1. Pathology of respiratory system
Lecture on pathomorphology by Filonenko T.G.
Pathology of respiratory system

2. Patterns of Lung disorders:
Airway
Bronchitis, Bronchiectasis, Bronchiolitis.
Tumors / Cancer
Parenchyma
Pneumonia.
Lung abscess, TB
Hyaline membrane dis (HMD & ARDS)
Pneumoconiosis
Pleura:
Pleural effusion (TB)
* Infections

3. PNEUMONIAS
Pneumonia is defined as acute inflammation of the lung parenchyma distal to the terminal bronchioles which consist of the respiratory bronchiole, alveolar ducts, alveolar sacs and alveoli.

4. Pathogenesis of Pulmonary Infections
Step 1: Entry
Aspiration (ie Pneumococcus)
Inhalation (ie Mtb and viral pathogens)
Inoculation (contaminated equipment)
Colonization (in patients with COPD)
Hematogenous spread (patients with sepsis)
Direct spread (adjacent abscess)

5. Step 2: Failure of t defense mechanisms
PATHOGENESIS
Step 2: Failure of t defense mechanisms
Decreased resistance - General/immune
Virulent infection
Defective Clearing mechanism
Depressed cough and glottic reflexes– Coma, paralysis, sick.
Impaired mucociliary transport– smoking, toxin aspiration
Impaired alveolar macrophage function
Leucocyte dysfunctions.
Low Alveolar defense - Immunodeficiency
Pulmonary edema – Cardiac failure, emboli.
Endobronchial obstruction – foreign body, tumors

6. Pathogenesis:

7. Pathogenesis:

8. Pneumonia Types: Etiologic Types: Infective Non Infective
Viral
Bacterial
Fungal
Tuberculosis
Non Infective
Toxins
chemical
Aspiration
Morphologic types:
Lobar
Broncho
Interstitial
Duration:
Acute
Chronic
Clinical:
Primary / secondary.
Typical / Atypical
Community / hospital

9. Lobar Pneumonia: whole lobe, exudation - consolidation
95% - Strep pneum.(Klebsiella in aged, alcoholics)
High fever, rusty sputum, Pleuritic chest pain.
Four stages: (*also in bronchopneumonia)
Congestion – 1d – vasodilatation congestion
Red Hepatization 2d - Exudation+RBC
Gray Hepatizaiton 4d- neutro & Macrophages
Resolution – 8d few macrophages, normal

10. Pathogenesis of Pneumonia
Grey Hepatization
Resolution
Pathogenesis of Pneumonia
Congestion
Red Hepatisation

11. Lobar Pneumonia: Congestion

12. Lobar Pneumonia: Red hepat.

13. Lobar Pneumonia: Grey hepat.
This is a high-power view of the fibrinous exudate covering the pleural surface. A few macrophages are present.

14. Lobar pneumonia

15. Lobar Pneumonia – Gray hep…

16. Bronchopneumonia (patchy)
Extremes of age. (infancy and old age)
Staph, Strep, Pneumo & H. influenza
Patchy consolidation – not limited to lobes.
Suppurative inflammation
Usually bilateral
Lower lobes common

17. Bronchopneumonia

18. Bronchopneumonia:

19. Broncho – Pneumonia - Lobar
Extremes of age.
Secondary.
Both genders.
Staph, Strep, H.infl.
Patchy consolidation
Around Small airway
Not limited by anatomic boundaries.
Usually bilateral.
Middle age – 20-50
Primary in a healthy
males common.
95% pneumoc (Klebs.)
Entire lobe consolidation
Diffuse
Limited by anatomic boundaries.
Usually unilateral

20. Broncho – Pneumonia - Lobar

21. Interstitial / atypical Pneumonia
Primary atypical pneumonia in the immunocompetant host (Mycoplasma or Chlamydia)
Interstitial pneumonitis
immunocompromised host : Pneumocystic carinii; CMV
Immunocompetant host: Influenza A
Gross features:
Lungs are heavy but not firmly consolidated
Microscopic features:
Septal mononuclear infiltrate
Alveolar air spaces either ‘empty’ or filled with proteinaceous fluid with few or no inflammatory cells

22. Interstitial Pneumonia:
Lymphocyte Infiltrate in alveloar wall

23. Complications of Pneumonia
Abscesses
Localized suppurative necrosis, Right side often in aspiration.
Staphylococcus; Klebsiella; Pneudomonas
Pleuritis / Pleural effusion.
Inflammation of the pleura ( Streptococcus pneumoniae)
Blood rich exudate (esp. rickettsial diseases)
Empyema
Pus in the pleural space.
Septicemia
Organisation (carnification)

24. Abscess formation

25. CHRONIC NONSPECIFIC DISEASES OF LUNGS (CNDL)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
(COPD)
Chronic Bronchitis
Bronchial Astma
Chronic Obstructive Emphysema
Bronchiectatic Disease
Chronic abscess
CHRONIC RESTRICTIVE PULMONARY DISEASE (CRPD)
Restriction due to chest wall disorder (Kyphoscoliosis, Poliomyelitis, severe obesity, pleural diseases)
Restriction due to interstitial and infiltrative diseases (Pneumoconiosis, Immunologic lung diseases, Idiopathic pulmonary fibrosis, Sarcoidosis)

26. Patho- and morphogenetic mechanisms of lungs
BRONCHITOGENIC (Chronic Obstructive Pulmonary Diseases) 1. Chronic Diffuse Bronchitis 2. Bronchial Astma 3. Chronic Diffuse Obstructive Emphysema 4. Bronchiectatic Disease
PNEUMONITOGENIC (Chronic Intersitial Pulmonary Diseases)
1. Idiopathic pulmonary fibrosis
PNEUMONIOGENIC (Chronic Nonobstructive Pulmonary Diseases)
1. Chronic pneumonia
2. Chronic abscess

27. CHRONIC BRONCHITIS   Chronic bronchitis is present in any patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years. Etiopathogenesis - Smoking - Atmospheric pollution - Occupation - Infection - Familial and genetic factors

28. Pathologic changes
Hypersecretion of mucus in the large airways, and is associated with hypertrophy of the submucosal glands in the trachea and bronchi.
Increase in goblet cells of small airways – small bronchi and bronchioles – leading to excessive mucus production that contributes to airway obstruction.
Squamous metaplasia with mucus plugging of the lumen.
Clustering of pigmented alveolar macrophages.
Iinflammatory infiltration.
Fibrosis of bronchiolar wall.

29. Chronic bronchitis: increased numbers of chronic inflammatory cells in the submucosa.

30. Outcomes and complications
- Pulmonary emphysema; - Right heart failure and formation of “cor pulmonale”; - Atypical metaplasia and dysplasia of the respiratory epithelium, providing a possible soil for cancerous transformation; - Amyloidosis of kidneys; - Development of Bronchiectasis.

31. BRONCHIECTASIS (BE)   BE is defined as abnormal and irreversible dilatation of the bronchi and bronchioles developing secondary to inflammatory weakening of the bronchial wall.

32. Etiopathogenesis of BE
1.     Endobronchial obstruction by tumor, foreign bodies, and compression by enlarged hilar lymph nodes and post-inflammatory scarring, lung fibrosis. 2.     Congenital or hereditary factors, including congenital BE, cystic fibrosis, intralobar sequestration of the lung states, and immune cilia and Kartagener’s syndromes. 3.     Necrotizing pneumonias, most often caused by tubercle bacillus, staphylococci or mixed infections, measles may develop BE as secondary complication.

33. BE usually affects distal bronchi and bronchioles beyond the segmental bonchi. The lungs may be involved diffusely or segmentally. The pleura is usually fibrotic and thickened with adhesions to the chest wall. Cut surface has honey-combed appearance. The walls of bronchi are thickened and the lumen are filled with mucus.       

34. Classification of BE
 Cylindrical: long, tube-like enlargements in 1 to 4 type of bronchus.
Fusiform: having spindle-shaped bronchial dilatation.
Saccular: having rounded sac-like distention in 6-10 types of bronchus.
Varicous: having irregular bronchial enlargements.

35. The histologic findings of BE
An intense acute and chronic inflammatory exudation within the walls of dilated bronchi and bronchioles. The mucosa and wall is not clearly seen because of the necrotizing inflammation with destruction.
Desquamation of the lining epithelium and extensive areas of necrotizing ulceration.
Squamous metaplasia of the remaining epithelium

36. Outcomes and complications 1
Outcomes and complications 1.    Obstructive ventilatory insufficiency can lead to marked dyspnea and cyanosis. 2.    Pulmonary hemorrhage 3.    Pulmonary abscess 4.    Empyema of the pleura 5.    Metastatic brain abscess 6.    “Cor pulmonale” and chronic cardiac-pulmonary insufficiency 7.    Amyloidosis are less frequent complications of BE.

37. EMPHYSEMA   The WHO has defined pulmonary emphysema as combination of permanent dilatation of air spaces distal to the terminal bronchioles and the destruction of the walls of dilated air spaces.

38. Classification of Emphysema
TRUE EMPHYSEMA
Centriacinar (centrilobular)
Panacinar (panlobular)
Paraseptal (distal acinar)
Irregular (para-cicatricial)
Mixed (unclassified)
B. OVERINFLATION
Compensatory overinflation
Senile hyperinflation (aging lung, senile emphysema)
Obstructive overinflation (infantile lobar emphysema)
Unilateral translucent lung (Unilateral emphysema)
Interstitial emphysema (surgical emphysema)
Bullous emphysema

39. Centriacinar (cenrolobular) emphysema
Centriacinar (cenrolobular) emphysema The distinctive feature of this type is the pattern of involvement of the lobules; the central or proximal parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared. The walls of the emphysematous spaces often contain large amount of black pigment. Moderate-to-severe degrees of emphysema occur predominantly in heavy smokers and coal workers’ pneumoconiosis , often in association with chronic bronchitis.

40. Panacinar emphysema
Panacinar emphysema occurs with loss of all portions of the acinus from the respiratory bronchiole to the alveoli. This pattern is typical for alpha-1-antitrypsin deficiency.
Panacinar emphysema produces voluminous lungs, often overlapping the heart and hiding it when the anterior chest wall is removed.
Lungs is pale pink color.
The crunch takes place when the lungs are cuted; the pitish appears after finger’s pressure.  

41. Bullous emphysema
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.

42. Microscopic examination
The abnormal fenestrations in the walls of the alveoli.
The complete destruction of septal walls.
The distribution of damage within the pulmonary lobule.
Adjacent alveoli fuse, producing even larger abnormal airspaces.
The respiratory bronchioles and vessels of the lung are deformed and compressed by the emphysematous distortion of the airspaces.
Capillary's reducing may lead to the development of the capillary-alveolar block and pulmonary insufficiency.

43. Pathogenesis of emphysema ·       Disease is accompanied with destruction of elastic and collagen fibers of lungs due to action of leukocytes proteases (in inflammation). ·       Thus, emphysema is seen to result from the destructive effect of the high protease activity in subjects with low antiprotease activity. ·       Main pathogenic mechanism is genetically determined deficiency of alpha-1-Antitripsin

44. BRONCHIAL ASTHMA (BA)
Asthma is a disease of airways that is characterized by increased responsiveness of the tracheobronchial tree to a variety of stimuli resulting in widespread spasmodic narrowing of the air passages which may be relieved spontaneously or by therapy.

45. BRONCHIAL ASTHMA (BA) ·        A severe and unremitting type of the disease termed status asthmaticus may prove fatal. ·        BA has traditionally been divided into two basis types: 1.      Extrinsic asthma: there is typically an association with atopy (allergies) mediated by type 1 hypersensitivity, and asthmatic attacks are precipitated by contact with inhaled allergens. This form occurs most often in childhood. 2.      Intrinsic asthma: asthmatic attacks are precipitated by respiratory infections, exposure to cold, exercise, stress, inhaled irritants, and drugs such as aspirin. Adults are most often affected.

46. The classic asthmatic attack lasts up to several hours and is followed by prolonged coughing; the raising of copious mucous secretions provides considerable relief of the respiratory difficulty. In some patients, these symptoms persist at a low level all the time. In its most severe form, status asthmaticus, the severe acute paroxysm persists for days and even weeks, and, under these circumstances, ventilatory function may be so impaired as to cause severe cyanosis and even death.

47. This cast of the bronchial tree is formed of inspissated mucus and was coughed up by a patient during an asthmatic attack. The outpouring of mucus from hypertrophied bronchial submucosal glands, the bronchoconstriction, and dehydration all contribute to the formation of mucus plugs that can block airways in asthmatic patients.

48. Histologic findings
of BA
1. Thickening of the basement membrane of the bronchial epithelium; 2. Edema and inflammatory infiltrate in the bronchial walls, with a prominence of eosinophils; 3. An increase in size of the submucosal glands; 4. Submucosa widened by smooth muscle hypertrophy;
5. Bronchitis and Emphysematous changes.

49. These lungs appear essentially normal, but are normal-appearing because they are the hyperinflated lungs of a patient who died with status asthmaticus.

50. Idiopathic pulmonary fibrosis
Diffuse interstitial fibrosis occurs as a result of different pulmonary diseases such as pneumoconiosis, hypersensitivity pneumonitis (“farmer's lung”, “bird fancier's disease”, “silo filler's disease”) and collagen-vascular disease. It is so called “idiopathic pulmonary fibrosis” or “cryptogenic fibrosing alveolitis” or “chronic interstitial pneumonitis”

51. PATHOGENESIS
The pathogenesis of idiopathic pulmonary fibrosis is unknown and the condition is diagnosed by excluding all known causes of interstitial fibrosis: - High levels of autoantibodies such as rheumatoid factor and antinuclear antibodies. - Elevated titres of circulating immune complexes. - Immunofluorescent demonstration of the deposits of immunoglobulins and complement on the alveolar walls in biopsy specimens.

52. Morphology
Pathological changes are bilateral and widespread. ·      Macroscopically the lungs are dense, reduced volume. ·      Honey-combing (i.e. enlarged, thick-walled air spaces) develops in parts of lung. Microscopically, changes vary according to the stage of the disease with formation of hyaline membranes. ·      There is edema and cellular infiltrate in the alveolar septa in early stage. ·      There is organization of the alveolar exudate and replacement fibrosis in the alveoli and in the interstitial septal wall with variable amount of inflammation in advanced stage.

53. Hypersensitivity pneumonitis
Hypersensitivity pneumonitis occur when there is an inhaled organic dust that produces a localized for of type III hypersensitivity (Arthus) reaction from antigen-antibody complexes.
Alveolar wall is enlarged with chronic inflammatory cells and giant cells

54. Idiopathic pulmonary fibrosis
This is an example of pulmonary fibrosis. The alveolitis that produces fibroblast proliferation and collagen deposition is progressive over time.

55. "honeycomb" lung
Regardless of the etiology for restrictive lung diseases, many eventually lead to extensive fibrosis. The gross appearance, as seen here in a patient with organizing diffuse alveolar damage, is known as "honeycomb" lung because of the appearance of the irregular air spaces between bands of dense fibrous connective tissue.
                   
             

56. Diffuse alveolar damage (DAD) in the lung.
DAD is simply the final common pathway for a variety of severe lung injuries.
In early DAD, there are hyaline membranes, as seen here, lining alveoli.
Later, type II pneumonocyte proliferation and then interstitial inflammation and fibrosis are seen.

57. PNEUMOCONIOSES
The factors which determine the extent of damage caused by inhaled dusts are:
size and shape of the particles;
their solubility and physico-chemical composition;
the amount of dust retained in the lungs;
the additional effect of other irritants such as tobacco smoke;
host factors such as efficiency of clearance mechanism and immune status of the host.

58. The tissue response to inhaled dust may be one of the following three types:
Fibrous nodules e.g. in coal-workers' pneumoconiosis and silicosis.
Interstitial fibrosis e.g. in asbestosis.
Hypersensitivity reaction e.g. in berylliosis.

59. Anthracotic pigment ordinarily is not fibrogenic, but in massive amounts (as in "black lung disease" in coal miners) a fibrogenic response can be elicited to produce the "coal worker's pneumoconiosis" seen here.

60. Silicosis
It is composed mainly of bundles of interlacing pink collagen. There is a minimal inflammatory reaction. The greater the degree of exposure to silica and increasing length of exposure determine the amount of silicotic nodule formation and the degree of restrictive lung disease. Silicosis increases the risk for lung carcinoma about 2-fold.
                   
             

61. Cor pulmonale