11. Lung Infection Flashcards
What percentage of people admitted to hospital with pneumonia die?
5%
What 3 types of defences are present in the respiratory tract?
- Mechanical: URT filtration, mucociliary clearance, surfactant, epithelial barrier
- Local - BALT, secretory IgA, lysozyme, transferring, antiproteinases, alveolar macrophages
- Systemic - polymorphonuclear leucocytes, complement, immunoglobulins
How sterile is a healthy lung?
Sterile from the first bronchial division
Describe the overall structure of the ciliated epithilium
- Tight junctions - cohesive layer
- Ciliated cells and goblet cells
- 200 cilia for 1 cell
- Cilia surrounded by a watery periciliary fluid
- Mucus floats on top of the cilia - sticky and gel-like
Describe the movement of the cilia
- Beats 15 times per second - metachronal rhythm
- Vertical, engages with mucus, pushes forward
- Cilium withdrawn within the periciliary fluid in a curved fashion
- Repeats
Describe the ultrastructure of a cilium
- 9+2 microtubule structure
- 9 outer microtubule pairs have dynein arms
- Dynein arms have ATPase - energy for microtubules to move up and down
- Central 2 microtubules are used as an axis to move against
- People can be born with abnormalities
What are the 2 most common causes of acquired defects of the mucociliary system?
- Cigarette smoking - destroy the cilia, makes mucus more viscous
- Viral infection - destroy cilia, more watery mucus, separate tight junctions
Why can mucus become a yellow-green colour following a viral infection, despite feeling better?
A bacterial infection capitalises on the weakness of the respiratory epithelium
Describe the restoration of the cilia following an infection
- Mucociliary system is disabled for around 6 weeks
- Sometimes the cilia grow back abnormally (compound cilia are useless)
- Most vulnerable in the first 3-4 days after infection
- Fully defended after around 3 weeks
What generally causes acute, overwhelming respiratory infection syndromes?
- Could be a very virulent bug
* Could be a host defence disorder
What generally causes recurrent-acute (slow to resolve) respiratory infection syndromes?
- Bronchial
- Pneumonic
- Host defence abnormalities
How does phlegm react to antibiotics in respiratory infection syndromes?
- Daily purulent sputum only temporarily responds to antibiotics
- Daily yellow/green phlegm is unusual
What happens to the heart if the cilia don’t work?
- Side of the body that the heart is on is random
- 50% of people born without functioning cilia have dextrocardia (heart on right)
- Microtubules used to guide cells during embryological development
- Abnormality e.g. dynein arm defect - no outer dynein arm
How are defective cilia identified?
- Biopsy from the nose - looked at under the microscope
* Painful and uncomfortable
How does the amount of nitric oxide differ in people with primary ciliary dyskinesia?
- Primary ciliary dyskinesia - malfunctioning cilia
- Less NO
- Normal NO - no nasal biopsy needed
Give an example of a virulent and less virulent pathogenic species in a respiratory disease
- Streptococcus pneumoniae - pneumonia
* Encapsulated haemophilius influenza - bronchitis/sinusitis
How do bacteria avoid the movement of the cilia?
- Hair like fimbriae
- Act as anchors to the epithelial surface
- Stick to damaged epithelium, not where there is cilia
What are bacterial strategies to avoid clearance from the airways?
- Exoproducts which impair mucuciliary clearance - slow and disorganise ciliary beat, stimulate mucus production, affect ion transport
- Enzymes - break down local immunoglobulins
- Exoproducts - impair leukocyte function
- Adherence - increased by epithelial damage and tight junction separation
- Avoid immune surveillance - using surface heterogeneity, biofilm formation, surrounding gel and endocytosis
What can bacterial persistence lead to?
- Lung abscess
* Chronic airway infection
What causes bronchiectasis?
- Chronic airway infection
- Chronic inflammation
- Progressive damage to wall
- Brochiectasis - enlarged airway
What does pneumonia look like on an X-ray?
- White area
* Due to solid lung - alveoli full of pus (trying to fight infection)
What are the clinical features of pneumonia?
- Cough
- Sputum
- Fever
- Dyspnoea
- Pleural pain
- Headache
What causes the stabbing pleuritic chest pain?
- Pain fibres on the surface of lungs
* Solid lung => inflammation reaches the periphery
Describe streptococcus pneumoniae
- Negatively charged polysaccharide capsule
- Difficult to bind to the epithelium but more virulent
- Can invade the bloodstream => systemic
- Produces a toxin (pneumolysin) that punches holes in cells, killing them
What causes gas trapping in the lungs?
- Diseased lungs
- Lost elasticity
- Collapses back down
- Closed airways traps air
- Higher residual volume
What does trapped air look like in medical imaging?
• String of pearls
- dilated airways strung together by scar tissue
• Whitening at the bottom of the dilations
- pooling of phlegm
What are common complaints of patients with bronchiectasis?
- Daily sputum production
- Recurrent respiratory infections
- Breathlessness
- Fatigue
How can you help someone remove excess phlegm and why is it important?
- Postural physiotherapy at set points each day
- Remove the stimulus for neutrophils to move in
- Reduces inflammation
What are the causes of chronic bronchial sepsis?
- Congenital e.g. pulmonary sequestration (tissue not connected to pulmonary arterial blood supply)
- Mechanical obstruction
- Inflammatory pneumonitis e.g. gastric contents, caustic gas
- Fibrosis
- Postinfective
- Impaired mucociliary clearance
- Immune deficiency
What can Marfan’s syndrome lead to in the lungs?
• Bronchiectasis
• Structures that make joints hyper-reflexive are also in the airways
(• Fibrillin 1 defect)
Describe the cycle of infection and inflammation
- Chronic infection
- Chronic inflammation
- Damage
- Impaired lung defence
- Further inflammation
- Further damage
What changes the protease anti protease balance?
• Most important mechanism in inflammation
- Neutrophil phagocytoses the bacterium and produces proteases that kills it
- Protease spills into surrounding secretions
- Anti-proteases (alpha 1 antitrypsin) in the airways normally neutralise the protease to prevent damage
- They can be overwhelmed by the proteases if there are too many neutrophils during chronic inflammation
- Free proteases in yellow-green sputum
- More epithelial damage => more frequent infections
