Lecture 25 - Benign Respiratory Pathology Flashcards
What is asthma?
chronic inflammatory disorder of the airways.
Paroxysmal bronchospasm
wheeze
cough
variable bronchoconstriction that is at least partially reversible
is asthma reversible or obstructive or restrictive and is it reversible?
Asthma is an obstructive airway condition and is largely and partially reversible.
what are the symptoms of asthma?
mucosal inflammation and oedema
hypertonic mucous glands (high osmotic pressure than other bodily fluid) and mucus plugs in bronchi
hyperinflated lungs
what is the clinicopathological classification of asthma
4 types -
atopic, non-atopic, aspirin-induced, allergic bronchopulmonary aspergillosis (ABPA)
what are the features of atopic asthma
Type 1 hypersensitivity reaction
Persistent or irreversible changes
What happens in a type 1 hypersensitivity reaction?
Degranulation of IgE bearing mast cells
- histamine initiated bronchoconstriction and mucus production obstructing air flow
- eosinophil chemotaxis
what can cause a type 1 hypersensitivity reaction
Allergen - dust, pollen, animal products
cold, exercise, respiratory infections
many different cell types and inflammatory mediators involved
Persistent or irreversible changes in asthma
bronchiolar wall smooth muscles hypertrophy
mucus gland hyperplasia
respiratory bronchiolitis leading to centrilobular emphysema
Describe the epidemiology of Atopic asthma
- Occurs in children and young adults
- It is common
- 33.9% UK children 12-14 years with “wheeze” in 2002.
- 1 in 10 UK children diagnosed with asthma
- 590,000 teenagers
- 9-15% onset asthma is occupational
- The commonest occupational lung disease
Acute asthma histology
a mucus plugged small bronchus with eosinophils
What causes localised or diffuse obstruction of air flow in Obstructive pulmonary disease?
Tumour or foreign body
Distal alveolar collapse or over expansion
Distal retention pneumonitis (endogenous lipid pneumonia ) and bronchopneumonia
Distal bronchiectasis (bronchial dilatation)
What is bronchiectasis?
Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue
- Results from chronic necrotizing infection
- Rare
What is the site of bronchiectasis?
bronchus/bronchioles
Cause of bronchiectasis?
infection
What are the signs and symptoms of bronchiectasis?
cough, fever, copious amounts of foul smelling sputum
what are the predisposing conditions of bronchiectasis?
infections (immunocompromisation)
- cystic fibrosis
-primary ciliary dyskinesia or Kartagener syndrome
Bronchial obstruction: tumour, foreign body
-Lupus, rheumatoid arthritis, inflammatory bowel disease, GVHD
treatment for bronchiectasis
may be localised - resectable
Complications of bronchiectasis
Pneumonia, septicaemia, metastatic infection, amyloid
What is COPD?
A combination of chronic bronchitis and emphysema
What is chronic bronchitis?
cough and sputum for 3 months in each of 2 consecutive years
Site of bronchitis
bronchus
Cause of bronchitis
chronic irritation
smoking and air pollution
At what age is chronic bronchitis
Middle aged and old
1 in 20 of over 65 year olds consult their GP per year.
What is the pathology of chronic bronchitis
Mucus gland hyperplasia and hypersecretion, secondary infection by low virulence bacteria, chronic inflammation
-chronic inflammation of small airways of the lung causes wall weakness and destruction thus centrilobular emphysema
What is emphysema
Emphysema is a type of COPD involving damage to the air sacs (alveoli) in the lungs. As a result, your body does not get the oxygen it needs. Emphysema makes it hard to catch your breath. You may also have a chronic cough and have trouble breathing during exercise.
Classification of emphysema
Centrilobular (centacinar) - due to coal dust and smoking
Panlobular (panacinar) - more than 80% alpha1 antitrypsin deficient, (rare, autosomal dominant), severest in lower lobe bases
Paraseptal (distal acinar)-
Upper lobe subpleural bullae adjacent to fibrosis. Pneumothorax if rupture.
Site of emphysema
acinar
Symptoms of emphysema
Dyspnoea: progressive and worsening
Difference between Predominant bronchitis and emphysema
Bronchitis age - 40-45 Dyspnea - Mild, late in disease Cough - early in disease, copious sputum Infections- common Respiratory insufficiency - Repeated Cor pulmonale - common Chest Xray - Prominent vessels, large heart Stereotype - Blue bloater
Emphysema
50-75 Dyspnoea - severe, early cough - late, scanty, sputum Infections - rare Respiratory insufficiency - terminal cor pulmonale - rare, terminal Chest x-ray - Small heart, hyperinflated lungs Stereotype - pink puffer
what was observed in coal miners since 1992?
Chronic bronchitis and emphysema
what caused chronic bronchitis and emphysema in coal miners
over 20 years of underground work
compensation depends on degree of disability and smoking history
No CXR or history of dust exposure needed
Coal miners compensation scheme
4000 occupational disease deaths per year
592000 claims since 1993
575,000 settled
£2.3 billion paid in compensation
What is interstitial lung disease?
restrictive rather than obstructive
very heterogenous group
diseases of pulmonary connective tissue
-Main alveolar walls
what is the nature of Interstitial lung disease?
diffuse and chronic
What are the causes of interstitial lung disease?
Causes often unknown
what occurs in interstitial lung disease?
- increased tissue in alveolar-capillary wall
- inflammation and fibrosis
- limited morphological patterns that differ with site and with time in any individual but with many causes and clinical associations
- decreased lung compliance
- increased gas diffusion distance
What occurs in Acute interstitial lung disease?
Diffuse alveolar damage
- exudate and death of type 1 pneumocytes from hyaline membranes lining alveoli followed by type 2 pneymocyte hyperplasia
- Histologically acute interstitial pneumonia
- Adult respiratory distress syndrome (shock lung)
- shock, trauma, infections, smoke, toxic gases, oxygen paraquat, narcotics, radiation , aspiration, DIC
What occurs in Chronic interstitial lung diseases?
Dyspnoea increasing from months to years
Clubbing, fine crackles, dry cough
Interstitial fibrosis and chronic inflammation with varying radiological and histological patterns
- Common end-stage fibrosed “honeycomb lung”
-examples
-idiopathic pulmonary fibrosis
many pneumoconioses (dust diseases)
- sarcoidosis
-collagen vascular diseases - associated lung diseases
What is idiopathic pulmonary fibrosis
crytogenic fibrosing alveolitis
Epidemiology of Idiopathic pulmonary fibrosis
- 5000 new cases per year in uk, middle aged and elderly
- 3 & 5 year mortality 43% and 57% (expected 12% and 19%)
What areas are affected in Idiopathic Pulmonary fibrosis?
Sub-pleural, lower lobes affected first and most severely
Describe the histology of pulmonary fibrosis
Usual interstitial pneumonia (UIP) - Interstitial chronic inflammation & variably mature fibrous tissue
- Adjacent normal alveolar walls
- Similar pattern of fibrosis in collagen vascular disease associated interstitial lung disease and in asbestosis.
What is idiopathic Pulmonary fibrosis?
Bosselated (‘cobblestone”) pleural surface due to contraction of interstitial fibrous tissue accentuates lobular architecture
What is sarcoidosis?
Non-caseating perilymphatic pulmonary granulomas, then fibrosis
Hilar nodes usually involved
-other organs may be affected,-skin, heart, brain
- Hypercalcaemia and elevated serum ACE
- Typically young adult females, aetiology unknown
What is pneumoconioses?
The dust diseases
- Originally defined as the non neoplastic lung diseases due to inhalation of mineral dusts in the workplace
- Now also includes organic dusts, fumes and vapours
What are the different kinds of inhaled dusts
inert fibrogenic allergenic oncogenic -causes lung carcinoma & pleural mesothelioma
How big does dust have to be to reach the alveoli
less than 3Mm
What is coal workers’ pneumoconiosis?
Also called Anthracosis (milder, asymptomatic Pneumoconiosis)
- Simple (macular) CWP
- Nodular CWP
- Progressive massive fibrosis
- COPD (‘ chronic bronchitis & emphysema’) if more than 20 years of underground mining
What is coal worker’s pneumoconiosis associated with?
Right ventricular hypertrophy
What is silicosis caused by?
Silica - sand and stone dust
What occurs in silicosis?
- Kills phagocytosing macrophages
- Fibrous & fibrous silicotic nodules, also in nodes
- Possible reactivation of tuberculosis
What can silicosis increase risk of developing?
- Increased risk of lung carcinoma - lung carcinoma with silicosis is a UK “ prescribed occupational disease”
- Mixed dust pneumoconiosis - silica with other dusts
What is hypersensitivity pneumonitis?
- also called extrinsic allergic alveolitis
- Type 3 hypersensitivity reaction organic dusts
- Farmers’ lung - actinomycetes in hay
- pigeon fancier’s lung - pigeon antigens
- peribronchiolar inflammation with poorly formed non-caseating granulomas extends alveolar walls
- repeated episodes leads to interstitial fibrosis
What is cystic fibrosis?
- An inherited multiorgan disorder of epithelial cells affecting fluid secretion in exocrine glands and the epithelial lining of the respiratory, gastrointestinal and reproductive organs
- Mostly affects caucasians
- Incidence 0.4 per 1000 live births
What kind of inheritance is cystic fibrosis?
autosomal recessive inheritance
What occurs in cystic fibrosis?
- Bronchioles distended with mucus
- Hyperplasia mucus secreting glands
- Multiple repeated infections
- Severe chronic bronchitis and bronchiectasis
- exocrine gland ducts plugged by mucus
-Atrophy and fibrosis of gland
-Impaired fat absorption, enzyme secretion, vitamin deficiencies (pancreatic insufficiency)
Small bowel: mucus plugging - meconium ileus
Liver: plugging of bile cannaliculi – cirrhosis
Salivary glands: Similar to pancreas: atrophy and fibrosis
95% of males are infertile
What bowel condition is associated with cystic fibrosis?
Meconium ileus - bowel obstruction when meconium is thicker and stickier than normal so causes obstruction of the ileum
What are the screening processes available for CF?
Part of newborn screening in UK
sweat test
genetic testing
What is the median age of survival in the uk for CF
41
What is the treatment available for CF?
Physiotherapy
Mucolytics
Heart/lung transplants
ethics of new drug for CF
The cost of lumacaftor–ivacaftor is £8,000 per 112‑tablet pack (excluding VAT; company’s evidence submission). The cost of a 1‑year course of treatment is £104,000 (excluding VAT). Costs may vary in different settings because of negotiated procurement discounts
