This document discusses fat-soluble vitamin deficiencies, focusing on vitamins A, D, E, and K. It provides details on the biochemical functions, dietary sources, clinical signs of deficiency, diagnosis, and treatment of each vitamin. Some key points include: - Vitamin A is important for vision, growth, immune function, and epithelial integrity. Deficiency can cause xerophthalmia and increased infection risk. - Vitamin D deficiency often affects infants and causes rickets, with associated bone deformities and hypocalcemia. It is prevented by adequate sunlight exposure and dietary intake. - Vitamin E acts as an antioxidant and its deficiency can cause neurological or hematological issues. - Vitamin K

1. DR HINA QAYYUM
FAT SOLUBLE VITAMIN
DEFICIENCIES

2. INTRODUCTION
 Fat soluble vitamins
 Vitamin A
 Vitamin D
 Vitamin E
 Vitamin K

3. VITAMIN A
 Vitamin A is a fat-soluble micronutrient that cannot be synthesized by the body,
thus it is an obligatory dietary factor
 Biochemical actions of vitamin A
 In vision, as retinal, for synthesis of the visual pigments rhodopsin and iodopsin

4.  In:
 Growth and reproduction
 Embryonic and fetal development
 Bone growth
 Immune and epithelial functions
 Regulating genes involved in cellular processes

5. DIETARY SOURCES
 Liver, fish liver oils
 Dairy products, except skim milk
 Egg yolk, fortified margarine, fortified skim milk
 Carotenoids from plants: green vegetables, yellow fruits, and vegetables

6. VITAMIN A DEFICIENCY
 If the growing child has a well-balanced diet and obtains vitamin A from foods
that are rich in vitamin A, the risk of vitamin A deficiency is small.
 Deficiency states in developed countries are rare
 Vitamin deficiencies can also occur as complications in children with various
chronic disorders or diseases.

7.  Requirement for the maintenance of epithelial functions.
 In the intestines, a normal mucus-secreting epithelium (normal goblet cell function)
is an effective barrier against pathogens that can cause diarrhea.
 In the respiratory tract, a mucus-secreting epithelium is essential for the disposal of
inhaled pathogens and toxicants

8.  Characteristic changes as a result of vitamin A deficiency in the epithelia include
 A proliferation of basal cells, hyperkeratosis, and formation of stratified cornified
squamous epithelium
 Epithelial changes in the skin caused by vitamin A deficiency are manifested as
 Dry, scaly, hyperkeratotic patches, commonly on the arms, legs, shoulders, and
buttocks.

9.  Insufficient vitamin A, can cause poor growth and serious health problems in
children due to the combination of
 Defective epithelial barriers to infection
 Low immune response
 Lowered response to inflammatory stress

10. EYE LESIONS
 Lesions caused by vitamin A deficiency develop insidiously and rarely occur
before 2 year of age.
 An early symptom is delayed adaptation to the dark, a result of reduced
resynthesis of rhodopsin
 Later, when vitamin A deficiency is more advanced, it leads to night blindness
as a consequence of the absence of retinal in the visual pigment, rhodopsin, of
the retina.

11.  Photophobia is a common symptom.
 The pigment epithelium, the structural element of the retina, keratinizes. When
the pigment epithelium degenerates, the rods and cones have no support and
eventually break down, resulting in blindness.
 In early vitamin A deficiency, the cornea keratinizes, becomes opaque, is
susceptible to infection, and forms dry, scaly layers of cells (xerophthalmia).

12.  The conjunctiva keratinizes and develops plaques (Bitot spots).
 In later stages, infection occurs, lymphocytes infiltrate, and the cornea becomes
wrinkled; it degenerates irreversibly (keratomalacia and corneal ulceration),
resulting in blindness.
 Advanced xerophthalmia and xerophthalmia with permanent damage to the eye
may develop if untreated.

13. BITOT SPOTS

14. RECOVERY FROM XEROPHTHALMIA, SHOWING A PERMANENT
EYE LESION.

15. ADVANCED XEROPHTHALMIA WITH AN OPAQUE, DULL CORNEA

16. OTHER CLINICAL SIGNS
 Poor overall growth
 Diarrhea
 Susceptibility to infections
 Anemia
 Apathy, mental retardation, and increased intracranial pressure
 Malnutrition, particularly protein deficiency, can cause vitamin A deficiency by
the impaired synthesis of retinol transport protein

17. DIAGNOSIS
 Dark adaptation tests can be used to assess early-stage vitamin A deficiency
 Plasma retinol level
 Not an accurate indicator of vitamin A status unless the deficiency is severe and liver
stores are depleted, in which case low plasma retinol is likely to be evident.
 In children, plasma retinol values of
 <0.35µmol/L----very deficient
 0.35-0.7 µmol/L---deficient
 0.7-1.05 µmol/L----marginal
 >1.05µmol/L----adequate

18. TREATMENT OF VITAMIN A DEFICIENCY
 For latent vitamin A deficiency
 A daily supplement of 1,500 µg of vitamin A
 After which intake at RDA level (400-600µg/day ) should be the goal.
 In children without overt vitamin A deficiency
 Morbidity and mortality rates from viral infections, such as measles, have been
reduced by administration of
Higher doses of 30-60 mg of retinol (100,000- 200,000 IU) given once or
twice

19.  Xerophthalmia is treated by giving 1,500 µg/kg body weight orally for 5 days
followed by intramuscular injection of 7,500 µg of vitamin A in oil, until recovery
 Vitamin A is also used in preterm infants for improvement of respiratory
function and prevention of the development of chronic lung disease.

20. VITAMIN D
 Vitamin D can be synthesized in skin epithelial cells.
 Cutaneous synthesis is normally the most important source of vitamin D
 Conversion of 7-dehydrochlesterol to vitamin D3 (3-cholecalciferol) by
ultraviolet B radiation from the sun.
 Vitamin D is transported bound to vitamin D–binding protein to the liver

21.  In liver,25-hydroxlase converts vitamin D into 25- hydroxyvitamin D (25-D)
 Little regulation of this liver hydroxylation step, measurement of 25-D is the
standard method for determining a patient’s vitamin D status.
 The final step in activation occurs in the kidney, where 1α-hydroxylase adds a
second hydroxyl group, resulting in 1,25-D.
 The 1α-hydroxylase is upregulated by PTH and hypophosphatemia;
hyperphosphatemia and 1,25-D inhibit this enzyme

22.  In the intestine, binding of 1,25-D to its receptor results in a marked increase in
calcium absorption, which is highly dependent on 1,25-D.
 There is also an increase in phosphorus absorption, but this effect is less
significant because most dietary phosphorus absorption is vitamin D
independent.
 1,25-D also has direct effects on bone, including mediating resorption

23. SOURCES OF VITAMIN D
 Exposure to sunlight (UV light)
 Fish oils, fatty fish
 Egg yolks
 Vitamin D– fortified formula, milk, cereals, bread

24. ETIOLOGY OF NUTRITIONAL VITAMIN D
DEFICIENCY
 Most common in infancy because of a combination of poor intake and
inadequate cutaneous synthesis.
 Infants who receive formula receive adequate vitamin D.
 Because of the low vitamin D content of breast milk, breastfed infants rely
on cutaneous synthesis or vitamin supplements.

25.  Cutaneous synthesis can be limited because of the :
 Ineffectiveness of the winter sun in stimulating vitamin D synthesis
 Avoidance of sunlight because of concerns about cancer, neighborhood safety, or
cultural practices
 Decreased cutaneous synthesis because of increased skin pigmentation such as in
dark skinned persons

26. CLINICAL FEATURES
 Rickets
 Symptoms of hypocalcemia
 Tetany
 Seizures
 Prolonged laryngospasm is occasionally fatal.
 An increased risk of pneumonia and muscle weakness leading to a delay in
motor development

27. CLINICAL FEATURES OF RICKETS
 GENERAL
 Failure to thrive
 Listlessness
 Protruding abdomen
 Muscle weakness (especially proximal)
 Fractures
 HEAD
 Craniotabes
 Frontal bossing
 Delayed fontanel closure
 Delayed dentition; caries
 Craniosynostosis

28.  CHEST
 Rachitic rosary
 Harrison groove
 Respiratory infections and atelectasis
 BACK
 Scoliosis
 Kyphosis
 Lordosis

29.  EXTREMITIES
 Enlargement of wrists and ankles
 Valgus or varus deformities
 Windswept deformity (combination of valgus deformity of 1 leg with varus deformity
of the other leg)
 Anterior bowing of the tibia and femur
 Leg pain

30. RACHITIC ROSARY IN A YOUNG INFANT.

31. HARRISON GROOVE

32. LABORATORY FINDINGS
Ca ---- N, ↓
Pi ---- ↓
PTH---- ↑
25-(OH)D ---- ↓
1,25-(OH)2D ----- ↓, N, ↑
Alk Phos ----- ↑
URINE Ca ---- ↓
URINE Pi ---- ↑

33. RADIOLOGY
• Decreased calcification leads to thickening of the growth plate.
• The edge of the metaphysis loses its sharp border, which is described as fraying.
• The edge of the metaphysis changes from a convex or flat surface to a more concave surface. This
change to a concave surface is termed cupping and is most easily seen at the distal ends of the
radius, ulna, and fibula.
• There is widening of the distal end of the metaphysis, corresponding to the clinical observation
of thickened wrists and ankles, as well as the rachitic rosary

34. Wrist x-rays in a normal child (A) and in a child with rickets (B). The child with rickets has
metaphyseal fraying and cupping of the distal radius and ulna.

35. TREATMENT
 With stoss therapy
 300,000-600,000 IU of vitamin D are administered orally or intramuscularly as 2-4
doses over 1 day.
 The alternative is daily, high-dose vitamin D, with doses ranging from 2,000-
5,000 IU/day over 4-6 wk.
 Either strategy should be followed by daily vitamin D intake of 400 IU/day.
 Children should receive adequate dietary calcium and phosphorus; usually
provided by milk, formula, and other dairy products

36.  Children who have symptomatic hypocalcemia might need:
 Intravenous calcium acutely, followed by oral calcium supplements
 Prevention
 Administration of 400 IU of vitamin D to infants who are breastfed. Older children
should receive 600 IU/day of vitamin D.

37. VITAMIN E
 Vitamin E is a fat-soluble vitamin and functions as an antioxidant
 Protection of cell membranes from lipid peroxidation and formation of free radicals
 Its precise biochemical functions are not known.
 Bile acids necessary for absorption

38.  Vitamin E deficiency can cause hemolysis or neurologic manifestations and
occurs in:
 Premature infants
 Patients with malabsorption
 An autosomal recessive disorder affecting vitamin E transport.

39. DIETARY SOURCES
 Vegetable oils
 Seeds
 Nuts
 Green leafy vegetables
 Margarine

40. CLINICAL FEATURES
 A severe, progressive neurologic disorder occurs in patients with prolonged
vitamin E deficiency.
 Patients may have cerebellar disease, posterior column dysfunction, and retinal
disease.
 Loss of deep tendon reflexes is usually the initial finding.

41.  Subsequent manifestations include:
 Limb ataxia (intention tremor, dysdiadochokinesia)
 Truncal ataxia (wide-based, unsteady gait)
 Dysarthria
 Ophthalmoplegia (limited upward gaze)
 Nystagmus
 Decreased proprioception (positive Romberg test)
 Decreased vibratory sensation

42.  Some patients have pigmentary retinopathy.
 Visual field constriction can progress to blindness.
 In premature infants, hemolysis as a result of vitamin E deficiency typically
develops during the 2nd mo of life.

43. DIAGNOSIS
 Serum vitamin E levels increase in the presence of high serum lipid levels
 Vitamin E status is best determined by measuring the ratio of vitamin E to serum
lipids
 Abnormal nerve conduction studies.
 Abnormalities on electroretinography(ERG) in patients with retinal
involvement.

44. TREATMENT
 For correction of deficiency in neonates
 The dose of vitamin E is 25-50 units/day for 1 wk, followed by adequate dietary
intake.
 Children with deficiency as a result of malabsorption
 Should receive 1 unit/kg/day

45. VITAMIN K
 Vitamin K is necessary for the synthesis of clotting factors II, VII, IX, and X
 Deficiency of vitamin K can result in clinically significant bleeding.
 Vitamin K deficiency typically affects
 Infants, who have inadequate dietary intake
 Patients of any age who have decreased vitamin K absorption.

46.  Bile salts necessary for intestinal absorption
 Dietary sources
 Green leafy vegetables
 Liver
 Certain legumes and plant oils

47. CLINICAL FEATURES
 Early VKDB (vitamin K deficiency bleeding) was formerly called classic
hemorrhagic disease of the newborn and occurs at 1-14 days of age.
 It is secondary to low stores of vitamin K at birth as a result of the poor transfer
of vitamin K across the placenta and inadequate intake during the 1st few days of
life.
 The most common sites of bleeding are the gastrointestinal (GI) tract, mucosal
and cutaneous tissue, the umbilical stump, and the postcircumcision site

48.  Late VKDB most commonly occurs at 2-12 wk of age, although cases can occur up to 6 mo after
birth.
 Occur in breastfed infants because of the low vitamin K content of breast milk.
 VKDB as a result of fat malabsorption can occur in children of any age. present with bruising,
mucocutaneous bleeding, or more serious bleeding. Potential etiologies include
 Cholestatic liver disease
 Pancreatic disease
 Intestinal disorders (celiac sprue, inflammatory bowel disease).

49. LABORATORY FINDINGS
 The prothrombin time (PT) is prolonged
 The partial thromboplastin time is usually prolonged, but it may be normal in
early deficiency
 The platelet count and fibrinogen level are normal.

50. TREATMENT
 Infants with VKDB should receive 1 mg of parenteral vitamin K.
 For rapid correction in adolescents, the parenteral dose is 2.5-10 mg.
 Children with vitamin K deficiency as a consequence of malabsorption
 Require chronic administration of high doses of oral vitamin K (2.5 mg twice/wk to 5
mg/day).

51. THANK YOU