Congenital Bone Diseases & Osteomyelitis PDF

PATHOLOGY OF BONES & JOINTS Congenital abnormalities of the skeleton Frequently result from inherited mutations, the spectrum of developmental disorders of bone is broad. Congenital anomalies can result from localized abnormalities in the migration and condensation of mesenchyme (dyso...

PATHOLOGY OF BONES & JOINTS Congenital abnormalities of the skeleton Frequently result from inherited mutations, the spectrum of developmental disorders of bone is broad. Congenital anomalies can result from localized abnormalities in the migration and condensation of mesenchyme (dysostosis) or global disorganization of bone and/or cartilage (dysplasia). Dysostoses result from defects in the formation of mesenchymal condensations and their differentiation into the cartilage anlage. The most common forms include the complete absence of a bone or a digit (aplasia), extra bones or digits (supernumerary digit). In contrast, dysplasia arise from mutations in genes that control development or remodeling of the entire skeleton, the commonest anomalies include: 1-Achondroplasia The most common skeletal dysplasia and a major cause of dwarfism, is an autosomal dominant disorder resulting from retarded cartilage growth. The disease is caused by gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). Normally, FGF inhibits endochondral growth. FGFR3 mutation results in a constitutively active receptor, thereby exaggerating this effect and suppressing growth. 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. Histologically Growth plate abnormalities, the zones of proliferation are narrow and disorganized. At the end of growth plate bone are deposited that seal the plate. 2-Osteogenesis Imperfecta Osteogenesis imperfecta (OI), the most common inherited disorder of connective tissue, caused by deficiencies in the synthesis of type I collagen. The disease affects bone and other tissues rich in type I collagen (joints, eyes, ears, skin, and teeth). It usually results from autosomal dominant mutations in the genes that encode the α1 and α2 chains of type I collagen. These defects cause misfolding of the mutated collagen polypeptides. The fundamental abnormality in OI is : 1- Too little bone, resulting in extreme skeletal fragility. 2- Blue sclerae caused by decreased collagen content, making the sclera translucent and allowing partial visualization of the underlying choroid. Page 1 of 4  PATHOLOGY OF BONES & JOINTS 3- Hearing loss related to a sensorineural deficit and impeded conduction due to abnormalities in the bones of the middle ear. 4- Dental imperfections (small, misshapen, and blue-yellow teeth) secondary to a deficiency in dentin. OI can be separated into multiple clinical subtypes that vary widely in severity. The type 2 variant is at one end of the spectrum and is uniformly fatal in utero or during the perinatal period. In contrast, individuals with the type 1 form have a normal life span despite a susceptibility to fractures, particularly during childhood. 3-Osteopetrosis Also known as marble bone disease, it is 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 bone has stone like quality and at same time it is 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. 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 which is essential for breaking down bone. Bones involved by osteopetrosis lack a medullary canal leaving no room for the hematopoietic marrow, and the ends of long bones are bulbous and misshapen. The neural foramina are small and compress exiting nerves. Severe infantile osteopetrosis is autosomal recessive and is often fatal because of leukopenia, despite extensive extramedullary hematopoiesis that can lead to prominent hepatosplenomegaly. The mild 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. Inflammatory lesions of the bones It is inflammation of bone and marrow, but in common use it is virtually synonymous with infection & the most common etiologic agents are pyogenic bacteria and Mycobacterium tuberculosis. Osteomyelitis can be primary isolated focus of disease (more frequently occurs) or secondary to systemic infection it can be an acute process or a chronic, debilitating illness. Page 2 of 4  PATHOLOGY OF BONES & JOINTS 1- Pyogenic Osteomyelitis: Most cases of acute osteomyelitis are caused by bacteria. Among them Staphylococcus aureus is the most frequent causative organism; The offending organisms reach the bone by one of three routes: (1) Hematogenous dissemination (most common); (2) Extension from an infection in adjacent joint or soft tissue; (3) Traumatic implantation after compound fractures or orthopedic procedures. Escherichia coli and group B streptococci are important causes of acute osteomyelitis in neonates, and Salmonella is an especially common pathogen in persons with sickle cell disease. Mixed bacterial infections, including anaerobes, are responsible for osteomyelitis secondary to bone trauma. In as many as 50% of cases, no organisms can be isolated. MORPHOLOGY Causal bacteria proliferate, inducing an acute inflammatory reaction, with consequent cell death. Entrapped bone rapidly becomes necrotic; this non- viable bone is called a sequestrum. Bacteria and inflammation can percolate throughout the Haversian systems to reach the periosteum. In children, the periosteum is loosely attached to the cortex; so subperiosteal abscesses can form and extend for long distances along the bone surface. Lifting of the periosteum further impairs the blood supply to the affected region, and both suppurative and ischemic injury can cause segmental bone necrosis. In infants epiphyseal infection can spread into the adjoining joint to produce suppurative arthritis. After the first week of infection, chronic inflammatory cells become more numerous. Leukocyte release cytokine that stimulates osteoclastic bone resorption, fibrous tissue growth, and bone formation in the periphery. Reactive woven or lamellar bone can be deposited; when it forms a shell of living tissue around a sequestrum, it is called an involucrum. Viable organism can persist in the sequestrum for years after the original infection. CLINICAL FEATURES Osteomyelitis classically manifests as an acute systemic illness, with malaise, fever, leukocytosis, and throbbing pain over the affected region. Symptoms also can be subtle, with only unexplained fever, particularly in infants, or only localized pain in the adult. Chronicity may develop with delay in diagnosis. Page 3 of 4  PATHOLOGY OF BONES & JOINTS COMPLICATIONS OF CHRONIC OSTEOMYELITIS 1-Occasional acute flare ups 2- Pathologic fracture, 3-Secondary amyloidosis, 4- Endocarditis, 5- Sepsis 6- Malignancy: development of squamous cell carcinoma of overlying skin if the infection creates a sinus tract, and rarely osteosarcoma. 2- Tuberculous Osteomyelitis Mycobacterial infection of bone has long been a problem in developing countries; bone infection complicates an estimated 1%-3% of cases of pulmonary tuberculosis. The organisms usually reach the bone through the bloodstream. With hematogenous spread, long bones and vertebrae are favored sites. The lesions often are solitary but can be multifocal, particularly in patients with an underlying immunodeficiency. Because the tubercle bacillus is microaerophilic, the synovium, with its higher oxygen pressures, is a common site of initial infection. The infection then spreads to the adjacent epiphysis, where it elicits typical granulomatous inflammation with caseous necrosis and extensive bone destruction. Tuberculosis of the vertebral bodies is a clinically serious form of osteomyelitis. Infection at this site causes vertebral deformity, collapse, and posterior displacement (Pott disease), leading to neurologic deficits. Page 4 of 4