muscolskeletal.pdf

Congenital bone disease  congenital abnormalities of the skeleton frequently result from inherited mutations and first become manifest from during the early stages of bone formation. the spectrum of developmental disorders of bone is broad, and the classification system is not standar...

Congenital bone disease  congenital abnormalities of the skeleton frequently result from inherited mutations and first become manifest from during the early stages of bone formation. the spectrum of developmental disorders of bone is broad, and the classification system is not standardized. Cont. …. Congenital anomalies can result from localized abnormalities in the migration and condensation of mesenchyme (dysostosis) or global disorganization of bone and/or cartilage (dysplasia). Achondroplasia autosomal dominant disorder resulting from retarded cartilage growth. the most common skeletal dysplasia and a major cause of dwarfism. the disease is caused by gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). normally, FGF inhibits endochondral growth. Cont. …. affected individuals have shortened proximal extremities, a trunk of relatively normal length, and an enlarged head with bulging forehead and conspicuous depression of the root of the nose. the skeletal abnormalities are usually not associated with changes in longevity, intelligence, or reproductive status. Type I Collagen Diseases (Osteogenesis Imperfecta)(OI) the most common inherited disorder of connective tissue, is a phenotypically diverse disorder caused by deficiencies in the synthesis of type I collagen. it principally affects bone and other tissues rich in type I collagen (joints, eyes, ears, skin and teeth). Cont. …. it autosomal dominant. the fundamental abnormality in OI is too little bone, resulting in extreme skeletal fragility. Cont….. other findings include:  blue sclerae caused by decreased collagen content  hearing loss related to a sensorineural deficit and impeded conduction due to abnormalities in the bones of the middle ear  dental imperfections (small, misshapen, and blue- yellow teeth) secondary to a deficiency in dentin.  Osteopetrosis it known as marble bone disease, refers to a group of rare genetic diseases that are characterized by reduced bone resorption and diffuse symmetric skeletal sclerosis resulting from impaired formation or function of osteoclasts. the bones are abnormally brittle and fracture easily, like a piece of chalk. Osteopetrosis is classified into variants based on both the mode of inheritance and the severity of clinical findings. Cont….. most of the mutations underlying osteopetrosis interfere with the process of acidification of the osteoclast resorption pit, which is required for the dissolution of calcium hydroxyapatite within the matrix. bones involved by osteopetrosis lack a medullary canal, and the ends of long bones are bulbous (Erlenmeyer flask deformity) and misshapen. Cont….. the neural foramina are small and compress exiting nerves. the primary spongiosa, which is normally removed during growth, persists and fills the medullary cavity, leaving no room for the hematopoietic marrow. severe infantile osteopetrosis is autosomal recessive and is often fatal because of leukopenia, despite extensive extramedullary hematopoiesis that can lead to prominent hepatosplenomegaly. Cont….. the mild autosomal dominant form may not be detected until adolescence or adulthood, when it is discovered on radiographic studies for repeated fractures. these individuals also may have mild cranial nerve deficits and anemia. Metabolic disorders of bone  Osteopenia and Osteoporosis Osteopenia refers to decreased bone mass. Osteoporosis is defined as osteopenia that is severe enough to significantly increase the risk of fracture. Radiographically, osteoporosis is considered bone mass at least 2.5 standard deviations below mean peak bone mass, whereas osteopenia is 1 to 2.5 standard deviations below the mean. Cont. …… the disorder may be localized or generalized although osteoporosis can be secondary to endocrine disorders (e.g., hyperthyroidism) the most common forms of osteoporosis are the senile and postmenopausal types. Pathogenesis peak bone mass is achieved during young adulthood. its magnitude is influenced by hereditary factors, especially polymorphisms in the genes that influence bone metabolism  Factors affect the bone: 1. Age-related changes 2. Reduced physical activity 3. Genetic factors: single gene defects (e.g., LRP5 mutations) 4. Calcium nutritional state 5. Hormonal influences Morphology the hallmark of osteoporosis is histologically normal bone that is decreased in quantity. the trabecular plates become perforated, thinned, and lose their interconnections , leading to progressive microfractures and eventual vertebral collapse. Clinical Course vertebral fractures that frequently occur in the thoracic and lumbar regions are painful, and, when multiple, can cause significant loss of height and various deformities, including lumbar lordosis and kyphoscoliosis. Cont. …… the best estimates of bone loss, aside from biopsy (which is rarely performed), are specialized radiographic imaging techniques, such as dual-energy x-ray absorptiometry and quantitative computed tomography, both of which measure bone density.  Rickets and Osteomalacia both rickets and osteomalacia are manifestations of vitamin D deficiency or its abnormal metabolism. Rickets refers to the disorder in children, in whom it interferes with the deposition of bone in the growth plates. Cont. …… Osteomalacia is the adult counterpart, in which bone formed during remodeling is under-mineralized, resulting in a predisposition to fractures. the fundamental defect is an impairment of mineralization and a resultant accumulation of unmineralized matrix.  Hyperparathyroidism excess production and activity of PTH result in increased osteoclast activity, bone resorption and osteopenia. isolated hyperparathyroidism peaks in middle adulthood and slightly earlier if presenting as a component of multiple endocrine neoplasia (MEN, types I and IIA). Pathogenesis PTH plays a central role in calcium homeostasis through the following effects:  osteoclast activation, increasing bone resorption, and calcium mobilization, PTH mediates the effect indirectly by increased RANKL expression on osteoblasts.  increased resorption of calcium by the renal tubules. Cont. ……  increased urinary excretion of phosphates.  increased synthesis of active vitamin D, 1,25(OH)2-D, by the kidneys, which in turn enhances calcium absorption from the gut and mobilizes bone calcium by inducing RANKL on osteoblasts. Cont. …… the net result of the actions of PTH is an elevation in serum calcium, which, under normal circumstances, inhibits further PTH production. however, excessive or inappropriate levels of PTH can result from autonomous parathyroid secretion (primary hyperparathyroidism) or can occur in the setting of underlying renal disease (secondary hyperparathyroidism)  hyperparathyroidism with osteoclasts boring into the center of the trabecula resembling a train track  resected rib, harboring an expansile brown tumor adjacent to the costal cartilage. Clinical Course as bone mass decreases, affected patients are increasingly susceptible to fractures, bone deformation, and joint problems. Osteomyelitis  Osteomyelitis denotes inflammation of bone and marrow, virtually always secondary to infection. Osteomyelitis may be a complication of any systemic infection but frequently manifests as a primary solitary focus of disease.  Pyogenic Osteomyelitis Pyogenic osteomyelitis is almost always caused by bacteria and rarely by fungi. organisms may reach the bone by (1) hematogenous spread (2) extension from a contiguous site (3) direct implantation after compound fractures or orthopedic procedures. Cont. … Staphylococcus aureus is responsible for 80% to 90% of the cases of culture-positive pyogenic osteomyelitis. Escherichia coli, Pseudomonas and Klebsiella are more frequently isolated from individuals with genitourinary tract infections Cont. … Haemophilus influenza and group B streptococci are frequent pathogens in an intravenous drug abusers. individuals with sickle cell disease are predisposed to Salmonella infection. Clinical Course Hematogenous osteomyelitis sometimes manifests as an acute systemic illness with malaise, fever, chills, leukocytosis, and marked throbbing pain over the affected region. in other instances the presentation is subtle, with only unexplained fever (most often in infants) or localized pain (most often in adults). Diagnosis strongly suggested by the characteristic radiographic findings of a lytic focus of bone destruction surrounded by a zone of sclerosis. biopsy and bone cultures are required to identify the pathogen in most instances. the combination of antibiotics and surgical drainage is usually curative. Cont. … in 5% to 25% of cases, acute osteomyelitis fails to resolve and persists as chronic infection. chronic infections may develop when there is:  delay in diagnosis  extensive bone necrosis  inadequate antibiotic therapy or surgical debridement  weakened host defenses.  Complications of chronic osteomyelitis pathologic fracture, secondary amyloidosis, endocarditis, sepsis, development of squamous cell carcinoma in the draining sinus tracts and sarcoma in the infected bone.  Mycobacterial Osteomyelitis overall, approximately 1% to 3% of individuals with pulmonary or extrapulmonary tuberculosis exhibit osseous infection the organisms are usually blood borne and originate from a focus of active visceral disease during the initial stages of primary infection. direct extension (e.g., from a pulmonary focus into a rib or from tracheobronchial nodes into adjacent vertebrae) also may occur Cont. … typically, affected individuals present with localized pain, low-grade fevers, chills, and weight loss. infection is usually solitary except in immunocompromised individuals. histologic findings, namely caseous necrosis and granulomas. Cont. … Tuberculous spondylitis (Pott disease)  is a destructive infection of vertebrae.  the spine is involved in 40% of cases of mycobacterial osteomyelitis.  the infection breaks through intervertebral discs to affect multiple vertebrae and extends into the soft tissues. Bone tumors and tumor like lesions  Bone tumors may present in a number of ways. the more common benign lesions are often asymptomatic incidental findings. many tumors, however, produce pain or a slow-growing mass. in some circumstances the first hint of a tumor’s presence is a pathologic fracture. Cont. …  Radiographic imaging studies : have an important role in diagnosing these lesions. It providing the exact location and extent of the tumor, imaging studies can detect features that narrow the diagnostic possibilities. in almost all instances biopsy is necessary for definitive diagnosis. Classification of bone tumors Cont. ….. Benign tumors greatly outnumber their malignant counterparts and occur with greatest frequency within the first three decades of life. in older adults, a bone tumor is more likely to be malignant. Arthritis  Osteoarthritis (OA) characterized by degeneration of cartilage that results in structural and functional failure of synovial joints. it is the most common disease of joints. it appears insidiously, without apparent initiating cause, as an aging phenomenon (idiopathic or primary osteoarthritis). In these cases the disease is usually oligoarticular (affects few joints). Cont….. in about 5% of cases, OA appears in younger individuals with some predisposing condition, such as joint deformity, a previous joint injury, or an underlying systemic disease that places joints at risk. In these settings the disease is called secondary osteoarthritis. the prevalence of OA increases exponentially beyond the age of 50, and about 40% of people older than 70 are affected. Pathogenesis the lesions of OA stem from degeneration of the articular cartilage and its disordered repair. articular cartilage serves as a low-friction surface that transmits loads to the underlying bone, it resists compression through the viscoelastic properties of the extracellular matrix secreted by chondrocytes. repeated biomechanical stress contributes to development of OA, but genetic factors, including genes encoding components of the matrix and signaling molecules, also play a role. Cont….. these factors are thought to predispose to chondrocyte injury, which in turn leads to alteration of the extracellular matrix.. Matrix metalloproteases MMPs secreted by chondrocytes degrade the type II collagen network Cytokines and diffusible factors from chondrocytes and synovial cells, particularly TGF-β (which induces MMPs), TNF, prostaglandins, and nitric oxide, have been implicated in OA. Schematic view of osteoarthritis (OA). OA is thought to be initiated by chondrocyte injury (1) in a genetically predisposed patient leading to changes in the extracellular matrix. (2) Although chondrocytes may proliferate and attempt to repair damaged matrix, continued degradation exceeds repair in early OA. (3) Late OA is evidenced by loss of both matrix and chondrocytes with subchondral bone damage. Clinical Course primary OA usually presents in patients they are in their 50s. if a young person search for some underlying cause. Characteristic symptoms include joint pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement. impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression and radicular pain, muscle spasms, muscle atrophy, and neurologic deficits. Cont….. the joints commonly involved include the hips, knees, lower lumbar and cervical vertebrae. Heberden nodes, prominent osteophytes at the distal interphalangeal joints, are common in women (but not in men). with time, joint deformity can occur, but joint fusion does not take place the level of disease severity detected radiographically, however, does not correlate well with pain and disability.  Severe osteoarthritis of the hip. The joint space is narrowed, and there is subchondral sclerosis with scattered oval radiolucent cysts and peripheral osteophyte lipping (arrows).  Septic Arthritis Joints can become infected from hematogenous dissemination, direct inoculation through the skin, or from contiguous spread from a soft tissue abscess or osteomyelitis. Septic arthritis is potentially serious, because it can cause rapid, permanent joint destruction.  Supportive Arthritis Bacterial infections that cause acute suppurative arthritis usually enter the joints from distant sites by hematogenous spread. In neonates, however, contiguous spread from underlying epiphyseal osteomyelitis may occur. In children younger than 2 years of age the H. influenza arthritis predominates, Cont.….. In older children and adults the S. aureus is the main agent, In adolescence and young adulthood the gonococcus is prevalent common Cont.….. individuals with sickle cell disease are prone to infection with Salmonella. these joint infections affect the sexes equally except for gonococcal arthritis, which is seen mainly in sexually active women. individuals with deficiencies of complement components (C5, C6, C7, or C9) are susceptible to disseminated gonococcal infections and hence arthritis. Cont.….. the classic presentation is the sudden development of an acutely painful, warm, and swollen joint that has a restricted range of motion. systemic findings of fever, leukocytosis, and elevated sedimentation rate are common. in 90% of nongonococcal cases, the infection involves only a single joint, most commonly the knee, followed in decreasing frequency by the hip, shoulder etc Cont….. the axial joints are more often involved in drug users. Joint aspiration is diagnostic if it yields purulent fluid in which the causative agent can be identified. prompt recognition and effective anti-microbial therapy is vital to prevent permanent joint destruction.  Crystal-Induced Arthritis Articular crystal deposits are associated with a variety of joint disorders. Endogenous crystals shown to be pathogenic include monosodium urate (MSU) (gout), calcium pyrophosphate dehydrate (pseudogout), and basic calcium phosphate. Cont. … Exogenous crystals, such as silicone, polyethylene, and methyl methacrylate used in prosthetic joints, and the debris that accumulates with their erosion, may result in local arthritis. Crystals produce disease by triggering an inflammatory reaction that destroys cartilage.  Gout Gout is marked by transient attacks of acute arthritis initiated by urate crystals deposited within and around joints. it primary or secondary. the common feature is excessive uric acid in tissues and body fluids. In the primary form (90% of cases), gout is the major manifestation of the disease and the cause is usually unknown. Pathogenesis Hyperuricemia (plasma urate level above 6.8 mg/dL) is necessary, but not sufficient, for the development of gout. Uric acid metabolism can be summarized as follows:  Synthesis. uric acid is the end product of purine catabolism.  Excretion. uric acid is filtered from the circulation by the glomerulus and virtually completely resorbed by the proximal tubule of the kidney. Cont….. in primary gout, elevated uric acid most commonly results from reduced excretion, the basis of which is unknown in most patients. a small minority of primary gout is caused by uric acid overproduction as a result of identifiable enzymatic defects. the inflammation in gout is triggered by precipitation of urate crystals in the joints, stimulating the production of cytokines that recruit leukocytes Pathogenesis of acute gouty arthritis Cont….. only about 10% of patients with hyperuricemia develop clinical gout. Other factors contribute symptomatic gout:  age of the individual and duration of the hyperuricemia. Gout usually appears after 20 to 30 years of hyperuricemia.  genetic predisposition. In addition to the well-defined X- linked abnormalities of HGPRT, polymorphisms in genes involved with urate or ion transport and possibly inflammation are also associated with gout. Cont…..  Alcohol consumption.  Obesity.  Drugs (e.g. thiazides) that reduce excretion of urate. Four clinical stages are recognized: Asymptomatic hyperuricemia appears around puberty in men and after menopause in women. Acute arthritis presents after several years as sudden onset painful joint pain, localized hyperemia, and warmth. Most first attacks are monoarticular; 50% occur in the first metatarsophalangeal joint. Untreated, acute gouty arthritis may last for hours to weeks, but gradually there is complete resolution. Cont. … Asymptomatic intercritical period: resolution of the acute arthritis leads to a symptom-free interval. In the absence of appropriate therapy, the attacks recur at decreasing intervals and frequently become polyarticular. Chronic tophaceous gout develops on average about 12 years after the initial acute attack. At this stage, radiographs show characteristic juxtaarticular bone and loss of the joint space.