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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 (5000-10000 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 α-ketoacids
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