General Pathology 601 for Dental Students

Pathology of Bacterial Pneumonia and Abscess, Tuberculosis, 
& Chronic Obstructive Pulmonary Disease

Margaret M Grimes, MD, M.Ed. Surgical Pathology Sanger Hall, 5th Floor (804) 828-9739 mmgrimes@vcu.edu

Bacterial Pneumonia and Abscess

Objectives
Upon completion of this section of the lecture you will be able to:

1. Define pneumonia.
2. Name 4 routes of infection and 4 important defense mechanisms.
3. List 6 clinical situations associated with impairment of the defense mechanisms.
4. Recognize the 4 classical stages of lobar pneumonia.
5. Describe the character, cause and typical involvement of bronchopneumonia.
6. Identify complications of bacterial pneumonia.
7. Define abscess and list 4 etiologic mechanisms of lung abscess formation.

Important Terms in Pneumonia and Abscess
Hyperemia
Vascular Permeability
Exudate
Aspiration
Inhalation 
Bacteremia
Abscess

Pathology of Bacterial Pneumonia

Pneumonia is an inflammatory disease of the lung characterized by the production of a vascular response (hyperemia and vascular permeability) and an exudate. Bacteria, viruses, fungi and parasites may all cause pneumonia. The pattern of tissue response typically varies for each of these, although there may be overlap. The following description applies to typical cases of bacterial pneumonia.

Routes of Infection
Several possible routes of infection of the lung exist:

1. Aspiration of contaminated secretions--most common
2. Inhalation of infected airborne droplets
3. Bacteremia, and 
4. Direct extension of an acute inflammatory process from an adjacent organ or structure

Defense Mechanisms
In the normal respiratory system there are a number of important defense mechanisms that protect the lung from infection. These include:

1. Reflex closure of the vocal cords
2. Cough reflex
3. Mucociliary clearance
4. Macrophage activity and immune competence

An increased risk of bacterial infection is associated with impairment of the defense mechanism, as in any of these clinical situations:

1. Loss of consciousness
2. Immunodeficiency state
3. Pulmonary edema
4. Neutropenia
5. Chronic airway obstruction
6. Viral infection

Exudate
The exudate in bacterial pneumonia is typically composed of varying proportions of:

• edema fluid
• red blood cells
• leukocytes (principally neutrophils)
• fibrin

The cellular exudate in acute bacterial pneumonia is in the alveolar spaces and distal bronchioles though in severe cases the major airways may also be filled with purulent secretion.

Classification
Bacterial pneumonias may be classified on the basis of the causative organism (clinically most important!), or the pattern of anatomic involvement: lobar pneumonia or bronchopneumonia. These two patterns sometimes overlap, but their description is useful to demonstrate the pathologic evolution of bacterial pneumonia.

Lobar Pneumonia
Lobar pneumonia is exudative inflammation involving a whole lobe, or a large portion of a lobe of lung.

*90-95% of cases are caused by Streptococcus pneumoniae. Occasional cases are due to Klebsiella pneumoniae, Staphylococus, Streptococcus, Hemophilus influenzae, or Gram-negative bacteria.

*This type of pneumonia typically affects adults. *Four stages are classically described:

1. Congestion: This stage is characterized histologically by vascular engorgement, intra-alveolar fluid, small numbers of neutrophils, often numerous bacteria. Grossly, the lung is heavy and hyperemic.
   
2. Red hepatization: Vascular congestion persists, with extravasation of red cells into alveolar spaces, along with increased numbers of neutrophils and fibrin. The filling of airspaces by the exudate leads to a gross appearance of solidification, or consolidation, of the alveolar parenchyma. This appearance has been likened to that of the liver, hence the term "hepatization".
   
3. Gray hepatization: Red cells disintegrate, with persistence of the neutrophils and fibrin. The alveoli still appear consolidated, but grossly the color is paler and the cut surface is drier.
   
4. Resolution: The exudate is digested by enzymatic activity, and cleared by macrophages or by cough mechanism.

Bronchopneumonia 
Bronchopneumonia is characterized by focal areas of suppurative inflammation, in a patchy distribution, involving one or multiple lobes.

Cause
Infection by many types of bacteria may produce bronchopneumonia; Streptococcus pneumoniae is the most common cause of community-acquired bronchopneumonia. 

Some cases of bronchopneumonia, when severe, may show confluent areas of involvement that resemble the pattern of lobar pneumonia.

The inflammatory exudate in each of the foci of involvement typically involves a small airway and surrounding alveolar spaces. Histologically, the same stages of evolution are believed to occur, but the relatively small areas of involvement, and temporal differences among these foci, makes demonstration of this evolution more difficult than in lobar pneumonia.

Although the majority of the bacterial pneumonias resolve, with return of the parenchyma to (near) normal, in some cases complications occur. These include: 

1. Abscess formation
2. Spread of the infection to the pleural cavity (empyema)
3. Organization of the exudate (replacement of exudate by fibroblasts)
4. Bacteremia, with spread of the infection to distant sites.

Abscess

An abscess is a localized suppurative process characterized by necrosis of tissue. In the lung, an abscess may occur in the setting of a pneumonia, or as an isolated process. Etiologic mechanisms include:

1. aspiration of infected material
2. septic embolism
3. direct trauma
4. spread from adjacent structures

Abscesses may occur in any location in the lung; they may be single or multiple. Abscesses due to aspiration occur most commonly in the right lung (because of the more vertical course of the right main stem bronchus) and are usually single.

Morphologically an abscess is a cavity filled with suppurative debris. If communication exists with an airway, the exudate may drain, leading to air in the cavity, and an air-fluid level on chest x-ray. In chronic abscesses, there may be peripheral fibroblastic proliferation resulting in a fibrous wall.

The clinical course of an abscess is variable. Treatment with antibiotics may lead to resolution; alternatively, the infection may spread to involve adjacent structures or distant sites.

Tuberculosis

Objectives
Upon completion of this section of the lecture you will be able to:

1. Describe the appearance, proliferation, dissemination and course of primary and secondary phases of pulmonary tuberculosis.

Important Terms in TB
Ghon Complex
Caseous necrosis

Pulmonary Tuberculosis

Pulmonary infection with Mycobacterium tuberculosis is acquired as a result of inhaling the tubercle bacillus suspended in the aerosolized sputum coughed up by an infected individual with "open" tuberculosis (i.e. a tuberculous focus communicating with a bronchus). Non-specific inflammatory response is followed by development of delayed type cell-mediated hypersensitivity with granuloma formation.

Two phases of this disease occur:

1. Primary tuberculosis--By definition, this infection occurs in an individual not previously exposed and sensitized to tubercle bacilli.
2. Secondary (reactivation) tuberculosis--By definition, this is tuberculosis which becomes clinically evident in an individual already sensitized to the tubercle bacillus.

The location of the inflammatory foci and host response to the infection differ in these two phases.

Primary tuberculosis
The sequence of events in primary infection typically involves:

• inhalation of infected airborne droplet
• particle size (approximately 3 microns) favors deep inhalation and retention of the organism
• the bacilli tend to locate in the subpleural midzone of lung
• the earliest radiographic appearance is an ill-defined localized "atypical" pneumonia
• after a brief acute inflammatory reaction associated with a neutrophilic response, the bacilli invoke granuloma formation.
• Bacilli drain to lymph nodes; granulomas form in nodes
• by 2 to 8 weeks, the pneumonic focus becomes a more defined radiographic opaque single spheroidal lesion--(Ghon focus); the combination of the pulmonary granuloma and the lymph node granuloma is known as the Ghon complex.

Secondary/Reactive tuberculosis
Reactivation of dormant bacilli is considered the most common source of secondary tuberculosis, but reinfection from an outside source is believed to occur in some cases. The cause of reactivation is presumed to be a decline in host immunocompetence. There is increased risk for reactivation in patients with AIDS, alcoholism, diabetes, certain malignancies, or undergoing steroid or radiation therapy.

Table--primary and secondary TB

Phase	Appearance	Proliferation	Dissemination	Course
Primary pulmonary tuberculosis (Previously unexposed individual)	Combination of the original peripheral Ghon focus plus hilar node granuloma =Ghon complex. Granulomas of tuberculosis typically become centrally necrotic. When macroscopically visible, the cut surface of these necrotic granulomas resembles yellowish-white cheese, hence the term "caseous" necrosis.	Tubercle bacilli in the Ghon lesion can enter into lymphatics, and drain to regional hilar nodes where granulomas also form.	Entrance into the lymphatics permits multiorgan dissemination.	Subsequent course varies: -occasionally because of the virulence of the organism or poor host resistance, infection spreads either via airspaces, leading to a tuberculous bronchopneumonia, or via the bloodstream, leading to formation of myriads of small granulomas in one or several organs (miliary tuberculosis). The more usual course is the fibrosis and calcification of the Ghon complex; tubercle bacilli lie dormant even with fibrosis and calcification of the granulomas. This latent phase may persist throughout life, the only index of infection being a positive PPD (purified protein derivative) reaction and the presence of the obsolete fibrocalcific Ghon complex.
Phase	Appearance	Proliferation	Dissemination	Course
Secondary (reactivation) tuberculosis (Previously sensitized individual-- re-activation of dormant focus or re-exposure to exogenous source)	Granulomas form quickly--caseation is usually pronounced. The location of granulomas is typically in the apices of the lungs. This is probably due to relatively high tissue oxygen levels in this portion of the lung. The tubercle bacillus is aerophilic.	The fibrotic reaction tends to confine the typical lesion, but concurrently there is an increased tendency to tissue destruction and cavitation. Cavitation favors proliferation of organism and spread to contacts.	Entrance into the lymphatics permits multiorgan dissemination. "Miliary" tuberculosis is characterized by numerous minute granulomas in lung and/or extrapulmonary sites.	Sensitization to the bacillus in the primary phase appears to confer both an advantage and a disadvantage. Hypersensitivity enhances resistance and induces a more prompt response by activated macrophages and fibroblasts. It is the variable spectrum of the interaction of hypersensitivity and fibrotic reaction which determines the natural course of the disease, which ranges from cure through continuous progression, or multiple exacerbations to death.

Chronic Obstructive Pulmonary Disease

Objectives
Upon completion of this section of the lecture you will be able to:

1. Recall that COPD is strongly correlated with air pollution and smoking.
2. Recognize changes associated with chronic bronchitis and emphysema.
3. Compare and contrast pathologic changes in centrilobular (centriacinar) and panacinar (panlobular) emphysema.

Important Terms In COPD
Reid Index
acinus
alpha-1 antitrypsin deficiency
bulla
protease-antiprotease

Pathology of Chronic Obstructive Pulmonary Disease:
Chronic Bronchitis and Emphysema

Although chronic bronchitis and emphysema frequently occur together, each may be seen clinically and pathologically as separate entities. The incidence and severity of COPD are strongly correlated with air pollution and smoking. Although the mortality from lung cancer exceeds that of COPD, the earlier onset and prolonged morbidity of COPD lends it a greater socioeconomic impact. Both chronic bronchitis and emphysema are more common in men than in women.

Chronic Bronchitis
This condition is defined by clinical parameters, specifically the presence of a persistent cough productive of sputum for at least 3 months, in at least 2 consecutive years.

Involvement and Pathologic Changes
The pathologic changes of chronic bronchitis are found in the bronchi and/or bronchioles. In some cases, involvement of both small and large airways is present, whereas in others, one may predominate or be absent.

Large airway (bronchial) involvement is clinically manifest as cough and sputum production. The histologic changes consist of :

• increased numbers of goblet cells in the epithelium
• increased volume of the submucosal mucus glands

The latter is judged by determining the Reid index, which is defined as the ratio of the width of the submucosal gland mass to the distance from the basal lamina of the mucosa to the inner perichondrium. A ratio greater than 0.4 indicates mucus gland enlargement.

In addition to the increase in mucus-secreting cells and glands, there is usually a component of chronic inflammation in the airway wall, but the amount of this infiltrate may be highly variable.

The histology of small airway (bronchiolar) involvement consists of the presence of goblet cells in the lining epithelium. Goblet cells are normally rare or absent in the distal airways. Involvement of bronchioles may be manifest as a decrease in maximum forced expiratory flow, since mucus in the lumen of the small airways can produce an increased resistance to flow. As in the large airways, there may also be a component of inflammation.

Superimposed acute inflammation in the airways of a patient with chronic bronchitis may contribute to exacerbation of symptomatology due to increased cellular infiltrates and edema.

Emphysema
Emphysema is defined by morphologic parameters, i.e. abnormal permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls. The component of wall destruction distinguishes emphysema from simple over-inflation.

Emphysema occurs in different forms, based on the anatomic distribution of the process.

The pulmonary acinus comprises those components of the lung distal to a terminal bronchiole, i.e., respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli. The acinus is not exactly the same as the pulmonary lobule, but for practical purposes, these two terms are often interchanged, hence the terminology that follows for the different types of emphysema.

Grossly, this form of emphysema typically affects the upper lobes earlier and more severely than the lower lobes. Patients are typically cigarette smokers. Cut surface of the lung parenchyma typically shows foci of dilated spaces surrounded by relatively normal tissue.

Microscopically, the distribution of the lesions may be difficult to discern. The destruction of alveolar septal walls is evident by the presence of septa unattached to adjacent alveoli. Fibrosis is not a feature of diffuse centrilobular emphysema.

Late in the course of the disease, the destruction of septa and dilatation of airspaces may extend to involve all portions of the acinus, creating an appearance that resembles panacinar emphysema. Usually, however, one can still find areas of the lung where there is the patchy dilatation typical of centrilobular emphysema.

Grossly, cut surface of the lung shows diffuse enlargement of airspaces in the affected parenchyma. Often the enlarged spaces are traversed by delicate, spider-web-like strands representing the residual alveolar walls. As in centrilobular emphysema, fibrosis is not seen.

In any of the forms of emphysema, dilated airspaces may enlarge to a size greater than 2 cm in dimension. An enlarged space of this size may be referred to as a "bulla." The term "bullous emphysema" does not connote a specific type of emphysema. Bullae may be clinically important because of their tendency to rupture, resulting in pneumothorax.

In centrilobular and panacinar emphysema, the clinical symptoms of obstructive lung disease result from the increased resistance to expiratory flow that occurs as small airways, no longer supported by the elastic recoil of alveolar septa, collapse during expiration.

Pathogenesis
The destruction of portions of the alveolar septal walls has been related to an imbalance of protease-antiprotease activity in the lung. Patients with alpha-1 antitrypsin deficiency have a relative increase in protease activity. Cigarette smokers tend to have more neutrophilis and macrophages recruited to the alveolar parenchyma, compared with non-smokers. These two cell types are the major source of proteases and elastases in the lung.

Digital Legends for Labs
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Updated June 22, 2011