach
Inhibition of B12 –intrinsic factor complex
Abnormalities of receptors on ileum
Abnormalities of transcobolamin
Deficiency manifestations





Glossitis , peripheral sensory problems
Gross deficiency results in pernicious
anemia
Arrested RBC development with
accumulation of megaloblasts and
myeloblasts
Macrocytic anemia
Degeneration of posterior and lateral
columns of spinal cord
Glossitis
Deficiency manifestations





Pernicious anemia is autosomal recessive
Deficiency of gastric intrinsic factor
Symptomatic at 9 years of age
Anorexia, irritability, painful red tongue
Ataxia, decreased reflexes, clonus and
coma
Pernicious anemia
Diagnosis






Anemia- macrocytic, megaloblastic
Hypersegmented neutrophils
Elevated LDH
Low serum levels of B12
Excessive methylmalonic acid in urine
Schilling’s test may be abnormal even
after therapy
Treatment

Prompt hematological response is seen in
2-4 days after treatment with 1mg of the
vitamin
Folate



Synthesized by intestinal bacteria
Folinic results from reduction
Ascorbic acid and B12 are required
Sources





Green leafy vegetables
Cauliflower
Yeast
Liver
kidney
Functions



Important in the synthesis of nucleic acids
Helps with maturation of red blood cells
Required for normal metabolic pathway of
histidine
Deficiency





Occurs in very low birth weight infants
Following intestinal resection
Megaloblastic anemia
Diarrhea, glossitis can occur
Failure to gain weight, irritability
Diagnosis




Macrocystic, megaloblastic anemia
Hypersegmented neutrophils
Neutropenia, thrombocytopenia
Levels of folate may be < 3ng/ml
Treatment


1-5 mg of folate orally or parenterally
Treating pernicious anemia with folate
may cause cure of anemia without
change in neurological abnormalities
Vitamin C




Potent reducing agent
Present in citrus fruits, spinach, cauliflower
Liver, kidney, adrenals
Requirement is 75-100mg/day
Function



Forms the ground substance between
capillary walls, osteoid tissue, collagen
Involved in oxidation reduction eractions
Required for normal growth and
maturation of cells
Deficiency - causes





Occurs in infants with mothers whose
diets are deficient in the vitamin
Infants fed with unsupplemented
evaporated milk
Fever
Diarrhea
Protein depletion
Clinical findings







Irritability
Generalized tenderness causing
pseudoparalysis
Frog position of legs
Peripheral edema
Swelling of gums
Petechial hemorrhages
Scorbitic beads in the ribs
Scurvy
Scurvy
Scurvy
Diagnosis






X-ray findings:
Ground glass appearance of bones
Pencil thin cortex
Zone of calcified cartilage at the
metaphysis (white line of Fraenkel)
Zone of rarefaction proximal to this
Vitamin C level of zero in the buffy layer
Scurvy
Treatment

100-200 mg/day produces quick healing