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YR5 Histopathology > Pathology of Respiratory Disease > Flashcards

Pathology of Respiratory Disease Flashcards

1
Q

Define asthma.

A

A condition in which breathing is periodically rendered difficult by widespread narrowing of the airways that changes in severity over short periods of time

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2
Q

What are 5 signs and symptoms of asthma?

A

Wheezing
Acute SOB
Chest tightness
Night-time cough
Severe attack: status asthmaticus.

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3
Q

Give 8 aetiology/ risk factors for asthma.

A

Atopy (house dust mites)
Pollution
Drugs: NSAIDs
Occupational: inhaled gases/ fumes
Diet
Physical exertion: “cold”
Intrinsic
Genetic factors

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4
Q

What is involved in the immediate phsae of asthma?

A

Mast cells degranulate on contact with antigen

Mediators released cause vascular permeability, eosinophil + mast cell recruitment, + bronchospasm.

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5
Q

What acute changes are seen in asthma?

A

Bronchospasm: constricted
Oedema + Hyperaemia: swollen

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6
Q

What is involved in the late phase of asthma?

A

Tissue damage

Increased mucus production

Muscle hypertrophy (GFs triggered)

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7
Q

What are 3 chronic changes seen in asthma?

A

Muscle hypertrophy

Airway narrowing

Mucus plugging

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8
Q

What is this? What disease is this associated with?

A

Mucus plug
Asthma

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9
Q

What is this? What disease is this associated with?

A

Hyperaemia: v dilated blood vessel
Asthma

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10
Q

What is this? What disease is this associated with?

A

Eosinophilic inflammation + goblet cell hyperplasia
Asthma

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11
Q

What is this? What disease is this associated with?

A

Hypertrophic constricted muscle
Asthma

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12
Q

What is this? What disease is this associated with?

A

Mucus plugging + inflammation
Asthma

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13
Q

Define COPD.

A

Chronic cough productive of sputum – Most days for at least 3/12 over at least 2 consecutive years.
Mix of airway + alveolar pathology
(chronic bronchitis + emphysema)

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14
Q

Explain the aetiology/ risk factors for COPD.

A

Chronic injury to airways elicits local inflammation + reactive changes which predispose to further damage.

Common causes:
* Smoking
* Air pollution
* Occupational exposures

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15
Q

Give 4 pathological features of COPD

A

Dilated airways- lose structure
Mucus gland hyperplasia
Goblet cell hyperplasia
Inflammation

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16
Q

What are 4 complications associated with COPD?

A

Repeated infections (most common cause of hospital admission + death)

Chronic hypoxia + reduced exercise tolerance

Chronic hypoxia results in pulmonary HTN + right HF (cor pulmonale)

Increased risk of lung cancer independent of smoking

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17
Q

Define bronchiectasis.

A

Permanent abnormal dilatation of bronchi with inflammation + fibrosis extending into adjacent parenchyma

Inflamed scarred lungs with dilated airways

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18
Q

What are 9 causes of bronchiectasis?

A

Congenital

Inflammatory:
Infection
* Post-infectious (esp. kids/ CF patients)
* Ciliary dyskinesia 1º [Kartagener’s] + 2º
*Abnormal host defence1º [hypogammagl] + 2º [chemo, NG]
* Obstruction (extrinsic/ intrinsic/ middle lobe syn.)
* Post-inflammatory (aspiration)
* Secondary to bronchiolar disease (OB) + interstitial fibrosis (Idiopathic PF, sarcoidosis)
* Systemic disease (connective tissue disorders)
* Asthma

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19
Q

What are 4 complications associated with bronchiectasis?

A

Recurrent infections (massively dilated + full of mucus)

Haemoptysis (severe infection causes erosion into vessels)

Pulmonary HTN + right HF

Amyloidosis

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20
Q

Explain the aetiology of cystic fibrosis.

A

Affects 1 in 2,500 live births

  • Autosomal recessive (~ 1/20 of pop. heterozygous carriers)
  • Chr7q3 = CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator) = ion transporter protein.
  • Abnormality leads to defective ion transport across cell membranes leading to excessive resorption of water from secretions of exocrine glands.
  • Abnormally thick mucus secretion - affects all organ systems.
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21
Q

What is the most common mutation causing cystic fibrosis?

A

Delta F508

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22
Q

Which organs are affected in cystic fibrosis?

A

GIT: Meconium ileus, malabsorption

Pancreas: Pancreatitis, secondary malabsorption

Liver: Cirrhosis

Male reproductive system: Infertility

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23
Q

How is the lung affected in cystic fibrosis?

A

Airway obstruction
Recurrent infections
Resp. failure + cor pulmonale
Haemoptysis
Pneumothorax

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24
Q

What are treatment options for cystic fibrosis?

A

Physio
Abx
Enzyme supplements
Parenteral nutrition
Lung transplantation

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25
Define pulmonary oedema.
Accumulation of fluid in alveolar spaces as consequence of “leaky capillaries” or “backpressure” from failing left ventricle.
26
What is pulmonary oedema commonly associated with?
Heart failure (acute or chronic) Common cause hospital admission + resp. failure.
27
List 4 causes of pulmonary oedema
* Left HF * Alveolar injury: drugs, inhalation, infection, pancreatitis * Neurogenic following head injury * High altitude: altitude sickness
28
What is shown here? What condition is this?
Iron laden macrophages (Haemosideren) Pulmonary oedema: "Heart failure cells"
29
What is shown here? What condition is this?
Alveolar spaces full of plasma Pulmonary oedema
30
What is the pathology of pulmonary oedema?
**Acute:** Heavy watery lungs, intra-alveolar fluid on histology **Chronic:** Iron laden macrophages, fibrosis Poor gas exchange therefore hypoxia + resp failure.
31
What is diffuse alveolar damage?
Pattern of acute diffuse lung injury in which patients present with rapid onset resp. failure, requiring ventilation on ITU. CXR shows “white out” all lung fields.
32
What is the pathogenesis of diffuse alveolar damage?
Acute damage to endothelium +/- alveolar epithelium leading to exudative inflammatory reaction. Diffuse alveolar damage
33
What is diffuse alveolar damage also known as in adults?
Acute respiratory distress syndrome “shock lung”. Common on ITU.
34
List 10 causes of diffuse alveolar damage in adults
Infection (local or generalised sepsis) Aspiration Trauma Inhaled irritant gases Shock Blood transfusion DIC Drug OD Pancreatitis Idiopathic
35
What is diffuse alveolar damage also known as in neonates? Describe the aetiology
Hyaline membrane disease of newborn. Insufficient surfactant production leading to stiff lungs + secondary alveolar epithelial damage. Premature babies.
36
What is the clinical outcome of diffuse alveolar damage?
Death ~ 40% of cases Superimposed infection **Resolution:** Lung returns to normal Residual fibrous scarring of lung leading to chronic respiratory impairment
37
What is seen here? What condition is this?
Fluffy white infiltrates in all lung fields, filled with liquid + exudate "white out" Diffuse alveolar damage
38
Describe the lung in diffuse alveolar damage as seen here
Lungs expanded + firm Plum coloured Airless Often weigh >1kg
39
What is the general clinical presentation of bacterial pneumonia?
Variety of patterns of lung involvement depending upon organism + other cofactors. * Bronchopneumonia (most common) * Lobar pneumonia * Abscess formation * Granulomatous inflammation
40
What are features of bronchopneumonia?
**Compromised host defense** - Elderly **Often low virulence organisms** - Staphylococcus, Haemophilius, Streptococcus, Pneumococcus. **Pathology** - Patchy bronchial + peribronchial distribution, often lower lobes
41
What can be seen on a histology slide of a patient with bronchopneumonia?
Peribronchial distribution Acute inflammation surrounding airways and within alveoli
42
What are features of lobar pneumonia?
Acute bacterial infection of a large portion of a lobe or entire lobe. Infrequent with advent of antibiotics. High virulence organism: 90-95% pneumococci (S. pneumoniae). Widespread fibrinosuppurative consolidation.
43
What can be seen on a histology slide of lobar pnuemonia in each stage?
1. **Congestion**: Hyperaemia + Intra-alveolar fluid 2. **Red hepatization**: Hyperaemia + Intra-alveolar neutrophils 3. **Grey hepatization**: Intra-alveolar connective tissue 4. **Resolution**: Restoration normal architecture
44
What are 5 complications associated with infectious respiratory disease?
Abscess formation Pleuritis and pleural effusion Infected pleural effusion (EMPYEMA) Fibrous scarring Septicaemia
45
In which patients are abscesses a more common complication of infectious respiratory disease? Give an example
Immune compromised Alcoholics a/w Klebsiella abscess
46
Define emphysema.
Permanent loss of the alveolar parenchyma distal to the terminal bronchiole. Damage to alveolar epithelium: * SMOKING * Alpha 1 antitrypsin deficiency * Rare: IVDU, connective tissue disease
47
How does the pattern of damage differ in different causes of emphysema?
Smoking: Loss centred on bronchiole- CENTRILOLOBULAR Alpha-1-antitrypsin deficiency: Diffuse loss of alveolae- PANACINAR
48
What are 3 complications associated with emphysema?
* **Large air spaces (bullae)**: Rupture - pneumothorax * **Respiratory failure**: Loss of area for gas exchange + Compression of adjacent normal lung. * **Pulmonary HTN + cor pulmonale**
49
What is a granuolma?
Collection of histiocytes/ macrophages +/- multinucleate giant cells. Necrotising or non necrotising.
50
What are 5 causes of granulomatous disease?
* Infection: ?TB, fungi, parasites * Sarcoidosis * Foreign body: aspiration or IVDU * Drugs * Occupational lung disease
51
Define fibrosing lung disease.
Chronic + progressive fibrosing diseases of lung
52
What are 3 important types of fibrosing lung disease?
**Idiopathic pulmonary fibrosis** aka. Cryptogenic fibrosing alveolitis **Extrinsic allergic alveolitis** aka Farmers lung **Industrial lung diseases** aka Pneumoconiosis
53
What is idiopathic pulmonary fibrosis? What symptoms does it cause? Describe the epidemiology
Aka. cryptogenic fibrosing alveolitis Chronic SOB + cough >50y M > F
54
How is idiopathic pulmonary fibrosis diagnosed? What is seen?
Dx: HRCT +/- biopsy * **Macro:** Basal + peripheral fibrosis + cyst formation * **Micro:** Interstitial fibrosis at varying stages
55
What is the prognosis in idiopathic pulmonary fibrosis?
Progressive disease >50% die in 2-3y
56
What is pulmonary thromboembolism?
Occlusion of pulmonary artery by embolisation of peripheral thrombus to lung. Common cause of admission to A&E/ Medical Admission Unit.
57
What are common site formations of thromboembolism?
Deep veins of leg (95%): * Present with swelling of leg (DVT) * Present with Sx of spread to lung (PE)
58
What promotes thrombus formation?
Virchows triad 1. Factors promoting blood STASIS: obesity, immobility, cardiac failure, pregnancy, abdo masses 2. DAMAGE to ENDOTHELIUM: local trauma, cannulation 3. Increased COAGULATION: malignancy, haemoconcentration, polycythaemia, DIC, OCP, cannulation, anti-phospholipid syndrome
59
What are small emboli? What do they cause?
Small peripheral pulmonary arterial occlusion Cause local haemorrhagic infarct Repeated emboli cause increasing occlusion of pulmonary vascular bed + pulmonary HTN. Present with pleuritic chest pain, acute SOB +/- chronic progressive SOB
60
What are large emboli? What do they cause?
Large emboli can occlude the main pulmonary trunk (saddle embolus). Sudden death, acute right HF, or cardiovascular shock occurs in 5% of cases when \>60% of pulmonary bed is occluded. If patient survives, the embolus usually resolves. 30% develop 2nd or more emboli.
61
What are 6 non-thrombotic emboli?
Bone marrow Amniotic fluid Trophoblast Tumour Foreign body Air
62
What is pulmonary hypertension?
Mean pulmonary arterial pressure \> 25mmHg at rest (Normal pulmonary circulation is low pressure ~12mmHg)
63
What are 9 precapillary causes of pulmonary hypertension?
**Vasoconstrictive:** * Chronic hypoxia * Hyperkinetic congenital heart disease * Unknown (Primary pulmonary HTN) * Chronic liver disease * HIV infection * Connective tissue disease **Embolic:** * Thromboembolic * Parasitic (schistosomal) * Tumour emboli
64
What are capillary causes of pulmonary hyptertension?
Widespread pulmonary fibrosis: mechanical vascular distortion + chronic hypoxia
65
What are 2 post-capillary causes of pulmonary hypertension?
Veno-occlusive disease Left-sided heart disease
66
What are 2 features of benign lung tumours? Give an example
Do not metastasise Can cause local complications e.g. Airway obstruction e.g. Chondroma
67
What are 2 features of malignant lung tumours?
Potential to metastasise, but variable clinical behaviour from indolent to aggressive. Commonest are epithelial tumours
68
Which are the main types of malignant lung tumour?
**NON-small cell carcinoma**: * Squamous cell carcinoma (30%) * Adenocarcinoma (30%) * Large cell carcinoma (20%) **SMALL cell carcinoma**: * Small cell carcinoma (20%)
69
Which lung cancers does smoking have the strongest association with?
Squamous cell carcinoma + Small cell carcinoma.
70
What are 5 other risk factors for lung cancer?
25% of lung cancers worldwide is in non-smokers. **Asbestos exposure** **Radiation** (Radon, theraputic radiation, miners) **Air pollution** **Other:** Heavy metals (Chromates, arsenic, nickel) **Genetics:** Familial lung cancers rare.
71
Describe the pathway of development of squamous cell carcinoma
Normal epithelium Hyperplasia Squamous metaplasia Dysplasia Carcinoma in situ Invasive carcinoma
72
What are features of invasive squamous cell carcinoma? Frequency Risk factors Site Behaviour
**Freq:** 35% of pulmonary carcinoma. **Risk factor:** Closely a/w smoking **Site:** Traditionally CENTRAL arising from bronchial epithelium (but increasing number of peripheral SCCs) **Behaviour:** Local spread, metastasise late.
73
What is the pathway of development of adenocarcinoma?
Precursor lesion: Atypical adenomatous hyperplasia. Proliferation of atypical cells lining alveolar walls. Increases in size + eventually can become invasive. AAH-> Non-mucinous adenocarcinoma in situ-> Mixed pattern invasive adenocarcinoma
74
What are features of invasive adenocarcinoma? Frequency Risk factors Site Behaviour
**Freq:** Increasing incidence- 27% pulmonary carcinomas. **Risk factor:** Smoking. Commoner in far east, females + non-smokers. **Site:** Peripheral + more often multicentric **Behaviour:** Extrathoracic metastases common + early.
75
Describe the histology of invasive adenocarcinoma
Evidence of glandular differentiation. Variety of patterns relate to underlying molecular abnormalities + prognosis.
76
What are large cell carcinomas?
Poorly differentiated tumours composed of large cells. Peripheral or central 10% of tumours. No histological evidence of glandular or squamous differentiation- on EM may show glandular, squamous or NE differentiation= probs v poorly differentiated adeno/ squamous cell carcinomas. Poorer prognosis.
77
What are small cell carcinomas? Frequency Risk factors Site Behaviour
**Freq:** 20% tumours. **Risk factor:** Very close a/w smoking. **Site:** Often central near bronchi. **Behaviour:** 80% present with advanced disease. Although very chemosensitive, have an abysmal prognosis. Paraneoplastic syndromes.
78
Describe the histology and common mutations seen in small cell carcinoma
Small poorly differentiated cells p53 + RB1 mutations common.
79
Which lung cancer has the worst prognosis?
Small cell carcinoma
80
What is the prognosis and treatment of small cell carcinomas?
Survival 2-4 months untreated 10-20 months with current therapy Chemoradiotherapy (surgery rarely undertaken as most have spread at time of dx)
81
What is the prognosis and treatment of non-small cell carcinomas?
**Early Stage 1:** 60% 5y survival **Late Stage 4:** 5% 5y survival 20-30% have early stage tumours suitable for surgical resection. Less chemosensitive.
82
How is non-small cell carcinoma sub-typed? Why is this important?
Adenocarcinoma: target mutations- EFGR, ALK translocation, Ros1 translocation SCC: may develop fatal haemorrhage with new chemotherapeutic drugs e.g. Bevacizumab
83
What are common clinical presentations for lung cancer?
**Asymptomatic:** * Incidental finding of mass on CXR **Symptomatic:** * Cough * Haemoptysis * Recurrent infections * Other: Weight loss, metastasis
84
What is cytology and how can pathologists study this?
Looking at cells. * Sputum * Bronchial washings + brushings * Pleural fluid * Endoscopic fine needle aspiration of tumour/ enlarged LNs
85
What is histology and how can pathologists study this?
Looking at tissue. * **Biopsy at bronchoscopy:** Central tumours * **Percutaneous CT guided biopsy:** Peripheral tumours * **Mediastinoscopy + LN biopsy:** For staging * **Open biopsy at time of surgery if lesion not accessible otherwise:** Frozen section * **Resection specimen:** Confirm excision + staging
86
List 10 causes of diffuse alveolar damage in adults
Infection (local or generalised sepsis) Aspiration Trauma Inhaled irritant gases Shock Blood transfusion DIC Drug OD Pancreatitis Idiopathic
87
I've been smoking for 30y, stopping now is not going to reduce my risk of lung cancer. True or false.
FALSE Even at older age, stopping smoking significantly reduces risk of lung cancer

YR5 Histopathology (27 decks)

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