1. RESPIRATORY PATHOLOGY  Congenital abnormalities  Atelectasis  Acute Pulmonary Injury (eg:pulmonary oedema)  Pulmonary Infections  O bstructive P ulmonary D isease ( COPD )  Restrictive (Infiltrative) Pulmonary Disease  Vascular Pulmonary Diseases  Tumors

2. Pathology of Common Respiratory Conditions Part [3] OBJECTIVES TO DISCUSS CAUSES, PATHOGENESIS, TYPES, MORPHOLOGY,CLINICAL COURSE OF ATELETASIS BRONCHIETASIS PNEUMOCONIOSIS

3. LEARNING OUTCOMES At the end of this lecture student will be able to Define actelectasis Compare resorption actelectasis, compression actelectasis and contraction actelectasis in regards predisposing factors,etiology and morphology Define bronchiectasis Discuss the predisposing conditions,pathogenesis,gross &microscopic morphology,clinical course and prognosis of bronchiectasis Discuss the etiology, pathogenesis, basic morphology and pulmonary reaction and complications of occupational lungs diseases (pneumoconiosis- anthracosis, silicosis, asbetosis)

4. BRONCHIECTASIS permanent dilation of bronchi and bronchioles and is secondary to cycles of obstruction and infection Irreversible Dilation of Bronchi and bronchioles Caused by Destruction of Bronchial Wall Muscle and Elastic Elements

5. BRONCHIECTASIS

6. Associated with chronic necrotizing infection A characteristic symptom complex dominated by Cough expectoration of copious amounts of purulent sputum

7. ETIOLOGY & PATHOGENESIS Predisposing conditions Obstruction & infection are the major influences Obstruction is caused by Tumors Inhaled foreign bodies Mucous plugs in asthma lymph node enlargement Under these conditions, the bronchiectasis is localized to the obstructed lung segment

8. Post infectious conditions including Necrotizing pneumonia Caused by Bacteria ( Mycobacterium tuberculosis, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas ) viruses ( adenovirus, influenza virus, HIV ) fungi ( Aspergillus )

9. Congenital or hereditary conditions  Cystic fibrosis (genetic defect, abnormal viscid mucus secretion → obstruction organ passages)  Intralobar pulmonary sequestrations presence of a discrete mass of lung tissue without normal connection to the airway system  Immunodeficiency states  Primary ciliary dyskinesia  Kartagener syndrome (bronchiectasis, sinusitis, and situs inversus or partial lateralizing abnormality )

10. Other conditions :  rheumatoid arthritis  SLE  inflammatory bowel disease  post transplantation ( chronic lung rejection & chronic graft-versus-host disease after bone marrow transplantation)

11. MORPHOLOGY Gross Site : Obstructive bronchiectasis is localized to a single segment of the lungs Nonobstructive bronchiectasis may be localized or generalized

13. Size : Airways are dilated up to 4 times normal size → sufficiently dilated that they can be followed directly out to the pleural surfaces Shape :  cylindrical  fusiform  saccular Bronchial lumens : filled with thick mucopurulent secretion

16. Bronchiectasis The resected upper lobe shows widely dilated bronchi, with thickening of the bronchial walls and collapse and fibrosis of the pulmonary parenchyma

17. Bronchiectasis Cross-section of lung demonstrating dilated bronchi extending almost to the pleura

18. Histology vary with activity & chronicity of the disease In the full blown active case, intense acute & chronic inflammatory exudates desquamation of lining epithelium & extensive areas of necrotizing ulceration pseudostratification of columnar cells squamous metaplasia of remaining epithelium abscess formation chronic case – fibrosis of bronchial and bronchiolar walls  total or subtotal obliteration of lumen

19. CLINICAL FEATURES Due to accumulation of pus in dilated bronchi & bronchioles  Chronic cough with production of copious amount of purulent sputum severe, persistent, worse in morning, induced by change in posture, may be paroxysmal Purulent sputum (foul-smelling) – copious amount On standing → 3 layered sputum 1st – frothy layer 2nd – clear mucous layer 3rd – suppurated & necrotic debris, RBC

20. Chronic cough with production of copious amount of purulent sputum severe, persistent, worse in morning, induced by change in posture, may be paroxysmal Purulent sputum (foul- smelling) – copious amount On standing → 3 layered sputum 1st – frothy layer 2nd – clear mucous layer 3rd – suppurated & necrotic debris, RBC CLINICAL FEATURES Due to accumulation of pus in dilated bronchi & bronchioles

21. CLINICAL FEATURES due to inflammatory response of the lung parenchyma & pleura  Fever → febrile episodes  Chest pain due to pleuritis  Haemoptysis or sometimes bloody sputum caused by rupture of thin walled vessels situated in wall of dilated bronchioles  Other respiratory symptoms  Dyspnoea, orthopnoea, cyanosis, clubbing of fingers & toes.

22. COMPLICATIONS  Lung abscess- the necrosis destroys the bronchial or bronchiolar walls  Pneumonia – infection spread to whole lung parenchyma  Bacteremia, septicemia with metastatic abscess formation e.g. brain abscess, meningitis  Emphysema – secondary to obstruction  Secondary amyloidosis  peribronchiolar fibrosis in chronic widespread disease → increase pressure in pulmonary circulation → Cor pulmonale and cardiac failure

23. COMPLICATIONS

26. Chronic Diffuse Interstitial (Restrictive) Diseases Chronic interstitial diseases are heterogeneous group of disorders characterized predominantly by inflammation and fibrosis of the pulmonary connective tissue, principally the most peripheral and delicate interstitium in the alveolar walls

27. PNEUMOCONIOSIS Pneumoconioses are pulmonary diseases caused by mineral dust inhalation in workplace The specific types of pneumoconioses are named by the substance inhaled (e.g., silicosis, asbestosis, anthracosis)

29. PNEUMOCONIOSIS Mineral Dust-Induced Lung Disease Coal dust Simple coal workers' pneumoconiosis: macules and nodules Complicated coal workers' pneumoconiosis: PMF Coal mining Silica Silicosis Sandblasting, quarrying, mining, stone cutting, foundry work, ceramics Asbestos Asbestosis pleural effusions, pleural plaques, or diffuse fibrosis; mesothelioma; carcinoma of the lung and larynx Mining, milling, and fabrication of ores and materials; installation and removal of insulation

31. Pathogenesis The reaction of the lung to mineral dusts depends on size, shape, solubility, and reactivity of the particles PNEUMOCONIOSIS

32. Pathogenesis The development of a pneumoconiosis depends on (1) the amount of dust retained in the lung and airways (2) the size, shape, and buoyancy of the particles (3) solubility and physiochemical reactivity (4) the possible additional effects of other irritants (e.g., concomitant tobacco smoking) PNEUMOCONIOSIS

33. Pathogenesis (1)The amount of dust retained in the lungs is determined by  dust concentration in surrounding air  duration of exposure  effectiveness of clearance mechanisms PNEUMOCONIOSIS

34. Pathogenesis (2) the size, shape, and buoyancy of the particles The most dangerous particles range from 1 to 5 μm in diameter because they may reach the terminal small airways and air sacs and settle in their linings PNEUMOCONIOSIS

35. (3)The solubility and cytotoxicity of particles modify the nature of the pulmonary response Smaller particles tend to cause acute lung injury Larger particles resist dissolution and so may persist within the lung parenchyma for years - tend to evoke fibrosing collagenous pneumoconioses PNEUMOCONIOSIS

36. Pathogenesis The key factor in the gene-sis of symptomatic pneumoconioses is the capacity of inhaled dusts to stimulate fibrosis The pulmonary alveolar macrophage is a key cellular element in the initiation and perpetuation of lung injury and fibrosis PNEUMOCONIOSIS

37. The more reactive particles trigger the macrophages to release a number of products that mediate an inflammatory response and initiate fibroblast proliferation and collagen deposition PNEUMOCONIOSIS

38. Pathogenesis (4) the possible additional effects of other irritants (e.g., concomitant tobacco smoking)  tobacco smoking worsens the effects of all inhaled mineral dusts PNEUMOCONIOSIS

39. In simple coal workers’ pneumoco-niosis massive amounts of dust are inhaled and engulfed by macrophages macrophages pass into the interstitium of the lung and aggregate around the respiratory bronchioles Pathogenesis

40. In silicosis the silica particles are toxic to macrophages, which die and release a fibrogenic factor In turn, the released silica is again phagocytosed by other macrophages The result is a dense fibrotic nodule the sili-cotic nodule

41. Pathogenesis Asbestosis is characterized by little dust and much interstitial fibrosis Asbestos bodies are the classic features

43. PNEUMOCONIOSIS Coal Workers’ Pneumoconiosis Is Due to Inhalation of Carbon Particles The spectrum of lung findings in coal workers is wide, varying from (1)asymptomatic anthracosis (2)simple CWP with little to no pulmonary dysfunction (3)complicated CWP (4)progressive massive fibrosis (PMF),

44. PNEUMOCONIOSIS Morphology Anthracosis Accumulation of carbon particles in the lungs (in the connective tissue along the lymphatics, including the pleural lymphatics, or in organized lymphoid tissue along the bronchi or in the lung hilus)

45. Coal Workers’ Pneumoconiosis Morphology Simple CWP is characterized by coal macules (1 to 2 mm in diameter, consists of carbon-laden macrophages) larger coal nodules (contains small amounts of a delicate network of collagen located primarily adjacent to respiratory bronchioles

46. Complicated CWP (progressive massive fibrosis) is characterized by multiple intensely blackened scars larger than 2 cm, sometimes up to 10 cm in greatest diameter Occur on background of simple CWP by coalescence of coal nodules and generally requires many years to develop Coal Workers’ Pneumoconiosis

47. Microscopically The lesions consist of dense collagen and pigment The center of the lesion is often necrotic, most likely due to local ischemia Coal Workers’ Pneumoconiosis

48. Clinical Course Simple CWP -minor impairment of lung function Complicated CWP -cause significant respiratory impairment Caplan syndrome was first described as rheumatoid nod- ules (Caplan nodules) in the lungs of coal miners with rheumatoid arthritis Coal Workers’ Pneumoconiosis

49. Silicosis Is Caused by Inhalation of Silicon Dioxide (crystalline Silica) Silica occurs in both crystalline and amorphous forms crystalline forms (including quartz, crystobalite, and tridymite) are much more fibrogenic

50. After inhalation, the particles interact with epithelial cells and macrophages Causing activation and release of mediators IL-1, TNF, fibronectin, lipid mediators, oxygen- derived free radicals, and fibrogenic cytokines Pathogenesis

51. Silicosis SIMPLE NODULAR SILICOSIS most common form of silicosis occur in any worker with long-term exposure to silica silicotic nodules less than 1 cm in diameter (usually 2 to 4 mm)

52. Morphology slowly progressing, nodular, fibrosing pneumoconiosis Silicotic nodules are characterized grossly in their early stages by tiny, barely palpable, discrete, pale-to-blackened (if coal dust is also present) nodules in the upper zones of the lungs

53. Silicotic nodules characteristic whorled appearance, with concentrically arranged hyalinized collagen.At the periphery are aggregates of mononuclear cells,mostly lymphocytes and fibroblasts.

54. As the disease progresses, the individual nodules may coalesce into hard, collagenous scars, with eventual progression to PMF The intervening lung parenchyma may be compressed or overexpanded, and a honeycomb pattern may develop Silicosis

55. Fibrotic lesions may also occur in the hilar lymph nodes and pleura Thin sheets of calcification occur in the lymph nodes and are seen radiographically as eggshell calcification

56. Advanced silicosis (transected lung). Scarring has contracted the upper lobe into a small dark mass (arrow). Note the dense pleural thickening

57. Clinical Course Simple silico-sis  does not usually lead to significant respiratory dysfunction Pro-gressive massive fibrosis  dyspnea on exertion and later at rest  Silicosis is associated with an increased susceptibility to tuberculosis

58. Asbestos-Related Diseases Asbestos (Greek, “unquenchable”) includes a group of fibrous silicate minerals that occur as thin fibers Asbestos is a family of crystalline hydrated silicates that form fibers

60. 2 forms of asbestos a)serpentine (i.e., curly and flexible) b) amphibole (i.e., straight, stiff and brittle) Asbestosis

61. Asbestos  Causing fibrosis by interacting with lung macrophages  also functions as both a tumor initiator and a promoter

62. Morphology Asbestosis is marked by diffuse pulmonary interstitial fibrosis Characterized by the presence of asbestos bodies which are seen as golden brown, fusiform or beaded rods with a translucent center coated with an iron-containing proteinaceous material Asbestosis

63. Asbestos body

64. Asbestos bodies These ferruginous bodies are golden brown and beaded, with a central, colorless, nonbirefringent core fiber

65. Pleural plaque. The dome of the diaphragm is covered by a smooth, pearly white, nodular plaque Asbestos-related pleural plaques Large, discrete fibrocalcific plaques are seen on the pleural surface of the diaphragm

66. Which of the following inhaled pollutants is most likely to produce extensive pulmonary fibrosis? (A) Silica (B) Tobacco smoke (C) Ozone (D) Wood dust (E) Carbon monoxide (A) Silica crystals incite a fibrogenic response after ingestion by macrophages. The greater the exposure and the longer the time of exposure, the greater is the lung injury.

67. A 63-year-old male worked for 20 years in the sand- blasting business, and he used no respiratory precautions during that time. He now has increasing dyspnea without fever, cough, or chest pain. Which of the following inflammatory cell types is most crucial to the development of his underlying disease? (A) Plasma cell (B) Mast cell (C) Eosinophil (D) Macrophage (E) Natural killer (NK) cell

68. The correct answer is (D) Silica is a major component of sand, which contains the mineral quartz. The small silica crystals are inhaled, and their buoyancy allows them to be carried to alveoli. There they are ingested by macrophages, which then secrete cytokines that recruit other inflammatory cells and promote fibrogenesis. Plasma cells secrete immunoglobulins, which are not a major component of this process. Mast cells and eosinophils are prominent in type I hypersensitivity response. NK lymphocytes are more likely to be a prominent component of inflammatory processes directed against infectious agents.

69. A 75-year-old male experienced increasing dyspnoea. The microscopic appearance of the lung is shown here. This is most characteristic for (A) Anthracosis (B) Berylliosis (C) Silicosis (D) Calcinosis (E) Asbestosis

70. The answer is (E) The ferruginous bodies shown here are long, thin crystals of asbestos that have become encrusted with iron and calcium. The inflammatory reaction incited by these crystals promotes fibrogenesis and resultant pneumoconiosis. Berylliosis is marked by noncaseating granulomas. Anthracosis is a benign process seen in all city dwellers as a consequence of inhaled carbonaceous dust. Silica crystals are not covered by iron and tend to result in formation of fibrous nodules (i.e., silicotic nodules). Calcium deposition may occur along alveolar walls with a high serum calcium (i.e., metastatic calcification).

71. Which of the following morphologic changes can be seen in advanced cases of both obstructive and restrictive lung disease? (A) Marked medial thickening of pulmonary arterioles (B) Destruction of elastic tissue in the alveolar walls (C) Fibrosis of the alveolar walls (D) Hemorrhage in the alveolar lumen (E) Hyaline membranes lining the airspaces The correct answer is (A) Changes of pulmonary hypertension are characteristic for restrictive and obstructive lung diseases. This explains, for example, the occurrence of cor pulmonale and right-sided CHF in persons with chronic obstructive pulmonary disease or with pneumoconiosis

72. Atelectasis (Collapse) Atelectasis Neonatal atelectasis  incomplete expansion of the lungs Acquired atelectasis  collapse of previously inflated lung producing areas of relatively airless pulmonary parenchyma

74. Acquired atelectasis may be divided into  Resorption (or obstruction)  Compression  Contraction atelectasis ATELETASIS (Collapse)

75. Resorption atelectasis is the consequence of complete obstruction of an airway leads to resorption of the oxygen trapped in the dependent alveoli without impairment of blood flow through the affected alveolar walls lung volume is diminished the mediastinum shifts toward the atelectatic lung ATELETASIS (Collapse)

76. Airway obstruction is caused by  excessive secretions (e.g., mucus plugs) or exudates within smaller bronchi (bronchial asthma, chronic bronchitis, bronchiectasis)  postoperative states  aspiration of foreign bodies  bronchial neoplasms (rarely) ATELETASIS (Collapse)

77. Compression atelectasis results whenever pleural cavity is partially or completely filled by fluid exudate, tumor, blood, or air (pneumothorax) or with tension pneumothorax, when air pressure impinges on and threatens the function of the lung and mediastinum, especially the major vessels mediastinum shifts away from the affected lung ATELETASIS (Collapse)

78. Compression atelectasis

79. Contraction atelectasis occurs when local or generalized fibrotic changes in the lung or pleura prevent full expansion ATELETASIS (Collapse)

80. reduces oxygenation predisposes to infection collapsed lung parenchyma can be re- expanded (reversible disorder) except that caused by contraction ATELETASIS (Collapse)

81. ANY QUESTIONS?