Pathology - Lung Flashcards
Describe the pathogenesis of ARDS
- initial injury to alveolar capillary membrane leading to increased capillary permeability and edema
- activation of lung macrophages leading to release of antioxidants, proteases and cytokines
- aggregation of activated neutrophils leading to further damage of endothelium and epithelium
- fibrin deposition
- formation of hyaline membranes
- loss of surfactant leading to atelectasis
What conditions are associated with the development of ARDS
- infection: sepsis, diffuse pulmonary infection, gastric aspiration
- physical injury: drowning, burns, radiation, smoke inhalation
- chemical injury: heroin, barbiturates
- haematological conditions: DIC, uremia
What are the outcomes of ARDS
death
survival with organisation and scarring
What is the definition of asthma and what cells are involved?
- disorder of the conducting airways usually caused by an immunologic reaction
- bronchoconstriction due to airway sensitivity, inflammation of bronchial walls and increased mucus secretion
cells involved: lymphocytes, eosinophils, mast cells, macrophages, neutrophils
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 bradykinin PAF histamine prostaglandin D2 leukotrienes
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 their walls without fibrosis
pathogenesis:
1) smoke causes inflammation with recruitment of macrophages and neutrophils
2) neutrophils release elastase that causes loss of alveolar elastic tissue
3) oxidants and free radicals inactivate alpha 1 antitripsin which normally inhibits elastase
4) small airway inflammation leads to goblet cell metaplasia and mucus plugging
complications: bullae, expiratory airflow limitation, infection, respiratory failure, pneumothorax, cor pulmonale
What is the role of cigarette smoke in emphysema
- stimulates neutrophil chemotactic factors, activates complement and stimulates neutrophil release of elastase
- reactive oxygen species in smoke inactivates alpha 1 antitripsin
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
What type of emboli are there and what factors determine the severity of pulmonary embolisms
types: fat, amniotic fluid, foreign body, thrombus
severity: size of clot, extent of circulation obstructed, number of emboli, location of emboli, overall CVS status
What factors pre-dispose to lung cancer
smoking
environment (radiation, air pollution, asbestos)
genetics (gene mutations)
What are the classic clinical features of lung cancer
cough weight loss chest pain dyspnea haemoptysis
What are the clinical effects of local tumour spread
airway obstruction (causing lung collapse, pneumonia, abscess)
SVC obstruction
pleural effusions
tamponade
hoarseness, dysphagia
diaphragmatic paralysis (phrenic nerve compression)
horner syndrome
How do malignant tumours spread
local invasion
direct seeding
lymphatics
haematogenously
What paraneoplastic syndromes are associated with lung carcinoma
SIADH: due to excess ADH Cushing syndrome: due to excess ACTH Hypercalcaemia: due to excess PTH Hypocalcaemia: due to excess calcitonin Carcinoid syndrome: due to excess serotonin
What are the main categories of primary lung cancer
adenocarcinoma: most common form and seen in non-smokers
squamous cell carcinoma: highly associated with tobacco smoke
small cell carcinoma: strongest association with tobacco smoke, most malignant and high metastasis rate
large cell carcinoma: least common
Describe the link between asbestos exposure and malignant mesothelioma
- increased risk in people with heavy asbestos exposure with a lifetime risk of 7-10%
- asbestos bodies found in lungs of people with mesothelioma
- no increased risk in asbestos workers who smoke
Where can malignant mesothelioma arise
pleura peritoneum pericardium tunica vaginalis genital tract
What are the common causes of bacterial pneumonia and what predisposes people to pneumonia
causes:
strep pneumonia, h influenzae, staph aureus, klebsiella, pseudomonas, legionella, moraxella catarrhalis
predisposition:
extremes of age, chronic disease (COPD, diabetes), immune deficiencies (HIV), lack of spleen
What are the pathological patterns of bacterial pneumonia
lobar pneumonia: consolidation of a large portion of a lobe or an entire lobe
bronchopneumonia: consolidation may be patchy though one lobe but is more often multilobar
Describe the stages of inflammation seen in lobar pneumonia
1) congestion: vascular engorgement and intra-alveolar fluid present
2) red hepatisation: massive exudation with neutrophils, red cells and fibrin filing the alveolar spaces
3) gray hepatisation: progressive disintegration of red cells and persistence of fibrinosuppurative exudate
4) resolution: exudate in alveolar space undergoes enzymatic digestion
Describe the pathogenesis of aspiration pneumonia
- aspiration of gastric contents: partly chemical (gastric acid), partly bacterial (mixed oral flora)
- often necrotizing with lung abscess as a common complication
What is atypical pneumonia and what organisms are involved
- acute febrile respiratory disease characterised by patchy inflammatory changes in the lungs
- usually confined to alveolar septa and lacks exudate, no findings of consolidation
clinical:
fever, headache, myalgia, cough not prominent, lower mortality than typical pneumonia
causes:
mycoplasma is most common, q fever, legionella, rsv, parainfluenza
Compare organisms that cause typical and atypical pneumonia
typical:
strep pneumonia, h influenza, moxarella catarrhalis, staph aureus, klebsiella, pseudomonas
atypical:
mycoplasma, chlamydiae, legionella, rsv, parainfluenza, adenovirus
What are complications of pneumonia
abscess formation
bacterial dissemination
sepsis
respiratory failure
How is legionella contracted, what are at risk groups and how is it diagnosed
cause:
artificial aquatic environments, inhalation of aerosolised droplets, aspiration of contaminated drinking water
risks:
underlying co-morbidities (cardiac/renal/immune/transplant), smokers, chronic lung disease, elderly
diagnosis:
urinary antigen or fluorescent antibodies on sputum, culture is gold standard
Outline the natural history of tuberculosis
1) Primary infection
- entry of Tb (aerobic non-spore forming non-motile bacillus with waxy cell wall) into alveolar macrophage
- mycobacterium in phagosome of macrophage but is able to prevent fusion with lysosome
- replication in alveolar macrophage unchecked initially, leading to bacteraemia and mild illness
- activation of cell mediated immunity creates a granuloma to wall off the bacteria
- tissue inside the granuloma dies = caseous necrosis = creating area known as a Ghon focus
- ghon focus undergoes fibrosis and calcification, becoming a ranke complex
- bacteria in Ghon focus is either killed or remains latent
2) Secondary infection
- if immunocompromised or in ageing, Ghon focus can become re-activated and spread to apex of upper lobes
- usually years after initial infection
- bacilli elicit a prompt tissue response that walls off infection leading to further caseous necrosis and cavitation
- bacilli may then spread to other areas, including vascular system causing systemic miliary Tb
Describe the pathological features in the lung of secondary infection with tuberculosis
- apical upper lobe location with area of inflammation/granuloma
- central caseous necrosis and cavitation
- healing by fibrosis and calcification
complications: tissue destruction, erosion of blood vessels, miliary spread, pleural effusions, empyema
How is tuberculosis diagnosed
clinical features:
at risk patients, CXR showing apical lung consolidation/cavitation
microbiological:
acid fast smears and cultures, PCR, mantoux test
What are the different types of asthma?
1) Atopic (allergic) = most common, caused by IgE reaction, triggered by dust, pollens, food, ect
2) Non-atopic = triggered by viral infections, chemical irritants, cold, exercise
3) Drug-induced = triggered by drugs such as nsaid
4) Occupational = triggered by fumes, organic acid, chemical dust, gases
