nutrition children

1. VITAMIN D DEFICIENCY
RICKETS
Lian Guoli

2. Vitamin D Deficiency Rickets
Clinical manifestations
etiology
Etiopathogenesis and Pathology
prevention
treatment
Diagnosis and difference diagnosis
introduction
Metabolism & function of Vitamin D

3. Introduction
Definition
Epidemiology

4. Rickets
• a term signifying failure to mineralize
growing bone or osteoid tissue
• many causes, mainly vitamin D
deficiency
• Synonym of rachitis

5. Vitamin D
• Fat soluble, stable to heat, acid alkali, and oxidation
• bile necessary for absorption
• In 1824, cod-liver oil was firstly be prescribed for
the treatment of rickets by D. Scheutte.
• In1906, Hopkins postulated the existence of
essential dietary factors necessary for the
prevention of rickets.
• In 1928, the Nobel prize for chemistry was awarded
to Adolf Windaus for his discovery of vitamin D.

6. Epidemiology
 rare in industrialized countries
 Common in China
20% in the South of China
30-40% in the North of China

7. Vitamin D Deficiency Rickets
Clinical manifestations
etiology
Etiopathogenesis and Pathology
prevention
treatment
Diagnosis and difference diagnosis
introduction
Metabolism & function of Vitamin D

8. Source of Vit D
Metabolism & function of Vitamin D
Metabolism & function of Vitamin D

9. Sun exposure
Mother
Vit D
Food
Support two
weeks
Natural foods:
inadequate
Major source
What are the sources of vitamin D?

10. Correlation Between Maternal and Cord 25 OHD

11. Natural foods
Breast milk 1 µg /L
Cow’s milk 0.5-1µg /L
Egg 1.75 µg/100g
Butter 0.75-1.5µg/100g
* Vit D 1 µg = 40IU
Content of Vit D

12. Ultraviolet light
In the
skin: 7-dehydrocholesterol
Vitamin D3
(an inactive form)
25-hydroxy vitamin D3
Hydroxylation
In the
Liver:
foods
1, 25-hydroxy vitamin D3
(active form)
Hydroxylation
In the
kidneys:
Metabolism of Vitamin D
Provitamin D3

13. function of Vitamin D
provide the proper
balance of calcium and
phosphorus
1, 25-hydroxy
vitamin D3
PTH

14. Physiological functions of vitamin D
Bone:
induces the expression of osteoclacin
stimulates differentiation of osteoclsts
deposition and reabsorption of Ca and P
Intestine:
stimulates the expression of calbindin,
enhances absorption of calcium and phosphate
Kidney:
stimulates renal tubular reabsorption of
calcium and phosphate

15. •Cell differentiation: particularly of
collagen & skin epithelium
•Immunity: important for Cell Mediated
Immunity & coordination of the immune
response.

16. Parathyroid hormone
Bone:
stimulate osteoclasts to reabsorb bone mineral,
liberate calcium into blood.
Intestine:
indirectly enhances absorption of calcium and P
Kidney:
stimulates renal tubular reabsorption of calcium
but loss of phosphate
released in response to low extracellular
concentrations of free calcium through calcium-
sensing receptor

17. Vitamin D Deficiency Rickets
Clinical manifestations
etiology
Etiopathogenesis and Pathology
prevention
treatment
Diagnosis and difference diagnosis
introduction
Metabolism & function of Vitamin D

18. Etiology
I need the
sunshine
Inadequate direct exposure to sunlight

19. Etiology
Vitamin D requirement increase
neonate
50cm
5month
65cm
1y
2y
75cm
85cm

20. Etiology
Inadequate intake of vitamin D
Vit D 4-100 IU/L
Vit D 3- 40 IU/L

21. Etiology
• Improper ratio of calcium to phosphorus in the diet
• VitD deficiency in perinatal period
calcium : phosphate absorption
breast 2 ： 1 high
milk 1.2 ： 1 low
Preterm infant, low birth-weight infant

22. Etiology
• Disease and medicine role
Interfere with the
absorption of vitamin D
Disturbance of vitamin
D hydroxylation
Interfere with the
metabolism of vitamin D
Gastrointestinal
affection
liver and kidney
Disease
some drugs

23. GROUPS AT RISK
•Infants
•Elderly
•Dark skinned
•Covered women
•Kidney failure patients
•Patients with chronic liver disease
•Fat malabsorption disorders
•Genetic types of rickets
•Patients on anticonvulsant drugs

24. Vitamin D Deficiency Rickets
Clinical manifestations
etiology
Etiopathogenesis and Pathology
prevention
treatment
Diagnosis and difference diagnosis
introduction
Metabolism & function of Vitamin D

25. Pathology
• Bone growth
osteoanagenesis within cartilage
subperiosteal osteoanagenesis
• Osteoid tissue stack ：
• Cortical bone of shaft is replaced by soft
osteoid tissues ：

26. Proliferation
layer
Hypertrophy
layer
Degeneratio
layer

27. Long bone metaphysis pathology
normal VitD deficiency
Calcifed
trabecular
bone
Osteoid
tissue

28. Pathogenesis
• Vitamin D deficiency
• Absorption of Ca, P
• Serum Ca
• Function of Parathyroid

29. Pathogenesis
• PTH
•
• High secretion
• P in urine Decalcification of old bone
• P in blood Ca in blood normal or low slightly
• Ca, P product
• Rickets

30. Pathogenesis
• Low secretion of PTH
• Failure of decalcification of bone
• Low serum Ca level
• Rachitic tetany

31. 1.Less of rickets happen in toddler
children, More in infants?
2.Why different age have different
clinical manifestation?
why ？？？
3. Why have nonspecific neuropsychic
symptoms?

32. Clinical manifestation
• Rickets is a systematic disease with
skeletons involved most, but the
nervous system, muscular system and
other system are also involved.

33. Clinical manifestation
• The early phase of rickets ：usually <3-6mo
–symptom：nonspecific neuropsychic symptoms
irritability
restlessness
sudden crying at night
alopecia in occiput
increased sweating particularly around the head
–X-ray：normal or zone of provisional calcification frayed
– Laboratory examination ：
25-(OH)D3↓
Calcium & phosphorus: normal or↓
PTH↑
AKP normal or ↑

34. Itch friction on pillow hair lose
occipital bald

35. intense Period
< 6months ：Craniotabes
( ping-pong-ball sensation )
Change of the growth bone
Skeleton changes
moto development delayed

36. >6months
accumulation of osteoid tissue
Total body muscule relaxation , muscle
tonus weakness
Head: frontal bossing, boxlike appearance of
skull,wide open anterior fontanels,
Teeth:delayed eruption, with abnormal order,
defects
Secondary Hyperparathyroidism

37. • Chest: rachitic Rosary, Harrison’s
groove, pigeon chest, funnel-shaped
chest, flaring of ribs
• Spinal column: scoliosis, kyphosis, and
lordosis
• Extremities: Enlargement of wrists
and ankles, Bow-leg & knock-knee
• Rachitic dwarfism

38. funnel breast
rachitic rosary

39. Rachitic Rosary
Enlargement of wrists and ankles
Box-like head

40. Pigeon-breast deformity Harrison’ groove
Bow-leg knock-knee

41. Others:
Muscles lack of tone : potbelly
Retardation of motor development

42. biochemistry :
25-(OH)D3↓↓
PTH↑↑
Calcium↓or normal
Phosphorus↓↓
AKP↑↑

43. • zone of provisional calcification slightly blurred or
vanished
• Cupping, fraying and flaring of epiphysis instead of
calcification line
• rachitic metaphyses （＞2mm）
• greenstick fractures, rarefaction of the bone
• Late appearance of ossification center
Radiography of bone
Wrist is the best site for watching the changes

44. Normal forearm Forearm of rickets
Metaphyseal fraying and cupping
of the distal radius and ulna

45. Normal legs Legs of rickets

46. Recovery Period
Clinical manifestation
sings and symptoms alleviate、vanishing
Laboratory examination
Blood Ca, P,25- (OH)D3 -- Normal
AKP -- Normal after 1~2mo treatment
X-ray
after２～３weeks treatment, zone of provisional
calcification reappear
rachitic metaphyses gradually put back（<2mm）

47. Re-appear of PCZ Normal PCZ

48. Sequela Period
Clinical manifestation
﹥2yr，bony abnormalities
X-ray：
Image changes -- disappear
Skeletal deformities
Laboratory examination ：Normal

49. knock knee

50. Diagnosis
• The diagnosis of rickets is based on
a history of inadequate intake of
vitamin D and so on
clinical manifestations
biochemical changes
Radiographic changes

51. • Hypothyroidism
growth development lag, dwarfism, tooth eruption
delayed, anterior large and close late,
Mentally disabled, special facies, TSH, T3, T4
Differential Diagnosis

52. •chondrodystrophy:(软骨发育不良)：
heredity, large head 、 frontal bossing
Hydrocephalus：anterior fontanelle increased progressively

53. Hypophosphatic vitamin D-resistant rickets :
tubular reasorption phosphorus and intesetines absorb phosphorus
deficiency
vit D therapy is no effect, need to give phosphorus also
distal renal tubular acidosis :
distal tubule secrete H+ deficiency ，a lot of Na+ K+ Ca++ were lost from
urine, secondary hyperparathyroidism, diuresis, alkaline urine
VitD dependency rickets：
autosomal recessive transmission.
Two typeⅠ 1-αhydroxylase deficiency
Ⅱ 1，25-（OH)2D receptor defects
Renal ricket
Other reasons cause of rickets

54. Lower extremities physical bent：
Normal extremities growth process

55. Treatment
• purpose：control activity、prevent skeletal malformation
• Method ：Combined Modality
• general treatment:exposure to sunlight
– Using vitamin D ：
Oral vitamin D
• VitD 2000-4000IU/d（10ug=400IU） for 2-4 weeks,
then change to preventive dosage (400IU)
Intramuscular injection vitamin D : For severe case, or
Rickets with complication or can’t take orally
• VitD3 200-300 thousandIU，3 month later change to
preventive dose
Recheck after 1 month treatment
Using calcium
• orthopaedic

56. Prevention
• Exposure to ultraviolet light
• Pregnant woman do more outside
activity, have calcium、phosphor and
protein diet
• Oral administration of vitamin D for
neonate ，400IU-800IU per day

57. Focal points
• etiology
• pathogenesis
• manifestation
• treatment, prevention

58. Tetany of vitamin D deficiency

59. Conception
• Because of vitamin D deficiency and
incompensation of parathyroid, hypocalcemia
(calcium ion) results in increase of
neuromuscular excitability, which can cause
convulsion of systemic or partial muscle.
• Tetany of vitamin D deficiency occurs most
frequently under the ages of 3yr, especially
less than 6 mo.

60. Etiology and pathogenesis
Basic knowledge
• Existent status of calcium in the blood
non-diffused calcium: calcium binding protein,
accounts for 40% (1.13mmol/L)
diffused calcium: accounts for 60%.
ionized calcium account for 80% of diffused
calcium，most of remainder is calcium citrate.
• Only ionized calcium has physiological activity.
• Normal serum calcium level is from 2.2 to 2.7mmol/L.
• Normal serum ionized calcium is 1.25mmol/L

61. • Factors which affect level of serum calcium
ion:
– Blood pH:
diffused calcium non-diffused calcium
– Concentration of plasma protein:
plasma-albumin ↓ , binding calcium ↓ , ionized
calcium relatively high
– Concentration of phosphorus
p ↓ inhibit 25-OH-D transferred to 1，25-（OH)2D →
calcium ↓
PH↑（alkalosis ）
PH↓（acidosis ）

62. Etiology and pathogenesis
• Inadequate direct exposure to sunlight
• Inadequate intake of vitamin D
• Vitamin D requirement increase
• Improper ratio of calcium to phosphorus
in the diet
• Disease and medicine role

63. Etiology and pathogenesis
– Vitamin D deficiency → serum Ca↓,
incompensation of parathyroid → serum
Ca↓↓（serum calcium level＜1.75-
1.88mmol/L or 7-7.5mg/dl，calcium ion ＜
1.0mmol/L or 4mg/dl）→N.M excitability
→carpopedal spasm，laryngospasm，and
convulsion

64. Etiology and pathogenesis
– Tetany may occur in infants with rickets shortly
when direct exposure to sunlight suddenly, or after
vitamin D treatment starts.
Increase of vitamin D in body can cause
deposition of calcium in rachitic bones, which may
reduce the serum calcium level and cause
hypocalcemic tetany.
– Fever, infection and starvation → catabolism in
tissue and cells ↑ → release of tissue P → serum P↑
synthesis of 1,25-(OH)2D3 ↓ hypocalcaemia in the
rachitic child → tetany

65. Clinical manifestation
• Typical clinical symptoms:
serum calcium <7-7.5mg/dl or <1.75-1.88mmol/L
– Convulsion
• Convulsion of extremities, binocular fixation,
and loss of consciousness for a few seconds
or minutes without fever, attacks 1 to more
10 times/day or 1 time in several days.

66. Clinical manifestation
– Laryngospasm
• Spasm of laryngeal muscle and glottis
cause inspiratory dyspnea, high-pitched
crowing sound. In sever cases
respirations may cease, the infant
becomes cyanotic and Occasionally an
infant was died during such an attack.

67. Clinical manifestation
– Carpopedal spasm
• Manifest wrist flexion, the thumb adducting into
the cupped palm and the other fingers rigidity.
The ankle joint is extended, and the toes are
flexed to pes arcuatus, shape of the foot takes
after foot of ballet dancer. This is occurs in older
infants and children.

68. Clinical manifestation

69. Clinical manifestation
• Recessive signs of tetany:
serum calcium<1.75-1.88mmol/L
– Because of hypocalcemia and neuromuscular
excitability increase, recessive signs may be
elicited by the mechanical means.
– These recessive signs are more common in infants
under age of 6 months old.

70. – Recessive signs:
• Chvostek ’s sign (facial nerve’ sign ): a unilateral
contraction of the facial muscles around the
mouth, nose, and eye when facial nerve is
stimulated.
• Lust ’s sign (sign of peroneal nerve reflex):
elicited by knocking at the peroneal nerve just
below the head of the fibula. A positive response
is contraction of foot top toward outside.
• Trousseau ’s sign (sign of artificial fingers spasm):
elicited by maintaining Bp between systolic
pressure and diastolic pressure for 5 minutes. A
positive response is the spasm of fingers.

71. Diagnosis
• History
• Typical symptoms and Recessive signs of tetany
• Rickets manifestation
• Low serum calcium level

72. history：end of winter and primary of spring；mother
at the pregnant period have musclar spasms；artifical
feeding ；outdoor activity few，didn’t take VitD drugs.
features：infant abrupt have convulsion and no fever，
and recurrent attacks，after the attacks mind is clear,
no nervous system signs.
Rickets manifestation
serum calcium 〈1.75～1.88mmol/L，ionized calcium
〈1.0mmol/L to make a definite diagnosis
Diagnosis

73. differential diagnosis
• Diseases causing convulsive without fever:
– hypoglycemia
• Hypoglycemia easily occurs before breakfast in
the morning. especially infant with diarrhea, blood
sugar﹤2.2mmol/L.
• The infant appears pale, convulsion and coma.
• If GS was administered by oral or iv,
manifestation disappear.
– Infantile spasm
• Occurs in infant under 1 year old
• Special manifestation and lower intelligence
• EEG abnormal
• Epilepsy

74. Differential diagnosis
• Diseases causing convulsive with fever: Infection of central
nervous system. ( Intracranial hypertension)
– Purulent meningitis
– Viral meningitis, encephalitis
– Tuberculous meningitis
These diseases are differentiated by signs of intracranial
hypertension, fever, cerebrospinal fluid.
• Acute laryngitis -----laryngospasm
– There are symptoms of upper respiratory tract, fever and
attacking inspiratory dyspnea, hoarseness, cough like dog bark
without hypocalcaemia, the treatment of calcium is no effective.

75. Treatment
• Principle:controlling convulsions, laryngospasm, Supply
calcium, Using vitamin D
– Emergency treatment
• controlling convulsions:
Convulsion and laryngospasm should be controlled
rapidly. 10% chloral hydrate (0.5ml/kg retention
enema), diazepam (0.1~0.3mg/kg intravenous
injection) can be given.
• Oxygen inhalation: convulsion seizures
• Keeping airway unobstructed: For laryngospasm,
the tongue should be pulling out immediately.
Sometimes intubation is necessary.

76. Treatment
– Supplement of calcium： to raise the serum calcium to
normal level. 10% calcium gluconate 1~2ml/kg, 2~3 fold
dilution with 10% glucose, is dripped by intravenation(>10’)
• Notice: If calcium was injected rapidly intravenously,
the heart beats may stop suddenly . If calcium was
given by subcutaneous or intramuscular injection, focal
skin or hypoderm may necrosis.
• After convulsion controlled, oral administration of
calcium chloride in 1-2% solution should be given.(10%
calcium chloride may causes gastric ulceration and
acidosis)

77. Treatment
– Vitamin D administration：After the acute
manifestations have been controlled,
vitamin D treatment should be started. The
daily dose of vitamin D is 50-100µg by oral
administration, then decreases to the
prevent dose.

78. TOXICITY
•Hypervitaminosis D
causes hypercalcemia, which manifest as:
Nausea & vomiting
Excessive thirst & polyuria
Severe itching
Joint & muscle pains
Disorientation & coma.

79. Vitamin D Toxicity
• Calcification of soft tissue
– Lungs, heart, blood vessels
– Hardening of arteries (calcification)
• Hypercalcemia
– Normal is ~ 10 mg/dl
– Excess blood calcium leads to stone
formation in kidneys
• Lack of appetite
• Excessive thirst and urination

80. • Which of the following clinical
manifestations could be presented in 4-
month-old infant who suffer from
rickets（ ）
• A . Pigeon breast
• B. Craniotabes
• C. Enlargement of the wrists
• D. Cephalous quadratus
• E. Bowlegs knees
exercise

81. • Which of the following is the most
common cause of rickets （ ）
• A. A lack of exposure to sunlight
• B. Calcium deficiency
• C. Liver & renal disease
• D. Growth & development too fast in infant
• E. Malabsorptive states

82. • A pre-term baby of one month and two days old,
gestational age 35 weeks, born in winter, breast
feeding, weight is increasing from 2.0kg to 3.0kg.
Now which supplementary food is added to at
first and why?
• A. rice-water, for supplementation of energy
• B. vegetable soup,for supplementation of
mineral substances
• C. rice-paste,for supplementation of energy
• D. cod liver oil, for supplementation of Vit A
• E. cod liver oil, for supplementation of Vit D

83. • The ratio of Calcium and Phosphorus in
breast-milk is
A. 1:2
B. 1.5:1
C. 2:1
D. 1.2:1
E. 1.5:2

84. • Please list the skeleton changes of Vit D
deficiency in intense period