Contents. Musculoskeletal System. Developmental abnormality. Contents 3/7/2014
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1 Musculoskeletal System Jatuwit Howannapakorn, M.D. Contents Bones Developmental abnormalities Adactyly, amelia, arachnodactyly, syndactyly Dwarfism (Achondroplasia, osteogenesis imperfecta) Osteopetrosis Metabolic disorder Osteoporosis Osteomalacia, hyperparathyroidism, renal osteodystrophy Fracture Osteonecrosis (Avascular necrosis) Infections Bone tumors and tumor-like lesions Contents Joints Arthritis and osteoarthritis Tumor and tumor-like lesions of joints Skeletal muscle Muscular dystrophy Inflammatory myopathy Developmental abnormality Adactyly = absence of fingers Amelia = absence of upper/lower extrimities Syndactyly = fusion of the fingers or toes Polydactyly = supernumerary fingers or toes Arachnodactyly = is a condition in which the fingers are abnormally long and slender in comparison to the palm of the hand / is a feature of Marfan and Ehlers-Danlos syndrome 1
2 Developmental abnormality Achondroplasia: Major cause of dwarfism Autosomal dominant (80% new mutation) Point mutation of FGFR3 (Inhibits proliferation and terminal differentiation, resulting in reduced bone growth) Thanatophoric dwarfism: Most common lethal form of dwarfism 1 in 20,000 live births Mutation of FGFR3 Shortening of limbs, frontal bossing, small chest cavity, bellshaped abdomen 2
3 Developmental abnormality Osteogenic Imperfecta (brittle bone disease) Type 1 collagen diseases Deficiency in the synthesis of type 1 collagen Bone (weak and fragile), joint, eyes (blue sclerae), ears (hearing loss), skin, teeth (dental imperfections) Four major subtypes: Type II: fatal in utero Type I: normal life span with increased fracture Type 2, 10, and 11 collagen disease Early destruction of joint (osteoarthritis) Note: the main functions of collagen 1,2,3,4: bone, cartwolage, threeticulin, basement membrane floor (four). Developmental abnormality Osteopetrosis Reduced osteoclast mediated bone resorption Defective bone remodelling, specifically reduced bone demineralization AR;AD Abnormal dense bone (marble bone) AR: Severe form, anemia, nerve entrapment, hydrocephalus, infections, fractures AD: Milder Extramedullary hematopoiesis Wider metaphyseal and diaphyseal areas (Erlenmeyer flask) Lack medullary canal 3
4 Metabolic disorder:osteoporosis Osteoporosis Increased porosity of skeleton resulting from reduced bone mass Localized: disused osteoporosis Generalized: metabolic bone disease Primary: Senile, postmenopausal, idiopathic Secondary: Vit D deficiency, Steroids Most common: Senile osteoporosis postmenopausal osteoporosis Metabolic disorder:osteoporosis Pathogenesis Age-related change: Osteoblast replication and biosynthesis Reduced physical activity: Mechanical force bone remodeling Genetic factors: Type of Vitamin D receptor maximal peak mass Body calcium nutritional state: Calcium deficiency bone mass Metabolic disorder:osteoporosis Pathogenesis Hormonal influences: Menopause estrogen IL-1, IL-6, TNF from monocytes and bone marrow cells osteoclast activity (30-40 yrs 35-50% bone loss) High turnover variant Glucocorticoids bone resorption & bone formation Alcoholism Inhibition of osteoblasts, absorption of calcium Biphosphonate prevent bone loss 4
5 Metabolic disorder:osteoporosis y Clinical course: y Veterbral fractures: thoracic and lumbar regions, painful y Multiple fractures Æ loss of height, lumbar lordosis and kyphoscoliosis y Diagnosis: y 30-40% bone loss Æ detected by radiographs y Dual-energy absorption and quantitative CT y Biopsy 5
6 Metabolic disorder:osteoporosis Prevention and treatment: Exercise Calcium and vitamin D intake Estrogen replacement Biphosphonate Recombinant PTH Metabolic disorder:osteomalacia Softening of bones,literally Defect in matrix mineralization Normal thickness of bone trabeculae but incompletely calcified Lack of vitamin D or disturbance of its metabolism Children rickets Skeletal deformities Adults osteomalacia Usually GI malabsorption, renal defect or chronic kidney or liver diseases. Elderly often affected due to inadequate diet or lack of outdoor activity Osteopenia fracture 6
7 Metabolic disorder:hyperparathyroidism PTH osteoclastic activity Leads to resorption of cortical bone Osteitis fibrosa cystica (brown tumor) Brown tumor of hyperparathyroidism Expansile, tumor-like proliferations of osteoclasts Clinical features: Fracture, bone deformities Joint pain and dysfunction Metabolic disorder:renal osteodystrophy Skeletal changes of chronic renal disease: High turnover osteodystrophy Osteoclastic bone resorption (osteoporosis) Low turnover or aplastic disease Matrix mineralization (osteomalacia) Osteosclerosis alternating with osteoporosis call rugger jersey spine Pathogenesis: Vitamin D def. hypocalcemia PTH Hyperphosphatemia PTH Metabolic acidosis bone resorption Aluminum deposit bone mineralization 7
8 Fractures Classification: Complete vs. incomplete Closed (simple) vs. Opened (compound) Comminuted (splintered) Displaced Pathologic fracture (underlying bone dis.) Stress fracture (repetitive loads) Fractures Reparative process: 1 st week organizing hematoma (soft tissue callus, procallus) 2 nd or 3 rd week bony callus (cartilage and bone formation) Delayed healing: nonunion Displaced, comminuted, compound fractures Inadequate immobilization Infections Calcium, phophorus, Vitamin def. diabetics, vascular insufficiency Osteonecrosis (AVN) Ischemia infarction Mechanisms: Vascular interruption (fracture) Corticosteroids Thrombosis and embolism (nitrogen bubbles, dysbarism) Vessel injury (vasculitis, radiation) Intraosseous pressure and vascular compression Venous hypertension 8
9 Osteonecrosis (avascular necrosis:avn) Clinical course: Subchondral infarcts chronic pain, 2 nd osteoarthritis Medullary infarcts clinically silent, painful, collapse Infections Osteomyelitis Pyogenic osteomyelitis Bacterial infections: S. aureus (80-90%) E. coli, Pseudomonas, Klebsiella: IVDU, GU tract Mixed organisms: fracture, direct spread H. influenzae: neonatal period Salmonella: sickle cell anemia Spread: hematogenous, extension from contiguous sites, direct implantation Infections Osteomyelitis Pyogenic osteomyelitis Sites: Neonate: Metaphysis, epiphysis Children: Metaphysis Adult: Epiphysis, subchondral Clinical course: Acute systemic illness, fever, malaise, leukocytosis, throbbing pain X-ray: lytic bone destruction Threatment: antibiotics and surgical drainage 5-25% chronic osteomyelitis Dead bone ( sequestrum ) is surrounded by new bone formation ( involucrum ) 9
10 Infections Osteomyelitis Tuberculous osteomyelitis 1-3% of patients with pulmonary or extrapulmonary TB have osseous infection Hematogenous spread from visceral organs or direct extension Spine infection (Pott disease): thoracic and lumbar vertebrae More destructive and resistance to therapy than pyogenic osteomyelitis Bone tumors and Tumor-like lesions Hematopoietic (40%) Chondrogenic (22%) Osteogenic (19%) Unnown origin (10%): giant cell tumor Micellaneous: Fibrous and histiocytic Vascular Lipogenic Neurogenic Bone tumors and Tumor-like lesions Characteristic: Osteosarcoma: Adolescence, metaphysis around the knees Chondrosarcoma Adulthood, trunk, limb girdle, proximal long bones Giant cell tumors and chondroblastoma: Epiphysis of long bones Ewing sarcoma, osteofibrous dysplasia, adamantinoma Diaphysis Bone-forming tumor Osteoma: skull, facial bones Middle-aged adults Obstruction of sinuses, cosmetic problems Osteoid osteoma, osteoblastoma: Osteoid osteoma: <2 cm in size Teens and twenties, femur, tibia, painful lesion Osteoblastoma: >2 cm in size Spine, dull pain X-ray: nidus 10
11 Bone-forming tumor Osteosarcoma: Most common primary bone tumor Age: 75% (children, <20 yo) 25% (elderly) Secondary osteosarcoma: Paget disease, bone infarct, irradiation Sites: metaphyseal region of long bone Clinical: painful enlarging mass X-ray: destructive, lytic and blastic mass with permeative margin, Codman Triangle Treatment: Chemotherapy, limb salvage Cartilage-forming tumor Osteochondroma: Exostosis Solitary and multiple (hereditary) Late adolescence and early adulthood Metaphysis of long bones Clinical: slow-growing mass, can be painful, rare (<1%) chondrosarcoma 11
12 Cartilage-forming tumor Chondroma: Intramedullary: enchondroma Metaphysis of short tubular bones of hands & feet Surface of bone: Subperiosteal or juxtacortical chondroma Clinical: asymtomatic, painful, pathologic fracture X-ray: well-circumscribed oval lucencies (O ring sign) Cartilage-forming tumor Chondrosarcoma: Second most common malignant matrix-producing tumor of bones Age 40 or older Malignant transformation from enchondroma, osteochondroma, chondroblastoma Sites: central portions of skeleton, pelvis, shoulder, and ribs Clinical: painful enlarging mass, fracture X-ray: Destructive radiolucent mass Treatment: Surgical excision, chemotherapy 12
13 Miscellaneous tumors Giant cell tumor Benign but locally aggressive tumor Age :20-40 yr Sites: epiphysis and metaphysis of any bones Common site: distal femur and proximal tibia X-ray: large, lytic, eccentric and erode into subchondral bone plate 40-60% recurrent, 4% metastasis to lung Metastatic disease Adults: Prostate, breast, kidney, and lung Children: Neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, rhabdomosarcoma X-ray: Multifocal or solitary (kidney, thyroid) Lytic: Kidney, lung, GI and melanoma Blastic: Prostate 13
14 Joints Osteoarthritis: Degenerative joint disease Progressive erosion of articular cartilage Idiopathic (primary OA): aging phenomenon Secondary oateoarthritis (5%): diabetics, ochronosis, hemochromatosis, obesity Women: knees and hands Men: hips Osteoarthritis Pathogenesis: Aging and mechanical effects Genetic factors: high bone density Clinical course: Primary OA: old age (>50 yr) Secondary OA: younger age, underlying dis. Deep achy pain, worsen with use Morning stiffness, crepitus, limitation of movement Nerve root compression (osteophytes) Rheumatoid arthritis Chronic systemic inflammatory disorder: skin, blood vessels, heart, lungs, muscles, joints Pathogenesis: Autoimmune disease: arthritogenic antigen CD4+ helper T cells inflammatory cytokines Genetic susceptibility: HLA-DR1*0401, *0404 Antigens: unknown 14
15 Rheumatoid arthritis Clinical course: 50%, slow and insidious onset: malaise, fatigue, musculoskeletal pain, joint pain 10% acute onset with sever symptoms Site: small joints > large joints: MCP, PIP, MTP, IP, wrists, ankles, elbows, knees 20%, partial or complete remission period Joint destruction, deformity: swan neck, boutonniere of fingers X-ray: juxta-articular osteopenia, bone erosion with narrowing of joint space Rheumatoid arthritis Laboratory tests and Dx: Serum rheumatoid factor (IgM to Fc portion): not specific Synovial fluid analysis: inflammatory exudate Clinical criteria: 4 criteria Morning stiffness Arthritis in three or more joints Arthritis of typical hand joints Symmetric arthritis Rheumatoid nodules Serum rheumatoid factor Typical radiographic changes 15
16 Rheumatoid arthritis Treatment: Anti-inflammatory drugs (aspirin, NSAIDs) Steroids Anti-TNF antibody, soluble TNF receptor Infectious arthritis Suppurative arthritis: Bacteria: gonococcus, Staphylococcus, Strepcoccus, Haemophilus influenza, E. coli, salmonella, Pseudomonas Children <2 yr: H. Influenzae Adults: S. aureus Young women: Gonococcus Sickle cell anemia: Samonella Painful joint, fever, leukocytosis Knees, hip, shoulder, elbow, wrist Gout and Gouty arthritis Transient attacks of arthritis initiated by crystallization of monosodium urates (needle shape, neg. birefringent) within joints Pathogenesis: hyperuricemia gout Age: yr after hyperuricemia Genetic: Lesch-Nyhan syndrome Heavy alcohol consumption Obesity Drugs: thiazides Lead toxicity 16
17 Gout and Gouty arthritis Clinical course: four stages Asymptomatic hyperuricemia: puberty male or menopause women Acute gouty arthritis: 50% MTP joint, ankles, heels, knees, wrists, fingers, elbows Intercritical gout Chonic tophaceous gout: 12 years after first attack Extra-articular: atherosclerosis, hypertension, renal colic, gouty nephropathy Pseudogout Calcium pyrophosphate crystal deposit disease (CPPD) Age: over age 50 Type: Idiopathic, hereditary and secondary (joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism) Clinical: aymptomatic, acute, sunacute, chronic arthritis of knees, wrists, elbows, shoulder, ankles 17
18 Tumor and Tumor-like lesions Ganglion cysts: Size: 1 to 1.5 cm near joint capsule or tendon Site: wrists, fingers Etiology: Cystic degeneration Synovial cysts: Baker cyst of knees in RA patients Synovial protrusion (diverticulum) Soft tissue tumors and tumor-like lesions Mesenchymal proliferations that occur in the extraskeletal, nonepithelial tissue Classification: muscle, fat, fibrous, vesels, nerves Location: lower ext. (40%), upper ext. (20%), head&neck (10%), trunk&retroperitoneum (30%) Prognosis: histologic classification, grade I-III, Staging, superficial vs. deep-seated Fatty tumors Lipoma: Most common soft tissue tumor of adult Well-encapsulated mass, mature adipocytes Soft, mobile, painless (exp. Angiolipoma) Liposarcoma: Most common sarcoma of adult (40s-60s) Deep seat soft tisue Well-differentiated (indolent), myxoid (intermediate), round cell, pleomorphic (aggressive) 18
19 NORMAL FAT Tumors of skeletal muscle Rhabdomyoma: Hamartomatous? Heart, tongue, external genitalia Rhabdomyosarcoma: Most common soft tissue sarcoma of childhood and adolescence Most occur in head& neck or genitourinary tract Type: embryonal, alveolar, pleomorphic Aggressive tumor, also chemotherapy Rx 19
20 Tumors of smooth muscle Leiomyoma: Often arise in the uterus Erector pili: skin, nipples, scrotum, labia Surgical removal Leiomyosarcoma: 10 to 20% of soft tissue sarcoma Adult, W>M Superficial or cutaneous lesion good prognosis Deep soft tissue local extension, metastasis MUSCULAR DYSTROPHIES X linked inheritance (Duchene and Becker muscular dystrophy) Pathogenesis Dystrophin gene in Xp 21 (Mutation results in a virtual absence of dystrophin protein) Normal at birth with onset of symptoms by age 5, with progressive muscular weakness of proximal,shoulder and pelvic girdles. CALF PSEUDOHYPERTROPHY Progressive respiratory failure and pulmonary infections Increased serum creatine kinase Muscle fibers of various sizes, necrosis, degeneration and regeneration fibers Fibrosis Fatty infiltration. 20
21 Myasthenia Gravis Muscular fatigability caused by circulating Abs to acetylcholine receptor at the myoneural junction Extraocular muscles, swelling muscles, extremities W>M, Age<40 Pts can develop other autoimmune diseases 15% patients have thymoma 65% of remaining thymic hyperplasia Removal of thymus can be curative Reference Kumar, Kabbas, fausto: Robbins and Cotran Pathologic Basis of Disease: 7 th ed 21
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