1. Chronic Obstructive Pulmonary Diseases (COPD)
Emphysema
Chronic Bronchitis
Bronchial Asthma
Bronchiectasis

2. Chronic Bronchitis
Chronic bronchitis is defined clinically. It is present in any patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years, in the absence of any other identifiable cause.

3. (1) Progress to chronic obstructive airway disease
(2) Lead to cor pulmonale and heart failure
(3) Cause atypical metaplasia and dysplasia of
the respiratory epithelium and
(4) cancerous transformation.

4. Pathogenesis Tobacco smoke – 90% of patients are smokers.
Grain, cotton, and silica dust
Air pollution
Infection
– Bacterial and viral infections are important in
triggering acute exacerbation of the disease.
Others

5. simple chronic bronchitis: Most patients have
The productive cough raises mucoid sputum, but airflow is not obstructed.
chronic asthmatic bronchitis-chronic bronchitis may demonstrate hyper-responsive airways with intermittent bronchospasm and wheezing.
chronic obstructive bronchitis-Heavy smokers, develops chronic outflow obstruction, usually with evidence of associated emphysema.

6. The earliest feature of chronic bronchitis is hyper secretion of mucus, beginning in the large airways.
Squamous metaplasia or dysplasia of bronchial epithelium.
Histologically, in the trachea and larger bronchi there is enlargement of the mucus-secreting glands.
 Bronchial or bronchiolar mucous plugging, inflammation and fibrosis.
Increased number of goblet cells and inflammatory cells in the epithelium of peripheral airways.
A normal Reid index is less than 0.4 and is increased in chronic bronchitis.

7. Chronic bronchitis. The lumen of the bronchus is above
Chronic bronchitis. The lumen of the bronchus is above. Note the marked thickening of the mucous
gland layer (approximately twice normal) and squamous metaplasia of lung epithelium.

8. Clinical course Prominent cough Production of sputum
("blue bloaters"). Hypercapnia, hypoxemia, and cyanosis
Pulmonary hypertension and cardiac
Failure
Recurrent infections and respiratory failure

9. Complication Emphysema Corpulmonale Bronchiectasis Bronchopneumonia
Bronchogenic carcinoma of lung

10. Emphysema
Emphysema is characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis.

11. CAUSES Smoking cigarettes is the most common cause.
Alpha 1 antitrypsin deficiency

12. Alpha 1 antitrypsin deficiency
It is autosmal dominant disorder.
It is mainly synthasized in liver.
It is a serine protease inhibitor,
It inhibits the proteases (particularly elastase) secreted by neutrophils during inflammation. .

13. The defects is the result of alleles at the Pi ("protease-inhibitor") locus -- "M" is the common allele,
Homozygous Z type decreases the liver synthesis of AAT.
Emphysema develops at early age.
Homozygous patients may also get cirrhosis

14. Pathogenesis of Emphysema
Emphysema result from the destructive effect of high protease activity in subjects with low antiprotease activity.
A consequence of two critical imbalances
– The protease-antiprotease imbalance
– Oxidant-antioxidant imbalance.

15. The chest cavity is opened at
autopsy to reveal numerous large
bullae apparent on the surface of
the lungs in a patient dying with
emphysema. Bullae are large
dilated airspaces that bulge out
from beneath the pleura.
Emphysema is characterized by
a loss of lung parenchyma by
destruction of alveoli so that
there is permanent dilation of
airspaces.

17. Pathogenesis of emphysema
The protease-antiprotease imbalance and oxidant-antioxidant imbalance are additive in their effects and contribute to tissue damage. α1-antitrypsin (α1-AT) deficiency can be either congenital or
"functional" as a result of oxidative inactivation.

18. Protease-Antiprotease Imbalance Hypothesis
1.Genetic deficiency of the antiprotease α1-antitrypsin
2.The effect of cigarette smoking in the development of emphysema
 Increased elastase availability and decreased antielastase.
Functional AAT deficiency
Oxidant-Antioxidant Imbalance
Tobacco smoke,
Chemo tactic factor for neutrophils and macrophages, in turn they releases,Large number of
Free radicals and elastases
 Inactivates AAT and Antioxidants. .

19. Types of Emphysema According to its anatomic distribution within
the lobule
Four major types
– Centriacinar
– Panacinar
– Paraseptal
– Irregular
Only the first two cause clinically significant
airflow obstruction.

20. Centriacinar (Centrilobular) Emphysema
The central or proximal parts of the acini, formed
by respiratory bronchioles, are affected,
whereas distal alveoli are spared.
The lesions are more common and
severe in the upper lobes,
particularly in the apical segments.
Centriacinar emphysema occurs
Predominantly in heavy smokers,
often in association with
chronic bronchitis.

21. Panacinar Emphysema-Uniform destruction and enlargement of the acinus
Tends to occur more commonly in the lower
zones and in the anterior margins of the lung,
and it is usually most severe at the bases.
Common in-Alpha1-antitrypsin deficiency

22. centrilobular emphysema
are "dirty holes" that appear focally where the central portions of lung acini have lost lung parenchyma while collecting anthracotic pigment at the same
time. This pattern is typical for smokers.

23. Distal Acinar (Paraseptal) Emphysema
The proximal portion of the acinus is normal, but
the distal part is predominantly involved.
The characteristic findings are of multiple,
continuous, enlarged airspaces from less than
0.5 cm to more than 2.0 cm in diameter,
sometimes forming cystlike structures.
Seen in Spontaneous pneumothorax
in young adults.

24. Airspace Enlargement with Fibrosis (Irregular Emphysema)
The most common form of emphysema
– Autopsy shows one or more scars from a
healed inflammatory process.
– In most instances, these foci of irregular
emphysema are asymptomatic and clinically
Insignificant.

25. Interstitial Emphysema
The entrance of air into the connective tissue stroma of the lung, mediastinum, or subcutaneous tissue. Increase in intra-alveolar pressure (as with vomiting or violent coughing) that causes a tear, with dissection of air into the interstitium. A perforating injury (e.g., a fractured rib).  Children with whooping cough and bronchitis,  Patients on respirators who have partial obstruction to the airways.

26. Compensatory Hyperinflation (Emphysema)
Surgical removal of a diseased lung or
lobe.
Designate dilation of alveoli but not
destruction of septal walls.

27. Bullous Emphysema Produces large subpleural blebs or bullae
(spaces more than 1 cm in diameter in the
distended state)
Most often subpleural, and occur near the
apex
Pneumothorax

28. Bullous emphysema with large apical and subpleural bullae.

29. Morphology
The diagnosis and classification of emphysema depend largely on the macroscopic appearance of the lung.  Panacinar emphysema Produces pale, voluminous lungs that often obscure the heart when the anterior chest wall is removed at autopsy.  Centriacinar emphysema The upper two-thirds of the lungs is more severely affected than the lower lungs and more pinkish and less voluminous.

30. Microscopy Thinning and destruction of alveolar walls
Adjacent alveoli become confluent,
creating large airspaces
Loss of elastic tissue in the surrounding
alveolar septa
The number of alveolar capillaries is
diminished.

31. Microscopically at high magnification, the loss of alveolar walls
with emphysema is demonstrated. Remaining airspaces are
dilated.

32. Pulmonary emphysema. There is marked enlargement of airspaces, with thinning and destruction of alveolar septa.

33. Clinical features Inspection-barrel-chest,
Dyspnea is usually the first symptom
prolonged expiration, sitting forward in a hunched-over position, attempting to squeeze the air out of the lungs
Because of prominent dyspnea and adequate oxygenation of hemoglobin, these patients are sometimes called "pink puffers.”
Steadily progressive,
Cough and wheezing,
Weight loss,
Pulmonary function tests, FVC is reduced and ratio of FEV1 to FVC is reduced.

34. Complications Secondary pulmonary hypertension develops gradually.
Cor pulmonale
Pneumothorax
Respiratory failure. (respiratory acidosis, hypoxia, and coma.)

35. Anatomic distribution of pure chronic bronchitis and pure emphysema. In
chronic bronchitis the small-airway disease (chronic bronchiolitis) results in
airflow obstruction, while the large-airway disease is primarily responsible for
the mucus hyper secretion.

36. Bronchiectasis
Bronchiectasis is the permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic supporting tissue, resulting from or associated with chronic necrotizing infections.
It is not a primary disease,
It is secondary to persisting infection or obstruction.

37. The conditions that leads to bronchiactasis are,
Bronchial obstruction causes,
tumors,
foreign bodies, and
occasionally impaction of mucus.
In cystic fibrosis both obstruction and infection accounts for bronchiactsis

38. In immunodeficiency states, increased susceptibility to infections.
Necrotizing, or suppurative, pneumonia, particularly with virulent organisms such as Staphylococcus aure.us or Klebsiella species.
postinfective bronchiectasis was sometimes in childhood pneumonias.
Post-tubercular bronchiectasis continues to be a significant cause of morbidity in endemic areas.

39. Bronchiectasis is likely to develop because of an increased susceptibility to repeated bacterial infections,
Kartagener syndrome,
It is an autosomal recessive disorder, is frequently associated with
bronchiectasis,
sinusitis and
situs inversus
Sterility in males.

40. Pathogenesis Two processes in the pathogenesis of bronchiectasis:
1.obstruction and
2.chronic persistent infection.

41. Morphology
Bronchiectatic involvement of the lungs usually affects the lower lobes bilaterally, particularly those air passages that are most vertical,
Foreign bodies,or tumorslocalized to a single segment of the lung.
The airways dilated as four times their usual diameter.

42. Intense acute and chronic inflammatory exudate within the walls of the bronchi and bronchioles -extensive areas of ulceration. Culturestaphylococci, streptococci, pneumococci, enteric organisms, anaerobic and microaerophilic bacteria,
Children Haemophilus influenzae and Pseudomonas aeruginosa.

43. Healing -the lining epithelium may regenerate completely;
Fibrosis of the bronchial and bronchiolar walls and peribronchiolar fibrosis develop in chronic cases.
Might lead to lung abscess.

44. clinical manifestations
severe, persistent cough with expectoration of mucopurulent, sometimes fetid, sputum.
The sputum may contain flecks of blood;
frank hemoptysis can occur.
Symptoms are often episodic and are precipitated by upper respiratory tract infections.
Clubbing of the fingers
pulmonary hypertension,
and (rarely) cor pulmonale.
Metastatic brain abscesses.

45. BRONCHIAL ASTHMA
Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or early in the morning.
IT is a triad of intermittent and reversible airway obstruction, chronic bronchial inflammation with eosinophils, and bronchial smooth muscle cell hypertrophy and hyperreactivity.

46. Atopic ( extrinsic) asthma and
70% of cases are of atopic type.
IgE and TH2-mediated immune responses to environmental antigens. .

47. Non atopic (Intrinsic )asthma.
Aspirin
pulmonary infections, especially those caused by viruses;
cold
psychological stress
Exercise
Inhaled irritants

48. Drug induced asthma aspirin
Occupational asthma,
Exposure to fumes, organic chemical dust and plastics.

49. Pathogenesis type I hypersensitivity ("atopy"),
acute and chronic airway inflammation, and bronchial hyper-responsiveness to a variety of stimuli.
inflammatory mediators type 2 helper T (TH2)
-IL-4 IgE production,
IL-5 Activates eosinophils,
and IL-13 -mucus production.
epithelial cells are activated to produce chemokines that promote recruitment of more TH2 cells and eosinophils, other leukocytes, and triggers the inflammation.

50. Leukotrienes C4, D4, and E4: extremely potent mediators that cause prolonged bronchoconstriction, increase vascular permeability, and increase mucin secretion.
Platelet-activating factor: causes aggregation of platelets and release of histamine from their granules.
Histamine: causes bronchospasm and increases vascular permeability,

53. morphology
Occlusion of bronchi and bronchioles by thick, tenacious mucus plugs.
Histologically, the mucus plugs contain whorls of shed epithelium (Curschmann spirals).
Curschmann spirals

54. Numerous eosinophils and Charcot-Leyden crystals (collections of crystalloids made up of eosinophil proteins) are also present.
Charcot-Leyden crystals

55. morphology
"airway remodeling-Thickening of the basement membrane of the bronchial epithelium.
Edema and an inflammatory infiltrate in the bronchial walls, eosinophils and mast cells.
An increase in the size of the submucosal glands.
Hypertrophy of the bronchial muscle walls.

57. Clinical Course Severe dyspnea with wheezing; Dry or productive cough,
In the usual case, attacks last from 1 to several hours and subside either spontaneously or with Therapy--bronchodilators and corticosteroids.
status asthmaticus  Occasionally a severe dyspnea that does not respond to therapy and persists for days and even weeks The associated hypercapnia, acidosis, and severe hypoxia may be fatal.