Week 4 - Pneumonia, COPD & Smoking Flashcards
Outline pulmonary defence mechanisms.
- The normal lung parenchyma remains sterile because of the efficiency of a number of immune and non-immune defence mechanisms in the respiratory system, extending from the nasopharynx all the way into the alveolar air spaces.
- Despite the multitude of defence mechanisms, weaknesses do exist, predisposing even healthy persons to infection. Defects in innate immunity (including neutrophils and complement defects) and humoral immunodeficiency typically lead to an increased incidence of infections with pyogenic bacteria.
- In addition to inherited anomalies, several aspects of lifestyle interfere with host immune defence mechanisms and facilitate infections e.g. cigarette smoking compromises mucociliary clearance and pulmonary macrophage activity, and alcohol not only impairs cough and epiglottic reflexes, thereby increasing the risk of aspiration but also interferes with neutrophil mobilisation and chemotaxis.
Identify the innate and adaptive immune defences of the lung.
Innate:
- Entrapment of microbial organisms in the mucous blanket and removal by means of the mucociliary elevator.
- Phagocytosis by alveolar macrophages that can kill and degrade organisms and remove them from the airspaces by migrating onto the mucociliary elevator.
- Phagocytosis and killing by neutrophils recruited by macrophage factors.
- Serum complement may enter the alveoli and be activated by the alternate pathway to provide the opsonin C3b which enhances phagocytosis.
- Organisms including those ingested by phagocytes may reach the draining lymph nodes to initiate immune responses.
Adaptive:
- Secreted IgA can block attachment of microorganisms to epithelium in the upper respiratory tract.
- In lower respiratory tract, serum antibodies (IgM, IgG) are present in the alveolar lining fluid. They activate complement more efficiently by the classic pathway, yielding C3b.
- Accumulation for immune T cells is important for controlling infections by viruses and other intracellular microorganisms.
Outline the classification of pneumonia.
- Pneumonia can be very broadly defined as any infection in the lung.
- Respiratory infection causing inflammation of the alveoli - lower respiratory tract.
Etiologic types: • Infective - Viral - Bacterial (most common) - Fungal - Tuberculosis • Non-infective - Toxins - Chemical - Aspiration (of toxic chemical e.g. gut bacteria entering lungs after vomiting - infective).
Morphologic types:
• Lobar
• Broncho
• Interstitial
• Clinical:
- Acute/chronic
- Typical/atypical
- Community acquired/hospital acquired.
Outline the aetiology of pneumonia.
• Community acquired acute pneumonia (lobar pneumonia):
- Streptococcus pneumoniae (>90% - gram positive diplococci, indication for pneumococcal vaccine).
- Haemophilus influenzae.
- Moraxella catarrhalis.
• Nosocomial (hospital) pneumonia (broncho pneumonia):
- H. influenzae (gram negative bacilli - rods).
- Klebsiella (most frequent cause of gram negative bacterial pneumonia).
- Pseudomonas.
- E. coli.
- Staph. aureus.
• Atypical pneumonia:
- Mycoplasma.
• Aspiration pneumonia:
- Anaerobic oral flora (bacteroides).
• Chronic pneumonia:
- TB.
- Atypical mycobacteria.
- Fungi.
• Pneumonia in the immunocompromised:
- CMV.
- Pneumocystis.
- Atypical mycobacteria.
- Candida.
- Aspergillosis.
Explain the pathogenesis of pneumonia.
Phases of pneumonia:
1. Congestion.
• Bacteria enter alveoli (overcome defence mechanisms) and release bacterial toxins causing severe inflammation → results in vasodilation of alveolar capillaries.
• Alveolar walls become congested with RBCs.
• Leakage → fluid (plasma) accumulates in alveolar space/lumen.
• Characteristic features of pneumonia - chest pain, fever (release of inflammatory mediators) and dyspnoea (fluid accumulation in alveoli).
- Red hepatisation.
• RBCs and WBCs leak out of capillaries into the lumen (diapedesis). More RBCs than WBCs.
• Alveolar air spaces are packed with neutrophils, RBCs and fibrin.
• Lung appears red and heavy/solid - liver like consistency (normal lung is grey and light/spongy). - Grey hepatisation.
• Neutrophils and macrophages begin eating away bacteria → inflammation reduces, bacteria removed.
• Removing all the dead tissue (loss of exudate/RBCs in alveolar space, loss of congestion in alveolar walls).
• Lung is dry, grey and firm. - Resolution.
• Clearing of the area by macrophages. Once removed all the dead cells/bacteria → lung is back to normal with only a few macrophages remaining.
• Resolution follows in uncomplicated cases as exudates within the alveoli are enzymatically digested to produce granular, semifluid debris that is resorbed, ingested by macrophages, coughed up or organised by fibroblasts growing into it.
Outline lobar pneumonia (community acquired):
- Epidemiology/aetiology.
- Pathogenesis.
- Clinical features.
- Complications.
• Typical acute pneumonia that occurs in healthy adults and is commonly due to the spread of bacteria (mostly bacterial in origin).
• 1-3 days, short history of high fever, pleuritic chest pain, rusty sputum, productive mucopurulent cough, shaking, chills.
• Unilateral, whole lobe or segment.
• 95% Streptococcus pneumoniae (Klebsiella in aged, DM, alcoholics).
• 4 pathogenic stages:
- 1 day - congestion phase - vasodilation and congestion.
- 2 days - red hepatisation phase - exudation + cells (RBC).
- 4 days - grey hepatisation phase - neutrophils and macrophages.
- 8 days - resolution phase - few macrophages/normal (clears after 1 week if the body is able to handle the infection).
• Complications (rare as the bacteria is less virulent plus the immune capacity is high) - lung abscess, pleuritis, pleural effusion, pleural adhesions, fibrosis, emphysema.
Outline bronchopneumonia (hospital acquired):
- Epidemiology/aetiology.
- Pathogenesis.
- Clinical features.
- Complications.
- Patchy bilateral, lower lobes (usually limited to lower lobes) in aged or immunosuppressed individuals in hospital settings (occurs in diseased lung or person - immunocompromised - diabetes, cancer, steroid/immunosuppression therapy).
- Bilateral, multiple patches that do not respect any anatomical boundaries (bacteria highly virulent → damage alveoli walls and spread → complications more common).
- Gram negative bacilli - Haemophilus influenzae (most common), Klebsiella pneumonia, Moxarella catarrhalis, Staph aureus.
- High fever, rusty sputum, pleuritic chest pain.
- Pathogenic phases are not clear. Different patches in different phase (within each patch, each alveoli measures a different phase of inflammation → mixture of phases within area affected - characteristic of bronchopneumonia).
- Complications (more common because of more virulent bacteria) - lung abscess, pleuritis, pleural effusion, pleural adhesions, fibrosis, emphysema.
Differentiate lobar and bronchopneumonia.
Lobar: • Middle age (20-50). • Primary in a healthy adult. • Males common. • 95% pneumococcus (Klebs.) • Entire lobe consolidation. • Diffuse. • Limited by anatomic boundaries. • Usually unilateral. • Uniform distribution.
Broncho: • Extremes of age (infancy/old age). • Secondary in sick. • Both genders, • Staph, Strep, H. infl. • Patchy consolidation. • Around small bronchi. • Not limited by anatomic boundaries. • Usually bilateral. • Patchy distribution.
What are the complications of pneumonia?
- Spread of infection, septicaemia. Meningitis, infective endocarditis, arthritis.
- Lung abscess, empyema (pus in pleural cavity), bronchiectasis.
- Pneumothorax.
- Lung fibrosis (scarring).
- Pleural fibrosis, adhesions.
- Atelectasis, emphysema (irregular).
- Scar cancer (adenocarcinoma) - rare.
- Complications more likely with serotype 3 pneumococci*
- Although complications can occur, pneumonia usually heals without complication.
Outline atypical/mycoplasma pneumonia.
- Usually caused by mycoplasma and viruses e.g. influenza.
- Children (over age 3 years) and young adults - common in young age.
- Slow, gradual onset, malaise, headache, fever for > 3 days to weeks.
- Cough constant, harsh, dry, hacking non-productive.
- Maximum symptoms - minimal signs* (patient’s have maximal symptoms but minimal signs). Characteristic feature - patients will have very severe symptoms but very minimal signs clinically because the involvement is only in the walls of the alveoli. Lumen is reasonably empty - few inflammatory cells but walls are thick. Does not show as strong white areas in X-ray because there is still air but oxygen is not able to be taken in because the walls have become thick/inflamed (inflammatory cells) - interstitial pneumonia.
- No physical findings of consolidation, no alveolar exudate.
- Inflammation - limited to alveolar walls. Interstitial pneumonia.
- Wheezing may be present unlike bacterial pneumonia.
- Macrolide antibiotics (erythromycin).
- In contrast with acute pneumonias, atypical pneumonias are characterised by respiratory distress out of proportion to the clinical and radiologic signs and by inflammation that is predominantly confined to alveolar septa, with generally clear alveoli.
- Most common causes of atypical pneumonias include those caused by M. pneumonia, viruses include influenza viruses type A and B, metapneumovirus, C. pneumonia and C. burnetii (agent of Q fever).
Outline chronic pneumonia.
• Chronic, lymphoid infiltrate, no classical stages (lymphoid infiltrate with extensive destruction of the lungs. Large cavities and scarring → maximum damage). • Lung destruction - granuloma, cavity, abscess (cavity formation, granulomas (chronic inflammation), abscess formation). • Organisms: - Mycobacterium tuberculosis. - Histoplasma capsulatum. - Aspergillosis (fungus). - Actinomyces. - Candidiasis.
Outline non-infective pneumonias.
- Aspiration pneumonia - lower lobe, secondary infection, abscess formation common complication. Aspiration of gastric contents either while unconscious or during repeated vomiting.
- Lipid pneumonia - airway obstruction causing atelectasis and necrosis with fat deposits. Develops when lipids enter the bronchial tree. Sources may be exogenous (e.g. inhaled nose drops with oil base, inhalation of cosmetic oils, GORD) or endogenous (foamy macrophages and giant cells fill the lumen of the disconnected airspace). Presents as foreign body reaction causing cough, dyspnoea and often fever. Haemoptysis has also been reported.
- Eosinophilic pneumonia - Asthma, Loffler’s syndrome.
- Bronchiolitis Obliterans Organising Pneumonia (BOOP) - reactive (irritants), type II cell hyperplasia. Due to irritants causing hyperplasia of the type II cells - macrophages increasing and filling up alveolar air space.
Describe the morphology of Streptococcus pneumoniae.
- Gram negative diplococci.
- Circular colonies raised with depressed centres.
- Alpha (partial) haemolysis - dark green area around colony (clearing around central disc of optochin is diagnostic).
- Staphylococcus aureus - beta haemolysis (bright clear area around colony).
- Klebsiella pneumoniae - gamma haemolysis.
Outline tuberculosis:
- Aetiology.
- Pathogenesis.
- Morphology.
- Clinical features.
- Diagnosis.
- Management.
Aetiology:
• Typically Mycobacterium tuberculosis.
• Droplet spread.
Pathogenesis:
• Airborne bacilli deposited in lungs and ingested by pulmonary macrophages.
• Macrophages destroyed by ingested bacteria → pneumonitis → primary infection/focus (infection is usually controlled by cellular immunity).
• 3 subsequent outcomes:
- No clinical disease.
- Progression primary lesion to further lung involvement → active disease.
- Reactivation of primary focus years after primary infection.
Morphology:
• Microscopy - caseating granuloma - zone of caseation necrosis surrounded by chronic inflammatory cells (epitheloid cells (highly stimulated macrophages) and Langerhan’s giant cells) and fibrosis.
Clinical features:
• Lethargy, weight loss, night sweats, fever.
• Cough with mucopurulent sputum or haemoptysis.
• Can have miliary spread → systemic symptoms.
Diagnosis: • Clinical suspicion. • Ziehl-neelson stain. • Acid-fast bacilli culture. • PCR. • Mantoux (tuberculin) skin test (hypersensitivity reaction). • Quantiferon assay.
Management: • Isolation. • Contact tracing. • 6 month drug regime (DOTS program). • Increase in drug resistance TB and HIV/TB co-infection is a concern.
- Primary TB - initial infection.
- Secondary TB - reactivation of latent infection.
- Miliary TB - widespread dissemination of M. tuberculosis via haematogenous spread e.g. liver, spleen.
- Pulmonary TB - infection of lungs.
- Extra-pulmonary TB - infection of organs other than the lungs, such as lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meninges etc.
- Ghon focus - primary lesion in the lung caused by mycobacteria. Small area of granulomatous inflammation.
- Ghon complex - if the Ghon focus also involves infection of adjacent lymphatics and hilar lymph nodes, it is known as the Ghon’s complex.
Outline chronic obstructive pulmonary disease (COPD).
• Progressive irreversible chronic airflow limitation due to inflammatory response to noxious substances. Progressive decrease in pulmonary function.
• Incidence increasing around the world (important disease compared to others which are decreasing).
• 4th leading cause of death.
• Women more.
• Smoking >80%.
• Commonest cause is smoking but also caused by congenital disorders, pollution and other causes (less common).
• Components:
1. Emphysema - alveolar wall destruction, overinflation.
2. Chronic bronchitis - productive cough, airway inflammation.
3. Asthma - reversible obstruction (bronchial hyper-responsiveness triggered by allergens, infection etc.)
