Definition

Pneumonia is an infection of the lung parenchyma. Community-acquired pneumonia refers to pneumonia acquired outside of hospitals or extended-care facilities. Nursing homeacquired pneumonia refers to infection acquired in an extended-care facility. Nosocomial pneumonia and hospital-acquired pneumonia describe infections acquired in the hospital setting. The signs and symptoms of acute pneumonia develop over hours to days, whereas the clinical presentation of chronic pneumonia often evolves over weeks to months.

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Prevalence
Despite a broad armamentarium of antimicrobials available to treat the disease, pneumonia remains the seventh leading cause of death in the United States.1 In 2003, the age-adjusted death rate caused by influenza and pneumonia was 20.3 per 100,000 persons.1 Estimates of the incidence of community-acquired pneumonia range from 4 million to 5 million cases per year, with about 25% requiring hospitalization.2 Nosocomial pneumonia is estimated to occur in 250,000 persons per year, representing about 15% to 18% of all nosocomial infections.3,4

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Figure 1: Click to Enlarge

Microbiology
Streptococcus pneumoniae remains the most commonly identified pathogen in community-acquired pneumonia (Fig. 1). Other pathogens have been reported to cause pneumonia in the community, and their order of importance depends on the location and population studied (Table 1). These include long-recognized pathogens such asHaemophilus influenzae, Mycoplasma pneumoniae, and influenza A, along with newer pathogens such as Legionella species and Chlamydophilia pneumoniae. Other common causes in the immunocompetent patient include Moraxella catarrhalis, Mycobacterium tuberculosis, and aspiration pneumonia. The causative agent of community-acquired pneumonia remains unidentified in 30% to 50% of cases. Table 1: Identified Pathogens in Community-Acquired Pneumonia Pathogen Streptococcus pneumoniae Cases (%) 20-60
5

Haemophilus influenzae Staphylococcus aureus Gram-negative bacilli Legionella species Mycoplasma pneumoniae Chlamydia pneumoniae Viruses Aspiration Others

3-10 3-5 3-10 2-8 1-6 4-6 2-15 6-10 3-5

Adapted from Mandell LA, Bartlett JG, Dowell SF, et al: Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003;37:1405-1433. 2002 The Cleveland Clinic Foundation.

Previously seen mainly in extended-care facilities and acute-care hospitals, strains of methicillinresistant Staphylococcus aureus (MRSA) have emerged as prevalent pathogens in community settings.6 Necrotizing pneumonia is a characteristically severe manifestation of these virulent strains. A new human pathogen, severe acute respiratory syndrome (SARS)-associated coronavirus, emerged and spread worldwide in the winter of 2002 to 2003. No cases have been identified since 2004. Data regarding this virus and its
7 associated syndrome, SARS, can be found on the SARS page of the website of the Centers for Disease Control and

Prevention (CDC), available at http://www.cdc.gov/ncidod/sars. Influenza continues to be a prevalent seasonal disease in the United States, causing considerable morbidity, loss of productivity, and mortality. A strain of H5N1 influenza has spread rapidly through avian flocks in Asia and Europe. Cases of transmission from birds to humans with severe disease have led to international concern about a possible avian influenza pandemic. Readers are encouraged to check the CDC influenza page, available at http://www.cdc.gov/flu/avian/index.htm, for updated prevention and treatment guidelines, as well as the latest epidemiologic information. Other viral causes of respiratory tract infections include parainfluenza virus, adenovirus, human metapneumovirus, herpes zoster virus (HSV), varicella-zoster virus (VZV), and measles. Many pathogens listed as potential agents of bioterrorism are spread by the respiratory route. Among the most likely candidates are Bacillus anthracis, Francisella tularensis, and Yersinia pestis. A more extensive discussion of the agents of bioterrorism can be found elsewhere in this section (Biologic Weapons and the Primary Care Clinician).

Nursing homeacquired pneumonias are often caused by community-acquired pathogens. However, there is an increased influence of pathogens seen with relatively low frequency in the community, such as S. aureus and gramnegative organisms.

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Pathophysiology
Six mechanisms have been identified in the pathogenesis of pneumonia in immunocompetent adults (Table 2). Inhalation of infectious particles is probably the most important pathogenetic mechanism in the development of community-acquired pneumonia, with particular importance of pneumonia caused by Legionella species and M. tuberculosis. Table 2: Pathogenetic Mechanisms in Pneumonia Mechanism Inhalation of infectious particles Aspiration of oropharyngeal or gastric contents Hematogenous deposition Invasion from infection in contiguous structures Direct inoculation Reactivation
2002 The Cleveland Clinic Foundation.

Frequency Common Common Uncommon Rare Less common More common in immunocompromised hosts

The aspiration of oropharyngeal or gastric contents is the most prevalent pathogenetic mechanism in nosocomial pneumonia, with several contributing factors. Swallowing and epiglottic closure may be impaired by neuromuscular disease, stroke, states of altered consciousness, or seizures. Endotracheal and nasogastric tubes interfere with these anatomic defenses and provide a direct route of entry for pathogens. Impaired lower esophageal sphincter function and nasogastric and gastrostomy tubes increase the risk of aspiration of gastric contents. Fortunately, aspiration rarely leads to overt bacterial pneumonia. Direct inoculation rarely occurs as a result of surgery or bronchoscopy but may play a role in the development of pneumonia in patients supported with mechanical ventilation. Hematogenous deposition of bacteria in the lungs is also uncommon but is responsible for some cases of pneumonia caused by S. aureus, Pseudomonas aeruginosa, andEscherichia coli. The direct extension of infection to the lung from contiguous areas, such as the pleural or subdiaphragmatic spaces, is rare.

Reactivation of pathogens can take place in the setting of deficits of cell-mediated immunity. Pathogens such asPneumocystis jiroveci, Mycobacterium tuberculosis, and cytomegalovirus can remain latent for many years after exposure, with flares of active disease occurring in the presence of immune compromise. Reactivation tuberculosis occasionally occurs in immunocompetent hosts. Once bacteria reach the tracheobronchial tree, defects in local pulmonary defenses can make infection more likely. The cough reflex can be impaired by stroke, neuromuscular disease, sedatives, or poor nutrition. Mucociliary transport is depressed with the aging process, tobacco smoking, dehydration, morphine, atropine, prior infection with influenza virus, and chronic bronchitis. Anatomic changes such as emphysema, bronchiectasis, and obstructive mass lesions prevent the clearance of microbes. Inflammatory cells drawn to infected areas of the pulmonary tree release proteolytic enzymes, altering the bronchial epithelium and ciliary clearance mechanisms and stimulating the production of excess mucus. Community-acquired MRSA strains contain Panton-Valentine leukocidin, a toxin that creates holes in neutrophil cell membranes, releasing chemotactic and inflammatory factors.7 A blunted cellular and humoral immune response can also increase the risk of pneumonia. For example, granulocyte chemotaxis is reduced with aging, diabetes mellitus, malnutrition, hypothermia, hypophosphatemia, and corticosteroids. Granulocytopenia may be caused by cytotoxic chemotherapy. Alveolar macrophages are rendered dysfunctional by corticosteroids, cytokines, viral illnesses, and malnutrition. Diminished antibody production or function can accompany hematologic malignancies such as multiple myeloma or chronic lymphocytic leukemia.

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History and physical examination

Because the clinical syndromes characterizing pneumonic infections caused by various agents often overlap one another and because interobserver variability regarding physical findings of pneumonia is high, the diagnosis of pneumonia can be challenging. A diligent history (Table 3) and physical examination can help narrow the differential diagnosis. In general, typical bacterial pathogens such as S. pneumoniae, H. influenzae, and the enteric gramnegative organisms usually manifest acutely with high fever, chills, tachypnea, tachycardia, and productive cough. Examination findings are localized to a specific lung zone and can include rales, rhonchi, bronchial breath sounds, dullness, increased fremitus, and egophony. In contrast, atypical pathogens such as Mycoplasma, Chlamydophilia, and viruses can manifest in a subacute fashion with fever, nonproductive cough, constitutional symptoms, and absent or diffuse findings on lung examination. Rapid progression of disease to respiratory failure can be seen in severe pneumococcal or Legionella pneumonia. Influenza may be complicated by bacterial pneumonia caused by S. aureus or S. pneumoniae. Table 3: Microbiologic Differential Diagnosis of Pneumonia: Historical Features History Associated Organisms

Alcoholism Chronic obstructive lung disease (COPD) Exposure to bat or bird droppings, construction sites, caves Exposure to birds Exposure to rabbits HIV infection

Streptococcus pneumoniae, oral anaerobes, Mycobacterium tuberculosis S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionellaspp.

Histoplasma capsulatum

Chlamydia psittaci Francisella tularensis Typical bacterial pathogens, M. tuberculosis, Pneumocystis jiroveci, cytomegalovirus, Cryptococcus spp., Histoplasma spp., Coccidioides spp.

Travel to desert, southwest United States Farm exposure Postinfluenza Aspiration Marijuana smoking Anatomic abnormality of lung parenchyma, e.g., bronchiectasis, cystic fibrosis Injection drug use Obstruction of large airway Incarceration Neutropenia Asplenia

Coccidioides spp., Hantavirus (Sin Nombre virus)

Coxiella burnetii (animals), Aspergillus spp. (barns, hay) S. pneumoniae, S. aureus, Streptococcus pyogenes, H. influenzae Mixed aerobic, anaerobic Aspergillus spp. Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus

S. aureus, anaerobes, M. tuberculosis, and S. pneumoniae Anaerobes, S. pneumoniae, H. influenzae, S. aureus

M. tuberculosis Aspergillus spp., Zygomycetes S. pneumoniae, H. influenzae

Adapted from Mandell LA, Bartlett JG, Dowell SF, et al: Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003;37:1405-1433. 2002 The Cleveland Clinic Foundation.

SARS manifests with high fever and myalgia for 3 to 7 days, followed by a nonproductive cough and progressive hypoxemia, with progression to mechanical ventilation in 20% of cases. This can be distinguished from other viral infections by the higher fever and lack of conjunctivitis, sneezing, rhinorrhea, and pharyngitis. Inhalation anthrax can manifest with flulike symptoms of myalgia, fatigue, and fever before rapidly progressing to respiratory distress, mediastinitis, meningitis, sepsis, and death. The age of the patient can play an important role in disease presentation. Older patients often have humoral and cellular immunodeficiencies as a result of underlying diseases, immunosuppressive medications, and the aging process. They are more commonly institutionalized with anatomic problems that inhibit the pulmonary clearance of pathogens. The presentation is often more subtle than in younger adults, with more-advanced disease and sepsis, despite minimal fever and sputum production. Extrapulmonary physical findings can provide clues to the diagnosis. Poor dentition and foul-smelling sputum can indicate the presence of a lung abscess with an anaerobic component. Bullous myringitis can accompany infection with M. pneumoniae. An absent gag reflex or altered sensorium raises the question of aspiration. Encephalitis can complicate pneumonia caused by M. pneumoniae or Legionella pneumophila. Cutaneous manifestations of infection can include erythema multiforme (M. pneumoniae), erythema nodosum (C. pneumoniae and M. tuberculosis), or ecthyma gangrenosum (P. aeruginosa).

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Figure 2: Click to Enlarge

Diagnostic and treatment considerations

The composition of the diagnostic workup for pneumonia has been the subject of some disagreement among experts (see later, National Guidelines), but a well-chosen evaluation can support a diagnosis of pneumonia and identify a pathogen.

Radiography
A cornerstone of diagnosis is the chest x-ray, which is recommended for diagnosis in every circumstance and usually reveals an infiltrate (Fig. 2) at presentation. However, this finding may be absent in the dehydrated patient. Also, the

radiographic manifestations of chronic diseases such as congestive heart failure, chronic obstructive pulmonary disease (COPD), and malignancy can obscure the infiltrate of pneumonia. Although radiographic patterns are usually nonspecific, they can suggest a microbiologic differential diagnosis (Table 4). Table 4: Radiographic Patterns of Common Etiologic Agents Chest Radiographic Pattern Focal; large pleural effusion Cavitary Miliary Rapid progression/multifocal Interstitial Mediastinal widening without infiltrate
2002 The Cleveland Clinic Foundation.

Pathogen Usually bacteria Bacterial abscess, fungi, acid-fast bacilli, Nocardia Acid-fast bacilli, fungi Legionella spp., Pneumococcus, Staphylococcus Viruses, Pneumocystis jiroveci, Mycoplasma, Chlamydia psittaci Inhalation anthrax

Initial Management: Risk Stratification and Treatment Setting

When community-acquired pneumonia is strongly suspected on the basis of history, physical examination, and chest radiography, the next critical management decision is whether the patient requires hospital admission. Health care budgetary constraints have given rise to a number of studies addressing the need for hospitalization in communityacquired pneumonia. A study by the Patient Outcome Research Team (PORT) investigators has validated a risk scale, now called the pneumonia severity index (PSI), for mortality in community-acquired pneumonia. Point values are assigned to patient characteristics, comorbid illness, physical examination, and basic laboratory findings (Table 5).8 Patients younger than 50 years without comorbid illness or significant vital sign abnormalities (risk class I) were found to have a low risk for mortality. The authors suggested that such patients might be eligible for outpatient antibiotic therapy without extensive laboratory evaluation. Table 5: Pneumonia Severity Index: Point Assignments in Community-Acquired Pneumonia Risk Factor Age Men Women Age (in yr) Age (in yr) 10 Point Value

Nursing home resident Comorbid Illnesses Neoplastic disease Liver disease Kidney disease Cerebrovascular disease Congestive heart failure Physical Findings Altered mentation Tachypnea (>30 breaths/min) Systolic hypotension (<90 mm Hg) Body temperature (<35 or >40 C) Heart rate >125 beats/min Laboratory and Radiographic Findings Blood pH (arterial) <7.35 Hypoxemia (arterial Pao2<60 mm Hg or O2 saturation <90%) Serum urea nitrogen (BUN) >30 mg/dL Na <130 mEq/L Blood sugar >250 mg/dL Anemia (hematocrit <30%) Pleural effusion

+10

+30 +20 +10 +10 +10

+20 +20 +20 +15 +10

+30 +10 +20 +20 +10 +10 10

Adapted from Kolleff MH, Micek ST: Methicillin-resistant Staphylococcus aureusa new community-acquired pathogen? Curr Opin Infect Dis 2006;19:161-168. 2002 The Cleveland Clinic Foundation.

All others were evaluated with the laboratory tests listed in Table 5 and assigned to risk classes by point totals (Table 6). Those in classes I and II are considered excellent candidates for outpatient oral therapy, assuming no

hemodynamic instability, no chronic oxygen dependence, immunocompetence, and the ability to ingest, absorb, and adhere to an oral regimen. Patients in risk class III may be considered for outpatient or brief inpatient therapy, depending on clinical judgment. Patients in risk classes IV and V are recommended for hospital admission. Ultimately, each decision to admit must be individualized. Table 6: Pneumonia Severity Index: Risk of 30-Day Mortality By Point Total Risk Class I II III IV V Point Score No points assigned <70 71-90 91-130 >130 Mortality (%) 0.1 0.6 2.8 8.2 29.2

Adapted from Kolleff MH, Micek ST: Methicillin-resistant Staphylococcus aureusa new community-acquired pathogen? Curr Opin Infect Dis 2006;19:161-168. 2002 The Cleveland Clinic Foundation.

A slightly less complex scheme is the CRB-65. In this algorithm, patients are felt better served by hospitalization if they they meet more than of the following criteria: confusion, respiratory rate greater than 30 breaths per minute, blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic, or age older than 65 years.9

Diagnostic Testing
When the patient is not severely ill (ie outpatient treatment or not severely ill in the inpatient setting) and has few risk factors, the consensus guidelines of the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS)10 suggest empirical therapy without extensive laboratory evaluation (Box 1). When identification of a pathogen might change therapy, further studies are indicated (see Box 1). The value of such studies is not uniformly agreed on (see later, National Guidelines). However, pathogen identification has important implications for the breadth of therapeutic antibiotic spectrum, development of resistance, and epidemiology.

Box 1: Diagnostic Testing for Community-Acquired Pneumonia All patients with suspected pneumonia Chest radiography Complete blood count Complete metabolic profile

y y y

Blood gases or pulse oximetry

Severely ill or immunocompromised patients, patients with anatomic lung disease Sputum Gram stain and culture Blood cultures: two sets before antibiotics Legionella serology, urinary antigen, direct fluorescent antibody testing Pneumococcal urinary antigen testing

y y y y

Inpatients with appropriate history or physical findings HIV serology Mycoplasma serology Chlamydia serology Fungal serology SARS-associated coronavirus serology or PCR Stains or cultures for fungi, mycobacteria, Pneumocystis jiroveci Analysis or cultures of pleural or cerebrospinal fluid Nasopharyngeal swab for viral direct fluorescent antibody or other rapid technique Tuberculin skin testing

y y y y y y y y y

Deteriorating patient without definitive diagnosis of cause Bronchoscopy (bronchoalveolar lavage, protected catheter, transbronchial biopsy) Thoracoscopic or open-lung biopsy Radiographically guided transthoracic aspirate Legionella, Chlamydia, Mycoplasma serology Fungal serology Evaluation for congestive heart failure, pulmonary embolus, neoplasm, connective tissue disease

y y y y y y

PCR, polymerase chain reaction; PORT, Patient Outcome Research Team; SARS, severe acute respiratory syndrome. Adapted Mandell LA, Wunderink RG, Anzueto A, et al; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27-S72. 2004 The Cleveland Clinic Foundation.

A Gram-stained sputum specimen can help focus empirical therapy. Unfortunately, sputum is often difficult to obtain from older patients because of a weak cough, obtundation, and dehydration. Nebulized saline treatments might help mobilize secretions. Nasotracheal suctioning can sample the lower respiratory tract directly but risks oropharyngeal contamination. A sputum specimen reflects lower respiratory secretions when more than 25 white blood cells (WBCs) and fewer than 10 epithelial cells are seen in a low-powered microscopic field.11 Empirical therapy based on a predominant organism in such a specimen is likely to contain appropriate coverage.12 Other stains, such as the acid-fast stain for mycobacteria, modified acid-fast stain for Nocardia, or toluidine blue and Gomori's methenamine silver stains should be used when directed by the history or clinical presentation. Direct fluorescent antibody (DFA) staining of sputum, bronchoalveolar lavage fluid, or pleural fluid can help identify Legionellaspecies. Similarly, DFA testing of nasopharyngeal specimens provides rapid diagnosis of influenza types A and B, as well as other common respiratory viruses such as respiratory syncytial virus, adenovirus, and parainfluenza virus. In an outbreak setting, DFA and other rapid techniques can assist in decision making for therapy and infection control. The sputum culture remains a controversial tool but is useful to help tailor therapy when the patient is severely ill, has a history of structural lung disease or alcohol abuse, has pleural effusion, or has evidence of pneumococcal or Legionellainfection. Culture is particularly helpful for identifying organisms of epidemiologic significance, either for patterns of transmission or resistance. Expectorated morning sputum specimens should be sent for mycobacterial culture when the history is suggestive. Blood cultures can also shed light on a pathogen, and samples should be drawn in severely ill or immunocompromised patients (see later, Outcomes). Pleural or cerebrospinal fluid should be sampled when infections in these spaces are suspected. When these procedures fail to yield a microbiologic diagnosis and when the patient does not respond to empirical antibiotic therapy, more-invasive diagnostic techniques may be indicated. Fiberoptic bronchoscopy allows the use of several techniques for the diagnosis of pneumonia. Bronchoalveolar lavage with saline can obtain deep respiratory specimens for the gamut of stains and cultures mentioned earlier. Transbronchial biopsy of lung parenchyma can reveal alveolar or interstitial pneumonitis, viral inclusion bodies, and fungal or mycobacterial elements. The protected brush catheter is used to distinguish quantitatively between tracheobronchial colonizers and pneumonic pathogens. A more substantial amount of lung tissue may be obtained for culture and histologic examination by thoracoscopic or open lung biopsy. Because these procedures can carry considerable morbidity, they are usually reserved for the deteriorating patient with a pneumonia that defies diagnosis by less-invasive techniques.

Serologic Testing
Often relegated to retrospective or epidemiologic interest because of delays in testing or reporting, serologic testing for such pathogens as Legionella species, Mycoplasma species, and C. pneumoniae should include sera drawn in

the acute and convalescent phases for comparison. A fourfold increase in the immunoglobulin G (IgG) titer suggests recent infection with these organisms. An IgM microimmunofluorescence titer of more than 1:16 is considered diagnostic of C. pneumoniae infection. Infection with SARS-associated coronavirus is most often diagnosed by antibody testing and polymerase chain reaction (PCR) testing. A sensitive enzyme immunoassay has been developed for the detection of L. pneumophila type 1 antigen in urine. Because the antigen persists for up to 1 year after infection, it is difficult to differentiate between past and current infections when using this assay. A urinary assay is also available for detecting S. pneumoniae cell wall polysaccharide. This assay may offer some advantage for the rapid diagnosis of pneumococcal pneumonia in culture-proven or unknown cases, but assay specificity is an ongoing question.

Molecular Techniques
Powerful molecular techniques are now being applied to the early diagnosis of pneumonia. DNA probes have been used to detect Legionella species, M. pneumoniae, and M. tuberculosis in sputum. These probes have excellent sensitivity and specificity but can yield false-positive results. The PCR assay has been used for the early detection of various pathogens that are difficult or slow to culture from sputum specimens, including atypical bacteria, viruses (e.g., influenza), and mycobacteria. Given the large percentage of pneumonia cases for which no microbial cause is identified, it is likely that molecular tools will eventually be applied to the identification and antimicrobial susceptibility testing of almost all causative agents of pneumonia.

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Summary
y y y
The patient's history can help narrow the microbial differential diagnosis. The chest radiograph is the cornerstone of diagnosis. The sputum Gram stain and culture are controversial, but they are still useful for targeting antimicrobial therapy when the patient is severely ill or immunocompromised.

y y y

Serologic testing is slow and therefore often not useful for real-time diagnosis. Molecular methods are playing an increasing role in identifying difficult-to-culture pathogens. The pneumonia severity index uses history, examination, chest radiograph, and initial laboratory test results to identify low-risk patients for outpatient treatment.

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Antimicrobial treatment
Community-Acquired Pneumonia

Antibiotic therapy for community-acquired pneumonia should always be selected with patient characteristics, place of acquisition, and severity of disease in mind. With concerns about antimicrobial overuse, health care costs, and bacterial resistance increasing, many experts believe that therapy should always follow confirmation of the diagnosis of pneumonia and should always be accompanied by a diligent effort to identify a causative agent (see later, National Guidelines). When a specific pathogen is identified, pathogen-specific therapy can be used (Table 7). Table 7: Pathogen-Specific Therapy for Community-Acquired Pneumonia in Adults Organism Streptococcus pneumoniae,penicillinsusceptible S. pneumoniae, penicillin-resistant Cefotaxime, ceftriaxone, fluoroquinolone, vancomycin, others, based on susceptibility studies Haemophilus influenzae Second- or third-generation cephalosporin, doxycycline, beta-lactam or beta-lactamase inhibitor, azithromycin, TMP-SMX Moraxella catarrhalis Second- or third-generation cephalosporin, TMP-SMX macrolide, beta-lactam or beta-lactamase inhibitor Legionella spp. Mycoplasma pneumoniae Chlamydia pneumoniae Anaerobes Enteric gram-negative bacilli Pseudomonas aeruginosa Macrolide, tetracycline, fluoroquinolone alone Doxycycline, macrolide Doxycycline, macrolide Beta-lactam or beta-lactamase inhibitor, clindamycin Third-generation cephalosporin Primary Therapy Penicillin G; amoxicillin

Aminoglycoside + ticarcillin, piperacillin, mezlocillin, ceftazidime, cefepime, aztreonam, or carbapenem

Staphylococcus aureus, methicillinsusceptible S. aureus, methicillin-resistant Bacillus anthracis

Nafcillin or oxacillin

Vancomycin or linezolid Ciprofloxacin or doxycycline + two of the following: rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, clarithromycin

Influenza A, within 48 hr of symptom

Amantidine, rimantadine, oseltamivir, zanamivir

aminoglycoside; carbapenem

onset or immunocompromised host Influenza B, within 48 hr of symptom onset or immunocompromised host

*

Oseltamivir, zanamivir

For community-acquired methicillin-resistant S. aureus, some clinicians add agents that inhibit toxin production, such as clindamycin, when

susceptibility patterns allow. TMP-SMX, trimethoprim-sulfamethoxazole. Adapted from Mandell LA, Wunderink RG, Anzueto A, et al; Infectious Diseases Society of America; American Thoracic Society: Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27-S72. 2003 The Cleveland Clinic Foundation.

When a pathogen is yet to be identified, empirical therapy is instituted. A number of expert panels have recommended empirical pneumonia therapy, most prominently IDSA and ATS (Table 8). Table 8: Empirical Antimicrobial Therapy for Community-Acquired Pneumonia In Immunocompetent Adults Patient, Setting Outpatients <60 yr No comorbid diseases Streptococcus pneumoniae Mycoplasma pneumoniae Chlamydia pneumoniae Haemophilus influenzae Viruses >65 yr or with comorbid disease or antibiotic therapy within last 3 mo S. pneumoniae (drugresistant) M. pneumoniae C. pneumoniae H. influenzae Viruses Gram-negative bacilli S. aureus Inpatients Not severely ill S. pneumoniae H. influenzae Polymicrobial Macrolide and cefotaxime or ceftriaxone, or betalactam or beta-lactamase inhibitor; fluoroquinolonealone Macrolide or doxycycline fluoroquinolone* Beta-lactam and macrolide Macrolide or doxycycline Common Pathogens Empirical Therapy

Anaerobes S. aureus C. pneumoniae Viruses Severely ill S. pneumoniae Legionella spp. Gram-negative bacilli M. pneumoniae Viruses S. aureus Azithromycin, or fluoroquinolone and cefotaxime, ceftriaxone, or beta-lactam or beta-lactamase inhibitor If P. aeruginosa possibleIV macrolide or fluoroquinolone and aminoglycoside IV, or antipseudomonal quinolone and antipseudomonal beta-lactam If MRSA possible, add vancomycin or linezolid
*

In the outpatient setting, many authorities prefer to reserve fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin) for patients with

comorbid diseases or risk factors.

In most cases, patients with pneumonias caused by these organisms should be hospitalized. Levofloxacin, gatifloxacin, moxifloxacin. Critically ill patients in areas with significant rates of high-level pneumococcal resistance and a suggestive sputum Gram stain should receive

vancomycin or a newer quinolone pending microbiologic diagnosis.

Piperacillin-tazobactam or ampicillin-sulbactam.

Cefpodoxime, cefuroxime, high-dose amoxicillin, amoxicillin-clavulanate, or parenteral ceftriaxone followed by oral cefpodoxime. **Cefotaxime, ceftriaxone, ampicillin-sulbactam, or high-dose ampicillin Adapted from Mandell LA, Wunderink RG, Anzueto A, et al; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27-S72. 2003 The Cleveland Clinic Foundation.

Aspiration Pneumonia
Clindamycin is preferred over penicillin for the treatment of community-acquired aspiration pneumonia because of its superiority for treating oral anaerobes such as Bacteroides melaninogenicus. Amoxicillin-clavulanic acid also provides excellent coverage in this setting. When large-volume aspiration is documented in the hospital, a beta-lactambetalactamase inhibitor combination or the combination of clindamycin and an antipseudomonal agent should be used.

Other Considerations
Anthrax
Suspected or proven inhalation anthrax should be treated with ciprofloxacin or doxycycline and two other agents (see Table 7). Clinical experience has suggested that rifampin may be an important agent in empirical regimens.13

Duration of Therapy
Although few data specifically address the duration of therapy, many cases of pneumonia are adequately treated with 10 to 14 days of antibiotics. Longer courses may be required for certain organisms that cause tissue necrosis,

(e.g., Legionellaspp., S. aureus, Pseudomonas aeruginosa), organisms that live intracellularly (e.g., C. pneumoniae), or comorbidities that compromise local (COPD) or systemic (hematologic malignancy) immunity.

Oral and Switch Therapies

The use of oral or switch therapies offers potential reductions in duration of stay, antibiotic administration costs, complications of venous access, and disruption of families and careers. Many antibiotics are well absorbed from the gastrointestinal tract, suggesting the possibility of effective fully oral treatment. Because well-controlled, risk-stratified data comparing oral and intravenous therapies are few, appropriate patient populations and treatment settings for fullcourse oral therapy have yet to be fully defined. Better data exist for the use of IV to oral switch therapies for the stable patient who has good gastrointestinal and swallowing function and adequate social support.
14

Failure to Respond to Initial Therapy

Worsening of clinical status despite adequate antibiotic therapy should trigger a reassessment of the original clinical impression. First, the diagnosis of infection must be questioned. Entities such as cancers, pulmonary edema, pulmonary embolus, pulmonary hemorrhage, connective tissue diseases, or drug toxicity can mimic the clinical and radiographic appearance of pneumonia. Organisms with inherent (e.g., fungi, mycobacterial, P. jiroveci) or acquired (Pseudomonas aeruginosa) resistance to drugs commonly used in pneumonia therapy must also be considered. A secondary infection, such as postinfluenza staphylococcal pneumonia, might prove resistant to initial therapy. The patient might fail to respond for reasons of poor adherence, poor drug absorption, or drug interaction. Finally, immunodeficiency (e.g., HIV, hematologic malignancy) or anatomic derangement (e.g., COPD, bronchiectasis, neoplasm) can alter the clinical course of pneumonia and treatment.

Discharge Criteria
Criteria for hospital discharge in community-acquired pneumonia are based on common sense. Candidates for discharge should have no more than one of the following poor prognostic indicators: temperature higher than 37.8 C, pulse higher than 100 beats/min, respiratory rate higher than 24/min, systolic blood pressure lower than 90 mm Hg, oxygen saturation lower than 90%, and inability to maintain oral intake.

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Summary
y
Antibiotic therapy for community-acquired pneumonia should always be selected with patient characteristics, place of acquisition, severity of disease, and local resistance patterns in mind.

y y y y

Antimicrobial therapy should be narrowed whenever a pathogen is identified. Most pneumonias, with some exceptions, can be cured with 10 to 14 days of antibiotic therapy. Switching to oral therapy is possible and desirable once the patient stabilizes. Failure to respond to initial therapy should raise questions of diagnosis, treatment adherence, and antimicrobial resistance.

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Prevention
Immunization against influenza and increasingly resistant pneumococci can play a critical role in preventing pneumonia, particularly in immunocompromised and older adults. The influenza vaccine is formulated and administered annually. The Centers for Disease Control and Prevention (CDC) recommends that vaccines be offered to persons older than 50 years, residents of extended-care facilities, and patients who have chronic heart and lung disorders, chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression.15 The pneumococcal vaccine has been shown to be 60% to 70% effective in immunocompetent patients. Side effects are rarely serious and consist of local pain and erythema, which occur in up to 50% of recipients. The CDC recommends that vaccines be offered to all persons 65 years of age or older, those at increased risk for illness and death from pneumococcal disease because of chronic illness, those with functional or anatomic asplenia, and immunocompromised persons.16 Patients who are immunosuppressed by chronic disease or treatment might not have sustained titers of protective antibody and should be considered for revaccination after 6 years. Residual immunity against Bordetella pertussis wanes over time, leading to transmission from older adults to other adults and infants. Because secondary bacterial pneumonia occurs in a significant number of cases of pertussis, the ACIP (Advisory Committee on Immunization Practices) has recommended that the tetanus-diphtheria-acellular pertussis (Tdap) vaccine replace the tetanus-diphtheria (Td) vaccine in the adult immunization schedule.
17

The emergence of SARS, with significant spread in hospitals, forced an extensive reassessment of respiratory infection control in many institutions. Measures to prevent the spread of SARS-associated coronavirus include close attention to cough hygiene, hand hygiene, contact precautions, and respiratory droplet precautions.

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National guidelines
A number of expert bodies have developed guidelines for the diagnosis and management of community-acquired pneumonia. The most often cited are the guidelines of IDSA and ATS.2 Thoughtful and comprehensive, these guidelines provide recommendations for the evaluation and treatment of the patient with community-acquired pneumonia driven by data, when available. Recommendations are classified by strength of supporting data; recommendations formed on the basis of opinion rather than data are identified. There is support for the use of the PSI and CRB scoring systems for risk stratification. Treatment recommendationsare closely aligned with prior guidelines from the individual organizations. Compromise has been reached between the two organizations regarding the diagnostic evaluation of community-acquired

pneumonia. Concerns of drug resistance and epidemiologic tracking have been noted, as have been concerns about lack of sensitivity and specificity in microbiologic testing. The resulting recommendations minimize testing for uncomplicated cases of pneumonia, allowing more extensive testing for sicker patients. Guidelines for the home care of pneumonia have been published. These seek to ensure the administration of welltolerated antimicrobial therapy and ongoing professional evaluation.18 When new respiratory pathogens emerge or major flares of well-known respiratory diseases occur, information develops quickly and guidelines are altered on a real-time basis. In such situations, the websites of the CDC, World Health Organization, IDSA, and state and local health departments often contain updated authoritative information and guidelines to assist the practitioner.

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Outcomes and performance measures

Pneumonia-related outcomes have been measured in several areas. In the area of microbiology, Metlay and colleagues have noted that patients with pneumococci not susceptible to penicillin are more likely to develop
19 suppurative complications than patients infected with susceptible isolates. Overall, pneumococcal pneumonia has

been shown by Fine and associates to carry a mortality rate of 12%.20 This level of mortality is exceeded only by Legionella species among community-acquired pathogens. Several pathogens more associated with long-term care facilities, including P. aeruginosa(61%) and S. aureus (32%), carry substantially higher mortality. Samples for blood cultures drawn within 24 hours of hospital admission have been associated with improvement in 30-day mortality.21 Antibiotic therapy initiated within 4 hours of hospital admission has been shown to improve mortality and length of hospital stay in all pneumonia patients.5,22 Adherence to the IDSA guidelines for antimicrobial therapy improves mortality in patients with community-acquired pneumonia in intensive care units.23 With regard to site of care, the PORT data have suggested a less than 1% risk of 30-day mortality for pneumonia sufferers falling into risk classes I and II of the pneumonia severity index, suggesting the possibility of outpatient care for this group. A home hospital model of care with daily home physician visits can reduce the duration of acute care and overall treatment costs in older patients. IV-to-oral switch therapy has been shown to yield no significant reduction in outcome when the switch is instituted after clinical stability.12 The Centers for Medicare and Medicaid Services are moving forward with pay-for-performance measures, including certain parts of the IDSA/ATS practice guidelines, as a means of promoting hospital quality. Among the measures adopted are assessment of oxygenation, screening for pneumococcal vaccination, blood cultures before first antibiotic dose, assessment for smoking cessation, antibiotics within 4 to 6 hours of arrival at the hospital, and correct choice of antibiotics.
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Pathophysiology and clinical features of acute mitral regurgitation

Philip J Podrid, MD Jan 11, 1999

Patients with acute mitral regurgitation (MR) are often gravely ill with significant hemodynamic abnormalities that require urgent medical and often surgical treatment. These changes are due in part to the lack of time for the left atrium and left ventricle to adapt to the mitral regurgitation, in contrast to chronic MR where these adaptations can preserve hemodynamic stability. This card will review the pathophysiology and clinical features of acute MR. The changes that occur in chronic MR are discussed separately. (See "Pathophysiology and stages of chronic mitral regurgitation" and see "Clinical features of chronic mitral regurgitation"). ETIOLOGY There are many causes of acute mitral regurgitation (MR), many of which can, under other circumstances, also cause chronic MR. The causes can be categorized based in part upon the site of involvement: leaflets, chordae tendineae, or papillary muscles. Leaflets traumatic rupture, infective endocarditis, left atrial myxoma Chordae tendineae traumatic rupture, spontaneous rupture, infective endocarditis, rupture due to acute rheumatic fever Papillary muscles dysfunction or rupture due to acute myocardial or severe ischemia, traumatic rupture, acute left ventricular dilatation. Prosthetic or tissue valve dysfunction deterioration of tissue leaflets, ring or strut fracture, perivalvular leak from ruptured sutures, infective endocarditis, dislodgement, dysfunction (sticking in opened position) or deterioration of disc, ball or leaflet of prosthetic or tissue valve MR has recently also been described in association with the combination use of the anorectic agents fenfluramine and phentermine. The histopathological features of the valves were identical to those seen in carcinoid orergotamine-induced valve disease.

(See "Drug therapy of obesity"). PATHOPHYSIOLOGY The degree of hemodynamic deterioration depends upon the etiology and degree of the mitral regurgitation, which is often dramatic and rapid in onset. An important factor is left atrial compliance which is usually normal unless the acute regurgitation is superimposed upon chronic MR. Since the normal left atrium is not compliant, the sudden and marked increase in left atrial volume from acute MR results in a abrupt elevation in pressure within the left atrium. This is immediately reflected back into the pulmonary circulation, often leading to pulmonary edema. Effective forward flow is limited (depending upon the extent of the regurgitation) and cardiac output falls, possibly precipitating cardiogenic shock. The neurohumoral response to the reduction in cardiac output is an increase in vascular resistance or afterload, which exacerbates the regurgitation. (See "Hemodynamics of valvular disorders as measured by cardiac catheterization"). If the degree of regurgitation is limited and left atrial compliance increases, the pressures within the left atrium and pulmonary circulation falls and hemodynamics improve. However, this does not occur in most cases because the amount of regurgitation is often large and the left atrium does not accommodate well. Thus, urgent surgical intervention to repair or replace the valve is usually essential. CLINICAL MANIFESTATIONS Acute mitral regurgitation typically presents as a dramatic event with the sudden onset and rapid progression of pulmonary edema, hypotension, and signs and symptoms of cardiogenic shock. In some cases, the pulmonary hypertension can lead to acute right sided heart failure. The presentation may not be as dramatic if acute is superimposed upon chronic mitral regurgitation. Such patients may note a sudden and marked increase in symptoms of congestive heart failure and a low output state, with increasing shortness of breath, dyspnea on exertion, fatigue, and weakness. Physical examination The patient with acute MR is often in pulmonary edema and there is evidence of poor tissue perfusion with peripheral vasoconstriction, pallor, and diaphoresis. The arterial pulse is often rapid and of low amplitude or thready due to the reduction in forward output. (See "Examination of the arterial pulse"). When there is an associated increase in right sided pressure, the neck veins become distended;

they may also become pulsatile with a marked "v" wave if the elevated right ventricular pressure leads to tricuspid regurgitation. (See "Examination of the jugular venous pulse"). The cardiac impulse is usually normal in location but very hyperkinetic. If, however, acute regurgitation is superimposed upon chronic MR, the cardiac impulse may be displaced due to the underlying left ventricular enlargement. There is often a hyperdynamic precordium with a right ventricular lift due to the acute increase in pressure within this chamber and the development of tricuspid regurgitation. Cardiac auscultation The murmur of acute mitral regurgitation may be early, midsystolic, or holosystolic. However, since the pressure within the left atrium markedly increases during ventricular systole and the pressure gradient between the left atrium and ventricle diminishes or disappears by the end of systole, the systolic murmur is often soft, low pitched and decrescendo, ending before A2. (See "Auscultation of cardiac murmurs-I" andsee "Auscultation of heart sounds-I"). The murmur is often best heard along the left sternal border and base of the heart, generally without a thrill, and may radiate to the back. It can be confused with an acute ventricular septal defect which, like acute MR, is a complication of an acute myocardial infarction. An S4 is commonly heard. With the development of pulmonary hypertension, P2 is increased in intensity and the murmurs of pulmonary and tricuspid regurgitation may be appreciated. (See "Auscultation of heart sounds-I").

What is Mitral Regurgitation? What Are The Symptoms? How Severe?

By Adam Pick, Patient & Author of The Patient's Guide To Heart Valve Surgery
When I began my heart valve disease research, I quickly learned that mitral valve regurgitaiton is a unique disorder in which the mitral valve leaflets, which are comprised of two tissue flaps, do not seal properly. As a result of this valvular defect, blood can leak backwards in your heart forcing a constant strain on your cardiac muscle. Over time, mitral regurgitation can result in many complications including an enlarged heart, atrial fibrillation and congestive heart failure. So you know, mitral regurgitation is also referred to as mitral incompetence and mitral insufficiency, although most patients refer to this mitral disorder as a leaking heart valve. A mitral valve prolapse is the most common anatomical defect that causes mitral regurgitation. As you can see in the diagram below, the mitral leaflets do not seal evenly across the valve.

Mitral regurgitation is a very common heart defect. In fact, The Mayo Clinic suggests that as many as one in five people (20%) over the age of fifty-five have some degree of mitral regurgitation. Like most valvular disorders, there are different degrees, or levels, of mitral regurgitation diagnosis. The main types of mitral valve regurgitation are mild, moderate and severe regurgitation.

When Does Mitral Regurgitation Require Surgical Treatment?

It is critical to note that being diagnosed with mitral regurgitation or a mitral valve prolapse does not guarantee your need for open heart surgery. Considering that mitral regurgitation progresses over time, most mitral valve operations - mitral valve repair or mitral valve replacement - are an elective procedure. Typically, surgical treatment for this form of mitral disorder occurs only when the patient is diagnosed with "severe" regurgitation. While some patients, and even cardiologists, feel that surgery is only required when symptoms manifest, this can be a very dangerous mistake. Recently, three of four research papers indicated that asymptomatic patients with severe mitral regurgitation should undergo treatment to preserve proper ventricular function and avoid damage to the cardiac muscle.

Mitral Valve Repair - Annuloplasty Diagram That said, I encourage all patients who have been diagnosed with mitral regurgitation, a mitral valve prolapse, or a heart murmur to get regular echocardiograms. So you know, I have met several patients who have experienced rapid progressions of mitral valve disease. In one case, a female patient saw her moderate regurgitation advance to severe regurgitation in just six months. Again, if mitral regurgitation is not properly monitored and treated, it could result in an enlarged heart, abnormal heart rhythms (arrhythmias, atrial fibrillation) or even congestive heart failure.

What Are Mitral Valve Regurgitation Symptoms?

Mitral regurgitation symptoms typically appear as the disease develops. Most of the time, mitral regurgitation progesses slowly from mild to moderate to severe. As suggested above, many asymptomatic patients will be unaware of this dangerous progression. Interestingly, most physicians do not need a high-tech device to detect a leaking heart valve. Alternatively, mitral regurgitation is often detected when your doctor hears a heart murmur with a stethescope. According to The Cleveland Clinic, the common mitral valve regurgitation symptoms are: y Shortness of breath, especially during exercise or when you are laying still y Fatigue, especially during exercise
y y y y y

Cough, often during the night, when in bed Heart palpitations, or fluttering heartbeats Swollen feet or swollen ankles Heart murmur, muffled heartbeat Excessive urination

Again, mitral regurgitation can be asymptomatic. To ensure proper cardiac function, please remember to get regular, annual check-ups if you have been diagnosed with a heart murmur, a mitral valve prolapse or mitral regurgitation.

Diagnosing The Severity Of Mitral Regurgitation

An echocardiogram is often used to determine the severity of mitral regurgitation. The two main determinants in quantifying the severity of mitral regurgitation are: y Regurgitation volume (RVOL) which is the difference between the mitral and aortic stroke volumes; and y Effective regurgitant orifice (ERO) which ratio of regurgitant volume to regurgitant time velocity integral The table below shows how regurgitation volume and effective regurgitant orifice measurements are used to diagnose mitral regurgitation in patient s with degenerative mitral disease.

A transesophageal echocardiogram, MRI, stress echo or cardiac catheterization may also be used to further diagnose the valvular disorder, the cardiac damage and the recommended surgical treatment of your mitral regurgitation. >> NEXT: To learn more about mitral valve regurgitation and the medical procedures used to repair or replace defective mitral valves, please click here.

MITRAL REGURGITATION

Background
Mitral regurgitation (MR) is defined as an abnormal reversal of blood flow from the left ventricle to the left atrium. It is caused by disruption in any part of the mitral valve apparatus, which comprises the mitral annulus, the leaflets (a large anterior [aortic] leaflet and a small posterior [mural] leaflet), the chordae tendineae, and the papillary muscles (anteromedial and posterolateral). The most common etiologies of MR include mitral valve prolapse (MVP), rheumatic heart disease, infective endocarditis, annular calcification, cardiomyopathy and ischemic heart disease. The pathophysiology, clinical manifestations and management of MR differ with the chronicity of the disease and the etiology.

Pathophysiology
MR can be caused by organic disease (eg, rheumatic fever, ruptured chordae tendineae, myxomatous degeneration, leaflet perforation) or a functional abnormality (ie, a normal valve may regurgitate [leak] because of mitral annular dilatation, focal myocardial dysfunction, or both). Congenital MR is rare but is commonly associated with myxomatous mitral valve disease. Alternatively, it can be associated with cleft of the mitral valve, as occurs in persons with Down syndrome, or a ostium primum atrial septal defect.

Acute mitral regurgitation

Acute MR is characterized by an increase in preload and a decrease in afterload causing an increase in end-diastolic volume (EDV) and a decrease in end-systolic volume (ESV). This leads to an increase in total stroke volume (TSV) to supranormal levels. However, forward stroke volume (FSV) is diminished because much of the TSV regurgitates as the regurgitant stroke volume (RSV). This, in turn, results in an increase in left atrial pressure (LAP). According to the Laplace principle, which states that ventricular wall stress is proportional to both ventricular pressure and radius, LV wall stress in the acute phase is markedly decreased since both of these parameters are reduced.

Chronic compensated mitral regurgitation

In chronic compensated MR, the left atrium (LA) and ventricle have sufficient time to dilate and accommodate the regurgitant volume. Thus LA pressure is often normal or only minimally elevated. Because of the left ventricular dilatation via the process of eccentric hypertrophy, TSV and FSV are maintained. Wall stress may be normal to slightly increased as the radius of the LV cavity increases but the end-diastolic LV pressure remains normal. As the LV progressively enlarges, the mitral annulus may stretch and prevent the mitral valve leaflets from coapting properly during systole, thus worsening the MR and LV dilatation.

Chronic decompensated mitral regurgitation

In the chronic decompensated phase, muscle dysfunction has developed, impairing both TSV and FSV (although ejection fraction still may be normal). This results in a higher ESV and EDV, which in turn causes a elevation of LV and LA pressure, ultimately leading to pulmonary edema and, if left untreated, cardiogenic shock.

Epidemiology
Frequency
United States Acute and chronic MR affect approximately 5 in 10,000 people. Mitral valve disease is the second most common valvular lesion, preceded only by aortic stenosis. Myxomatous degeneration has replaced rheumatic heart disease as the leading cause of mitral valvular abnormalities. Mitral valve prolapse has been estimated to be present in 4% of the normal population. With the aid of color Doppler echocardiography, mild MR can be detected in as many as 20% of middle-aged and older adults. MR is independently associated with female sex, lower body mass index, advanced age, renal dysfunction, prior

myocardial infarction, prior mitral stenosis, and prior mitral valve prolapse. It is not related to dyslipidemia or diabetes. International In areas other than the Western world, rheumatic heart disease is the leading cause of MR.

History
Acute mitral regurgitation
When associated with coronary artery disease and acute myocardial infarction (typically, inferior myocardial infarction, which may lead to papillary muscle dysfunction), significant acute mitral regurgitation (MR) is accompanied by symptoms of impaired LV function, such as dyspnea, fatigue, and orthopnea. In these cases, pulmonary edema is often the initial manifestation because of rapid volume overload on the left atrium and the pulmonary venous system.

Chronic mitral regurgitation

y y Often results from a primary defect of the mitral valve apparatus with subsequent progressive enlargement of the left atrium and ventricle. In this state, patients may remain asymptomatic for years. Patients may have normal exercise tolerance until systolic dysfunction of the LV develops, at which point they may experience symptoms of a reduced forward cardiac output (ie, fatigue, dyspnea on exertion, or shortness of breath). With time, patients may feel chest palpitations if atrial fibrillation develops as a result of chronic atrial dilatation. For related information, see Medscape'sAtrial Fibrillation Resource Center. Patients with LV enlargement and more severe disease eventually progress to symptomatic congestive heart failure with pulmonary congestion and edema. At this stage of LV dilatation, the myocardial dysfunction often becomes irreversible. For related information, see Medscape's Heart FailureResource Center.

y y

Physical
Palpation
y y y y y y y Brisk carotid upstroke and hyperdynamic cardiac impulse Prominent LV filling wave may be present Auscultation S1 may be diminished in acute MR and chronic severe MR with defective valve leaflets. Wide splitting of S2 may occur due to early closure of the aortic valve. S3 may be present due to LV dysfunction or as a result of increased blood flow across the mitral valve. P2 may be accentuated if pulmonary hypertension is present. Murmur y Quality y Usually high-pitched, blowing y Location y Usually best heard over the apex y Usually radiates to the left axilla or subscapular region y Posterior leaflet dysfunction causes murmur to radiate to the sternum or aortic area y Anterior leaflet dysfunction causes murmur to radiate to the back or top of the head y Duration y Usually holosystolic y May be confined to early systole in acute MR y May be confined to late systole in MVP or papillary muscle dysfunction y S1 will probably be normal in these cases since initial closure of mitral valve cusps is unimpeded. y A midsystolic click preceding murmur is suggestive of MVP.

y y y

Intensity Little correlation exists between intensity of murmur and severity of MR. Intensity may be diminished in severe MR caused by LV dysfunction, acute myocardial infarction, or periprosthetic valve regurgitation.

Causes
Acute mitral regurgitation
Coronary artery disease (ischemia or acute myocardial infarction) Papillary muscle dysfunction y The posteromedial papillary muscle is supplied by the terminal branch of the posterior descending artery and is more vulnerable to ischemic insult than the anterolateral papillary muscle, which is usually supplied by both the left anterior descending and circumflex arteries. y Transient ischemia may result in transient MR associated with angina. y Myocardial infarction or severe prolonged ischemia produces irreversible papillary muscle dysfunction and scarring. y Chordae tendineae dysfunction or rupture y Infectious endocarditis y Abscess formation y Vegetations y Rupture of chordae tendineae y Leaflet perforation y Status post valvular surgery y Trauma y Percutaneous valvuloplasty y Suture interruption y Tumors (most commonly atrial myxoma) y Myxomatous degeneration y Mitral valve prolapse y Ehlers-Danlos syndrome y Marfan syndrome y Systemic lupus erythematosus (Libman-Sacks lesion) y Acute rheumatic fever (Carey Coombs murmur) y Acute global left ventricular dysfunction y Prosthetic mitral valve dysfunction Chronic mitral regurgitation y y y y y y y y y y y y y y y y y y y Rheumatic heart disease Systemic lupus erythematosus Scleroderma Myxomatous degeneration Mitral valve prolapse Ehlers-Danlos syndrome Marfan syndrome Calcification of mitral valve annulus Infective endocarditis (can affect normal, abnormal, or prosthetic mitral valves) Ruptured chordae tendineae Trauma Mitral valve prolapse Endocarditis Spontaneous Rupture or dysfunction of papillary muscles Coronary artery disease (see causes for acute MR) Dilation of mitral valve annulus and/or left ventricular cavity (functional MR)

y y y y y y y y y y

Dilated cardiomyopathies Aneurysmal dilation of the left ventricle Hypertrophic cardiomyopathy Perivalvular prosthetic leak Congenital Mitral valve clefts Mitral valve fenestrations Parachute mitral valve abnormality Drug-related Ergotamine, methysergide, pergolide, anorexiant medications

Diagnostic Considerations
Calcified aortic stenosis also produces a prominent murmur at the apex (Gallavardin phenomenon) and may be confused with mitral valve regurgitation. Tricuspid regurgitation also causes a holosystolic murmur. However, it is located at the left lower sternal border rather than the apex, it does not radiate to the axilla, and it increases in intensity with inspiration, whereas MR does not. A ventricular septal defect produces a harsh holosystolic murmur at the lower left sternal border, but it generally radiates to the right of the sternum rather than the axilla and typically has a thrill.

Differentials
y y y y y y y y Aortic Regurgitation Aortic Stenosis Complications of Myocardial Infarction Mitral Stenosis Mitral Valve Prolapse Pulmonic Regurgitation Pulmonic Stenosis Ventricular Septal Defect

Pathophysiology of COPD
COPD is a chronic lung disease caused due to the narrowing and/or blockage of the airways or alveoli. The pathophysiology of COPD reveal the structural changes of the airways, dysfunction of cilia and inflammatory responses.

Chronic obstructive pulmonary disease (COPD) encompasses a group of lung conditions that cause narrowing of the airways, leading to the shortness of breathand difficulty in breathing. It is a progressive disease in which symptoms worsen with time. Chronic bronchitis and emphysema are the most common forms of COPD. In chronic bronchitis, the lining of the airways is thickened as a result of constant irritation, which leads to an excess secretion of mucous. In case of emphysema, the elasticity of mucous lining is reduced, resulting in the obstruction of airflow. Majority of the cases of chronic obstructive pulmonary disease are caused due to long-term smoking. Inhalation of lung irritants such as pollens, air pollutants, dust, smoke and other chemicals may also contribute to developing COPD. The early signs of COPD are chronic cough and coughing up mucous secretions. Other symptoms of COPD may include breathing difficulty, chest tightness or discomfort, wheezing and other respiratory symptoms. A patient with COPD is more susceptible to constant chest infections than a healthy person. COPD is one of the leading causes of illness and death in many countries. Pathophysiology of COPD The pathophysiology of COPD is very complex and is not clearly identified as yet. A resistance to the airflow can be attributed to many factors such as mucociliary disorders, inflammatory responses and structural changes. In short, the blockage and/or narrowing of the airways may be caused due to loss of elasticity of the airways, damage or inflammation in the walls of the airways, secretion of excess mucous in the airways and decrease in the surface area for the exchange of air. According to medical studies, it is revealed that chronic inflammatory responses of the airways is the major contributing factor to the development of COPD. It is stated that inflammatory responses resulted from COPD and those from asthma are different. COPD associated inflammation induces the production of neutrophils, macrophages and lymphocytes.

These cells along with reactive oxygen and proteases enzymes are responsible for causing damage to the airways (alveoli). When smoking, the number of neutrophils is increased than the normal level. Gradually, the airways are thickened, excess smooth muscles and connective tissues are produced by the body, leading to fibrosis in the airways. All these inflammatory responses are caused due to prolonged cigarette smoking and at times, frequent exposure to lung irritants. The pathophysiology of COPD thus includes the narrowing of the airways, damage to the lungs and other supportive tissues, hyperactivity of the lungs, dysfunction of the cilia in the airways and constant damage of the alveolar walls. As the COPD condition progresses, patients of COPD manifest wheezing, productive cough, difficulty in clearing alveoli and shortness of breath (dyspnea). As the pressure in the chest increases, the patient faces more difficulty during exhaling air, rather than inhalation. There is no cure for COPD, as damage in the airways cannot be reversed back. However, there are certain treatment options in order to manage the breathlessness symptoms. The effective treatment of COPD is to quit smoking; one can opt for nicotine replacement therapy to cope up the withdrawal symptoms. Other treatment options of COPD include oxygen therapy (if necessary) and medications such as corticosteroids and antibiotics (for chest infection).

Chronic obstructive pulmonary disease (COPD) is the umbrella term used to describe emphysema and chronic bronchitis. Along with asthma and cystic fibrosis, COPD is part of a larger class of lung diseases characterized by the obstruction of airflow through the respiratory system. While COPD pathophysiology is still not fully understood, the symptoms and progression of COPD seem to be closely tied to lung tissue inflammation. Long-term exposure to cigarette smoke or other irritants trigger the inflammatory response of the lungs, resulting in structural and cellular changes to the tissues of the respiratory system. COPDpathophysiology usually manifests as either emphysema, chronic bronchitis, or in many patients it is a combination of the two. Cigarette smoking is usually cited as the most common risk factor for COPD. Other risk factors include workplace exposure to inhaled irritants such as coal dust or cadmium. Women, having proportionately smaller lungs and airways than men, are more likely to develop symptoms ofCOPD. There is also a genetic variant of the disease associated with a congenital absence of an important pulmonary enzyme; however, this form of COPD has a clearly definedpathophysiology that is distinct from irritant related COPD pathophysiology. Ads by Google

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ThrombosisAdviser www.Thrombosisadviser.com
The common factor that causes emphysema and chronic bronchitis to be grouped together under the single diagnosis of COPD is airflow restriction. Since many patients exhibit symptoms of both diseases and the two share a common etiology and pathophysiology, it can make sense to refer to them as a single entity. Airflow restriction can occur as a result of loss of elasticity of the lung tissue due to emphysema, chronic mucus congestion associated with chronic bronchitis, or persistent narrowing of the airways due to inflammation. As a result,COPD patients are often prescribed medicine inhalers designed to open up the airways and make breathing easier. Healthy lungs contain millions of tiny air sacs known as alveoli, through which oxygen is exchanged for carbon dioxide by way of a complex network of blood vessels. Emphysema causes these delicate sacs to rupture and blood vessels to be destroyed, leaving existing air sacs badly damaged. When this occurs, the lungs function less efficiently. It becomes increasingly difficult to get enough oxygen or to expel carbon dioxide, and the patient may suffer symptoms associated with a lack of oxygen. While emphysema affects primarily the small air sacs and blood vessels of the lungs, chronic bronchitis targets the larger airways. When respiratory tissues are damaged, the body's inflammatory response causes the airways to become swollen and narrowed, and excess mucus is secreted in an effort to protect the lungs from inhaled irritants. Unfortunately, the airway inflammation and increased mucus lead to congestion and breathing difficulty. The combined COPD pathophysiology of emphysema and chronic bronchitis leads to shortness of breath, weakness, dizziness, fatigue, and a persistent, productive cough. In the early stages of COPD, these symptoms may not be particularly noticeable or bothersome, and could easily be ignored or assumed to be just another part of aging. As the disease progresses, COPD is characterized by frequent exacerbations in which symptoms abruptly worsen following a period of illness. These exacerbations will often lead to the patient being hospitalized and treated with steroids and supplementary oxygen. Over time, COPDpathophysiology can come to include a barrel chest caused by hyperinflation of the lungs, bluing of the mouth and fingers from chronic lack of oxygen, and a persistent wheeze caused by narrowing and congestion of the airways. If allowed to progress, COPD pathophysiology eventually will require constant oxygen supplementation and specialized nursing care. Complications of endstage COPD include heartfailure, collapsed lung, and sudden respiratory failure. COPD is an irreversible disease that results in a shortened overall lifespan and a drastically reduced quality of life. The most important step in a treatment plan is to quit smoking. Quitting smoking has been shown to slow the progression of the disease significantly, and if caught early, lung function can be retained and quality of life preserved well into the later years.

Before contemplating canonically on COPD pathophysiology let s find out what the terms COPD and pathophysiology stand for. Used with pathophysiology the COPD actually is a short form of lung disease, known as chronic obstructive pulmonary disease (COPD). Caused due to narrowing down or blockage of alveoli, the COPD disease embarrasses the affected individuals with dysfunction of cilia and lung inflammation. As far as pathophysiology is concerned it causes lungs of human body to become partially dysfunctional, paving the way for many peculiar diseases with abnormal

syndromes contributing in the emergence of COPD. The pathophysiology can be described as a branch of medicine as well researching on health disturbances and diseases of body. Going through the definitions of COPD and pathophysiology each, you must have perceived well that COPD is a problem of chronic obstructive pulmonary disease caused directly or indirectly by the pathophysiology. How COPD Affects Human Lungs Advertisement Being the pulmonary disease, the COPD affects mostly the lungs of individuals causing the airways of it to narrow or get extensively contracted which resultantly causes suffocation or shortness of breath to the person, a most critical condition studied and analyzed by the scientists as pathophysiology. Once the COPD affects someone it continues exacerbating the condition of the affected patient s lungs day by day if unchecked by the health experts. Some specific diseases such as chronic bronchitis and emphysema are the pathophysiology of chronic obstructive pulmonary disease. Following extensive study it has been divulged that chronic bronchitis disease and emphysema contribute in the occurrence of COPD or the pathophysiology of chronic obstructive pulmonary disease. The chronic bronchitis disease causes the passage of airways to get thicker following which excessive amount of mucus is formed and secreted in the lungs, embarrassing the diseased person with tremendous irritation, obfuscation and lung inflammation. It is the emphysema disease also due to which mucus lining is lessened to a great extent causing the passage to become contracted and embarrass the patients with embarrassing symptoms matching with chronic bronchitis disease. COPD-caused lung-inflammation produces some peculiar cells, identified as the neutrophils, macrophages and lymphocytes which with the support of reactive oxygen and proteases enzymes, damage damage the airways (alveoli) making the diseased ones feel much suffocated. Dwelling on pathophysiology we come across smoking as a major cause of neutrophilsm affecting the individuals with chronic-obstructive-pulmonary-disease (COPD). It is the pathophysiology that substantiates occurrence of COPD due to arbitrary smoking, a condition identified by thickened tissues of lungs. The lungs get affected with injury and infection embarrassing the person with inflammation and suffocation. Be it smoking or production of noxious enzymes, the airways passage is thickened or narrowed extensively, clinically identified as the fibrosis. Such embarrassing condition is taken as

chronic obstructive pulmonary disease (COPD) associated with pathophysiology. Damage in the lungs/tissues, dysfunction of cilia and damage of alveolar are the pathophysiology of chronic obstructive pulmonary disease (COPD). What is COPD? COPD is a chronic obstructive pulmonary disease, caused due to ingestion of harmful particles, gas, and smoke or arbitrary use of tobacco. The people affected with chronic obstructive pulmonary disease experience tremendous inflammation within their lungs or the chest which if not brought into the notice of a doctor gets much worsened-off causing short-breathiness, breathlessness and suffocation. Inflammation on main airways of lungs also can be taken as chronic bronchitis disease, a vivid sign of pathophysiology. Alveoli matching with COPD by symptoms also cause lung inflammation, a condition identified as the emphysema.

Causes of COPD

Caused as pathophysiology some specific factors are responsible for the chronic obstructive pulmonary disease (COPD), such as heavy smoking, allergy (caused due pollens), environmental pollution, dust, smoke, noxious chemicals, etc. Loss of muscular tissues elasticity or damage of inner walls, inflammation in the passage of air-flow and excessive secretion of mucus also are the causes of chronic obstructive pulmonary disease COPD. Signs/symptoms of COPD Chronic coughing, mucus secretion, chest congestion, wheezing, respiratory syndrome and breathing-difficulty are a few common symptoms of the chronic obstructive pulmonary disease. Almost all the people, susceptible to chest infection are prone to COPD, for such type of disease affects only those with weaker immunity. It is pathophysiology that in its shocking revelation divulges a high figure of deaths due only to COPD in many countries. Can pathophysiology-associated COPD be cured? No. There is no cure of pathophysiology of COPD as the pulmonary disease once triggers on it doesn t recede and keeps worsening-off rendering diseased person s physical immunity weak. Only some short respite can be had and that with some over-the-counter (OTC) drugs to deal with short breath, breathlessness or suffocation. As even the OTC drugs are not a permanent solution of

chronic pulmonary disease, the patients of such type of lung disease are left with no option except avoiding the smoking and living in a pollution-free environment. But at the critical stage the patients, affected with chronic obstructive pulmonary disease (COPD) are administered the oxygen-therapy. Some drugs like corticosteroids and antibiotics also can be taken to deal with pathophysiology of (COPD). Pathophysiology of COPD Getting well introduced with irreversible symptoms of COPD you must now be focusing your attention on pathophysiology or the effects of diseases causing a disturbance in the natural function of human lungs, a condition known as chronic obstructive pulmonary disease (COPD). But what you might be curious in is not going to make you feel complacent anymore as even the medicalresearchers have not managed to explore the pathophysiology or COPD-causing effects. Though it has been substantiated that intemperance in smoking causes chronic obstructive pulmonary disease, it has yet not been unearthed how the minute particles of cigarettes smoke, after reaching inside the human lungs, damage the smallest cells thereof, affecting the smoker with inflammation of lungs. But some specific and outstanding revelations no doubt draw our attention on some remarkable findings or pathophysiology of COPD. Contrary effects of some diseases triggering chronic obstructive pulmonary disease also are the oxidative stress (tobacco-caused), cytokine release (harmful environmental irritants) and tobacco smoke. Dysfunction of some enzymes such as alpha 1-antitrypsin also is the pathophysiology of chronic obstructive pulmonary disease allowing the protease enzymes to cause great damage in the human lungs. Narrowing of airways or passage of airflow also is the pathophysiology of COPD affecting the natural flow of air that affects the individual with suffocation or shortness of breath. The individuals affected with COPD experience tremendous breathing problem on exhaling air from their lungs. It is due only to dearth of oxygenated air in the lungs following scanty expansion of airways, felt as compression within the chest. If the diseased person attempts to inhale fresh oxygenated air inside the lungs there starts a noise, heard in a form of wheezing, a vivid sign of COPD identified as expiratory flow limitation. As the passage of airways are extensively contracted or narrowed the individuals feel uncomfortable as the fresh oxygenated air doesn t reach inside his lungs in plenty forcing him to take one more breath just after another indiscriminately. Such type of pathophysiology of chronic obstructive pulmonary disease can easily be fathomed either during physical exercises or laborious

work when fresh oxygenated air is needed to be inhaled plenteously. Dwelling on the pathophysiology of chronic obstructive pulmonary disease (COPD) we come across dynamic hyperinflation as another condition or disease erupting pulmonary disease. The individuals affected with such type of chronic disease also suffer from breathing problem or COPD due to failure of deoxygenated air s exiting from the lungs and a pressure caused within the lungs due to fresh oxygenated reaching inside the lungs. It also is another pathophysiology of COPD caused due to scantiness of area inside the lungs due to swelling of airways. Due to such condition the oxygenated air can t be breathed easily. Even removing the carbon dioxide becomes too difficult for a person due to cramped passage. Such condition paves the way for COPD perpetuating enormous amount of carbon dioxide in the lungs putting the diseased individuals into much critical condition. In simple words, it is complete failure in compensating the oxygenated air and eliminating noxious carbon dioxide. The diseased people suffering from COPD encounter different types of problems likeweight loss (aka cachexia), pulmonary hypertension and heart failure (cor pulmonale). Osteoporosis, heart disease, muscle wasting and depression also are the complicating conditions affecting the individuals substantiating the COPD pathophysiology.