Pathology of chronic obstructive
airway diseases
Definition
• Chronic obstructive pulmonary disease
(COPD) is defined as ‘a disease state
characterized by airflow limitations that is not
fully reversible. The airflow limitation is
usually both progressive and associated with
an abnormal inflammatory response of the
lungs to noxious particles or gases’ (Global
Initiative for Obstructive Lung Disease: GOLD).
Two Ways to Limit Airflow
1. Reduced outflow pressure due to loss of
elastic recoil (emphysema)
2. Increased airway resistance (chronic
bronchitis, bronchiolitis)
Three Obstructive Airway Diseases
• emphysema (destruction of air spaces and
loss of elastic recoil)
• chronic bronchitis (mucus hypersecretion and
luminal narrowing of airways)
• bronchiolitis (narrowing of small airways by
inflammation and fibrosis)
Emphysema: Protease-antiprotease
imbalance
• Nicotine and reactive oxygen species attract neutrophils into
alveoli
• Cigarette smoke activates NF-KB transcription factor ->
increased TNF & IL-8 attracting and activating neutrophils.
Neutrophil elastase, proteinase, cathepsin-G is released
• Reactive oxygen species inactivate α1-antitrypsin causing
functional α1-antitrypsin deficiency
• Neutrophil destruction of alveolar and respiratory bronchiolar
walls, as well as the elastic tissue within the alveolar septa
occurs unabated in the absence of α1-antitrypsin
• Macrophages, present in greater numbers, can release their
own elastase which is normally not inhibited by α1-antitrypsin
Emphysema: protease-antiprotease imbalance and
oxidant-antioxidant imbalance
Enlargement of airspaces and thinning
of alveolar septa in emphysema
Types of Emphysema
• (B & C) Centriacinar (D&E) Panacinar
Bronciolitis
• Inflammation, caused by macrophage and
lymphocyte infiltration of the small bronchiole
(< 2mm) walls, is an early sign of functional
airway obstruction caused by smoking
Chronic Bronchitis
• Long term inhalation of cigarette smoke and/or air pollution
(nitrogen dioxide, sulfur dioxide) causes increased transcription of
the mucin gene resulting in:
– Hypertrophy of mucus glands in trachea and main branch bronchi
causing a chronic productive cough
– Metaplasia of goblet cells in small bronchi and bronchioles causing
mucus plugging
– inflammation with infiltration of CD8+ T cells, macrophages, and
neutrophils (differentiated from asthma by lack of eosinophils) causing
damage, permanent lumen narrowing and bronchiole wall thickening
by fibrosis and ultimately closure (bronchiolitis obliterans)
– Often accompanied by emphysema
– Chronic respiratory failure develops (compensated by kidneys (bicarb
retention & EPO secretion -> normal pH & polycythemia)
– Recurrent microbial infections exacerbate the symptoms, accelerate
the course of the disease and cause bouts of acute (uncompensated)
respiratory failure requiring emergency treatment
Chronic bronchitis showing doubling of
thickness of mucus gland layer of a bronchus
Chronic Respiratory Failure
• Acute hypercapnic respiratory failure is compensated by
buffering only because it rapidly develops over minutes to
hours; therefore, pH is less than 7.3 (respiratory acidosis)
• Chronic respiratory failure develops over several days or
longer, allowing time for renal compensation and
bicarbonate retention. Therefore, the pH usually is only
slightly decreased.
• The distinction, however, between acute and chronic
hypoxemic respiratory failure should not be made on the
basis of ABGs but rather by clinical markers of such as
polycythemia or cor pulmonale, suggesting a long-standing
disorder
Quick Review of Pathology of Asthma
Changes To The Bronchiole Walls Due To Asthma