Lung pathology 2

Obstructive Lung Diseases

Dr.G.Bhanu prakash , www.gims-org.com,www.usmletutor.org


1.Chronic Bronchitis• It is defined clinically as the presence of

productive cough for At least 3 months in at least 2 consecutive yrs in absence of any other identifiable cause.

• The most important initiating agent is smoking resulting in airways irritation leading to mucus hypersecretion, the latter may cause airways obstruction. Infection plays a secondary role particularly in maintaining chronic bronchitis and are also responsible for the acute exacerbations.


• Histologic features Include chronic lymphocytic infiltration of the airways and submucosal gland hypertrophy. There is also increase in Reid index (it is the ratio of the thickness of the mucus gland layer to the thickness of the wall. The bronchial epithelium may also have squamous metaplasia and dysplasia.

• clinical features: Late onset of dyspnea with productive cough(copious sputum), recurrent infections, hypoxemia and mild cyanosis (BLUE BLOATERS). Long standing chronic bronchitis can cause cor pulmonale (right sided heart failure due to pulmonary hypertension).


2.EmphysemaIt is abnormal permanent enlargement of the air

space distal to terminal bronchioles and is associated with destruction of their walls.

• Most imporant etiological agent for emphysema is smoking which causes inflammation in airways resulting in increased neutrophils and macrophages. These inflammatory cells release elastase responsible for destruction of lung tissue resulting in emphysema.


• Normally, the pulmonary tissue destruction by elastase is prevented by the presence of anti-

elastase activity which is primarily due to α1- AT (with minor contribution from secretory leukoprptease inhibitor in bronchial mucus and

serum α1- macroglobulin). So any increase in neutrophils (usually in smokers) or deficiency of

α1-AT would contribute to development of emphysema. Characteristically, there is loss or reduction of elastic recoil of the lung.


•α1-AT is synthrsized in the liver. The normal α1-AT phenotype is PiMM. The abnormal

phenotype is PiZZ which is associated with α1-AT deficiency and development of emphysema at earlier age and greater severity.+


Emphysema

IrregularDistal acinarPanacinar Centriacinar


Centriacinar Panacinar Distal acinar Irregular

• Involvement of central part of acinus with sparing of alveoli .

• Seen in smokers .

• Usually more sever in upper lobes (due to relative deficiency of serum α1-AT to this less perfused region).

• MC type of emphysema seen clinically.

•Involvement of the entire acinus

•Seen with α1-AT deficiency

•Occurs more severely in lower lobes at base of lung (due to lower lung distribution of netrophils because of more perfusion of this region).

•Distal part of acinus is affected with sparing of proximal part of acinus

• Seen in smokers .

•Involvement of lung adjacent to pleura

•Associated with the development of spontaneous pneumothorax.

•Irregular acinar involvement associated with fibrosis/ scarring

•Most common type of emphysema histologically


• Clinical features: progressively increasing dyspnea, weight loss, late onset of cough with scanty sputum. The patient is non- cyanotic, uses accessory muscle of respiration and shows pursed lip breathing.(PINK PUFFERS)

• Management: Cessation of smoking and use of bronchodilators is the mainstay of the management.

Mnemonic: emPhysema had letter P (and not B). So Pink

Puffer.Chronic Bronchitis has letter B(and not P) so blue

Bloater.


3.AsthmaHyperactivity of the airways resulting in reversible

bronchoconstriction and air flow obstruction on exposure to some external stimuli is called asthma.

ASTHMA

Extrinsic asthma Intrinsic asthma


Extrinsic asthma Intrinsic asthma

• Type I hypersensitivity reaction

• Commoner type of asthma

• Positive family history

• Serum IgE levels are elevated

•Viral pulmonary infection• Cold• Inhaled irritants • Stress• Exercise • Drug induced (most commonly by aspirin ingestion)• Negative family history • Serum IgE levels are normal


• Pathogenesis: Primary exposure of an allergen causes T H2 cell dominated inflammatory response resulting in IgE production and eosinophil recruitment (called sensitization). Exposure to the same allergen causes cross linking of IgE bound to IgE receptors on mast cells in the airways which cause opening up of epithelial cells due to released mediators.

• Antigens then cause activation of mucosal mast cells and eosinophils and this along with neruonal reflexes (subepithelial vagal receptors)cause bronchospasm, increased vascular permeability and mucus production (Acute or immediate response).


• Later on, leukocytic infiltration causes release of more mediators and damage to the epithelium (late Phase Reaction). Eosinophils in airways release major basic protein which causes epithelial damage and more airways constriction.

• Leukotrienes C4, D4, E4 and acetylocholine have definite role in bronchoconstriction whereas agents like histamine, PGD2 and platelet activating factor (PAF) may also role in the features of the disease.


• In intrinsic asthma, aspirin causes shift of the arachidonic acid metabolism towards the lipoygenase pathway resulting in formation of the bronchoconstrictor leukotrienes.

• Virus induced inflammation lowers the threshold of the subepithelial vagal receptors to irritants.

• Exercise causes loss of water and heat from the respiratory tract. The water loss causes mucosal hyperosmolarity which stimulates release from the mast cells. This explains the pahtogenesis of exercise induced asthma.


• Important fact: IL- 13 gene polymorphism is strongly associated

with bronchial asthma. ADAM-33 is another gene causing proliferation of smooth muscle cells and fibroblasts in bronchi resulting in bronchial hyperreactivity and subepithelial fibrosis.


• Clinical features:Acute asthmatic attack is characterized wheezing,

cough and severe dyspnea.• Morphology: The most stroking macroscopic finding is

occlusion of the bronchi and bronchioles by mucus plugs.

Histologically, there are numerous eosiphils, Charcot leyden crystalsQ (composed of eosinophil membrane protein called as galectin-10) and Curschmann spirals Q (whorls of shed airways epithelium).


Structural changes in the bronchial wall called “airway remodelling” is characterized by presence of eosiphilic inflammation and edema of bronchial walls, increased size of submucosal glands, hypertrophy of bronchial wall smooth muscle and deposition of subepithelial collagen in the bronchial wall. Individual epithelial cells presents in the sputum of the patients are called Creola bodies.

Management is done with bronchodilators and corticosteroids (for details, refer to the review of pharmacology by the same authors.


4. Bronchiectasis• Abnormal permanent airways dilation resulting

from chronic necrotizing infection is called bronchiectasis.

Cause

Bronchial Obstruction Congenital Necrotizing

pneumonias Miscellaneous

Tumor

Foreign body

Cystic fibrosis

Kartagener syndrome(triad of Bronchiectasis+Situs inversus+ sinusitis)

Mycobactrium

Staph. aureus

Aspergillus

Influenza virus

SLERheumatoidarthritis

Post trasplanation


• Obstruction and infection are the chief contributors to the damages of airways wall associated with destruction of smooth muscle and elastic tissue fibrosis and further dilation of bronchi.


• Clinical features:Chronic cough, fever, foul smelling sputum

production, recurrent pulmonary infection, sinusitis and immune deficiencies.

It usually affects vertical air passages of the lower bilaterally with involvement of left side more frequent than right.

The dilated bronchi can be followed directly out to the pleural surfaces. There is usually presence of inflammatory cell in the walls of bronchi and bronchioles which may also exhibit squamous metaplasia.


• Complications include massive hemoptysis, amyloidosis, visceral abscess and cor pulmonale.

• Management is done by chest physiotherapy, natural drainage, bronchilators and antibiotics. High Resolution CT scan (HRCT) is the best investigation for the detection of bronchiectasis.







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Lung pathology 2