vitamins usha sethuraman, md emergency medicine 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


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

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


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


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


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

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


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


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

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

vitamins usha sethuraman, md emergency medicine children’s hospital of michigan

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