Q1

What is the pathological definition of emphysema?

  • Emphysema is a condition of the lung characterised by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, & without obvious fibrosis

Pass criteria:

  • Bold to pass
  • Permanent Enlargement + destruction

Describe the pathogenesis of emphysema.

  • Protease – antiprotease theory
  • Alveolar wall destruction results from an imbalance between proteases (mainly elastase) and antiproteases
  • Elastases from Neutrophils, also Macrophages, Mast cells, pancreas, bacteria
  • Anti-elastases: alpha1AT, secretory leukoprotease inhibitor, serum alpha1macroglobulin
  • alpha 1AT inhibits neutrophil proteases.
  • PiZZ variant predisposes to emphysema
  • Neutrophils normally sequestered in lung (L > U) and a few gain access to the alveolar space.
  • Any stimulus that increases the number of leukocytes (neutrophils / macrophages) in lung or release of their elastase containing granules increases elastocytic activity. – Stimulated neutrophils also release oxygen free radicals which inhibit alpha 1-AT activity meaning process of elastic tissue destruction is unchecked

Pass Criteria:

  • Know that key is imbalance between proteases (mainly elastase) and antiproteases

What is the role of cigarette smoke?

  • Smokers have increased neutrophils & macrophages in alveoli, – smoking stimulates neutrophil chemotactic factor (e.g. IL-8), nicotine chemotactic, smoke activates alternative complement pathway
  • Smoking stimulates release of neutrophil elastase, proteinase 3, Catepsin G
  • Smoking increased elastase activity in macrophages (not inhib by alpha1-AT)
  • Reactive oxygen species in cigarette smoke deplete glutathione and superoxide dismutase

Note centri-acinar distribution due to impaction of smoke particles in small bronchi / bronchioles with neutrophil influx. Differs to pan-acinar emphysema associated with a1-AT deficiency and chronic low level proteolysis from neutrophils in transit through the lung circulation.

Pass criteria:

  • 2 effects

 


Q2

What disorders can precipitate the Adult Respiratory Distress Syndrome, ARDS?
Prompt: What clinical conditions are associated with development of ARDS.

  • Infection:  sepsis*, diffuse pulmonary infections*, gastric aspiration*
  • Trauma:  lung injury, head injury*, burns, radiation
  • Inhalation:  oxygen, smoke, irritants
  • Chemical injury:  heroin, salicylate, barbiturate, paraquat
  • Haematology:  transfusions, DIC
  • Other:  pancreatitis, uremia, CP bypass, hypersensitivity reactions
  • (50% of ARDS cases associated with *)

Pass criteria:

  • 4 groups, 1 example from each
  • Need to include infection

What is the pathogenesis of ARDS?

  • Diffuse alveolar capillary damage, variety of insults, initiated by different mechanisms.
  • Capillary injury causes inc. vascular permeability, alveolar flooding & oedema, fibrin exudation, formation of hyaline membranes, loss of diffusion capacity, abnormalities of surfactant.
  • Consequence of uncontrolled activation of acute inflammatory response; most injury by neutrophils
  • Macrophages alternative source of injury

Pass Criteria:

  • 3 out of 4 bold to pass

What are the outcomes of ARDS?

  • Death, survival with organisation and scarring

 


Q3

Describe the relationship between asbestos exposure and malignant mesothelioma.

  1. Increased incidence among people with heavy exposure to asbestos. Lifetime risk up to 7-10%.
  2. Asbestos bodies found in increased numbers in lungs of patients with mesothelioma.
  3. Long latent period for mesothelioma (25-45 yrs).
  4. No increased risk in asbestos workers who smoke (in contrast to asbestos related lung carcinoma). Asbestos workers more at risk of dying from lung carcinoma (especially if they smoke).

Pass: 2 of 4

Where can malignant mesothelioma arise?

1.            Pleura

2.            Peritoneum

3.            pericardium

4.            tunica vaginalis

5.            genital tract

Pass: Bold

 


Q4

What is emphysema?

Abnormal permanent enlargement of air spaces distal to terminal bronchioles with alveolar wall destruction and minimal fibrosis.

Pass Criteria:

  • Bold to pass.

What are the anatomical types of emphysema?

•             Ceniriacinar — involves centra


Q5

What are the clinical features of PE?

Usually present with respiratory compromise:

  • SOB
  • Hypoxia
  • Tachypnoea
  • Shock
  • Collapse
  • Hypotension
  • Right heart failure
  • Pleural rub
  • Pleuritic pain
  • Fever
  • Cough
  • Haemoptysis
  • Death

NB. 60-80% are silent.

Pass Criteria:

  • 5 features to pass.

Name some risk factors for PE.

  • Primary
    • Factor V Leiden
    • Antiphospholipid syndrome
    • Prothrombin mutations
  • Secondary
    • Obesity
    • OCP
    • Cancer
    • Immobilisation
    • Long haul flights
    • Pregnancy
    • Indwelling CVL
    • Hip fractures

Pass Criteria:

  • 1 primary and 3 secondary to pass.

What factors determine the severity of the pathophysiological response to PE?
Prompt: What are some features of the emboli?

  • Extent of the pulmonary artery blood flow obstructed
  • Size of the vessel occluded
  • Number of emboli
  • Overall CVS status
  • Release of vasoactive factors (e.g. thromboxane A2).

Pass Criteria:

  • Bold to pass
  • Also will accept 2 of the others as a pass.

Q6

What is emphysema?

Chronic lung condition characterised by irreversible enlargement of the airspace distal to the terminal bronchiole, accompanied by destruction of alveolar walls without fibrosis.

Pass Criteria:

  • 2 out of 3 bold to pass

Describe the pathogenesis of emphysema.

  • Loss of cellular homeostasis caused by exposure to toxic substances such as tobacco smoke and inhaled pollutants which induces ongoing inflammation, epithelial cell death and extracellular matrix proteolysis
  • Accumulation of neutrophils, macrophages and lymphocytes results in release of elastases, cytokines (including IL-8) and oxidants that cause epithelial injury and proteolysis of the extracellular matrix
  • Elastin degradation products further increase the inflammation
  • End result in destruction of the alveolar walls without fibrosis

Pass Criteria:

  • 2 bold 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 the disease
  • Blue bloater – Chronic Bronchitis
    • Hx of recurrent chest infections
    • Purulent sputum
    • Less dyspnoea
    • Decreased respiratory drive
    • Patient is hypoxic and cyanotic
    • Peripheral oedema results from cor pulmonale and RV failure

Pass Criteria:

  • 2 distinguishing clinical features to pass.

Q7

What are the main categories of primary lung cancer?

  • Adenocarcinoma (more common in females)
  • Squamous cell carcinoma (more common in males)
  • Small cell carcinoma (very malugnant)
  • Large cell carcinoma (undifferentiated)

Pass Criteria:

  • Bold to pass.

What are the pathways by which a malignant tumour may spread?

  • Local invasion
  • Direct seeding of cavities/surfaces
  • Lymphatics
  • Haematogenous spread
  • Surgical instruments
  • Nerves

Pass Criteria:

  • 3 of 4 Bold to pass.

What paraneoplastic syndromes can be associated with lung carcinomas?

  • SIADH (Hyponatraemia as per CBB, small cell carcinoma)
  • ACTH (Cushing’s disease)
  • PTH, PTHrP, PGE (Hypercalcaemia)
  • Calcitonin (Hypocalcaemia)
  • Gonadotrophins (Gynaecomastia)
  • Serotonin/bradykinin (Carcinoid syndrome)

Pass Criteria:

  • SIADH and 1 other to pass.