Respiratory histopathology Flashcards
Normal Lung
lined by ciliated respiratory epithelium
Ciliated epithelium waft pathogen-containing mucous up the ‘mucociliary escalator’
The mucous is coughed up and swallowed (protective function)
The small airways are important for respiration
Alveoli are characterised by very fine capillaries lined by type 1 pneumocytes (short diffusion distance)
pulmonary oedema definition
CXR
Associated with
Very common cause of what condition
Defined by the accumulation of fluid in the alveolar spaces either due to “leaky capillaries” or “backpressure” from a failing left ventricle. This leads to poor gas exchange, hypoxia and respiratory failure.
Radiologically, pulmonary oedema presents with very fluffy opacities.
Associated with HF (acute/chronic)
VERY COMMOM cause of acute and chronic respiratory failure in A+E and community
Common finding at post-mortem
Causes of pulmonary oedema
Left heart failure (commonest cause)
Alveolar injury or capillary injury (drug, inhalation, pancreatitis)
Neurogenic (following head injury)
High altitude
Pulmonary oedema pathology
Heavy, congested watery lungs
Intra-alveolar fluid on histology (often slightly fibrinous)
Acute Lung Injury Pattern/Diffuse Alveolar Damage
Important cause of what condition
adults and neonates
Important cause of RAPID onset respiratory failure
Adults: Acute Respiratory Distress Syndrome (ARDS)
- ‘Shock lung’
- Numerous causes in adults:
- Infection (local or generalised sepsis)
- Aspiration
- Trauma
- Inhaled irritant gases
- Shock
- Blood transfusion
- DIC
- Drug overdose
- Pancreatitis
- Idiopathic
Neonates: Hyaline Membrane Disease of the Newborn (Respiratory Distress Syndrome)
- Insufficient surfactant production (surfactant needed for lung expansion at birth)
- Seen in premature babies (these babies aren’t yet producing surfactant)
White out in all lung fields CXR
Acute Lung Injury Pattern/Diffuse Alveolar Damage pathology
This is acute respiratory failure NOT due to pulmonary oedema
It is caused by acute damage to the endothelium and/or alveolar epithelium (frequently both)
Basic pathology is the same in all cases: diffuse alveolar damage
The lungs are expanded and firm
On post-mortem examination, the lungs are plum-coloured, heavy (> 1 kg) and airless
Acute Lung Injury Pattern/Diffuse Alveolar Damage pathophysiology
Initially, the capillaries are markedly dilated and congested
Following capillary and epithelial damage, there is fluid leakage into the air spaces (exudative phase)
Proteinaceous deposits line the alveolar walls
They will then develop hyaline membranes (serum proteins and dead cells that have leaked out and end up lining the alveolar spaces, making gas exchange very difficult
Eventually, you get organisation of the exudates to form granulation tissue sitting within the alveolar spaces (organising pneumonia) as the body attempts to repair the damage
prognosis of diffuse alveolar damage
Death (in around 40%)
- Superimposed infection due to fluid accumulation (e.g. pneumonias)
Resolution (in some): lung function returns to normal
Residual fibrosis: leads to chronic respiratory impairment
asthma definition
Chronic inflammatory airway disorder with recurrent episodes of widespread narrowing of the airways that changes in severity over short periods of time.
Prevalence increased in recent decades (10% = children, 5% = adults)
Presents with wheezing, chest tightness, shortness of breath, night-time cough
In a SEVERE attack, patients develop status asthmaticus
- extreme form of asthma exacerbation characterized by hypoxemia, hypercarbia, and secondary respiratory failure
It can be an atopic condition (genetic tendency to develop allergic reaction to common environmental antigens (e.g. house dust mite))
Non-atopic triggers:
- Air pollution
- Drugs (NSAIDs)
- Occupational (inhaled gases/fumes)
- Diet
- Genetic factors
- Physical exertion (“cold”)
- Intrinsic
Asthma: acute and chronic changes
Acute Changes
- Bronchospasm
- Oedema (of the mucosa)
- Hyperaemia
- Inflammation
The trigger for acute changes is the binding of an antigen to the surface of the bronchi epithelium, and a dendritic cell (which presents it in turn to a T cell) release of cytokines, recruitment of inflammatory cells etc. inflammatory mediators damage the airway epithelium and cause excess mucous production and muscular contraction.
Chronic change
- Muscular hypertrophy
- Airway narrowing
- Mucus plugging
NOTE: once you’ve plugged a large airway, the distal lung will collapse.
mucus plug
This is a mucus plug coughed up by someone who had had a severe asthma attack.
When we look at the lungs of patients who have died from an acute asthma attack, they are pale and over-inflated.
histological features of asthma
Very dilated and congested blood vessels (as is seen in any inflammatory reaction)
There are a lot of eosinophils and mast cells infiltrating the surface epithelium
You will also see goblet cell hyperplasia
Mucus plugs can be seen within the airway
The bronchial smooth muscle becomes thick and the blood vessels become dilated
COPD definition
- Very common cause of chronic respiratory failure
- May present with acute exacerbations
- 80% are smokers
- Smoking causes inflammation leading to secondary damage to the airways and interstitium
- There is a mix of airway and alveolar pathology (chronic bronchitis and emphysema), resulting in progressive airway obstruction
We see a mixture of airway damage (bronchitis) and interstitial damage (damage to the terminal parts of the lungs i.e. emphysema).
Chronic bronchitis definition, pathology and complications
Defined as a chronic cough productive of sputum, most days for at least 3 months over 2 consecutive years.
Chronic injury to the airways elicits reactive changes which predispose to further damage
Pathology
- Dilated airways
- Mucus gland hyperplasia
- Goblet cell hyperplasia
- Mild inflammation
Complications
- Recurrent infections (most common cause of admission and death)
- Chronic respiratory failure (with hypoxia and reduced exercise tolerance)
- Chronic hypoxia results in pulmonary hypertension and right heart failure (cor pulmonale)
- Increased risk of lung cancer (independent of smoking)
Patients may have acute infectious exacerbations with large amounts of pus sitting in the airways as a result of chronic bronchitis.
Emphysema definition
Defined as a permanent loss of the alveolar parenchyma distal to the terminal bronchiole.
- This disease results in much more peripheral changes in the alveolar structure
- Damage to alveolar epithelium is secondary to inflammation
- Smoking (most common cause)
- Alpha-1 antitrypsin deficiency (anti-protease)
- RARE: cadmium exposure, IVDU, connective tissue disorder
Neutrophils and macrophages that are activated by smoking, will release proteases which degrade tissues.
emphysema pathophysiology
- Normal lung looks like a tightly packed sponge
- Emphysema lungs have a loss of the alveolar structure
- Destroyed alveoli results in large air spaces
Smoking causes inflammation within the lung (including neutrophil and macrophage activation)
- Smoking tends to cause centrilobular damage to the alveolar tissue due to protease activation
Most of the damage takes place in the airways that feed into the lung lobules
- Patients with alpha-1 antitrypsin deficiency have damage throughout the lung (panacinar)
Complications
- Bullae (large air spaces) – can rupture and cause pneumothorax
- Respiratory failure
- Pulmonary hypertension and right heart failure
Bronchiectasis definition
Defined as a permanent abnormal dilation of the bronchi with inflammation and fibrosis extending into adjacent parenchyma.Bronchiectasis tends to affect the larger airways of the lung.
- Varies in site depending on cause (idiopathic often involves lower lobe)
- Lungs experience repeated infections -> inflammation and scarring
- Leads to inflamed and scarred lungs with dilated airways
We see that the airway is dilated (much larger than the size of the accompanying artery, which is normally around the same size). We see a lot of scarring and inflammation around the airways.
Causes of bronchiectasis
Infection (most common cause)
- Post-infectious (especially in children or cystic fibrosis)
- Abnormal host defence (primary (hypogammaglobulinemia) or secondary (chemotherapy)
- Ciliary dyskinesia (primary (Kartagener’s syndrome) or secondary) situs inversus, chronic sinusitis, and bronchiectasis
Obstruction
Post-inflammatory (aspiration)
Secondary to bronchiolar disease and interstitial disease (e.g. sarcoidosis)
Systemic disease (connective tissue disorders)
Asthma
Congenital
bronchiectasis complications
Recurrent infections
Haemoptysis (due to erosion into vessels by inflammation)
Pulmonary hypertension and right sided heart failure
Amyloidosis
Cystic Fibrosis definition
An autosomal recessive (approximately 1/20 are carriers) inherited disease (commonest cause of bronchiectasis in the UK). Affects 1 in 2,500 live births.
- Chromosome 7q3 = CFTR gene (codes for a chloride ion transporter protein)
- There are over 1400 mutations, but the delta F508 mutation is the most common
- Abnormality leads to defective ion transport across cell membranes due to excessive resorption of water from secretions of exocrine glands
It is a generalised disorder of the exocrine glands resulting in abnormally thick mucus secretion in all organs.
- GI: meconium ileus, malabsorption
- Pancreas: pancreatitis, malabsorption
- Liver: cirrhosis
- Male reproductive system: infertility