respiratory pathology

Question 1

Describe the pathogenesis of ARDS

Answer 1

● Injury to alveolar capillary membrane
● Acute inflammatory response (neutrophil mediated)
● Increased vascular permeability - leads to alveolar flooding
● fibrin deposition
● Formation of hyaline membranes
● Widespread surfactant abnormalities (damage to type II pneumocytes)
● Eventually leads to organisation with scarring

Question 2

What conditions are associated with the development of ARDS?

Answer 2

● Infection - sepsis, diffuse pulmonary infection, gastric aspiration
● Physical/injury - trauma to head, near drowning, burns or radiation
● Inhaled irritants - O2 toxicity, smoke, irritant gases and chemicals
● Chemical injury - barbiturates, heroin, paraquat
● Haematological conditions - multiple transfusions, DIC
● Other - pancreatitis, uraemia, cardiopulmonary bypass

Question 3

What is the definition of asthma?

Answer 3

Asthma is a chronic disorder of the conducting airways, usually caused by an immunological
reaction, which is marked by episodic bronchoconstriction due to increased airway sensitivity to
a variety of stimuli, inflammation of the bronchial walls and increased mucus secretion

Question 4

Describe the pathogenesis of acute atopic asthma

Answer 4

● It is a classic example of IgE mediated (Type 1) hypersensitivity
● Atopic triggers include: environmental allergens e.g. dust, pollen, dander, food
● On re-exposure to the antigen, the antigen induces cross linking of IgE bound to
previously sensitised mast cells .
● These mast cells release preformed mediators that directly and indirectly via neuronal
reflexes result in bronchospasm, increased vascular permeability, mucus production and
recruitment of leukocytes

Question 5

What are potential triggers for non-atopic asthma?

Answer 5

● Respiratory viruses, air pollutants, exercise, cold
● Can also be drug induced i.e. aspirin
● Occupational triggers - fumes from epoxy or resins, organic and chemical dusts (wood,
cotton), gases or other chemicals (formaldehyde/penicillin)
● Cigarette smoke also a trigger

Question 6

Bronchiectasis
What is bronchiectasis?

Answer 6

A disease characterised by permanent dilation of bronchi and bronchioles caused by destruction
of the muscle and elastic tissue, resulting from or associated with chronic necrotizing infections.
Also involves scarring and persistent infections

Question 7

What conditions are associated with the development of bronchiectasis?

Answer 7

● Congenital/hereditary conditions - cystic fibrosis, immunodeficiency, ciliary dyskinesia
● Post infectious - usually necrotising pneumonia - staph aureus, haemophilus, TB,
pseudomonas, some viral and fungal infections
● Bronchial obstruction - tumour or foreign body, mucous impaction
● Idiopathic in 25-50% of cases

Question 8

What clinical conditions can cause a fat embolism?

Answer 8

● Anything that results in fat globules travelling within the circulation
● Most commonly long bone fractures - common in severe trauma but <10% are clinically
significant
● Can rarely occur with burns and soft tissue trauma

Question 9

What is the pathogenesis of fat embolism syndrome?

Answer 9

● Mechanical obstruction of microvasculature in the lungs and brain by fat globules,
aggregated platelets and RBCs
● Biochemical injury from FFAs from fat globules causing endothelial injury, platelet
activation and mediator release

Question 10

What are the potential clinical sequelae of fat embolism?

Answer 10

● Majority are asymptomatic
● Neurological - altered LOC
● Pulmonary - tachypnoea, dyspnoea, hypoxia
● Haematological - thrombocytopaenia and anaemia

Question 11

Describe the pathogenesis of thrombotic pulmonary embolism

Answer 11

PEs originate from deep vein thrombosis (the majority from the 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, the artery bifurcation or the smaller branching arteries

Question 12

What factors determine the severity of the pathophysiological response to a pulmonary
embolism?

Answer 12

● Extent of pulmonary artery blood flow obstructed (Main one and the answer needed to
pass)
● Size of the vessel occluded
● Number of emboli
● Overall cardiovascular status
● Release of vasoactive factors, such as thromboxane A2

Question 13

What are the symptoms and signs of a pulmonary embolism?

Answer 13

Most PEs are small and produce no symptoms or signs at all (estimated 60-80% are
asymptomatic)

Symptoms
● Chest pain - typically pleuritic
● Dyspnoea
● Syncope
Signs
● Hypoxia
● Tahypnpoea
● Tachycardia
● Hypotension
● Shock/sudden death
● Acute right heart failure
● Fever
● Haemoptysis

Question 14

What are some risk factors for PE?

Answer 14

Primary factors - factor V leiden, antiphospholipid syndrome, prothrombin mutations
Secondary factors - obesity, OCP, cancer, immobilisation, long haul flights, pregnancy, central
venous line, hip fractures

Question 15

What are the potential clinical sequelae of a pulmonary thrombo-embolism?

Answer 15

Again, this relates to the size and number of emboli and overall state of the underlying
cardiovascular status.
● Majority are asymptomatic
● Severe PEs can cause sudden death
● Large PEs can cause haemodynamic compromise and shock
● PE can lead to pulmonary infarction causing some of the signs and symptoms listed
above
● May also cause pulmonary hypertension

Question 16

List other types of emboli

Answer 16

● Fat embolism
● Air embolism
● Amniotic fluid embolism
● Foreign body i.e. fragment of a catheter
● Tumour embolism

Question 17

What is emphysema?

Answer 17

A chronic lung condition characterised by irreversible enlargement the airspaces distal to the
terminal bronchiole, accompanied by destruction of alveolar walls without fibrosis

Question 18

Describe the pathogenesis of emphysema

Answer 18

● 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
● Protease-antiprotease imbalance leading to destructive protease activity
● Alpha 1 antitrypsin is a major protease inhibitor and a hereditary deficiency can lead to
emphysema at a younger age
● Accumulation of neutrophils, macrophages and lymphocytes results in the release of
elastases, cytokines and oxidants that cause epithelial injury and proteolysis of the
extracellular matrix
● Elastin degradation products further increase the inflammation
● Smoke depletes antioxidant mechanisms, further adding to the damage
● The end result is destruction of the alveolar walls without fibrosis

Question 19

What are the anatomical types of emphysema?

Answer 19

● Centriacinar - involves the central or proximal parts of the respiratory unit - the acinus -
sparing the distal alveoli. Involves the upper lobes and apices, primarily occurs in male
smokers associated with chronic bronchitis (MOST COMMON - 95%)
● Panacinar - uniform - alpha-1-antitrypsin deficiency . Pattern of destruction is chronic
low level destruction. Lower basal zones, uniform destruction.
● Distal acinar or paraseptal - causes spontaneous pneumathoraces
● Irregular - airspace enlargement
● Bulous - blebs
● Interstitial emphysema
● Compensatory - following lobectomy
● Obstructive overinflation - from a partial blockage

Question 20

What are the possible complications of emphysema?

Answer 20

● Bullous lung disease
● Expiratory airflow limitation
● Infection
● Respiratory failure
● Pneumothorax
● Cor pulmonale and congestive heart failure

Question 21

What is the role of cigarette smoke?

Answer 21

● Smokers have higher numbers of macrophages and neutrophils in the alveoli because
smoking stimulates neutrophil chemotactic factors and also activates the alternative
complement pathway
● Smoking stimulates release of neutrophil elastase, proteinases
● Smoking increases elastase activity in macrophages
● ROS in smoke deplete glutathione and superoxide dismutase

Question 22

How do the clinical features of emphysema differ to those with chronic bronchitis?

Answer 22

This is referring to the syndromes of pink puffer (emphysema) vs blue bloater (chronic
bronchitis)

The pink puffer syndrome phenotype is barrel chested, dyspnoeic, prolonged expiration,
hyperventilation. Relatively normal gas exchange until late stage in the disease process.

Blue bloater describes a phenotype of recurrent chest infections with purulent sputum, less
dyspnoea, decreased respiratory drive. Patient is typically hypoxic and cyanotic. Peripheral
oedema results from cor pulmonale and RV failure.

Question 23

What factors predispose to lung cancer?

Answer 23

● Tobacco smoking is the key factor - associated with daily amount and duration of habit
● Environmental exposures - radiation, asbestos, air pollution (particulates), occupational
inhaled substances (nickel, chromates, arsenic)
● Genetic mechanisms - dominant oncogenes (c-MYC, k-RAS) & loss of tumour suppressor
genes (p53, RB)
● Precursor lesions - squamous dysplasia, carcinoma in situ, atypical adenomatous
hyperplasia

Question 24

What are the classical clinical features of lung carcinoma?

Answer 24

● Cough
● Weight loss
● Chest pain
● Dyspnoea

Question 25

What are the main categories of primary lung cancer?

Answer 25

Adenocarcinoma - more common in women
● Squamous cell carcinoma - more common in men
● Small cell carcinoma - very malignant
● Large cell carcinoma

Question 26

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

Answer 26

● Local invasion
● Direct seeding of cavities/surfaces
● Lymphatic spread
● Haematogenous
● Surgical instruments
● Nerves

Question 27

What are the clinical effects of local spread of lung tumour?

Answer 27

● Airway obstruction = pneumonia, abscess, lobar collapse
● Obstruction of the SVC leading to SVC syndrome
● Pleural effusion
● Pericarditis or tamponade
● Hoarseness (from involvement of the laryngeal nerve)
● Dysphagia (from oesophageal obstruction)
● Pain from rib destruction
● Diaphragmatic paralysis (due to phrenic nerve involvement)
● Horner syndrome (from sympathetic ganglia)

Question 28

What paraneoplastic syndromes are associated with lung carcinoma?

Answer 28

Paraneoplastic syndromes are clinically significant in less that 10% of patients
● SIADH - hyponatraemia (predominantly small cell)
● ACTH excess - cushing’s syndrome (predominantly small cell)
● Parathyroid hormone/PTH-related peptide - hypercalcaemia (predominantly small
cell/squamous)
● Calcitonin - Hypocalcaemia
● Gonadotropins - gynaecomastia
● Serotonin/bradykinin - carcinoid syndrome

Question 29

Describe the relationship between asbestos exposure and malignant mesothelioma

Answer 29

● There is an increased incidence of malignant mesothelioma among people with heavy
exposure to asbestos. The lifetime risk is approximately 7-10%
● Asbestos bodies are found in increased numbers in the lungs of patients with
mesothelioma
● There is a long latent period for mesothelioma of approximately 25-45 years
● There is no increased risk in asbestos workers who smoke (in contrast to asbestos
related lung carcinoma)
● Asbestos workers are more at risk of dying from lung carcinoma than mesothelioma,
especially if they smoke

Question 30

Where can malignant mesothelioma arise?

Answer 30

● Pleura
● Peritoneum
● Pericardium
● Tunica vaginalis
● Genital tract

Question 31

What are the most common causes of community acquired pneumonia?

Answer 31

● Strep pneumoniae
● Mycoplasma pneumoniae
● Haemophilus influenzae
● Moraxella catarrhalis
● Staph aureus
● Klebsiella pneumoniae
● Pseudomonas aeruginosa
● Legionella pneumoniae

Question 32

What factors predispose patients to the development of acute bacterial pneumonia?

Answer 32

● Extremes of age
● Underlying chronic disease such as COPD, diabetes, cardiac failure, malnutrition
● Immunodeficiency from abnormal splenic function or asplenia

Question 33

What are the pathological patterns of bacterial pneumonia?

Answer 33

● Bronchopneumonia: patchy consolidation of the lung, areas of acute suppurative
inflammation, may be patchy through one lobe but is more often multilobar and
frequently bilateral and basal because of the tendency of secretions to gravitate into the
lower lobes

● Lobar pneumonia: fibrinosuppurative consolidation of a large portion of a lobe or an
entire lobe. Patterns overlap, patchy involvement may become confluent producing
lobar consolidation

Question 34

Describe the stages of the inflammatory response seen in lobar pneumonia

Answer 34

Four stages
● Congestion - vascular engorgement, intra-alveolar fluid with few neutrophils and often
the presence of numerous bacteria. The lung appears heavy, boggy and red

● Red Hepatisation - massive confluent exudation with neutrophils, red cells and fibrin
filling the alveolar spaces, the lobe appears red, firm and airless with a liver, like
consistency

● Gray hepatisation - progressive disintegration of red cells and the persistence of a
fibrinosuppurative exudate, lobe appears greyish brown and dry surface.

● Resolution - exudate within the alveolar spaces undergoes progressive enzymatic
digestion to produce granular semifluid debris that is resorbed, ingested by
macrophages, expectorated or organised by fibroblasts growing into it.

Question 35

What are the complications of pneumonia?

Answer 35

● Abscess formation - occurs as a result of tissue destruction and necrosis. Particularly
common with type 3 pneumococci or klebsiella infection
● Empyema - spread of infection into the pleural cavity, causing intrapleural
fibrinosuppurative reaction
● Bacteraemic dissemination - with seeding to heart valves, pericardium, brain, kidneys,
spleen or joints causing metastatic abscesses, endocarditis, meningitis or other
suppurative arthritis
● Local extension - pleuritis
● Bronchopleural fistula
● Parapneumonic effusion
● Respiratory failure/ARDS
● Pulmonary fibrosis
● Sepsis
● Death

Question 36

Describe the pathogenesis of aspiration pneumonia

Answer 36

● Aspiration of gastric contents
● Typically occurs in a patient with a decreased level of consciousness, abnormal
swallow/gag reflex or repeated vomiting
● Chemical and bacterial contents
● Usually >1 organism (aerobes >anaerobes)
● Necrotizing
● High risk of progression to abscess formation or dissemination and death

Question 37

What is atypical pneumonia?

Answer 37

A type of pneumonia characterised by interstitial pneumonitis, lack of exudate and a different
clinical picture to typical pneumonia.

Question 38

What organisms are usually involved with atypical pneumonia

Answer 38

● Mycoplasma
● Q fever (coxiella burnetii)
● Legionella
● Psittacosis (the bird one)
● Chlamydia
● Other viruses - RSV, parainfluenza, SARS, adenovirus

Question 39

Describe the clinical features of atypical pneumonia

Answer 39

● Usually less sputum
● No physical findings of consolidation
● Only a moderate increase in WCC
● Typical symptoms include fevers, myalgias, headache - cough is not prominent and is
usually dry
● Has a lower mortality compared to typical or classic pneumonia

Question 40

How is legionella contracted?

Answer 40

● Artificial aquatic environments e.g. water cooling tower, water supply tubing
● Inhalation of aerosol droplets
● Aspiration of contaminated drinking water

Question 41

How is legionella diagnosed?

Answer 41

Urinary antigen PCR or the gold standard is sputum culture - done in a special medium

Question 42

Tuberculosis
Describe the pathogenesis of tuberculosis in a previously unexposed immunocompetent
person

Answer 42

● Infection by mycobacterium tuberculosis via airborne exposure
● The organism enters alveolar macrophages, which cannot digest it. It then replicates in
the macrophages by blocking phagosome/lysosome fusion, leading to bacteraemia,
which manifests as a mild flu-like illness or can be asymptomatic.
● There is a delayed hypersensitivity reaction, where T cells contribute to tissue
destruction, granuloma formation and caseation
● The macrophage response also causes tuberculin positivity
● Re-exposure or reactivation causes a heightened immune reaction as well as tissue
destruction
● The infection may be contained or may progress.
● It can reactivate with any form of immunosuppression from any cause

Question 43

Outline the natural history of TB infection

Answer 43

● Primary infection
● Primary complex (Ghon focus) of local caseation (the calcified scar from this infection is
called the Ghon complex)
● It may heal OR become latent TB OR progressive primary TB
● If there is no clearance, reactivation or progression can lead to secondary TB
● Localised caseating lesions may form OR it may progress to secondary disease i.e. miliary
TB

Question 44

How may infection occur in secondary TB?

Answer 44

● May follow shortly after a primary infection (<5% of cases)
● Reactivation of latent organisms (occurs in areas of low disease prevalence)
● Reinfection (occurs typically in areas of high prevalence)

Question 45

Describe the pathological features in the lung during secondary infection with TB

Answer 45

● Usually the lesion occurs in the apical upper lobe
● It is an area of inflammation/granuloma with multinucleate giant cells
● Typified by cavitation and caseous necrosis
● There is simultaneous healing with fibrosis and calcification

Question 46

What are the complications of secondary TB?

Answer 46

● Tissue destruction
● Erosion of blood vessels
● Miliary TB spread
● Pleural effusion
● Empyema
● Fibrous pleuritis

Question 47

Outline the diagnosis of TB

Answer 47

● Clinical features plus CXR changes
● Sputum microscopy x 3
● PCR
● Mantoux test