Consequences of Vitamin D deficiency

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Consequences of Vitamin D deficiency
Excess
By Prof. M. Y. JAN
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Hypervitaminosis D

• DEFINITION
• A disorder due to the excessive ingestion of
  Vitamin D resulting in neurologic,
  gastrointestinal, and renal manifestations.
• Alternative Name Vitamin D Toxicity
• EPIDEMIOLOGY
• incidence ?
• age of onset any
• risk factors
• patients on vitamin D for chronic
  hyperphosphatemic states

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Hypervitaminosis D

• Pathogenesis
• 1. Chronic Hypervitaminosis
• may occur after the ingestion of excessive
  amounts of vitamin D over weeks (gt500 ug/d) or
  months (gt45 ug/d)
• may lead to (malignant) calcification of soft
  tissues
• heart - aortic valvular stenosis
• blood vessels - hypertension
• renal tubules - nephrocalcinosis -gt secondary
  nephrogenic DI -gt polyuria, polydipsia
• stomach - anorexia, nausea and vomiting, etc

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Hypervitaminosis D

• CLINICAL FEATURES
• Neurological Manifestations
• hypotonia
• 
  irritability
• Gastrointestinal Manifestations
• anorexia
  with weight loss
• 
  constipation or diarrhea
• nausea and
  vomiting
• Renal Manifestations
• polydipsia
• 
  polyuria/nocturia /- dehydration
• Ocular Manifestations
• conjunctiva
  - clouding
• cornea
  clouding
• retinopathy
  

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Hypervitaminosis D

• Other Manifestations
• aortic valvular stenosis
• hypertension
• pallor
• Fanconi Syndrome
• episodes of vomiting, dehydration, weakness,
  and unexplained fever anorexia, constipation
  polydipsia, polyuria failure to thrive growth
  failure rickets

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Hypervitaminosis D

• INVESTIGATIONS
• 1- Serum
• hypercalcemia
• evidence of dehydration - elevated BUN,
  creatinine
• 2- Urine
• hypercalciuria
• proteinuria

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Hypervitaminosis D

• Imaging Studies
• 1- Renal Ultrasound
• nephrocalcinosis /- metastatic calcification
• 2- Skeletal X-Rays
• metastatic calcification of long bones
• generalized osteoporosis
• 3- 2D Echo
• aortic valve stenosis

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Hypovitaminosis D

• Children
• Vitamin D Deficiency Rickets
• Adults
• Osteomalacia

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• Rickets is the most common form of metabolic bone
  disease worldwide.

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• Clinical features
• Abnormal gait, hypocalcemic tetany/ seizures,
  developmental delay, failure to thrive
• Skeletal findingsgtgtgt

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• Skeletal and Radiological findings
• Bowing or widening of physis
• Costochondral beading (rachitic rosary)
• Craniotabes
• Delayed closure of anterior fontanel
• Dental abnormalities
• Flaring of ribs at diaphragm level (Harrison's
  groove)
• Flaring of wrists
• Fractures
• Fraying and cupping of metaphysis
• Frontal bossing of skull
• Genu valgum or varum
• Lordosis/kyphosis/scoliosis
• Osteopenia
• In addition, the anteroposterior diameter of the
  pelvis can shrink,
• resulting in a flat pelvis, in girls may
  lead to obstructed labor

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• Nonskeletal effects of vitamin D deficiency
• Hypocalcaemic seizures secondary to vitamin D
  deficiency occur
• typically in infants under 6 months, usually
  before radiological
• features are apparent.
• Hypocalcaemic tetany, apnea and stridor may also
  present.
• Hypocalcaemic cardiac myopathy may lead to
  potentially dilated or
• hypertrophic cardiomyopathy, arrhythmias,
  hypotension, and heart
• failure.

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Biochemistry and Physiology of Vitamin D
Endocrine System
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• In the skin, photo-conversion of
  7-dehydrocholesterol to vitamin D3 or dietary
  intake of vitamin D3

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• Metabolism of vitamin D3 by the liver to
  25(OH)D3, which is the major form of vitamin D
  circulating in the blood compartment.

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• Conversion by the kidney of 25(OH)D3 to
  produce the two principal dihydroxylated
  metabolites, namely 1a,25(OH)2D3 and
  24R,25(OH)2D3.

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• Systemic transport of the dihydroxylated
  metabolites 1a,25(OH)2D3 and 24R,25(OH)2D3 to
  distal target organs.

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• Binding of the dihydroxylated metabolites,
  particularly 1a,25(OH)2D3, to a nuclear receptor
  at the target organs followed by the subsequent
  generation of appropriate biological responses.

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• An additional key component in the operation
  of the vitamin D endocrine system is the plasma
  vitamin D binding protein (DBP) that carries
  vitamin D3 and all of its metabolites to their
  various target organs

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• Apart from Vitamin D two other Hormones share
  in the regulation of Calcium and Phosphate
  Metabolism
• Parathormon
• Calcitonin

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Renal osteodystrophy is a global term applied to
all pathologic features of bone in patients with
renal failure. Primary retention of phosphate
? hyperphosphatemia ? hypocalcemia ?
secondary hyperparathyroidism Therefore, the
spectrum of clinical and radiographic findings in
renal osteodystrophy .
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What are the sources of vitamin D for humans?
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Salt water fish
Small quantities of vitamin D3 are also found in
eggs, veal, beef, butter, and vegetable oils -
while plants, fruits, and nuts are extremely poor
sources of vitamin D.
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Factors affecting dermal synthesis (sun exposure)
of vitamin D 1- season and latitude 2- Only
locations 30 or closer to the equator have
consistently intense UV-light. 3- duration of
UV sunlight 30 min per week for an
infant wearing only a nappy (diaper)
or 2 h a week fully clothed without a head cover
4- darker skin requires longer sun exposure,
however, as melanin competes with
7-dehydrocholesterol for UV-B photons 5- use of
sunscreens
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increased indoor activities, and industrial
pollution means inadequate skin exposure, means
deficient resource on Vit D.
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Treatment of Rickets

• Preventive 400 1000 IU/day
• Nutritional Rickets 3000 -6000 IU/day
• Resistant Rickets 1alpha Calcitriol
• Calcium supplemetation