Respiratory pathology 290921

Question 1

asthma pathogenesis

Answer 1

 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 2

Histology of asthma

Answer 2

 [Top left] Hyperaemia
 [Top right] Eosinophils and goblet cell hyperplasia
 [Bottom left] Hypertrophic constricted muscle
 [Bottom right] Mucus plugging and inflammation

Question 3

Histology of COPD

Answer 3

 Dilatation of airways
 Hypertrophy of mucous glands
 Goblet cell hyperplasia

Question 4

Complications of COPD

Answer 4

 Repeat infections
 Chronic hypoxia (reduced exercise tolerance, pul. HTN  RHF)
 Lung cancer risk

Question 5

Bronchiectasis causes

Answer 5

congenital e.g. CF, ciliary dyskinesia

more commonly - inflammatory, post infectious, secondary to bronchiolar disease

Question 6

Complications of bronchiectasis

Answer 6

 Recurrent infections Haemoptysis
 Cor pulmonale Amyloidosis
 Absesses

Question 7

Common infections in CF

Answer 7

• S. aureus H. influenzae

* P. aeruginosa B. cepacia

Question 8

Pulmonary oedema pathology

Answer 8

fluid accumulation in alveolar spaces
o Causes – LHF, alveolar injury, neurogenic, high altitude
o Pathology:
 Intra-alveolar fluid on histology (left)
 “Heart failure cells” = iron-laden macrophages (right)

Question 9

Aetiology of ARDS/RDS

Answer 9

o Acute damage to endothelium ± alveolar epithelium leading to an exudative inflammatory reaction
 Adults = acute respiratory distress syndrome / ARDS
• Infection Aspiration Trauma
• Inhaled irritant Shock Blood transfusion
• DIC Drug overdose Pancreatitis
 Neonates = hyaline membrane disease of the newborn / RDS (HMD of newborn = RDS)
• Insufficient surfactant
• Premature babies

Question 10

Gross pathology of ARDS

Answer 10

 Fluffy white infiltrates in all lung fields
 Lungs expanded/firm LIKE LIVER
 Plum-coloured lungs, airless
 >1kg mass

Question 11

Micro-pathology of ARDS

Answer 11

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

Question 12

bronchopneumonia

Answer 12

 Elderly
 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

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 normal architecture
 Complications  abscess, pleuritis, effusion, empyema (infected effusion), fibrosis, sepsis

Question 14

emphysema

Answer 14

o	Causes = damage to alveolar epithelium:
	Smoking					centrilobular loss
	A1AT deficiency				panacinar loss 
	Rare (IVDU, connective tissue disease) 
o	Complications:
	Bullae formation  pneumothoraces 
	Respiratory failure
	Cor pulmonale

Question 15

A1AT

Answer 15

inhibited by smoke, inhibits proteases that damage the alveoli

Question 16

Pulmonary thromboembolism

Answer 16

 Small emboli:
• Pleuritic chest pain or chronic progressive SoB due to pulmonary HTN
• Repeated emboli  increasing occlusion of pulmonary vascular bed and pulmonary HTN
 Large emboli:
• Occlude main pulmonary tract  saddle embolus  sudden death / RHF / shock
• 30% will develop a second embolus

Question 17

What are the different lung cancers sites

Answer 17

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

Question 18

Squamous cell carcinoma

Answer 18

smokers, central, spread locally, late metastasis

Question 19

Adenocarcinoima

Answer 19

o Peripheral (terminal airways) with multi-centric pattern (many tumours at different stages of differentiation)
o Precursor lesion: atypical adenomatous hyperplasia [LEFT picture]
 This is proliferation of atypical cells lining the alveolar walls
 This will increase in size and eventually become invasive
o Molecular Pathways in the Development of Adenocarcinoma [RIGHT picture]
 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)
o Frequency of adenocarcinoma:
 Incidence is INCREASING
 More common in females, far East and non-smokers
o Extra-thoracic metastases are COMMON and occur EARLY (80% present with metastases)

o Histology will show evidence of glandular differentiation and…
 Gland formation
 Papillae formation
 Mucin

Question 20

Large cell carcinoma

Answer 20

o Poorly differentiated tumours composed of large cells
o There is NO histological evidence of glandular or squamous differentiation
o NOTE: on electron microscopy  may be evidence of glandular, squamous or neuroendocrine differentiation
o POORER prognosis

Question 21

small cell carcinoma

Answer 21

smokers, central, SIADH, ATCH, Lambert-Eaton, metastases, very poor prognosis

Question 22

Adenocarcinoma molecular targets

Answer 22

 Adenocarcinoma molecular targets:
• EGFR mutation (responder or resistance)
• ALK translocation responds to Crizotinib
• Ros1 translocation