1. Restrictive lung diseases
Acute and Chronic

2. Restrictive lung diseases (Diffuse Interstitial Lung Disease)
A heterogeneous group of disorders characterized predominantly by diffuse and usually chronic involvement of the pulmonary connective tissue

3. Fibrosis Stiff lung Which level?
principally the most peripheral and delicate interstitium in the alveolar walls
Fibrosis
Stiff lung
This result in reduced expansion of lung with reduction in total lung capacity

4. Restrictive lung diseases
Characterized by reduced compliance of the lung.
Caused by:
2. parenchymal disease: Prominent changes in the interstitium (interstitial lung disease)
1. Chest wall abnormalities
Kyphoscoliosis
sever obesity
Guilian Barrre’ syndrome
Guilian Barrre’ syndrome is an acute inflammatory demyelinating polyneuropathy , an autoimmune disease affecting the peripheral nerveous system, usually triggered by an acute infectious process.
exhibits as an ascending paralysis noted by weakness in the legs that spreads to the upper limbs
With prompt treatment by plasmapheresis or intravenous immunoglobulins, the majority of patients will regain full functional capacity.

5. Restrictive lung diseases (Interstitial lung disease)
Important signs and symptoms:
- Dyspnea.
- Hypoxia (caused by damage to the alveolar epithelium and interstitial vasculature produces abnormalities in the ventilation-perfusion ratio)
- With progressive severe hypoxia,
respiratory failure and cor pulmonale.
- Chest radiographs show diffuse infiltration by small nodules, irregular lines, or "ground-glass shadows

6. Restrictive lung diseases (Interstitial lung disease)
Chronic
chronic inflammation &fibrosis
e.g.
Pneumoconiosis
Idiopathic pulmonary fibrosis
Sarcoidosis
Hypersensitivity pneumonitis
Immune mediated: SLE
Chemical related: berylliosis
Acute
edema in acute respiratory distress syndrome
e.g.
Adult respiratory distress syndrome
Neonatal respiratory distress syndrome

7. ACUTE LUNG INJURY Adult respiratory distress syndrome (ARDS)
Progressive respiratory insufficiency caused by diffuse alveolar damage in the setting of sepsis, severe trauma, and diffuse pulmonary infections.

8. Causes of ARDS Common Causes Uncommon Causes Direct Lung Injury
Indirect Lung Injury
Common Causes
Pneumonia
Sepsis
Aspiration of gastric contents
Severe trauma with shock
Uncommon Causes
Pulmonary contusion
Cardiopulmonary bypass
Fat embolism
Acute pancreatitis
Near-drowning
Drug: bleomycin
overdose heroin
Inhalational injury
Transfusion of blood products
Reperfusion injury after lung transplantation
Uremia

9. Causes of ARDS
ARDS can be a manifestation of sever acute respiratory syndrome (SARS)
SARS is a coronavirus that destroys the type II pneumocytes and causes diffuse alveolar damage

10. ACUTE LUNG INJURY Adult respiratory distress syndrome (ARDS)
Diffuse alveolar damage with result in increase in alveolar capillary permeability
 leakage of protein-rich fluid into alveoli
 formation of an intra-alveolar hyaline membrane composed of fibrin and cellular debri

11. ACUTE LUNG INJURY ARDS
The pulmonary infiltrates in acute lung injury are usually caused by damage to the alveolar capillary membrane by neutrophils or by ROS
Result in noncardiogenic pulmonary edema.

12. Acute Respiratory Distress Syndrome Morphology
intra-alveolar hyaline membrane

13. Acute Respiratory Distress Syndrome Morphology
There is marked proliferation of type II pneumocytes in an attempt to regenerate the alveolar lining.
Resolution is unusual

14. Acute Respiratory Distress Syndrome fade
organization of the fibrin exudates, with resultant intra-alveolar fibrosis.
Marked thickening of the alveolar septa ensues, caused by proliferation of interstitial cells and deposition of collagen.

15. ACUTE LUNG INJURY ARDS Clinical Manifestations
acute onset of dyspnea
decreased arterial oxygen pressure (hypoxemia)
development of bilateral pulmonary infiltrates on radiographs
absence of clinical evidence of primary left-sided heart failure
Manifestations appear within 72 hours of the initiating insult

16. Acute Respiratory Distress Syndrome (ARDS)
Could progress to life-threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia that is refractory to oxygen therapy and that may progress to multisystem organ failure.

17. Clinical Course Historically, mortality rates approached 100%.
Despite improvements in supportive therapy the mortality is still about 60%.
Predictors of poor prognosis in ARDS include :
advanced age,
underlying bacteremia (sepsis)
the development of multisystem (especially cardiac, renal, or hepatic) failure.

18. RESPIRATORY DISTRESS SYNDROME OF THE NEWBORN
hyaline membrane disease
Pathogenesis RDS
is a disease of premature infants.
It occurs in about 60% of infants born at less than 28 weeks of gestation
Other causes:
maternal diabetes
cesarean section before the onset of labor
twin gestation.

20. Hyaline membrane disease

22. Chronic restrictive lung disease (Chronic interstitial lung disease)
Are a heterogenous group with little uniformity regarding terminology and classification.

23. Chronic restrictive lung disease
Major Categories of Chronic Interstitial Lung Disease (CILD)
-Fibrosing:
Pneumoconiosis
Usual interstitial pneumonia (idiopathic pulmonary fibrosis) Cryptogenic organizing pneumonia
Associated with collagen vascular diseases
Drug and Radiation Reactions
-Granulomatous: Sarcoidosis
Hypersensitivity pneumonitis.
Wegener’s granulomatosis
-Eosinophilic granuloma
-Smoking related: Desquamative interstitial pneumonia
Respiratory bronchiolitis-associated interstitial lung disease

24. Chronic Interstitial Lung disease CILD
Many entities are of unknown cause and pathogenesis
Similar clinical signs, symptoms, radiographic alterations and pathophysiologic changes.
Patient have reduced forced vital capacity, however the FEV1/ FVC is normal
Account for about 15% of non-infectious lung diseases.

25. Idiopathic pulmonary fibrosis Hypersensitivity pneumonitis
CILD
Idiopathic pulmonary fibrosis
Hypersensitivity pneumonitis
Smoking related
Pneumoconiosis

26. Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) (Usual interstitial pneumonia) UIP

27. Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) (Usual interstitial pneumonia) UIP
A clinicopathologic syndrome with characteristic radiologic, pathologic and clinical features.
Radiology: Bilateral lung nodular infiltratre
Histology: diffuse interstitial fibrosis and inflammation.
Clinical features:
Dyspnea, advanced cases result in sever hypoxemia and cyanosis.
Males are more affected than female
2/3 of pt. older than 60 years

28. Pathogenesis
Some form of alveolar wall injury result in interstitial edema and alveolitis. Type I pneumocyte is more susceptible to injury. Type II pneumocyte hyperplasia (regenerate). Fibroblast proliferation with progressive fibrosis of intra-alveolar exudate and interalveolar septa. IgG deposits are seen in alveolar wall.
FGF, TGF-, PDGF
IL-8 leukotriens

29. Morphology of IPF Gross -The lungs are firm.
-Pulmonary edema.
The morphologic changes vary according to the stage of the disease.
Early cases:
-Intraalveolar exudate.
-Hyaline membranes.
-Infiltration of the alveolar
septa with mononuclear
cells.
-Hyperplasia of type II
pneumocytes -

30. Morphology of IPF Advancing disease:
-Organization of the intraalveolar exudates by fibrous tissue.
-Thickening of the alveolar septa owing to fibrosis and variable amounts of inflammation.
-Alternating areas of fibrosis and normal tissue.
- Geographic variation
- Temporal variation
In the end, the lung consists of spaces lined by cuboidal or columnar
epithelium separated by inflammatory fibrous tissue (honeycomb lung).

31. honeycomb lung

32. Prognosis of IPF Gradual onset of dyspnea with respiratory difficulty.
Hypoxemia and cyanosis.
Cor pulmonale and cardiac failure may result.
The progression in individual cases is unpredictable.
The median survival is about 2 to 4 years.

33. Idiopathic pulmonary fibrosis Hypersensitivity pneumonitis
CILD
Idiopathic pulmonary fibrosis
Hypersensitivity pneumonitis
Smoking related
Pneumoconiosis

34. Smoking related CILD Desquamative interstitial pneumonia
Age : fourth decade
Dyspnea and cough
Complete recovery after
cessation of smoking

35. Idiopathic pulmonary fibrosis Hypersensitivity pneumonitis
CILD
Idiopathic pulmonary fibrosis
Hypersensitivity pneumonitis
Smoking related
Pneumoconiosis

36. Hypersensitivity pneumonitis
An immunologically mediated inflammatory lung disease that primarily affects the alveoli and is therefore often called allergic alveolitis.
Hypersensitivity to inhaled antigens in the form of organic substance: moldy hay, e.g. farmer’s lung, humidified lung or pigeon breeder’s lung.

37. Hypersensitivity pneumonitis
May present either as an acute reaction with fever, cough, dypsnea and constitutional complains 4 to 8 hours after exposure or
as a chronic disease with insidious onset of cough, dyspnea, malaise and weight loss.

38. Hypersensitivity pneumonitis
Acute form
result from the combination of:
- A direct irritant effect.
- Activation of the complement pathway
- Immune complex
Chronic form
of the disease is mediated by delayed hypersensitivity reactions.

39. Selected cause of hypersensivity pneumonitis
Syndrome Exposure Antigens
Plant product:
Farmer’s lung Moldy hay Micropolyspora faeni.
Bagassosis sugar cane Thermophilic Actinomycet
Maple bark disease Maple bark Cryptostroma Corticale
Animal products:
Pigeon breeder’s lung Pigeons Pigeon serum proteins
Chemicals:
Trimelitic anhydried Chemical industry Haptenated protein
pneumonia

40. Morphology of hypersensitivity pneumonitis
Mononuclear cell infiltrates in the alveoli and alveolar walls and around terminal bronchioles. Interstitial non-caseating granulomas reflecting type IV hypersensitivity reaction are present in more than two thirds of cases.
Diffuse interstitial fibrosis in chronic exposure.

41. Prognosis of hypersensitivity pneumonitis
Clinical course is variable
Early, stop antigen exopsure  pt. improve
Late, Diffuse interstitial fibrosis in chronic exposure  no improvement

42. Idiopathic pulmonary fibrosis Hypersensitivity pneumonitis
CILD
Idiopathic pulmonary fibrosis
Hypersensitivity pneumonitis
Smoking related
Pneumoconiosis

43. Pneumoconiosis
Non-neoplastic lung reaction to inhalation of mineral dusts.
Most common dusts are coal dust, silica, asbestos and beryllium.

44. Pneumoconiosis Pathogenesis
The development of pneumoconiosis is dependent on:
- The amount of dust retained in the lung and airways.
a. Concentration of the dust in the ambient air.
b. Duration of the exposure.
c. Effectiveness of the clearance mechanisms.
- The size (1-5) shape.
- Their solubility and physiochemical activity.
- The possible additional effects of other irritants, tobacco
smoking.
The particles are impacted at alveolar duct macrophage, accumulate inflammatory response fibrosis.

45. Coal worker’s pneumoconiosis (CWP)
Silicosis
Asbestosis

47. Coal worker’s pneumoconiosis (CWP)
Occurs in coal workers after many years of underground mine work.
Two forms:
- The simple form:
- Focal aggregations of coal dust-laden macrophages
(coal macules, 1 to 2 mm) mainly in upper lobes.
- Patients have slight cough and blackish sputum.
- emphysema ( smoking related).
- The complicated form:
With heavier pulmonary burdens of coal dust, fibrous scarring appears (complicated CWP) also callled progressive massive fibrosis (PMF).

48. Coal worker pneumoconiosis
Morphology:
Complicated CWP:
-Black scars exceed 2 cm in diameter some times up to 10 cm
-It consists of dense collagen and carbon pigments.
-Cor pulmonale.
-Miners who have rheumatoid arthritis and PMF are called Caplan’s syndrome.

49. Coal worker pneumoconiosis
Clinical course:
CWP is usually benign disease with little symptom
Minor cases progress to PMF
No increased risk to bronchogenic carcinoma

50. Coal worker’s pneumoconiosis (CWP)
Silicosis
Asbestosis

51. Silicosis Long exposure to silica particles.
Nodular densely fibrosing pneumoconiosis.
Encountered in a diversity of industries: mining of gold, tin, copper and coal, sandblasting, metal grinding, ceramic manufacturing, drilling and tunneling.
Pathogenesis:
Crystalline silica is highly fibrogenic.
Scattered lymphocytes and macrophages are drawn rapidly with fibrosis.
Some particles are transported to lymph nodes.

52. Morphology of Silicosis
Tiny collagenous nodules that enlarge forming stony-hard large fibrous scars usually in the upper lobes.
The lung parenchyma between the scars may be compressed or emphysematous.
Calcifications may appear (eggshell calcification) .
Similar collagenous nodules within the lymph nodes.
Fibrous pleural plaques may develop.

53. Morphology of Silicosis
Micro:
-Hyalinized collagen fiber surround an amorphous center (fibrous nodules).
- Scarring progress to PMF.
-Scarring extending and encroching the pulmonary arteries.
-Cor pulmonale.

54. Clinical features of Silicosis
depend on form of silicosis

55. Forms of Silicosis Acute silicosis: Chronic silicosis:
results from exposure to high dose of silica. Fluid in alveoli.
Pt. Have rapid onset of tachypnea, cough and repiratory failure.
Chronic silicosis:
Inhalation of silica for long time with fibrotic nodules ( present in upper lobe of lung & in subpleural spaces
Complicated silicosis:
Progression of chronic silicosis with PMF with chronic hypoxia
Other pulmonary disease:
Increased susceptibility to TB
Caplan syndrome ( uncommon)
Lung cancer

56. Silica and lung cancer
The relationship between silica and lung cancer has been a contentious issue, but in 1997, based on evidence from several epidemiologic studies, the International Agency for Research on Cancer concluded that crystalline silica from occupational sources is carcinogenic in humans.
However, this subject continues to be controversial.

57. Coal worker’s pneumoconiosis (CWP)
Silicosis
Asbestosis

58. Asbestosis
Asbestos is a family of crystalline hydrated silicates with a fibrous geometry.
Two forms:
Serpentine chrysotile (flexible fiber), more common
Amphibole (straight and stiff fiber), more pathogenic
Both forms are fibrogenic.

59. Asbestosis Inhalation of asbestos leads to: - Asbestos pneumoconiosis.
- Pleural effusion.
- Pleural adhesions.
- Parietal pleural fibrocalcific plaques.
- Increased incidence of mesothelioma, bronchogenic carcinoma, laryngeal cancer.
These consequences occurs decades after exposure has ended.
An increased incidence of asbestos-related cancers in family members of asbestos workers has alerted the general public to the potential hazards of asbestos in the environment.

60. Morphology Of Asbestosis diffuse pulmonary interstitial fibrosis
scarring containing asbestos bodies (ferrougenous bodies).

61. Pleural plaque in asbestos
Parietal pleura over dome of diaphragm

62. Asbestosis
In asbestosis, pt. develop progressively worsened dyspnea with cough and sputum progressing to cor pulmonale and death.
Both bronchogenic carcinoma and mesothelioma develop in workers exposed to asbestos.
The risk of bronchogenic carcinoma is fivefold and for mesothelioma is 1000 fold greater.
The risk of bronchogenic carcinoma in 50 X increased in smoking asbestos workers (but not that of mesothelioma)

64. Malignant Mesothelioma
Rare cancer of mesothelial cells
Arise from parietal or visceral pleura
Can arise from peritoneum and pericardium
50% of pt. have history of exposure to asbestos at work
It also appeared in relatives of asbestos worker or in people living near asbestos factory
The latent period between exposure and malignant mesothelioma is long (25 to 40 years)
Nearly all cases are related to amphibole asbestos
These minerals cannot be removed from the lung and the risk for malignant mesothelioma is life long
Simian virus 40 (SV40) T antigen is found in 60 to 80% of malignant mesothelioma
Characteristic E/M finding : numerous long microvilli on cell surface

65. SUMMARY
ARDS is a clinical syndrome of progressive respiratory insufficiency caused by diffuse alveolar damage
The setting are :
sepsis, severe trauma, and diffuse pulmonary infections.
There is an imbalance of pro- and anti-inflammatory mediators causing acute inflammatory injury to the alveolar epithelium and capillary endothelium.
Neutrophils and their products have a crucial role in the pathogenesis of ARDS.
The characteristic histologic picture is that of alveolar edema, epithelial necrosis, accumulation of neutrophils, and presence of hyaline membranes lining the alveolar ducts.

66. Idiopathic pulmonary fibrosis Hypersensitivity pneumonitis
CILD
Idiopathic pulmonary fibrosis
Usual interstitial pneumonia
Pneumoconiosis
Coal worker’s pneumoconiosis (CWP)
Silicosis
Asbestosis
Hypersensitivity pneumonitis
Desquamative interstitial pneumonia