The topic of the lesson “Osteomyelitis.” According to the evidence-based data from UpToDate extracted March of 19, 2020 Provide a conspectus in a format of .ppt (.pptx) presentation of not less than 50 slides containing information on: 1. Classification 2. Etiology 3. Pathogenesis 4. Diagnostic 5. Differential diagnostic 6. Treatment With 10 (ten) multiple answer questions. Pathogenesis of osteomyelitis - UpToDate Official reprint from UpToDate® www.uptodate.com ©2020 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Print Options Print | Back Text References Graphics Pathogenesis of osteomyelitis Contributor Disclosures Author: Madhuri M Sopirala, MD, MPH Section Editor: Denis Spelman, MBBS, FRACP, FRCPA, MPH Deputy Editor: Elinor L Baron, MD, DTMH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Feb 2020. | This topic last updated: Jan 17, 2020. INTRODUCTION Osteomyelitis is an infection involving bone. The pathogenesis and pathology of osteomyelitis will be reviewed here. The clinical manifestations, diagnosis, and treatment of osteomyelitis are discussed separately. (See "Osteomyelitis in adults: Clinical manifestations and diagnosis" and "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis" and "Osteomyelitis associated with open fractures in adults" and "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities" and "Vertebral osteomyelitis and discitis in adults".) CLASSIFICATION Osteomyelitis may be divided into two major categories based upon the pathogenesis of infection: (1) hematogenous osteomyelitis and (2) nonhematogenous osteomyelitis, which develops adjacent to a contiguous focus of infection or via direct inoculation of infection into the bone [1-3]. (See "Osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Classification'.) Either hematogenous or contiguous-focus osteomyelitis can be classified as acute or chronic. Acute osteomyelitis evolves over several days to weeks and can progress to a chronic infection [1]. The hallmark of chronic osteomyelitis is the presence of dead bone (sequestrum). Other common features of chronic osteomyelitis include involucrum (reactive bony encasement of the sequestrum), local bone loss, and, if there is extension through cortical bone, sinus tracts. Brodie abscess is a form of subacute osteomyelitis that is usually hematogenous in origin but can occur as a the result of trauma; the classic presentation of Brodie abscess consists of a cavity filled with suppurative and/or granulation in a long bone metaphysis, surrounded by dense fibrous tissue and sclerotic bone [4]. https://www.uptodate.com/...rint?search=osteomyelitis&source=search_result&selectedTitle=7~150&usage_type=default&display_rank=7[19.03.2020 15:32:22] Pathogenesis of osteomyelitis - UpToDate PATHOGENESIS Normal bone is highly resistant to infection. Osteomyelitis develops when there is a large inoculation of organisms, presence of bone damage, and/or presence of hardware or other foreign material. The pathogenesis of osteomyelitis is multifactorial and poorly understood; important factors include the virulence of the infecting organism(s), the host immune status, and the bone vascularity. Bacteria have a number of virulence determinants that may contribute to development of osteomyelitis in the appropriate clinical setting. Staphylococcus aureus, the most common cause of osteomyelitis, has been used extensively as a model to study pathogenesis and is therefore discussed in detail in this section. It is an important cause (though not the only cause) of hematogenous and contiguous focus osteomyelitis. S. aureus produces several extracellular and cell-associated factors that may contribute to virulence by promoting bacterial adherence, resistance to host defense mechanisms, and proteolytic activity. Bacterial adherence — Adherence appears to play a central role in the early stages of S. aureus- induced osteomyelitis or arthritis. S. aureus adheres to a number of components of bone matrix including fibrinogen, fibronectin, laminin, collagen, bone sialoglycoprotein, and clumping factor A [5-9]. Adherence is mediated by expression of specific adhesins, called microbial surface components recognizing adhesive matrix molecules [5,10]. The potential importance of adhesins was illustrated in a study in which mice were inoculated with positive and negative mutants for the collagen adhesin gene: septic arthritis occurred with greater frequency in the mutant-positive compared with mutant-negative strains (>70 versus 27 percent) [11]. The adhesin-positive strains were also associated with the production of high levels of immunoglobulin G (IgG) and interleukin 6. In other experimental studies, S. aureus adhesion was blocked by antibodies directed against the collagen receptor [12]. It has been speculated that bone and other invasive S. aureus infections might be prevented by an adhesin-derived vaccine [13]. Collagen-binding adhesin (CNA) of S. aureus is a virulence factor for arthritis in several animal models [14,15]. The expression of CNA permits the attachment of pathogen to cartilage [16]. How CNA contributes to virulence and whether it is important in humans are unclear. Fibronectin-binding protein rapidly coats implanted foreign bodies in vivo and adheres to biomaterials coated with host proteins. It may be particularly important in infections associated with prosthetic joints [7]. Atomic-force microscopy has demonstrated that fibronectin-binding proteins A and B (FnBPA and FnBPB) form bonds with host fibronectin and may play a key role in binding S. aureus to implants [17]. (See "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis".) Resistance to host defense — The ability of microorganisms to resist host defense mechanisms at the cellular and matrix levels presents difficulties in the management of osteomyelitis. https://www.uptodate.com/...rint?search=osteomyelitis&source=search_result&selectedTitle=7~150&usage_type=default&display_rank=7[19.03.2020 15:32:22] Pathogenesis of osteomyelitis - UpToDate As an example, S. aureus can survive intracellularly in cultured osteoblasts. Persistence of intracellular pathogens within osteoblasts may also be an important factor in the pathogenesis of osteomyelitis. When digested by osteoblasts, S. aureus undergoes phenotypic alteration, which renders it more resistant to the action of antimicrobials. This may explain in part the high relapse rate of osteomyelitis treated with antimicrobials for a short duration [2,18]. Osteoblast persistence of S. aureus in chronic osteomyelitis has been described [19,20]. Arachidonic acid metabolites, such as prostaglandin E2, a strong osteoclast agonist, decrease the bacterial inoculum needed to produce infection. S. aureus expresses a 42-kDa protein, protein A, which is bound covalently to the outer peptidoglycan layer of their cell walls. Protein A binds to the Fc portion of IgG on polymorphonuclear leukocytes, interfering with opsonization and phagocytosis of S. aureus [21]. Loss of protein A activity reduces virulence [22]. S. aureus secretes two toxins, exotoxin and toxic shock syndrome toxin (TSST-) 1, which exert important effects on the immune system when administered parenterally. The toxins act as superantigens and suppress plasma cell differentiation; they also stimulate production of cytokines, such as interleukin 1 [23], interferon-gamma, and tumor necrosis factor-alpha [24]. Animals infected with strains of S. aureus isogenic for TSST-1 develop frequent and severe arthritis [25]. Staphylococcal enterotoxin and TSST-1 subvert the cellular and humoral immune system, which may determine whether a local infection is eliminated or develops into osteomyelitis or septic arthritis. HISTOPATHOLOGY Overview — Acute osteomyelitis demonstrates suppurative infection with acute inflammatory cells, accompanied by edema, vascular congestion, and small vessel thrombosis (picture 1 and picture 2). In early acute disease, the vascular supply to the bone is compromised by infection extending into the surrounding soft tissue. When both the medullary and periosteal blood supplies are compromised, large areas of dead bone (sequestra) may form [26]. Within this necrotic and ischemic tissue, bacteria can be difficult to eradicate even in the setting of an intense host response, surgery, and antibiotic therapy. Clinically and histologically, acute osteomyelitis blends into chronic osteomyelitis. Pathologic features of chronic osteomyelitis include necrotic bone, the formation of new bone, and polymorphonuclear leukocyte exudation joined by large numbers of lymphocytes, histiocytes, and occasional plasma cells (picture 3). Necrosis of normal tissue is an important feature of osteomyelitis. Dead bone is absorbed by the action of granulation tissue developing at its surface. Absorption takes place earliest and most rapidly at the junction of living and necrotic bone. If the area of the dead bone is small, it is entirely destroyed by granulation tissue, leaving a cavity behind. The necrotic cancellous (trabecular) bone in localized https://www.uptodate.com/...rint?search=osteomyelitis&source=search_result&selectedTitle=7~150&usage_type=default&display_rank=7[19.03.2020 15:32:22] Pathogenesis of osteomyelitis - UpToDate osteomyelitis, even though extensive, is usually absorbed. Some of the dead cortical bone is gradually detached