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