Chronic obstructive

pulmonary diseases (COPDs)

Dr. waiswa Ali
MBchB, MMED Pathology
Anatomical and clinical Pathologist
Definitions
• Chronic obstructive pulmonary disease, or COPD, refers to a group of
diseases that cause airflow blockage and breathing-related problems
• COPD is a type of progressive lung disease characterized by long-term
respiratory symptoms and airflow limitation
• COPD is a progressive lung condition characterized by irreversible
airflow limitation
• Emphysema and chronic bronchitis are often clinically grouped together
and referred to as chronic obstructive pulmonary disease (COPD)
• Majority of patients have features of both because they share a major
trigger—cigarette smoking.
• In addition, small-airway disease, a variant of chronic bronchiolitis, is
now known to contribute to obstruction both in emphysema and
chronic bronchitis.
• While asthma is distinguished from chronic bronchitis and emphysema
by the presence of reversible bronchospasm
• Some patients with otherwise typical asthma also develop an
irreversible component
• Conversely, some patients with otherwise typical COPD have a reversible
component.
• It is clinically common to label such patients as having COPD/asthma
Epidemiology
• Affects about 32 million people in the US and is the 3rd leading cause of
death
• The prevalence is higher for men.
• However, women prevalence is also raising
• About 35-50% of heavy smokers develop COPD; 80% of COPD is due to
smoking.
• Other risk factors include environmental and occupational pollutants,
airway hyperresponsiveness and genetic polymorphisms
• Recognizing that there is overlap between various forms of COPD, it is
still useful to discuss each individually in order to highlight the
pathophysiologic basis of different causes of airflow obstruction.
Emphysema
• Emphysema is characterized by irreversible enlargement of the
airspaces distal to the terminal bronchiole, accompanied by
destruction of their walls without obvious fibrosis
• Emphysema is classified according to its anatomic distribution within
the lobule.
• Recall that the lobule is a cluster of acini, the terminal respiratory
units.
• Based on the segments of the respiratory units that are involved,
emphysema is classified into four major types:
• (1) centriacinar, (2) panacinar, (3) paraseptal, and (4) irregular
• Of these, only the first two cause clinically significant airflow
obstruction
• Centriacinar emphysema is the most common form, constituting
more than 95% of clinically significant case
Centriacinar (centrilobular) emphysema.
• In this type of emphysema the central or proximal parts of the acini,
formed by respiratory bronchioles, are affected, whereas distal alveoli
are spared
• Both emphysematous and normal airspaces exist within the same
acinus and lobule.
• The lesions are more common and usually more severe in the upper
lobes, particularly in the apical segments.
• Inflammation around bronchi and bronchioles is common.
• In severe centriacinar emphysema, the distal acinus may also be
involved, making differentiation from panacinar emphysema difficult.
• Centriacinar emphysema occurs predominantly in heavy smokers,
often in association with chronic bronchitis (COPD)
• Panacinar (panlobular) emphysema
• In this type, the acini are uniformly enlarged from the level of the
respiratory bronchiole to the terminal blind alveoli .
• The prefix “pan” refers to the entire acinus, not the entire lung.
• In contrast to centriacinar emphysema, panacinar emphysema tends to
occur more commonly in the lower zones and anterior lung margins
• It is usually most severe at the bases and is associated with α1-
antitrypsin deficiency
• Distal acinar (paraseptal) emphysema.
• In this type, the proximal portion of the acinus is normal, and the
distal part is predominantly involved.
• The emphysema is more striking adjacent 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 of multiple, continuous, enlarged
airspaces, sometimes forming cyst-like structures.
• This type of emphysema probably underlies many cases of
spontaneous pneumothorax in young adults
Pathogenesis of emphysema.
• Inhaled cigarette smoke and other noxious particles cause lung
damage and inflammation, which results in parenchymal destruction
(emphysema)
• Factors that influence the development of emphysema include the
following
• 1. Inflammatory mediators and leukocytes.
• A wide variety of mediators have been shown to be increased in the
affected parts (including leukotriene B4, IL-8, TNF, and others)
• These mediators are released by resident epithelial cells and
macrophages
• These attract inflammatory cells from the circulation (chemotactic
factors), amplify the inflammatory process and induce structural
changes
• [Link]-antiprotease imbalance.
• Several proteases are released from the inflammatory cells and
epithelial cells that break down connective tissue components.
• In patients who develop emphysema, there is a relative deficiency of
protective antiproteases, which in some instances has a genetic basis
• Patients with a genetic deficiency of the antiprotease α1-antitrypsin
have a markedly enhanced tendency to develop pulmonary emphysema
• About 1% of all patients with emphysema have this defect. α1-
antitrypsin
• Injury (e.g., that induced by smoking) increases activation and influx
of neutrophils into the lungs
• Leading to local release of proteases, which in the absence of α1-
antitrypsin activity result in excessive digestion of elastic tissue and
emphysema.
• [Link] stress.
• Substances in tobacco smoke, alveolar damage, and inflammatory
cells all produce oxidants, which may beget more tissue damage and
inflammation.
• Infection is not thought to play a role in the initiation of tissue
destruction, bacterial and/or viral infections but may exacerbate the
associated inflammation and chronic bronchitis
• A number of factors contribute to airway obstruction in emphysema.
• Small airways are normally held open by the elastic recoil of the lung
parenchyma
• Therefore, loss of elastic tissue in the walls of alveoli that surround
respiratory bronchioles causes the respiratory bronchioles to collapse
during expiration
• In addition, there is inflammation in the small airways that causes;
• Goblet cell hyperplasia, with mucus plugging of the lumen
• Inflammatory infiltrates in bronchial walls consisting of neutrophils,
macrophages, B cells and T cells
• Thickening of the bronchiolar wall due to smooth muscle
hypertrophy and peribronchial fibrosis

• Together these changes narrow the bronchiolar lumen and contribute to

airway obstruction
Clinical features
• Productive cough or chest tightness
• Dyspnea usually appears first, beginning insidiously but progressing
steadily
• Wheezing is the chief complaint, easily confused with asthma.
• Cough and expectoration are extremely variable and depend on the
extent of the associated bronchitis
• Weight loss is common and can be so severe as to suggest an occult
cancer.
• Classically, the patient with severe emphysema is barrel-chested and
dyspneic, with obviously prolonged expiration
• Impaired expiratory airflow, best measured through spirometry, is the
key to diagnosis.
 Normal chest Barrel
chest
• In individuals with severe emphysema, cough is often slight,
overdistention is severe, diffusion capacity is low, and blood gas
values are relatively normal at rest.
• Such patients may over ventilate and remain well oxygenated, and
therefore are somewhat designated as pink puffers
• Development of cor-pulmonale and eventually congestive heart failure,
related to secondary pulmonary hypertension, is associated with a poor
prognosis.
• Death in most patients with emphysema is due to
coronary artery disease
Respiratory failure
Right sided heart failure
massive collapse of the lungs secondary to pneumothorax.
Chronic Bronchitis
• Chronic bronchitis is defined clinically as persistent cough with sputum
production for at least 3 months in at least 2 consecutive years, in the
absence of any other identifiable cause of the cough
• Common in habitual smokers and inhabitants of smog-laden cities,
chronic bronchitis is one end of the spectrum of COPD, with emphysema
being the other.
• Over years, it may accelerate decline in lung function, lead to cor
pulmonale and heart failure, or cause atypical metaplasia and dysplasia
of the respiratory epithelium, providing a rich soil for cancerous
transformation.
Pathogenesis of chronic
bronchitis
• The primary or initiating factor is exposure to noxious or irritating
inhaled substances such as tobacco smoke. 90% of patients are smokers
• Dust from grain, cotton, and silica exposure can as well initiate.
• 1. Mucus hypersecretion.
• The earliest feature of chronic bronchitis is hypersecretion of mucus in
the large airways, associated with hypertrophy of the submucosal glands
in the trachea and bronchi.
• The basis for mucus hypersecretion is incompletely understood, but it
appears to involve inflammatory mediators such as histamine and IL-13.
• With time, there is a marked increase in goblet cells in small airways—
small bronchi and bronchioles—leading to excessive mucus production
that contributes to airway obstruction
• Submucosal gland hypertrophy and the increase in goblet cells are
protective reactions against tobacco smoke or other pollutants
• 2. Inflammation
• Inhalants that induce chronic bronchitis cause cellular damage,
eliciting both acute and chronic inflammatory responses involving
neutrophils, lymphocytes, and macrophages.
• Long-standing inflammation and accompanying fibrosis involving
small airways (small bronchi and bronchioles) can also lead to chronic
airway obstruction.
• This feature is similar to that described earlier in emphysema and is a
common denominator in COPD.
• Infection does not initiate chronic bronchitis, but is probably
significant in maintaining it and may be critical in producing acute
exacerbations.
Clinical Features.

• Persistent cough with productive sputum for many years no other

respiratory functional impairment is present
• Eventually dyspnea on exertion develops.
• With the passage of time, and usually with continued smoking, other
elements of COPD may appear, including hypercapnia, hypoxemia, and
mild cyanosis (“blue bloaters”).
• Long-standing severe chronic bronchitis commonly leads to cor
pulmonale and cardiac failure.
• Death may also result from further impairment of respiratory function
due to superimposed acute infections.
• END