Respiratory Pathology PDF by Dr. Elnemr

SMART VISION INSTITUTE PATHOLOGY RESPIRATORY SYSTEM DR AHMED ELNEMR EDITOR : DR.SOMIA AHMED HUSSEIN DR.ELNEMR RESPIRATORY PATHOLOGY Nose, Pharynx & Paranasal Sinuses Inflammatory Disorders Acute Infections Of The Upper Respiratory Tract: 1) Rhinitis (common cold): ¶ Most frequently manifesti...

SMART VISION INSTITUTE PATHOLOGY RESPIRATORY SYSTEM DR AHMED ELNEMR EDITOR : DR.SOMIA AHMED HUSSEIN DR.ELNEMR RESPIRATORY PATHOLOGY Nose, Pharynx & Paranasal Sinuses Inflammatory Disorders Acute Infections Of The Upper Respiratory Tract: 1) Rhinitis (common cold): ¶ Most frequently manifesting as common cold ¶ Manifests as rhinitis (nasal congestion and watery discharge, slight fever). ¶ Pathogens: • rhinovirus, respiratory syncytial virus, para-influenza and influenza virus. ¶ Morphology: It’s an acute catarrhal inflammation with excess mucus. 2) Acute Sinusitis: ¶ It is commonly preceded by acute or chronic rhinitis (edema impairs sinus drainage leading to retention of secretions and secondary infection); ¶ Example: maxillary sinusitis can occur by extension of a periapical tooth infection. ¶ Etiology: The same pathogens as rhinitis. ¶ Morphology: It starts as a catarrhal inflammation and with secondary infection, it becomes purulent inflammation. 3) Acute pharyngitis: ¶ Mild pharyngitis manifesting as sore throat accompany common cold. ¶ A more severe form is associated with marked hyperemia and exudate ¶ Occurs with B hemolytic streptococcal and adenovirus infection. Just…..Keep moving forward © 1 DR.ELNEMR RESPIRATORY PATHOLOGY 4) Acute Tonsillitis: ¶ Infection with B hemolytic streptococci, common in children. ¶ Gross: Tonsils are swollen, red with spots of pus on surface (pus in tonsillar crypts draining suppurating lymphoid follicles). ¶ Microscopic: Acute Inflammation + pus in lymphoid follicles. ¶ Complications: 1. Spread of infection: a. Direct: Peritonsillar abscess (Quinzy) - otitis media – pharyngitis- laryngitis. b. Lymphatic spread: Cervical lymph nodes (lymphadenitis). c. Blood spread: Bacteremia- septicemia- toxemia- pyemia. 2. Hypersensitivity : to streptococcal sore throat or URT infections may result in © Rheumatic Fever Or © Post Streptococcal Glomerulonephritis. 3. Chronicity: Chronic tonsillitis. Just…..Keep moving forward © 2 DR.ELNEMR RESPIRATORY PATHOLOGY 5) Otitis Media: ¶ Infection of the middle ear, often associated with upper respiratory tract infection. ¶ The Eustachian tube may become swollen and blocked, leading to trapping of exudate in the middle ear. ¶ Eardrum perforation may occur, following by draining of the exudate. ¶ Complications: - include mastoiditis, meningitis, and brain abscess. - Inflammation may persist and become chronic with hear loss. Just…..Keep moving forward © 3 DR.ELNEMR RESPIRATORY PATHOLOGY 6) Diphtheria: ¶ Definition: Diphtheria is a life-threatening disease characterized by a pseudo-membranous inflammation of throat and tonsils of young children. ¶ Etiology: Droplet infection by Corynebacterium diphtheria ¶ Incubation period: is 2-5 days. ¶ Sites: Tonsils, soft palate, larynx & trachea. ¶ Pathological features: 1. Pseudo-membranous inflammation: Ø Gross: • Multiple small yellowish foci of necrosis gradually enlarge, fuse together and form a continuous membrane. • The membrane: is slightly raised and adherent, but if removed by force it leaves bleeding ulcerating surface and reforms again. Ø Microscopic: • The membrane: is formed of fibrin network entangling dead epithelial cells, polymorphs, pus cells and macrophages. • The submucosa: shows dilated congested vessels, oedema, fibrin, and acute inflammatory cells. 2. Acute cervical lymphadenitis: Cervical lymph nodes on both sides are ( enlarged - separate - mobile - soft - painful - tender ) 3. Severe acute toxemia. Just…..Keep moving forward © 4 DR.ELNEMR RESPIRATORY PATHOLOGY ¶ Complications: 1) Asphyxia: caused by the oedema, membrane & laryngeal spasm. 2) Acute toxaemia_may cause: • Toxic Myocarditis and acute heart failure. • Cloudy swelling & focal necrosis of parenchymal organs, • Hemorrhage & necrosis of supra-renal cortex resulting in acute insufficiency. • Temporary paralysis of muscles of palate, pharynx, larynx, eye, face, etc., (nerve affection by bacterial toxins). Allergic Rhinitis & Nasal Polyp Ä Allergic Rhinitis: ¶ Definition: Atopic disease, immunoglobulin E (Ig.E)-mediated immune reaction caused by different antigens. ¶ Etiology: pollen/grass/dust etc., produce Type I hypersensitivity (atopy). ¶ Gross: Marked mucosal edema and erythema of the nasal mucosal membranes ¶ Microscopic: Acute allergic inflammation rich in eosinophils & increased submucosal edema. ¶ Complications: Repeated attacks result in nasal polyp rich in § plasma cells, § lymphocytes & § eosinophils. Just…..Keep moving forward © 5 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Nasal Polyp: ¶ Nasal polyps occur with recurrent allergic rhinitis; these are edematous mucosal protrusions infiltrated by esinophils, and plasma cells. ¶ When multiple or large, they obstruct the airway. ¶ Gross: Multiple, soft, pink polyps projecting from mucosa of nose & sinuses ¶ Microscopic: 2 C [ cover + core ] Ø Cover: • Pseudostratified columnar ciliated (respiratory) epithelial cover, but with chronic irritation it may changes to squamous (metaplasia) • Thickened, pink basement membrane Ø Core: • Thick, very wide edematous core with many eosinophils, • lymphocytes and plasma cells. • Increased number of mucous glands (hyperplasia). ¶ Complications: Nasal obstruction leading to 2ry infection & spread of the infection, & epistaxis. Ä Adenoids: ¶ Definition: Adenoids denote hyperplastic lymphoid tissue at the posterior wall of the nasopharynx, due to chronic infection in infants and children. ¶ Effects: • Mouth breathing with characteristic adenoid face: Opened mouth, short upper lip, protruding upper incisors, narrow nasal openings, absent nasolabial folds. • Spread of infection leading to otitis media, pharyngitis. Just…..Keep moving forward © 6 DR.ELNEMR RESPIRATORY PATHOLOGY Chronic Specific Infections Ä Rhinoscleroma ¶ Definition: • A granulomatous inflammation of the nose. • May affect other site as the larynx (laryngoscleroma), and pharynx. ¶ It is due to : • Infection with Klebsiella rhinoscleromatis bacteria which is endemic in Egypt. • The bacteria multiplies in macrophages producing a foamy appearance of the cytoplasm. (Mickulicz cells) ¶ Morphology: Ä Gross: • The lesions appear as small hard nodular mass or masses filling the nasal cavity. Ä Microscopic: • There is a chronic inflammatory infiltrate involving the submucosa , • The inflammatory cells comprise: Þ Mickulicz cells: o these are the predominant cells. o They are macrophages with foamy cytoplasm. o They are large with a small pyknotic nucleus. Þ Plasma cells and Russell bodies: ( Plasma cells with hyaline change due to accumulated immunoglobulin) • Later there is fibrosis. ¶ Complications: • Nasal obstruction and deformity • Ulceration and secondary infection. Just…..Keep moving forward © 7 DR.ELNEMR RESPIRATORY PATHOLOGY Tumors Of The Nasopharynx Juvenile Angiofibroma ¶ ¶ ¶ ¶ An uncommon benign mesenchymal tumor of the nasopharynx. It occurs exclusively in males, usually during adolescence. Micro: It is formed of proliferating fibroblasts with wide blood vessels. Complications: They are extremely vascular and lead to nasal bleeding (epistaxis) Nasopharyngeal Carcinoma ¶ Incidence: • Nasopharyngeal carcinoma is a rare neoplasm linked to EBV • It is common among the Chinese. ¶ Micro: [It may take one of three histological variants]: • Keratinizing squamous cell carcinoma. • Non-keratinizing squamous cell carcinoma. • Undifferentiated carcinoma with excess lymphocytes in the stroma lymphoepitheliomal. [It is the most common and the one most commonly linked to EBV.] ¶ Spread: It may spread directly, by lymphatics to cervical lymph nodes and late by blood. ¶ Treatment & prognosis: • They tend to be radiosensitive. • Lymphoepithelioma gives better results than squamous cell carcinoma with irradiation. Epistaxis ¶ Definition: Bleeding through the nose ¶ Causes: 1) Trauma 2) Foreign bodies 3) Tumors: angiofibroma 4) Nasal polyp 5) Rhinoscleroma 6) General causes: Hypertension, hemophilia , leukemia, VitC & K deficiency Just…..Keep moving forward © 8 DR.ELNEMR RESPIRATORY PATHOLOGY The Larynx Inflammatory Disorders Acute Laryngitis: Ä Definition: • Acute catarrhal inflammation of laryngeal mucosa. Ä Etiology: • It can result from inhalation of irritant fumes or allergy. • In children, parainfluenzae virus is the most common cause of laryngotracheobronchitis, known as croup. Ä It is characterized: by harsh persistent cough, and inspiratory stridor. Tuberculosis Of The Larynx: Ä It is a complication of secondary pulmonary tuberculosis. Ä Infection of the larynx occurs as sputum is coughed up. Ä Gross: The result is a laryngeal ulcer with undermined edges and caseous floor. Tumors Of The Upper Respiratory Tract 1) Squamous Cell Papilloma Of Larynx: ¶ A benign epithelial lesion, caused by human papilloma virus (HPV 6 & 11). • They may be multiple and recurrent especially. In children • The most likely cause of their occurrence is vertical transmission from infected mothers during delivery. In adults usually single in adults. ¶ Gross: Fine finger-like surface protrusions. ¶ Microscopic: 2 C [cover + core ] Ø Cover: covered by hyperplastic stratified squamous epithelium, showing hyperkerotosis, parakeratosis and acanthosis. Ø Core: Papillary thin fibrovascular core Just…..Keep moving forward © 9 DR.ELNEMR RESPIRATORY PATHOLOGY 2) Laryngeal Nodule (singer’s nodule) ¶ Definition: Nodule in middle third of vocal cords. ¶ Etiology: Caused by : • heavy smoking (unilateral) • excessive use of voice (bilateral) as in singer’s nodule” ¶ Clinical picture: It generally causes hoarseness of voice ¶ Gross: Smooth, hemispheric protrusions less than 0.5 cm in diameter. It is firm & covered by mucosa. ¶ Microscopic: • Surface: is covered by stratified squamous epithelium. • The subepithelium: shows vascularized fibrous tissue with pink hyalinosis. ¶ Complications: • Hoarseness of voice. • Recurs after removal. 3) Squamous Cell Carcinoma- Larynx ¶ Incidence: • It accounts for >95% of laryngeal cancer • Common in males > females (7:1), 40 years of age ¶ Predisposing factors: • Chronic irritation e.g. smoking or exposure to asbestos may have a role. • Cancer larynx is preceded by dysplasia & carcinoma insitu, which later develops into invasive carcinoma. ¶ Site: • Most of laryngeal carcinomas arise on the vocal cords, however it may arise above the vocal cords (supraglottic) or below (subglottic). Just…..Keep moving forward © 10 DR.ELNEMR RESPIRATORY PATHOLOGY ¶ Morphology: Ø Gross: Ulcerating or fungating tumors. Ø Microscopic: Squamous cell carcinoma. Glottic tumors are usually keratinizing and better differentiated than others. ¶ Clinical Picture: • Hoarseness of voice. • This should raise suspicion of malignancy in smoker males over 40. ¶ Complications: Ø Spread: ü Direct to nearby structures (esophagus, trachea & pharynx) ü Lymphatic to cervical lymph nodes, especially supraglottic tumors because this area is rich in lymphatics. The Lung Just…..Keep moving forward © 11 DR.ELNEMR RESPIRATORY PATHOLOGY Pulmonary Infections ü Acute Bronchitis (Acute Tracheo-Bronchitis) ¶ Causes: • Viral infections: common cold, influenza and measles. • Bacterial infections: Streptococci, Staphylococci & Pneumococci. • Chronic irritation: by dust, smoke or irritant gases. ¶ Pathology: • Catarrhal inflammation: Congested mucosal lining with mucoid or mucopurulent exudate. ü Pneumonia ¶ Definition: Inflammation of the lung parenchyma. ¶ Acute bacterial pneumonias can manifest in two anatomic patterns: Lobar pneumonia Part or all of a lobe is filled with exudate and identified by radiographs as consolidation. • a patchy distribution of inflammation that generally involves more than one lobe. Bronchopneumonia • This pattern results from initial infection of the bronchi and bronchioles and with extension into lung alveoli. ¶ Clinical picture of pneumonia: o Commonly follows a viral upper respiratory tract infection. o Abrupt onset with high fever, chills, pleuritic chest pain and a productive cough with muco-purulent sputum, occasionally there is hemoptysis. Just…..Keep moving forward © 12 DR.ELNEMR RESPIRATORY PATHOLOGY Lobar pneumonia Ä Definition: Acute diffuse fibrinous inflammation of the alveoli, occurring in one or more lobes of the lung Ä Organism: Streptococcus pneumoniae (pneumococci) in more than 90% of lobar pneumonias. Ä Route: airborne by droplet infection. Ä Occurs in : previously healthy young individuals & middle aged people (organism is highly virulent) Just…..Keep moving forward © 13 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Pathology: The pathology of lobar pneumonia is a classic example of acute inflammation involving four stages: Congestion Red hepatization Lasts For 24 hours. Gross ü The lung: is heavy edematous And red. ü The capillaries: Micro show hyperemia ü The lung alveoli: Filled with a protein rich exudate. Grey hepatization Lasts for a few days. Resolution On the 8 -1 0 days in untreated cases. ü The lung: is red, solid and airless, and consistency resembles fresh liver ü The alveoli : § Show fibrin § Massive accumulation of Polymorphs with some lymphocytes and macrophages. § Many red cells are extravasated. Just…..Keep moving forward © ü The lung : is grey, and solid ü The alveoli: § show more accumulation of fibrin [which shrinks away from the alveolar wall.] § Lysis of red blood cells. The lung returns to normal. ü Represents: liquefaction and absorption of the exudate, and enzymatic digestion of inflammatory debris 14 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Fate of lobar pneumonia: Most cases end by resolution. Ä Complications (not common): 1) Carniflcation Failure of resolution results in: ( organization of the alveolar exudate and the lung becomes like a piece of flesh) 2) Toxemia: occurs on 9th day may lead to acute heart failure due to toxic myocarditis 3) Spread: • Direct: empyema, pericarditis & mediastinitis • Blood: toxemia and septicemia leading to meningitis, arthritis and infective endocarditis. 4) Post pneumonic lung abscess & gangrene: focal tissue necrosis and suppuration in a consolidated area produces an abscess & gangrene can follow under the effect of putrefactive organisms. Just…..Keep moving forward © 15 DR.ELNEMR RESPIRATORY PATHOLOGY Bronchopneumonia (Commonly known as septic bronchopneumonia) Ä Definition: Bronchopneumonia is inflammation of the lung Ä characterized by: • patchy areas of consolidation centered on inflamed bronchioles. • These areas are distributed in one or several lobes, commonly basal and bilateral. • The inflammation is suppurative in nature. Ä Etiology: Þ Predisposing factors: • It occurs most commonly in extreme of age: infants and old age. • Commonly in patients with debilitating diseases such as : diabetes, cancer and cardiac failure. • It may complicate viral infections as viral bronchitis. Þ Causative Organisms: • Streptococcus pneumoniae, Hemophilus influenza, staphylococcus aureus. • In Hospital-Acquired pneumonias: Methiciilin resistant staphylococcus aureus (MERSA), Pseudomonas spp. And Klebsiella spp. Ä Morphology: Þ Gross: Usually bilateral lower lobe affection • Bronchioles: contain pus • Patchy areas of yellow consolidation (purulent exudate in alveoli), some areas may become confluent. • Pleurisy. • Enlarged hilar lymph nodes (lymphadenitis). Just…..Keep moving forward © 16 DR.ELNEMR RESPIRATORY PATHOLOGY Þ Microscopic: § Suppurative (neutrophilic) exudation filling bronchi, bronchioles, and alveoli. § Alveoli: The alveoli are full of pus (patchy areas of consolidation). Ä Complications: very common 1) Death, especially in debilitated patients. 2) Post pneumonic lung abscess & gangrene. 3) Spread: to the pleura causing empyema, pericarditis, mediastinitis. 4) Toxemia causing toxic myocarditis. 5) Septicemia causing meningitis, arthritis, osteomyelitis and infective endocarditis. 6) Fibrosis is common, due to tissue destruction by suppuration. 7) Bronchiectasis: healing of bronchial walls by fibrosis, results in weakened walls and permanent dilatation of the lumen due to traction on wall by peribronchial fibrosis. Just…..Keep moving forward © 17 DR.ELNEMR RESPIRATORY PATHOLOGY Atypical pneumonia (viral or mycoplasma pneumonia) Ä Definition: Atypical pneumonia is characterized by inflammation, confined to the alveolar septa and interstitium. It was called atypical due to absence of consolidation on physical examination and lack of alveolar exudates on radiology. Ä Etiology: C/O: Mycoplasma pneumoniae. Viruses such as influenza viruses, adenoviruses, syncytial viruses. Ä Pathogenesis: A common mechanism is attachment of the organism to the respiratory epithelium, followed by necrosis of the cells and inflammatory response. Þ Gross: The process may be patchy or involve whole lobes bilaterally or unilaterally. Þ Microscopic: - The inflammatory infiltrate (mononuclear cells: lymphocytes, macrophages and few plasma cells.) is confined to the interstitium with little or no alveolar exudates, - In severe cases there is diffuse alveolar cell damage with formation of a hyaline membrane of fibrin.(adult respiratory distress syndrome ARDS). Ä Clinical picture: § May simulate severe upper respiratory tract infection,( fever, headache, malaise, cough) § There may be respiratory distress out of proportion to physical or radiological findings because the inflammatory infiltrate in the alveolar wall blocks the gas exchange, § Superimposed bacterial infection can occur. Just…..Keep moving forward © 18 DR.ELNEMR RESPIRATORY PATHOLOGY ü Lung Abscess: Ä Definition: Localized suppurative inflammation of the lung tissue, resulting in the formation of one or more cavities containing pus. Ä Organisms: Staphylococci, pneumococc , Klebsiella pneumoniae, streptococcus pyogenes. Just…..Keep moving forward © 19 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Causes and types: due to aspiration of a. Blood clots or infected material during oral surgery b. Vomitus during anesthesia c. Foreign body or food in comatosed patients or patients with depressed cough reflex 1. A single abscess develops, more common on the right side. 2. It is usually in the posterior segment of upper lobe or apical segment of lower lobe. 3. These locations represent the more direct course for the Pathology Aspiration lung abscess aspirated material from the trachea when the patient is recumbent. 4. The abscess wall is irregular and congested. The lining is shreddy yellow (pyogenic membrane) and the contents of cavity is yellow pus. 5. Overlying pleura shows pleurisy. Post pneumonic abscess Bronchial obstruction with bronchogenic carcinoma Pathology One or more abscesses in a background of lobar or Bronchopneumonia Distal atelactasis and aspiration of blood and tumor fragments contribute to the development of lung abscess. Septic emboli from septic thrombophlebitis of systemic veins, or infective endocarditis of the right side of the heart. Pyemic abscess Multiple, very small and always next to a blood vessel. Pathology Yellow spots surrounded by a zone of congestion (usually too small to form cavities) Direct traumatic punctures or spread of infection from adjacent Organs. Just…..Keep moving forward © 20 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Fate and complications of acute lung abscess: 1) Small size: Resolve with proper treatment 2) Rupture into a bronchus: results in hemoptysis & cough of purulent sputum 3) Rupture into a pleural cavity: results in empyema and pyopneumothorax. 4) Lung gangrene: ( the cavity is irregular with a necrotic lining but black in color & has a foul odor). 5) Embolization of septic mterial to the brain results in meningitis and brain abscess. 6) Chronic lung abscess: ü Well-defined cavity with a thick fibrous wall. ü The lining is smooth & the contents are inspissiated (thick pus). ü Secondary amyloidosis may complicate long standing cases. ü Granulomatous Inflammation Of The Lung: Ä Causes: a. Tuberculosis (see module 103). b. Fungal diseases: Cryptococcosis, aspergillosis. c. Sarcoidosis (non-infectious). Just…..Keep moving forward © 21 DR.ELNEMR Obstructive RESPIRATORY VS Restrictive PATHOLOGY Lung Diseases • Diffuse pulmonary diseases can be classified into 2 categories: 1) Obstructive airway disease: § characterized by an increase in resistance to air flow due to partial or complete obstruction at any level (excluding tumors and foreign body). § The major diffuse obstructive airway diseases are: 1) Emphysema. 2) Chronic bronchitis. 3) Bronchiectasis. 4) Bronchial asthma. 2) Restrictive lung diseases: § characterized by reduced lung expansion. § Itoccurs in two general categories: 1) Chest wall disorders in the presence of normal lungs. Eg. : severe obesity, diseases of the pleura, neuromuscular disorders 2) Chronic interstitial lung diseases: Eg . pneumoconiosis and interstitial fibrosis. Obstructive lung disease: Just…..Keep moving forward © 22 DR.ELNEMR RESPIRATORY PATHOLOGY 1) Emphysema Ä Definition: Permanent over distention of air spaces distal to the terminal bronchioles, with destruction of their walls. Ä Types of emphysema: § Emphysema is classified according to its anatomic distribution within the lobule. § The acinus is the structure distal to the terminal bronchioles, formed of respiratory bronchiole, alveolar duct and alveoli. § The cluster of three to five acini are called a lobule: § Distention of the central part of the acinus formed by the respiratory bronchioles while distal alveoli are spared. Centriacinar § The lesions are more common and severe in the upper lobes, particularly the upper (bronchiolar segments. emphysema) § This type is common in cigarette smokers & coal workers’ Pneumoconiosis Panacinar (panlobular) Distal acinar (Paraseptal) § Distention of all air spaces distal to the terminal bronchiole i,e. the whole lobular unit. § Occurs more commonly in the lower lung zones. § It is the type of emphysema that occurs with alpha 1 antitrypsin deficiency. The proximal part of the acinus is normal. The distal part of the acinus is affected. It is usually subpleural, or along the lobular connective tissue septae. It occurs adjacent to areas of pulmonary scarring, or atelectasis. It is usually in the upper half of the lung, and forms multiple adjacent dilated air spaces, some forming cystic structures called bullae. § It is a cause of spontaneous pneumothorax in young adults. § § § § § Just…..Keep moving forward © 23 DR.ELNEMR Just…..Keep moving forward © RESPIRATORY PATHOLOGY 24 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Pathogenesis: § Alveolar wall destruction in emphysema likely results from imbalances between pulmonary proteases and their inhibitors. § Tobacco smoke and air pollutants: ü recruit neutrophils and macrophages. ü Smoking enhance elastase release from macrophages and neutrophils ü at the same time inhibit alpha 1 antitrypsisn. § The elastases unless checked by anti-elastases (e.g. alpha 1 antitrypsin), degrade the extracellular matrix and elastic tissue of the alveoli thus preventing alveoli from returning to normal size after their inflation with air during inspiration. § Patients with congenital alpha 1 antitrypsin deficiency develop panacinar emphysema at a young age if they smoke § There is marked individual variation in susceptibility to the development of emphysema. § Multiple genetic factors control the response to injury after smoking. Just…..Keep moving forward © 25 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Morphology: Þ Gross: Panacinar emphysema produce pale, dry, voluminous lungs that obscure the heart. § the lungs are less pale and less voluminous. centriacinar emphysema § upper two thirds of the lung are more severely affected. Þ Microscopic: § There is marked enlargement and dilatation of the air spaces with thinning and destruction of the alveolar wall. § The number of alveolar capillaries is diminished. Just…..Keep moving forward © 26 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Conditions related to emphysema: § compensatory dilatation of alveoli in response to loss of lung substance nearby. Compensatory § E.g. next to fibrosis or atelectasis. emphysema § Commonly asymptomatic Bullous emphysema Senile or atrophic emohvsema Interstitial emphysema § It is not a separate type of emphysema. § It is a localized accentuation of any form of emphysema. § There are large cystic spaces (bullae) greater than 1 cm. § Occurs as a result of senile loss of elasticity of tissues accompanying the atrophic changes of aging. § Asymptomatic § air collects out of the air spaces in the connective tissue septa of the lung and track into the connective tissue of the mediastinum and the neck. § It may occur spontaneously with sudden increase in intraalveolar pressure (as violent coughing in children with whooping cough), or from perforating injuries of the lung. § There is marked swelling of the neck with crepitus under the skin. § Air is absorbed spontaneously. Ä Clinical picture of emphysema 1) Dyspnea starts insidiously and is steadily progressive. 2) If associated with chronic bronchitis there is coughing and wheezing. 3) Barrel chest (increased antero-posterior diameter) due to lung overinflation. 4) Finger clubbing due to hypoxia. Ä Complications: 1) Pulmonary hypertension and right sided heart failure (cor pulmonale) 2) Respiratory failure from defective ventilation, perfusion & diffusion of gases with increased C02 in blood, respiratory acidosis & death. 3) Rupture bullae containing air into pleura producing pneumothorax (air in pleural cavity). Just…..Keep moving forward © 27 DR.ELNEMR RESPIRATORY PATHOLOGY 2) Chronic Bronchitis Ä Definition: • Chronic bronchitis is defined clinically as persistent productive cough for at least 3 consecutive months, for 2 consecutive years. • A subset of these patients, especially heavy smokers, develop chronic outflow obstruction, usually with associated emphysema. N.B: § Chronic bronchitis and emphysema are clinically grouped together under the name chronic obstructive pulmonary disease (COPD). § Previously bronchial asthma was included In this group but not anymore. Ä Etiology: • The most important causative factor is cigarette smoking. • Clinical episodes are associated with low grade bronchial infections by Hemophilus influenzae and streptococcus pneumonia. Ä Pathology: • The most important feature of chronic bronchitis is: hypersecretion of mucus in trachea and large bronchi due to hypertrophy of submucosal mucous glands at these sites. Ä Bronchiolitis (small airway disease): • Affection of the bronchioles is in the form of goblet cell metaplasia in the lining epithelium with formation of mucus plugs, inflammation and bronchiolar wall fibrosis. • It is the submucosal fibrosis that leads to luminal narrowing and outflow obstruction. Just…..Keep moving forward © 28 DR.ELNEMR RESPIRATORY PATHOLOGY 3) Bronchial Asthma Ä Definition: It is a chronic inflammatory disorder of the airways, characterized by paroxysmal reversible bronchospasm due to smooth muscle hyper-reactivity and increased mucus production. Ä Types: Ä § It is the most common type, § it is caused by a type I hypersensitivity reaction (Ig EAtopic (allergic) mediated) triggered by environmental antigens (e.g. pollen, asthma certain foods). Positive family history of atopy is common with high serum IgE level. § Hyper-reactivity of airways can be triggered by respiratory tract infections, chemical irritants. Non-atopic asthma § No family history and serum IgE level is not elevated. Aspirin induced Exact mechanism not known. asthma Ä Pathology: The pathology in the lung has been described from autopsy of patients who died of prolonged severe attack of asthma (status asthmaticus). Þ Gross: Lungs Bronchial wall Bronchial lumen Just…..Keep moving forward © are overinflated is thick, swollen & red. contains large amounts of thick mucus plugs 29 DR.ELNEMR RESPIRATORY PATHOLOGY Þ Microscopic: § Occlusion of bronchi and bronchioles by mucus plugs which contain whorls of shed epithelium known as Curschmann spirals. Bronchial lumen § Numerous eosinophils and Charcot-Leyden crystals derived from eosinophils are also present. § mucous gland hypertrophy. Bronchial wall § smooth muscle hypertrophy, § thickening of basement membrane Ä Clinical Picture: Ü Wheezing (due to bronchospasm) & Ü cough with scanty, tenacious mucus. Ä Complications: § Repeated attacks and bronchiolar inflammation can cause outflow obstruction and centriacinar emphysema. § An acute prolonged attack is termed status asthmaticus which may end in death from respiratory failure. Just…..Keep moving forward © 30 DR.ELNEMR RESPIRATORY PATHOLOGY 4) Bronchiectasis Ä Definition: it is abnormal permanent dilatation of medium sized bronchi and bronchioles associated with chronic suppurative infection. Ä Etiology: 1- Congenital or hereditary conditions Kartagener’s syndrome Mucoviscidosis (cystic fibrosis) § A rare hereditary disorder associated with bronchiectasis. § Structural abnormalities of the cilia impair mucus clearance in the airways resulting in persistent infections. § A hereditary disease associated with thick mucus in exocrine glands, respiratory, gastrointestinal and reproductive tracts. § Abnormally thick mucus secretions predisposes to obstruction & 2ry infection. 2- Septic bronchopneumonia particularly in children. 3- Bronchial obstruction (e.g., by tumor or foreign body). Ä Mechanism (pathogenesis): © Two processes are involved: obstruction and chronic persistent infection. © Either of them may come first. In septic bronchopneumonia § Severe persistent suppurative inflammation in bronchi or bronchioles causes: ü loss of cough reflex and accumulation of secretions, ü inflammation of the wall and weakening of the wall by fibrosis ü peribronchial fibrosis and traction on the weak bronchial walls, leading to their dilatation. In case of obstruction § § § § caused by foreign body or lung cancer: There is accumulation of secretions which favor infection, Infection damages the bronchial walls leading to their weakening The obstruction causes collapse of lung parenchyma , and the week bronchial wall are exposed to the negative intrathoracic pressure with each inspiration leading to its dilatation. Just…..Keep moving forward © 31 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Pathology: Þ Gross: § Site: is mostly bilateral, Most severe changes occur in peripheral lower lobes. § Medium sized bronchi & bronchioles: ü Airways can be dilated up to four times the normal size. ü The bronchi appear thickened, with suppuration of their lining. ü The dilated bronchi could be seen from hilum till the pleura (In the normal lung only the bronchi around hilum are seen, but the smaller bronchi towards the pleura are not seen by the naked eye due to their small diameter) § The pleura : is thickened , fibrotic with adhesions § There are 3 types of dilatation Saccular bronchiectasis Fusiform Cylindrical Just…..Keep moving forward © dilatation involves a part of the circumference of a segment ® sac like dilatation dilatation involves the whole circumference of a segment of the bronchus dilatation involves the whole circumference of the whole length of the bronchus. 32 DR.ELNEMR RESPIRATORY PATHOLOGY Þ Microscopic: § Lumen: filled with pus & blood. § Lining respiratory epithelium shows areas of ulceration. Bronchi § Wall shows intense acute and chronic inflammatory cells and fibrosis. Alveoli § Adjacent alveoli undergo fibrosis. § Patches of compensatory emphysema (to compensate for nonfunctioning alveoli). Pleura § Fibrosis and adhesions. Ä Clinical presentation: § Persistent, severe cough, fever, and abundant purulent sputum. § Symptoms may be episodic and precipitated by upper respiratory tract infection § Coughing can be associated with morning rising and positional changes that drain collected pus and secretions into the bronchi. § Culture reveals mixed flora: staphylococci, streptococci, pneumococci, enteric organisms, Hemophilus influenza and pseudomonas aeruginosa. Ä Complications: a. Hemoptysis with abundant foul smelling, yellowish red sputum (pus + blood). b. Lung abscess- gangrene. c. Spread of infection (see septic bronchopneumonia). d. Bilateral lung fibrosis , pulmonary hypertension & right sided heart failure (cor pulmonale). e. Secondary amyloidosis (chronic destructive condition). f. Squamous metaplasia (due to chronic irritation) which may lead to squamous cell carcinoma. Just…..Keep moving forward © 33 DR.ELNEMR RESPIRATORY PATHOLOGY 1- Restrictive Lung Diseases Chronic Interstitial Lung Diseases (CILDs) Ä Definition: Chronic interstitial lung diseases are a heterogeneous group of disorders characterized by bilateral, patchy, chronic Involvement of the interstitium of the lung. Ä Aetiology: Many are of unknown cause. Ä Pathogenesis: § The hallmark of these diseases is reduced compliance. § More pressure is required to expand the lungs because they are stiff. So the main clinical manifestation is dyspnea. § Affection of the ventilation and perfusion causes hypoxia. § Chest X-rays in many conditions show diffuse infiltration by tiny nodules (ground glass shadows). § Advanced forms of disease end in scarring and honey-comb lung appearance. § Patients may finally end with respiratory failure often with pulmonary hypertension and cor pulmonale. Ä Types: 1) Idiopathic pulmonary fibrosis. 2) Non- specific chronic interstitial pneumonia 3) Cryptogenic organizing pneumonia 4) Pulmonary involvement in collagen diseases as rheumatoid arthritis and systemic lupus erythematosus). 5) Sarcoidosis. 6) Pneumoconiosis Just…..Keep moving forward © 34 DR.ELNEMR RESPIRATORY PATHOLOGY Pneumoconiosis Ä Definition: Lung disease caused by inhaled dust. Dust may be inorganic (mineral) or organic. Ä Examples: A) Coal-worker’s pneumoconiosis: • Used to be common among coal workers. Now much reduced. • The disease has several stages: Simple anthracosis Macules and nodules Complicated stage presence of coal dust pigments which are taken by alveolar macrophages. § of dust-laden macrophages with delicate collagen fibers. § Can lead to centilobular emphysema. Progressive massive fibrosis with black pigment. B) § § § § Silicosis: Silicosis is the most prevalent occupational disease. Silica is present in sand. Workers involved in sand blasting or rock mining are affected. Silica is engulfed by macrophages which then die and release their proteolytic enzymes which damage lung tissue followed by fibrosis. § The lung shows characteristic nodules of whorling fibrosis, in which silica particles can be detected by polarized light. § And finally a honeycomb pattern may develop. § Silicosis increase the susceptibility to tuberculous infection. C) Asbestosis: § Asbestosis is used for insulation and manufacture of brake-linings and other friction materials. § Asbestosis manifests with dyspnea and dry cough. § Histologically, there is diffuse pulmonary fibrosis and honey- comb lung. § Asbestos bodies may be recognized in the alveoli as golden brown beaded rods § Both cancer lung and mesothelioma (cancer of the pleura) occur in asbestos workers, but the relative risk for mesothelioma (which is normally a very rare tumor) is more than 1000 times greater. Just…..Keep moving forward © 35 DR.ELNEMR RESPIRATORY PATHOLOGY Atelectasis & Collapse Ä Definition: Atelectasis is failure of expansion of the lung or collapse of previously inflated lung, affecting part or all of one lung, Ä Types: Resorption atelectasis Compression atelectasis § Occurs with complete airway obstruction e.g. mucus plugs postoperatively or with bronchial ashma, and foreign bodies in children. § Obstruction prevents air from reaching the alveoli, and the air already present becomes absorbed and the corresponding alveoli collapse. § Is associated with accumulation of fluid, blood or air in the pleural cavity, which compress and collapse the lung. § Effect: Atelectasis causes hypoxia and predisposes to bronchiectasis Just…..Keep moving forward © 36 DR.ELNEMR RESPIRATORY PATHOLOGY Tumors Of The Lung • • • • • a) Malignant Tumors: Malignant tumors of the lung are more common than benign tumors These include: - Metastases (more common). - Primary malignant tumors. The most important primary malignant tumor is carcinoma of the lung (95% of primary malignant tumors). The remaining 5% include carcinoid tumor, fibrosarcoma, leiomyosarcoma and lymphoma. b) Benign Tumors: The most common benign tumor is hamartoma which is a spherical (3- 4cm) coinlike shadow on X ray . It consists mainly of mature cartilage admixed with fat, fibrous tissue and blood vessels. Carcinoma Of The Lung (bronchogenic carcinoma, lung cancer) Ä Incidence: Lung cancer is the leading cause of death from cancer in the world, with the worst overall prognosis. The peak incidence is around the age of 50, with more male affection, but incidence in females is increasing. Ä Predisposing factors: • Cigarette smoking. • Air pollution. • Pneumoconiosis (inorganic dusts) e.g. Silicosis, asbestosis... • Bronchiectasis. Ä Types: The most common types of carcinoma of the lung are: 1. Squamous cell carcinoma. 2. Adenocarcinoma. 3. Large cell carcinoma. 4. Small cell carcinoma. Just…..Keep moving forward © 37 DR.ELNEMR RESPIRATORY PATHOLOGY 1. Squamous cell carcinoma Ä More common in men than women, closely related to smoking. Ä They are preceded by squamous metaplasia, dysplasia and carcinoma insitu which may last several years. Ä Gross: Þ Centrally located mass: 85% of tumors arise in major bronchi and present as; • An endobronchial growth • An infiltrative tumor that invade the bronchial wall and surrounding lung tissue. Ä Microscopic: Squamous cell carcinoma with various grades of differentiation and Keratin pearl formation. 2. Adenocarcinoma Ä Most common type of lung cancer in women. Ä Gross: • Most are peripherally located, and may be multiple. • Can occur centrally in men. • Seeding of the pleura occur early. Ä The precursor of adenocarcinoma is thought to be atypical adenomatous hyperplasia which progresses to adenocarcinoma in situ (previously called bronchiolo-alveolar carcinoma). Just…..Keep moving forward © 38 DR.ELNEMR RESPIRATORY PATHOLOGY 3. Large cell carcinoma Ä Large cell undifferentiated carcinoma that have no glandular or keratin formation (probably represents squamous cell carcinoma or adenocarcinoma that are so undifferentiated that they can no longer be recognized by light microscopy). 4. Small cell carcinoma Ä A rapidly growing and early metastasizing tumor. Ä Gross: A central mass. Ä Microscopic: • Cells are twice the size of small lymphocytes with scant cytoplasm. • Necrosis is always present and may be extensive. • These tumors often secrete a variety of polypeptide hormones that may result in paraneoplastic syndromes (see later). • The tumor cells can be stained by anti chromogranin which is a marker of neuroendocrine cells. Ä Spread and complications of lung cancer: A) Spread: Ä Direct: § to the pericardium, mediastinum and esophagus. § Pleural seeding especially in adenocarcinoma. Þ Pancoasf tumors: Apical neoplasms may invade the branchial or cervical sympathetic plexusus to cause pain in the distribution of ulnar nerve, Horner syndrome (ipsilateral miosis, ptosis and anhydrosis). Just…..Keep moving forward © 39 DR.ELNEMR RESPIRATORY PATHOLOGY Ä Lymphatic: § To the hilar and mediastinal lymph node. § The supraclavicular node affection (Virchow’s node) may be the first presentation. Ä Blood spread: To the brain, bones, liver, adrenals or other lung. B) Hemoptysis. C) Obstruction leading to collapse, secondary infection, bronchiectasis or lung abscess. D) Paraneoplastic syndrome: § 3-10% of patients with lung cancer develop clinical paraneoplastic syndrome due to secretion of polypeptide hormones. § It presents in one or more of the following forms: ü Hypercalcemia. ü Cushing syndrome. ü Myasthenia gravis. ü Excess ADH. Ä Clinical Presentation: Cough, dyspnea, hemoptysis, chest pain (pleuritic pain), and cachexia. Secondary Lung Tumors § More common than primary tumors. § Reach the lung by blood or lymphatic spread. § The secondaries appear as discrete nodules scattered throughout the lung. § Both carcinoma and sarcoma can metastasize to the lung. § Carcinomas that commonly give rise to secondaries in the lung are those of the breast, kidney, and GIT. Just…..Keep moving forward © 40 DR.ELNEMR RESPIRATORY PATHOLOGY Pulmonary Diseases of Vascular Origin ü Pulmonary Hypertension: Ä Causes: a. Chronic obstructive or interstitial lung disease. b. Recurrent pulmonary emboli. c. Mitral stenosis. d. Congenital left to right shunt due to increased pulmonary blood flow e. Idiopathic or primary pulmonary hypertension. Ä Pathology: • Vascular changes similar to those seen in systemic hypertension. a. Main elastic artery show atheroma. b. Medium sized arteries: cellular and smooth muscle hyperplasia leading to thick wall vessels and narrow lumen. c. Small arteries and arterioles: hyalinosis and elastosis and narrow lumen. Just…..Keep moving forward © 41 DR.ELNEMR RESPIRATORY PATHOLOGY Diseases Of the Pleura Inflammatory Disorders ü Pleural effusion: Ä Definition: Accumulation of fluid in the pleural cavity. This fluid may be: § Transudate (as in heart failure and liver cirrhosis) and is then called hydrothorax. § Exudate. Ä Causes of exudative pleural effusion: § Infections as TB, lung abscess, pneumonia. § Metastatic tumors to the pleura (frequently hemorrhagic). § Pulmonary infarction § Viral pleurisy § Collagen diseases as rheumatoid arthritis and systemic lupus erythematosus. Ä Pathology of exudative pleural effusion: Serofibrinous inflammation ü Hemothorax: It is accumulation of blood .in the pleural cavity due to rupture of aneurysm or trauma. ü Chylothorax: § is accumulation of milky white fluid (lymph). § It is usually left sided, caused by thoracic duct obstruction due to malignancy. Just…..Keep moving forward © 42 DR.ELNEMR RESPIRATORY PATHOLOGY ü Pneumothorax Ä Definition: Air in pleural cavity. Ä Etiology: air is sucked through a chest wall defect or enters the pleura from Trauma laceration of the lung by a broken rib. Spontaneous as a complication of rupture of an emphysematous bulla or after a pneumothorax bout of severe coughing. Ä Clinical Picture: sudden onset of severe chest pain & dyspnea Physical examination reveals hyperresonace over one lung with decreased breath sounds by auscultation. Ä Complications: lung collapse. ü Empyema: Ä Definition: Suppurative inflammation of the pleura with pus in the pleural cavity, Ä Etiology: pyogenic organisms: Staph, strept, pneumococci………… Ä Spread: § Direct spread from lung infection, abscess, bronchiectasis, pneumonia. § Trauma e g. penetrating infected stab wounds § Blood spread in septicemia Ä Pathology: Diffuse total empyema (usually acute): pleural cavity is filled with purulent effusion resulting in collapse of underlying lung tissue Localized pus in pockets, as a result of fibrous adhesions (more common) Ä Complications: § § § § Chest sinuses discharging pus. Spread: direct to pericardium and mediastinum. Toxemia , septicemia, pyemia Chronic empyema resulting in secondary amyloidosis. Just…..Keep moving forward © 43 DR.ELNEMR Just…..Keep moving forward © RESPIRATORY PATHOLOGY 44 DR.ELNEMR RESPIRATORY PATHOLOGY Pleural Tumors ü Malignant Mesothelioma: Ä Incidence: § Occurs in patients with asbestos exposure (miners, insulator factories or living in nearby areas) usually above 50 years, but may occur in younger ages. § There is also increased incidence of mesothelioma in family members of asbestos workers. § (Asbestos exposure through contaminated clothes). Ä Gross: § Mesothelioma is usually unilateral, starting as small nodules on the visceral pleura and extends to cover the whole lung and obliterate the pleural cavity. § The tumor is yellowish white. Ä Microscopic: Epithelioid type Cuboidal cells forming papillae and acini (looks like adenocarcinoma) Sarcomatoid type sheets of spindle malignant cells (looks like sarcoma) Mixed type (biphasic): Epithelial + sarcomatous Ä Complications: a) Spread: direct spread to pericardium, mediastinum, aorta and esophagus. b) Compression collapse of the lung. Ä Prognosis: poor Just…..Keep moving forward © 45 DR.ELNEMR RESPIRATORY PATHOLOGY ü Pleural metastasis: § This a very common condition. § Metastasis from any malignant tumor in the body. § The most common primary tumors are breast and lung reaching § pleura through blood spread or lymphatic spread. ü Hemoptysis: Ä Definition: Coughing of blood Ä Causes: 1. Bronchitis, bronchiectasis, pneumonia, lung abscess 2. Chronic fibrocaseous tuberculosis 3. Carcinoid tumor, carcinoma of the lung and secondaries of the lung. 4. Chronic venous congestion of the lung 5. General causes as leukemia, hemophilia , purpura, vitamin C and K deficiency. 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