Anemia

Background
Anemia, like a fever, is a symptom of disease that requires investigation to determine the underlying etiology. Often, practicing physicians overlook mild anemia. This is similar to failing to seek the etiology of a fever. The purpose of this article is to provide a method of determining the etiology of an anemia.

Anemia is strictly defined as a decrease in red blood cell (RBC) mass. Methods for measuring RBC mass are time consuming, are expensive, and usually require transfusion of radiolabeled erythrocytes. Thus, in practice, anemia is usually discovered and quantified by measurement of the RBC count, hemoglobin (Hb) concentration, and hematocrit (Hct). These values should be interpreted cautiously because they are concentrations affected by changes in plasma volume. For example, dehydration elevates these values, and increased plasma volume in pregnancy can diminish them without affecting the RBC mass.
Pathophysiology
Erythroid precursors develop in bone marrow at rates usually determined by the requirement for sufficient circulating Hb to oxygenate tissues adequately. Erythroid precursors differentiate sequentially from stem cells to progenitor cells to erythroblasts to normoblasts in a process requiring growth factors and cytokines. This process of differentiation requires several days. Normally, erythroid precursors are released into circulation as reticulocytes.

Reticulocytes remain in the circulation for approximately 1 day before reticulin is excised by reticuloendothelial cells with the delivery of the mature erythrocyte into circulation. The mature erythrocyte remains in circulation for about 120 days before being engulfed and destroyed by phagocytic cells of the reticuloendothelial system. Read more »

Dengue Fever

Background
Dengue, the most common arboviral illness transmitted worldwide, is caused by infection with 1 of the 4 serotypes of dengue virus, family Flaviviridae, genus Flavivirus (single-stranded nonsegmented RNA viruses). Dengue is transmitted by mosquitoes of the genus Aedes, which are widely distributed in subtropical and tropical areas of the world, and is classified as a major global health threat by the World Health Organization (WHO).

Initial dengue infection may be asymptomatic (50%-90%), may result in a nonspecific febrile illness, or may produce the symptom complex of classic dengue fever (DF). A small percentage of persons who have previously been infected by one dengue serotype develop bleeding and endothelial leak upon infection with another dengue serotype. This syndrome is termed dengue hemorrhagic fever (DHF), although dengue vasculopathy has been proposed as a better term, as fluid loss into tissue spaces can lead to prolonged shock and complications, including gastrointestinal bleeding, a greater fatality risk than bleeding per se. Some patients with dengue hemorrhagic fever develop shock (dengue shock syndrome [DSS]), which may cause death.

Dengue virus transmission follows two general patterns—epidemic dengue and hyperendemic dengue. Epidemic dengue transmission occurs when dengue virus is introduced into a region as an isolated event that involves a single viral strain. If the number of vectors and susceptible pediatric and adult hosts is sufficient, explosive transmission can occur, with an infection incidence of 25%-50%. Mosquito-control efforts, changes in weather, and herd immunity contribute to the control of these epidemics. Transmission appears to begin in urban centers and then spreads to the rest of a country. This is the current pattern of transmission in parts of Africa and South America, areas of Asia where the virus has reemerged, and small island nations. Travelers to these areas are at increased risk of acquiring dengue during these periods of epidemic transmission.

Hyperendemic dengue transmission is characterized by the continuous circulation of multiple viral serotypes in an area where a large pool of susceptible hosts and a competent vector (with or without seasonal variation) are constantly present. This is the predominant pattern of global transmission. In these populations, antibody prevalence increases with age and most adults are immune. Hyperendemic transmission appears to be a major risk for dengue hemorrhagic fever. Travelers to these areas are more likely to be infected than are travelers to areas that experience only epidemic transmission. Read more »

Brain Abscess

Background

Intracranial abscesses are uncommon, serious, life-threatening infections. They include brain abscess and subdural or extradural empyema and are classified according to the anatomical location or the etiologic agent. The term brain abscess is used in this article to represent all types of intracranial abscesses.

Intracranial abscesses can originate from infection of contiguous structures (eg, otitis media, dental infection, mastoiditis, sinusitis) secondary to hematogenous spread from a remote site (especially in patients with cyanotic congenital heart disease), after skull trauma or surgery, and, rarely, following meningitis. In at least 15% of cases, no source can be identified.

In recent years, the complex array of etiologic agents that cause brain abscess has become better understood.

Pathophysiology

Brain abscess is caused by intracranial inflammation with subsequent abscess formation. In at least 15% of cases, the source of the infection is unknown (cryptogenic). Infection may enter the intracranial compartment directly or indirectly via 3 routes.

Contiguous suppurative focus (45-50% of cases)

Direct extension may occur through necrotic areas of osteomyelitis in the posterior wall of the frontal sinus, as well as through the sphenoid and ethmoid sinuses.This direct route of intracranial extension is more commonly associated with chronic otitic infection and mastoiditis than with sinusitis. Odontogenic infections can spread to the intracranial space via direct extension or a hematogenous route. Contiguous spread could extend to various sites in the central nervous system, causing cavernous sinus thrombosis; retrograde meningitis; and epidural, subdural, and brain abscess. Read more »

Tetanus

Background

The word tetanus comes from the Greek tetanos, which is derived from the term teinein, meaning to stretch. Tetanus appears in military medical documents throughout the ages. Slapping infected dung on the umbilical cords of newborns (ie, as part of ritualistic ceremonies) caused rampant tetanus neonatorum or trismus nascentium in the West Indies and in Africa. Osler’s textbook describes the “eight days sickness” caused by umbilical sepsis, which killed 84 of 125 children within a fortnight of birth in St. Kilda, Scotland. During World War I, tetanus occurred in 1.47 per 1000 British wounded and in 12.5 per 1000 persons involved in the Peninsular campaign. Nicolaier discovered the anaerobic bacillus Clostridium tetani in 1885. In 1889, Koch’s pupil, Kitasato, obtained the bacillus of tetanus in pure culture and associated the disease to animals.

Although rare, the disease has not been eradicated, and early diagnosis and intervention are life saving. Prevention is the ultimate management strategy for tetanus. The 4 clinical types of tetanus are generalized, local, cephalic, and neonatal.

Neonatal tetanus is a major cause of infant mortality in underdeveloped countries, but this form is rare in the United States. Infection results from cord contamination during unsanitary delivery conditions, coupled with a lack of maternal immunization. At the end of the first week of life, infected infants become irritable, feed poorly, and develop rigidity with spasms. This form of tetanus has a very poor prognosis for survival.

Cephalic tetanus is uncommon and usually occurs following head trauma or otitis media. Patients with this form present with cranial nerve palsies. The infection may be localized or may become generalized.

Patients with local tetanus present with persistent rigidity in the muscle group close to the injury site. The muscular rigidity is caused by a dysfunction in the interneurons that inhibit the alpha motor neurons of the affected muscles. No further CNS involvement occurs, and this form has very low mortality rates. Read more »

Mycoplasma Infections

Background

Mycoplasma species are the smallest free-living organisms. These organisms are unique among prokaryotes in that they lack a cell wall, a feature largely responsible for their biologic properties such as their lack of a reaction to Gram stain and their lack of susceptibility to many commonly prescribed antimicrobial agents, including beta-lactams. Mycoplasmal organisms are usually associated with mucosal surfaces, residing extracellularly in the respiratory and urogenital tracts. They rarely penetrate the submucosa, except in the case of immunosuppression or instrumentation, when they may invade the bloodstream and disseminate to different organs and tissues throughout the body.

Although scientists have isolated at least 17 species of Mycoplasma from humans, 4 types of organisms are responsible for most clinically significant infections that may come to the attention of practicing physicians. These species are Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma species. The focus of this article is infections caused by M pneumoniae; articles on Ureaplasma infections (eg, Ureaplasma Infection) and genital mycoplasmal infections contain discussions of infections caused by other mycoplasmal species.

Pathophysiology

M pneumoniae is perhaps best known as the cause of walking or atypical pneumonia, but the most frequent clinical syndrome caused by this organism is actually tracheobronchitis or bronchiolitis, often accompanied by upper respiratory tract manifestations. Pneumonia develops in only 5%-10% of persons who are infected. Acute pharyngitis and myringitis are less common.

After inhalation of respiratory aerosols, the organism attaches to host cells in the respiratory tract. The P1 adhesin and other accessory proteins mediate attachment, followed by induction of ciliostasis, local inflammation that consists primarily of perivascular and peribronchial infiltration of mononuclear leukocytes, and tissue destruction that may be mediated by liberation of peroxides. Recently, M pneumoniae has been shown to produce an exotoxin that is believed to play a role in the damage to the respiratory epithelium that occurs during acute infection. The organism also has the ability to exist intracellularly. Additionally, acute mycoplasmal respiratory tract infection may be associated with exacerbations of chronic bronchitis and asthma. More extensive information on the pathogenesis of mycoplasmal respiratory infections is available in a recent review article.

Spread of infection throughout households is common, although person-to-person transmission is slower than for many other common bacterial respiratory tract infections; close contact appears necessary. Generally, the incubation period is 2-3 weeks. The organism may persist in the respiratory tract for several months, and sometimes for years in patients who are immunosuppressed, after initial infection. Read more »