Lung

Question 1

One-sentence summary of asthma pathogenesis

Answer 1

Widespread reversible narrowing of the airways that changes in severity over short periods of time

Question 2

Asthma pathogenesis (immediate and late phase)

Answer 2

Sensitisation to allergen; followed by…

Immediate phase = mast cell degranulation –> mediator release –> inc. vascular permeability, eosinophil and mast cell recruitment and bronchospasm

Late phase = tissue damage, increased mucous production, muscle hypertrophy

Question 3

Histological features of asthma

Answer 3

Hyperaemia
Eosinophils w/ Charcot Leyden crystals
Goblet cell hyperplasia 
Hypertrophic constricted muscle
Mucus plugging (may be spiral-shaped- Curschmann's spiral)
Inflammation

Question 4

COPD definition

Answer 4

Chronic cough productive of sputum; most days for ≥3 months over ≥2 consecutive years

Question 5

One-sentence summary of COPD pathogenesis

Answer 5

Chronic injury to airways elicits local inflammation and reactive changes

Question 6

Histological features of COPD

Answer 6

Dilatation of airways
Hypertrophy of mucous glands
Goblet cell hyperplasia

Question 7

One-sentence summary of bronchiectasis pathogenesis

Answer 7

Permanent abnormal dilatation of the terminal bronchi

Question 8

Causes of bronchiectasis

Answer 8

Congenital (CF, ciliary dyskinesia [i.e. Kartagener’s syndrome])
Inflammatory (post-infectious, obstruction, 2nd to bronchiolar disease and interstitial fibrosis, asthma)

Question 9

Pathophysiology of CF

Answer 9

Autosomal recessive
CFTR gene on Chr 7 –> abnormal –> defective Cl- ion transfer so less water transfer to secretions
S/S affect all organs (from abnormally thick secretions)

Question 10

Histological features of pulmonary oedema

Answer 10

Intra-alveolar fluid on histology

“Heart failure cells” = iron-laden macrophages

Question 11

Histological features of ARDS and RDS

Answer 11

Basic pathology the same = diffuse alveolar damage

Gross pathology:
	Fluffy white infiltrates in all lung fields
	Lungs expanded/firm
	Plum-coloured lungs, airless
	>1kg mass

Micro-pathology:

1. Capillary congestion
2. Exudative phase
3. Hyaline membranes
4. Organising phase

Question 12

Pathology and organisms of bronchopneumonia

Answer 12

Low virulence organisms (staph, H. influenzae, strep, pneumococcus)

Pathology = patchy bronchial and peribronchial distribution, lower lobes, inflammation surrounding the airways themselves and is within the alveoli

Question 13

Pathology and organisms of lobar pneumonia

Answer 13

Affects entire lobe; infrequent due to ABx; 90-95% pneumococci (i.e. strep)

Stages of lobar pneumonia:

(1) Congestion Hyperaemia, Intra-alveolar fluid
(2) Red hepatization Hyperaemia, Intra-alveolar neutrophils (non-atypical)
(3) Grey hepatization Intra-alveolar connective tissue
(4) Resolution Restoration of normal architecture

Question 14

Pathology and organisms of atypical pneumonia

Answer 14

Mycoplasma, viruses (CMV, influenza), Coxiella, chlamydia, etc. i.e. CMV pneumonia in those immunosuppressed

Interstitial inflammation without the accumulation of intra-alveolar inflammatory cells
Chronic inflammatory cells within alveolar septa with oedema ± viral infections

Question 15

What type of alveolar parenchyma loss is caused by smoking?

Answer 15

Centred on bronchioles- centrilobular

Question 16

What type of alveolar parenchyma loss is caused by alpha-1 antitrypsin deficiency?

Answer 16

Diffuse loss- panacinar

Question 17

What is a granuloma?

Answer 17

Collection of histiocytes, macrophages ± giant multinucleate cells

Question 18

Pathogenesis of sarcoidosis

Answer 18

Abnormal host immunological response to variety of commonly encountered antigens, probably environmental in origin

Question 19

Lung pathology of sarcoidosis

Answer 19

Discrete epithelioid and giant cell granulomas, preferential distribution in upper zones with a tendency to peri-lymphatic and peri-bronchial –> advanced disease becomes fibrocystic

Question 20

Diagnostic features of sarcoidosis

Answer 20

Non-caseating granuloma, elevated serum ACE, hypercalcaemia (1a-hydroxylase)

Question 21

Presentation of pulmonary vasculitis

Answer 21

Present as life threatening haemorrhage, chronic haemoptysis, mass lesion, interstitial lung disease

Question 22

Match the site of origin to the type of lung cancer:

Airways, pleura, central/peripheral, peripheral alveolar spaces

Adenocarcinoma, mesothelioma, SCLC, SCC

Answer 22

Airways (SCC)
Peripheral alveolar spaces (Adenocarcinoma)
SCLC can arise either centrally or peripherally
Mesothelioma is a tumour of the pleura

Question 23

Name a benign lung tumour

Answer 23

Chondroma

Question 24

Pathogenesis of SCC

Answer 24

Squamous epithelium is much more resilient, but it does NOT have cilia –> leads to a build-up of mucus
Within this mucus, you will get loads of carcinogens –> more carcinogens accumulate

Normal epithelium –> hyperplasia –> squamous metaplasia –> dysplasia –> carcinoma in situ –> invasive carcinoma

Question 25

Mutations in adenocarcinoma, smokers vs non-smokers

Answer 25

In smokers, the main mutations are K-ras, issues with DNA methylation and p53
In non-smokers, EGFR mutations are very important (these are drug targets)

Question 26

Histological features of adenocarcinoma

Answer 26

Glandular differentiation
Gland formation
Papillae formation
Mucin

Question 27

What pattern is seen in adenocarcinoma?

Answer 27

Multi-centric pattern; many tumours at different stages of differentiation

Question 28

Histology of large cell carcinoma

Answer 28

Poorly differentiated tumours composed of large cells
There is NO histological evidence of glandular or squamous differentiation

NOTE: on electron microscopy –> may be evidence of glandular, squamous or neuroendocrine differentiation
POORER prognosis

Question 29

Key features of SCLC

Answer 29

Very close association with SMOKING
Often CENTRAL and near the bronchi
80% will present with advanced disease –> very chemosensitive but VERY POOR PROGNOSIS
May cause paraneoplastic syndromes (i.e. SIADH)

Question 30

Histology and cytology of SCLC

Answer 30

Histology:
Small poorly differentiated cells
Common mutations: p53, RB1

Cytology:
Small cells
Ciliated normal respiratory cell

Question 31

Of SCLC and NSCLC, which is more chemosensitive?

Answer 31

SCLC

Question 32

How do you get cytological samples of lung cancer?

Answer 32

Sputum
Bronchial washings and brushings
Pleural fluid
Endoscopic fine needle aspiration of tumour/enlarged lymph nodes

Question 33

How do you get histological samples of lung cancer?

Answer 33

Biopsy at bronchoscopy – central tumours
Percutaneous CT guided biopsy – peripheral tumours
Mediastinoscopy and lymph node biopsy – for staging
Open biopsy at time of surgery if lesion not accessible otherwise - frozen section
Resection specimen - confirm excision and staging

Question 34

Lung cancer management

Answer 34

Curative –> Surgery ± radical radiotherapy ± immunomodulatory therapy

Palliative –> Chemoradiotherapy, immunomodulatory, targeted therapy (i.e. EGFR-targeted)
N.B. high levels of PD1 or PDL1 protein expression (IHC) may inhibit immune response
Drug response typically develops after 11m

Question 35

Endocrine and non-endocrine paraneoplastic syndromes in lung cancer

Answer 35

Endocrine:
(1) Antidiuretic hormone (ADH)
“Syndrome of inappropriate antidiuretic hormone” causing hyponatremia (especially SCC)
(2) Adrenocorticotropic hormone (ACTH)
Cushing’s syndrome (especially small cell carcinoma)
(3) Parathyroid hormone-related peptide
Hypercalcaemia (especially squamous carcinoma)
(4) Other:
Calcitonin –> Hypocalcaemia
Gonadotropins –> Gynecomastia
Serotonin –> “Carcinoid syndrome” (especially carcinoid tumours; rarely SCC)

Non-endocrine:
Haematologic/coagulation defects, skin, muscular, miscellaneous disorders