Respiratory System Fall 2023 Final PDF

10/13/2023 49 Atelectasis (Collapse) Acquired atelectasis • Resorption Atelectasis occurs when obstruction prevents air from reaching distal airways • most common cause is obstruction by mucus plug in bronchus • Compression Atelectasis is associated with accumulation of fluid, blood or air with...

10/13/2023 49 Atelectasis (Collapse) Acquired atelectasis • Resorption Atelectasis occurs when obstruction prevents air from reaching distal airways • most common cause is obstruction by mucus plug in bronchus • Compression Atelectasis is associated with accumulation of fluid, blood or air within pleural cavity which collapse the adjacent lung (pleural effusion, pneumothorax) • Contraction Atelectasis occurs when local or generalized fibrotic changes in lung or pleura hamper expansion and increase elastic recoil during expiration 50 51 17 10/13/2023 Emphysema WITHOUT fibrosis, Tobacco, fuel, TGF-Beta1 polymorphisms or Alpha1-anti trypsin deficiency • Condition of lung • irreversible enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their (e.g. alveolar) walls without fibrosis • Characterized by mild chronic inflammation And its distal to terminal bronchioles • epithelium and macrophages release leukotriene B4, TNF, IL‐8 Recruit neutrophils Complement • Macrophages, CD8+ & CD4+ T differentiation factors 8 lymphocytes and 4 of immune system, • Recruitment of neutrophils Important for recruitment • Destruction of connective tissue a of T-Cells, helper cells, regulatory cells, and consequence of imbalance of protease‐antiprotease and oxidative cytotoxic cells. Players in lymphocyte recruitment stress Decreases ECM • Neutrophils are principal source of proteases • Inflammatory cells produce ROS • Clear association between heavy cigarette smoking and emphysema 52 Emphysema Formalin fixed Gas filled patches Destruction of alveolar sac and its expanded Figure 12‐08. Pulmonary emphysema. There is marked enlargement of air spaces, with destruction of alveolar septa but without fibrosis. Note presence of black anthracene pigment. Figure 12‐09. Bullous emphysema with large apical and subpleural bullae. (From the Teaching Collection of the Department of Pathology, University of Texas Southwestern Medical School, Dallas, Texas.) 53 Acute Respiratory Distress Syndrome (ARDS) • A manifestation of severe acute lung injury • In many cases, due to a combination of predisposing conditions e.g. shock, oxygen therapy, sepsis. Due to some condition: end result is oxygen wont be able to get absorbed and transported to cels • Clinical syndrome of progressive respiratory insufficiency associated with inflammation‐induced increase in vascular permeability, edema and epithelial cell death. Vascular permeability can be increased in case of allergy, shock, any inflammation. Edema is accumulation of fluid in thoracic cavity etc. • Associated with direct injury to the lung or systemic disorders • diffuse alveolar damage • rapid onset of life threatening respiratory insufficiency  cyanosis & hypoxemia 54 Gas exchange doesnt happen readily in pneumocyte 2 because they’re more like pluripotent and produce pneumocyte 1 cells. 18 10/13/2023 Cuboidal bronchial epithelial, there can be clara cells here, are ciliated Pathogenesis of ARDS acute injury to the alveolar epithelium and capillary endothelium → increasing inflammation and pulmonary damage • Endothelial activation ‐ dt pneumocyte damage or circulating inflammatory mediators • Neutrophils and their products play a crucial role (ROS, proteases, platelet‐activating factor, leukotrienes) • MIF 55 Macrophage: bean shaped nucleus, lots of cytoplasm, pseudopodia which can engulf anything, and granules Macrophage when it gets activated secretes: secretes Tumor necrosis factor (TNF) and interleukin 1 (IL-1). These factors recruit neutrophils already in the alveolus and also they are sending signal to the neutrophils circulating within the capillaries using TNF and interleukin 8 (IL-8). When neutrophils are inside the alveoli they begin to secrete Leukotrines (plays role in necrosis of pneumocyte 1), proteases (act on endothelial for vasodilation), reactive oxygen species (good in terms of clearing up infection but you dont want inflammation to go Hayward because they will then become detrimental to pneumocyte), and platelet activation factors. These contribute to local tissue damage. They also Act on blood vessels for vasodilation. This leads to edema fluid in air spaces, Surfactant inactivation, and hyaline membrane (very thin) formation (hypereosinophilic) which is not good for oxygen diffusion. MIF: migration inhibition factor. Good in certain extend when there is small infection. In ARDS, MIF increases a lot. If too much inflammation, clinician prescribes a steroid to decrease inflammation so damage does not happen. MIF stops glucocorticoid steroids to work. Histopathology of ARDS Exudative Early (exudative) stage: edema, epithelial necrosis, accumulation of neutrophils, hemorrhage, and hyaline membranes, which consist of inspissating protein/fibrin‐rich edema fluid admixed with remnants of necrotic alveolar epithelial cells Organizing stage: marked proliferation of type II pneumocytes; resorption of the hyaline membranes and thickening of the alveolar septa by inflammatory cells, fibroblasts and collagen Thick septum More fibrinous and collagenous hyaline membrane when chronic Hyaline membrane ARDS Figure 13‐3A. Diffuse alveolar damage in acute lung injury and acute respiratory distress syndrome. Some alveoli are collapsed; others are distended. Many are lined by bright pink hyaline membranes (arrow). B, The healing stage is marked by resorption of hyaline membranes with thickening of alveolar septa containing inflammatory cells, fibroblasts, and collagen. Numerous reactive type II pneumocytes also are seen at this stage (arrows), associated with regeneration and repair. A, 56 Resorption of hyaline membrane but thickening of septum, containing fibroblasts, inflammatory cells. Lots of type 2 pneumocytes (hyperplasia). More alveolar macrophages. Outcome of ARDS • Mortality rate approximately 60% • deaths attributable to sepsis or multiorgan failure or direct lung injury • improvements in therapy for sepsis, mechanical ventilation and supportive care has reduced mortality two approximately 40% in US. • Survivors may have persistent impairment. 57 19 10/13/2023 Obstructive Pulmonary Disease Small airway disease: not affecting upper tract • Characterized by a limitation of airflow • Due to increase in resistance in airflow: caused by partial or complete obstruction at any level from trachea to bronchioles • Characterized by a decreased expiratory rate, although total lung capacity can be either normal or increased. • May result from: • Anatomic airway narrowing (asthma) • Loss of elastic recoil (emphysema) • The major diffuse obstructive disorders are: • emphysema ] • chronic bronchitis ] • asthma and • bronchiectasis COPD Ectasia is dilation Figure 12‐05. Schematic representation of overlap between chronic obstructive lung diseases 58 Asthma • Chronic inflammatory disorder of the conducting airways that causes recurrent episodes of wheezing, breathlessness, chest tightness and cough • Characterized by • reversible and intermittent bronchoconstriction caused by airway sensitivity to variety of stimuli / allergens • chronic bronchial inflammation • increased mucus production Actually worsens situation by clogging, despite goblet cells effort to clear away allergens. • Between attacks, patients may be virtually asymptomatic Two major types: • Atopic • Evidence of allergen sensitization and immune activation Brochnoconstriction, vasodilation, hypersensitivity type 1 • Type I hypersensitivity • Non‐atopic ‐ No evidence of allergen sensitization 59 Non‐atopic (intrinsic) asthma: triggered by non‐immune stimuli such as aspirin, pulmonary infections (virus), cold, physiologic stress, exercise and inhaled air pollutants e.g. cigarette smoke Atopic (extrinsic) asthma: genetic predisposition to type I hypersensitivity Can grow out of it. Wen young more • immune response to environmental allergens predisposed • T cells (Th2) and their mediators promote inflammation and stimulate B cells: In atopic: Th2 cells is the mediator that stimulate B cell reaction. • IL‐4 ‐ stimulates IgE production Interleukin 4- stimulates IgE (immunogloin E) - mast cells recruitment • IL‐5 ‐ activates eosinophils • IL‐13 ‐ stimulates mucus production IL-5 - degranulate and the substance released from granules cause the immune reaction. Important for eosinophils and mast cells IL-13 stimulates the mucus production 60 20 10/13/2023 Atopic (extrinsic) asthma: smooth muscle contraction Fairly quickly • Acute (immediate) phase: pre‐formed inflammatory mediators, mast cells. • Bronchoconstriction – parasympathetic stimulation, central + local, triggered by mediators Chemokynes secreted by mast cells or eosinophils • Increased mucus production • Vasodila on + ↑ permeability Cause edema • Late (4‐8 h later) phase : • more inflammatory cell infiltration: eosinophils, neutrophils and T cells (Th2 + Th17) In the late phase expect to see th2 and th17 • synthesis of cellular mediators Released by tcells • leukotrienes C4, D4, E4 (prolong bronchoconstric on, ↑ permeability+ mucus production) Remember leukotrines prolong bronchoconstriction • Acetylcholine release Para ACh, bronchoconstriction • Histamine, PGD2, PAF Platelet growth derived factor, histamine released by eosinophils • Others 61 Engulf antigen and present it to TH2 Cells Dendritic cells Contraction in smooth muscle 62 Clinical Outcomes • "Attacks" last up to several hours. The paroxysm may persists for day or Spasm of contraction even weeks. • May be fatal. Can be absolute obstruction • Acute airway obstruction due to bronchoconstriction, acute edema and mucus plugging • occlusion of bronchi and bronchioles by thick, tenacious mucus plugs • Over distention of lungs In chronic asthma • Thickening of airway wall, sub basement membrane fibrosis (type I and type III Type 1 and type 3 collagen deposits on basement membrane collagen) • hypertrophy of submucosal glands and increased number of airway goblet cells • hypertrophy and/or hyperplasia of the bronchial wallssmooth muscle. Hypertrophy of serous glands 63 21 10/13/2023 Pneumonia Alveolar spaces filled with exudate • Pneumonia is inflammation of the lung parenchyma INFLAMMATION of lung Interstitial characterized by consolidation of the affected part, e.g. PARENCHYMA pneumonia is alveolar spaces filled with exudate the same as pneumonitis• Pneumonitis refers to inflammation of the lung generally involving the alveolar interstitium and without exudate in the alveoli Interstitium: Connective tissue , smooth muscle, elastic fibers, capillaries where pneumocytes lie on, all the alveoli tissue • Classification according to a variety of different features • Presumed cause • e.g. viral, verminous VIRAL, or VERMINOUS (PARASITIC) • Type of inflammatory exudate • e.g. suppurative, fibrinous, granulomatous Exudate is inflammatory cells and substances which accummulate in alveolar sacs. • e.g. embolic, proliferative Supparative pneumonia: is when there is more inflammation by neutrophils. Fibrinious pneumonia: is fibrin filling up alveoli, more acute Granulomatous pneumonia: inflammation by macrophages • Morphologic features • Distribution of lesions, • e.g. cranioventral, diffuse, lobar • Attributes of the pneumonic process • e.g. enzootic, contagious, atypical 64 Embolic or proliferative pneumonia: Distribution of lesion: Lung has cranial, ventral, caudal lobe. Can be diffuse, lobar, or cranioventral In many septic conditions where there is bacterial thrombosis in heart, then you can see embolic shower, or aka many different emboli break from the valves of the heart and lodge in the lungs and inflammation occurs around those emboli. (Septic, bacterial inflammation). Attributes of the pneumonic process: enzootic, contagious, atypical (hypersensitivity plays role) Proliferative is when a certain type of cell is hyperplastic/proliferative. Can be type 2 pneumocyte, macrophage • Two of the anatomic or radiographic patterns of pneumonia: Broncho or lobar pneumonia Broncho: patchy consolidation involving more than 1 lung lobe, and extends into the alveoli. Bronchopneumonia will be bilateral mostly and generally starts from the initial airway or bronchiole infection • Bronchopneumonia: patchy consolidation involving more than one lobe (initial infection of bronchi with extension to alveoli) • Lobar pneumonia: regional consolidation –contiguous spaces of part or all of a lobe filled with exudate Morphology of lobar pneumonia: evolves through 4 stages: (1) congestion, (2) red hepatization, (3) grey hepatization, (4) resolution Congestion Red hepatization Turning grey Grey hepatization Lobar is regional consolidation. All. Of the lobes, filled with exudate. Only regional, can be unilateral. In gross presentation we can see the lung almost starts to look like liver. It’s much firmer. 65 Acute pneumonia: exudate, supparative, bronchopneumonia Neutrophils Alveolar septa Macrophages, lymphocytes Fine fibrin threads Macrophage 66 Septa not affected much its mainly the sacs. 22 10/13/2023 Early organization of intraalveolar exudates. Grey hepatization. fibrosis 67 More collagen and fibroblast cells deposit and transform. Fibrin is evident is most of the area. Fibromyxoid 68 Further classifications of pneumonia • Bronchopneumonia • Refers to pneumonia in which inflammatory process occurs in the bronchial, bronchiolar, and alveolar lumens • exudate collects in the bronchial, bronchiolar and alveolar lumina leading to consolidation • Most common type in domestic animals Is bronchopneumonia • Characterized by a cranioventral consolidation of the lungs • Comparable to anteriosuperior in human anatomy • Caused by viruses bacteria, mycoplasmas, aspiration • Route of entry of injurious agents (e.g. bacteria) causing Mode of infection bronchopneumonia is via the inspired air, i.e. aerogenous. is inhaled • Source is aerosolized droplets containing infectious particles or from the nasal flora 69 23 10/13/2023 Why cranioventral pneumonia in animals and superior interior pneumonia in humans? • when an animal breaths it will reach rail portion most quickly and easily. Because of gravity. Normal Patchy white fibrin deposition Interlobular septa is edematous Airways filled with exudate Fig. 9‐56A Suppurative bronchopneumonia, enzootic pneumonia, lung, calf. A, Cranioventral consolidation (C) of the lung involves approximately 40% of pulmonary parenchyma. Most of the caudal lung is normal (N). B, Cut surface. Consolidated lung is dark red to mahogany (C), and a major bronchus contains purulent exudate (arrow). N, Normal. (A courtesy Dr. A. López, Atlantic Veterinary College. B courtesy Ontario Veterinary College.) 70 Lobes and interlobular septa. Cranioventral portion affected. Fibrinous coating within 24-48 hours. Fig. 9‐58A Fibrinous bronchopneumonia (pleuropneumonia), right lung, steer. A, The pneumonia has a cranioventral distribution that extends into the middle and caudal lobes and affects approximately 80% of the lung parenchyma. The lung is firm, swollen, and covered with yellow fibrin (*). The dorsal portion of the caudal lung is normal (N). B, Cut surface. Affected parenchyma appears dark and hyperemic as compared with more normal lung (top quarter of figure). Interlobular septa are prominent (yellow bands) due to the accumulation of fibrin and edema fluid. This type of lesion is typical of Mannheimia haemolytica infection in cattle (shipping fever). (A courtesy Ontario Veterinary College. B courtesy Dr. A. López, Atlantic Veterinary College.) 71 Interlobular septal area necrotic Fibrin coating Coagulative necrosis Fibrin Hepatized Congested vessels and hemorrhages are the red spots Neutrophils Fig. 9‐72A Pneumonic Mannheimiosis (Mannheimia haemolytica), lung, steer. A, Cut surface. Interlobular septa (arrowheads) are notably distended by edema and fibrin. In the lung parenchyma are irregular areas of coagulative necrosis (arrows) surrounded by a rim of inflammatory cells. C, Note alveoli filled with fibrin (asterisks) and with neutrophils (N). The interlobular septa (IS) is distended with proteinaceous fluid. H&E stain. (A, B, and C courtesy Dr. A. López, Atlantic Veterinary College. D courtesy Dr. J.F. Zachary, College of Veterinary Medicine, University of Illinois.) 72 24 10/13/2023 Atypical pneumonia X-ray or radiograph doesnt look so bad but the symptoms are very bad. • Characterized by respiratory distress disproportionate to clinical and radiologic signs, and by inflammation that is confined to alveolar septae, i.e. alveoli devoid of exudate • Most common cause in humans is Mycoplasma pneumoniae. • Other causes: intracellular bacteria (chlamydia), viruses (influenza A & B, severe acute respiratory syndrome (SARS), Coxiella burnetti (Q fever) Pathogenesis: microbial a achment to epithelium → cell necrosis → inflammation within alveolar walls (interstitial), type II pneumocyte hypertrophy Within alveolar walls  Predisposition to secondary bacterial infection Told not to take antibiotics unless you have a secondary bacterial infection. 73 Further classifications of pneumonia Common in veterinary field. • Interstitial pneumonia • Refers to pneumonia in which the inflammatory process is localized to the components of the alveolar walls, i.e. the endothelium, basement membrane and alveolar epithelium (pneumocytes) and the contiguous bronchiolar interstitium Means interstitium around cartilage, glands, Submucosa glands • Can be the consequence of injury to pneumocytes from aerogenously delivered agents, or from injury to alveolar capillary endothelium or basement membrane from hematogenously delivered agents 74 Further classifications of pneumonia • Interstitial pneumonia • Aerogenous agents include inhaled toxic gases or inhaled pneumotropic viruses (e.g. influenza) • Hematogenous agents include bacterial toxins (sepsis, endotoxemia), endotheliotropic viruses • Injury to type I pneumocytes or capillary endothelium disrupts blood‐air barrier and leads to an acute exudative reaction that includes neutrophil infiltration of alveolar interstitium…characterizes acute interstitial pneumonia • Persistent injury leads to fibrosis of alveolar walls, infiltration by macrophages, lymphocytes, fibroblasts, and proliferation of type II pneumocytes…characterizes chronic interstitial pneumonia 75 25 10/13/2023 Lung is not collapsed and there is certain rib impressions, meaning the lung is edematous. Fig. 9‐60A Interstitial pneumonia, lung, feeder pig. A, The lung is heavy, pale, and rubbery in texture. It also has prominent costal (rib) imprints (arrows), a result of hypercellularity of the interstitium and the failure of the lungs to collapse when the thorax was opened. B, Transverse section. The pulmonary parenchyma has a “meaty” appearance and some edema, but no exudate is present in airways or on the pleural surface. This type of lung change in pigs is highly suggestive of a viral pneumonia. (Courtesy Dr. A. López, Atlantic Veterinary College.) 76 Small alveoli Thick interstitial Fig. 9‐61A Interstitial pneumonia, lung, aged ewe. A, The alveolar septa are notably thickened by severe interstitial infiltration of inflammatory cells. H&E stain. B, Higher magnification view of A showing large numbers of lymphocytes and other mononuclear cells infiltrating the alveolar septal interstitium. H&E stain. (A courtesy Western College of Veterinary Medicine. B courtesy of Dr. A. López, Atlantic Veterinary College.) 77 Further classifications of pneumonia • Embolic pneumonia • Refers to pneumonia in which the inflammatory process is centered on blood vessels because the injurious agent is hematogenously delivered to the lung from a site of infection outside the lung • Inflammatory response is typically centered on pulmonary arterioles and alveolar capillaries (small diameter blood vessels) Narrower the diameter the easier it is to occlude. Alveolar sacs around it will go under inflammation, necrosis etc, 78 26 10/13/2023 Further classifications of pneumonia • Embolic pneumonia • Requires that circulating bacteria or fungi attach to pulmonary endothelium AND evade phagocytosis by pulmonary intravascular macrophages or neutrophils • Characterized by multifocal lesions randomly distributed in the lobes of the lungs • Sources of septic emboli include hepatic abscesses (which rupture into the caudal vena cava), omphalophlebitis, chronic bacterial or fungal skin, mouth (or hoof) infections, and contaminated intravascular catheters • Agents include Streptococcus spp. Staphylococcus spp, and other bacteria, as well as fungi, e.g. Aspergillus spp. Emboli can be from thrombus, or air emboli, or bone marrow emboli, cartilage emboli from rib fracture Requires circulating bacteria or fungi attach to pulmonary endothelium and evade or immune to phagocytosis 79 Sources of septic emboli: Hepatic abscesses → can rupture into caudal vena cava and rupture into lung Omphalophlebitis → inflammation of umbilical cord Newborns are susceptible to this Bacteria or virus can lodge in this area and enter the circulatory system and cause sepsis Chronic bacterial or fungal skin, mouth or hoof infections Contaminated catheters aspergillus pneumonia notorious: fungus will invade endothelial cells, cause embolic pneumonia in multiple places Fig. 9‐63 Embolic pneumonia, lungs, 6‐week‐old puppy. Large hemorrhagic foci are scattered relatively uniformly throughout all pulmonary lobes (arrows). These hemorrhagic foci are the sites of lodgment of Pseudomonas aeruginosa emboli (septic) that originated from necrotizing enteritis. Note the multifocal distribution of the inflammatory foci, which is typical of embolic pneumonia. Septic emboli were also present in the liver. (Courtesy Atlantic Veterinary College.) Multifocal embolic pneumonia 80 6 week old puppy. Most probably embolic pneumonia because it is a lung animal interstitial pneumonia can be left side vs right side. Pseudomonas agent. Fig. 9‐64A Embolic pneumonia, lung, cow. A, Foci of necrosis and infiltration of neutrophils (arrows) resulting from septic emboli. Note the multifocal distribution of the lesion, which is typical of embolic pneumonia. Vegetative endocarditis involving the tricuspid valve was the source of septic emboli in this cow. H&E stain. B, Embolic focus in the lung. Note bacterial colonies (arrows) mixed with neutrophils and cellular debris. H&E stain. (Courtesy Dr. A. López, Atlantic Veterinary College.) 81 Embolic pneumonia in a cow: This is a major bronchiole → no cartilage Interlobular septa, multifocal areas Arrows point at multifocal areas which are centered around Blood Vessel → inflammation, infiltrate, alveoli are occluded, hemorrhage, septa and alveolar sacs are affected 27 10/13/2023 Further classifications of pneumonia • Granulomatous pneumonia • Refers to pneumonia in which the injurious agent evokes a granulomatous inflammatory response • Injurious agent can be delivered to the lung aerogenously or hematogenously • Granulomatous pneumonia can share portals of entry or sites of initial injury with other types of pneumonias, e.g. interstitial or embolic…unique quality of granulomatous pneumonias is the inflammatory response Agent is entrapped by macrophages, but macrophages are unable to destroy agent → this causes long term inflammatory response Shares sites of entry with embolic or interstitial pneumonia agents 82 Further classifications of pneumonia • Granulomatous pneumonia • Characterized by activation of alveolar and interstitial macrophages together with lymphocytes (CD4 T cells), and can involve neutrophils and multinucleate giant cells • Most common causes include systemic fungal diseases, e.g. cryptococcosis, coccidioidomycosis, histoplasmosis, blastomycosis…and also by bacteria, particularly mycobacteria • Entry is typically via the aerogenous route Characterized by the activation of alveolar and interstitial macrophages and together with lymphocytes called CD4 T cells, and involve neutrophils and multinucleate giant cells. CONTINUOUS ACTIVATION OF Macrophages initiate CD4 t cells due to persistence of agent and in turn recruit giant cells (macrophages with multiple nuclei) and more neutrophils. 83 Most common causes: Systemic fungal diseases TB in third world areas (mycobacterium) Fig. 9‐67A Granulomatous pneumonia (Rhodococcus equi), lungs, foal. A, Cranioventral consolidation of the lungs with subpleural granulomas. Note that the pneumonic lesions in this foal are unilateral. This was an experimental case in which a foal was intratracheally inoculated with a suspension of Rhodococcus equi. B, Cut surface. Note the large, confluent, caseated granulomas. (Courtesy Drs. J. Yager and J. Prescott, Ontario Veterinary College.) 84 Granulomatous pneumonia: due to rhodococcus equi mycobacteria Multifocal to coalescing 28 10/13/2023 Tuberculosis • Communicable chronic granulomatous disease caused by Mycobacterium tuberculosis (acid-fast rod), usually affecting the lungs and lymph nodes • Initial exposure results in development of immune response that confers resistance but also leads to hypersensitivity (determined by a positive tuberculin test – type IV hypersensitivity reaction) • CD4 T cells of the Th1 subset play a crucial role in the cell-mediated immunity against mycobacteria – Mediators of inflammation and bacterial containment include IFN-γ, IL-12, TNF and nitric oxide synthase • Characterized histologically by granulomas, usually with central necrosis • Tb can result in systemic seeding, causing life-threatening forms such as miliary Tb and tuberculous meningitis. • HIV infection is a high risk factor for development or recrudescence of active Tb 85 Granuloma Formation 86 Multifocal, coalescing (coming together the lesions are coming together) Granuloma s Central area of necrosis, then macrophage, fibroblast then multinucleate giant cells Cheesy Fig. 9‐65B Pulmonary tuberculosis, lung, aged cow. A, Multifocal, coalescing granulomatous pneumonia involves most of the lung, except for the dorsal portion of the caudal lung lobe. B, Transverse section. Large multifocal to confluent caseating granulomas are present in the pulmonary parenchyma. Note the caseous (“cheesy,” pale yellow‐white) appearance of the granulomas, which is typical of bovine tuberculosis. (A courtesy Facultad de Medicina Veterinaria y Zootecnia, UNAM, México. B courtesy Dr. J.M. King, College of Veterinary Medicine, Cornell University.) Fig. 9‐66 Granulomatous pneumonia, lung, cow. There are several noncaseous granulomas (arrows), each with a small necrotic center filled with neutrophils, surrounded by histiocytes and mononuclear cells, and with an outer rim of connective tissue. H&E stain. (Courtesy Western College of Veterinary Medicine.) 87 29 10/13/2023 Granulomatous: Mycobacterium is engulfed with macrophages when it enters are body but it has an ability to evade dissolution of its membrane, so it persists in the macrophages → this is why the major comp of granulomas is macrophages Giant cells Central area of necrosis Lots of macrophages Fibrin Lymphocytes Giant cell at top right big macrophage has multiple nucleus, bc of coalesence ON exam: Macrophages are loaded with mycobacterium Acid fast stain: special stain 88 Pleural Lesions • Pleural effusion is the presence of fluid in pleural space, and it can be transudate or exudate • Effusion that is transudate is hydrothorax More watery • Causes of pleural exudate: microbial invasion (pleuritis/empyema), cancer, pulmonary infarction, viral pleuritis 89 Pleural Lesions • Pneumothorax refers to air or gas in pleural sac; spontaneous or secondary to thoracic/lung disorder. ‐ Consequences: tension, compromise of pulmonary circulation, lung collapse, infection • Hemothorax is the collection of blood in pleural cavity due to ruptured aortic aneurysm • Chylothorax is pleural collection of milky lymphatic fluid containing microglobules of lipid, and implies obstruction of major lymph ducts • Pyothorax is the collection of pus in the pleural cavity due to infection by pyogenic bacteria 90 30 10/13/2023 Fig. 9‐100 Hemothorax, right pleural cavity, dog. The right pleural cavity is filled with a large clot of blood from a ruptured thoracic aortic aneurysm, which caused unexpected death. Canine aortic aneurysms are associated with migration of Spirocerca lupi larvae along the aortic wall before their final migration into the wall of the adjacent esophagus. In other cases like this dog, the cause remains unknown (idiopathic aortic aneurysm). (Courtesy Dr. L. Gabor and Dr. A. López, Atlantic Veterinary College.) 91 Blood in the thoracic cavity. Compression Atelectasis Due to accumulation of blood in the pleural cavity Alveoli septa rupture (bullae) Fig. 9‐101 Chylothorax (cause unknown), thoracic (pleural) cavity, mink. Lymph (chyle) fills both the left and right pleural cavities. The heart (H) and pericardium are essentially normal because the chyle does not adhere to the outer surface of the pericardial sac, as typically happens with suppurative and fibrinous exudates in the thoracic cavity. (Courtesy Western College of Veterinary Medicine.) 92 Chylothorax, lymphatic fluid (chyle) (white blood cells and triglycerides) Fig. 9‐102 Pyothorax (Pasteurella multocida), right pleural cavity, cat. Pus in the thoracic cavity is called pyothorax or empyema. Purulent exudate also covers the visceral and parietal pleurae. This lesion is also referred to as suppurative pleuritis. (Courtesy Dr. A. López, Atlantic Veterinary College.) 93 Pyothorax 31 10/13/2023 Lung Tumors • Carcinomas • Squamous cell carcinoma arise centrally in major bronchi, preceded by metaplasia or dysplasia • Adenocarcinomas are peripherally located • Bronchioloalveolar carcinomas are subtype of adenocarcinoma • Metastatic tumors • Hemangiosarcoma • Smoking is most important risk factor for lung cancer Carcinomas: means there is a metastatic tumor of epithelial cells 94 Squamous cell carcinoma arise centrally in major bronchi Very common, especially in condition of smoking : columnar epithelium go through dysplasia, then metaplasia and turn into squamous cells Adenocarcinomas are peripherally located Involve glands and alveoli • Bronchoalveolar carcinomas are subtype of adenocarcinoma Metastatic tumor • Hemangiosarcoma → common in right atrium and then spreads to lungs Smoking : biggest risk factor for lung cancer Sarcoma: tumor of mesenchymal cells like smooth muscle or striated muscle Squamous metaplasia Dysplastic, basal cells, Squamous cell carcinoma. Goblet cells becoming hyperplastic Disordered squamous epithelia Infiltration cells 95 Squamous cell carcinoma 96 Start at hilar region (place where bronchiole enters lung, where BV enters) White discoloration: squamous cell carcinomas which are spreading 32 10/13/2023 Alveoli wall thickened Type 2 pneumocyte hyperplasia Most progressive state; cant see alveoli. connective tissue is iniltrated with inflammatory cells 97 98 99 Adenocarcinoma bronchioalveolar ]normal alveoli on left, on the right its cancerous. Alveoli are covered in pseudostratified columnar which is not supposed to be here Radio opaque - lung should look black (radio dense) Adenocarcinoma pictured here Nodiular or spread everywhere 33 10/13/2023 100 Hemangioma sarcoma Right atrium is dark red Hemangioma sarcoma will spread in lung; distributed red nodules in the lungs Can look like embolic pneumonia but difference is that they are more modular and raised whiile embolic pneumonia is more flat. 34