Lecture 21. Lungs diseases.

Adult Respiratory Distress Syndrome

Adult respiratory distress syndrome (ARDS) is known by various synonyms such- as shock-lung
syndrome, diffuse alveolar damage (DAD), acute alveolar injury, traumatic wet lungs and post-
traumatic respiratory insufficiency. ARDS is a syndrome caused by diffuse alveolar capillary
damage and clinically characterised by sudden and severe respiratory distress, tachypnoea,
tachycardia, cyanosis and severe hypoxaemia that fails to respond to oxygen therapy and assisted
ventilation unlike neonatal RDS. The chest radiographs of these patients show diffuse bilateral
alveolar infiltrates which may progress.
PATHOGENESIS. The basic initiating event in the pathogenesis of ARDS is diffuse damage to
the alveolocapillary wall by one of the injurious factors listed above. The mechanism of damage
depends upon the etiologic agentit may be by oxygen-derived free radicals, by intravascular
aggregation of neutrophils, or by liberation of mediators of inflammation. Injury to the capillary
endothelium leads to increased vascular permeability. Injury to epithelial cells, especially to type
I alveolar cells, causes necrosis of these cells. The net effect of injury to both capillary
endothelium and alveolar epithelium is interstitial and intra-alveolar oedema, congestion, fibrin
deposition and formation of hyaline membranes as seen in neonatal RDS. As a result of lining of
the alveoli with hyaline membranes, there is loss of surfactant causing collapse with pulmonary
oedema called 'stiff lung There is an attempt at regeneration of alveolar cells by proliferation of
type II alveolar cells. A stiff lung of ARDS may undergo complete recovery or may undergo
organisation resulting in proliferation of interstitial cells leading to interstitial fibrosis or even
death.
PATHOLOGIC CHANGES. Grossly, the lungs are characteristically stiff, congested and heavy.
Microscopically, the following features are evident:
1. Interstitial and intra-alveolar oedema.
2. Necrosis of alveolar epithelial cells with formation of hyaline membranes. The hyaline
membranes are chiefly composed of fibrin admixed with necrotic epithelial cells.
3. Congestion and intra-alveolar haemorrhages
4. Changes of bronchopneumonia
5. In organising stage, there may be interstitial fibrosis and regenerating flat alveolar epithelial
cells lining the denuded alveoli.
PULMONARY INFECTIONS
Pneumonias. Pneumonia is defined as acute inflammation of the lung parenchyma distal to the
terminal bronchioles which consist of the respiratory bronchiole, alveolar ducts, alveolar sacs and
alveoli.
PATHOGENESIS. The microorganisms gain entry into the lungs by:
1. Inhalation of the microbes present in the air.
2. Aspiration of organisms from the nasopharynx or oropharynx.
3. Haematogenous spread from a distant focus of infection.
4. Direct spread from an adjoining site of infection.
CLASSIFICATION. On the basis of the anatomic part of the lung parenchyma involved,
pneumonias are traditionally classified into 3 main types:
1. Lobar pneumonia, 2. Bronchopneumonia (or Lobular pneumonia), 3. Interstitial pneumonia
I. Lobar Pneumonia Lobar pneumonia is an acute bacterial infection of a part of a lobe, the
entire lobe, or even two lobes of one or both the lungs.
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ETIOLOGY. Based on the etiologic microbial agent causing lobar pneumonia, the following
types are described: Pneumococcal pneumonia, Staphylococcal pneumonia, Streptococcal
pneumonia, Pneumonia by gram-negative aerobic bacteria (Less common causes of lobar
pneumonia are gram-negative bacteria like Haemophilw influenzae, Klebsiella pneumoniae
(Friedlander's bacillus), Pseudomonas, Proteus and Escherichia coll. H. Influenzae)
PATHOLOGIC CHANGES. Laennec's original description divides lobar pneumonia into 4
sequential pathologic phases: stage of congestion (initial phase), red hepatisation (early
consolidation), grey hepatisation (late consolidation) and resolution. However, these classic
stages seen in untreated cases are found much less often now-a-days due to administration of
antibiotics and improved medical care.
In lobar pneumonia, as the name suggests, part of a lobe, a whole lobe, or two lobes are in-
volved sometimes bilaterally. The lower lobes are affected most commonly. The sequence of
pathologic changes described below represents the inflammatory response in bacterial infection:
1. STAGE OF CONGESTION : INITIAL PHASE. The initial phase represents the early acute
inflammatory response to bacterial infection and lasts for 1 to 2 days.
Grossly, the affected lobe is enlarged, heavy, dark red and congested. Cut surface exudes blood-
stained frothy fluid.
Histologically, typical features of acute inflammatory response to the organisms are seen. These
are: i) Dilatation and congestion of the capillaries in the alveolar walls.
ii) Pale eosinophilic oedema fluid in the air spaces.
iii) A few red cells and neutrophils in the intra-alveolar fluid.
iv) Numerous bacteria demonstrated in the alveolar fluid by Gram's staining.
2. RED HEPATISATION: EARLY CONSOLIDATION. This phase lasts for 2 to 4 days. The
term hepatisation in pneumonia refers to liver-like consistency of the affected lobe on cut section.
Grossly, the affected lobe is red, firm and consolidated. The cut surface of the involved lobe is
airless, red-pink, dry, granular and has liver-like consistency. The stage of red hepatisation is
accompanied by serofibrinous pleurisy.
Histologically, the following features are observed:
i) The oedema fluid of the preceding stage is replaced by strands of fibrin.
ii) There is marked cellular exudate of neutrophils and extravasation of red cells.
iii) Many neutrophils show ingested bacteria.
iv) The alveolar septa are less prominent than in the first stage due to cellular exudation.
3. GREY HEPATISATION : LATE CONSOLIDATION. This phase lasts for 4 to 8 days.
Grossly, the affected lobe is firm and heavy. The cut surface is dry, granular and grey in
appearance with liver-like consistency. The change in colour from red to grey begins at the hilum
and spreads towards the periphery. Fibrinous pleurisy is prominent.
Histologically, the following changes are present:
i) The fibrin strands are dense and more numerous.
ii) The cellular exudate of neutrophils is reduced due to disintegration of many inflammatory
cells as evidenced by their pyknotic nuclei. The red cells are also fewer. The macrophages begin
to appear in the exudate.
iii) The cellular exudate is often separated from the septal walls by a thin clear space.
iv) The organisms are less numerous and appear as degenerated forms.

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4. RESOLUTION: This stage begins by 8th to 9th day if no chemotherapy is administered and is
completed in 1 to 3 weeks. However, antibiotic therapy induces resolution on about 3rd day.
Resolution proceeds in a progressive manner.
Grossly, the previously solid fibrinous constituent is liquefied by enzymatic action, eventually
restoring the normal aeration in the affected lobe. The process of softening begins centrally and
spreads to the periphery. The cut surface is grey-red or dirty brown and frothy, yellow, creamy
fluid can be expressed on pressing. The pleural reaction may also show resolution but may
undergo organisation leading to fibrous obliteration of pleural cavity.
Histologically, the following features are noted:
i) Macrophages are the predominant cells in the alveolar spaces, while neutrophils diminish in
number. Many of the macrophages contain engulfed neutrophils and debris.
ii) Granular and fragmented strands of fibrin in the alveolar spaces are seen due to progressive
enzymatic digestion.
iii) Alveolar capillaries are engorged.
iv) There is progressive removal of fluid content as well as cellular exudate from the air spaces,
partly by expectoration but mainly by lymphatics, resulting in restoration of normal lung
parenchyma with areation.
COMPLICATIONS. Since the advent of antibiotics, serious complications of lobar pneumonia
are uncommon. However, they may develop in neglected cases and in patients with impaired
immunologic defenses. These are as under:
1. Organisation. In about 3% of cases, resolution of the exudate doesnot occur but instead it is
organised. There is ingrowth of fibroblasts from the alveolar septa resulting in fibrosed, tough,
airless leathery lung tissue. This type of post-pneumonic fibrosis is called carnification.
2. Pleural effusion. About 5% of treated cases of lobar pneumonia develop inflammation of the
pleura with effusion. The pleural effusion usually resolves but sometimes may undergo
organisation with fibrous adhesions between visceral and-parietal pleura.
3. Empyema. Less than 1% of treated cases of lobar pneumonia develop encysted pus in the
pleural cavity termed empyema.
4. Lung abscess. A rare complication of lobar pneumonia is formation of lung abscess, especially
when there is secondary infection by other organisms.
5. Metastatic infection. Occasionally, infection in the lungs and pleural cavity in lobar
pneumonia may extend into the pericardium and the heart causing purulent pericarditis, bacterial
endocarditis and myocarditis. Other forms of metastaric infection encountered rarely in lobar
pneumonias are otitis media, mastoiditis, meningitis, brain abscess and purulent arthritis.
II. Bronchopneumonia (Lobular Pneumonia)
Bronchopneumonia or lobular pneumonia is infection of the terminal bronchioles that extends
into the surrounding alveoli resulting in patchy consolidation of the lung. The condition is
particularly frequent at extremes of life (i.e. in infancy and old age), as a terminal event in
chronic debilitating diseases and as a secondary infection following viral respiratory infections
such as influenza, measles etc.
ETIOLOGY. The common organisms responsible for bronchopneumonia are staphylococci,
streptococci, pneumococci, Klebsiella pneumoniae, Haemofihilus influenzae, and gram-negative
bacilli like Pseudomonas and coliform bacteria.
PATHOLOGIC CHANGES. Grossly, bronchopneumonia is identified by patchy areas of red or
grey consolidation affecting one or more lobes, frequently found bilaterally and more often
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involving the lower zones of the lungs due to gravitation of the secretions. On cut surface, these
patchy consolidated lesions are dry, granular, firm, red or grey in colour, 3 to 4 cm in diameter,
slightly elevated over the surface and are often centred around a bronchiole. These patchy areas
are best picked up by passing the fingertips on the cut surface.
Histologically, the following features are observed:
i) Acute bronchiolitis.
ii) Suppurative exudate, consisting chiefly of neutrophils, in the peribronchiolar alveoli.
iii) Thickening of the alveolar septa by congested capillaries and leucocytic infiltration.
iv) Less involved alveoli contain oedema fluid.
COMPLICATIONS. The complications of lobar pneumonia may occur in bronchopneumonia as
well. However, complete resolution of bronchopneumonia is uncommon. There is generally
some degree of destruction of the bronchioles resulting in foci of bronchiolar fibrosis that may
eventually cause bronchiectasis.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Chronic obstructive pulmonary disease (COPD) or chronic obstructive airways disease (COAD)
are commonly-used clinical terms for a group of pathological conditions in which there is
chronic, partial or complete, obstruction to the airflow at any level from trachea to the smallest
airways resulting in functional disability of the lungs. The obstructive pulmonary disease must be
distinguished from restrictive pulmonary disease. The following 4 entities are included in COPD:
I. Chronic bronchitis, II. Emphysema, III. Bronchial asthma, IV. Bronchiectasis
Chronic bronchitis and emphysema are quite common and often occur together. More
recently, small airways disease involving inflammation of small bronchi and bronchioles
(bronchiolitis) has been added to the group of COPD.
I. CHRONIC BRONCHITIS
Chronic bronchitis is a common condition defined clinically as persistent cough with
expectoration on most days for at least three months of the year for two or more consecutive
years. The cough is caused by oversecretion of mucus. In spite of its name, chronic inflammation
of the bronchi is not a prominent feature. The condition is more common in middle-aged males
than females; approximately 20% of adult men and 5% of adult women have chronic bronchitis,
but only a minority of them develop serious disabling COPD or cor pulmonale. Quite frequently,
chronic bronchitis is associated with emphysema.
ETIOPATHOGENESIS. The two most important etiologic factors responsible for majority of
cases of chronic bronchitis are: cigarette smoking and atmospheric pollution. Other contributory
factors are occupation, infection, familial and genetic factors.
PATHOLOGIC CHANGES. Grossly, the bronchial wall is thickened, hyperaemic and
oedematous. Lumina of the bronchi and bronchioles may contain mucus plugs and purulent
exudate.
Microscopically, the characteristic features are as follows:
1. The cartilage-containing large airways have hypertrophy and hyperplasia of submucosal mu-
cous glands. The increase in thickness can be quantitatively assessed by Reid index which is the
ratio between thickness of the submucosal glands to that of the bronchial wall. The bronchial
epithelium may show squamous metaplasia and dysplasia.
2. The non-cartilage containing small airways show goblet cell hyperplasia and intraluminal and
peribronchial fibrosis.
II. EMPHYSEMA
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The WHO has defined pulmonary emphysema as combination of permanent dilatation of air
spaces distal to the terminal bronchioles and the destruction of the walls of dilated air spaces.
Thus, emphysema is defined morphologically, while chronic bronchitis is defined clinically. Since
the two conditions coexist frequently and show considerable overlap in their clinical features, it is
usual to label patients as 'predominant emphysema' and 'predominant bronchitis' .
CLASSIFICATION. By strictly adhering to the WHO definition of pulmonary emphysema, it is
classified, according to the portion of the acinus involved, into 5 types: centriacinar, panacinar
(panlobular) para-septal (distal acinar), irregular (para-cicatricial) and mixed (unclassified)
emphysema.
IV. BRONCHIECTASIS
Bronchiectasis is defined as abnormal and irreversible dilatation of the bronchi and bronchioles
(greater than 2 mm in diameter) developing secondary to inflammatory weakening of the bron-
chial walls. The most characteristic clinical manifestation of brochiectasis is persistent cough
with expectoration of copious amounts of foul-smelling, purulent sputum. Post-infectious cases
commonly develop in childhood and in early adult life.
ETIOPATHOGENESIS. The origin of inflammatory destructive process of bronchial walls is
nearly always a result of two basic mechanisms: obstruction and infection.
PATHOLOGIC CHANGES. The disease characteristically affects distal bronchi and bronchioles
beyond the segmental bronchi.
Macroscopically, the lungs may be involved diffusely or segmentally. Bilateral involvement of
lower lobes occurs most frequently. More vertical air passages of left lower lobe are more often
involved than the right. The pleura is usually fibrotic and thickened with adhesions to the chest
wall. Cut surface of the affected lobes, generally the lower zones, shows characteristic honey-
combed appearance. The bronchi are extensively dilated nearly to the pleura, their walls are
thickened and the lumina are filled with mucus or muco-pus. The intervening lung parenchyma is
reduced and fibrotic. The dilated airways, depending upon their gross or bronchographic
appearance, have been subclassified into the following different types:
i) Cylindrical: the most common type characterised by tube-like bronchial dilatation.
ii) Fusiform: having spindle-shaped bronchial dilatation.
iii) Saccular : having rounded sac-like bronchial distension.
iv) Varicose ; having irregular bronchial enlargments.
CLINICAL FEATURES. The clinical manifestations of bronchiectasis typically consist of
chronic cough with foul-smelling sputum production, haemoptysis and recurrent pneumonia.
Sinusitis is a common accompaniment of diffuse bronchiectasis. Development of clubbing of the
fingers, metastatic abscesses (often to the brain), amyloidosis and cor pulmonale are late
complications occurring in cases uncontrolled for years.
CHRONIC RESTRICTIVE PULMONARY DISEASE
The second large group of diffuse lung disease is 'chronic restrictive pulmonary disease'
characterised by reduced expansion of lung parenchyma with decreased total lung capacity. This
group of diseases must be distinguished from the foregoing COPD.
Restriction due to interstitial and infiltrative diseases. These are diseases characterised by
non-infectious involvement of the interstitial connective tissue of lung parenchyma. The term
'infiltrative' is used here to denote the radiologic appearance of lungs in chest radiographs which
show ground-glass shadows due to diffuse infiltration by small nodules or irregular lines. The
conditions included in this group are as under: I. Pneumeconiosis, II. Immunulogic lung diseases
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III. Collagen-vascular diseases, IV. Idiopathic pulmonary fibrosis, V. Sarcoidosis.
INFLUENZA VIRUSES
Influenza viruses are larger and more complex than rhinoviruses. The genome of influenza virus
is composed of eight helices of single-stranded RNA, each encoding a single gene and each
bound by a nucleoprotein that determines the type of influenza virus (A, B, or C). Influenza
viruses of type A infect humans, pigs, horses, and birds and are the major cause of pandemic and
epidemic influenza infections. A single subtype of influenza virus A predominates throughout the
world at a given time.
MORPHOLOGY. Viral upper respiratory infections are marked by mucosal hyperemia and
swelling with a predominantly lymphomonocytic and plasmacytic infiltration of the submucosa
accompanied by overproduction of mucous secretions. The swollen mucosa and viscid exudate
may plug the nasal channels, sinuses, or eustachian tubes and lead to suppurative secondary
bacterial infection. Virus-induced tonsillitis with enlargement of the lymphoid tissue within
Waldeyer ring is frequent in children, although lymphoid hyperplasia is not usually associated
with suppuration or abscess formation, such as is encountered with streptococci or staphylococci.
In laryngotracheobronchitis and bronchiolitis, there is vocal cord swelling and abundant mu-
cous exudation. Impairment of bronchociliary function invites bacterial superinfection with more
marked suppuration. Plugging of small airways may give rise to focal lung atelectasis. In the
more severe bronchiolar involvement, widespread plugging of secondary and terminal airways by
cell debris, fibrin, and inflammatory exudate may, when prolonged, cause organization and
fibrosis, resulting in obliterative bronchiolitis and permanent lung damage. Viral pneumonias,
like bacterial pneumonias, take a variety of anatomic forms.
Measles
Measles (rubeola) virus is the cause of 1.5 million deaths per year among third world children.
Pathogenesis. Measles virus is an RNA virus of the paramyxovirus family. There is only one
strain of measles virus. Measles virus is spread by respiratory droplets and multiplies within
upper respiratory epithelial cells and mononuclear cells, including and lymphocytes and
macrophages. A transient viremia spreads the measles virus throughout the body and may cause
croup, pneumonia, diarrhea with protein-losing enteropathy, keratitis with scarring and blindness,
encephalitis, and hemorrhages ("black measles"). Most children, however, develop cell-
mediated immunity to measles virus that controls the viral infection and produces the measles
rash, a hypersensitivity reaction to viral antigens in the skin. Antibody-mediated immunity to
measles virus protects against reinfection.
MORPHOLOGY. The blotchy, reddish brown rash of measles virus infection on the face, trunk,
and proximal extremities 1s produced by dilated skin vessels, edema, and a moderate,
nonspecific, mononuclear perivascular infiltrate. Ulcerated mucosal lesions in the oral cavity near
the opening of Stensen ducts (the pathognomonic Koplik spots) are marked by necrosis,
neutrophil exudate, and neovascularization. The lymphoid organs typically have marked
follicular hyperplasia, large germinal centers, and randomly distributed multinucleate giant cells,
called Warthin-Finkeldey cells, which have eosinophilic nuclear and cytoplasmic inclusion
bodies. These are pathognomonic of measles and are also-found in the lung and sputum. The
milder forms of measles pneumonia show the same peribronchial and interstitial mononuclear
infiltration seen in other nonlethal viral infections. In severe or, neglected cases, bacterial
superinfection may be a cause of death.