Obstructive Obstructive Pulmonary DiseasesPulmonary Diseases

Obstructive Obstructive Pulmonary DiseasesPulmonary Diseases

1. Localised (Mechanical Obstruction) - Acute

• Tumor

• Trauma

• Foreign body

2. Diffuse - Distal airway disease (COPD) - Chronic

• Chronic bronchitis

• Bronchiectasis

• Emphysema

• Asthma

Chronic Obstructive Chronic Obstructive Pulmonary DiseasesPulmonary Diseases

COPD is defined as a disease state characterized by the presence of airflow obstruction due to Chronic bronchitis

Bronchiectasis

Emphysema

Asthma

The airflow obstruction generally is progressive, may be accompanied by airway hyperreactivity, and may be partially reversible.

The term “chronic obstructive pulmonary disease” (COPD) refers to a group of conditions; They are accompanied by chronic or recurrent

obstruction to air flow within the lung,

They share a major symptom: dyspnea.

Pathophysiology Pathological changes in COPD occur in:

the large (central) airways,

the small (peripheral) bronchioles,

the lung parenchyma.

1. The increased number of activated polymorphonuclear leukocytes and macrophages release elastases lung destruction

2. Increased oxidative stress free radicals (released by phagocytes, and polymorphonuclear leukocytes) apoptosis or necrosis of exposed cells

Factors in COPD

Smoking

Air pollution and COPD

Other factors Airway hyperresponsiveness

Alpha1-antitrypsin (a 1-AT) deficiency

SMOKING The primary cause of COPD is exposure to tobacco

smoke.

Chronic bronchitis is primarily a disease of cigarette smokers: 90% of cases occur in smokers.

Chronic bronchitis occurs in less than 5% of nonsmokers, 10% to 15% of moderate smokers, and more than 25% of heavy smokers.

Smoke

The primary cause of COPD Clinically significant COPD

• chronic bronchitis

• emphysema

Almost 4000 chemicals, 43 carcinogens

Neoplastic and Non-neoplastic diseases

Neoplastic diseases (cancers): Lung

Bladder

Stomach

Pancreas

Oral cavity

Larynx

Cervix

Non-neoplastic diseases: Lung diseases

Gastritis

Atherosclerosis

Ischemic heart disease

Hypertension

Bürger’s disease

Pathophysiology of COPD in smokers

Smokers have greater numbers of neutrophils and macrophages in their alveoli

Smoking

• Stimulates release of elastase from neutrophils

• Enhances elastolytic protease(s) activity in macrophages

• Inhibition of antielastase activity– oxidants in cigarette smoke – oxygen free radicals secreted by neutrophils inhibit

1-AT.

AIR POLLUTION

The use of solid fuels for cooking and heating may result in high levels of indoor air pollution and the development of COPD sulfur dioxide

nitrogen dioxide

OTHER FACTORS IN COPD Airway hyperresponsiveness

Smokers with airway hyperresponsiveness are at increased risk of developing COPD with an accelerated decline in lung function

1-antitrypsin deficiency 1-antitrypsin deficiency is the only known genetic risk

factor for developing COPD (panacinar emphysema) and accounts for less than 1% of all cases

(1-antitrypsin is a protease inhibitor produced by the liver that acts predominantly by inhibiting neutrophil elastase in the lungs)

Chronic BronchitisChronic Bronchitis

BronchiectasisBronchiectasis

EmphysemaEmphysema

AsthmaAsthma

Chronic bronchitis is four to ten times more common in heavy smokers irrespective of age, sex, and occupation.

When persistent for years, it may

(1) lead to cor pulmonale and heart failure,

(2) cause atypical metaplasia and dysplasia of the respiratory epithelium (cancerous transformation).

Chronic BronchitisChronic Bronchitis

Productive cough

Acute & Chronic inflammation of mucosa

Secondary Pulmonary Infections (Haemophilus influenzae and Streptococcus pneumoniae)

Inflammation retention infection obstructioninflammation....... (circulus viciosus).

Acute respiratory failure in patients with advanced chronic bronchitis

Clinical observations: Chronic bronchitis

Pathology: Chronic bronchitis

Mucous gland enlargement is the histologic hallmark of chronic bronchitis

Increased ratio of mucous cells to serous ones

Excess mucus in airways

Increase in the number of goblet cells (hyperplasia)

Lack of cilia

Thickening of the bronchial wall

Mucous gland enlargement and edema (which leads to encroachment on the bronchial lumen)

Increased smooth muscle (which may indicate bronchial hyperreactivity)

Squamous metaplasia of the bronchial epithelium (epithelial damage from tobacco smoke)

HistologyHistology

Earliest features of chronic bronchitis are hypersecretion of mucus in the large airways,

hypertrophy of the submucosal glands in the trachea and bronchi.

As chronic bronchitis persists, marked increase in goblet cells of small airways (small

bronchi and bronchioles)

excessive mucus production that contributes to airway obstruction.

Chronic Bronchitis: HistologyHistology

BronchiBronchiectasisectasis Bronchiectasis is a chronic necrotizing infection of

the bronchi and bronchioles leading to or associated with abnormal dilation of these airways.

It is manifested clinically by cough,

fever,

the expectoration of copious amounts of foul-smelling, purulent sputum.

To be considered bronchiectasis, the dilation should be permanent; reversible bronchial dilation often accompanies viral and

bacterial pneumonia

Etiology: Bronchial obstruction

Localized (to the obstructed lung segment): tumor

foreign bodies

mucous impaction

Diffuse (obstructive airway diseases): asthma

chronic bronchitis

Pathogenesis

Smoking irritation of mucosa Mucus hypersecretion Obstruction, Cough

Atelectasis

Metaplasia loss of ciliated epithelium

Retention of secretion

Secondary infection

Recurrent Inflammation and Fibrosis

Destruction of bronchial wall

Dilated bronchus filled with pus

The dilatation ("-ectasis") results from recurrent inflammations, and

contraction of scar surrounding the bronchus.

Gross Pathology

Generalized bronchiectasis is usually bilateral and is most common in the lower lobes

The left more commonly involved than the right

Bronchi are dilated and have white or yellow thickened walls

Bronchial lumens frequently contain thick, mucopurulent secretions

Gross Pathology

On gross examination, bronchial dilation is saccular, cylindrical or varicose (they may produce cystic pattern):

Saccular bronchiectasis: bronchi are severely dilated and end blindly in dilated sacs, with collapse and fibrosis of the distal lung parenchyma.

Cylindrical bronchiectasis shows uniform, moderate dilation. It is a milder disease than saccular bronchiectasis and leads to fewer

clinical symptoms.

Varicose bronchiectasis: bronchi resemble varicose veins when visualized by radiologic bronchography, with irregular dilations and constrictions. Bronchiolar obliteration is not as severe, and parenchymal

abnormalities are variable.

Bronchiectasis

Bronchiectasis

Pleural adhesions

Microscopy

Severe inflammation of bronchi and bronchioles

Destruction of all components of the bronchial wall

Collapse of distal lung parenchyma, the damaged bronchi dilate

Hypersecretion of mucus

Abnormalities of the surface epithelium squamous metaplasia

increased goblet cells

Lymphoid follicles are often seen in the bronchial walls

Scarred and often obliterated bronchi and bronchioles (distal ones)

The bronchial arteries increase in size to supply the inflamed bronchial wall and fibrous tissue

In the full-blown, active case:

Intense acute and chronic inflammatory exudation within the walls of the bronchi and bronchioles,

A vicious circle

pool of mucus is liable to further infection, which leads to progressive destruction of the bronchial walls more mucus new infection .......

Desquamation of the lining epithelium and extensive areas of ulceration (necrosis),

Pseudostratification of the columnar cells or squamous metaplasia of the remaining epithelium,

Necrosis (destroys the bronchial or bronchiolar walls and forms a lung abscess),

In chronic cases:

Fibrosis of the bronchial and bronchiolar walls.

Bronchiectasis

intense acute and chronic inflammatory exudation

desquamation of the lining epithelium

Bronchiectasis

Necrosis (destroys the bronchial or bronchiolar walls and forms a lung abscess).

Complications

amyloidosis

meningitis

brain abscesses

cor pulmonale

pneumonia

empyema

septicemia

EmphysemaEmphysema Emphysema is a chronic lung disease characterized

by enlargement of airspaces distal to the terminal bronchioles, with destruction of their walls but without fibrosis.

Loss of elasticity of the lung with some destruction of the alveoli.

Emphysema is a condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to

the terminal bronchiole, accompanied by destruction of their walls, and without

obvious fibrosis.

Emphysema causes obstruction to air flow.

Classification of Emphysema

(1) Centrilobular (centriacinar)

(2) Panacinar (panlobular)

(3) Localised (paraseptal)

(4) Senile Of these, the first two are the most important

clinically

1.1. CCentrilobular emphysemaentrilobular emphysema Most frequent

Usually associated with cigarette smoking (often in association with chronic bronchitis)

Destruction of the cluster of terminal bronchioles near the end of the bronchiolar tree in the central part of the pulmonary lobule

Dilated respiratory bronchioles form enlarged airspaces that are separated from each other and from the lobular septa by normal alveolar ducts and alveoli

Distal structures also may be involved

Bronchioles proximal to the emphysematous spaces are inflamed and narrowed

Centrilobular emphysema is most severe in the upper zones of the lung, the upper lobe, and the superior segment of the lower lobe

The walls of the emphysematous spaces often contain large amounts of black pigment.

Inflammation around bronchi and bronchioles and in the septa is common.

Focal dust emphysema, a disease of coal miners, resembles centrilobular emphysema but differs in that the enlarged spaces are smaller and more regular and inflammation of the bronchioles is not apparent.

Smokers lung Normal Lung

Smokers lung – Emphysema

Centrilobular Emphysema

Severe Centrilobular Emphysema

Microscopy

22. . Panacinar Panacinar (Panlobular)(Panlobular) Emphysema Emphysema

The acinus is uniformly involved, with destruction of the alveolar septa from the center to the periphery of the acinus (entire alveolus distal to the terminal bronchiole)

In the final stage, panacinar emphysema leaves behind a lacy network of supporting tissue (cotton-candy lung)

This variant occurs in several situations

Diffuse panacinar emphysema is typically associated with a 1-AT deficiency [a congenital disease caused by a1-protease inhibitor ("antitrypsin") deficiency]

It is also often found in cigarette smokers in association with centrilobular emphysema In such cases, the panacinar pattern tends to

occur in the lower zones of the lung, whereas centrilobular emphysema is seen in the upper regions

Grossly, cut surface of the lung shows diffuse enlargement of airspaces in the affected parenchyma.

Often the enlarged spaces are traversed by delicate, spider-web-like strands representing the residual alveolar walls.

As in centrilobular emphysema, fibrosis is not seen.

Panacinar (Panlobular) Emphysema

33. Localised . Localised ((Paraseptal)Paraseptal) Emphysema Emphysema

Characterized by destruction of alveoli and resulting emphysema in only one or at most a few locations

The remainder of the lungs is normal

The lesion is usually found at the apex of an upper lobe, although it may occur anywhere in the pulmonary parenchyma, such as in a subpleural location.

Progression of localized emphysema can result in a large area of destruction, termed a bulla, which ranges in size from as small as 2 cm to a large lesion (Bullous Emphysema).

Although it is of no clinical significance itself, rupture of an area of localized emphysema produces spontaneous pneumothorax (sudden death).

Bullous Emphysema

Bullous Emphysema

4. Senile emphysema4. Senile emphysema

This form of emphysema is usually associated with "old age“

It may occur anywhere in the pulmonary parenchyma

Pathophysiology

TOBACCO: The major cause of emphysema

Emphysema results when elastolytic activity increases or antielastolytic activity is reduced.

Increased numbers of neutrophils, which contain serine elastase and other proteases, are found in the bronchoalveolar lavage fluid of smokers.

Smoking also interferes with alpha1-antitrypsin (a1-AT) activity.

1-AT DEFICIENCY: A hereditary deficiency 1-AT: a circulating glycoprotein produced in the liver

Major inhibitor of a variety of proteases, including elastase, trypsin, chymotrypsin, thrombin, and bacterial proteases

Its most important action to inhibit neutrophil elastase, an enzyme that digests elastin and other structural components of the alveolar septa