VIVA: Pathology - Respiratory Flashcards
Describe the pathogenesis of thrombotic pulmonary embolism (PE)
- PEs originate from deep vein thrombosis* (95% from lower limb)
- Fragmented thrombi from DVTs are carried through the venous system and into the right side of the heart before lodging in the pulmonary arterial vasculature*, including the main pulmonary artery, pulmonary artery bifurcation or smaller branching arteries
*needed to pass
What are the symptoms and signs of pulmonary embolism?
- Clinical manifestations depend on size and location of the thrombus in the pulmonary vasculature
- Most PEs (60-80%) are small and produce no symptoms or signs
- Symptoms include pleuritic chest pain, dyspnoea, cough, haemoptysis and collapse/syncope*
- Signs include hypoxaemia, tachypnoea, hypotension, fever, acute right heart failure, pleural rub, shock, sudden death*
*total of 5 symptoms and signs to pass
List two other types of emboli
2 to pass:
- Fat (bone marrow)
- Air, other gas
- Amniotic fluid
- Foreign body (e.g. fragment of catheter)
Describe the pathogenesis of ARDS
Type of acute lung injury:
- Initial injury to alveolar capillary membrane* (endothelium)
- Acute inflammatory response* (neutrophil-mediated)
- Results in increased vascular permeability* and alveolar flooding
- Fibrin deposition
- Formation of hyaline membranes
- Widespread surfactant abnormalities* (damage to type II pneumocytes)
- Eventually leads to organisation with scarring
*3/4 needed to pass
What conditions are associated with the development of ARDS?
- Infection*: sepsis, diffuse pulmonary infection, gastric aspiration
- Physical/injury: head trauma, pulmonary trauma, fractures, near drowning, burns, radiation
- Inhaled irritants: O2 toxicity, smoke, irritant gases and chemicals
- Chemical injury: opiates, barbiturates, paraquat, acetylsalicylic acid, gastric aspiration
- Haematological conditions: multiple transfusions, DIC
- Other: pancreatitis, uraemia, cardiopulmonary bypass, hypersensitivity, organic solvents, drugs
*needed to pass + 2 other categories with 1 example each
What is the definition of asthma?
Asthma is a chronic disorder of the conducting airways, usually caused by immunological reaction, which is marked by:
- Episodic bronchoconstriction* due to increased airway sensitivity to a variety of stimulation
- Inflammation* of the bronchial walls
- Increased mucus secretion*
*needed to pass
Describe the pathogenesis of acute atopic asthma
- Classic example of IgE-mediated (type I) hypersensitivity*
- Atopic triggers: environmental allergens (e.g. dust, pollens, dander, food)
- On re-exposure to antigen, the Ag induces cross-linking of IgE bound to Fc receptors on mast cells
- Mast cells degranulate* and release preformed mediators that act directly and via neuronal reflexes to induce bronchospasm, increased vascular permeability, mucus production, and recruitment of leucocytes
*needed to pass
What are the potential triggers agents for non-atopic asthma?
2 to pass:
1. Non-atopic:
- Respiratory viruses
- Air pollutants
- Exercise
- Cold
2. Drug-induced (e.g. aspirin)
3. Occupational triggers:
- Fumes (e.g. epoxy resins, plastics)
- Organic and chemical dusts (e.g. wood, cotton, platinum)
- Gases (e.g. toluene)
- Other chemical (e.g. formaldehyde, penicillin products)
4. Asthmatic bronchitis in smokers
Name the main inflammatory cells involved in the pathogenesis of asthma
Wide range of inflammatory cells are involved, including (2 to pass):
- Lymphyocytes
- Eosinophils
- Mast cells
- Macrophages
- Neutrophils
How is asthma categorised pathologically?
2/4 to pass:
1. Atopic:
- Most common
- IgE-mediated (type I) hypersensitivity reaction
- Also involves TH2 cells
- Characterised by an immediate (bronchoconstriction) and late-phase (inflammation) reactions
- TH2 cytokines including IL-4, IL-5 and IL-13 are important mediators (IL-17 and IL-9 in some)
2. Non-atopic:
- No evidence of allergen sensitisation and negative skin test
- Family Hx is rare
3. Drug-induced (e.g. aspirin)
4. Occupational (e.g. epoxy fumes)
Name some common triggers of asthma
Atopic:
- Environmental factors (e.g. dust, pollens, food) in synergy with other pro-inflammatory cofactors such as respiratory viral infection
- Positive family Hx and skin test for allergens
Non-atopic:
- Triggers are less clear
- Viral respiratory infections (e.g. rhinovirus, parainfluenza, RSV)
- Inhaled air pollutants (e.g. smoking, sulfur dioxide, ozone, nitrogen dioxide)
- Exercise-induced
- Exposure to cold
What are the pathological features of acute asthma?
3/4 to pass:
- Increased airway responsiveness
- Episodic bronchoconstriction
- Bronchial wall inflammation
- Increased mucus
What happens in the early phase reaction in atopic asthma?
- Allergen exposure* produces IgE
- Re-exposure triggers mast cell degranulation and cytokine release
- Mediators induce bronchoconstriction, mucus production, and vascular changes (vasodilation, increased vascular permeability)
*needed to pass + concept
What is bronchiectasis?
Bronchiectasis is a disease characterised by permanent dilation of bronchi* and bronchioles caused by the destruction of the smooth muscle and elastic tissue *, resulting from or associated with chronic necrotising infections *
Also involves scarring and persistent infection
*needed to pass
What conditions are associated with the development of bronchiectasis?
4 examples to pass:
1. Congenital/hereditary:
- Cystic fibrosis
- Immunodeficiency
- Ciliary dyskinesia
- Kartagener’s syndrome
2. Post-infectious (necrotising pneumonia):
- Staph aureus
- Haemophilus
- TB
- Pseudomonas
- Adenovirus
- HIV
- Influenza
- Fungi
- Aspergillosis
3. Bronchial obstruction:
- Tumour, foreign body, mucous impaction
4. Other:
- Rheumatoid arthritis
- SLE
- Inflammatory bowel disease
- Post transplantation
5. Idiopathic (25-50%)
Name some risk factors for pulmonary embolism
- Primary*:
- Factor V Leiden
- Antiphospholipid syndrome
- Prothrombin mutations - Secondary*:
- Obesity
- OCP
- Cancer
- Immobilisation
- Long haul flights
- Pregnancy
- Indwelling central venous line
- Hip fracture
*1 primary and 3 secondary needed to pass
What factors determine the severity of pathophysiological response to pulmonary embolism?
- Extent of pulmonary artery blood flow obstructed*
- Size of vessel occluded
- Number of emboli
- Overall cardiovascular status
- Release of vasoactive factors (e.g. TxA2)
*needed to pass (or 2 others)
What is emphysema?
Chronic lung condition characterised by irreversible enlargement * of the airspaces distal to the terminal bronchiole *, accompanied by destruction of alveolar walls without obvious fibrosis *
*2/3 to pass
Describe the pathogenesis of emphysema
- Loss of cellular homeostasis:
- Caused by exposure to toxic substances * such as tobacco smoke and inhaled pollutants
- Induces ongoing inflammation, epithelial cell death and ECM proteolysis - Mild chronic inflammation *:
- Accumulation of neutrophils, macrophages and lymphocytes and release of mediators (e.g. LTB4, IL-8, TNF), elastases and oxidants which cause epithelial injury and proteolysis of the ECM - Protease-antiprotease imbalance *:
- Destructive effect of high protease activity in patients with low anti-protease activity (1% of patients with emphysema have alpha1-antitrypsin deficiency, which normally inhibits protease activity)
- Elastin degradation * products further increase the inflammation - Oxidant-antioxidant imbalance *:
- Abundant reactive oxygen species (e.g. superoxide dismutase, glutathione) in smoke depletes antioxidant mechanisms and incites tissue damage - End result is destruction of the alveolar walls without fibrosis
*2 to pass
How do the clinical features of emphysema differ from those with chronic bronchitis?
“Pink puffer” (emphysema)*:
- Barrel-chested, dyspnoeic, prolonged expiration, hyperventilation
- Relatively normal gas exchange until late in disease
“Blue bloater” (chronic bronchitis)*:
- Hx of recurrent chest infections with purulent sputum
- Less dyspnoea, decreased respiratory drive
- Patient is hypoxic and cyanotic
- Peripheral oedema results from cor pulmonale and RV failure
*2 distinguishing clinical features
What are the possible complications of emphysema?
3 to pass:
- Bullous lung disease
- Expiratory airflow limitation
- Infection
- Respiratory failure
- Pneumothorax
- Cor pulmonale, congestive heart failure (“pink puffers”)
What factors predispose to lung carcinoma?
- Tobacco smoking:
- 10x increase in risk
- Statistically associated with daily amount, inhalation tendency, duration of habit, histologic changes in respiratory epithelium - Environmental exposures:
- Radiation
- Asbestos
- Air pollution (particulates, radon)
- Occupational inhaled substances (nickel, chromates, arsenic, uranium) - Genetic mechanisms:
- Dominant oncogenes (c-MYC, k-RAS)
- Loss of tumour suppressor genes (e.g. p53, RB) - Precursor lesions:
- Squamous dysplasia
- Carcinoma in situ
- Atypical adenomatous hyperplasia
- Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
What are the classic clinical features of lung carcinoma?
3/4 to pass:
- Cough (75%) and haemoptysis
- Weight loss (40%)
- Chest pain (40%)
- Dyspnoea (20%)
What paraneoplastic syndromes are associated with lung carcinoma?
Clinically significant in 1-10% of patients:
- SIADH* (hyponatraemia; predominantly small cell)
- ACTH* (Cushing’s syndrome; predominantly small cell)
- PTH, PTHrP or PGE* (hypercalcaemia; predominantly small and squamous cell)
- Calcitonin (hypocalcaemia)
- Gonadotropins (gynaecomastia)
- 5HT, bradykinin (carcinoid syndrome)
- Others: Lambert-Eaton myaesthenic syndromes, peripheral neuropathy, acanthosis nigricans, clubbing (hypertrophic pulmonary osteoarthropathy)
*2/3 to pass + 1 other
