ATELECTASIS (COLLAPSE)
Atelectasis, also known as collapse, is loss of lung volume caused by
inadeqwate expansion ofairspaces. It results in shunting of inadequately
oxygenated blood from pulmonary arteries into veins, thus giving rise to a
ventilation-perfusion imbalance and hypoxia. On the basis of the
underlying mechanism or the distribution of alveolar collapse, atelectasis
is classified into three forms
1-Resorption Atelectasis. Resorption atelectasis occurs when an
obstruction prevents air from reaching distal airways. The air already
present gradually becomes absorbed, and alveolar collapse follows.
Depending on the level of airway obstruction, an entire lung, a complete
lobe, or one or more segments may be involved. The most common cause
of resorption collapse is obstruction of a bronchus by a mucous or
mucopurulent plug. This frequently occurs postoperatively but may also
complicate bronchial asthma, bronchiectasis, chronic bronchitis, or
the aspiration of foreign bodies, particularly in children.
2- Compression Atelectasis. Compression atelectasis (sometimes called
passive or relaxation atelectasis) is usually associated with accumulations
of fluid, blood, or air within the pleural cavity, which mechanically
collapse the adjacent lung. This is a frequent occurrence with pleural
effusions, caused most commonly by congestive heart failure (CHF).
Leakage of air into the pleural cavity (pneumothorax) also leads to
compression arelectasis
3-Contraction Atelectasis. Contraction (or cicatrization) atelectasis occurs
when either local or generalized fibrotic changes in the lung or pleura
hamper expansion and increase elastic recoil during expiration.
Atelectasis (except that caused by contraction) is potentially reversible
and should be treated promptly to prevent hypoxemia and superimposed
infection of the collapsed lung
1
Obstructive airway diseases
The major diffuse obstructive disorders are emphysema, chronic
bronchitis, bronchiectasis, and asthma. Ln patients with these diseases,
total lung capacity and forced vital capacity (FVC) are either normal or
increased, and the hallmark is a decreased expiratory flow rate, usually
measured by forced expiratory volume at 1 second (FEV'). Thus, the ratio
of FEVI to FVC is characteristically decreased. Expiratory obstruction
may result either from anatomic airway narrowing, classically observed
in asthma, or from loss of elastic recoil, characteristic of emphysema
Emphysema
Emphysema is characterized by abnormal permanent enlargement of the
airspaces distal to the terminal bronchioles, accompanied by destruction
of their walls without obvious fibrosis
Types of Emphysema.
Emphysema is classified according to its anatomic distributioa within the
lobule; recall that the acinus is the structure distal to terminal bronchioles,
and a cluster of three to five acini is called a lobule. There are four major
types of emphysema: (1) centriacinar, (2) panacinar, (3) distal acinar, and
(4) irregular. Only the first two cause clinically significant airway
obstruction, with centriacinar emphysema being about 20-fold more
common than panacinar
1-Centriacinar (Centrilobular) Emphysema. The distinctive feature of this
type of emphysema is the pattern of involvement of the lobules: the
central or proximal parts of the acini, formed by respiratory bronchioles,
are affected, while distal alveoli are spared. Thus, both emohvsematous
and normal airspaces exist within the same acinus and lobule . The
lesions are more common and severe in the upper lobes, particularly in
the apical segments. In severe centriacinar emphysema the distal acinus
also becomes involved, and so, as noted,the differentiation from
panacinar emphysema becomes difficult. This type of emphysema is
most commonly seen as a consequence of cigarette smoking in people
who do not have congenital deficiency of alpha1-antitrypsin.
2
2- Panacinar (Panlobular) Emphysema. In this type of emphysema, the
acini are uniformly enlarged from the level of the respiratory bronchiole
to the terminal blind alveoli . In contrast to centriacinar emphysema,
panacinar emphysema tends to occur more commonly in the lower lung
zones and is the type of emphysema that occurs in u1-antitrypsin
deficiency.
3-Distal Acinar (Paraseptal) Emphysema. In this form, the proximal
portion of the acinus is normal but the distal part is primarily involved.
The emphysema is more striking madjacent to the pleura, along the
lobular connective tissue septa, and at the margins of the lobules. It
occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually
more severe in the upper half of the lungs. The characteristic findings are
the presence of multiple, contiguous, enlarged airspaces that range in
diameter from lesst han 0.5mm to more than 2.0cm, sometimesf orming
cystlike structures that with progressive enlargement are referred to as
bullae. This type of emphysema probably underlies many of the cases of
spontaneous pneumothorax in young adults.
4-lrregular Emphysema. Irregular empbysema, so named because the
acinus is irregularly inuolued, is almost inuariably associated with
scarring, such as resulting from healed inflammatory diseases. Although
clinically asymptomatic, this may be the most common form of
emphysema.
Pathogenesis
Current opinion favors emphysema arising as a consequence of two
critical imbalances: the protease-antiprotease imbalance and oxidantantioxidant imbalance
The protease-antiprotease imbalance hypothesis is based on the
observation that patients with a genetic deficiency of the antiproteasea 1antitrypsin have a markedly enhanced tendency to develop pulmonary
emphysema, which is compounded by smoking. About 1% of all patients
with emphysema have this defect. alpha1-Antitrypsin, normally present in
serum, tissue fluids, and macrophages, is a major inhibitor of proteases
(particularly elastases) secreted by neutrophils during inflammation.
The following sequence is postulated:
1. Neutrophils (the principal source of cellular proteases) are normally
sequestered in peripheral capillaries, including those in the lung, and a
few gain access to the alveolar spaces.
2. Any stimulus that increases either the number of leukocytes
(neutrophils and macrophages) in the lung or the release of their proteasecontaining granules increases proteolytic activity.
3. With low levels of serum alpha 1-antitrypsin, elastic tissue destruction
is unchecked and emohysema results.
The protease-antiprotease imbalance hypothesis also helps explain the
effect of cigarette smoking in the development of emphysema,
particularly the centriacinar form in subjects with normal amounts of
alpha1-antitrypsin:
- ln smokers, neutrophils and macrophages accumulate in alveoli. The
mechanism of inflammation is not entirely clear, but possibly involves
the direct chemoattractant effects of nicotine as well as the effects of
reactive oxygen species contained in smoke.
- Accumulated neutrophils are activated and release their granules, rich in
a variety of cellular proteases (neutrophil elastase, proteinase 3, and
cathepsin G), resulting in tissue damage.
- Smoking also enhances elastase activity in macrophages; macrophage
elastase is not inhibited by alpha1-antitrypsin and, indeed, can
proteolytically digest this antiprotease.
Smoking also has a seminal role in perpetuating the oxidant-antioxidant
imbalance in the pathogenesis of emphysema. Normally, the lung
contains a healthy complement of antioxidants (superoxide dismutase,
glutathione) that keep oxidative damage to a minimum Tobacco smoke
contains abundant reactive oxygen species (free radicals), which deplete
these antioxidant mechanisms,thereby inciting tissue damage Activated
neutrophils also add to the pool of reactive oxygen species in the alveoli.
A secondary consequence of oxidative injury is inactivation of native
antiproteases, resulting in "functional" alpha1-antitrypsin deficiencye ven
in patients without enzyme deficiency.
Morphology
The diagnosisa nd classi f icat ioonf emphysemad ependlargely on the
macroscopical appearance of the lung.
Panacinar emphysema, when well developed, produces pale, voluminous
lungs that often obscure the heart when the anterior chest wall is removed
at autopsy. The macroscopic features of centriacinar emphysema are less
impressive. The lungs are a deeper pink than in panacinar emphysema
and less voluminous,unless the disease is well advanced Generally,i n
centriacinar emphysema the upper two- thirds of the lungs is more
severely affected than the lower lungs. Histologically there is thinning
and destruction of alveolar walls. With advanced disease, adjacent alveoli
become confluent creating large airspaces Terminal and respiratory
bronchioles may be deformed because of the loss of septa that help tether
these structures in the parenchyma.
Clinical Course.
Dyspnea is usually the first symptom; it begins insidiously but is steadily
progressive. In patients with underlying chronic bronchitis or chronic
asthmatic bronchitis, cough and wheezing may be initial complaints.
Weight loss is common and may be so severe as to suggest a hidden
malignant tumor Most individuals with emphysema and COPD fall
somewhere between these two classic extremes. In all, secondary
pulmonary hypertension develops gradually, arising from both hypoxiainduced pulmonary vascular spasm and loss of pulmonary capillary
surface area from alveolar destruction. Death from emphysema is related
to either pulmonary failure with respiratory acidosis, hypoxia, and coma,
or right-sided heart failure (cor pulmonale).
Chronic Bronchitis
it is defined as a persistent productiue cougb for at least 3 consecutiue
monthsin at least 2 consecutiue years.
Pathogenesis.
The distinctive feature of chronic bronchitis is hypersecretion of mucus,
beginning in the large airways. Although the single most important cause
is cigarette smoking, other air pollutants, such as sulfur dioxide and
nitrogen dioxide, may contribute. These environmental irritants induce
hypertrophy of mucous glands in the trachea and main-stem bronchi and
lead to a marked increase in mucin-secreting goblet cells in the surface
epithelium of smaller bronchi and bronchioles. In addition, these irritants
cause inflammation with infiltration of CD8+ T cells, macrophages, and
neutrophils. In contrast to asthma, eosinophils are lacking in chronic
bronchitis unless the patient has asthmatic bronchitis.
Whereas the defining feature of chronic bronchitis (mucus
hypersecretion) is primarily a reflection of large bronchial involvement,
the morphologic basis of airflow obstruction in chronic bronchitis is more
peripheral and reswhs from (1) so-called "small airway disease," induced
by goblet cell metaplasia with mucus plugging of the bronchiolar lumen,
inflammation, and bronchiolar wall fibrosis, and (2) coexistent
emphysema
Microbial infection is often present but has a secondary role, chiefly by
maintaining the inflammation and exacerbating symptoms
Morphology
Grossly, the mucosal lining of the larger airways is usually hyperemic
and swollen by edema fluid. lt is often covered by a layer of mucinous or
mucopurulent secretions. The smaller bronchi and bronchioles may also
be filled with similar secret ions Histologically the diagnostic feature of
chronic bronchitis in the trachea and larger bronchi is enlargement of the
mucus-secreting glands. The magnitude of the increase in size is assessed
by the ratio of the thickness of the submucosal gland layer to that of the
bronchial wall (Reid index; normally 0.4). A variable density of
inflammatory cells ,largely mononuclear but sometimes admixed with
neutrophils, is frequently present in the bronchial mucosa.
Clinical Course.
In individuals with chronic bronchitis, a prominent cough and the
production of sputum may persist indefinitely without ventilatory
dysfunction. However, as alluded to earlier, some sufferers develop
significant COPD with outflow obstruction. This is accompanied by
hypercapnia, hypoxemia, and (in severe cases) cyanosis
with progression, chronic bronchitis is complicated by pulmonary
hypertension and cardiac failure . Recurrent infections and respiratory
failure are constant threats
Asthma
Asthma is a chronic inflammatory disorder of the airways that causes
recurrent episodes of wheezing, breathlessness, chest tightness, and
cough, particularly at night and or early in the morning. This clinical
picture is caused by repeated immediate hypersensitivity and late-phase
reactions in the lung that give rise to the triad of intermittent and
reversible airway obstruction, chronic bronchial inflammation with
eosinophils, and bronchial smooth muscle cell hypertrophy and
hyperreactivity.lt is thought that inflammation causes an increase in
airway responsiveness (bronchospasm) to a variety of stimuli.
Classification of asthma
According to pathophysiological points asthma can be classified into
1- Extrinsic (atopic) asthma: This most common type of asthma usually
begins in childhood. A positive family history of atopy is common, and
asthmatic attacks are often preceded by allergic rhinitis, urticaria, or
eczema.T he diseasei s triggered by environmental antigens, such as
dusts, pollen, animal dander, and foods, but potentially any anrigen is
implicated. A skin test with the offending antigen results in an immediate
wheal-and-flare reaction About 70"/" of cases are said to be "extrinsic" or
"atopic" and are due to IgE and TH2-mediated immune responses to
environmental antigens.
2-Intrinsic (non atopic) asthma ; In the remaining 30% of patients, asthma
is said to be "intrinsic" or "non-atopic" and is triggered by nonimmune
stimuli such as aspirin; pulmonary infections, especially those caused by
viruses; cold; psychological stress: exercise; and inhaled irritants.
Pathogenesis
The major etiologic factors of asthma are genetic predisposition to type I
hypersensitivity ("atopy"), acute and chronic airway inflammation, and
bronchial hyper-responsiveness to a variety of stimuli. The inflammation
involves many cell types and numerous inflammatory mediators, but the
role of type 2 helper T (T H2) cells may be critical to the pathogenesis of
asthma
1- Extrinsic asthma: In the airways there is an initial sensitization to the
inhaled inciting antigens, which stimulates induction of Tr12-type cells
and release of interleukins IL-4 and IL-5 . This leads to synthesis of IgE
that binds to mucosal mast cells. Subsequent IgE mediated reaction to
inhaled allergens elicits an immediate response and a late-phase reaction .
Exposure of lgE-coated mast cells to the same antigen causes crosslinking of IgE and the release of chemical mediators. Mast cells on the
respiratory mucosal surface are initially activated; the resultant mediator
release opens mucosal intercellular junctions, allowing penetration of the
antigen to more numerous mucosal mast cells. In addition, direct
stimulation of subepithelial vagal (parasympathetic)
receptors provokes reflex bronchoconstriction through both central and
local reflexes. This occurs within minutes after stimulation and is
therefore called the acute, or immediate, response, which consists of
bronchoconstriction edema (due to increased vascular permeability), and
mucus secretion. A variety of inflammatory mediators have been
implicated in the acute-phase response, although their relative importance
in an actual asthma attack varies widely. Nevertheless, a partial list
includes:
- Leukotrienes C4, D4, and E4
-Acetylcholine:
- Histamine.
- Prostaglandin D2
- Platelet-activating factor
. Eosinophils are particularly important in the late phase. As mentioned,
their accumulation at sites of allergic inflammation is favored by several
mast cell-derived chemotactic factors, as well as chemokines (e.g.,
eotaxin) produced by activated bronchial epithelial cells themselves. The
accumulated eosinophils exert a variety of effects. Their armamentarium
of mediators is as extensive as that of mast cells and includes major basic
protein and eosinophil cationic protein, which are directly toxic to airway
epithelial cells. Eosinopbil peroxidase causes tissue damage through
oxidative stress. Activated eosinophils are also a rich source of
leukotrienes, especially leukotriene C4, which contribute to
bronchoconstriction. Thus, eosinophils can amplify and sustain the
inflammatory response
Morphology
The morphologic changes in asthma have been described in persons who
die of prolonged severe attacks (status asthmaticus) and in mucosal
biopsy specimens of persons challenged with allergens In fatal cases
grossly, the lungs are overdistended because of over inflation and there
may be small areas of atelectasis. The most striking macroscopic
findingis occlusion of bronchi and bronchioles by thick, tenacious mucus
plugs. Histologically the mucus plugs contain whorls of shed epithelium
(Curschmann spiralsl). Numerous eosinophils and Charcot-Leyden
crystals( collections of crystalloids made up of eosinophil proteins) are
also present. The other characteristicf indings of asthma,
collectively called "airway remodeling" include
. Thickening of the basement membrane of th bronchial epithelium.
. Edema and an inflammatory infiltrate in the Bronchial walls with a
prominence of eosinophils and mast cells.
. An increasein the size of the submucosal glands.
. Hypertrophy of the bronchial muscle walls.
Clinical Course. An attack of asthma is characterized by severe dyspnea
with wheezing; the chief difficulty lies in expiration.
Bronchiectasis
Bronchiectasis is the permanent dilation of bronchi and bronchioles
caused by destruction of the muscle and elastic supporting tissue,
resulting from or associated with chronic necrotizing infections. It is not a
primary disease but rather is secondary to persisting infection or
obstruction caused by a variey of conditions
The conditions that most commonly predispose to bronchiectasis include
the following:
- Bronchial obstruction. Common causes are tumors, foreign bodies, and
occasionally impaction of mucus. Under these conditions,the
bronchiectasis is localized to the obstructed lung segment. Bronchiectasis
can also complicate atopic asthma and chronic bronchitis.
. Congenital or hereditary conditions. Only a few are cited:
In cystic fibrosis, widespread severe bronchiectasis results from
obstruction and infection caused by the secretion of abnormally viscid
mucus.
- In immunodeficiency states, particularly immunoglobulin deficiencies,
bronchiectasis is likely to develop because of an increased susceptibility
to repeated bacterial infections; localized or diffiuse bronchiectasis can
occur.
- Kartagener syndrome, an autosomal recessive disorder, is frequently
associated with bronchiectasis and with sterility in males. Structural
abnormalities of the cilia impair mucociliary clearance in the airways,
leading to persistent infections, and reduce the mobility of spermatozoa.
Necrotizing, or suppurative, pneumonia, particuIarly with virulent
organisms such as Staphylococcus aureus or Klebsiella spp., may
predispose to bronchiectasis.
In the past, postinfective bronchiectasis was sometimes a sequel to the
childhood pneumonias that complicated measles, whooping cough, and
influenza, but this has substantially decreased with the advent of
successful immunization. Post-tubercular bronchiectasis continues to be a
significant cause of morbidity in endemic areas.
Pathogenesis. Two processes are crucial and intertwined in the
pathogenesis of bronchiectasis: obstruction and chronic persistent
infection. Either of these two processes may come first. Normal clearance
mechanisms are hampered by obstruction, so secondary infection soon
follows; conversely, chronic infection in time causes damage to bronchial
walls, leading to weakening and dilation. For example, obstruction caused
by a bronchogenic carcinoma or a foreign body impairs clearance of
secretions, providing a fertile soil for superimposed infection. The
resultant inflammatory damage to the bronchial wall and the
accumulating exudate further distend the airways, leading to irreversible
dilation. Conversely, a persistent necrotizing inflammation in the bronchi
or bronchioles may cause obstructive secretions, inflammation throughout
the wall (with peribronchial fibrosis and traction on the walls),
Morpbology
Bronchiectatic involvement of the lungs usually affects the lower lobes
bilaterally, particularly those air passages that are most vertical When
tumors or aspiration of foreign bodies lead to bronchiectasis, involvement
may be sharply localized to a single segment of the lungs. Usually the
most severe involvements found in the more distal bronchi and
bronchioles The airways may be dilated to as much as four times their
usual diameter and on gross examination of the lung can be followed
almost to the pleural surfaces . By contrast ,in normal lungs, the
bronchioles can not be followed by ordinary gross examination beyond a
point 2-3cm from the pleural surfaces.) The histologicf indings vary with
the activity and chronicity of the disease. In the full-blown active case, an
intense acute and chronic inflammatory exudate within the walls of the
bronchi and bronchioles and the desquamation of lining epithelium
cause extensive areas of ulceration. In the usual case a mixed flora can be
cultured from the involved bronchi, including staphylococci,
streptococci, pneumococci, enteric organisms, anaerobic and
microaerophilic bacteria and (particularly in children) Haemophilus
influenzae and Pseudomonas aeruginosa.
When healing occurs the lining epithelium may regenerate completely;
however, usually so much injury has occurred that abnormal dilation and
scarring persist.
Fibrosis of bronchial and bronchiolar walls and peri bronchiolar fibrosis
develop in more chronic cases