1 / 30

Diseases of the Musculoskeletal System

Diseases of the Musculoskeletal System. Lecture 9 Thursday, February 1, 2007 Refs. Basic Pathology Chapter 21, p. 136-139 and 771-777 Review of Medical Physiology Ganong Chapter 21. Bone disease associated with hyperparathyroidism. Parathyroid hormone activates osteoclasts.

missy
Download Presentation

Diseases of the Musculoskeletal System

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Diseases of the Musculoskeletal System Lecture 9 Thursday, February 1, 2007 Refs. Basic Pathology Chapter 21, p. 136-139 and 771-777 Review of Medical Physiology Ganong Chapter 21

  2. Bone disease associated with hyperparathyroidism • Parathyroid hormone activates osteoclasts. • Primary hyperparathyroidism • Rare, tumor of parathyroid gland secreting PTH • Secondary hyperparathyroidism • Renal disease factors in addition to high PTH: • Decreased production of vitamin D. • Decreased calcium absorption from gut. • Metabolic acidosis. • Paraneoplastic syndrome • Nutritional • Lack of calcium in diet

  3. Paget Disease (Osteitis Deformans) • Etiology unknown, possibly paramyxovirus • Higher incidence in whites in England, France, Australia, New Zealand, USA • Rare in Scandinavia, China, Japan, and Africa • Affects middle-aged or older adults • Often asymptomatic • 3 phases (repeating and overlapping) • Osteolytic, haphazard, inappropriate osteoclastic activity • Mixed- osteolysis and rapid bone formation • Osteosclerotic • Net effect more bone (woven bone), but weaker • Pain and predisposition to fractures and tumors

  4. Paget Disease Mosaic pattern PBD 28-13BP 21-5New bone is woven bone--lacks normal lamellar architecture.

  5. Osteomyelitis (infection of bone and marrow) • Acute osteomyelitis • Pyogenic bacteria • 80-90% are Staphylococcus aureus • Pneumococci and gram negative organisms • Mixed bacteria -- common after trauma • Route • Hematogenous - more common in infants and young children • Penetrating injury- compound or open fracture • Extension from adjacent infection • Sequestrum (necrotic bone) • complicates healing • Acts as a foreign body and haven for microorganisms

  6. Chronic osteomyelitis with sequestrum BP 21-3PBD 28-19Often draining tracts open onto the skin.

  7. Osteosarcoma • The most common primary malignant tumor of bone. • The neoplastic mesenchymal cells produce osteoid. • 75% of cases occur in patients < 20 years old. • Males are more often affected. • Hereditary Rb gene mutation increases risk. • Mutations in other tumor supressor (p53) or oncogenes are often found in sporadic tumors • May metastasize before diagnosis, often to lungs. • Long-term survival now 60%.

  8. Osteosarcomadistribution PBD 28-22

  9. Osteosarcoma Gross lesion PBD 28-23(or see BP 21-6)

  10. Osteosarcoma WHP. 22.6

  11. Diseases of cartilage • Achondroplasia • Usually due to autosomal dominant mutation of gene for fibroblast growth receptor 3. • 80% of cases represent spontaneous mutation • Affects bones formed by endochondral ossification. • Disproportionate shortening of the proximal extremities • Osteochondroma (exostosis) a tumor-like lesion • Mature bone with cartilage cap. • Chondroma (benign tumor of cartilage) • Chondrosarcoma • Arise in central region of skeleton. • Lungs are common site of metastases.

  12. Osteochondroma WHP 22-10See BP 21-8 for gross appearance.

  13. Chondroma WHP 22.7

  14. Diseases of skeletal muscle • Muscle atrophy • Myasthenia gravis • antibodies to the AChR • early signs ptosis and double vision • Inflammatory myopathies • polymyositis, dermatomyositis • Muscular dystrophies • Neoplasia • rhabdomyoma • rhabdomyosarcoma

  15. Denervation atrophy BP21-20Typical angular shrunken appearance of denervated cells.

  16. Infantile spinal muscular atrophy BP 21-21Many rounded atrophic fibers and few hypertrophic fibers.

  17. Muscular Dystrophies • A group of inherited disorders • Spontaneous, progressive degeneration of fibers • Duchenne- most severe, short life expectancy • X-linked, deletions in dystrophin gene • Dystrophin cannot be detected in muscle. • Becker- slower, less severe, near normal lifespan • X-linked, mutation in dystrophin gene • Reduced levels of dystrophin • Autosomal recessive forms involve other genes related to muscle cytoskeleton

  18. Dystrophin • A huge protein (mol wt. 427,000). • Connects actin filaments to b-dystroglycan in the sarcolemma. • b-dystroglycan is attached to laminin in the ECM and associated with other transmembrane sarcoglycans proteins. • The dystrophin-glycoprotein complex appears provide structural support to transmit the force of contraction to the cytoskeleton of the muscle.

  19. Dystrophin-glycoprotein complex Ganong 3.4

  20. Duchenne muscular dystrophy PBD 29-10Variable size and shape of fibers; some regeneration (basophilic with enlarged nuclei).

  21. Stain for dystrophin BP21-23Left has normal dystrophin; right is Becker muscular dystrophy; no dystrophin would be seen in Duchenne muscular dystrophy.

  22. Duchenne Muscular dystrophy • Clinical manifestations begin at about 5 years. • Muscle weakness-- especially proximal muscles. • Progress to wheelchair-bound by teens and usually death in 20s. • Death is usually due to progressive respiratory failure or pneumonia. • Cardiac muscle also requires dystrophin; congestive heart failure and other cardiac abnormalities occur.

  23. Oculopharyngeal muscular dystrophy • Autosomal dominant • Gene localized to 14q11-q13 • Onset of disease in mid adult life • Ptosis and weakness of extraocular muscles • Difficulty swallowing • Similar clinical signs are seen in early myasthenia gravis. • Histology- dystrophic myopathy with vacuoles in type 1 fibers

  24. Overview of joint diseases • Degenerative joint disease (Osteoarthritis) • Loss of articular cartilage, eburnation • Pain, limitation of movement • Rheumatoid arthritis • Systemic disease, symmetrical joints, destruction of joints, infectious trigger ?, autoimmune disease • Infectious arthritis • Suppurative- hematogenous, local extension, trauma • Lyme-80% of infected develop arthritis • Gout • Long-standing hyperuricemia • Deposition of urate crystals -inflammation

  25. Osteoarthritis BP 21-13Fibrillation of articular cartilage

  26. Osteoarthritis BP 21-14Left: erosion of articular cartilage; right: eburnation

  27. Rheumatoid arthritis WHP 22.13aDestruction of articular cartilage and replacement by fibrovascular granulation tissue (pannus)

  28. Comparison of osteoarthritis and rheumatoid arthritis BP 21-15

  29. Pathogenesis of gouty arthritis BP 21-17

  30. Tophus (urate crystals) BP 21-18

More Related