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Manifestations may be local (eg, cellulitis, abscess) or systemic, most often fever. Manifestations may develop in multiple organ systems. Severe, generalized infections may produce life-threatening manifestations (eg, sepsis, septic shock—see Sepsis and Septic Shock). Most manifestations improve with successful treatment of the underlying infection. Infectious diseases commonly increase the numbers of mature and immature circulating neutrophils. Mechanisms include demargination and release of immature granulocytes from bone marrow, IL-1– and IL-6–mediated release of neutrophils from bone marrow, and colony-stimulating factors elaborated by macrophages, lymphocytes, and other tissues. Exaggeration of these phenomena (eg, in trauma, inflammation, and similar stresses) can result in release of excessive numbers of immature leukocytes into the circulation (leukemoid reaction, with leukocyte counts up to 25 to 30 × 109/L).
Conversely, some infections (eg, typhoid fever, brucellosis) commonly produce neutropenia. In overwhelming, severe infections, profound neutropenia is often a poor prognostic sign. Characteristic morphologic changes in the neutrophils of septic patients include Döhle bodies, toxic granulations, and vacuolization.
Anemia can develop despite adequate tissue iron stores. If chronic, plasma iron and total iron-binding capacity may be decreased. Serious infection, particularly with gram-negative organisms, may cause disseminated intravascular coagulation (DIC—see Coagulation Disorders: Disseminated Intravascular Coagulation (DIC)).
Although most infections increase the pulse rate, others, such as typhoid fever, tularemia, brucellosis, and dengue, may not elevate the pulse rate commensurate with the degree of fever. Hypotension can result from hypovolemia or septic shock.
Hyperventilation and respiratory alkalosis are common. Subsequently, pulmonary compliance may decrease, progressing to acute respiratory distress syndrome (ARDS) and respiratory muscle failure.
Renal manifestations range from minimal proteinuria to acute renal failure, which can occur due to shock and acute tubular necrosis, glomerulonephritis, or tubulointerstitial disease.
Hepatic dysfunction, including cholestatic jaundice (often a poor prognostic sign) or hepatocellular dysfunction, occurs with many infections, even though the infection does not localize to the liver. Upper GI bleeding due to stress ulceration may occur during sepsis.
Alterations in sensorium (encephalopathy) may occur in severe infection regardless of whether there is CNS infection. Encephalopathy is most common and serious in the elderly and may produce anxiety, confusion, delirium, stupor, seizures, and coma.
Endocrinologic dysfunctions include increased production of thyroid-stimulating hormone, vasopressin , insulin , and glucagon; breakdown of skeletal muscle proteins and muscle wasting secondary to increased metabolic demands; and bone demineralization. Hypoglycemia occurs infrequently in sepsis and may be an early sign of infection in diabetics.
Fever
Fever is elevated body temperature (eg, > 37.8 ° C orally or 38.2 ° C rectally, or an elevation of body temperature above the normal daily variation). During a 24-h period, temperature varies from lowest levels in the early morning to highest in late afternoon. The maximum variation is about 0.6 ° C. Body temperature is determined by the balance between heat production from tissues, particularly the liver and muscles, and heat loss from the periphery. In health, the hypothalamic thermoregulatory center maintains body temperature of the internal organs from 37 to 38° C. Fever raises the hypothalamic set point, triggering the vasomotor center to begin vasoconstriction, shunting blood from the periphery to decrease heat loss, and sometimes inducing shivering, which increases heat production until the temperature of the blood bathing the hypothalamus reaches the new set point. Resetting the hypothalamic set point downward (eg, with antipyretic drugs) initiates heat loss through sweating and vasodilation. The capacity to generate a fever is diminished in certain patients (eg, alcoholics, the very old, the very young).
Etiology
The cause of fever may be infectious or noninfectious (eg, inflammatory, neoplastic, environmental, and drug-mediated and immunologically mediated causes). Fever may be intermittent, characterized by daily spikes followed by a return to normal temperature, or remittent, in which the temperature does not return to normal until the cause resolves.
Pyrogens are substances that cause fever. Exogenous pyrogens are usually microbes or their products. The best studied are the lipopolysaccharides of gram-negative bacteria (commonly called endotoxins) and the Staphylococcus aureus toxin that produces toxic shock syndrome.
Exogenous pyrogens usually cause fever by inducing release of endogenous pyrogens (IL-1, tumor necrosis factor, interferon-γ, and IL-6). These are polypeptides produced by host cells, particularly monocyte-macrophages, that elevate the hypothalamic set point. Prostaglandin E2 synthesis appears to play a critical role.
Symptoms and Signs
Fever can be very uncomfortable. A minority of children are at risk for febrile seizures. Fever can increase O2 demands by 13% for every 1 °C increase over 37 °C, which is particularly problematic in adults with preexisting cardiac or pulmonary insufficiency. Fever can also worsen mental status in patients with dementia.
Diagnosis
Fever is most accurately diagnosed by measuring rectal temperature. Oral temperatures are normally about 0.6°C lower. Oral measurement produces falsely low temperatures in many situations (eg, recent cold drink, mouth-breathing, hyperventilation, inadequate time of measurement [up to several minutes are occasionally required]). Measurement by tympanic membrane is inaccurate compared with rectal temperature.
Fever suggests infection. However, it can have other causes, and patients incapable of generating fever may have normal or low temperatures during severe infections. The degree of elevation in temperature usually does not predict the likelihood or cause of infection.
Treatment
Whether to treat fever due to infection is controversial. Experimental evidence, but not clinical studies, suggests that fever enhances host defenses. Patients at particular risk for whom treatment of fever is indicated include children with previous febrile seizures, adults with cardiac or pulmonary insufficiency, and those with dementia. Drugs that inhibit brain cyclooxygenase are effective in reducing fever; those used most often are acetaminophen , aspirin , and other NSAIDs. Treatment of fever in children is discussed in Approach to the Care of Normal Infants and Children: Treatment.
Last full review/revision November 2005
Content last modified November 2005
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