15/5/2016. Pathology #06. Restrictive lung diseases. Mohammed Al-Qudah Farah Behari

Transcription

1 15/5/2016 Pathology #06 Restrictive lung diseases Mohammed Al-Qudah Farah Behari

2 The doctor started with a brief revision of the last lecture: Obstructive lung diseases are mainly diseases of expiration while restrictive lung diseases are diseases of inspiration. However, with time, obstructive might involve inspiration and restrictive might involve expiration. But stick to the main concept of each. The hallmark of restrictive and obstructive diseases is that the ratio of FVC to FEV remains the same (normal) in restrictive diseasesand decreases in obstructive diseases. Restrictive lung diseases are mainly caused by the loss of lung compliance; the lungs will not be able to take air as usual and this isan inspirational defect. Keep in mind that the lung is like a sponge, it opens and closes easily due its compliance. Inspirational defects are worse than expirational defects because in expirational defects you will at least still be able to take enough oxygen for the needs of the body unlike inspirational defectswhere you won t be able to take enough oxygen so the manifestation will start earlier. Any disease whether it s a primary lung disease or a non-lung disease that affects the lung compliance will end up by causing a restrictive pattern of disease. Examples on non-lung diseases which cause restrictive patterns are: changes in bones, chest wall defects, and obesity. Patients with non-lung diseases ending up in a restrictive lung disease are presented with abnormal breathing, a normal FVC: FEV ratio and the biopsy will not reveal any pathological issue. The hallmark of restrictive lung disease is in the activation of macrophages; macrophages will fail in managing the situation for a reason or another leading to an inability of damaging the microorganism and antigens resulting in an over production of interleukins, tissue necrosis factor and other factors that will initiate inflammation and fibrosis. 1 P a g e

3 Restrictive lung diseases were categorized into 4 main categories: 1. Firbosing: Idiopathic pulmonary fibrosis (UIP):the patient presents with severe hypoxia and cyanosis so you put him in an oxygen tent to be supplied with his oxygen needs, however the patient will die in 2 to 4 years. Patients with this disease will also be presented with clubbing and dry crackles (damaged alveoli are closed and hard andthey ll open when you inspire air, this will produce the crackle). The only cure for this condition is lung transplantation. When you take an open biopsy of a patient you will see patchy involvement affecting the upper and lower lobes of the lung although it s a diffuse disease. In a biopsy there can be seen different patterns of involvement (in the same biopsy piece you might see diseased and undiseased areas) and different ages of involvement (you can see old or recent lesions). Nonspecific interstitial pneumonia : There will be no heterogeneity. 2. Granulomatous 3. Eosinophilic 4. Smoking related New lecture: Smoking Fibrosing related Granulomato us Eosinophilic Sarcoidosis Hypersensitivity pneumonitis Pneumoconiosis Drugs and radiation associated Anthracosis Silicosis Asbestos induced lesions 2 P a g e

4 5) Pneumoconiosis A.Pulmonary Anthracosis (Coal Worker s Pneumoconiosis) : Isthe most common pattern of coal-related diseases. In general this disease ends up with fibrosis due to coal, silica, and asbestos exposure. Coal miners and smokers will inhale carbon and carbon will accumulate in the connective tissue of their lungs (it will be engulfed by macrophages in the CT specifically). On microscopic examination,we will be able to see this pigment in the lungs. This is a photomicrograph showing carbon inside the macrophages of the connective tissue. Anthracosis could be: 1. SimpleCWP: you will either have a macule (a cluster of macrophages filled with carbon) or a nodule (a larger cluster of macrophages filled with carbon and collagen). Because this disease is seen in smokers, this simple pattern of diseasewill involve the upper lobes of the lung and will be associated with centrilobular emphysema. 2. Comlicated CWP : where the nodules open and join with each other (coalescence of the nodules) forming a large mass (2-10 cm) causing an obstruction. This complicated pattern of the disease happens on a background of simple CWP and requires years to develop. 3. Progressive massive fibrosis: with time massive fibrosis will develop and this is the hallmark of the disease. The patient will not have severe symptoms unless this massive fibrosis develops so this particular stage is what leads to restrictive lung disease. 3 P a g e

5 These lesions (macules and nodules) will not increase the risk of lung cancer; however, carbon that resulted in these lesions will cause lung cancer. In other words, if a person is having nodules in his lungs or not, he will be at the same risk of developing lung cancer. VERY IMPORTANT: the stage of progressive massive fribrosis(which will develop if the patients didn t stop smoking) is what causes the interstitial(restrictive) lung disease. Macules and nodules will not cause the disease but will result in obstructive symptoms or a mass inside the lung. B. Silicosis: The commonest occupational lung disease People working with ceramic, glass, or sand will inhale a lot of crystalline silica. The most common type of silica is quartz but there are other amorphous types of silica that could be inhaled. Acute phase of silicosis: Acute heavy exposure of silica will cause acute respiratory distress syndrome (ARDS) and will not cause lung fibrosis. In this case the person is exposed to a huge amount of silica which will accumulate inside the alveolar spaces and initiate a reaction causing acute failure. Chronic phase of silicosis: it will take years of exposure to silica for lung fibrosis to develop. How does fibrosis develop?when silica is inhaled, it will reach the alveolar spaces and will be engulfed by macrophages, however these macrophages won t be able to degrade silica and will release them again into the alveolar spaces together with interleukins and TNF. These chemicals will initiate inflammation and fibrosis.damage will occur with time. Someone asked a question which I couldn t really hear but this was the answer: IF the exposure is very heavy, silica will accumulate inside the alveoli initiating a response (release of macrophages and neutrophils), there will be no proper gas exchange so the large amount of toxins together with the inflammatory cells will remain in the lungs causing an acute respiratory distress syndrome. However, the person might have minimal exposure to silica instead of heavy exposure but for a long period of time (20 years) and develop a chronic disease and fibrosis. 4 P a g e

6 Pathology of silicosis: In most of the cases, there will be small nodules (4 ml) in the upper lobe and these nodules might become larger (10 cm) with time. This is the appearance of a large silicotic nodule under the microscope : concentrically arranged hyalinized collagen fibers surrounding an amorphous acellular center Patients with silicosis will develop with time fibrosis and restrictive lung disease. You can only treat this disease by performing a lung transplant. Clinical picture of silicosis: Many patients are asymptomatic. Most patients do not develop shortness of breath until late in course (after PMFprogressive massive fibrosis is present). It is associated with an increased risk of TB (tuberculosis) and lung cancer. C. Asbestos induced lesions: Found a lot in people working in ship industry Family members of those workers are also at a high risk (their wives and children) of having this disease. Within 10 years the person might have symptoms of asbestosis (long latency but less than that of silicosis) Confirmed diagnosis by asbestos bodies in the lungs. There are two forms of asbestos: Serpentine: the most common Amphibole : straight & stiffpatterns 5 P a g e

7 These asbestos bodies (Ferruginous Bodies) are found in the lung tissue, lung pleura, sputum, and in bronchial secretions. They are composed of asbestos fibers+ proteins+ iron. The iron is positive for per l stain, it turns blue. Asbestos bodies in macrophages Ferrugiounoius asbestos body Any patient having asbestos in his lung or body will develop one of the following diseases: 1. Asbestosis: which is a chronic diffuse interstitial fibrosis of the lower lobes (remember silica and carbon where in the upper lobes) resulting in an end stage disease and death. 2. Pleural effusion 3. Pleural plaque: the most common disease associated with asbestosis, this includes a plaque found on the surface of the pleura. Asbestos lesions increase the risk of malignant mesothelioma, lung cancer, and laryngeal and stomach colon cancer. These are the pleural plaques once you remove them from the lungs of a patient.6- Drug & Radiation Induced Pulmonary Diseases. 6 P a g e

8 The largest pattern caused by drugs is fibrosis. Any medication can have a complication, and there are certain medications that cause fibrosis of the lung tissue, therefore don t abuse medications. The other pattern is interstitial lung disease. Granulomatous reaction: 1. Sarcoidosis Is a disease that affects US black/african American people and is seen in non-smokers. A multisystem disease that might affect the lung, hilar lymph nodes, skin, eyes, salivary glands, liver and any other organ. The commonest areas involved in sarcoidosis are the lung tissue and the hilum of the lungs. Usually sarcodiosis is a cause of interstitial lung disease Etiology: an abnormal immune response of a genetic background, there will be an imbalance between the ratio of CD4 and CD8 lymphocytes in the blood (the relation between CD4 and CD8 is decreased and this is revealed by taking a blood sample) and an increase of T cells in the alveolar lavage. Thislarge amount of T cells in the alveolar lavage will implicate that this is a T cell disease while it s not. The hall mark of this disease: when you take a lung biopsy, you will find non-caseating granulomas with giant cells containingschaumann and asteroid bodies. Remember: Caseating granulomas be a fungal infection) TB and chronic pneumonia(could Non-caseating granuloms Sarcoidosis Those schaumann (layers of calcification) and asteroid bodies (star-fish shaped) which are sometimes seen in giant cells in the granulomas are not diagnostic of sarcodiosis but will suggest that this is sarcodiosis, it will push you towards diagnosis of sarcoidosis, more than other differentials. 7 P a g e

9 This disease is lung labeled although it can affect many different organs because in most cases (79-90%) of sarcoidosis hilar lymphadenpathy will be observed whichever organ was involved. 90% of the patients will have lung interstitial involvement. This lung interstitial involvement might be severe enough to cause granulomas obstructing the whole lung tissue leading to restrictive lung disease. Not every patient having sarcodiosis will have restrictive lung disease. Patients who have massive sarcodiosis will also have abnormal compliance of the lung which will end up with a restrictive lung disease. Pathology: If there is lung involvement with ocular and lacrimal gland involvement, this is called SICCA syndrome. If the parotid gland is involved however it s called MIKULICZ Syndrome. Lung involvement + Occular involvement + Lacrimal Gland=SICCA Syndrome Lung involvement+ Parotid involvement =MIKULICZ Syndrome Sarcoid granulomas 8 P a g e

10 Schaumann bodies NON-Caseating Granulomas are the RULE Asteroid bodies within these granulomas are virtually diagnostic Clinical picture:most sarcodiosis patients are asymptomatic because the disease will not be severeat first, there will be hilar lymphadenopathies but no further complications. If we started having a more severe disease with time and ended up with granulomas all over the lung, then we will enter the phase of restrictive lung disease. This happensin only10 to 15% of the patients. In order to confirm your diagnosis of sarcoidosis, you need to exclude all other causes of granulomas and this is done using the kaveim test. 9 P a g e

11 Additional information that the doctor asked me to look up: The Kveim test, Nickerson-Kveim or Kveim-Siltzbach test is a skin test used to detect sarcoidosis, where part of aspleen from a patient with known sarcoidosis is injected into the skin of a patient suspected to have the disease. If non-caseating granulomas are found (4 6 weeks later), the test is positive. Why is hypercalcemia a complication of sarcoidosis? Hypercalcemia is a well-described complication. Hypercalcemia is caused by the increased conversion of 25- hydroxyvitamin D to 1,25- dihydroxyvitamin D [1,25(OH)2D] by the enzyme 25-hydroxyvitamin-D 1a-hydroxylase (CYP27B1) in pulmonary alveolar macrophages. 1,25(OH)2D increases serum calcium primarily through increasing intestinal calcium absorption, but it also acts at bone and kidney to increase serum calcium 2. Hypersensitivity pneumonitis : The other pattern of granulomatous disease causing restrictive lung disease It s usually a type 3 or type 4 hypersensitivity reaction Remember sarcidosis is a type 3 and 4 hypersensistivity reaction. Asthma is type 1 A patient with asthma due to a certain allergen (this allergen by inducing type 1 hypersensitivity reaction has resulted in asthma), might end up with hypersensitivity pneumonitis because with time this same allergen will initiate type 3 hypersensitivity reaction. Those patients once diagnosed with hypersensitivity pneumonitis might have acute attacks caused in the same way as asthma so they are given ventolin as a treatment. So the same allergen gradually ends up causing a chronic illness (hypersensitivity pneumonitis).the presentation of this disease depends on the duration & intensity of exposure: acute, subacute or chronic 10 P a g e

12 The doctor mentioned this case: A female patient in her mid 30s had a granulomatous disease and was checked for all antigens that might have caused this irritation but nothing was found. Then by examining her clinical history, it was discovered that she was addicted to her hair spray and that resulted in hypersensitivity pneumonitis. Hypersensitivity pneumonitis is an immunologically mediated disorder affecting the airways and the interstitium and isacquired byfarmers, from pigeons, ACs, etc The allergen might cause an acute response (direct irritant effect) which is asthma or a chronic disease (hypersensitivity pneumonitis) and features of this disease will take time to develop. In chronic disease cases, there will be patchy interstitial inflammatory infiltrates in terminal bronchioles andvague granulomas around the bronchial tree and the vessels; so biopsies taken from those patients will show fibrosis and vague (small) granulomas. Remember large granulomas are seen in patients with sarcodiosis. Eosinophilic diseases are diseases associated with high levels of eosinophils and will end up causing a restrictive pattern of diseases. That s all you need to know about them. Smoking related diseases: Smokers usually have many diseases in their lungs including emphysema, chronic bronchitis, bronchilitis, and desquamativeinterstitial pneumonia (desquamative: we will have macrophages filled with carbon and not squamous cells and those macrophages will fill the alveolar spaces). DIP is not the same as carbon related diseases where macules and nodules (carbon without macrophages will accumulate) are found in the soft tissue or the interstitium of the lungs. Sometimes these smoking related disease are so severe that patient presents with ARDS (the patient in this case might have been smoking and for a reason or another he has some other disease so this one cigarette of smoke will cause a sudden gush of macrophages in the alveoli and result in respiratory failure.) These patients usually will have a good, dramatic response to steroids. 11 P a g e

13 Summary: We have talked about: How we can differentiate between restrictive and obstructive lung diseases by performing the pulmonary function test ( the test for obstructive will reveal a decreased ratio while for restrictive the ratio will be normal). The main patterns that cause restrictive lung disease which are fibrosing, granulomatous, eosinophilic, and smoking related and we have discussed each. Diffuse lung diseases Obstructive Restrictive Asthma Emphysema Chronic bronchitis Bronchoesctasis In all obstructive diseases, the bronchial tree will be involved except in emphysema where acini are affected instead of the bronchial tree. Most of these diseases are associated with smoking, mainly chronic bronchitis and emphysema. For emphysema, we have centriacinar and panacinar. Centriacinar Smoke will be concentrated at the entrance of the acini and result in their damage, this will lead to an imbalance between oxidant and antioxidant proteases. High protease level will cause destruction of the acini Panacinar Genetic massive destruction of the alveoli will cause this kind of emphysema. There will be a genetic deficiency in anti1-antitrypsin; this defcould also be acquired 12 P a g e

14 Patients having pure emphysema are pink puffers; they will not have cyanosis early in life. Their alveoli will be destructed so they won t be able to produce the pressure needed to push air outside the lung; and in this case they will need to open their lips and have a prolonged period of inspiration in order to get rid of the air inside. Smokers having emphysema and chronic bronchitis are blue bloaters (they will have cyanosis over their lips) because emphysema and bronchitis will cause damage to the blood vessels and this damage along with infection will lead to more severe symptoms which means abnormal gas exchange which means earlier chance to have cyanosis compared to patients who are having emphysema alone. In chronic bronchitis,the read index will show that the thickness of the layer of mucous (mucin) producing cells is more than 50% (normally it equals 40%), and those patients will have clear sputum unless they have a super added infection. Chronic bronchitis by default is not an infection, it might develop super added infection butit s not part of its pathology. Infection is the main cause of disease in diseases like bronchiectasis. Bronchiectasis patients will have their bronchial wall damaged by the infection, and will also have stagnation of sputum and mucus material. This provides a good mediumfor bacterial and other microorganism s overgrowth. And infection after infection will result in damage to the elastic and muscular layers, dilatation of the bronchial tree and no proper contraction or pressure to push the mucus outside. They will start losing the reflux and they will form an even better medium for more infection. Asthma; we have atopic and non-atopic asthma. Atopy asthma means that the patient is having an increased inflammatory response in his bronchial tree as this allergen willinitiate many things and produce many interleukins from mast cells and eosinophils; this response will lead to bronchospasm, contraction of the muscles, edema and mucus secretionwhich will narrow the lumen of the respiratory tract and prevent air from getting outside. Patients with atopy can be treated within the first minutes and everything will disappear and go back to normal. Sometimes however this atopic patient will enter a protracted phase in which the antigen will go deep inside the tissue and a more massive reaction will occur; now we need steroidsbecause regular bronchodilators will not solve the 13 P a g e

15 problem. We mentioned before that these atopic patientshave a genetic abnormality called ADAM33 (this gene is responsible for the increased response of the bronchial tree. Although asthma is reversible, these patients with time will have remodeling of their bronchial tree which means they will have increased thickness of muscles and more narrowing of the bronchial tree. At the same time those patients might not be allergic to the antigen again, in other words they will develop a response to this antigen and not be atopic anymore so they will not have attacks of asthma from this antigen again. Reviewed by: Alina Salaimeh 14 P a g e