lecturer: prof. pavlyshyn g.a. rickets: etiology, pathogenesis, clinical features, diagnostics,...

Lecturer: prof. Pavlyshyn G.A.Lecturer: prof. Pavlyshyn G.A.

Rickets:Rickets:Etiology, pathogenesis, clinical features, Etiology, pathogenesis, clinical features, diagnostics, treatment and preventiondiagnostics, treatment and prevention

Rickets is a childhood disorder involving softening and weakening of the bones.

It is primarily caused by lack of vitamin D, calcium, or phosphate.

Vitamin D is a fat-soluble vitamin that may be absorbed from the intestines or may be produced by the skin when the skin is exposed to sunlight (ultraviolet light of sunlight helps the body to form vitamin D).

The absorbed vitamin D is converted into its active form to act as a hormone to regulate calcium absorption from the intestine and to regulate levels of calcium and phosphate in the bones.

If there is a deficiency of Vitamin D, the body is unable to properly regulate calcium and phosphate levels. When the blood levels of these minerals become too low, it results in destruction of the support matrix of the bones.

Sunlight as a source of vitamin D

Lack of vitamin D production by the skin may occur if a person is confined indoors, or works indoors during

the daylight hours, or lives in climates with little

exposure to sunlight.

Sunlight is important to skin production of vitamin D and environmental

conditions where sunlight exposure is limited may

reduce this source of vitamin D.

Sunlight as a source of vitamin D

Adequate supplies of vitamin D3 can be

synthesized with sufficient exposure to solar

ultraviolet B radiation

Melanin, clothing or sunscreens that absorb

UVB will reduce cutaneous production of vitamin D3

Rickets In rickets, another mechanism in the body works to increase

the blood calcium level. The parathyroid gland may increase its functioning rate to compensate for decreased levels of calcium in the bloodstream.

To increase the level of calcium in the blood the hormone destroys the calcium present in the bones of the body and this results in further loss of calcium and phosphorous from the bones. In severe cases, cysts may develop in the bones.

Vitamin D deficiency could be caused due to numerous

reasons

• What are the causes for deficiency of Vitamin D?

Reasons of vitamin D deficiency• Environmental conditions where sunlight exposure

is limited like indoor confinement or working indoors during daylight hours may reduce source of vitamin D;

• Inadequate daily consumption - a lack of vitamin D in the diet, a dietary lack of calcium and phosphorous may also play a part in nutritional causes of rickets, have trouble digesting milk products, people who are lactose intolerant;

• Liver Failure;• Dark Pigmentation

Reasons of deficiency vitamin D • Problem of malabsorption called steatorrhea, in

which the body is unable to absorb fats, and they are passed directly out the body in the stool. The result of this problem is that Vitamin D, which is usually absorbed with fat, and calcium are poorly absorbed. This poor absorption can be a result of digestive disorders. Steatorrhea could also lead to other deficiencies.

• Kidney Failure (congenital or acquired kidney disorders) - due to tubular acidosis in which there is an increased amount of acid in the body;

Etiology

1. Lack of sunshine due to:

• 1) Lack of outdoor activities

• 2) Lack of ultraviolet light in fall and winter

• 3) Too much cloud, dust, vapour and smoke

Etiology

2. Improper feeding:

1) Inadequate intake of Vitamin D

• Breast milk 0-10IU/100ml

• Cow’s milk 0.3-4IU/100ml

• Egg yolk 25IU/average yolk

• Herring 1500IU/100g

2) Improper Ca and P ratio

Etiology

3. Fast growth, increased requirement (relative deficiency)

4. Diseases and drug:

• Liver diseases, renal diseases

• Gastrointestinal diseases

• Antiepileptic

• Glucocorticosteroid

Cholecalciferol (vitamin D-3) is formed in the skin from 7-dihydrotachysterol. This steroid undergoes hydroxylation in 2 steps.

Pathophysiology - Metabolism of vitamin D

• The first hydroxylation occurs at position 25 in the liver, producing calcidiol (25-hydroxycholecalciferol), which circulates in the plasma as the most abundant of the vitamin D metabolites and is thought to be a good indicator of overall vitamin D status.

• Cholecalciferol (vitamin D-3) is formed in the skin from 7-dihydrotachysterol. This steroid undergoes hydroxylation in 2 steps.

Pathophysiology

• The second hydroxylation step occurs in the kidney at the 1 position, where it undergoes hydroxylation to the active metabolite calcitriol (1,25-dihydroxycholecalciferol - DHC). This cholecalciferol is not a vitamin, but a hormone.

Vitamin D: The Sunshine Vitamin

• Not always essential– Body can make it if

exposed to enough sunlight

– Made from cholesterol in the skin

Pathway of Vitamin D Production

Calcitriol acts on regulation of calcium metabolism:

• Calcitriol promotes absorption of calcium and phosphorus from the intestine,

• increases reabsorption of phosphate in the kidney,

• acts on bone to release calcium and phosphate;

• Calcitriol may also directly facilitate calcification.

Calcitriol (1,25-DHC) – acts as a hormone rather than a vitamin, endocrine and paracrine properties

• These actions increase the concentrations of calcium and phosphorus in extracellular fluid.

• The increase of Ca and P in extracellular fluid, in turn, leads to the calcification of osteoid, primarily at the metaphyseal growing ends of bones but also throughout all osteoid in the skeleton.

• Parathyroid hormone facilitates the 1-hydro-xylation step in vitamin D metabolism

Pathogenesis

• Vitamin D deficiency

• Absorption of Ca, P

• Serum Ca

• Function of Parathyroid

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

Pathogenesis

• Low secretion of PTH

• Failure of decalcification of bone

• Low serum Ca level

• Rachitic tetany(Spasmophylia)

• In the vitamin D deficiency state, hypocalciemia develops, which stimulates excess parathyroid hormone, which stimulates renal phosphorus loss, further reducing deposition of calcium in the bone.

• Excess parathyroid hormone also produces changes in the bone similar to those occurring in hyperparathyroidism.

• Early in the course of rickets, the calcium concentration in the serum decreases.

• After the parathyroid response, the calcium concentration usually returns to the reference range, though phosphorus levels remain low.

• Alkaline phosphatase, which is produced by overactive osteoblast cells, leaks to the extracellular fluids so that its concentration rises to anywhere from moderate elevation to very high levels.

The history in patients with rickets may include the following:

• The infant's gestational age, diet and degree of sunlight exposure should be noted.

• A detailed dietary history should include

specifics of vitamin D and calcium intake.

• A family history of short stature, orthopedic abnormalities, poor dentition, alopecia, parental consanguinity may signify inherited rickets.

Evaluation

Clinical signs

Rickets

• is a systematic disease with

skeletons involved most, but the

nervous system, muscular system

and other system are also involved.

• Generalized muscular hypotonia is observed in the most patients with clinical signs of rickets.

• Craniotabes manifests early in infants, although this feature may be normal in infants, especially for those born prematurely.

Clinical signs

• If rickets occurs at a later age, thickening of the skull develops. This produces frontal bossing and delays the closure of the anterior fontanelle.

Frontal bossing

Protruding foreheadasymmetrical or odd-shaped skull

• Skeletal deformities including Bow legs, Forward projection of the breastbone - pigeon chest or pectus carinatum),Funnel chest(pectus excavatum), "Bumps" in the rib cage (rachitic rosary) and asymmetrical or odd-shaped skull;

Chest deformity

Funnel chest – pectus excavatum

Pigeon chest

Clinical signs

• In the chest, knobby deformities results in the rachitic rosary along the costochondral junctions.• The weakened ribs pulled by muscles also produce flaring over the diaphragm, which is known as Harrison groove. • The sternum may be pulled into a pigeon-breast deformity. Rib beading

(rachitic rosary)

Pathway of Vitamin D Production

• Bowlegs and knock-knees.

Clinical signs

Knock knee deformity (genu valgum)

Bowleg deformity (genu varum)

Vitamin D Deficiency - Rickets

Bowlegs and knock-knees

Pelvic deformities

A teenage male with rickets. Note deformities of legs (bow legs) and compromised height.

• The ends of the long bones demonstrate that same knobby thickening. At the ankle, palpation of the tibial

Clinical signs

malleolus gives the impression of a double epiphysis (Marfan sign).

Clinical signs

• Increased tendency toward bone fractures. Because the softened long bones may bend, they may fracture one side of the cortex (greenstick fracture).

• In the long bones, laying down of uncalcified osteoid at the metaphases leads to spreading of those areas, producing knobby deformity (cupping and flaring of the metaphyses).

• Spine deformities (spine curves abnormally, including scoliosis or kyphosis). • In more severe instances in children older than 2 years, vertebral softening leads to kyphoscoliosis

Clinical signs

• Pain in the bones of Arms, Legs, Spine, Pelvis.

• Dental deformities

• Delayed formation of teeth

• Defects in the structure of teeth

• Holes in the enamel

• Increased incidence of cavities in the teeth (dental caries)

Clinical signs

• Progressive weakness• Decreased muscle tone (loss of muscle

strength)• Muscle cramps• Impaired growth• Short stature (adults less than 5 feet tall)• Fever or restlessness, especially at night

Clinical signs

Bowlegs and knock-knees

Short stature

In children with rickets, complete physical and dental examinations should be performed. The entire skeletal system must be palpated to search for tenderness and bony abnormalities. Rickets should be suspected in older bowlegged children and in cases associated with asymmetry, pain, or progression in severity.

Physical examination

Gait disturbances and neurologic abnormalities (such as hyperreflexia) in

all children should be sought.

The review of systems should focus on growth

and orthopedic concerns and signs and symptoms of hypocalcemia, such as

muscle cramps, numbness, paresthesias,

tetany and seizures.

Laboratory findings

Laboratory investigation may include:• serum levels of calcium (total and ionized

with serum albumin), • phosphorus, • alkaline phosphatase (ALP) • parathyroid hormone, • urea nitrogen, • calcidiol• urine studies include urinalysis and levels

of urinary calcium and phosphorus.

Decreases

in serum calcium, serum phosphorus, calcidiol, calcitriol, urinary calcium.

The most common laboratory findings in nutritional rickets are:

Parathyroid hormone, alkaline phosphatase,

urinary phosphorus levels are elevated.

• Early on in the course of rickets, the calcium (ionized fraction) is low; however it is often within the reference range at the time of diagnosis as parathyroid hormone levels increase.

• Calcidiol (25-hydroxy vitamin D) levels are low, and parathyroid hormone levels are elevated; however, determining calcidiol and parathyroid hormone levels is typically not necessary.

• Calcitriol levels may be normal or elevated because of increased parathyroid activity.

• The phosphorus level is invariably low for age.• Alkaline phospohatase levels are elevated.• A generalized aminoaciduria occurs from the parathyroid

activity; aminoaciduria does not occur in familial hypophosphatemia rickets (FHR).

Laboratory Studies

• Classic radiographic findings include:

widening of the distal epyphysis, fraying and widening of the metaphysis, and angular deformities of the arm and leg bones.

Classic radiographic findings include

Anteroposterior and lateral radiographs of the wrist of an 8-year-old boy with rickets demonstrates cupping and fraying of the

metaphyseal region

• Classic radiographic findings include:

Radiographs of the knee of a 3-year-old girl with hypophosphatemia depict severe fraying of the metaphysis.

Rickets in wrist - uncalcified lower ends of bones are porous, ragged, and saucer-shaped

(A) Rickets in 3 month old infant

(B) Healing after 28 days of treatment

(C) After 41 days of treatment

A

B C

Radiographic image of wrist and forearm showing pathologic fractures of radius and ulna with rachitic changes of distal end of radius and ulna.

X-ray in rickets

Clinical manifestationStages

• Early stage• Usually begin at 3 months old• Symptoms: mental psychiatric symptoms• Irritability, sleepless, hidrosis• Signs: occipital bald• Laboratory findings: Serum Ca, P normal or

decreased slightly, AKP normal or elevated slightly, 25(OH)D3 decreased

• Roentgen-graphic changes: normal or slightly changed

Clinical manifestation

Advanced stage• On the base of early rickets, osseous changes

become marked and motor development becomes delayed.

1. Osseous changes:1) Head: craniotabes, frontal bossing, boxlike

appearance of skull, delayed closure of anterior fontanelle

2) Teeth: delayed dentition with abnormal order, defects

3) Chest: rachitic rosary, Harrison’s groove, pigeon chest, funnel-shaped chest, flaring of ribs


4) Spinal column: scoliosis, kyphosis, lordosis

5) Extremities: bowlegs, knock knee, greenstick fracture

6) Rachitic dwarfism

2. Muscular system: potbelly, late in standing and walking

3. Motor development: delayed

4. Other nervous and mental symptoms


Laboratory findings:• Serum Ca and P decreased• Ca and P product decreased• AKP elevated

Roentgen-graphic changes: Wrist is the best site for watching the changesWidening of the epiphyseal cartilageBlurring of the cup-shape metaphyses of long bone


Healing stage:• Symptoms and signs of Rickets alleviate or

disappear by use of appropriate treatment. • The blood chemistries become normal, except

AKP, that may be slightly elevated.

Sequelae stage:• All the clinical symptoms and signs disappear.• Blood Chemistries and X-ray changes are

recovered, but osseous deformities may be left.• Usually seen in Children after 3 years old.

• I Mild form: small changes of nervous system, changes of one part of the skeleton;

• II Moderate form: changes of all organs and systems, changes of two parts of the skeleton;

• III Severe form: damaging function of all organs and systems, changes of three parts of the skeleton;

Classification

Types of Rickets

Nutritional

Nutritional rickets results from inadequate sunlight exposure or inadequate intake of dietary vitamin D, calcium, or phosphorus.

Vitamin D dependent

• Vitamin D-dependent rickets, type I is secondary to a defect in the gene that codes for the production of renal 25(OH)D3-1-alpha-hydroxylase.

• Vitamin D-dependent rickets, type II is a rare autosomal disorder caused by mutations in the vitamin D receptor. Type II does not respond to vitamin D treatment; elevated levels of circulating calcitriol differentiate this type from type I.

Vitamin D resistant

• Rickets refractory to vitamin D treatment may be caused by the most common heritable form, known as vitamin D-resistant rickets or familial hypophosphatemic rickets.

• Because of mutations of the phosphate-regulating

gene on the X chromosome, renal wasting of phosphorus at the proximal tubule level results in hypophosphatemia. Normal levels of calcitriol are found in this disorder.

Other Conditions That Can Cause Rickets• Medications

– Antacids– Anticonvulsants– Corticosteroids– Loop diuretics

• Malignancy• Prematurity• Diseases of organs associated with vitamin D and

calcium metabolism– Kidney disease– Liver and biliary tract disease

• Malabsorption syndromes– Celiac disease– Cystic fibrosis (rare)

Diagnosis

• Assessed according to the followings:

• 1. History

• 2. Physical examination

• 3. Laboratory findings

• 4. Roentgen-graphic changes

What's the treatment for rickets?

• The replacement of Vitamin D may correct rickets using these methods of ultraviolet light and medicine. Rickets heals promptly with 4000 IU of oral vitamin D per day administered for approximately one month.

• Parents are instructed to take their infants outdoors for approximately 20 minutes per day with their faces exposed. Children should also be encouraged to play outside.

• Foods that are good sources of vitamin D include cod liver oil, egg yolks, butter and oily fish. Some foods, including milk and breakfast cereals, are also fortified with synthetic vitamin D.

Treatment

1. Special therapy: Vitamin D therapy

• A. General method: Vitamin D 2000-4000 IU/day

for 2-4 weeks, then change to

preventive dosage – 400 IU.

• B. A single large dose: For severe case, or Rickets with complication, or those who can’t bear oral therapy.

Vitamin D3 200000 – 300000 IU, im,

preventive dosage will be used after 2-3 months.

TREATMENT

1 STAGE

• VITAMINE D – “VIDEIN – 3” - 2000 IU 1 TIME\DAY 30 DAYS

2 STAGE


3 STAGE


Then profilactic dose – 500 iu till the end of the second – third year of life

• Vitamin D• Fat-soluble vitamin used to treat vitamin D

deficiency or for prophylaxis of deficiency.•

Cholecalciferol (Delta-D)• Vitamin D-3 1 mg provides 40000 IU vitamin D

activity

Treatment

4. Calcium supplementation: Dosage: 1-3 g/day• only used for special cases, such as baby

fed mainly with cereal or infants under 3 months of age and those who have already developed tetany.

5. Plastic therapy:

In children with bone deformities after 4 years old plastic surgery may be useful.

Prevention

1. Pay much attention to the health care of pregnant and lactating women, instruct them to take adequate amount of vitamin D.

2. Advocate sunbathing

3. Advocate breast feeding, give supplementary food on time

Prevention

Vitamin D supplements• Because of human milk contains only a small amount

of vitamin D, the American Academy of Pediatrics (AAP) recommends that all breast-fed infants receive 400 IU of oral vitamin D daily beginning during the first two months of life and continuing until the daily consumption of vitamin D-fortified formula or milk is two to three glasses, or 500 mL.

• AAP also recommends that all children and adolescents should receive 400 IU a day of vitamin D.

Prevention

Vitamin D supplementation: In prematures, twins and weak babies, give

Vitamin D 800IU per day, For term babies and infants the demand of

Vitamin D is 400IU per day, For those babies who can’t maintain a daily

supplementation, inject muscularly Vitamin D3 100000-200000 IU.

Prevention

Calcium supplementation: 0.5-1gm/day, for premature, weak babies and babies fed mainly with

cereal

• Recommended daily intake of calcium is as follows: • 1 to 3 years of age. 500 mg (two servings of dairy products a day) • 4 to 8 years of age. 800 mg (two to three servings of dairy products a

day) • 9 to 18 years of age. 1,300 mg (four servings of dairy products a day) • 19 to 50 years of age. 1,000 mg a day (three servings of dairy products

a day)

Sources of Vitamin DSources of Vitamin D

Sunlight is the most important source

Fish liver oil

Fish & sea food (herring & salmon)

Eggs

Plants do not contain vitamin D3

Food (approximate serving)

Amount of calcium (approximate mg)

Breast milk (500 ml) 125

Formula, cow's milk-based (500 ml)

265

Dairy products

Cheddar cheese (30 g) 200

Cow's milk (1 cup) 250

Ice cream (1 cup) 150

Yogurt (120 g) 150

Fast foods

Cheeseburger 20

Chicken nuggets (four to six pieces)

13

French fries (small order) 10

Pizza (one slice) 145

Greens

Cabbage (collard) (1/2 cup, cooked)

150

Spinach (1 cup, cooked) 150

Spasmophylia (children's tetany)

disease, in the basis of which disturbances of mineral metabolism (decrease of concentration of ionized calcium in a blood) lies.

It is characterized increased nervous-muscle exiting and predilection to tonic and clonic cramps of separate groups of muscles, in particular larynxes, legs and arms.

Etiology: hypovitaminosis D, hypoparathyreoidis

Latent form

By a sign Hvostek — simple tapping the cheek over the facial nerve causes involuntary contraction of the muscles about the eye or mouth (spasm of facial muscles occurs when the facial nerve is tapped)

By Trousseau's Sign — is the carpal or pedal spasm, induced by compression of the arm or thigh during 3-5 minutes (by the cuff for measurement of arterial pressure) when hands assume the so-called “obstetrical position”, while the feet are held in a position of equinas;

By a sign Maslow — stop of breathing at a mild skin pricks

By a sign Еrba — increased reaction to electrical stimulation of the median or peroneal nerve (by a galvanic current smaller than 5 mа)

The manifestive form

The three most characteristic symptoms are:

• 1. Laryngo-spasm or laryngismus stridulus;

• 2. Tetany or carpo-pedal spasm;

• 3. Eclampsia, or general convulsions.

Treatment

I. First aid.• At a laryngospasm - to clap on cheeks, to wash by cold water;• At cramps - Seduxen (0,5 % solution, 0,1 mg/kg), simultaneously a calcium

drug - 20 mg/kg elemental calcium IV over 10-20 minutes• Equal to:

2 mL/kg 10% calcium gluconate0.7 mL/kg 10% calcium chloride

ІІ. Correction of a feed (limitation of the cow milk, increase vegetables and fruits).

• Drugs of calcium (10 % solution of calcium of a gluconate at the rate of 50mg/kg/day).

• After normalization of a level of calcium in a blood - treatment by vitamin D3 (2000-5000 МО 30-45 days depending on a degree of gravity of a rickets).

• What are the signs and symptoms associated with hypervitaminosis of Vit. D.

TOXICITYTOXICITY

•Hypervitaminosis DHypervitaminosis D

causes hypercalcemia, which manifest as:

Nausea & vomiting

Excessive thirst & polyuria

Severe itching

Joint & muscle pains

Disorientation & coma.

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

Rachitic vs. normal chick

develop signs of rickets.

lecturer: prof. pavlyshyn g.a. rickets: etiology, pathogenesis, clinical features, diagnostics,...

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