Porth's Essentials of Pathophysiology, 4e

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Mechanisms of Infectious Disease

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measles. Other, covert symptoms, such as an increased white blood cell count, may require laboratory testing to detect. Accurate recognition and documentation of symptomatology can aid in the diagnosis of an infectious disease. Site of Infection Inflammation of an anatomic location is usually des- ignated by adding the suffix - itis to the name of the involved tissue (e.g., bronchitis, inflammation of the bronchi and bronchioles; encephalitis, brain inflam- mation; carditis, inflammation of the heart). These are general terms, however, and they apply equally to inflammation from infectious and noninfectious causes. The suffix - emia is used to designate the presence of a substance in the blood (e.g., bacteremia, viremia , and fungemia describe the presence of these infectious agents in the bloodstream). The term sepsis , or septicemia , refers to the presence of a proven bloodstream infection combined with a systemic immune response. The site of an infectious disease is ultimately deter- mined by the type of pathogen, the portal of entry, and the competence of the host’s immunologic defense sys- tem. Many pathogenic microorganisms are restricted in their capacity to invade the human body. M. pneu- moniae , influenza viruses, and respiratory syncytial virus rarely cause disease outside the respiratory tract; infections caused by N. gonorrhoeae are generally con- fined to the genitourinary tract; and Clostridium dif- ficile , shigellosis, and giardiasis seldom extend beyond the gastrointestinal tract. These are considered local- ized infectious diseases. The bacterium Helicobacter pylori is an extreme example of a site-specific pathogen. H. pylori is a significant cause of gastric ulcers but has not been implicated in disease processes elsewhere in the human body. Bacteria such as N. meningitidis , a promi- nent pathogen of children and young adults; Salmonella typhi , the cause of typhoid fever, and B. burgdorferi , the agent of Lyme disease, tend to disseminate from the primary site of infection to involve other locations and organ systems. These are examples of systemic patho- gens disseminated throughout the body by the circula- tory system. An abscess is a localized pocket of infection composed of devitalized tissue, microorganisms, and the host’s phagocytic white blood cells: in essence, a stalemate in the infectious process. In this case, the dissemination of the pathogen has been contained by the host, but white cell function within the toxic environment of the abscess is hampered, and the elimination of microorgan- isms is inhibited. Abscesses usually must be surgically drained to affect a complete cure. Similarly, infections of biomedical implants such as catheters, artificial heart valves, and prosthetic bone implants are seldom cured by the host’s immune response and antimicrobial ther- apy. The infecting organism colonizes the surface of the implant, producing a dense matrix of cells, host pro- teins, and capsular material—a biofilm—necessitating the removal of the device.

listeriosis, and Legionnaires’ disease, are adapted to survive and reproduce within phagocytic white blood cells after ingestion, avoiding or neutralizing the usu- ally lethal products contained within the lysosomes of the cell. H. pylori , the infectious cause of gastritis and gastric ulcers, produces a urease enzyme on its outer cell wall. The urease converts gastric urea into ammonia, thus neutralizing the acidic environment of the stom- ach and allowing the organism to survive in this hostile environment. Other unique strategies used by pathogenic microbes to evade immunologic surveillance have evolved solely to avoid recognition by host antibodies. Strains of S. aureus produce a surface protein (protein A) that immobilizes immunoglobulin G (IgG), holding the anti- gen-binding region harmlessly away from the organ- isms. This pathogen also secretes a unique enzyme called coagulase. Coagulase converts soluble human coagulation factors into a solid clot, which envelops and protects the organism from phagocytic host cells and antibodies. H. influenzae and N. gonorrhoeae secrete enzymes that cleave and inactivate secretory IgA, neu- tralizing the primary defense of the respiratory and genital tracts at the site of infection. Borrelia species, including the agents of Lyme disease and relapsing fever, alter surface antigens during the disease course to avoid immunologic detection. Invasion Factors Infectious agents also produce invasive factors that facilitate the penetration of anatomic barriers and host tissue. Most invasive factors are enzymes capable of destroying cell membranes (e.g., phospholipases), con- nective tissue (e.g., elastases, collagenases), intercellular matrices (e.g., hyaluronidase), and structural protein complexes (e.g., proteases). The effects of the pathogen’s invasive factors and toxins, combined with the antimi- crobial and inflammatory substances released by host cells, mediate the tissue damage and pathophysiology of infectious diseases. Clinical Presentation The term symptomatology refers to the collection of signs and symptoms expressed by the host during the disease course. This is also known as the clinical pre- sentation and can be characteristic of any given infec- tious agent. In terms of pathophysiology, symptoms are the outward expression of the struggle between invading organisms and the retaliatory inflammatory and immune responses of the host. The symptoms of an infectious disease may be specific and reflect the site of infection (e.g., diarrhea, rash, convulsions, hemorrhage, and pneumonia). Conversely, symptoms such as fever, myalgia, headache, and lethargy are relatively nonspecific and can be shared by a num- ber of etiologic agents. The symptoms of a diseased host can be obvious, as in the case of chickenpox or