Airway & Airway Diseases

Question 1

What is an obstructive disorder? What are some example sof obstructive lung conditions?

Answer 1

Obstructive disorder - when there is obstruction of air flow into the airway, resulting in less inflow of gas into the alveolar space thus resulting in a reduction in gas exchange taking place

Examples include:
1. Asthma
2. Chronic Obstructive Pulmonary Disease (COPD)
3. Causing obstructive picture
a) Bronchiectasis
b) Cystic Fibrosis

Question 2

What are four variables that influence airway internal diameter?

Answer 2

1. Increased mucus production - quanitity and thickness
2. Anatomical features
3. Autonomic and Non-Adrenergic/Non Cholinergic (NANC) systems - constriction/dilation
4. Inflammation

Question 3

Outline how the autonomic and NANC nervous systems influencing constriction and dilation of airways.

Answer 3

1. Parasympathetic activation leading to acetyl-choline release - acts on M3 muscarinic receptors - drives constriction
2. Beta agonists in circulation bind to B2 adrenergic receptors - drives dilation
3. Non-autonomic inputs (not really used as drug targets)- VIP and NO drive bronchodilation / Substance P and neurokinis drive bronchoconstriction

Question 4

What are the main characterisitics associated with Asthma? What does the lung pathology look like?

Answer 4

Asthma – atopy and allergy exposure - associated with inflammatory exacerbations driven mainly by eosinophils

Asthma is reversible and biphasic (early and late response during an exacerbation)

Pathology
1. Smooth muscle thickening
2. Bronchoconstriction
3. Basement membrane thickening
4. Mucous plugging (more acute disease presentation)

Question 5

What are the main characterisitics associated with COPD? What does the lung pathology look like?

Answer 5

COPD - emphysema (breakdown of alveoli) and chronic bronchitis (inflammation - neutrophil mediated)

Several environmental triggers - major driver is smoking

Pathology
1. Increased mucous production
2. Destruction of alveoli and connective tissue leading to collapse of conducting airways

Question 6

What is cystic fibrosis? What are the associated characteristics?

Answer 6

Cystic fibrosis - genetic condition that arises from a mutations in both CFTR genes - codes for a pump that regulates water and Cl- flow in and out of a cell - dysfunction creates sticky thick mucus

Characteristics
- Walls become thickened
- Mucus builds up
- Dilation - bronchiectasis (abnormal dilation)

Question 7

What are the three ways that lung obstruction is measured?

Answer 7

1. Peak flow
2. Spirometry
3. Lung Volumes and flow

Question 8

What impact does a change in vessel radius have on levels of air resistance? What implications does this have for airflow through a tube?

Answer 8

Small change in radius has a significant impact on airflow resistance, and thus airflow.

Question 9

Outline how peak flow is used to measure lung obstruction.

Answer 9

Peak expiratory flow rate (PEFR) - Measures maximum speed of expiration - How fast is the air going out, indicates how fast air is going in

Crude measurement of conducting airway flow

Can aid in Asthma diagnosis/management

Excellent bedside and patient- based tool

Question 10

What are FEV1 and FVC?

Answer 10

FEV1 - Forced expiratory volume in 1 second

FVC - Forced vital capacity – total of volume of air that can be expired

Question 11

What is spirometry?

Answer 11

Spirometry - pulmonary function test

Two main measures
1. Forced expired volume in 1 second (FEV1)
2. Forced vital capacity (FVC) (measure ~ 6 seconds of expiration)

We compare to predicted values based on age, sex and height - Predicted values are based on population of healthy individuals

Question 12

What changes are seen in FEV1 and FVC in mild and moderate lung obstruction?

Answer 12

Mild to moderate airway obstruction – due to asthma, COPD, CF, etc. - reduction in FEV1is seen but eventually expiration volume will catch up and reach normal FVC

Severe obstruction – significantly reduced FEV1 and FVC – reduction in lung volume - Sign of severe disease

Question 13

What can the ratio of FEV1 to FVC tell us?

Answer 13

The ratio of FEV1 to FVC helps us to differentiate between obstruction (airflow problem) and restriction (lung volume problem)

If less than 0.7 - suggests am obstructive airways pathology - Loss of more FEV1 than FVC - mainly a reduction in airflow not volume

If more than 0.7 - suggests an restrictive airway pathology - loss of FVC more than FEV1 - mainly a lung volume problem

Note in cases of severe obstruction/disease - there is a significant loss in both FEV1 and FVC

Question 14

How is spirometry used as a diagnostic tool for asthma?

Answer 14

Revesibility of Spirometry

Couple the use of a bronchodilator with spirometry to see if levels can be reversed/improved - positive test = asthma

Look for a 12% change in spirometry – but usually analyze it in the context of the patients previous measurements

Can also use bronchial challenge agents (histamine) to induce bronchospasm and obstructive spirometry

Note this is possible for asthma as it is a reversible condition unlike COPD

Question 15

Are our airways normally colonised by bacteria?

Answer 15

Yes

Upper airway is not sterile, whereas the lower airway has low levels of microorganisms

It is thought that some microorganisms constantly move down to the lower airway from the upper airways – when we have pathogenic pathogen and/or susceptible to infection moving down we are more likely to suffer from a lower respiratory tract infection

Question 16

What are four factors that protect us from respiratory infections?

Answer 16

1. Colonisation - Commensal flora and colonisation resistance
2. Swallowing - Normal swallowing reflex, epiglottis
3. Lung anatomy - Neurological and anatomical factors, Mucus and Ciliated epithelium, (mucociliary escalator), and Cough reflex
4. Immunity (innate and adaptive)
   - Soluble factors; IgA, defensins, collectins, lysozyme
   - Alveolar macrophages
   - B- and T-cells

When these factors are not operating adequetly, they make people susceptible to respiratory tract infections

Question 17

What is the most common cause of an upper respiratory tract infection?

Answer 17

Most common cause – viruses – common cold– Main causal agents are the rhinoviruses, influenza A (known to cause systemic symptoms) and recently SARS-CoV2

Usually transient

May lead to complications - sinusitis, pharyngitis, otitis media, bronchitis, rarely pneumonia

Note
Respiratory Syncytial viruses - known to causes illness in children and severe illness in nursing home residents

Question 18

What is pharyngitis? What are the typical causes?

Answer 18

Pharyngitis = sore throat

Typically viral

But could also be…
1. beta-hemolytic streptococci
2. Glandular fever Epstein Barr virus
3. Acute HIV infection

Question 19

What is sinusitis? What are the most common causes?

Answer 19

Sinusitis - inflammation of your sinuses

• Usually viral (as per causes URI)
• Bacterial also possible - more likely if ther is unilateral pain and purulent discharge, with a fever of more than >10d or presenting acutely or with complications
• Bacteria that are most commonly associated
  a) Streptococcus pneumoniae (40%),
  b) Haemophilus influenzae (30-35%)

Complications - brain abscess, sinus vein thrombosis, orbital cellulitis

Question 20

What is acute epiglottitis? WHat is it associated with?

Answer 20

Inflammation of the epiglottis

Typically associated with children - 2-4 years old who presented with fever, dysphagia, drooling and stridor

Caused by Haemophilus infuenzae type B (Hib) - rare now due to vaccinations

But can also present in immunocompromised adults

Epiglottis is swollen and extends into the airway – medical emergency and requires intubation

Question 21

What are the symptoms associated with Bordatella pertussis infection?

Answer 21

Adults chronic cough, paroxysms of coughing and 50% post tussive (coughing) vomitting but fairly specific for pertussis infection.

Basically vomitting post coughing - think pertussis

Acellular vaccine does not give lifelong immunity – require boosting

Question 22

What is croup? What are it’s associated characteristics?

Answer 22

Acute laryngo-treacheobronchitis - infection of the larynx, trachea and bronchi

Disease of children – 3 months to 3 years

Associated with a barking cough, hoarse voice, difficulty breathing and cold-like symptoms

Mainly due to Parainfluenza viruses, ( also RSV, IAV and other respiratory viruses)

Question 23

What is bronchiolitis? What are it’s associated characteristics/symptoms?

Answer 23

Bronchiolitis - Infections due to respiratory syncytial virus (RSV) (80%) (rarely other viruses)

Inflammation of bronchioles and mucus production cause airway obstruction

A common chest infection that affects babies and children under 2.

Features - dry cough, increasing breathlessness, wheezing, inspiratory crackles and feedin difficulty

Question 24

What is bronchitis? What are it’s symptoms, investigations and treatment?

Answer 24

Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing.

Aetiology: Frequently viral (May be bacterial)

May cause acute exacerbations of COPD or asthma with increased wheeze

Symptoms: cough (productive or non-productive), shortness of breath, often a wheeze, fever but no systemic signs of infection,
Investigations: Arterial blood gas/oximetry - for those with chronic lung disease and X-ray to rule out pneumonia

Treatment:
a) Usually none especially if viral, sometimes antimicrobials
b) Manage exacerbation of COPD/asthma with steroids and increased inhalers

Question 25

What is bronchiectasis? What are some potential causes?

Answer 25

Bronchiectasis describes a permanent dilatation of the airways secondary to chronic infection or inflammation. There are a wide variety of causes are listed below: a) Congenital; Cystic fibrosis (most common cause in the pediatric population), ciliary dysfunction, hypogammaglobulinemia b) Post-infectious; TB, suppurative pneumonia, measles , whooping cough c) Other; Foreign body

Question 26

What are the symptoms and observations upon examination of bronchiectasis?

Answer 26

Symptoms 1. Chronic cough 2. Copius sputum 3. Recurrent pneumonia 4. Weight loss On examination (O/N): 1. Clubbing 2. Coarse ‘wet’ crackles Can be complicated by haemoptysis

Question 27

What is pneumonia?

Answer 27

Pneumonia is the inflammation of the parenchyma of the lung. In pneumonia, the air sacs (i.e. alveoli) become filled with microorganisms and inflammatory cells leading to poor lung function with features of cough, fever, and shortness of breath.

Question 28

What are the top five most common organisms that cause pneumonia?

Answer 28

1. Streptococcus pneumoniae (40%) – most common 2. Mycoplasma pneumoniae (~10% peaks in epidemic seasons) 3. Chlamydophila pneumoniae (~10%) 4. Legionella pneumophila and other spp (<5%) 5. Haemophilus influenzae (<5%)

Question 29

What people are at risk of pneumonia infection?

Answer 29

1. Infants and the elderly 2. COPD and certain other chronic lung diseases 3. Immunocompromised 4. Nursing home residents 5. Impaired swallow (neurological conditions etc.) 6. Diabetes 7. Congestive heart disease 8. Alcoholics and drug users

Question 30

How can pneumonia be categorised based on the source of infection?

Answer 30

1. Community Acquired Pneumonia (CAP) - majority of patients develop pneumonia within the community, i.e. outside of hospital 2. Hospital-acquired pneumonia - Patients who develop pneumonia within hospitals (occuring 48 hours or more after admission) are said to have hospital-acquired pneumonia The distinction is important as the causative organisms vary and hence first-line antibiotic guidelines are also different.

Question 31

What are some three key decisions that need to be made with a pneumonia diagnosis?

Answer 31

1. Does the patient need antimicrobials? 2. How sick is the patient?Should they be managed in hospital? 3. Is there an alternative diagnosis; - Heart failure - Pulmonary embolus - Cancer - TB - Interstitial lung disease

Question 32

What treatment should be used for pneumonia?

Answer 32

Prompt but appropriate initiation of antimicrobials; ideally establish diagnosis and start treatment ≤4h - Use narrowest spectrum to stop spread of resistance Mild severity pneumonia in community **Oral antimicrobial** e.g amoxicillin for short duration Severe **Intravenous antimicrobial** often in combinations e.g co-amoxiclav + oral clarithromycin Duration 7d mild-moderate 7-10d severe 14-21d S. aureus, Gram-negative bacteria, and Legionella sp (associated with water cooling towers/showers)

Question 33

What are the signs and symptoms associated with pneumonia?

Answer 33

Symptoms 1. cough 2. sputum 3. dyspnoea 4. chest pain: may be pleuritic 5. fever Signs 1. Signs of systemic inflammatory response - fever and tachycardia 2. Reduced oxygen saturations 3. Auscultation: reduced breath sounds and bronchial breathing

Question 34

What is tuberculosis? Suspectible groups?

Answer 34

Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis that most commonly affects the lungs. Specific epidemiological groups 1. Exposed to a case 2. Born in country of high incidence 3. Homeless, alcoholic, HIV infection, anti-TNF treatment

Question 35

What are the clinical features and radiological appearances for TB?

Answer 35

Clinical features; 1. Cough, hemoptysis (more common), shortness of breath 2. Weight loss, fever and night sweats 3. Swollen lymph nodes or other extrapulmonary features Multiple radiological appearances: 1. Upper lobe disease with cavities - **Upper lobe think TB!** 2. Pleural disease 3. Multiple tiny nodules (‘miliary’), 4. Lymphadenopathy in chest Failure to resolve with routine antibiotics also suggestive

Question 36

What is needed for a TB diagnosis and how is it treated?

Answer 36

TB diagnosis - Culture in special media e.g. Mycobacteria growth indicator tube (MGIT) and use of a special stain (Special stain Ziehl-Neelsen) Also possible to use PCR Treatment

Question 37

What is needed for a TB diagnosis and how is it treated?

Answer 37

TB diagnosis - Culture in special media e.g. Mycobacteria growth indicator tube (MGIT) and use of a special stain (Special stain Ziehl-Neelsen) Also possible to use PCR Treatment - prolonged (6 months or longer) Use of multiple drugs to avoid resistance 1. Isoniazid 2. Rifampicin 3. Pyrazinamide 4. Ethambutol

Question 38

Three examples of conditions that predispose people to airway infection?

Answer 38

1. Immunosuppression - disease or drug induced 2. Macrophage dysfunction 3. Pulmonary oedema

Question 39

What is bronchitis? What are it's associated features?

Answer 39

Bronchitis - Inflammation of bronchi May also involve larynx and trachea - laryngotracheobronchitis Causes: Often viral May be bacterial e.g. H influenzae - common in COPD Acute exacerbations of ‘chronic bronchitis’ are common

Question 40

What is bronchiolitis? What are it's associated features?

Answer 40

Bronchiolitis - Inflammation of bronchioles Primary bronchiolitis a) Usually in children b) Respiratory syncytial virus (RSV) c) Tachypnoea and dyspnoea Rare in adults – normally would result in pneumonia Also commonly seen as a feature of chronic bronchitis Rare types a) Follicular bronchiolitis b) Bronchiolitis obliterans

Question 41

What is a localised airway obstruction?

Answer 41

Localised Airway obstruction - is a localised blockage of respiration in the airway that hinders the free flow of air. Can be caused by: 1. Lesion outside the wall e.g. large lymph node 2. Lesion in the wall e.g. tumour 3. Lesion in the lumen e.g. foreign body Causes distal collapse or over-inflation (one-way valve) Can give a normal pulmonary function tests Localized airway obstruction normally presents with pneumonia Obstruction lesion, if present for long enough, can result in Bronchiectasis (destruction of airway)

Question 42

What are diffuse obstructive airways diseases? What are the characteristics? What are some examples?

Answer 42

Obstructive Airways Disease can be reversible and intermittent OR Irreversible and persistent Centred on bronchi and bronchioles - many different airways can be involved, hence diffuse Pulmonary function tests ‘obstructive’ a) Reduced vital capacity (VC) b) Reduced FEV1 / FVC ratio c) Reduced peak expiratory flow rate Examples 1. Chronic bronchitis 2. Emphysema 3. Asthma 4. Bronchiectasis - not included in the UK 5. COPD

Question 43

How do you define chronic bronchitis? What is its aetiology? What are some clinical features?

Answer 43

Clinical definition - Cough and sputum for 3 months in 2 consecutive years Aetiology - pollution, smoking (mainly) Clinical picture: 1. Middle-aged heavy smokers 2. Recurrent low-grade bronchial infections (exacerbations) - H. influenzae, S. pneumoniae, viruses 3. Airway obstruction may be partially reversible

Question 44

How does chronic bronchitis disease progress?

Answer 44

Progression of disease 1. Hypercapnia - elevated CO2 2. Hypoxia - Low O2 3. Pulmonary hypertension - right side of the heart has to work extra hard 4. ‘Cor pulmonale’ - right ventricular failure Later stages associated with increased fluid retention.

Question 45

What does the pathology of chronic bronchitis look like?

Answer 45

Pathology 1. Respiratory bronchiolitis 2. Centrilobar emphysema 3. Mucus hypersecretion 4. Chronic bronchial inflammation - Squamous metaplasia, increased risk of malignancy 'Blue Bloater'

Question 46

What is emphysema?

Answer 46

Anatomical definition - Irreversible dilatation of acinar spaces (alveolar space) with destruction of walls (loss of elasticity) Definition extends to respiratory bronchioles Associated with loss of surface area for gas exchange

Question 47

What are the four different types of emphysema? What are they associated with?

Answer 47

1. **Centrilobular Emphysema** - associated with smoking, coal workers, upper lobes, respiratory bronchiolitis often present 2. **Panlobular Emphysema** - usually lower lobes, lungs overdistended, associated with alpha-1-antitrypsin deficiency, accelerated in smokers with this deficiency 3. **Paraseptal** - Distension adjacent to pleural surfaces and may be associated with scarring 4. **Irregular** - Associated with scarring and overlap with paraseptal emphysema Others - - Bullous: distended areas >10mm - pop leading to pneuomothorax - Interstitial

Question 48

What are the clinical features of emphysema?

Answer 48

Clinical features 1. Hyperventilation 2. Normal pO2, pCO2 3. Weight loss 4. Right ventricular failure Often co-existing chronic bronchitis, in which case clinical features are mixed ‘Pink puffer’

Question 49

What is Chronic Obstructive Pulmonary disease (COPD)?

Answer 49

COPD - A combination of the features of chronic bronchitis and emphysema - leads to symptoms associated with airway obstruction and loss of surface area for gas exchange. Most patients exhibit a mixture of features Typically assessed using pulmonary function tests - FEV1/FVC < 0.7 for diagnosis and % predicted FEV1 to assess severity Presentation 1. Smoking, air pollution and alpha-1 antitrypsin deficiency 2. Breathless (dyspnoea) - upon exercise? upon rest? 3. Recurrent chest infections - exacerbations 4. Productive cough (due to mucus build-up) 5. Wheeze

Question 50

How does COPD appear on X-rays?

Answer 50

Main abnormalities visible: 1. Flattening of the diaghragm 2. Translucent lung fields (blacker than normal)

Question 51

How does the macroscopic appearance of the lung change in COPD?

Answer 51

The main abnormalities are: 1. Distended air spaces 2. More prominent in the lower lobe 3. The lung has a rather ‘flaccid’ appearance (rather than fibrotic)

Question 52

What lung abnormality defines the emphysema component of COPD?

Answer 52

Acinar wall destruction

Question 53

How is the diagnosis of COPD performed?

Answer 53

Diagnosis based on FEV1/FVC < 0.7 (airflow limitation) Severity assessed by percent predicted post- bronchodilator FEV1 GOLD criteria (global initiative for chronic obstructive lung disease) FEV1 ≥ 80 – mild FEV1 50– 79 – moderate FEV1 30 – 49 – severe FEV1 < 30 – very severe

Question 54

What are the microscope changes seen in COPD?

Answer 54

Question 55

Outline how the destruction of alveolar walls, ultimately leads to pulmonary hypertension?

Answer 55

1. Destruction of alveolar walls leads to loss of surface area for gas exchange 2. Increased respiratory drive compensates for the drop in pO2 3. pCO2 may be low due to the high respiratory rate 4. In some cases, respiratory drive may fall, with tolerance of a low pO2 and elevation of pCO2 - adapts to lower pO2/ high pCO2 5. Pulmonary vasoconstriction (due to hypoxia) and destruction of pulmonary vasculature lead to pulmonary hypertension

Question 56

What is the eventual consequence of chronic pulmonary hypertension?

Answer 56

Right Ventricular Failure Associated with... 1. Ankle swelling - odema 2. Hepatic congestion a) Pain b) Abnormal liver function tests c) ‘Nutmeg’ liver

Question 57

What is asthma? What are five different aetiological causes?

Answer 57

Definition - Reversible wheezy dyspnoea Related to the irritability of the bronchial tree – asthma is an exacerbation of the normal Five categories 1. Atopic – related to allergy 2. Non-atopic 3. Aspirin-induced 4. Occupational – wood workers lung 5. Allergic bronchopulmonary aspergillosis (ABPA) – fungus – difficult to treat without making the diagnosis

Question 58

What is atopic asthma?

Answer 58

Atopic Asthma - Associated with allergy Triggered by a variety of factors: Dust, pollen, house dust mite, etc. Often associated with eczema and hay fever Bronchoconstriction mediated by a type I hypersensitivity reaction

Question 59

What pathological process take place in atopic asthma?

Answer 59

Hypersensitivity reaction leads to: 1. Bronchial obstruction with distal overinflation or collapse 2. Mucus plugging of bronchi 3. Bronchial inflammation 4. Mucous gland hypertrophy 5. Bronchial wall smooth muscle hypertrophy 6. Thickening of bronchial basement membranes

Question 60

Outline the mechanism that drives the asthmatic reaction?

Answer 60

1. Antigen enters - binds to IgE 2. IgE binds to mast cells - priming them 3. Upon secondary exposure, the antigen binds to the anitbody on the mast cell - driving degranulation 4. Release of mediators - Histmaine, SRS-A, ECF-A and pAF 5. Results in bronchoconstriction, mucus hypersecretion and oedema

Question 61

What are non-atopic asthma, aspirin induced asthma, occupational asthma and allergic bronchopulmonary aspergillosis? What are they associated with?

Answer 61

1. **Non-atopic asthma** - asthma that is not related to an allergen Associated with... 1. Recurrent infections 2. Not immunologically mediated 3. Skin testing negative 2. **Aspirin-induced Asthma** - Associated with recurrent rhinitis, nasal polyps and urticaria (raised itchy rashes)- mechanism unclear 3. **Occupational asthma** - hypersensitivity related to allergens inhaled at work 4. **Allergic Bronchopulmonary Aspergillosis** - Specific allergic response to the spores of Aspergillus fumigatus - Mucus plugs common, associated with bronchiectasis - mixture of type 1 and 3 hypersensitivity

Question 62

Is sudden death due to asthma possible?

Answer 62

Sudden death due to asthma is possible but rare – extreme mucus plugging and diffuse bronchoconstriction

Question 63

What are different interventions/therapies that can be used to help the following features of asthma? a) Mucus Plugging b) Bronchoconstriction c) Bronchial oedema and inflammatory cell infiltration d) Smooth muscles hyperthrophy/basement membrane thickening

Answer 63

Question 64

What is bronchiectasis?

Answer 64

Permanent dilatation of bronchi and bronchioles Typically affects the 2nd to 8th order of segmental bronchi. Due to a combination of obstruction and inflammation (usually infection). May be localised or diffuse, depending on cause

Question 65

What are the clinical features of bronchiectasis?

Answer 65

Clinical features 1. Chronic cough productive of copious sputum 2. Finger clubbing Complications - Spread of infection - Pneumonia, Empyema, Septicaemia, Meningitis, Metastatic abscesses e.g. brain - Amyloidosis - Respiratory failure

Question 66

What are the mechanical and immunlogical defences present in the lungs?

Answer 66

**Mechanical** 1. Ciliated epithelium 2. Mucus 3. Cough **Immunological** 1. IgA & antimicrobials in mucus 2. Resident alveolar macrophages & dendritic cells 3. Innate / adaptive immune responses

Question 67

What does the lung parenchyma refer to?

Answer 67

The parts of the lungs involved in gas transfer including the alveoli, interstitium, blood vessels, bronchi and bronchioles.

Question 68

What are 6 categories of pneumonia with regards to the source of infection? Why is it important to differentiate?

Answer 68

Categories 1. Community acquired 2. Hospital acquired 3. Health care associated 4. Aspiration associated 5. Immunocompromised host 6. Necrotising / abscess formation Source of pneumonia is important as it will inform the whether and the type of antibiotic Note pneumonia can be caused by a range of bacteria, viruses and fungi

Question 69

What are the five cardinal signs of inflammation?

Answer 69

1. Heat 2. Redness 3. Swelling 4. Pain 5. Loss of function

Question 70

What are the two principal cellular responses to pneumonia?

Answer 70

Neutrophils 1. Chemotaxis - move to infection site 2. Degranulation 3. Reactive oxygen species 4. Extracellular traps 5. Phagocytosis Macrophages 1. Cytokine & chemokines 2. Phagocytosis (bacteria & dead cells) 3. Antimicrobial peptides 4. Resolution

Question 71

What are the common organisms that causes community and hospital acquired pneumonia?

Answer 71

Community acquired 1. Streptococcal pneumoniae 2. Haemophilus influenzae 3. Moraxella catarrhalis 4. Staphylococcus aureus Hospital acquired / Health care associated 1. Gram-negative rods, Enterobacteriaceae, Pseudomonas 2. Staphylococcus aureus (usually methicillin-resistant)

Question 72

What are the clinical presentations of pneumonia?

Answer 72

Clinical Presentation: 1. Cough 2. Sputum 3. Pyrexia 4. Pleuritic chest pain 5. Haemoptysis 6. Dyspnoea 7. Hypoxia

Question 73

What are two types of pneumonia based on symptomology

Answer 73

**Bronchopneumonia** - Most common pattern - **Patchy & diffuse consolidated areas** of acute suppurative inflammation - Often elderly with risk factors - Cancer, heart failure, renal failure, stroke, COPD **Lobar pneumonia** - Rust coloured sputum - S. pneumoniae - **Consolidation of a large portion** of a lobe or of an entire lobe

Question 74

What are the general and local risk factors associated with pneumonia?

Answer 74

General factors 1. Chronic diseases 2. Immunologic deficiency 3. Immunosuppressive agents 4. Leukopaenia - decreased number of leukocytes Local factors 1. Loss or suppression of the cough reflex - drugs 2. Injury to the mucociliary apparatus - viruses, gases 3. Accumulation of secretions - CF, obstruction (tumour) 4. Impaired alveolar macrophages function – alcohol, tobacco 5. Pulmonary congestion and oedema

Question 75

What are the local and systemic complications associated with pneumonia?

Answer 75

**Local** 1. Abscess formation - pus accumulation 2. Parapneumonic effusion - presence of exudate in pleural cavity 3. Empyema - pus accumulation in pleural cavity **Systemic** 1. Sepsis 2. Acute respiratory distress syndrome - fluid build up in lungs 3. Multi-organ failure - Liver / renal /cardiac etc. 4. Cancer?

Question 76

What is Acute respiratory distress syndrome (ARDS)?

Answer 76

Acute respiratory distress syndrome (ARDS) is caused by the increased permeability of alveolar capillaries leading to fluid accumulation in the alveoli, i.e. non-cardiogenic pulmonary oedema. Final common pathway for many conditions Clinical features are typically of an acute onset and severe: 1. Dyspnoea 2. Elevated respiratory rate 3. Bilateral lung crackles 4. Low oxygen saturations Clinical diagnosis 1. Hypoxia (PaO2/FiO2 ≤ 300mmHg ) 2. Non-cardiogenic pulmonary oedema

Question 77

What are some direct and indirect causes of ARDS?

Answer 77

Causes Direct – pneumonia, aspiration, hyperoxia, ventilation Indirect – sepsis, trauma, pancreatitis, acute hepatic failure

Question 78

What is TB? What are the two stages of infection? What are the predisposing factors for TB?

Answer 78

TB - Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis that most commonly affects the lungs. Most common cause of granulomatous inflammation in the world Stages 1. Primary TB - A non-immune host who is exposed to M. tuberculosis may develop a primary infection of the lungs - forms Gohn complex (Ghon focus and hilar lymph nodes) - normally cleared in healthy individuals. 2. Secodnary TB - reactivation of latent TB Predisposing factors 1. Alcoholism 2. Diabetes mellitus 3. HIV / AIDS 4. Some ethnic groups

Question 79

What are the treatments/preventions used for TB?

Answer 79

1. Drugs – antibiotic therapy - isoniazid and rifampicin, pyrazinamide and ethambutol - e.g. all four for 2 months, followed by single antibiotic use for 3-6 months 2. Prevention e.g. BCG vaccination

Question 80

Outline the development/progression of primary tuberculosis?

Answer 80

First 3-4 weeks 1. M. TB infects and multiplies within alveolar macrophages (naive, unable to kill) - secrete IFN causing increased recruitment to form local granuloma (necrosis in the middle) 2. Bacterium resides in phagosomes & carried to regional lymph nodes, from there to circulation 3-8 weeks 1. Onset of cellular immunity & delayed hypersensitivity 2. Activated lymphocytes further activate macrophages to kill 3. **Primary infection arrested in most immunocompetent people** 4. Few bacilli may survive dormant Visible features - Hilar lymph node and Subpleural lesion - Known as Ghon complex

Question 81

What happens if the immune system is unable to arrest the primary TB infection?

Answer 81

Infection not arrested - minority of people - Infants, children, immunocompromised Two outcomes 1. **Tuberculous bronchopneumonia** - Infection spreads via bronchi - Results in diffuse bronchopneumonia - Well developed granulomas do not form 2. **Miliary Tuberculosis** - Infection spreads via blood-stream - Scattered TB across lung parenchyma - Spread to multiple organs - lungs, liver, spleen, kidneys, meninges, brain

Question 82

What is secondary tuberculosis?

Answer 82

Secondary Tuberculosis - Also termed ‘Post-primary’ TB Reactivation of old, often subclinical infection More damage due to hypersensitivity 1. Apical region of lung 2. Tubercules develop locally, enlarge and merge 3. Erode into bronchus and cavities develop 4. May progress to tuberculous bronchopneumonia

Question 83

What is a granuloma?

Answer 83

A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate

Question 84

What is another important cause granulomatous pulmonary inflammation?

Answer 84

Sarcoidosis - autoimmune disease

Question 85

What are key features of fibrotic interstial lung disease?

Answer 85

Fibrotic interstial lung disease 1. Restrictive chronic lung disease 2. Symptoms - Dyspnoea, (cough), tachypnoea, crepitations, cyanosis (late stage) 3. Pulmonary function tests - Reduced transfer factor and total lung capacity - reduced gas transfer and capacity 4. Honeycomb/Ground glass changes in lower zones on x-ray - BIG YES to fibrosis Association with righ side heart failure - oedema

Question 86

What are the three different type of fibrotic lung diease?

Answer 86

1. Idiopathic pulmonary fibrosis - high level of mortality when compared to other types, pathogenesis is unknown (genetic causes, fibroblast changes and immune cell involvement), lung surrounded by fibrosis tissue = restriction 2. Autoimmune - hypersensitivity pneumonitis - in resposne to foreign antigens 3. External agent - e.g. asbestos (occupational lung disease) - pleural plaques, pulmonary fibrosis, different cancers - other triggers Silica, coal dust, berrylium

Question 87

Summary of parenchymal lung disease.

Answer 87

**Acute inflammation** 1. Pneumonia - Neutrophils & macrophages 2. ARDS & COVID **Granulomatous inflammation** - Tuberculosis - Host pathogen interactions **Fibrosing lung diseases** - Defective repair mechanisms - Failure of clearance