Pathophysiology of COPD

 The most consistent pathological finding is hypertrophy and increase in number of the mucus secreting goblet cells of the bronchial tree, evenly distributed throughout the lungs but mainly seen in the larger bronchi.
 In more advanced cases, bronchi themselves are inflamed ; there will be infiltration of the walls of the bronchi and bronchiole with acute and chronic inflammatory cells and lymphoid follicles.
 The epithelial layer may become ulcerated and when ulcers heal, squamous epithelium may replace the columnar cells – squamous metaplasia
 Inflammation is then followed by scarring and a remodeling process that thickens the walls and leads to widespread narrowing in the small airways.
 If the airway narrowing is combined with emphysema, then the resulting airflow is even more severe.


 The small airways are particularly affected in the initial stage of the disease, initially without the development of any significant breathlessness.
 The initial inflammation of the small airways are reversible ; there will be improvement if smoking stops early. In later stages, the inflammation continues even if smoking is stopped.


 Emphysema leads to expiratory airflow limitation and air trapping. The loss of lung elastics recoil increases total lung capacity while the loss of alveoli with emphysema results in decreased gas transfer.
 V/Q mismatch occurs because of damage and mucus plugging of smaller airways from chronic inflammation and partly because of the rapid closure of the smaller airways owing to loss of elastic recoil from emphysema.
 This leads to a fall in PO2 and an increase in the work of respiration.
 However, many patients will show low normal PCO2 values – pink puffers – seek to maintain their blood gases by increasing their respiratory effort.
 Other patients who fail to maintain their respiratory effort will have a high level of CO2.
 In the short term, the rise in CO2 level will stimulate the increase in respiration rate but in the long term, these patients become insensitive to CO2 and come to depend on hypoxemia to drive the ventilation.- adaptation of central chemoreceptors due to kidney compensation
 These patients appear less breathless, and because they run on low PO2 level, production of RBCs and retention of fluid will be stimulated and hence, polycythaemia.
 In consequence, they will become bloated, plethoric and cyanosed.
 Attempts to abolish hypoxemia may make the situation much worse by decreasing respiratory drive in patients who rely on hypoxia to drive their ventilation.
 In summary, 3 mechanisms are suggested for the limitation of airflow :
 Loss of elasticity and alveolar attachments of air airways due to emphysema.
 Inflammation and scarring – narrowing of airways
 Mucus secretion which blocks the airways
Pathophysiology of asthma
Airways of asthma patients are hypersensitive  type 1 hypersensitivity  bronchi spasm  inflammation
Parasympathetic of afferent nerve endings in the lining of the bronchus is stimulated and impulse travels to brain then efferent nerve endings releasing Ach and causing formation of inositol 1,4,5-triphosphate (IP3) in bronchial smooth muscles  shortening bronchoconstriction.
Bronchial inflammation
Allergens gets ingested by antigen-presenting cells and present the allergen to immune cells TH0 and gets ignored, but in asthma, TH0 transform into TH2.
Activates humoral immune system  antibodies against the inhaled allergen  Inflammation  wall of airway thicken, remodeling due to scaring of the airway, mucus producing cells grow larger and produce more and thicker.
The "hygiene hypothesis" postulates that an imbalance in the regulation of these TH cell types in early life leads to a long-term domination of the cells involved in allergic responses over those involved in fighting infection. The suggestion is that for a child being exposed to microbes early in life, taking fewer antibiotics, living in a large family, and growing up in the country stimulate the TH1 response and reduce the odds of developing asthma
Pathophysiology of Emphysema
 Panacinar (or panlobular) emphysema: The entire respiratory acinus, from respiratory bronchiole to alveoli, is expanded. Occurs more commonly in the lower lobes, especially basal segments, and anterior margins of the lungs.[2]
 Centroacinar (or centrilobular) emphysema: The respiratory bronchiole (proximal and cen-tral part of the acinus) is expanded. The distal acinus or alveoli are unchanged. Occurs more commonly in the upper lobes.[2]

Toxicants are breathed into the lungs, it is trapped in the alveoli  Localized inflammation
One of the inflammatory response, leucocyte elactase cause alveolar septum to disintegrate.(Septal rupture)  Deformed alveoli  Reduced surface area  Decrease gas exchange
Also decreased elastin, loss of support  alveoli tend to collapse  limiting air flow
With reduced surface area  Thoracic cage expansion (barrel chest), and diaphragm contraction (flat-tening)  CO2 exhalation impaired
As it continues to break down  hyperventilation unable to compensate for shrinking surface area  insufficient O2  vasoconstriction (hypoxic pulmonary vasoconstriction)  pulmonary hypertension  increased strain on right side of heart, right heart hypertrophy  jugular venous distension  blood start backing up (liver)
Alpha 1-antitrypsin (A1AT) breaks down elastase
Thus, increased risk in patients with alpha 1-antitrypsin deficiency for emphysema

However, more recent studies have brought into light the possibility that one of the many other numer-ous proteases, especially matrix metalloproteases might be equally or more relevant than neutrophil elastase in the development of non-hereditary emphysema.