Bone Pathology 1.pdf

BONE PATHOLOGY Objectives: Classify Metabolic diseases: (Rickets, Osteomalacia, Osteoporosis, Hyperparathyroidisism) Compare between the diseases regarding: clinical, radiographic, and histopathologic features Outline the Tumors: (Primary, Osteosarcoma, Ewing’s Sarcoma, Chondrosarcoma; Metastatic) I...

BONE PATHOLOGY Objectives: Classify Metabolic diseases: (Rickets, Osteomalacia, Osteoporosis, Hyperparathyroidisism) Compare between the diseases regarding: clinical, radiographic, and histopathologic features Outline the Tumors: (Primary, Osteosarcoma, Ewing’s Sarcoma, Chondrosarcoma; Metastatic) Introduction 206 bones Interconnected by joints Bones are composed of mineralized connective tissue admixture of organic matrix (35%) and inorganic elements (65%). The inorganic mineral component consists mainly of calcium hydroxyapatite The organic component includes the cells of bone and the proteinaceous osteoid. The bone-forming cells : osteoblasts and osteocytes, bone-digesting cells: osteoclast Vitamin D maintain normal plasma levels of calcium and phosphorus. it is required for the prevention of rickets (in children) osteomalacia (in adults), and hypocalcemic tetany. The major source is its endogenous synthesis in the skin by photochemical conversion of 7-dehydrocholesterol to form cholecalciferol (vitamin D3); 90% dietary sources, such as deep sea fih, plants, and grains Functions of The active form of vitamin D: Stimulates intestinal absorption of calcium through upregulation of calcium transport, Stimulates calcium reabsorption in renal distal tubules. Collaborates with PTH to regulate blood calcium. mineralization of osteoid matrix and epiphyseal cartilage during the formation of flat and long bones. stimulates osteoblasts to synthesize the calcium binding protein osteocalcin, which promotes calcium deposition. CONGENITAL DISORDERS OF BONE AND CARTILAGE: aplasia (e.g., congenital absence of a digit or rib), formation of extra bones (e.g., supernumerary digits or ribs) abnormal fusion of bones (e.g., premature closure of the cranial sutures or congenital fusion of the ribs Dysplasias: (osteodysplasias and chondrodysplasias) abnormal growth and does not imply precancerous lesions, Osteogenesis Imperfecta (brittle bone disease): autosomal dominant caused by defective synthesis of type I collagen (α1 or α2 chains ) premature bone degradation too little bone, resulting in extreme skeletal fragility extraskeletal manifestations (skin, joints, teeth, and eyes) blue sclerae, Hearing loss , small misshapen teeth Achondroplasia: the most common form of dwarfim. It is caused by activating point mutations in firoblast growth factor receptor 3 (FGFR3), growth of normal epiphyseal plates is suppressed, and the length of long bones is severely stunted. autosomal dominant but many cases arise from new spontaneous mutations short stature, disproportionate shortening of the proximal extremities, bowing of the legs, and frontal bossing with midface hypoplasia. ACQUIRED DISEASES OF BONE: Osteoporosis: Reduced bone mass, leading to bone fragility and susceptibility to fractures. Generalized osteoporosis may be primary or secondary insults, Primary forms of osteoporosis are most common associated with aging (senile osteoporosis) or the postmenopausal state in women. The bone loss is most prominent in the spine , femoral neck, vertebrae and the hips. MORPHOLOGY: The hallmark of osteoporosis is a loss of bone. The cortices are thinned, the trabeculae are reduced in thickness In postmenopausal osteoporosis, trabecular bone loss often is severe, resulting in compression fractures and collapse of vertebral bodies. In senile osteoporosis, cortical bone loss is prominent, predisposing to fractures in other weightbearing bones, such as the femoral neck PATHOGENESIS: Osteoporosis occurs when the dynamic balance between bone formation by osteoblasts and bone resorption by osteoclasts tilts in favor of resorption. The decline in estrogen levels associated with menopause correlates with an acceleration of cortical bone and trabecular (cancellous) bone loss. half of postmenopausal women will suffer an osteoporotic fracture reduced physical activity increases bone loss. This effect is obvious in an immobilized limb Clinical Course: Thoracic and lumbar vertebral fractures are extremely common, leading to loss of height and various deformities, including kyphoscoliosis, which can compromise respiratory function. Pulmonary embolism and pneumonia are common complications of fractures of the femoral neck, pelvis, or spine Paget Disease (Osteitis Deformans): characterized by: 1. repetitive episodes of regional osteoclastic activity and bone resorption (osteolytic stage), 2. followed by exuberant bone formation (mixed osteoclasticosteoblastic stage), and finally 3. by an apparent exhaustion of cellular activity (osteosclerotic stage). The net effect of this process is a gain in bone mass; however, the newly formed bone is disordered and weak, so bones may become enlarged and misshapen. MORPHOLOGY: Paget disease may manifest as a solitary lesion (monostotic) or may occur at multiple sites (polyostotic) In the initial lytic phase, osteoclasts are numerous, Osteoclasts persist in the mixed phase, but the bone surfaces become lined by prominent osteoblasts. The newly formed bone is remodeled into abnormal lamellar bone with a pathognomonic mosaic pattern The resulting cortex is softer than normal and prone to deformation and fracture under stress. PATHOGENESIS: It has long been postulated that a paramyxovirus infection (a slow virus) underlies Paget disease paramyxoviruses can induce IL-1 and IL-6 secretion from infected cells, and these cytokines— as well as macrophage colonystimulating factor (M-CSF)— are produced in large amounts in pagetic bone. these potently activate osteoclasts. Clinical Course: monostotic (tibia, ilium, femur, skull, vertebrae, and humerus) in 15% polyostotic in 85%; the axial skeleton or the proximal femur is involved in 80% of cases. Involvement of the ribs, fiulae, and small bones of the hands and feet is unusual. Elevations in serum alkaline phosphatase Increased urinary excretion of hydroxyproline The development of sarcoma 1% of patients. exception of vertebral bodies, which rarely harbor malignancy. Paget disease usually follows a relatively benign course. Rickets and Osteomalacia: Both are manifestations of vitamin D deficiency The fundamental defect is an impairment of mineralization and a resultant accumulation of unmineralized matrix. This contrasts with osteoporosis, in which the mineral content of the bone is normal and the total bone mass is decreased. Rickets refers to the disorder in children, in which it interferes with the deposition of bone in the growth plates. Osteomalacia is the adult counterpart, in which bone formed during remodeling is undermineralized, resulting in predisposition to fractures They may result from diets deficient in calcium and vitamin D, but probably more important is limited exposure to sunlight a deficiency of vitamin D tends to cause hypocalcemia. This in turn stimulates PTH production: (1) activates renal α1-hydroxylase, increasing the amount of active vitamin D and calcium absorption; (2) mobilizes calcium from bone; (3) decreases renal calcium excretion; and (4) increases renal excretion of phosphate. Thus, the serum level of calcium is restored to near normal, but hypophosphatemia persists, so mineralization of bone is impaired or there is high bone turnover. The gross skeletal changes: During infancy, the head and chest sustain the greatest stresses. The softened occipital bones may become flttened, the parietal bones can be buckled inward by pressure; with the release of the pressure, elastic recoil snaps the bones back into their original positions (craniotabes). frontal bossing and a squared appearance to the head. Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the “rachitic rosary.” The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles, causing them to bend inward and creating anterior protrusion of the sternum (pigeon chest deformity.) The inward pull at the margin of the diaphragm creates the Harrison groove When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing, most notably, lumbar lordosis and bowing of the legs In adults, the lack of vitamin D deranges the normal bone remodeling that occurs throughout life. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, producing the excess of persistent osteoid that is characteristic of osteomalacia. the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks. OSTEOMYELITIS: inflammation of bone and marrow Most commonly due to infection Primary or secondary acute or chronic, most common etiologic agents : staph aureus( pyogenic) and Mycobacterium tuberculosis Pyogenic Osteomyelitis: Most cases of acute osteomyelitis 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; or (3) traumatic implantation after compound fractures or orthopedic procedures. Staphylococcus aureus is the most frequent causative organism; Escherichia coli and group B streptococci are important causes of acute osteomyelitis in neonates. Salmonella is an especially common pathogen in persons with sickle cell Mixed bacterial infections, including anaerobes, typically are responsible for osteomyelitis secondary to bone trauma. 50% of cases, no organisms can be isolated. MORPHOLOGY: Sequestrum: infected Entrapped bone becomes necrotic subperiosteal abscesses Rupture of the periosteum can lead to abscess formation in the surrounding soft tissue that may lead to a draining sinus epiphyseal infection can spread into the adjoining joint to produce suppurative arthritis Reactive woven or lamellar bone can be deposited; when it forms a shell of living tissue around a sequestrum, it is called an involucrum Clinical Features: acute systemic illness, with malaise, fever, leukocytosis, and throbbing pain over the affected region. The diagnosis is suggested by characteristic radiologic findings: a destructive lytic focus surrounded by edema and a sclerotic rim blood cultures are positive, but biopsy and bone cultures are usually required to identify the pathogen A combination of antibiotics and surgical drainage usually is curative Chronicity may develop(quarter of cases ) with delay in diagnosis, extensive bone necrosis, abbreviated antibiotic therapy, inadequate surgical debridement, and/ or weakened host defenses chronic osteomyelitis also may be complicated by: 1. pathologic fracture, 2. secondary amyloidosis, 3. endocarditis, 4. Sepsis 5. development of squamous cell carcinoma if the infection creates a sinus tract, 6. rarely osteosarcoma. Tuberculous Osteomyelitis: Bone infection complicates an estimated 1% to 3% of cases of pulmonary tuberculosis organisms usually reach the bone through the bloodstream, although direct spread from a contiguous focus of infection (e.g., from mediastinal nodes to the vertebrae) also can occur. 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 inflmmation 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 deficit Extension of the infection to the adjacent soft tissues with the development of psoas muscle abscesses is fairly common