1. Interstial lung disease

2. Chronic diffuse interstitial restrictive lung disease
Heterogenous group of diseases characterized by Inflammation & fibrosis of most peripheral interstitial connective tissue in the alveolar walls
It concerns
alveolar epithelium,
pulmonary capillary endothelium,
basement membrane,
perivascular and perilymphatic tissues.

3. The “space” between the endothelium and the type-1 pneumocyte, is the blood air interface3

5. The Lung Interstitium
The interstitium of the lung is not normally visible radiographic- ally; it becomes visible only when disease (e.g., edema, fibrosis, tumor) increases its volume and attenuation.
The interstitial space is defined as continuum of loose connective tissue throughout the lung composed of three subdivisions:
(i) the bronchovascular (axial), surrounding the bronchi, arteries, and veins from the lung root to the level of the respiratory bronchiole
(ii) the parenchymal (acinar), situated between the alveolar and capillary basement membranes
(iii) the subpleural, situated beneath the pleura, as well as in the interlobular septae.

7. Patterns of Interstitial Lung Disease
Interstitial lung disease may result in four patterns of abnormal opacity on chest radiographs and CT scans:
linear,
reticular,
nodular,
Reticulonodular
These patterns are more accurately and specifically defined on CT

8. Patterns of Interstitial Lung Disease

9. Linear Pattern
A linear pattern is seen when there is thickening of the interlobular septa, producing Kerley lines.
Kerley B lines
Kerley A lines
The interlobular septa contain pulmonary veins and lymphatics.
The most common cause of interlobular septal thickening, producing Kerley A and B lines, is pulmonary edema, as a result of pulmonary venous hypertension and distension of the lymphatics.
Kerley A lines
Kerley B lines

10. DD of Kerly Lines: Pulmonary edema is the most common cause
Mitral stenosis
Lymphangitic carcinomatosis
Malignant lymphoma
Congenital lymphangiectasia
Idiopathic pulmonary fibrosis
Pneumoconiosis
Sarcoidosis

11. 11

12. b. Reticular Pattern
A reticular pattern results from the summation or superimposition of irregular linear opacities. The term reticular is defined as meshed, or in the form of a network. Reticular opacities can be described as fine, medium, or coarse, as the width of the opacities increases. A classic reticular pattern is seen with pulmonary fibrosis, in which multiple curvilinear opacities form small cystic spaces along the pleural margins and lung bases (honeycomb lung)

13. This 50-year-old man presented with end-stage lung fibrosis
PA chest radiograph shows medium to coarse reticular
B: CT scan shows multiple small cysts (honeycombing) involving predominantly the subpleural peripheral regions of lung. Traction bronchiectasis, another sign of end-stage lung fibrosis.

14. c. Nodular pattern
A nodular pattern consists of multiple round opacities, generally ranging in diameter from 1 mm to 1 cm
Nodular opacities may be described as miliary (1 to 2 mm, the size of millet seeds), small, medium, or large, as the diameter of the opacities increases
A nodular pattern, especially with predominant distribution, suggests a specific differential diagnosis

15. Disseminated histoplasmosis and nodular ILD.
CT scan shows multiple bilateral round circumscribed pulmonary nodules.

16. Hematogenous metastases and nodular ILD
Hematogenous metastases and nodular ILD. This 45-year-old woman presented with metastatic gastric carcinoma. The PA chest radiograph shows a diffuse pattern of nodules, 6 to 10 mm in diameter.

17. Differential diagnosis of a nodular pattern of interstitial lung disease
SHRIMP
Sarcoidosis
Histiocytosis (Langerhan cell histiocytosis)
Hypersensitivity pneumonitis
Rheumatoid nodules
Infection (mycobacterial, fungal, viral)
Metastases
Microlithiasis, alveolar
Pneumoconioses (silicosis, coal worker's, berylliosis)

18. d. Reticulonodular pattern results
A reticulonodular pattern results from a combination of reticular and nodular opacities. This pattern is often difficult to distinguish from a purely reticular or nodular pattern, and in such a case a differential diagnosis should be developed based on the predominant pattern. If there is no predominant pattern, causes of both nodular and reticular patterns should be considered.

21. Classification of interstitial / diffuse parenchymal lung disease
Idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP/CFA)
Non-specific interstitial pneumonia (NSIP)
Desquamative interstitial pneumonia (DIP)
Respiratory bronchiolitis/interstitial lung disease (RB/ILD)
Acute interstitial pneumonia (AIP)
Lymphoid interstitial pneumonia (LIP)
Cryptogenic organising pneumonia (COP)
Environmental and occupational diseases
Pneumoconiosis eg asbestosis, silicosis
Extrinsic allergic alveolitis (EAA), for example, bird fancier’s lung

22. Classification of interstitial / diffuse parenchymal lung disease
Multisystem diseases
Connective tissue diseases, for example, systemic sclerosis,
Sarcoidosis
Wegener’s granulomatosis
Tuberose sclerosis ,lymphangioleiomyomatosis (LAM)
Drug reactions, for example, amiodarone, methotrexate, bleomycin
Rare lung diseases
Pulmonary alveolar proteinosis
Pulmonary histiocytosis
Pulmonary eosinophilia
Idiopathic pulmonary haemosiderosis

23. Chronic diffuse interstitial lung diseases
RESTRICTIVE (INFILTRATIVE)
Dyspnea, tachypnea, end inspiratory crackles without airway obstruction.
↓ CO diffusing capacity, ↓lung volume. ↓compliance.
Honey-comb lung
Secondary pulmonary hypertention
Corpulmonale

24. Chronic diffuse interstitial lung diseases
Restrictive (infiltrative)
Reduced compliance, reduced gas exchange)
Are also diffuse
Heterogeneous main categories of CILD
FIBROSING
GRANULOMATOUS
EOSINOPHILIC
SMOKING RELATED
PAP (Pulmonary Alveolar Proteinosis)
If you “squeezed” a lung with restrictive lung disease, you would note it wasn’t as “spongy” as a normal lung. This is the definition of reduced compliance. It simply will not “comply” when squeezed (or moved by respiratory motion either)! In contract to the “obstructive” lung diseases, the chest x-ray shows diffuse INCREASE in density, NOT DECREASED, usually. Compliance is NOT crepitance. Another common denominator of the “restrictive” lung diseases is that they have anatomic/functional barriers to the classic gas exchange between an endothelial cell and a type-1 pneumocyte. 24

25. 1.FIBROSING
Usual interstitial pneumonia-Idiopathic pulmonary fibrosis (UIP-IPF-CFA).
Nonspecific interstitial pneumonia / fibrosis
Cryptogenic organizing pneumonia
Connective tissue (Collagen vascular) diseases
Pneumoconioses
Drug reactions
Radiation changes 25

26. IPF (UIP/CFA)
Cobblestone pleural surface by retraction scar along interlobular septa.
Lower lobe subpleural & interlobular septal fibrosis.
Fibroblastic foci - honeycomb fibrosis

27. IPF (UIP/CFA)
Would you see a lot of scar tissue here if you did a trichrome stain? Ans: yes 27

28. NON-SPECIFIC INTERSTITIAL PNEUMONIA
Fibroblastic foci & honey combing absent.
Cellular infiltrate (lymphs & plasma cells) 28

29. Cryptogenic organizing pneumonia (cop)
Idiopathic
“Bronchiolitis obliterans organizing peumonia” BOOP
Some alveolar spaces are filled by ball of fibroblast (masson bodies) but alveolar walls are normal.
All lesion are of same age.
No intertstitial fibrosis or honeycomb lung. 29

30. Connective tissue “Collagen” vascular diseases
Rheumatoid Arthritis
SLE (“Lupus”)
Progressive Systemic Sclerosis (Scleroderma) 30

31. Pneumoconioses
Non-neoplastic lung reaction to inhalation of mineral dust or chemicals or organic materials
“Occupational”-“Coal miners lung”
1-5µm diameter particles can reach airsacs & settle in their linning.
Coal (anthracosis)
Silica
Asbestos
Be, FeO, BaSo4, Tin oxide
HAY, FLAX, Benzene, Insecticides, etc.
Because these are also classified as “irritants” which may produce a bronchitic component as well, there may also be “chronic obstructive” components to these diseases. 31

32. Pneumoconioses Coal workers peumoconiosis CWP Asymtomatic anthracosis
Simple CWP
Complicated CWP or PMF
Silicosis
Hard collagenous scars in upper lobes of lung
Eggshell calcification of lymphnodes

33. Pneumoconioses Asbestos-related disease Localized fibrous plaque
Pleural effusions
Interstitial fibrosis
Carcinoma lung
Mesothelioma
Laryngeal or colonic carcinomas

34. Coal, “bagasse”, silica nodules, and asbestos, going clockwise.34

35. 2.Granulomatous
Sarcoidosis,
Hypersensitivity peumonitis 35

36. Sarcoidosis By excluding other causes of non-caseating granulomas
Bilateral hilar LA or lung involvement in 90%.
Disordered immune regulation.
Intra-alveolar & interstitial CD4/CD8 ratio 5:1 →15:1
↑Th1 cytokine IL-2 ,IFNϫ, TNF,IL-8
-ve tuberculin test
Polyclonal hyper-ϫglobulinemia
Stellete inclusions Asteroid bodies & ,laminated calcium concretion Schumann bodies in giant cells in 60% 36

37. NON-Caseating Granulomas are the RULE
This image was “googled” from tumorboard.com, the internet’s FIRST diagnostic pathology image base which started even BEFORE there was a world wide web, when it was only a BBS.
The fact that this is a mesenteric lymph node will remind you that sarcoidosis is NOT limited to the lungs.
NON-Caseating Granulomas are the RULE
“Asteroid” bodies within these granulomas are virtually diagnostic 37

38. The classical difference between a “caseating” and a “non-caseating” granuloma, is often the difference between TB and sarcoid. Which one might culture out acid-fast bacteria? Ans: The one on the LEFT (i.e., caseating) 38

39. 3-Hypersensitivity peumonitis
(dusts, bacteria, fungi,)
farmer’s lung →thermophilic actinomycosis,
pigeon breeder’s lung →proteins derived from birds
Histology
Interstitial peumonitis
Non-caseating granulomas in 2/3rd patients
Interstitial fibrosis, honeycombing & obliterative bronchiolitis
Intra-alveolar infiltrate 39

40. 4-Smoking related Alveolar Macrophages
Desquamative Interstitial Pneumonia ( DIP )
M>>F
Cigarettes
100% Survival
Why is it called “desquamative”? Ans: …because it looks like the alveolar wall “epithelium” is peeling off into the alveolus!
Alveolar Macrophages 40

41. 4-Smoking related
Respiratory Bronchiolitis-Associated Interstitial Lung Disease
Pigmented intraluminal macrophages within Resp. bronchioles. Macrophages are similar to those in DIP.

42. 5-PAP (Pulmonary Alveolar Proteinosis)
Accumulation of intra-alveolar & intra-bronchial acellular surfactant.
Acquired (anti-GM-CSF Ab),
Congenital immediate onset neonatal respiratory distress ABCA3, SP-B,SP-C
Secondary hemopoetic & inhalation syndrome
Pulmonary edema on left, PAP (Pulmonary Alveolar Proteinosis) on the right. 42

43. END