C) Contraction Atelectasis (or Cicatrization Atelectasis)

Atelectasis Occurs due to local or generalized fibrosis of the lung or pleura that prevents full
expansion of the lung.

Atelectasis (except when caused by contraction) is potentially reversible and should be

It is lung collapse. So, we lose lung volume due to inadequate expansion of air spaces. treated promptly to prevent hypoxemia and superimposed infection of the collapsed
Since there is a decrease in lung volume, the process of gas exchange will be affected lung
resulting in shunting of inadequately oxygenated blood from pulmonary arteries into
veins. This poorly oxygenated blood will be distributed across the body giving rise to
a ventilation perfusion imbalance and tissue hypoxia. We have three types based on:
1. Underlying Mechanism
2. Distribution of alveolar collapse

A) Resorption Atelectasis
Occurs due to total obstruction of a bronchus, thus air cannot reach the distal airways.
However, the air that was already present, is absorbed gradually until the alveoli
collapse.

Causes: (Resorption Atelectasis)

The most common cause is Obstruction of a bronchus. It could be by:
1. Accumulation of intrabronchial mucous or mucopurelant plugs in post-
operative patients
(especially the first 72hrs) so we always recommend these patients to do early
ampulation and to use the spirometer
2. Foreign body aspiration
especially in children (children have poorly developed collateral ventilation so once
one part is obstructed there’s no secondary airway to compensate)
2. Obstructive lung disease
Like bronchial asthma, bronchiectasis, chronic bronchitis.
3. Intrabronchial tumors.

B) Compression Atelectasis
Occurs due to accumulation of fluid/blood/air in the pleural cavity so the increase in
pressure causes mechanical collapse of the adjacent lung:

Causes: (Compression Atelectasis)

1. Pleural effusion like in Congestive Heart Failure
2. Pneumothorax: air in the pleural cavity due to an injury
 Clinical features (of severe ARDS)
Acute Respiratory Distress Syndrome (ARDS) [] Characterized by rapid onset of life-threatening:
[] Respiratory insufficiency (profound/intense dyspnea and tachypnea) followed by:
1. Cyanosis
The epidemiology and definition are evolving: 2. Severe arterial hypoxemia that may progress
Previously considered to be the severe end of the spectrum of acute lung injury to multisystem organ failure.
But now it is defined as respiratory failure where one or both of gas exchange Hypoxemia may be refractory to oxygen
processes fail, as the integrity of the alveolar-capillary membrane is compromised by therapy
endothelial and epithelial injury. [] Findings of bilateral opacities on chest
It occurs within 1 week of a known trigger. imaging. The chest imaging finding is NOT
fully explained by effusions, atelectasis, cardiac
Graded based on the severity of the changes in arterial blood oxygenation. failure or fluid overload.
Causes are diverse but all lead to extensive bilateral injury to alveoli known
histologically as diffuse alveolar damage (DAD) Microscopically,
In the acute phase:
Triggers: (clinical insults) [] Lungs are dark red, firm and heavy
Pneumonia (35%–45%) [] Capillary congestion,
Sepsis (30%–35) [] Necrosis of alveolar epithelium
Infections (includes COVID19) [] Interstitial and intra-alveolar edema and hemorrhage
Aspiration [] Collections of neutrophils in the capillaries
Trauma (including brain injury, abdominal surgery, and multiple fractures) [] Some alveoli are collapsed while others are distended
Pancreatitis [] Many alveolar spaces are lined by bright pink hyaline membrane
Transfusion reactions
[] However, the most characteristic finding is the presence of hyaline membranes.
Pathogenesis: The hyaline membrane consists of fibrin-rich edema fluid mixed with remnants of
In the early phase of ARDS, the first 30mins after the acute insult, the pulmonary necrotic epithelial cells (similar to respiratory distress syndrome of the newborn)
macrophages increase the synthesis of IL8, IL1, TNF, resulting in neutrophils
activation, chemotaxis, sequestration into the alveoli, and also the activation of In the organizing phase (Healing stage):
endothelial cells in the pulmonary capillaries
Activated neutrophils release ROS, proteases that damage the alveolar epithelium and [] Type II pneumocytes proliferate to regenerate
endothelium causing vascular leakiness, hyaline membrane formation, accumulation alveoli. Resolution is unusual.
of edema fluid and loss of surfactant. [] Hyaline membrane resorption (bright pink
As a result, the alveolar unit loses its ability to expand. membrane no longer seen)
[] Intra-alveolar fibrosis due to organization of
The destructive forces are counteracted by endogenous antiproteases and anti- the fibrin-rich exudates.
oxidants. The macrophages secrete fibrogenic cytokines (TGF-B, PDGF) which [] Marked thickening of the alveolar septa due
stimulate the fibroblasts to grow with collagen deposition which is the healing phase to proliferation of interstitial inflammatory cells
In the end, it is the balance between the destructive and protective factors that and collagen deposition.
determines the degree of tissue injury and clinical severity of the ARDS.

Neutrophils have an important role in the pathogenesis. Even early lung biopsies
show increased neutrophils, in the capillaries, interstitium and alveoli
Prognosis:
85% of cases develops within 72hrs of the initial insult. Mortality rate (38.5%): Chronic Obstructive Pulmonary Disease(COPD)
Mild 27%
Moderate 32% Emphysema and chronic bronchitis are often diagnosed together in one patient. This is
Severe 45% called chronic obstructive lung disease (COPD). Especially the fact that both are
caused by smoking. They can still be present alone though.
Most patients who survive the acute insult recover normal respiratory function within For example: pure emphysema in alpha antitrypsin deficiency
6 to 12 months, but the rest develop diffuse interstitial fibrosis leading to chronic
respiratory insufficiency Both diseases are irreversible especially if compared with asthma

Poor prognosis:
1. advanced age
2. bacteremia (sepsis)
3. development of multiorgan failure

Obstructive vs Restrictive
Diffuse pulmonary disease can be classified into two Categories:
1- Obstructive airway disease:
Characterized by an increase in resistance to airflow caused by partial or complete
obstruction at any level causing expiratory obstruction (emphysema, chronic
bronchitis, asthma)
In obstructive lung diseases, its hard to get the air out (exhale), So the air accumulates
2- Restrictive airway diseases:
in the lung → lung hyperinflation. So, lung capacity is either normal or increased
Characterized by reduced expansion of lung parenchyma and decreased total lung
Imagine this like a pair of socks, when you stretch them they go back to their shape,
capacity. And are divided to:
However, old socks will stretch but won’t go back to their shape (obstructive diseases)
A. Chest wall disorders in the presence of normal lungs:
(Severe obesity, diseases of the pleura, and neuromuscular disorders that affect the
respiratory muscles such Guillan Barre syndrome) So the lungs are easy to fill with air but hard
B. Acute or chronic interstitial lung diseases: to get out so we will have air trapping due to
The classic acute restrictive disease is ARDS. the decreased elastic recoil and increased
Chronic restrictive diseases include pneumoconioses, interstitial fibrosis of unknown compliance
etiology, and sarcoidosis.
Emphysema is diagnosed on the basis of
morphologic and radiologic features
Chronic bronchitis is diagnosed on the basis
of clinical features

Notice in this photo, the affected location for

each disease
Emphysema
Permanent enlargement of the airspaces distal to the terminal bronchioles with
destruction of their walls mainly due to nicotine, it also destructs the capillaries.
Has no significant fibrosis.

Site: Airways distal to terminal bronchioles + Acini are irreversibly damaged

• Classified according to its anatomic distribution
(The significant airway obstruction is mainly associated with the first two types)

1. Centriacinar (centrilobular) emphysema:

• affects the central or proximal parts of the acini first and more severly, formed by
respiratory bronchioles, while distal alveoli are spared.
• cigarette smokers - associated with chronic bronchitis 1% of patients with emphysema have alpha1 antitrypsin defciency
• more common and severe in the upper lobes, particularly in the apical segments
Clinical features:
2. Panacinar (panlobular) emphysema: • Panacinar emphysema:
• the acini are uniformly enlarged, from the level of the respiratory bronchiole to the Pale, voluminous lungs
terminal blind alveoli. • Centriacinar emphysema
• associated with α1-antitrypsin deficiency (genetic disease may affect lung or liver) Less impressive changes
• affects entire lung but more prominently in the lower lung zones Deeper pink and less voluminous lungs (late stage)
• Classic presentation of emphysema with no bronchitic component
3. Distal Acinar (Paraseptal) Emphysema: Dyspnea
• involves the distal portion of the acinus while the proximal part is normal. Barrel-chested (increase in anterior-posterior diameter of chest wall)
• present adjacent to the pleura, along the lobular connective tissue septa, at the Prolonged expiration
margins of the lobules Sitting forward in a hunched-over position (trying to squeeze the air out in expiration)
• adjacent to fibrosis, scarring or atelectasis. Hyperventilation (which is why in early stages, the gas exchange is adequate and they
• more severe in the upper half of the lungs. have prominent dyspnea = “pink puffers.”) pink refers to the face and ts good
• The cause is unknown. oxygenation while puffer refers to difficult breathing and breathing through lips
• The presence of multiple, enlarged air spaces may form large cystic structures that Cough and wheezing if coexistent asthma and chronic bronchitis.
give rise to bullae.
• the most common cause of spontaneous pneumothorax in young adults due to Microscopically,
rupture of emphysematous bullae • Enlarged air spaces due to destruction of alveolar walls and septa (see photo)
• No significant fibrosis
4. Irregular emphysema: • small airways collapse due to loss of elastic tissue in the
• The acinus is irregularly involved surrounding alveolar septa during expiration (chronic
• almost invariably associated with scarring airflow obstruction).
• clinically it’s asymptomatic • Bronchiolar inflammation and submucosal fibrosis in
• considered the commonest form of emphysema. advanced cases
Emphysema with pronounced chronic bronchitis and a history of recurrent
infections: Chronic Bronchitis
• Less dyspnea
• Absence of increased respiratory drive (lungs retain CO2) →more hypoxia & Common in cigarette smokers; air pollutants also contribute.
cyanosis Persistent productive cough for AT LEAST 3 consecutive months in AT LEAST 2
• For unclear reasons, patients with chronic bronchitis tend to be obese hence the consecutive years.  Diagnosis is clinical as mentioned before
designation “blue bloaters” BLUE = carbon dioxide retention, hypoxia, and cyanosis 22-25% of men in their 40-65yrs have the disease
BLOATER = overweight • In early stages the cough raises (kicks out) the mucoid sputum so the airflow is not
obstructed.
Complications: • Heavy smokers: develop chronic outflow obstruction,
• Destruction of the walls distal to the terminal bronchioles (=acini mainly affected) usually with associated emphysema COPD
→Hypoxia → Hypoxia-induced pulmonary vascular spasm • May coexist with hyper-responsive airways with intermittent bronchospasm and
→gradual development of secondary pulmonary Hypertension over years → in 20- wheezing → this is called asthmatic bronchitis
30% right-sided congestive heart failure (cor pulmonale).
• Death from emphysema is related to either respiratory failure or right-sided heart Pathogenesis
failure. Depends mainly on mucus hypersecretion and airflow obstruction:
Mucus hypersecretion begins in the large airways mainly caused by cigarette smoking
Conditions related to emphysema: or other air pollutants (SO2, NO2). The exposure to these chemicals causes
Compensatory emphysema: hypertrophy of mucous glands in the trachea and bronchi and increase goblet cells in
• Compensatory dilation of alveoli in response to loss of lung substance elsewhere. the epithelial surfaces of smaller bronchi and bronchioles. These irritants can also
• As hyper-expansion of residual lung parenchyma following surgical cause inflammation mainly composed of macrophages, neutrophils and lymphocytes
removal of a diseased lung but WITHOUT eosinophils.
Obstructive overinflation:
• Lung expands because air is trapped within it. Airflow obstruction results from:
• Commonly caused by subtotal obstruction of an airway by a tumor or foreign object. 1. Small airway disease (chronic bronchiolitis): results in early and mild airflow
• Can be Life-threatening emergency if extension increases to obstruction. Induced by mucus plugging of the bronchiolar
compress the remaining normal lung. lumen, inflammation, and bronchiolar wall fibrosis
Bullous emphysema: 2. Coexistent emphysema: The cause of significant airflow obstruction.
• Any form of emphysema, that produce large subpleural blebs
or bullae Clinical features:
• Most are subpleural Prominent cough with production of sputum
• Pneumothorax if bullae rupture • chronic bronchitis and COPD patients show frequent
Mediastinal (interstitial) emphysema: exacerbations, rapid disease progression, and poorer
•Caused by the entry of air in connective tissue of the lung outcomes than emphysema alone.
(interstitium) where it can extend to the mediastinum and subcutaneous tissue • Progressive disease is marked by the development of
pulmonary hypertension, cardiac failure,
recurrent infections;and ultimately respiratory failure
Morphology: Pathogenesis:
• Mucosal lining is hyperemic and swollen due to accumulation of edema fluid Upon exposure to the allergen for the first time, the allergen is recognized by APCs or
• Layers of mucinous or mucopurulent secretions, smaller bronchi and bronchioles dendritic cells in the epithelium lining. As a result, T helper cells are activated and start
also may be involved secreting inflammatory mediators resulting in IGE production (IL4, IL13) and
Photo: The lumen of the bronchus is above. Note the marked thickening of eosinophils recruitment and activation (IL5). IL13 stimulates production of mucus.
the mucous gland layer (approximately twice-normal) and squamous metaplasia of IGE coats the submucosal mast cells. On re-exposure of the mast cell to the same
lung epithelium which is one of the adaptive mechanisms to protect smoker’s lining antigen, two waves of action happen (early/immediate phase and late phase):
The yellow star (below) show the enlarged mucus glands (twice the size) and this is
the diagnostic feature in the trachea and larger bronchi. Lymphocytes can be seen. • The early-phase reaction is dominated by:
ü bronchoconstriction (by mast cell mediators such as histamine, prostaglandinD2,
Microscopically, Enlargement of the mucus-secreting glands leukotrienes, and also by reflux neural pathways)
• Inflammatory cells, largely mononuclear and neutrophils. ü increased mucus production
• Chronic bronchiolitis (small airway disease), characterized by ü vasodilation.
goblet cell metaplasia, mucous plugging, inflammation, and submucosal fibrosis The early phase occurs after re-exposure to antigen → immediate reaction
• Bronchiolitis obliterans in severe cases: complete obliteration of triggered by Ag-induced cross-linking of IgE bound to Fc receptors on mast cells.
the lumen as a consequence of fibrosis mast cells release previously formed mediators that directly and via neuronal reflexes
• Changes of emphysema often co-exist induce: (bronchospasm, increased vascular permeability, mucus production,
leukocytes recruitment)

• The late-phase reaction is inflammatory:

Asthma Inflammatory mediators stimulate epithelial cells to produce chemokines (Eotaxin, a
potent chemotactic and attractant to eosinophils). This recruits TH2 cells, eosinophils,
Chronic inflammatory disorder of the airways and other leukocytes amplifying the inflammatory reaction.
Causes recurrent episodes of wheezing, Dyspnea, chest tightness and cough
Leukocytes recruited to the site of reaction (neutro, eosino, basophils, lymphocytes, monocytes) release mediators that
particularly at night and/or early in the morning initiate the late phase of asthma.
Eosinophils release major basic protein and eosinophil cationic protein that causes
• its hallmarks are: damage to the epithelium
a) Intermittent and reversible airway obstruction (bronchospasm) • Repeated bouts of inflammation lead to structural changes in
b) Chronic bronchial inflammation with eosinophils the bronchial wall. This is called airway remodelling, including:
c) Bronchial smooth muscle cell hypertrophy and hyperreactivity. ü hypertrophy of bronchial smooth muscle
d) increased mucus secretion. ü hypertrophy of Mucus glands
ü increased vascularity
Risks: ü deposition of subepithelial collagen
ü Genetic predisposition to type I hypersensitivity (atopy)
ü Acute and chronic airway inflammation Photo: In asthma we have
ü Bronchial hyperresponsiveness to a variety of stimuli marked mucus
accumulation, goblet cells
Triggers: hyperplasia, basement
membrane thickening,
ü respiratory infections (especially viral) intense chronic inflammation
ü airborne irritants (smoke, fumes) in the lamina propria with
ü cold air different inflammatory cells,
ü Stress or exercise smooth muscle hypertrophy
and hyperplasia, submucosal glands hypertrophy
The details described in the previous photo are important and will reflect on the III. Drug-Induced Asthma
bronchial lumen as a whole. • Eg: Aspirin induced asthma
Such patients present with recurrent rhinitis, nasal polyps, urticaria, and bronchospasm.
Types of Asthma: • The precise pathogenesis is unknown. It may involve some abnormality in
I. Atopic Asthma (Allergic Asthma) prostaglandin metabolism from inhibition of cyclooxygenase (by aspirin)
• The most common type
• Classic example of type I IgE–mediated hypersensitivity reaction IV. Occupational Asthma
• Starts in childhood Atopy is the genetic tendency • Asthma attacks usually develop after repeated exposure to the triggering antigen.
• Positive family history of atopy and/or asthma is common to develop allergic diseases • triggered by fumes (epoxy resins, plastics), organic and chemical dusts (wood, cotton,
• attacks are preceded by allergic rhinitis, urticaria, or eczema platinum), gases (toluene), and other chemicals
• Attacks are triggered by allergens in dust, pollen, animal People at risk are farmers, animal-handlers, manufacturers of mattresses or metals,
Dander (material shed by animals), or food, or by infections. bakers, food processors, cotton workers
[] Pathogenesis (of Atopic Asthma):
• Exposure to the antigen causes excessive activation of type Morphology:
2 helper cells → Cytokines production which include: -Sub-basement membrane fibrosis (yellow)
IL-4 and IL-13 stimulate IgE production -Eosinophilic inflammation (red)
IL-5 activates eosinophils -Smooth muscle hypertrophy and
IL-13 also stimulates mucus production hyperplasia (green)
• IgE coats submucosal mast cells → release of Mast cell– -Occlusion of bronchi and bronchioles by
derived mediators (upon reexposure) → produce two waves of reaction: thick mucous plugs
The early (immediate) phase of reaction -Mucous plugs contain whorls of shed
The late phase of reaction epithelium called Curschmann spirals
[] Diagnosis (of Atopic Asthma) -The characteristic Airway remodelling,
• Skin test with the antigen: immediate wheal-and-flare reaction includes:
Skin prick test is the most common allergic skin test • Thickening of airway wall
What do we do? a tiny drop of a possible allergen—something you are allergic to— is • Sub-basement membrane fibrosis
pricked or scratched into the skin. If you are allergic to this substance, you will • Increased submucosal vascularity
develop a red and itchy rash • An increase in size of the submucosal glands and goblet cell
Can also be diagnosed by serum radioallergosorbent tests (RASTs) which uses • Metaplasia of the airway epithelium
radioimmunoassay to detect IgE antibodies • Hypertrophy and/or hyperplasia of the bronchial muscles
- In fatal cases distention of lungs due to air trapping, with small areas of atelectasis
II. Non-Atopic Asthma
• No evidence of allergen sensitization, Negative skin test
• A positive family history of asthma is less common. Charot-Leyden crystals are another
• Triggered by: finding, made up of the eosinophilic
viral respiratory infections (rhinovirus, parainfluenza virus) Curschmann Spirals protein galectin-10c
Eosinophils are the characteristic
inhaled air pollutants (sulfur dioxide, ozone, nitrogen dioxide). inflammatory cells in asthma
The ultimate humoral and cellular mediators of airway obstruction of both Atopic and
Non-Atopic Asthmas are the same, so they are treated similarly
An attack of asthma is characterized by: 3. Immunodeficiency states:
-Dry cough which is worse at night Due to recurrent bacterial infections, could be localized or diffuse
-Wheezing which is a whistling sound especially during expiration
-Chest tightness (feeling of chest squeezing or as if something is on the chest) 4. Primary ciliary dyskinesia (immotile cilia syndrome):
-Dyspnea or shortness of breath (cant breathe enough) Rare autosomal recessive disorder of abnormalities in cilia, causing persistent
-Difficulty of expiration infections. It causes both bronchiectasis + sterility in males (immobility of sperms)
Wheezing, chest pain and dyspnea mainly in the early morning
Asthmatic attacks last 1 to several hrs and subside either spontaneously or with an 5. Necrotizing, or suppurative, pneumonia:
intervention, the intervals between the attacks are free from respiratory difficulties. • particularly with virulent organisms such as Staph Aureus or Klebsiella spp.
Remember asthma is REVERSIBLE except in advanced severe cases
Pathogenesis:
Status asthmaticus: is a severe paroxysm that does not respond to therapy, it lasts Typically results from or is associated with chronic necrotizing infections, so it is not
from days to weeks, may be associated with hypercapnia (CO2 retention), acidosis primary, it is always secondary to infection or obstruction
and severe hypoxia, this can be fatal
Two intertwined processes contribute to bronchiectasis:
Treatment: Standard therapies include: 1. OBSTRUCTION impairs clearance of secretions causing superimposed
• Anti-inflammatory drugs (glucocorticoids) infections → inflammatory damage to the bronchial wall + the accumulating
• Bronchodilators (beta-adrenergic drugs) exudate which causes airway distention and irreversible dilation.
• Leukotriene inhibitors (potent bronchoconstrictors. However, can block immune
mediators such as IL4, IL5 which can be helpful in some patients) 2. PERSISTENT NECROTIZING INFECTION in the bronchi or bronchioles
thus we have poor clearance of secretions, obstruction, and inflammation with
peribronchial fibrosis and traction on the bronchi → irreversible dilation
Bronchiectasis Morphology:
Affects lower lobes of lungs bilaterally
Permanent dilation of bronchi and bronchioles caused by destruction of smooth The most severe involvement is found in the distal bronchi and bronchioles.
muscle and the supporting elastic tissue so its an irreversible dilation. The airways may be dilated to as much as four times their usual diameter
Microscopically,
Site: Bronchi and Bronchioles • In full-blown active cases:
• intense acute and chronic inflammatory exudate within the walls of the bronchi and
Diagnosis: appropriate history and radiographic demonstration of bronchial dilation. bronchioles → desquamation of lining epithelium and extensive ulceration
• mixed flora are cultured from the sputum.
Risks: (predisposing conditions,
• When healing occurs:
1. Bronchial obstruction: - The lining epithelium may regenerate completely however the injury cannot be
Caused by tumors, foreign bodies, and impaction of mucus OR as a complication of repaired completely and the abnormal dilation and scarring persist
atopic asthma and chronic bronchitis. bronchiectasis is localized -Fibrosis of bronchial and bronchiolar walls and peribronchiolar fibrosis
-In some cases, necrosis destroys the bronchial and bronchialor walls forming an
Congenital or hereditary conditions: abscess cavity
2. Cystic fibrosis:
Widespread severe bronchiectasis due to obstruction caused by abnormally viscid
(thick and sticky) mucus and secondary infections
 Photo: microscopic dilated bronchus in which the
mucosa and bronchial wall are not seen clearly because
of the necrotizing inflammation with tissue destruction.
Mostly it is desquamated (come off in scales or flakes)

Photo: markedly dilated bronchi filled and stuffed with

purulent mucus

Clinical features:
• cough and expectoration of copious amounts of purulent sputum ( made of WBCs,
cellular debris and mucus = yellow/green in color.)
• severe, persistent cough with mucopurulent sputum.
• Other symptoms: dyspnea, rhinosinusitis, and hemoptysis.
• Symptoms are often episodic, precipitated by URTI (upper respiratory tract
infections)
• Severe widespread bronchiectasis may lead to significant obstructive ventilatory
defects which can be associated with hypoxemia, hypercapnia, pulmonary
hypertension, and cor pulmonale

With current treatments, severe complications such as brain abscess or cor pulmonale
are less frequent