Porth's Essentials of Pathophysiology, 4e

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Mechanisms of Infectious Disease

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that an infectious agent survive the low pH and enzyme activity of gastric secretions and the peristaltic action of the intestines in numbers sufficient to establish infec- tion, deemed an infectious dose. Ingested pathogens also must compete successfully with the normal bacterial flora of the bowel for nutritional needs. Persons with reduced gastric acidity because of disease or medication are more susceptible to infection by ingestion because the number of ingested microorganisms surviving the gastric environment is greater. Ingested pathogens also must compete successfully for nutrients with the nor- mal bacterial flora of the colon. Ingestion has also been postulated as a means of transmission of HIV infection from mother to child through breast-feeding. Inhalation. The respiratory tract of a healthy person is equipped with a multilayered defense system to prevent potential pathogens from entering the lungs. The sur- face of the respiratory tree is lined with a layer of mucus that is continuously swept up and away from the lungs and toward the mouth by the beating motion of ciliated epithelial cells. Humidification of inspired air increases the size of aerosolized particles, which are effectively filtered by the mucous membranes of the upper respira- tory tract. Coughing also aids in the removal of particu- late matter from the lower respiratory tract. Respiratory secretions contain antibodies and enzymes capable of inactivating infectious agents. Particulate matter and microorganisms that ultimately reach the lungs are cleared by phagocytic cells. Despite this impressive array of protective mecha- nisms, a number of pathogens can invade the human body through the respiratory tract, including agents of bacterial pneumonia ( Streptococcus pneumoniae, L. pneumophila ), meningitis ( Neisseria meningitidis, Haemophilus influen- zae ), and tuberculosis, as well as the viruses responsible for measles, mumps, chickenpox, influenza, and the com- mon cold. Defective pulmonary function or mucociliary clearance caused by noninfectious processes such as cystic fibrosis, emphysema, or smoking can increase the risk of inhalation-acquired diseases. Source The source of an infectious disease refers to the location, host, object, or substance from which the infectious agent was acquired: essentially the “who, what, where, and when” of disease transmission. The source may be endogenous (acquired from the host’s own microbial flora, as would be the case in an opportunistic infec- tion) or exogenous (acquired from sources in the exter- nal environment, such as the water, food, soil, or air). The source of the infectious agent can also be another human being, as from mother to child during gestation (congenital infections); an inanimate object; an animal; or a biting arthropod. Inanimate objects that carry an infectious agent are known as fomites . For example, rhinoviruses and many other nonenveloped viruses can be spread by contact with contaminated fomites such as handkerchiefs and toys. Zoonoses are a category of infectious diseases passed from other animal species

to humans. Examples of zoonoses include cat-scratch disease, rabies, and Creutzfeldt-Jakob disease (vCJD). The spread of infectious diseases such as Lyme disease through biting arthropod vectors has already been mentioned. Source can denote a place. For instance, infections that develop in patients while they are hospitalized are called nosocomial or hospital acquired , and those that are acquired outside of health care facilities are called community acquired. The source may also pertain to the body substance that is the most likely vehicle for transmission, such as feces, blood, body fluids, respira- tory secretions, and urine. Infections can be transmit- ted from person to person through shared inanimate objects (fomites) contaminated with infected body fluids. An example of this mechanism of transmission would include the spread of the HIV and hepatitis B virus through the use of shared syringes by intravenous drug users. Infection can also be spread through a com- plex combination of source, portal of entry, and vec- tor. Infection with hantavirus pulmonary syndrome is a prime example. This viral illness is transmitted from mice to humans by inhalation of dust contaminated with saliva, feces, and urine of infected rodents. Mechanisms of Disease Production Infectious agents establish infection and damage tissues by entering host cells and directly causing their death; by inducing host responses that, although directed against the invader, cause additional tissue damage; and by generating virulence factors , substances or products generated by infectious agents that enhance their ability to cause disease. Although a large number of microbial products fit this description, they can be grouped into four categories: toxins, adhesion factors, evasive fac- tors, and invasive factors (Table 14-2). Toxins Toxins are substances that alter or destroy the normal function of the host or host’s cells. Toxin production is a trait chiefly monopolized by bacterial pathogens, although certain fungal and protozoan pathogens also produce substances toxic to humans. Bacterial toxins have a diverse spectrum of activity and exert their effects on a wide variety of host target cells. For classification purposes, however, the bacterial toxins can be divided into two main types: endotoxins and exotoxins. Bacterial endotoxins are lipopolysaccharides (LPS) found in the cell wall of gram-negative bacteria. Free LPS attaches to a circulating LPS-binding protein, and the complex then binds to specific leukocyte receptors that participate in activation of the innate immune sys- tem (see Chapter 15). The host response to low levels of LPS induces many important cytokines, as well as expression of costimulatory molecules, resulting in leu- kocyte recruitment and enhancement of T-lymphocyte activation. However, at high levels, LPS can precipitate septic shock, disseminated intravascular coagulation, and acute respiratory distress syndrome.