1. Obstructive Pulmonary Diseases

2. Obstructive Pulmonary Diseases
1. Localised (Mechanical Obstruction) - Acute
Tumor
Trauma
Foreign body
2. Diffuse - Distal airway disease (COPD) - Chronic
Chronic bronchitis
Bronchiectasis
Emphysema
Asthma

3. Chronic Obstructive Pulmonary Diseases

4. 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.

5. 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.

6. Pathophysiology Pathological changes in COPD occur in:
the large (central) airways,
the small (peripheral) bronchioles,
the lung parenchyma.
The increased number of activated polymorphonuclear leukocytes and macrophages release elastases  lung destruction
Increased oxidative stress  free radicals (released by phagocytes, and polymorphonuclear leukocytes)  apoptosis or necrosis of exposed cells

7. Factors in COPD Smoking Air pollution and COPD Other factors
Airway hyperresponsiveness
Alpha1-antitrypsin (a 1-AT) deficiency

8. 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.

9. Smoke The primary cause of COPD Neoplastic and Non-neoplastic diseases
Clinically significant COPD
chronic bronchitis
emphysema
Almost 4000 chemicals, 43 carcinogens
Neoplastic and Non-neoplastic diseases

10. Neoplastic diseases (cancers): Non-neoplastic diseases:
Lung
Bladder
Stomach
Pancreas
Oral cavity
Larynx
Cervix
Non-neoplastic diseases:
Lung diseases
Gastritis
Atherosclerosis
Ischemic heart disease
Hypertension
Bürger’s disease

11. 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 a1-AT.

12. 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

13. OTHER FACTORS IN COPD a1-antitrypsin deficiency
Airway hyperresponsiveness
Smokers with airway hyperresponsiveness are at increased risk of developing COPD with an accelerated decline in lung function
a1-antitrypsin deficiency
a1-antitrypsin deficiency is the only known genetic risk factor for developing COPD (panacinar emphysema) and accounts for less than 1% of all cases
(a1-antitrypsin is a protease inhibitor produced by the liver that acts predominantly by inhibiting neutrophil elastase in the lungs)

14. Chronic Bronchitis
Bronchiectasis
Emphysema
Asthma

15. Chronic Bronchitis
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).

16. Acute & Chronic inflammation of mucosa
Clinical observations: Chronic bronchitis
Productive cough
Acute & Chronic inflammation of mucosa
Secondary Pulmonary Infections (Haemophilus influenzae and Streptococcus pneumoniae)
Inflammation retention infection obstructioninflammation (circulus viciosus).
Acute respiratory failure in patients with advanced chronic bronchitis

17. 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)

18. Histology 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.

19. Chronic Bronchitis: Histology

20. Bronchiectasis
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

21. Etiology: Bronchial obstruction
Localized (to the obstructed lung segment):
tumor
foreign bodies
mucous impaction
Diffuse (obstructive airway diseases):
asthma
chronic bronchitis

22. 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

23. The dilatation ("-ectasis") results from
recurrent inflammations, and
contraction of scar surrounding the bronchus.

24. The left more commonly involved than the right
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

25. Cylindrical bronchiectasis shows uniform, moderate dilation.
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.

26. Bronchiectasis

27. Bronchiectasis

28. Pleural adhesions

29. Severe inflammation of bronchi and bronchioles
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

30. 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.

31. Bronchiectasis intense acute and chronic inflammatory exudation
desquamation of the lining epithelium

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

33. Complications amyloidosis meningitis brain abscesses cor pulmonale
pneumonia
empyema
septicemia

34. Emphysema
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.

35. Classification of Emphysema
(1) Centrilobular (centriacinar)
(2) Panacinar (panlobular)
(3) Localised (paraseptal)
(4) Senile
Of these, the first two are the most important clinically

36. 1. Centrilobular 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

37. 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.

38. Smokers lung Normal Lung

39. Smokers lung – Emphysema

40. Centrilobular Emphysema

41. Severe Centrilobular Emphysema

42. Microscopy

43. 2. Panacinar (Panlobular) 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

44. 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

45. 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.

46. Panacinar (Panlobular) Emphysema

47. 3. Localised (Paraseptal) 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).

48. Bullous Emphysema

49. Bullous Emphysema

50. 4. Senile emphysema
This form of emphysema is usually associated with "old age“
It may occur anywhere in the pulmonary parenchyma

51. Pathophysiology a1-AT DEFICIENCY: A hereditary deficiency
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.
a1-AT DEFICIENCY: A hereditary deficiency
a1-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