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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.
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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. • 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
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
Paget Disease Mosaic pattern PBD 28-13BP 21-5New bone is woven bone--lacks normal lamellar architecture.
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
Chronic osteomyelitis with sequestrum BP 21-3PBD 28-19Often draining tracts open onto the skin.
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%.
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.
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
Denervation atrophy BP21-20Typical angular shrunken appearance of denervated cells.
Infantile spinal muscular atrophy BP 21-21Many rounded atrophic fibers and few hypertrophic fibers.
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
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.
Duchenne muscular dystrophy PBD 29-10Variable size and shape of fibers; some regeneration (basophilic with enlarged nuclei).
Stain for dystrophin BP21-23Left has normal dystrophin; right is Becker muscular dystrophy; no dystrophin would be seen in Duchenne muscular dystrophy.
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.
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
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
Osteoarthritis BP 21-14Left: erosion of articular cartilage; right: eburnation
Rheumatoid arthritis WHP 22.13aDestruction of articular cartilage and replacement by fibrovascular granulation tissue (pannus)
Comparison of osteoarthritis and rheumatoid arthritis BP 21-15
