Respiratory Diseases 2023 PDF

Respiratory Diseases Dr. Beth Brint, Pathology Dept. [email protected]  What Will Be Covered Review of basic anatomy and physiology Respiratory Infections Emphysema/Chronic Bronchitis/COPD Asthma Lung Tumours  Components of Respiratory System The respiratory syste...

Respiratory Diseases Dr. Beth Brint, Pathology Dept. [email protected]  What Will Be Covered Review of basic anatomy and physiology Respiratory Infections Emphysema/Chronic Bronchitis/COPD Asthma Lung Tumours  Components of Respiratory System The respiratory system is made up of the organs involved in the interchanges of gases Divided into upper and lower respiratory tract Upper respiratory tract - nose ,nasal cavity ,ethmoidal air cells, frontal sinuses, maxillary sinus, larynx and trachea Lower respiratory tract - lungs, bronchi, alveoli Right Lung – 3 Lobes Left Lung- Two lobes  Passage of air in the Resp System Main-stem bronchi divide into smaller bronchi Bronchi divide into even smaller tubes called bronchioles Bronchioles end in tiny air sacs called alveoli Normal Histology - Bronchiole  Normal Histology - Respiratory bronchiole, alveolar ducts and alveoli Respiratory Bronchiole Alveolar Duct Alveolar Sacs Gaseous Exchange:  Infections of the Respiratory Tract surface area of 500 sq.m A potential for infection on every inhaled breath Bronchitis usually caused by viruses e.g. RSV– Can involve trachea and larynx as well as lungs. Cough and reduced airway function. Acute or can lead to chronic bronchitis Pneumonia = alveolar inflammation. Large no of neutrophils, lymphocytes and T cells. Infection (mostly bacterial) of the distal airways and alveoli with formation of inflammatory exudate. Can be either colonisation of bronchi or of whole lobe.  Bronchopneumonia Lobar pneumonia affects otherwise heathy adults Affects elderly, cancer patients, infants between 20-50 B = bronchi A = alveoli Staph, Strep, H. Influenzae Streptococcus pneumoniae Sars-CoV2 (Pneumococcus)  Infections of the Respiratory Tract SARS-CoV2 Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV- 2) is the name given to the novel coronavirus which first appeared in Wuhan, China, in 2019. Causes mild to moderate respiratory illness in most individuals Affects upper and lower respiratory tract. Invades respiratory epithelium through ACE2 receptor Complications caused by cytokine storm. The virus can lead to pneumonia, respiratory failure, heart problems, liver problems, septic shock, and death. Age-specific illness and mortality pattern  Infections of the Respiratory Tract Tuberculosis – leading cause of death from any infectious agent. (M. Tuberculosis) - 1.66 million die each year. Symptoms vary from insidious weight loss and a mild cough, to rampant bronchopneumonia - Granulomatous inflammation and caseation. Pulmonary lesion about 10mm in diameter. - Lung is commonest site for TB - Infection can lie dormant for many years (secondary TB) or spread systemically (Miliary TB). Often reactivation of a primary or secondary lesion Healed region of TB infection in an elderly man - Yellow mass of caseous necrosis (Ghon complex) Miliary tuberculosis of lung. If an enlarged caseous node drains into a pulmonary vein (a), there is systemic dissemination of organisms (kidneys, liver, spleen). If drainage is into a pulmonary artery, miliary dissemination into the lung occurs (b). This slice of the lung of a child shows numerous tiny yellow-white dots. Each of these is a small caseating tuberculous granuloma caused by bloodstream spread.  Obstructive Airway Disease Either reversible or irreversible abnormalities in small bronchi or bronchioles – limiting airflow Chronic Obstructive Pulmonary Disease(COPD) - Emphysema - Chronic Bronchitis Bronchial Asthma  Chronic Obstructive Pulmonary Disease (COPD) Combination of (1)chronic bronchitis and (2)emphysema. Major public health problem worldwide Clear-cut association between heavy cigarette smoking and COPD Mild chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature. Macrophages, CD8+ T lymphocytes, and neutrophils are increased in various parts of the lung.  (1) Chronic bronchitis Chronic irritation by inhaled substances such as tobacco smoke (90% of patients are smokers) and grain, cotton, and silica dust. Bacterial and viral infections are important in triggering acute exacerbation of the disease. hypersecretion of mucus may lead to mucus blockage of airways Defined as a productive cough on most days for at least 3 months a year/ for at least 2 successive years Chronic bronchitis – infiltration of inflammatory cells in the submucosal region of bronchioles  (2)Emphysema Condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls and without obvious fibrosis Usually seen in smokers- smoking induces inflammation, increases protease activity, destruction of alveoli The clinical manifestations of emphysema do not appear until at least one third of the functioning pulmonary parenchyma is damaged. - Dyspnea (shortness of breath) - Cough/wheezing - Purulent cough - Emphysema  Pathogenesis of COPD An imbalance between proteases released from neutrophils and macrophages and antiproteases leads to alveolar wall destruction (emphysema). Proteases also cause the release of mucous.  Asthma Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning Hyperreactivity of the bronchial tree Narrowing of the small airways (bronchoconstriction) and hypertrophy of bronchial smooth muscle Mucus production and mucus plugs in bronchi. At least partly reversible, either spontaneously or through treatment Can be classified as extrinsic or intrinsic. Clinical symptoms and pathology are almost all the same  Extrinsic/Allergic Asthma - Allergic reaction triggered by environmental antigens (dust, pollen, food) - Type I (IgE mediated) hypersensitivity reaction - Acute inflammatory phase: IgE coated mast cells release inflammatory mediators causing bronchospasm, oedema, mucous secretion and leucocyte recruitment. - Late Phase: mediated by recruited leucocytes (lymphocytes, eosinophils, neutrophils) causing bronchospasm, inflammation and bronchial damage Pathogenesis of allergic asthma. Inhalation of allergen (antigen) causes degranulation of mast cells bearing specific IgE molecules. Release of vasoactive substances from the mast cells causes bronchial constriction, oedema and mucus hypersecretion.  accumulation of mucus smooth muscle hypertophy increase in goblet cells thickening of basement membrane chronic inflammation Histological section of lung at autopsy showing occlusion of airways by oedema and mucus plugs accompanied by alveolar distension with entrapped gas  Lung Tumours 90% of Lung Tumours are carcinomas (arising from epithelial cells) Leading cause of cancer death world wide Cigarette smoking and industrial carcinogens (asbestos, uranium, radon gas) Types: Squamous cell carcinoma(25% to 40%) Adenocarcinoma(25% to 30%) Small cell carcinoma (oat cell carcinoma)(20% to 25%) Squamous cell Carcinoma Most common type of cancer of the bronchus Derived from metaplastic squamous epithelium This develops in order to line the main bronchi as the result of exposure to agents such as cigarette smoke Lung carcinoma. The gray-white tumor tissue is seen infiltrating the lung substance  Metaplasia of columnar to squamous epithelium A, Schematic diagram B, Metaplasia of columnar (left) to squamous epithelium GM1001 C.Hand (right) in a bronchus Squamous cell carcinoma of the lung. Squamous cell carcinoma of the lung shows a range of differentiation, from well-differentiated lesions producing lots of keratin (K), through to lesions with only a few keratin- producing cells.  Adenocarcinoma Adenocarcinoma is the most common type of lung cancer in women and nonsmokers. As compared to squamous cell cancers, the lesions are usually more peripherally located, and tend to be smaller Histologically vary from well-differentiated tumors to solid masses with only occasional mucin-producing glands and cells A peripheral Adenocarcinoma  Adenocarcinoma of the lung. This micrograph shows an acinar pattern of adenocarcinoma of the lung, with prominent gland-like spaces (S) lined by a columnar epithelium.  Small cell carcinoma Strong relationship to cigarette smoking (only about 1% occur in nonsmokers) Occur both in major bronchi and lung periphery There is no known pre invasive phase or carcinoma in situ. Most aggressive of lung tumors Metastasize widely and virtually incurable by surgical means. Small cell/oat cell carcinoma which is spreading along the bronchi. The speckled black rounded areas represent hilar lymph nodes with metastatic carcinoma  Small-cell anaplastic carcinoma of the lung. This type of carcinoma shows neuroendocrine differentiation. Cells are round to oval and have little cytoplasm. SUMMARY Bronchitis and pneumonia are manifestations of lung infection- we looked at 2 causes Sars-CoV2 and TB Emphysema is enlargement of the bronchioles or alveoli resulting in reduction of air supply COPD is a combination of Emphysema and chronic bronchitis Asthma is an inflammatory disorder resulting in bronchoconstriction Most lung cancers are carcinomas; most of these arise from inhaled carcinogens.