Problem Mr. B is 57 years old, high 157 cm and weight 76 kg. He has worked as the dump truck driver in the coal mine since 1980, and also smoked cigarette 1 pack/day more than 30 years. What are the risk factors of his disease or illness? SCPA502-Respiratory Pathology Associate Professor Dr. Wannee Jiraungkoorskul Department of Pathobiology, Faculty of Science, Mahidol University Tel: 02-201-5563, E-mail: wannee.jir@mahidol.ac.th 1 2 Pulmonary defense mechanisms 1. Nasopharyngeal clearance Sneezing and mucociliary escalator 2. Larynx Epiglotiic closure 3. Tracheobronchial clearance Coughing, mucociliary escalator 4. Alveolar clearance Phagocytosis by macrophages A - ciliated pseudostratified columnar epithelium B - lamina propria C - muscularis mucosae D - submucosa https://courses.stu.qmul.ac.uk/smd/kb/microanatomy/respiratory/images/l3a.jpg 3 http://ars.els-cdn.com/content/image/1-s2.0-s0300483x10001770-gr1.jpg 4
Pulmonary defense mechanisms Particulate matter PM > 5 microns are trapped and filtered in the nasopharynx PM 3-5 microns are handled by the action of mucous (which traps the particles) and cilia (which transports the particles up into the nasopharynx) PM < 2 microns reach the alveoli where they may be engulfed by macrophages Airway diseases Small airway obstruction Asthma Chronic bronchitis Emphysema Large airway disease Bronchiectasis Parenchymal diseases Infection Pneumonia TB Non-infection Pneumoconiosis 5 Lung Cancer 6 Asthma Asthma (Greek "panting") is the chronic inflammatory disease of the airways characterized bronchospasm (the tightening of the muscles surrounding the airways) inflammation (the swelling and irritation of the airways). Symptoms such as wheezing, coughing, chest tightness, and shortness of breath. 7 http://www.nhlbi.nih.gov/health/health-topics/images/asthma.jpg 8
9 10 http://www.drscottgraves.com/wp-content/uploads/2012/08/asthma-causes.jpg 11 12 http://littledoctors.files.wordpress.com/2011/01/3.jpg
Chronic bronchitis Chronic bronchitis Chronic bronchitis is a chronic inflammation of the bronchi (medium-size airways) in the lungs. It is defined clinically as a persistent cough that produces sputum and mucus, for at least three months per year in two consecutive years. Cause most often by exposure to airborne pollutants such as cigarette smoke, excessive dust in the air, or chemicals. 13 14 Chronic bronchitis Chronic bronchitis Increase in size and number of mucus gland, goblet cells Persistent irreversible diffuse changes 1. Hypertrophy and hyperplasia of submucosal glands (Reid Index) 2. Goblet cell hyperplasia 3. Mucous hypersecretion with plugging 4. Variable degree of chronic inflammation 15 16
Chronic bronchitis Chronic bronchitis Increased thickness of mucus gland layer in bronchial mucosa Normal mucosa Cigarette smoke paralyses cilia, predispose to bronchial infection 17 CB 18 Chronic bronchitis Emphysema Emphysema (Greek "inflate ) It is a lung disease involving damage to the alveoli. There is progressive destruction of alveoli and the surrounding tissue that supports the alveoli. With more advanced disease, large air cysts develop where normal lung tissue used to be. Cause most often by cigarette smoke 19 20
The clusters of dilated air spaces which are conspicuous in the middle and lower lobes of the right lung and the lower lobe of the left lung. Both lungs are markedly enlarged. http://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/media/medical/hw/h9991437_001.jpg 21 http://www.meddean.luc.edu/lumen/meded/radio/curriculum/mechanisms/emphysema.jpg 22 Lung showing centrilobular emphysema characteristic of smoking. Cut surface shows multiple cavities lined by heavy black carbon deposits. Emphysema Loss of alveolar septa, Enlarged air spaces http://upload.wikimedia.org/wikipedia/commons/a/ac/centrilobular_emphysema_865_lores.jpg 23 24
Emphysema This lung shows emphysema (dilated air spaces) throughout the whole lung, being gross in a zone about 4 cm wide along the lateral margin, and approximately 2 cm wide along the lower margin. The inner aspect of the lower lobe exhibits considerable destruction of the pulmonary tissue, being replaced by a large cystic cavity (bulla). There is a large amount of black pigment deposited in the lung. This Destruction of alveolar wall 25 is carbon, derived from tar in cigarette smoke. 26 Bronchiectasis Morphology of Bronchiectasis Bronchiectasis is a disease defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue, associated with, abnormal dilation of these airways. Patients have copious foul - smelling sputum, induced by postural change Cause bacterial infections, Staphylococcus or Klebsiella, Bordetella pertussis. Gross exam: Marked dilatation of bronchial and bronchiolar airways (up to 4x normal size); airways can be visibly followed out to the pleural surfaces Microscopic exam: Acute and chronic inflammation, ulceration, necrosis, abscess formation, squamous metaplasia and fibrosis 27 28
P399 Lung Fibrosis - Bronchiectasis http://upload.wikimedia.org/wikipedia/commons/8/8f/bronchiectasis.jpg 29 30 Bronchiectasis is an abnormal, permanent dilation of the bronchial tubes in the lungs. Pneumonia Pneumonia is an inflammatory affecting the alveoli, associated with fever, chest symptoms, and a lack of air space (consolidation) on a chest X-ray Infectious agents or injury caused by aspiration of dust or chemical agents (gastric contents) causes fluid to enter the alveolar spaces. http://www.sopandiagnostic.org/digitalpathology.htm 31 32
Pneumonia Lobar pneumonia affects a section (lobe) of a lung. Bronchial pneumonia (or bronchopneumonia) affects patches throughout both lungs. http://en.wikipedia.org/wiki/pneumonia 33 http://www.meddean.luc.edu/lumen/meded/medicine/pulmonar/images/hussain3/scan26.jpg 34 Lobar pneumonia demonstrates the distinct difference between the upper lobe and the http://library.med.utah.edu/webpath/jpeg1/lung010.jpg consolidated lower lobe http://4.bp.blogspot.com/-o98pssnulwy/uhh80kje_oi/aaaaaaaah5u/qclyes14gcu/ s1600/lobar_pneumonia_leukocytic_alveolitis.jpg 35 36
Bronchopneumonia, or bronchial pneumonia, is a type of pneumonia that originates in the bronchioles of the lungs, which are the smaller ducts of the bronchial tubes. http://2.bp.blogspot.com/_zwqgybroghw/tdwswwik- FI/AAAAAAAABQo/8GkY5nXUi9g/s1600/PAXIT018.JPG 37 http://upload.wikimedia.org/wikipedia/commons/d/da/bronchopneumonia_lung.jpg 38 White nail syndrome may also be called leukonychia. Leukonychia can occur with arsenic poisoning, heart disease, renal failure, pneumonia, or hypoalbuminemia. Tuberculosis http://images.nailsmag.com/post/m-na0306disease-pic2-lr-1.jpg 39 40
Mantoux tuberculin skin test http://health.state.tn.us/images/tb_smear.jpg http://en.wikipedia.org/wiki/file:mantoux_tuberculin_skin_test.jpg Charles Mantoux (1877-1947) French physician http://en.wikipedia.org/wiki/file:extrapulmonary_tuberculosis_symptoms.svg http://scielo.isciii.es/img/revista s/sanipe/v11n1/imagen_04.gif 41 42 Granuloma (tubercle) of tuberculosis with caseous necrosis Multinucleated Giant Cell (Langhan) http://1.bp.blogspot.com/_lkjzm3-fbye/tthjm2xyz4i/aaaaaaaaafu/ojhkfnaas7w/s1600/pulmonary_ tuberculosis_chronic_inflammation_01.jpg 43 Johann Ferdinand Friedrich Theodor Langhans (1839-1915) German pathologist 44
SCPA217 Lung Tuberculosis http://upload.wikimedia.org/wikipedia/commons/1/18/cavitary_tuberculosis.jpg 45 46 The upper lobe of the lung exhibits advanced cavitation from longstanding tuberculosis. Note the thrombosed blood vessel traversing the cavity. Pneumoconiosis Deposition of mineral dusts in lung causing fibrosis i.e., progressive massive fibrosis, silicosis, asbestosis. The rest of the upper lobe exhibits advanced tuberculosis. There are scattered foci of "caseation" (cheesy white areas of necrosis) throughout the lobe. The pleura is considerably thickened by fibrosis, particularly over the upper lobe. 47 48
Pulmonary interstitial fibrosis Interstitial lung diseases are a group of diseases, caused by inflammation and scarring of the alveoli (air sacs) and their supporting structures (the interstitium). This leads to the loss of the functional alveolar units and a reduction of the transfer of oxygen from air to Diffuse insult Persistent, chronic damage Interstitial inflammation Pulmonary interstitial fibrosis blood. 49 50 Pulmonary interstitial fibrosis Pulmonary interstitial fibrosis Chronic inflammation Fibroblasts proliferate, Fibrosis Acini simplified, become cystic spaces When patient presents, lung may show fibrosis 51 52
Pulmonary interstitial fibrosis Pulmonary interstitial fibrosis Honeycomb Lung (end-stage changes) 53 Chronic inflammatory cells Interstitial fibrosis Obliteration of some air spaces Cystic dilatation of others 54 Pulmonary interstitial fibrosis Clinical Features Dry cough Impaired gas exchange SOB, no wheeze Pulmonary interstitial fibrosis Cyanosis (purple colour of tissues due to low oxygen levels in blood) late symptom. Clubbing of fingers: usually late 55 Clubbing results from chronic low blood-oxygen levels. This can be seen with cystic fibrosis, congenital cyanotic heart disease, and several other diseases. The tips of the fingers enlarge and the nails become extremely curved from front to back. 56
Lung Cancer Lung cancer is a malignant tumor of the lungs. Gross classification into 2 types: 1. Central group: neoplasms arising in major bronchi, segmental bronchi or divisions up to 1 mm in diameter 2. Peripheral group: neoplasms arising in lung parenchyma Histological Classification 1. Squamous cell carcinoma 2. Adenocarcinoma 3. Small cell carcinoma (Oat cell) 4. Large cell carcinoma where bronchioles are less than 1 mm in diameter 57 58 Squamous cell carcinoma 30% of lung cancer Arise from bronchial epithelium Cavitation may also occur, slow growth, metastasis not common. Occurs most frequently in men and old people. It is strongly associated with smoking. The tumor involves the bronchus (probable site of origin) and extends deeply into lung parenchyma. Tumor nodules are present in the lower lung. The pleura is focally involved. 59 http://farm4.staticflickr.com/3508/3922611335_edb8666189_z.jpg 60
P90 Lung Squamous cell carcinoma Tissue obtained via ultrasound-guided biopsy showing squamous cell carcinoma in the left lower lobe. 61 http://casereports.bmj.com/content/2010/bcr.07.2010.3147/f1.large.jpg 62 40% of lung cancer Arise from bronchiole mucus gland Rarely cavity, slow growth Most common cancer among women, and non smoker Usually started near the outer edges of the lung. Invasion of pleura and mediastinal lymph node is common. Adenocarcinoma This is a peripheral adenocarcinoma of the lung. Adenocarcinoma is the one cell type of primary lung tumor that occurs more often in non-smokers and in smokers who have quit. 63 http://drugline.org/img/ail/266_267_2.jpg 64
P389 Lung Adenocarcinoma Gland production and/or mucin production is diagnostic of adenocarcinoma. 65 http://pathology.class.kmu.edu.tw/ch12/111-5.jpg 66 Small cell carcinoma or Oat cell CA It generally starts in one of the larger breathing tubes 15% of lung cancer Grows and spreads more quickly and aggressively. Found mostly in heavy smokers 67 Arising centrally in this lung and spreading extensively is a small cell anaplastic (oat cell) carcinoma. The cut surface of this tumor has a soft, lobulated, white to tan appearance. The tumor seen here has caused obstruction of the main bronchus to left lung so that the distal lung is collapsed. Oat cell carcinomas are very aggressive and often metastasize widely before the primary tumor mass in the lung reaches a large size https://library.med.utah.edu/webpath/lunghtml/lung073.html 68
Small cell carcinoma : sheets of cells, cells with scant cytoplasm, molded nuclei (nuclear molding, is conformity of adjacent cell nuclei to one another), uniform fine chromatin. Large cell carcinoma 15% of lung cancer Cavitation common Slow growth, metastasis may occur to kidney, liver or brain. May be located centrally, mid lung or peripherally location http://upload.wikimedia.org/wikipedia/commons/5/54/lung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg 69 70 This large cell carcinoma at autopsy shows a large multilobulated tumor adjacent to the hilum. A metastatically involved lymph node is present next to the bronchus. P418 Lung Large cell carcinoma http://www.ivline.info/2011/05/pathology-101-pulmonary-tumours.html 71 72
Large cell carcinoma : Tumor cells have abundant cytoplasm, clumped chromatin (blue), but no evidence of gland formation, mucin production, bridges, or pearls. References http://willroberts.com/lungcancer/image10.jpg 73 Color Atlas and Text of Pulmonary Pathology by Philip Cagle Roberto Barrios Timothy Allen 2008 Pulmonary Pathology 2 nd ed. by Dani Zander Carol Farver 2017 Respiratory Diseases. By Mostafa Ghanei 2012 Lung Pathology: A Consultative Atlas. by Stuart Houser Eugene Mark Ulysses Balis 2005 74 SCPA502 Respiratory Pathology 75