Respiratory System

PULMONARY INFECTIONS:

Pulmonary infections in the form of pneumonia are common cause for morbidity and mortality (responsible for one sixth of all deaths in USA). WHY?

Because: The epithelial surfaces of the lung are constantly exposed to liters of variously contaminated air. (2) Nasopharyngeal flora are regularly aspirated during sleep, even by healthy persons. (3) Other common lung diseases render the lung parenchyma vulnerable to virulent organisms.

So how can the normal lung parenchyma remains sterile?

Respiratory defense mechanism: This is due to the efficiency of pulmonary defense mechanisms, which include immune and non-immune defense mechanisms, extending from the nasopharynx all the way into the alveolar airspaces. They include:

Host Defense Mechanism

Location

Upper Airways

Nasal hair
Nasopharynx
Turbinates


Mucociliary apparatus

IgA secretion

Saliva
Oropharynx
Sloughing of epithelial cells

Local complement production

Interference from resident flora

Conducting Airways

Cough reflex
Trachea, bronchi
Sharp-angled branching of airways

Mucociliary apparatus

Immunoglobulin production (IgG, IgM, IgA)

Lower Respiratory Tract

Alveolar lining fluid (surfactant, immunoglobulin, complement, fibronectin)
Terminal airways, alveoli
Cytokines (interleukin 1, tumor necrosis factor)

Alveolar macrophages

Polymorphonuclear leukocytes

Several lifestyle factors interfere with host immune defense mechanisms and facilitate infections. For example: cigarette smoke compromises mucociliary clearance and pulmonary macrophage activity. alcohol not only impairs cough and epiglottic reflexes, thereby increasing the risk of aspiration, but also interferes with neutrophil mobilization and chemotaxis.

Pneumonia: Pneumonia can be very broadly defined as any infection in the lung

It may present as: Acute, fulminant clinical disease with fibrinopurulent alveolar exudates. Mostly bacterial. Chronic disease with a more protracted course, with mononuclear interstitial infiltrates (in viral and other atypical pneumonias), or granulomas.

Acute bacterial pneumonias can present as one of two anatomic and radiographic patterns: Bronchopneumonia: Lobar pneumonia:



Bronchopneumonia: Implies a patchy distribution of inflammation that generally involves more than one lobe. This pattern results from an initial infection of the bronchi and bronchioles with extension into the adjacent alveoli.

Lobar pneumonia: The contiguous airspaces of part or all of a lobe are homogeneously filled with an exudate that can be visualized on radiographs as a lobar or segmental consolidation. Streptococcus pneumoniae is responsible for more than 90% of lobar pneumonias.

The anatomic distinction between lobar pneumonia and bronchopneumonia can often become blurry. Therefore, it is best to classify pneumonias either by the specific etiologic agent or, if no pathogen can be isolated, by the clinical setting in which infection occurs

Pneumonia can arise in seven distinct clinical settings ("pneumonia syndromes"):

1- Community-Acquired Acute Pneumonia
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Staphylococcus aureus
Legionella pneumophila
Enterobacteriaceae (Klebsiella pneumoniae) and Pseudomonas spp.
2- Community-Acquired Atypical Pneumonia
Mycoplasma pneumoniae
Chlamydia spp. (C. pneumoniae, C. psittaci, C. trachomatis)
Coxiella burnetti (Q fever)
Viruses: respiratory syncytial virus, parainfluenza virus (children); influenza A and B (adults); adenovirus (military recruits)
3- Nosocomial Pneumonia
Gram-negative rods belonging to Enterobacteriaceae (Klebsiella spp., Serratia marcescens, Escherichia coli) and Pseudomonas spp.
Staphylococcus aureus (usually penicillin-resistant)

4- Aspiration Pneumonia

Anerobic oral flora (Bacteroides, Prevotella, Fusobacterium, Peptostreptococcus), admixed with aerobic bacteria (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilas influenzae, and Pseudomonas aeruginosa)
5- Chronic Pneumonia
Nocardia
Actinomyces
Granulomatous: Mycobacterium tuberculosis and atypical mycobacteria, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis
6- Necrotizing Pneumonia and Lung Abscess
Anerobic bacteria (extremely common)
Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pyogenes, and type 3 pneumococcus (uncommon)
7- Pneumonia in the Immunocompromised Host
Cytomegalovirus
Pneumocystis carinii
Mycobacterium avium-intracellulare
Invasive aspergillosis & candidiasis
"Usual" bacterial, viral, and fungal organisms (listed above)


COMMUNITY-ACQUIRED ACUTE PNEUMONIAS Bacterial in origin. Usually follows a viral upper respiratory tract infection. The onset is usually abrupt, with high fever, shaking chills, pleuritic chest pain, and a productive mucopurulent cough. Streptococcus pneumoniae (or pneumococcus) is the most common cause of community-acquired acute pneumonia.



Pneumococcal pneumonia: Occurs with increased frequency in three groups of individuals:


Those with: Chronic diseases such as congestive heart failure, COPD, or diabetes. Congenital or acquired immunoglobulin defects. Absent splenic function (e.g., sickle cell disease or post splenectomy). WHY?

Morphology:

Both pattern, lobar or bronchopneumonia, may occur; the latter is much more prevalent at the extremes of age. Pneumococcal pneumonia used to evolved through four stages: Congestion. red hepatization. gray hepatization. resolution. Early antibiotic therapy alters this typical progression.


Congestion: Early stage, the affected lobe is heavy and red. Histologically, vascular congestion can be seen, with proteinaceous fluid, scattered neutrophils, and many bacteria in the alveoli.

Red hepatization Ensues within few days, in which the lung lobe has a liver-like consistency; the alveolar spaces are packed with neutrophils, red cells, and fibrin

Gray hepatization: Later on the lung appears dry, gray, and firm, because the red cells get lysed, while the fibrinous exudate persists within the alveoli.

Resolution follows in uncomplicated cases, as exudates within the alveoli are enzymatically digested and either resorbed or expectorated, leaving the basic architecture intact.

In the bronchopneumonic pattern, foci of inflammatory consolidation are distributed in patches throughout one or several lobes, most frequently bilateral and basal


Complications: With appropriate therapy, complete restitution of the lung is the rule for both forms of pneumococcal pneumonia, but in occasional cases complications may occur include:


Complications: Tissue destruction and necrosis may lead to abscess formation. Suppurative material may accumulate in the pleural cavity, producing an empyema. Organization of the intra-alveolar exudate may convert areas of the lung into solid fibrous tissue. Bacteremic dissemination may lead to meningitis, arthritis, or infective endocarditis.


Diagnosis: Clinical features. Radiological examination. Gram stained sputum ( high false + result from normal flora). Isolation of pneumococci from blood cultures is more specific.


Vaccination: Commercial pneumococcal vaccines containing capsular polysaccharides from the common serotypes of pneumococcus are available, and their proven efficacy mandates their use in patients at risk for pneumococcal infections.


Community-Acquired Atypical Pneumonias Characterized by: Modest sputum production. There are no physical findings of consolidation. The white cell count is only moderately elevated. Bacteria could not be isolated.

Causes: Mostly caused by Mycoplasma pneumoniae. Other agents, include viruses, chlamydiae, and rickettsiae. Mycoplasma infections are particularly common among children and young adults. They occur sporadically or as local epidemics in closed communities (schools, military camps, prisons).


Pathogenesis: In the alveoli, there is usually interstitial inflammation. Damage to the respiratory epithelium inhibits mucociliary clearance and predisposes to secondary bacterial infections.

Clinical Course. The onset is that of an acute, nonspecific febrile illness characterized by fever, headache, and malaise, and, later, cough with minimal sputum.


NOSOCOMIAL (HOSPITAL-ACQUIRED) PNEUMONIA: Defined as pulmonary infections acquired in the course of a hospital stay.

Nosocomial infections are common in: Patients with severe underlying disease. Immunosuppression. Prolonged antibiotic therapy. Patients with invasive access devices such as intravascular catheters. Patients on mechanical ventilation.

Causes: Gram-negative rods (Enterobacteriaceae and Pseudomonas species) and S. aureus are the most common isolates.


ASPIRATION PNEUMONIA: occurs in: Debilitated patients. Aspiration of gastric contents either while unconscious (e.g., after a stroke) or during repeated vomiting.

The resultant pneumonia is partly chemical, owing to the extremely irritating effects of the gastric acid, and partly bacterial. Mostly caused by anaerobic bacteria, but recent studies implicate aerobes. This type of pneumonia is often necrotizing, and abscess formation is a common complication.


Lung abscess Lung abscess refers to a localized area of suppurative necrosis within the pulmonary parenchyma, resulting in the formation of one or more large cavities.

The causative organism may be introduced into the lung by any of the following mechanisms:

Aspiration of infective material (from carious teeth, infected sinuses,oral surgery, anesthesia, coma, or alcoholic). Aspiration of gastric contents, accompanied by infectious organisms from the oropharynx. As a complication of necrotizing bacterial pneumonias, esp caused by Staphylococcus aureus, Streptococcus pyogenes, K. pneumoniae, Pseudomonas species, and, rarely, type 3 pneumococci. Bronchial obstruction, as in bronchogenic carcinoma. Septic embolism, from infective endocarditis of the right side of the heart. Hematogenous spread of bacteria ( especially staph)

Causative agents: Anaerobic bacteria are present in almost all lung abscesses. Often there is a mixed anaerobic-aerobic infection; commonly S. aureus.



Morphology: Size: variable Single or multiple. The localization and number of abscesses depend on their mode of development ( abscesses resulting from aspiration of infective material are common on the right side, WHY?) Abscesses that develop in the course of pneumonia or bronchiectasis & those arising from hematogenous seeding are commonly multiple.

Histologically: there is suppuration surrounded fibrous scarring and mononuclear infiltration.


Clinical Course. Prominent cough yielding copious amounts of foul-smelling, purulent sputum; occasionally, hemoptysis occurs. Fever and malaise. Clubbing of the fingers, weight loss, and anemia may all occur.

Consequences & complications of lung abscess:

Rupture into the airways, the contained exudate may be partially drained. Rupture into the pleural cavity and produce pneumothorax or empyema. Embolization of septic material to the brain, giving rise to meningitis or brain abscess. Secondary amyloidosis may develop in chronic cases.


NOTE: Infective abscesses occur in 10% to 15% of patients with bronchogenic carcinoma. Thus, when a lung abscess is suspected in an older patient, underlying carcinoma must be considered.

Pulmonary Disease in HIV Infection

Pulmonary disease continues to be the leading cause of morbidity and mortality in HIV-infected patients. Caused by opportungistic microorganisms (as CMV, Pneumocystitis carinii, fungi..) but also may be caused by usual bacteria (as ) in which pneumonias are more severe, and more often associated with bacteremia than in those without HIV infection. The CD4+ count is often useful in narrowing the differential diagnosis. HOW?

P. carinii: An opportunistic infectious agent believed to be related to fungi. Pneumocystis occurs exclusively in those who are immunocompromised especially AIDS patients. Pneumocystis infections are largely confined to the lung, where they produce an interstitial pneumonitis.