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Muscoloskeletal SystemSakchai Chitpakdee, M.D.
ContentsBones
OsteoporosisRickets, osteomalacia, hyperparathyroidism, renal osteodystrophyFractureOsteonecrosis (Avascular necrosis)InfectionsBone tumors and tumor-like lesions
ContentsJoints
Arthritis and osteoarthritisTumor and tumor-like lesions of joints
Skeletal muscleMuscular dystrophiesInflammatory myopathiesMyasthenia Gravis
OsteoporosisIncreased porosity of skeleton resulting from reduced bone mass
Localized: disused osteoporosisGeneralized: metabolic bone disease
Primary: Senile, postmenopausal, idiopathicSecondary: Vit D deficiency, Steroids
Most common:Senile osteoporosispostmenopausal osteoporosis
OsteoporosisClinical course:
Veterbral fractures: thoracic and lumbar regions, painfulMultiple fractures loss of height, lumbar lordosis and kyphoscoliosis
Diagnosis:30-40% bone loss detected by radiographsDual-energy absorption and quantitative CTBiopsy
OsteoporosisPrevention and treatment:
ExerciseCalcium and vitamin D intakeEstrogen replacementBiphosphonateRecombinant PTH
Rickets and OsteomalaciaDefect in matrix mineralizationLack of vitamin D or disturbance of its metabolismChildren “rickets”
Skeletal deformities
Adults “osteomalacia”Osteopenia fracture
HyperparathyroidismPTH ↑osteoclastic activityOsteitis fibrosa cystica (brown tumor)Clinical features:
Fracture, bone deformitiesJoint pain and dysfunction
Renal OsteodystrophySkeletal changes of chronic renal disease:
High turnover osteodystrophy↑Osteoclastic bone resorption (osteoporosis)
Low turnover or aplastic disease↓Matrix mineralization (osteomalacia)
Pathogenesis:Vitamin D def. hypocalcemia PTH ↑Hyperphosphatemia PTH ↑Metabolic acidosis bone resorption ↑Aluminum deposit bone mineralization ↓
FracturesClassification:
Complete vs. incompleteClosed (simple) vs. Opened (compound)Comminuted (splintered)Displaced Pathologic fracture (underlying bone dis.)Stress fracture (repetitive loads)
FracturesReparative process:
1st week organizing hematoma (soft tissue callus, procallus)2nd or 3rd week bony callus (cartilage and bone formation)
Delayed healing: nonunionDisplaced, comminuted, compound fracturesInadequate immobilizationInfectionsCalcium↓, phophorus↓, Vitamin def. diabetics, vascular insufficiency
Osteonecrosis (AVN)Ischemia infarctionMechanisms:
Vascular interruption (fracture)CorticosteroidsThrombosis and embolism (nitrogen bubbles, dysbarism)Vessel injury (vasculitis, radiation)↑ Intraosseous pressure and vascular compressionVenous hypertension
Osteonecrosis (AVN)Clinical course:
Subchondral infarcts chronic pain, 2nd
osteoarthritisMedullary infarcts clinically silent, painful, collapse
Infections—Osteomyelitis Pyogenic osteomyelitis
Bacterial infections: S. aureus (80-90%)E. coli, Pseudomonas, Klebsiella: IVDU, GU tractMixed organisms: fracture, direct spreadH. influenzae: neonatal periodSalmonella: sickle cell anemia
Spread: hematogenous, extension from contiguous sites, direct implantation
Infections—OsteomyelitisPyogenic osteomyelitis
Sites:Neonate: Metaphysis, epiphysisChildren: MetaphysisAdult: Epiphysis, subchondral
Clinical course:Acute systemic illness, fever, malaise, leukocytosis, throbbing painX-ray: lytic bone destructionThreatment: antibiotics and surgical drainage5-25% chronic osteomyelitis
Infections—OsteomyelitisTuberculous osteomyelitis
1-3% of patients with pulmonary or extrapulmonary TB have osseous infectionHematogenous spread from visceral organs or direct extensionSpine infection (Pott disease): thoracic and lumbar vertebraeMore destructive and resistance to therapy than pyogenic osteomyelitis
Bone tumors and Tumor-like lesionsHematopoietic (40%)Chondrogenic (22%)Osteogenic (19%)Unnown origin (10%): giant cell tumorMicellaneous:
Fibrous and histiocyticVascularLipogenicNeurogenic
Bone tumors and Tumor-like lesionsCharacteristic:
Osteosarcoma:Adolescence, metaphysis around the knees
ChondrosarcomaAdulthood, trunk, limb girdle, proximal long bones
Giant cell tumors and chondroblastoma:Epiphysis of long bones
Ewing sarcoma, osteofibrous dysplasia, adamantinoma
Diaphysis
Bone-forming tumorOsteosarcoma:
Most common primary bone tumorAge: 75% (children, <20 yo) 25% (elderly)Secondary osteosarcoma: Paget disease, bone infarct, irradiationSites: metaphyseal region of long boneClinical: painful enlarging massX-ray: destructive, lytic and blastic mass with permeative margin, “Codman Triangle”Treatment: Chemotherapy, limb salvage
Cartilage-forming tumorOsteochondroma:
ExostosisSolitary and multiple (hereditary)Late adolescence and early adulthoodMetaphysis of long bonesClinical: slow-growing mass, can be painful, rare (<1%) chondrosarcoma
Cartilage-forming tumorChondrosarcoma:
Second most common malignant matrix-producing tumor of bonesAge 40 or olderMalignant transformation from enchondroma, osteochondroma, chondroblastomaSites: central portions of skeleton, pelvis, shoulder, and ribsClinical: painful enlarging mass, fractureX-ray: Destructive radiolucent massTreatment: Surgical excision, chemotherapy
Miscellaneous tumorsGiant cell tumor:
Benign but locally aggressive tumorPatients in twenties to fortiesSites: epiphysis and metaphysis of any bones (common: distal femur and proximal tibia)X-ray: large, purely lytic, eccentric and erode into subchondral bone plateTreatment: Conserative surgery40-60% recurrent, 4% metastasis to lung
Metastatic diseaseAdults:
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 melanomaBlastic: Prostate
JointsOsteoarthritis:
Degenerative joint diseaseProgressive erosion of articular cartilageIdiopathic (primary OA): aging phenomenonSecondary oateoarthritis (5%): diabetics, ochronosis, hemochromatosis, obesityWomen: knees and handsMen: hips
OsteoarthritisPathogenesis:
Aging and mechanical effectsGenetic factors: high bone density
Clinical course:Primary OA: old age (>50 yr)Secondary OA: younger age, underlying dis.Deep achy pain, worsen with useMorning stiffness, crepitus, limitation of movementNerve root compression (osteophytes)
Rheumatoid arthritisChronic systemic inflammatory disorder: skin, blood vessels, heart, lungs, muscles, jointsPathogenesis:
Autoimmune disease: arthritogenic antigen CD4+ helper T cells inflammatory cytokinesGenetic susceptibility: HLA-DR1*0401, *0404Antigens: unknown
Rheumatoid arthritisClinical course:
50%, slow and insidious onset: malaise, fatigue, musculoskeletal pain, joint pain10% acute onset with sever symptomsSite: small joints > large joints: MCP, PIP, MTP, IP, wrists, ankles, elbows, knees20%, partial or complete remission periodJoint destruction, deformity: swan neck, boutonniere of fingersX-ray: juxta-articular osteopenia, bone erosion with narrowing of joint space
Rheumatoid arthritisLaboratory tests and Dx:
Serum rheumatoid factor (IgM to Fc portion): not specificSynovial fluid analysis: inflammatory exudateClinical criteria: 4 criteria
Morning stiffnessArthritis in three or more jointsArthritis of typical hand jointsSymmetric arthritisRheumatoid nodulesSerum rheumatoid factorTypical radiographic changes
Rheumatoid arthritisTreatment:
Anti-inflammatory drugs (aspirin, NSAIDs)SteroidsAnti-TNF antibody, soluble TNF receptor
Seronegative spondyloarthropathiesAnkylosing spondylitisReactive arthritis (Reiter syndrome and enteritis associated arthritis)Psoriatic arthritisArthritis associated with inflammatory bowel disease
Ankylosing spondyloarthritisRheumatoid spondylitis and Marie-Strumpell diseaseSites: axial, sacriiliac & apophyseal jointsAge: 20-30 yr, M>F90% HLA-B27 positiveClinical: low back pain, spinal immobility (ankylosis), fracture of spine, aortitis, amyloidosis
Reactive arthritisNoninfectious arthritis of appendicular skeleton occurs within one months of primary infection localized elsewhere
GU: clamydiaGI: shigella, salmonella, Yersinia, CampylobacterReiter syndrome: arthritis, nongonococcal urethritis/cervicitis, conjunctivitis80% HLA-B27 positiveExtraarticular: balanitis, carditis
Infectious arthritisSuppurative arthritis:
Bacteria: gonococcus, Staphylococcus, Strepcoccus, Haemophilus influenza, E. coli, salmonella, PseudomonasChildren <2 yr: H. InfluenzaeAdults: S. aureusYoung women: GonococcusSickle cell anemia: SamonellaPainful joint, fever, leukocytosisKnees, hip, shoulder, elbow, wrist
Gout and Gouty arthritisTransient attacks of arthritis initiated by crystallization of monosodium urates (needle shape, neg. birefringent) within jointsPathogenesis: hyperuricemia gout
Age: 20-30 yr after hyperuricemiaGenetic: Lesch-Nyhan syndromeHeavy alcohol consumptionObesityDrugs: thiazidesLead toxicity
Gout and Gouty arthritisClinical course: four stages
Asymptomatic hyperuricemia: puberty male or menopause womenAcute gouty arthritis: 50% MTP joint, ankles, heels, knees, wrists, fingers, elbowsIntercritical goutChonic tophaceous gout: 12 years after first attackExtra-articular: atherosclerosis, hypertension, renal colic, gouty nephropathy
PseudogoutCalcium pyrophosphate crystal deposit disease (CPPD)Age: over age 50Type: Idiopathic, hereditary and secondary (joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism)Clinical: aymptomatic, acute, sunacute, chronic arthritis of knees, wrists, elbows, shoulder, ankles
Tumor and Tumor-like lesionsGanglion cysts:
Size: 1 to 1.5 cm near joint capsule or tendonSite: wrists, fingersEtiology: Cystic degeneration
Synovial cysts:Baker cyst of knees in RA patientsSynovial protrusion (diverticulum)
Muscular dystrophiesX-linked muscular dystrophy (Duchene and Becker muscular dystrophy)
Pathogenesis: Dystrophin gene, Xp21Deletion or frameshift mutation (DMD), Point mutation (BMD)
Clinical:DMD normal at birth, delayed walking, clumsinessWeakness begins in pelvic girdles, shoulder girdlesEnlargement of calf muscle (pseudohypertrophy)Increased serum creatine kinaseDeath from respiratory failure, pulmonary infection and cardiac decompensationBMD: later onset and less severe
Myasthenia gravisImmune-mediated loss of acetylcholine resectors (AChRs); autoimmune diseaseW>M, Age < 40Thymic hyperplasia (65%), thymoma (15%)Clinical: extraocular muscles (ptosis, diplopia) generalized weakness, respiratory paralysisRx: anticholinesterase agents, prednisone, plasmapheresis, resection of thymoma
ReferenceKumar, Kabbas, fausto: Robbins and Cotran Pathologic Basis of Disease: 7th edhttp://www.pathguy.com/lectures/bones.htm
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