Role of Zinc in paediatrics.

1. DR. M. S. PRASAD 1
ZincZinc
Dr. M. S. PrasadDr. M. S. Prasad
Consultant & Head
Dept. of Paediatrics
Safdarjung Hospital &
Vardhaman Mahavir Medical College
New Delhi
Dr. M. S. PrasadDr. M. S. Prasad
Consultant & Head
Dept. of Paediatrics
Safdarjung Hospital &
Vardhaman Mahavir Medical College
New Delhi

2. DR. M. S. PRASAD 2
ZincZinc
♦ Atomic No. 30
♦ Atomic Weight: 65.409
♦ Melting point: 7870
F [4200
C]
♦ Since 2500 yrs: in the production
of Brass.
♦ Romans used brass to make coins,
kettles and decorative items.

3. DR. M. S. PRASAD 3
Zinc in natureZinc in nature
♦ Zinc constitutes approximately
0.02% of the earth’s crust.
♦ Zinc is a poor conductor of
electricity and heat.

4. DR. M. S. PRASAD 4
ZincZinc
♦ Metallic zinc first produced in IndiaMetallic zinc first produced in India
sometime in 1400s.sometime in 1400s.
♦ Initial methodInitial method:: By heating mineralBy heating mineral
Calamine (ZnCOCalamine (ZnCO33) with wool.) with wool.
♦ Later methodLater method:: By heating calamineBy heating calamine
with charcoal [Andreas Sigismundwith charcoal [Andreas Sigismund
Marggraf 1746]Marggraf 1746]

5. DR. M. S. PRASAD 5
Industrial Uses
♦ Galvanization.
♦ Dry Cell Batteries.
♦ Roof Cladding.
♦ Die Casting.
♦ Making alloys: Brass, Prestal, German Silver,
Typewriter Metal, Nickel Silver, Spring Brass.
♦ Red Oxide: protects from rusting.

6. DR. M. S. PRASAD 6
Industrial Uses
 Paints.
 Rubber Products.
 Cosmetics
 Pharmaceuticals
 Plastic
 Printing Ink.
 Soap.

7. DR. M. S. PRASAD 7
Industrial Uses
 ZnS: Glows when exposed to UV light. Used in
 Luminous watch dials.
 Television Screen.
 Florescent light bulbs.
 ZnCl2: Protects wood from decay and insects.

8. DR. M. S. PRASAD 8

9. DR. M. S. PRASAD 9
1979
♦ A 3 yr old girl suffering from ALL
developed “common cold”.
♦ She took unsweetened zinc
gluconate lozenges.
♦ This cured her common cold.

10. DR. M. S. PRASAD 10
19841984
Numerous manufacturerNumerous manufacturer
placed on the marketplaced on the market
““improved”improved” zinc lozengeszinc lozenges
that were sweetened.that were sweetened.

11. DR. M. S. PRASAD 11
1985 - 1995
♦ Many patents.
♦ Many trials by manufacturers.
♦ Zinc Gluconate forms very bitter
complexes with all carbohydrates
(except fructose).
♦ At least two formulations made
the cold worse.
♦ Trials dropped and discovery
discredited.

12. DR. M. S. PRASAD 12

13. DR. M. S. PRASAD 13
Areas of Zinc concentrationAreas of Zinc concentration
♦ Pancreas,
♦ Prostate,
♦ Kidney,
♦ Liver,
♦ Muscles, and
♦ Retina.

14. DR. M. S. PRASAD 14
Co-factors of many enzymes
♦ As many as 300 enzymes require
zinc for optimum function.
♦ Carbonic Anhydrase.
♦ Alkaline Phosphatase.

15. CofactorsCofactors (continued)
♦ LDH
♦ Pancreatic Carboxypeptidase.
♦ Superoxide Dismutase.
♦ And many others.
DR. M. S. PRASAD 15

16. DR. M. S. PRASAD 16
Nucleic Acid Metabolism
and Protein synthesis
 Zinc Finger Motif.
 Receptor for Steroid-Thyroid,
1, 25 (OH)2 – D3
 TF III-A Protein.
 A single amino acid mutation
results in resistance to this
hormone and may lead to
Rickets.

17. DR. M. S. PRASAD 17
FUNCTIONS OF ZINCFUNCTIONS OF ZINC
♦ Zinc is anZinc is an antioxidantantioxidant nutrient.nutrient.
♦ Necessary for:Necessary for:
– Protein SynthesisProtein Synthesis
– Wound HealingWound Healing
♦ Vital for:Vital for:
– Development of Reproductive OrgansDevelopment of Reproductive Organs
– Prostate FunctionProstate Function
– Male Hormone ActivityMale Hormone Activity

18. DR. M. S. PRASAD 18
FunctionsFunctions [Continued][Continued]
 Governs theGoverns the contractility of musclescontractility of muscles
 Important forImportant for blood stabilityblood stability
 Maintains body’s alkaline balanceMaintains body’s alkaline balance
 Helps in normal tissue functionHelps in normal tissue function
 Helps in digestion and metabolismHelps in digestion and metabolism
of phosphate.of phosphate.

19. DR. M. S. PRASAD 19
FunctionsFunctions (Contd)(Contd)
♦ Involved in cell-membrane
structure.
♦ Anti-oxidant metallo-
thionine synthesis.
♦ Part of several transcription
factors: nucleophile.

20. DR. M. S. PRASAD 20
Functions (Continued)
AA component of many enzymes.component of many enzymes.
Multiple role in:Multiple role in:
 Nucleic Acid MetabolismNucleic Acid Metabolism
 Protein SynthesisProtein Synthesis
Important for membraneImportant for membrane
structure and functionstructure and function.
Acts as antibacterial in semen

21. DR. M. S. PRASAD 21
Daily Reference Intake
♦ 0 – 6 mo:0 – 6 mo: 2 mg/day2 mg/day
♦ 7 mo – 3 yr:7 mo – 3 yr: 3 mg/day3 mg/day
♦ 4 – 8 yr:4 – 8 yr: 5 mg/day5 mg/day
♦ 9 – 13 yr:9 – 13 yr: 8 mg/day8 mg/day
♦ 14 – 18 yr:14 – 18 yr:
– Male:Male: 11 mg/day11 mg/day
– Female:Female: 9 mg/day9 mg/day

22. DR. M. S. PRASAD 22
RDA [Elemental Zinc]
♦ 0 – 6 mo: 3 mg
♦ 6 – 12 mo: 5 mg
♦ 1 – 10 yrs: 10 mg
♦ Adults: 15 mg

23. DR. M. S. PRASAD 23
Dietary SourcesDietary Sources
 Oysters.
 Liver, Meat.
 Grains,
 Wheat Bran, Whole meal wheat
flour and Bread, Oatmeal.
 Sardines, Crab.
 Nuts, Legumes.
 Cheese.
 Milk.

24. DR. M. S. PRASAD 24
Causes of Zinc Deficiency
♦ Protein Energy Malnutrition.Protein Energy Malnutrition.
♦ DietaryDietary
– During periods of rapid growth
– High phytate intake in diet
♦ TPN without ZincTPN without Zinc
♦ Impaired AbsorptionImpaired Absorption
– Regional Enteritis
– Cystic Fibrosis
♦ Excessive LossesExcessive Losses [e.g. Chronic Diarrhoea]
♦ Inborn Error of Zinc MetabolismInborn Error of Zinc Metabolism
[Acrodermatitis enteropathica]

25. DR. M. S. PRASAD 25
Effects of Deficiencies
 Acrodermatitis Enteropathica.
 Hypogonadism.
 Growth Failure.
 Impaired Wound Healing.
 Decreased Taste and Smell acuity.
 Skin Ulcers.
 Decreased Immune Response.
 Iron Deficiency Anaemia.
 Altered Mood.
 Jitteriness.

26. DR. M. S. PRASAD 26
Effects of DeficiencyEffects of Deficiency
♦ PEM + Zn Deficiency = Atrophy
of Thymus.
♦ Zinc supplementation
accelerates healing of skin
lesions.

27. DR. M. S. PRASAD 27
Effects of Zinc DeficiencyEffects of Zinc Deficiency
♦ Impaired growth.
♦ Poor wound healing
♦ Bullous Dermatitis.
♦ Immunity Defects
– Particularly T-Cell function with increased susceptibility to infection.
♦ Alopacia
♦ Night Blindness.
♦ GIT Disturbances.
♦ Nervous System Disorders.
♦ Impaired Carbohydrate Metabolism.

28. DR. M. S. PRASAD 28
Biochemical Methods used in
diagnosis of Zn deficiency
♦ Plasma Zinc.
♦ WBC Zinc.
♦ Hair Zinc.
♦ Urine Zinc.

29. DR. M. S. PRASAD 29
Plasma Zinc Levels
[Before Breakfast][Before Breakfast]
♠ NormalNormal:: 60 – 100 μg60 – 100 μg//dldl
♠ Moderate DeficiencyModerate Deficiency:: 40 – 60 µg40 – 60 µg//dLdL
♠ Severe DeficiencySevere Deficiency:: < 40 µg/dL< 40 µg/dL
In patients with mild deficiency, plasma concentration may be within the normal range

30. DR. M. S. PRASAD 30
Acrodermatitis Enteropathica
♦ Zinc malabsorptionZinc malabsorption  DeficiencyDeficiency
♦ RashesRashes [around mucocutaneous jn and extremities]
♦ AlopaciaAlopacia
♦ Chronic DiarrhoeaChronic Diarrhoea [sometimes Steatorrhoea]
♦ FTTFTT
♦ Low Serum ZincLow Serum Zinc
♦ Low Serum Alkaline PhosphataseLow Serum Alkaline Phosphatase
♦ Paneth Cell InclusionPaneth Cell Inclusion in intestinal mucosal biopsy. .

31. DR. M. S. PRASAD 31
Acquired acrodermatitisAcquired acrodermatitis
with erythematous scalywith erythematous scaly
lesions and candidalesions and candida
albicans superinfectionalbicans superinfection
occurs in prematureoccurs in premature
neonates on parenteralneonates on parenteral
nutrition with insufficientnutrition with insufficient
zinc supplements.zinc supplements.

32. DR. M. S. PRASAD 32
Treatment
Zinc Sulfate:Zinc Sulfate:
1 – 2 mg/kg/day orally1 – 2 mg/kg/day orally
[Elemental Zinc]
Separately from meals and from Iron supplementations
Duration: 3 months
Acrodermatitis Enteropathica

33. DR. M. S. PRASAD 33
Wilson Disease
 Zinc has unique ability to impair theZinc has unique ability to impair the
gastrointestinal absorption of copper.gastrointestinal absorption of copper.
 Zinc acetate is given in adults at a dose ofZinc acetate is given in adults at a dose of
25 to 50 mg three times a day.25 to 50 mg three times a day.
 Pediatric dosing guidelines have not beenPediatric dosing guidelines have not been
established.established.

34. DR. M. S. PRASAD 34
Common Cold
 3C Protease is an essential enzyme3C Protease is an essential enzyme
for replication offor replication of rhinovirusrhinovirus..
 Zinc inhibits function of thisZinc inhibits function of this
enzyme.enzyme.
 Further studies requiredFurther studies required..

35. DR. M. S. PRASAD 35
HyperbilirubinemiaHyperbilirubinemia
 Zinc protoporphyrinZinc protoporphyrin oror mesophyrinmesophyrin
[ZnPP or ZnMP][ZnPP or ZnMP] are inhibitors ofare inhibitors of haemhaem
oxygenaseoxygenase, the enzyme that begins, the enzyme that begins
the break- down of haem.the break- down of haem.
 Studies are under way involving aStudies are under way involving a
single injection of these substancessingle injection of these substances
shortly after birth to prevent theshortly after birth to prevent the
formation of bilirubinformation of bilirubin..

36. DR. M. S. PRASAD 36
Zinc Supplements
♦ Infants & ChildrenInfants & Children:
0.5 – 1 mg/kg/24 hrs
in 1 – 3 doses.
♦ AdultsAdults:
25 – 50 mg/dose tid

37. DR. M. S. PRASAD 37
Advantages of Zinc Supplementation in Community
♥ Improved immunocompetenceImproved immunocompetence
♥ Reduction in incidence of AcuteReduction in incidence of Acute
and Persistentand Persistent DiarrhoeaDiarrhoea inin
communitycommunity
♥ Increased activity levelsIncreased activity levels

38. DR. M. S. PRASAD 38
TPN Supplement
♣ Preterm:Preterm: 400400 μgμg/kg/24 hr/kg/24 hr
♣ Infants < 3 mo:Infants < 3 mo: 250250 μgμg/kg/24 hr/kg/24 hr
♣ Infants > 3 mo:Infants > 3 mo: 100100 μμg/kg/24 hrg/kg/24 hr
♣ Children:Children: 5050 μμg/kg/24 hrg/kg/24 hr

39. DR. M. S. PRASAD 39
Other UsesOther Uses
 Zinc is also used as ingredient inZinc is also used as ingredient in
shampoo and paste.shampoo and paste.
 Zinc deficiency depresses appetite andZinc deficiency depresses appetite and
growth. It can be corrected with oralgrowth. It can be corrected with oral
zinc supplements given over 1-2 mo.zinc supplements given over 1-2 mo.
 20 mg Zinc daily for 14 days in Severe20 mg Zinc daily for 14 days in Severe
Malnutrition, Acute and PersistentMalnutrition, Acute and Persistent
Diarrhoea and Measles.Diarrhoea and Measles.

40. DR. M. S. PRASAD 40
Excess of ZincExcess of Zinc
causes cirrhosiscauses cirrhosis
Excess of zinc has been associated
with cirrhosis of liver in river Nile belt.

41. DR. M. S. PRASAD 41
Other features of Zinc Toxicity
♦ G. I. Irritation.
♦ Copper Deficiency.
♦ Decreased HDL.
♦ Zinc Pneumonia:
– A form of Aspiration Pneumonia due to inhalation of
baby powder containing Zinc Stearate.

42. DR. M. S. PRASAD 42
Zinc ToxicityZinc Toxicity
♦ Acute Zinc Toxicity:
– GIT Disturbances
♦ Chronic Zinc Toxicity:
– Interferes with absorption of other essential
elements such as calcium.
♦ Causes of acute toxicity:
– Ingestion.
– I. V. Infusion.
– I. V. contamination during hemodialysis.

43. DR. M. S. PRASAD 43
Other Symptoms
♦ Zinc Chloride has caustic action
and can cause lacerations and
dermatitis of the exposed skin.
♦ Zinc pyrithione, found in
shampoos, also is reported to
cause dermatitis.
♦ Zinc chloride and zinc sulfate
can cause significant eye
injuries.

44. DR. M. S. PRASAD 44
Symptoms (Contd)
♦ Eye manifestations:
♦ Delayed Pulmonary vascular fibrosis.
♦ Drinking acidic beverages from galvanized
containers.
♦ Microscaopic haematuria.
♦ Acute Tubular Necrosis.
♦ Zinc Metal Fume Fever.
[Page 303, Chapter 66, Pediatric and Adolescent Environmental Health 2004. Vol.2]

45. DR. M. S. PRASAD 45
Specific Treatment of Zinc Toxicity
♦ Dimercaprol:
2.5 – 5 mg/Kg deep I.M. every 4 hrs for 2 days,
then 2.5 mg/kg x 2 for 7 – 14 days.
♦ Penicillamine:
250 mg – 2 g daily orally in divided doses.

46. DR. M. S. PRASAD 46
ZincZinc
againstagainst
DiarrhoeaDiarrhoea

47. DR. M. S. PRASAD 47
DiarrheaZn def
+
+
Zn & Diarrhea
Vicious Cycle

48. DR. M. S. PRASAD 48
Effect of zinc on time of recovery
4.7
6.2
0
1
2
3
4
5
6
7
Zinc Control
Days
Zinc Control
Arch Dis Child. 1997 Sep;
77(3):196-200
25% reduction in time to recovery

49. DR. M. S. PRASAD 49
♦ 2002:2002: Zn deficiency included as aZn deficiency included as a
major risk factor in the global burden ofmajor risk factor in the global burden of
diseases.diseases.
♦ 2004:2004: WHO/UNICEF included ZnWHO/UNICEF included Zn
supplements in the treatment ofsupplements in the treatment of
acute diarrhoea.acute diarrhoea.

50. DR. M. S. PRASAD 50
Effects of zinc supplements on Diarrheal incidence
in LBW children < 1 yr
1.36
1.96
0
0.5
1
1.5
2
2.5
Zinc Placebo
Pediatrics 2003 Dec;112(6 Pt 1):1327-32

51. DR. M. S. PRASAD 51
ZincZinc
supplementationsupplementation
has shown 18%has shown 18%
reduction inreduction in
incidence ofincidence of
diarrhoea.diarrhoea.

52. DR. M. S. PRASAD 52
Therapeutic EffectsTherapeutic Effects
Zinc was found to have a
therapeutic benefit in seven trials
of acute diarrhoea and five of
persistent diarrhoea.

53. DR. M. S. PRASAD 53
Mechanism of action of Zinc
♦ Direct GI effects:
– Intestinal water and electrolyte transport.
– Brush Border Enzymatic Functions.
– Intestinal Tissue Repair.
– Improvement of Intestinal permeability.
♦ Immunomodulatory effects:
♦ Antimicrobial effect:
♦ Antioxidant effect:

54. DR. M. S. PRASAD 54
Immunomodulatory effects
 Enhances cellular immunity
 Higher levels of secretary antibodies.
 Facilitates functions of Neutrophils, NK Cells,
Monocytes and Macrophages.
 T-helper & cytotoxic T-Lymphocyte activity.

55. DR. M. S. PRASAD 55
Antimicrobial Effect
♦ Zinc Sulphate has been shown to have anZinc Sulphate has been shown to have an
antimicrobial effect on the enteric pathogen.antimicrobial effect on the enteric pathogen.
♦ The following enteric pathogens tested were
inhibited:
– S. typhi [20% inhibition at conc. 0.8 mg/ml]
– S. paratyphi [1.2 mg/ml]
– V. cholerae 01 and Shigella flexneri [1.4 mg/ml]
– Shigella sonnei [1.6 mg/ml]

56. DR. M. S. PRASAD 56
Antioxidant EffectAntioxidant Effect
♦ Scavenging effect against NOScavenging effect against NO
– The excess production of NO triggers formation of cyclic
nucleotides, which causes secretion and malabsorption.
♦ Stabilizes thiol groups andStabilizes thiol groups and
phospholipids in membrane.phospholipids in membrane.
♦ Occupies sites of redox activeOccupies sites of redox active
metals such as iron.metals such as iron.

57. DR. M. S. PRASAD 57
WHO/UNICEFWHO/UNICEF
Consensus StatementConsensus Statement
Zinc supplementation, given at a dose
of about 2 RDA per day (10 to 20 mg/d)
for 14 days, is efficacious in
significantly reducing severity of
diarrhoea as well as duration of the
episode.

58. DR. M. S. PRASAD 58
RecommendationsRecommendations
of IAP Task Forceof IAP Task Force
 A uniform dose of 20 mg of elemental
Zinc should be given during the period
of diarrhoea and for 7 days after
cessation of diarrhoea to children
older than 3 months.
 Recommendations for below 3 months
must await further research.

59. DR. M. S. PRASAD 59
RecommendationsRecommendations
of IAP Task Forceof IAP Task Force
Iron containing
formulations should
not be used with zinc
as iron interferes with
zinc absorption.

60. DR. M. S. PRASAD 60

61. DR. M. S. PRASAD 61
Sazawal S, Black RE, Bhan MK:
Zinc supplementation in young children with acute diarrhoea in India.
• This study evaluated the effects of daily
supplementation with 20 mg of elemental
zinc on the duration and severity of acute
diarrhoea.
• There was 23% reduction
(95% C. I.) in the risk of
continued diarrhoea.

62. DR. M. S. PRASAD 62
Sazawal et al (Contd.)
• The reductions in the duration and
severity of diarrhoea were greater in
children with stunted growth than in
those with normal growth.
• CONCLUSIONCONCLUSION:: For infants and young
children with acute diarrhoea, zinc
supplementation results in clinically
important reductions in the duration
and severity of diarrhoea.
N Engl J Med 1995 Sep 28; 333 (13): 839-44.

63. DR. M. S. PRASAD 63
Bhandari N, Bahl R, Taneja S.Bhandari N, Bahl R, Taneja S.::
Zinc Supplementation in Young North Indian ChildrenZinc Supplementation in Young North Indian Children
♦ Door to Door Survey.
♦ 4 months daily zinc supplementation.
♦ 6 to 30 months of age residing in urban
slums of Dakshinpuri in south Delhi.
♦ Zinc supplementation reduced the incidence
of severe, persistent and recurrent diarrhoea
PEDIATRICS Vol. 109 No. 6 June 2002, p e86

64. DR. M. S. PRASAD 64
Bhatnagar S, Bahl R, Sharma PK:
Zinc with oral rehydration therapy.
♦ The authors evaluated the effect of zinc
treatment as an adjunct to oral
rehydration therapy.
♦ Zinc treatment reduced total stool output
and stool output per day.
♦ The duration of diarrhoea was also low.
♦ The risk of persistent diarrhoea was low.
J Pediatr Gastroenterol Nutr. 2004 Jan; 38(1): 34-40

65. DR. M. S. PRASAD 65
Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat:
Therapeutic effects of Zinc.
♦ The effects of supplemental Zinc given
with Oral Rehydration Therapy.
♦ The study concluded that Zinc
supplementation reduces the duration
and severity of acute and persistent
diarrhoea.
Am J Clin Nutr 2000; 72: 15161522

66. DR. M. S. PRASAD 66
BMJ 2002; 325 (7372): 1059
♦ Children with diarrhoea were treated with
zinc 20 mg per day for 14 days.
♦ Bangla Desh: 8070 children aged 3 – 59
months studied.
♦ They had shorter duration and lower
incidence of diarrhoea.
♦ The incidence of ARI was also low.
♦ Hospital admission was low.

67. DR. M. S. PRASAD 67
Hospitalization due to diarrhoea
0.59
0.98
0
0.2
0.4
0.6
0.8
1
1.2
Zinc Placebo
Odds Ratio

68. DR. M. S. PRASAD 68
There is innumerableThere is innumerable
number of studies on thenumber of studies on the
role of Zinc in Diarrhoea,role of Zinc in Diarrhoea,
ARI and Malnutrition. AllARI and Malnutrition. All
show statisticallyshow statistically
significant beneficialsignificant beneficial
effect of zinceffect of zinc
supplementation.supplementation.

69. DR. M. S. PRASAD 69

70. DR. M. S. PRASAD 70
ZincZinc is especiallyis especially
important in adolescenceimportant in adolescence
because of its role inbecause of its role in
growth and sexualgrowth and sexual
maturation.maturation.

71. DR. M. S. PRASAD 71