2 Chronic diffuse interstitial restrictive lung disease Heterogenous group of diseases characterized by Inflammation & fibrosis of most peripheral interstitial connective tissue in the alveolar wallsIt concernsalveolar 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 interface 3
5 The Lung InterstitiumThe 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,ReticulonodularThese patterns are more accurately and specifically defined on CT
9 Linear PatternA linear pattern is seen when there is thickening of the interlobular septa, producing Kerley lines.Kerley B linesKerley A linesThe 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 linesKerley B lines
10 DD of Kerly Lines: Pulmonary edema is the most common cause Mitral stenosisLymphangitic carcinomatosisMalignant lymphomaCongenital lymphangiectasiaIdiopathic pulmonary fibrosisPneumoconiosisSarcoidosis
12 b. Reticular PatternA 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 reticularB: 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 patternA nodular pattern consists of multiple round opacities, generally ranging in diameter from 1 mm to 1 cmNodular 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 increasesA nodular pattern, especially with predominant distribution, suggests a specific differential diagnosis
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 SHRIMPSarcoidosisHistiocytosis (Langerhan cell histiocytosis)Hypersensitivity pneumonitisRheumatoid nodulesInfection (mycobacterial, fungal, viral)MetastasesMicrolithiasis, alveolarPneumoconioses (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.
22 Classification of interstitial / diffuse parenchymal lung disease Multisystem diseasesConnective tissue diseases, for example, systemic sclerosis,SarcoidosisWegener’s granulomatosisTuberose sclerosis ,lymphangioleiomyomatosis (LAM)Drug reactions, for example, amiodarone, methotrexate, bleomycinRare lung diseasesPulmonary alveolar proteinosisPulmonary histiocytosisPulmonary eosinophiliaIdiopathic 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 lungSecondary pulmonary hypertentionCorpulmonale
24 Chronic diffuse interstitial lung diseases Restrictive (infiltrative)Reduced compliance, reduced gas exchange)Are also diffuseHeterogeneous main categories of CILDFIBROSINGGRANULOMATOUSEOSINOPHILICSMOKING RELATEDPAP (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
29 Cryptogenic organizing pneumonia (cop) Idiopathic“Bronchiolitis obliterans organizing peumonia” BOOPSome 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
31 PneumoconiosesNon-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)SilicaAsbestosBe, FeO, BaSo4, Tin oxideHAY, 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 CWPComplicated CWP or PMFSilicosisHard collagenous scars in upper lobes of lungEggshell calcification of lymphnodes
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 testPolyclonal hyper-ϫglobulinemiaStellete 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 diagnostic37
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
40 4-Smoking related Alveolar Macrophages Desquamative Interstitial Pneumonia ( DIP )M>>FCigarettes100% SurvivalWhy is it called “desquamative”? Ans: …because it looks like the alveolar wall “epithelium” is peeling off into the alveolus!Alveolar Macrophages40
41 4-Smoking relatedRespiratory Bronchiolitis-Associated Interstitial Lung DiseasePigmented 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-CSecondary hemopoetic & inhalation syndromePulmonary edema on left, PAP (Pulmonary Alveolar Proteinosis) on the right.42