Diseases of joints

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Transcript of Diseases of joints

  • 1. JOINT PATHOLOGY www.freelivedoctor.com

2. www.freelivedoctor.com 3. Modeling/RE-modeling www.freelivedoctor.com 4. CELLS of BONE

  • OSTEOPROGENITOR (STEM) (TGF )
  • OSTEOBLASTS (surface of spicule)
  • OSTEOCYTES (completely within spicule)
  • OSTEOCLASTS (macrophage lineage)

www.freelivedoctor.com 5. Proteins (organic) of BONE

  • Type 1 collagen (90%)
  • Cell adhesion proteins
  • Calcium-binding proteins
  • Proteins involved in mineralization
  • Enzymes
  • Growth factors
    • GF-1, TGF-, PDGF
  • Cytokines
    • Prostaglandins, IL-1, IL-6, RANKL
  • Proteins Concentrated from Serum
    • 2 microglobulinAlbumin
    • IGF, insulin-like growth factor
    • TGF, transforming growth factor
    • PDGF, platelet-derived growth factor
    • IL, interleukin
    • RANKL, RANK ligand

www.freelivedoctor.com 6. Minerals (INorganic) of BONE

  • HYDROXY-APATITE
  • Ca5(PO4)3(OH)
  • Ca10(PO4)6(OH)2

www.freelivedoctor.com 7. ADJECTIVES of BONE

  • Compact
  • Spongy
  • Cancellous
  • Membranous
  • Dense
  • Cortical
  • Endosteal
  • Woven
  • Lamellar
  • Spicular

www.freelivedoctor.com 8. Woven vs Lamellar www.freelivedoctor.com 9. www.freelivedoctor.com 10. - BLASTS/-CLASTS www.freelivedoctor.com 11. BONE DISEASES

  • 1) MALFORMATIONS AND DISEASES CAUSED BY DEFECTS INNUCLEAR PROTEINS AND TRANSCRIPTION FACTORS,polydactyly, syndactyly, absence of a bone
  • 2) DISEASES CAUSED BY DEFECTS INHORMONES AND SIGNAL TRANSDUCTION MECHANISMS,achondroplasia, thanatophoria
  • 3) DISEASES ASSOCIATED WITH DEFECTS INEXTRACELLULAR STRUCTURAL PROTEINS
    • Type 1 Collagen Diseases (Osteogenesis Imperfecta)
    • Types 2, 10, and 11 Collagen Diseases
  • 4) DISEASES ASSOCIATED WITH DEFECTS INFOLDING AND DEGRADATION OF MACROMOLECULES
    • Mucopolysaccharidoses
  • 5) DISEASES ASSOCIATED WITH DEFECTS INMETABOLIC PATHWAYS(ENZYMES, ION CHANNELS, AND TRANSPORTERS)
    • Osteopetrosis
  • 6) DISEASES ASSOCIATED WITHDECREASED BONE MASS
    • Osteoporosis
  • 7) DISEASES CAUSED BYOSTEOCLAST DYSFUNCTION
    • Paget Disease (Osteitis Deformans)
  • 8) DISEASES ASSOCIATED WITHABNORMAL MINERAL HOMEOSTASIS
    • Ricketts and Osteomalacia
    • Hyperparathyroidism
    • Renal Osteodystrophy

www.freelivedoctor.com 12. 1) MALFORMATIONS AND DISEASES CAUSED BY DEFECTS INNUCLEAR PROTEINS AND TRANSCRIPTION FACTORS

  • Congenital absence of a, usually single, bone: phalanx, rib, clavicle
  • Supernumerary digit (polydactyly)
  • Syndactyly
  • CRANIORACHISCHISIS

www.freelivedoctor.com 13. www.freelivedoctor.com 14. 2) DISEASES CAUSED BY DEFECTS INHORMONES AND SIGNAL TRANSDUCTION MECHANISMS

  • Achondroplasia, dwarf (non-lethal)
  • Thanatophoria, dwarf (lethal)
  • a point mutation (usually Arg for Gly375) in the gene that codes for FGF receptor 3 (FGFR3), which is located on the short arm of chromosome 4.In the normal growth plate, activation of FGFR3inhibitscartilage proliferation;
  • A MUTATION causes FGFR3 to be constantly activated.

www.freelivedoctor.com 15. www.freelivedoctor.com 16. 3) DISEASES ASSOCIATED WITH DEFECTS INEXTRACELLULAR STRUCTURAL PROTEINS

  • OSTEOGENESS IMPERFECTA TYPES
  • (Brittle bone disease, too LITTLE bone),BLUEsclerae
  • Mutations in genes which code for the alpha-1 and alpha-2 chains of COLLAGEN 1
  • Mutations of COLLAGEN 2,10, 11 manifest themselves as CARTILAGE diseases, ranging from joint cartilage destruction to fatal

www.freelivedoctor.com 17. Osteogenesis Imperfecta www.freelivedoctor.com 18. 4) DISEASES ASSOCIATED WITH DEFECTS INFOLDING AND DEGRADATION OF MACROMOLECULES

  • MUCOPOLYSACCHARIDOSIS (one of MANY lysosome storage diseases)
  • DECREASES in ENZYMES which degrade:
    • DERMATAN
    • HEPAR A N
    • KERAT A N
  • Chiefly CARTILAGE disorders: short, chest wall, malformed bones

www.freelivedoctor.com 19. MUCOPOLYSACCHARIDOSES www.freelivedoctor.com 20. 5) DISEASESASSOCIATED WITHDEFECTS INMETABOLIC PATHWAYS(ENZYMES, IONCHANNELS, AND TRANSPORTERS)

  • OSTEOPETROSIS, 4 types
  • One common one has a CARBONIC ANHYDRASE deficiency
  • DECREASED osteoclast resorption
  • MARBLE bone, brittle, sclerosis

www.freelivedoctor.com 21. OSTEOPETROSIS www.freelivedoctor.com 22. 6) DISEASES ASSOCIATED WITHDECREASED BONE MASS

  • OSTEOPOROSIS
  • PEAK bone mass is early adulthood
  • Normal decline, slow
  • Osteoporosis is accelerated bone loss
  • Factors:
    • AGE
    • Physical activity
    • Estrogen
    • Nutrition (Ca++)
    • Genetics

www.freelivedoctor.com 23. www.freelivedoctor.com Categories of Generalized Osteoporosis Primary Postmenopausal Idiopathic Senile Secondary Endocrine disorders Rheumatologic disease Hyperparathyroidism Drugs Hypo-hyperthyroidism Anticoagulants Hypogonadism Chemotherapy Pituitary tumors Corticosteroids Diabetes, type 1 Anticonvulsants Addison disease Alcohol Neoplasia Miscellaneous Multiple myeloma Osteogenesis imperfecta Carcinomatosis Immobilization Gastrointestinal Pulmonary disease Malnutrition, Malbs., Hepatic Insuf., Vit C,D Homocystinuria Anemia 24. OSTEOPOROSIS www.freelivedoctor.com 25. 7) DISEASES CAUSED BYOSTEOCLAST DYSFUNCTION Paget Disease (Osteitis Deformans)

  • Matrix madness, Osteoblasts/-cytes gone wild
  • THREE PHASES:
    • 1) Increased osteoclast resorption
    • 2) Increased hectic bone formation (osteoblasts)
    • 3) Osteosclerosis
  • ELEVATED ALKALINE-PHOSPHATASE
  • ELEVATED urine HYDROXYPROLINE

www.freelivedoctor.com 26. PAGETs DISEASE (of BONE) 85% MONOSTOTIC, WHOLE BONE 15% POLY-OSTOTIC (skull, pelvis) JIGSAW, NOT LAMINAR, BONE CLINICAL:PAIN!!! (MICROFRACTURES) www.freelivedoctor.com 27. PAGETs DISEASE www.freelivedoctor.com 28. 8) DISEASES ASSOCIATED WITHABNORMAL MINERAL HOMEOSTASIS

    • Ricketts and Osteomalacia
      • VITAMIN D deficiency/dysfunction
    • Hyperparathyroidism, PRIMARY (PTH ADENOMA)
      • ENTIRE SKELETON
      • OSTEITIS FIBROSIS CYSTICA (von Recklinghausens disease (of bone)
      • BROWN TUMOR
    • Hyperparathyroidism, SECONDARY (RENAL) (NOT AS SEVERE AS 1 )
    • Renal Osteodystrophy=ANY bone disorder due to chronic renal disease

www.freelivedoctor.com 29. PRIMARY HYPERPARATHYROIDISM www.freelivedoctor.com OSTEITIS FIBROSA CYSTICA BROWN TUMOR 30. RENAL OSTEODYSTROPHY

  • PHOSPHATE RETENTION
  • HYPOPHOSPHATEMIA
  • HYPOCALCEMIA
  • INCREASED PTH
  • INCREASED OSTEOCLASTS
  • METABOLIC ACIDOSISrelease of HYDROXYAPATITES from matrix

www.freelivedoctor.com 31. FRACTURES www.freelivedoctor.com 32. FRACTURES, adjectives

  • Complete, incomplete
  • Closed, open (communicating)
  • Communited (splintered)
  • Displaced (NON-aligned)
  • PATHOGENIC, (non-traumatic, 2 to other disease, often metastases)
  • STRESS fracture

www.freelivedoctor.com 33. FRACTURES

  • THREE PHASES
    • HEMATOMA, minutes days PGDF, TGF- , FGF
    • SOFT CALLUS (PRO-CALLUS), ~1 week
    • HARD CALLUS (BONY CALLUS), several weeks
  • COMPLICATIONS
    • PSEUDARTHROSIS
    • INFECTION (especially OPEN [communicating] fractures)

www.freelivedoctor.com 34. FRACTURES www.freelivedoctor.com 35. OSTEONECROSIS

  • Also called AVASCULAR necrosis
  • Also called ASEPTIC necrosis
  • CAUSE:ISCHEMIA
    • Trauma