Pulmonary Defence Mechanisms Flashcards
How much oxygen is consumed by a human per day?
500 litres
How much oxygen is inhaled from the atmosphere by a human in a day?
8000 litres
What is the consequence of the high volume of oxygen inhaled?
- Makes the respiratory system a major site of contact between internal structures of body and atmosphere
Name two things that movement of oxygen from the atmosphere to internal structures, requires.
Fast movement of air in and out of lungs
Efficient gas exchange
What does the fast movement of air put limits on?
Limits on surfaces that have filtering and barrier properties
What does efficient gas exchange require?
- Large surface area
- Warm environments to allow for diffusion
- Innervation by blood vessels
- Thin membrane at gas-blood interface
What specific conditions make the respiratory system immunologically vulnerable?
- Thin membrane - delicate and vulnerable to damage
- Warm environments - good environment for microorganisms to thrive
Outline the types of harmful organisms commonly found in the air.
- Microorganisms
- Allergens - e.g dust, pollen
- Toxic gases
- Pollution
Give examples of large particulates found in the air
- Food
- Choke hazards
Give examples of fine particulate matter found in the air
- Pollution
- Dust
- Pollen
Give examples of pathogens found in the air
- Bacteria
- Viruses
- Fungi
Outline three ways a respiratory condition can be transmitted
- Droplet transmission
- Breathing
- Coughing
How can respiratory infections be distinguished?
- Type and identity of microorganism
- Respiratory structure affected
How do allergens such as dust and pollen, usually harm the respiratory system?
- Trigger extreme immune responses
- Causes local inflammation and tissue pathology
EXAMPLE: airway narrowing and obstruction
Some organic particles, when inhaled, can cause chronic restrictive conditions.
With an example of a condition, suggest how they do this.
EXAMPLES: fibrosis, pneumoconiosis
- Cause particle deposition on the respiratory structures
- Trigger inflammation
Give examples of physical obstructions that enhance immunological defence of the lungs and airways.
- Cilia
- Mucus
- Nasal hair
- Branching structure of the airways
Give examples of protective reflexes that enhance immunological defence of the lungs and airways.
- Coughing
- Expiratory reflex
Give examples of immune cells that enhance immunological defence of the lungs and airways.
- Antimicrobial proteins
- Innate immunity/epithelial cells
- Resident immune cells e.g macrophages
What are the usual roles of physical adaptions in immunological defence?
(FPATH RECAP)
- Prevents particles and microorganisms reaching a certain target
- With the respiratory system, it prevents them reaching the airways, lungs and bloodstream
What are the roles of the nasal hairs in the first 1cm of the nasal passage?
- Filters out large particles (>10μm) present in the air.
Briefly outline the structure of the nasal turbinates.
- Lined with mucous membranes
- Found in the nasal cavity after the nasal hairs
Briefly outline the structure of the nasal turbinates.
- Humidifies air before it reaches the lungs
- Further filtration of particles larger than ≈ 2μm
What can cause decreased nasal hair density/increased mouth breathing?
What is the effect of decreased nasal hair density/increased mouth breathing?
CAUSE: Upper respiratory occlusion
EFFECT: Greater risk of asthma
Where is mucus produced?
Submucosal glands and goblet cells
What is the purpose of mucus?
Traps inhaled particles
Outline the composition of mucus
- Gel with elastic and viscous properties - made up of water and solids(such as mucin, proteins and lipids)
- Lysozyme
- Antimicrobial proteins
What is the mucus gel layer found on top of?
Periciliary layer
Why is maintaining a sufficient periciliary layer depth important?
- The layer provides a media in which the cilia can function i.e for mucociliary clearance
What is the effect of coordinated beating of the cilia?
- Produces wave of movement
- This wave propels mucus gel layer towards the pharynx and allows it to be expelled
Each cilia’s movement consists of a reverse stroke as well as a forward stroke. Yet the mucus gel layer will ONLY move in one direction. Suggest a reason why.
- Cilia only makes contact with gel layer in forward stroke
- During reverse stroke, cilia bends and tip passes UNDER the gel layer
- Contact means layer will always move forward in one direction
What are the characteristics of healthy mucus?
- Clear colour
- Easily cleared
Why might mucus turn green following respiratory infection?
- Due to breakdown of granulocytes
Why might airway pathology change mucus viscosity?
- Breakdown of surrounding epithelium
- Mucus dehydration/ poor clearance - seen in cystic fibrosis
Outline two factors that can regulate the level of mucus synthesised and secreted into airways.
- Parasympathetic nervous system stimulation (e.g cholinergic activation of submucosal glands)
- Local inflammation
What is the effect of excessive mucus secretion?
- Airway obstruction
- Limited airflow
How does cystic fibrosis trigger reduced mucociliary clearance?
- CFTR Mutation
- Mucus dehydration
- Cilia dysfunction therefore reduced clearance
How does chronic bronchitis trigger reduced mucociliary clearance?
- Tobacco smoke exposure
- Airway inflammation
- Cilia damage and goblet cell hyperplasia therefore reduced clearance
What are the effects of reduced mucociliary clearance?
- More recurrent respiratory infections
- Greater inflammation and tissue damage
- Airway dysfunction and obstruction
What is the main purpose of neural reflexes within the airways?
- Trigger rapid expulsion of air
- Deposition of particles
What is the main purpose of neural reflexes within the airways?
- Trigger rapid expulsion of air
- Deposition of particles
Give three examples of the reflexes within airways
- Sneezing
- Coughing
- Laryngeal expiratory reflex
What is the basic mechanism for the reflexes within the airways?
- Activation of nociceptors by physical/chemical stimuli
- Activation of afferent sensory neurones - transmit impulse to respiratory centres e.g the medulla
- Efferent signals via parasympathetic/motor neurones transmitted to respiratory muscles (e.g diaphragm, intercostal muscles), the glottis (to close/open windpipe) and the airways. These muscles contract.
- Causes rapid expulsion of air
What is the difference between afferent and efferent nerve fibres?
- Afferent fibres transmit signals to the CNS, efferent transmits away from CNS
Outline the steps involved in sneezing
- Stimulation of sensory receptors within nasal cavity
- Deep inspiration phase
- Compression phase - glottis closes, so pressure increases
- Expiration phase - air is expelled
Outline the phases involved in coughing
- Stimulation of receptors within larynx
- Deep inspiration phase
- Compression phase
- Expiration phase - air is expelled
How does coughing differ from sneezing?
- Coughing can be voluntary
- Coughing also involves bronchoconstriction to increase expulsion pressure
How does the laryngeal reflex differ from coughing?
No preceding inspiration phase
What is the laryngeal reflex triggered by?
Activation of sensory receptors within vocal folds
What is the role of the laryngeal reflex?
Prevent entry of foreign bodies into the airways
What type of muscles are the following?
- GLOTTIS
- DIAPHRAGM
- INTERCOSTAL MUSCLES
- AIRWAYS
How are efferent signals transmitted towards these muscles?
- Airways - smooth muscle - transmit via parasympathetic neurones
- Glottis, diaphragm and intercostal muscles are skeletal muscle - transmit via motor neurones
How does the branching structure of the airways assist airway filtration?
- Airflow changes from laminar to semi-turbulent
- Greater particle deposition
- Greater contact between particles and mucus walls of airways
What are the roles of resident immune cells in the airways?
- Coordination of immune responses
- Removal of deposited cells
Where do alveolar macrophages derive from?
Progenitors produced in bone marrow
Where are alveolar macrophages found?
Airspaces
- So can travel between alveoli
What are the role of alveolar macrophages in phagocytosis?
- Phagocytose pathogens, dead cells and foreign material
- Digest these into residual material - removed by lymphatic system
Some particles such as asbestos fibers cannot be cleared by digestion and so cause inflammation.
How do macrophages respond to this?
- Toll-like receptor stimulation occurs
- Triggers further inflammation and adaptive responses by secreting cytokines and other inflammatory mediators
What is something that most macrophages can do, that alveolar macrophages don’t have the capacity to do?
- Most macrophages can form antigen-presenting cells
- Alveolar macrophages have very little capacity to do so
What is the result of Toll-like receptor stimulation?
- Initiates intracellular response
- Leads to proinflammatory response (e.g cytokine release)
What was determined from studies on mice with alveolar macrophage deficiencies?
- Increased biomarkers of infection
- Reduced survival following infection with pathogens
Why must the activity of the immune system be regulated?
Damage can be caused to airways by excessive inflammation
What type of bacteria lines the mucosal surfaces of the respiratory system?
Commensal bacteria
What is the current understanding of the role of commensal bacteria?
- Resist infection by other pathogens
- Development/modulation of healthy immune system
