Pathology - Lung Flashcards
Describe the pathogenesis of ARDS
- initial injury to alveolar capillary membrane, leading to acute inflammatory response mediated by neutrophils
- increased capillary permeability leads to oedema and alveolar flooding
- activation of lung macrophages leading to release of proteases and cytokines
- fibrin deposition
- formation of hyaline membranes
- widespread surfactant abnormalities due to the injury to type II pneumocytes leading to atelectasis
- eventually organisation with scarring
What conditions are associated with the development of ARDS?
- infection: sepsis, diffuse pulmonary infection, gastric aspiration
- inhaled irritants: smoke, gases and chemicals, oxygen toxicity
- physical injury: head/chest trauma, fractures, drowning, burns, radiation
- chemical injury: heroin, barbiturates, ASA, paraquat
- haematological: multiple transfusions, DIC
- other physiological insults: pancreatitis, uraemia, cardiopulmonary bypass, hypersensitivity
What are the outcomes of ARDS
death
survival with organisation and scarring
What is the definition of asthma and what cells are involved?
- chronic respiratory disorder of the conducting airways usually caused by an immunologic reaction
- featuredby: reversible bronchoconstriction due to airway sensitivity, inflammation of bronchial walls and increased mucus secretion (plugging)
Cells involved: lymphocytes, mast cells, eosinophils, neutrophils, macrophages, smc
What are the pathological features of acute asthma
increased airway responsiveness
episodic bronchoconstriction
bronchial wall inflammation
increased mucus
What is the underlying mechanism of atopic asthma and triggers
IgE mediated type 1 hypersensitivity
triggers: environmental allergens such as dust, pollens, foods, drugs
What happens in the early and late phase reaction in atopic asthma
1) initial sensitisation
- antigen triggers dendritic cells in airway epithelium to activated TH2 cells
- TH2 cells release IL-4 that stimulated B cells to produce IgE, that bind to mast cells
2) immediate phase reactions
- re-exposure, antigen cross links IgE, causing mast cell release of primary mediators (histamine, heparin, trypsin)
- causing bronchospasm, increased vascular permeability, increased mucus production, vasodilation
3) late phase reaction
- dominated by recruitment of leukocytes (eosinophils, neutrophils, T cells)
Name some inflammatory mediators involved in atopic asthma
IL-1, IL-6, TNF NO PAF histamine bradykinin PGD2 LKTs
What is bronchiectasis and describe the morphological features and associated conditions
- destruction of SMC and elastic tissue by chronic infection causing permanent dilation of bronchi and bronchioles
clinical: cough, fever, purulent sputum
associated conditions: congenital (cystic fibrosis), post infection (staph aureus pnumonia, Tb) bronchial obstruction (tumour, foreign body), other (arthritis)
What is emphysema, describe the pathogenesis and complications?
Irreversible enlargement of airways distal to terminal bronchiole with destruction of alveolar walls without fibrosis.
Pathogenesis:
- exposure to toxic substances such as tobacco smoke causes inflammation, epithelial cell death and ECM proteolysis
- recruitment of macrophages and neutrophils results in the release of elastase that degrades alveolar elastic tissue and inflammatory cytokines (LKB4, IL-8, TNF)
- oxidants and free radicals inactivate alpha 1 antitripsin which normally inhibits elastase, protease-antiprotease imbalance
- end result is destruction of the alveolar walls without fibrosis
Complications: bullae, expiratory airflow limitation, infection, respiratory failure, pneumothorax, cor pulmonale
What is the role of cigarette smoke in emphysema?
- chronic inflammation
- increases neutrophils and macrophages in alveoli
- activates complement pathway and stimulates chemotactic factors (IL-8)
- increases elastase activity, loses balance between protease-antiprotease, overwhelming alpha-1 antitrypsin
- oxidative stress from free radicals and reactive oxygen species in smoke depletes glutathione and superoxide dismutase
- impaired ciliary function (mucus plugging, secondary infections, further alveolar destruction)
(Centri-acinar distribution from smoking, rather than pan-acinar emphysema from AT deficiency)
What are the types of emphysema
1) centriacinar (centrilobular): involves the central and proximal parts of acinus, most common (smokers)
2) panacinar (panlobular): uniform involvement of acinus, strong association with alpha 1 antitripsin deficiency
3) distal acinar (paraseptal): involvement of distal acinus, usually near the pleura
4) irregular: irregular involvement of acinus
What clinical conditions may cause a fat embolism and what is the clinical sequelae
causes: long bone fracture, soft tissue trauma
clinical: most asymptomatic, altered LOC, increased respiratory rate, SOB, hypoxia, thrombocytopenia, aneamia
What is the pathogenesis of fat embolism syndrome
- fat globules and aggregated platelets/RBC cause mechanical obstruction of microvasculature
- free fatty acids from fat globules cause endothelial injury, platelet activation and mediator release
Describe the pathogenesis of thrombotic PE, where do they originate/lodge, symptoms and risk factors
- PE are artery occlusions, almost always embolic with DVT being the source in >95% of cases
- fragmented thrombi from DVT carried through the venous system into right side of heart, then pulmonary artery
-site of lodgement: main pulmonary artery, pulmonary artery bifurcation or smaller branching arteries
clinical: depends on size and location of thrombus in pulmonary vasculature, most are asymptomatic
- symptoms = chest pain, SOB, collapse, syncope, cough, haemoptysis, death
- signs = tachycardia, hypoxia, hypotension, acute heart failure, fever
risk factors:
- primary = factor 5 leiden, antiphospholipid syndrome, prothrombin mutations
- secondary = obesity, OCP, cancer, immobilisation, long haul flights, pregnancy
