Rickets_Metabolic_Bone_Diseases.ppt Homework: 1. Study material on the topic: Atopic dermatitis in children. Allergic rhinitis in children 2. Make a presentation on the topic: Congenital malformations of the bronchopulmonary system in children 6. Cytology. * Cell - the morphological basis of multicellular organisms. The general plan of cell structure. Cytoplasm - definition and composition. Classification of organelles and inclusions. ** Non-membranous organelles of general and special purpose. Cytoskeleton: intermediate filaments, microfilaments, microtubules. Classification, structure and functions of the microfilaments and microtubules. Organization of the microtubules in centrioles, axoneme, cilia and flagella. *** Molecular structure of microtubules, effect of polymerization and depolymerization of tubulins, role in cell life. Movement of organelles and vesicles along microtubules with the participation of kinesin and dynein proteins. 7. Cytology. * Cell theory is the basis of cytology. Structure of cells in multicellular organism. Structural composition of the cytoplasm. Cytoplasmic membranous organelles. Structure and functions of smooth endoplasmic reticulum. ** Relation of membranous structures in cytoplasm, and their cooperation in physiological cell processes. Synthesis, exocytosis, catabolism, endocytosis. *** Role of endoplasmic reticulum in dysfunction, aging and cell death. 8. Cytology. * The general plan of cell structure. The composition of the cytoplasm. Organelles - definition, classification. The value of organelles in cell life. Structure and functions of smooth endoplasmic reticulum. ** Specialization functions of smooth endoplasmic reticulum. Its role in the restoration of the nuclear envelope after mitosis. *** Detoxification system in the cell. Organelles and their functions. Peroxisome marker enzymes. 9. Cytology. * Definition of cytology. General structure of the cell. The cell is the smallest level of organization. Organelles: definition, classification. Structure and functions of Golgi complex. ** Connection of Golgi complex with endoplasmic reticulum. Role in lysosome formation. *** The role of the Golgi complex in plasmolemma remodeling and cell secretory activity. Exocytosis - mechanism and functional value. 10. Cytology. * The properties of the cell as a structural unit of life living. Mitochondria - features of the structure, functions. ** Features of structure of mitochondrial membranes and matrix. The role of mitochondria in lipid and carbohydrate catabolism, ATP production and thermoregulation, in the synthesis of steroid hormones. *** The concept of mitochondrial diseases. Mitochondrial regulators of apoptosis and cell survival. 11. Cytology. * Key points of cell theory. Membranous organelles of cells, their classification. Lysosomes and peroxisomes. Their similarity and difference. Types of lysosomes and role in cell lif

2.  Calcium
 Phosphate
 PTH
 Vitamin D
 Calcitonin

3.  > 99% in bone
 Muscle and nerve function
 Clotting mechanisms
 Free plasma Ca = Bound plasma Ca
 Active transport absorption in the duodenum
and passive diffusion in the jejunum
 98% reabsorption in the kidney

4.  600 mg/day in children
 1300 mg/day in adolescents and young
adults
 750 mg/day in adults
 1500 mg/day in pregnant women
 2000 mg/day in lactating women
 1500 mg/day in postmenopausal women and
patients with fractures

5.  Key component of bone mineral
 Enzyme systems and molecular interactions
 85% in bone
 Plasma Phosphate is mostly unbound
 1000-1500 mg/day

7. Vitamin D metabolism

8. Secondary role
Other Hormones
- Estrogen
- Corticosteroids
- Thyroxin
Non-hormonal Factors
- Mechanical stress
- Prostaglandin E
- Acid-base balance

10.  Normal bone growth & mineralization require adequate
availability of calcium & phosphate.
 Deficient mineralization can result in rickets and/or
osteomalacia.
 Rickets refers to the changes caused by deficient
mineralization at the growth plate.
 Osteomalacia refers to impaired mineralization of the bone
matrix.
 Rickets & osteomalacia usually occur together as long as the
growth plates are open; only osteomalacia occurs after the
growth plates have fused.

11.  Vitamin D disorders
◦ Nutritional vitamin D deficiency; Congenital vitamin D deficiency;
Secondary vitamin D deficiency; Malabsorption ; Increased
degradation; Decreased liver 25-hydroxylase; Vitamin D-dependent
rickets type 1; Vitamin D-dependent rickets type 2; Chronic renal
failure.
 Calcium deficiency
◦ Low intake, Calcium deficient Diet, Premature infants (rickets of
prematurity), Malabsorption, Dietary inhibitors of calcium absorption
 Phosphorus deficiency
◦ Inadequate intake, Premature infants (rickets of
prematurity), Aluminum-containing antacids

12.  RENAL LOSSES
◦ X-linked hypophosphatemic rickets; Autosomal dominant
hypophosphatemic rickets; Hereditary hypophosphatemic rickets
with hypercalciuria; Overproduction of phosphatonin (Tumor-
induced rickets, McCune-Albright syndrome, Epidermal nevus
syndrome, Neurofibromatosis), Fanconi syndrome, Dent disease
 DISTAL RENAL TUBULAR ACIDOSIS

13.  GENERAL Failure to thrive; Listlessness; Protuding abdomen; Muscle
weakness (especially proximal); Fractures.
 HEAD Craniotabes; Frontal bossing; Delayed fontanelle closure; Delayed
dentition; caries; Craniosynostosis
 CHEST Rachitic rosary; Harrison groove; Respiratory infections and atelectasis
 BACK Scoliosis ,Kyphosis ,Lordosis
 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; Coxa
vara; Leg pain.
 HYPOCALCEMIC SYMPTOMS Tetany ; Seizures; Stridor due to laryngeal spasm

14.  Extraskeletal manifestation of rickets vary depending upon
the mineral deficiency.
 Hypoplasia of the dental enamel is typical for hypocalcemic
rickets, whereas abscesses of the teeth occur more often in
phosphopenic rickets.
 Hypocalcemic seizures, decreased muscle tone leading to
delayed motor milestones, recurrent infections, increased
sweating.

21. Diagnostic approach to suspected rickets

22. Diagnostic approach to hypocalcimic rickets

23. Diagnostic approach to hypophosphatemic rickets

24. Biochemical findings in rickets

25.  Alkaline phosphatase usually is ↑in all forms of rickets.
 Serum phosphorus concentrations usually are↓ in both
hypocalcemic and hypophosphatemic rickets.
 Serum Ca is ↓only in hypocalcemic rickets.
 Serum parathyroid hormone typically is ↑in hypocalcemic
rickets, in contrast it is N in hypophosphatemic rickets.
 25-OH vitamin D reflect the amount of vitamin D stored in
the body, and is ↓in vit D deficiency.
 1,25-OH2 vitamin D can be↓, N or ↑in hypocalcemic rickets
and usually is N or slightly ↑in hypophosphatemic rickets.

26.  Vitamin D. Stoss therapy: 300,000-600,000 IU orally or IM in
2-4 divided doses over one day.
 High dose vit D 2000-5000 IU orally for 4-6wks followed by
400 IU daily orally as maintenance.
 Adequate dietary Calcium & phosphorus provided by milk,
formula & other dairy products.
 Symptomatic hypocalcaemia need IV Cacl as 20mg/kg or Ca
gluconate as 100mg/kg as a bolus, followed by oral calcium
tapered over 2-6 weeks.

30. *Primary
hyperplasia - adenoma - carcinoma
*Secondary
persistent hypocalcaemia
*Tertiary
secondary leads to hyperplasia

31. Pathology
- PTH overproduction
- Increased renal tubular absorption , intestinal
absorption and bone resorption of Ca
- Hypercalcaemia and hypercalciuria
- Suppressed phosphate tubular reabsorption
- Hypophosphataemia and hyperphosphaturia

32. Pathology
*Hypercalcaemia
calcinosis , stone formation , recurrent
infection and soft tissue calcification
*Bone resorption
loss of bone substance , subperiosteal
erosion
osteitis fibrosa cystica and brown tumors

33. Symptoms & Signs
*Hypercalcaemia
anorexia , nausea , depression and polyuria
*Bone rarefaction
pain , pathological fractures and
deformities
*Biochemistry
hypercalcaemia , hypophosphataemia ,
high
alk. Phosphatase and serum PTH

35. X-rays
- Subperiosteal bone resorption
- Generalized decrease in bone density
- Brown tumors
- Chondrocalcinosis
knee , wrist and shoulder

42. Treatment
 Surgical excision of adenoma or
hyperplastic parathyroid tissue
 Hungry bone syndrome
◦ Treated by vitamin D

43. * Normal mineralization
* Decrease bone mass
(amount of bone per unit volume)
* Age related
* Associated or manifestation of other
conditions

44. Causes
* Idiopathic
* Nutritional
* Endocrine disorders
* Drug induced
* Malignant diseases
* Miscellaneous

46. - Idiopathic osteoporosis - normal investigations
- In old patients we have to role out malignancy
and multiple myeloma
- Younger patients must be fully investigated
- Several causes may be involved
- Osteoporosis can be associated with
osteomalacia

47. Symptoms & Signs
- Bony aches
- Easy fractures
spine - lower radius - femoral neck
- Rib fracture , chest pain
- Normal biochemistry

49. X-rays
- Decrease bone density
- Wedging or biconcave vertebrae
- Thin cortex and deformities
- Dexa Scan
- Biopsy

56. Treatment
- Treat underlying cause
- Idiopathic , extremely difficult
- Calcium and vitamin D
- Fluoride and triple therapy
- Calcitonin , Diphosphonate
- Treat fractures

58. Prevention
* Good diet
* Exercise
* Exposure to sun light
* Ca supplement
* Hormone therapy

59.  Diminished renal P excretion
 Increased Ca excretion
 Impaired synthesis of Vit D
 Toxicity e.g. Aluminum and amyloidosis