Airway Function Flashcards
What are the basic functions of the airways?
- Gas exchange
- conduct O2 to the alveoli
- conduct CO2 out of the lung-
What is gas exchange facilitated by?
mechanical stability (cartilage)
control of calibre (smooth muscle)
protection and ‘cleansing’
What is the organisation of airways structure?
- Cartilage slightly offset for tensile strength
- C shaped
- Smooth muscle underneath cartilage
- Submucosal gland embedded into smooth muscle
- Pulmonary circulation
- Airway lumen
- Mucucs
- Epithelium
- Basement membrane
see notes
What are the types of cells in the airways and their function?
Lining cells: Ciliated, Intermediate, Brush, Basal
Contractile: Smooth muscle
Secretory: Goblet (epithelium), Mucous, Serous (glands)
Connective tissue: Fibroblast, Interstitial (elastin, gollagen, cartilage)
Neuroendrocrine: Nerves, Ganglia , Neuroendocrine cells , Neuroepithelial bodies
Vascular: Endothelial, Pericyte, Plasma, Smooth muslce
Immune: Mast cell, Dendritic cell, Lymphocyte, Eosinophil, Macrophage, Neutrophil
What is the structure of goblet cells and how do they produce mucus ?
Goblet cell bulges out into lumen
- Contains mucin granules
- Move apical surface and fuse with it
- Pore forms drawing water in
- As soon as hits airways takes in water and expands x100
What is the structure of the ciliated cell?
- Contain many mitochondria
How is mucous secreted by the human bronchial gland (ariway submucosal gland)?
- there areserous cellsperipheralto the mucus cells
- The serous cells produce awatery mucus(has antibacterial enzymes like lysozyme)
- The watery secretions from the serous cells flush over the mucus secretions and washes into the collecting duct
- The glands also secretewater- mucus, antibacterial enzymes, salt and water all come from these glands
What is the structure of the cilium?
- On top of ciliated cells
- Rods inside (slide over each other pushing cilia one way or another)
- Apical hooks (Engage with mucus)
- 9 outside + 2 middle in transverse
- Beat in metachronal time
What is metachronal rhythm?
One field beats
Field behind catches up
One that bear first is on backstroke
repeat
What are the functions of epithelium?
- Secretion of mucins, water and electrolytes
components of ‘mucus’ (+ plasma, mediators etc) - Movement of mucus by cilia – mucociliary clearance
- Physical barrier
- Production of regulatory and inflammatory mediators: NO (by nitric oxide synthase, NOS) - may control beating of cilia
CO (by hemeoxygenase, HO)
Arachidonic acid metabolites, e.g. prostaglandins (COX)
Chemokines, e.g. interleukin (IL)-8
Cytokines, e.g. GM-CSF
Proteases
What are the functions of airway smooth muscle in response to inflammation?
Structure
- Hypertrophy - Proliferation
Tone
- Airways calibre - Contraction - Relaxation
Secretion:
- Mediators - Cytokines - Chemokines
What happens to smooth muscle during respiratory disease e.g asthma?
Hypertrophy–>increased contractile force–>increase mediator secretion
What is an airway response to cytokines?
Upregulate NOS, PGD
Chemokines recruit inflammatory cells
Smooth muscle involvement
What is tracheo-bronchil circulation?
Massive plexus below epithelium of capillaries, veins and arteries
What is the blood flow to airway mucosa?
- 1-5% CO
- 100-150 ml/min/100g of tissue
Where to bronchial arteries arise?
- Aorta
- Intercostal arteries
How does blood return from tracheal circulation?
- Systemic veins
How does blood return from bronchial circulation?
- Bronchial veins
- Pulmonary veins
What are the function of the tracheo - pulmonary tree?
- Good gas exchange (airway tissues and blood)
- Contributes to warming of inspired air
- Contributes to humidification of inspired air
- Clears inflammatory mediators
- Clears inhaled drugs (good/bad, depending on drug)
- Supplies airway tissue and lumen with inflammatory cells
- Supplies airway tissue and lumen with proteinaceous plasma (‘plasma exudation’ – next slide)
How does plasma exudation occur in the airways?
Epithelium:
- Sensory nerves stimulated to contract by C fibre nerve and inflammatory mediators (histamine and platelet activating factor)
- Endothelial cells to contract
- Form little gaps which leak plasma out of post capillary venules to bathe tissue
- Exaggerted in pathology e.g asthma
How is airway function controlled?
Nerves:
parasympathetic (cholinergic)
(sympathetic – adrenergic?)
sensory
Regulatory and inflammatory mediators:
histamine
arachidonic acid metabolites (e.g. prostaglandins, leukotrienes)
cytokines
chemokines
Proteinases (e.g. neutrophil elastase)
Reactive gas species (e.g. O2-, NO)
How are airways innervated in humans ?
Constriction
- Irritant
- Vagus
- Nodose ganglion
- Activation of cholinergic (sensory pathway) reflex via vagus
- Bronchoconstriction
Relaxation
Adrenaline and NO relax airway
NO:
- Sensory
- Dorsal root ganglion
- Spinal cord
- Efferent pathway
What are some regulatory inflammatory cells in the airways?
Eosinophil: Neutrophil: Macrophages Mast cells: T lymphocyte: Structural cells e.g smooth muscle
What molecules do regulatory inflammatory cells release?
- Histamine
- Serotonin
- Adenosine
- Prostaglandins
- Leukotrienes
- Thromboxane
- PAF
- Endothelin
- Cytokines
- Chemokines
- Growth factors
- Proteinases
- Reactive gas species
What is the function mediators released by immune cells?
Smooth muscle (contraction, relaxation) Plasma exudation Chemotaxis Secretion (mucins, water, etc.) Neural modulation Remodeling
What are respiratory disease with loss of airways control?
- Asthma
- COPD
- CF
- Characterized with airways inflammation
- Leads to airway obstruction
- Due to airways remodeling
What is airway remodelling?
Airway changes in structure over a long period of time
What is asthma?
- A clinical syndrome characterised by increased airway responsiveness to a variety of stimuli
- Obstruction varies over short periods of time
- Reversible (spontaneoulsy or with drugs)
- Various degrees: mild to severe
What are the symptoms of asthma?
- Dyspnoea, wheezing and cough
- Airway inflammation leading to remodelling
What is the histopathology of asthma?
Inflammation
- eosinophils most prominent
- Basement membrane thickening
- Lumen filled with mucus plug
- Goblet cell hyperplasia
- Epithelial fragility
- Smooth muscle hypertrophy
- Gland hypertrophy
- Vasodilation (congested vessels)
- Cellular infiltrate
Bronchoconstriction
- Muscus plug in lumen
- Airways thrown into folds because airways smooth muscle contracted
What is the pathophysiology of asthma?
- Epithelial fragility
- Exposes sensory nerve
- Sets up a cholinergic reflex
- Causes bronchoconstriction and mucus secretion
- Repeated bronchoconstriction and mucus secretion associated with hypertrophy
- Influx of inflammatory cells
- Mast cells produce inflammatory mediators
- Leads to remodeling of airway
What is the difference betwene asthma and COPD?
Bronchoconstriction in asthma
Asthma is partially reversible
What sites does asthma affect?
Large and small ariways
What causes asthma?
Airway hyperesponsiveness
Increased mucus
What are the inflammatory cells in asthma?
Eosinophils
Mast cells
Th2 lymphocyte
What are the inflammatory mediators in asthma?
IL4
IL4
cysLTs
IL4
IL4
cysLTs
Bronchodilators
Corticosteroid
What is the histopathology of asthma?
Swollen and inflamed
Goblet cells inflamed so secreting lots of mucus –>mucus plug
Ariways constricted and blocked so can’t breathe
What is COPD?
Progressive ilness
Small airways disease
Chronic bronchitis
Emphyema
What are the stages of COPD?
Often misdiagnosed as asthma, so usually seen in later stage e.g 2
What causes COPD?
Smoking
Air pollution
What sites does COPD affect?
Bronchioles (small airways)
What inflammatory cells are present in COPD?
Neutrophils
Macrophages
Tc1 lymphocytes
What are the inflmmatory mediators in COPD?
Bronchodilators
Corticosteroids
What is the treatment for COPD?
Bronchodilators don’t work
What is the histopathology of chronic bronchitis?
Mucus Hypersecrection Mainly occurs in small ariways Can see little bits of cilia Lumen so small Mucus builds up until passage blocked
What is the histopathology of small airways disease?
Narrowing of airways
Alveolar attathcment keep bronchioles on –> damaged
If mess with smooth muscle and tension lumen size compromised
What is the pathology of emphysema?
Alveoli start dying Lung becomes destroyed, has holes in it Alveolar detachments Airway reduced Matrix thickening (of walls)
What happens to lung tissue in COPD?
In normal lung alveolar attachment outside lumen and smooth muscle matrix hold it ioen
Few mucus secreting cells – not secreting lots of mucus
Mainly ciliated cells
In COPD, due to emphysemetic destruction get disruption of alveolar attahcments so lumen smaller
Inner cells inflamed further reducing lumen diameter
Cell population changes – increased number of goblet cells
Mucus
Hypersecretion
What is the pathophysiology of COPD?
- Smoke affects epithelial cells
- Produce TGF beta
- Signal to fibroblast (underneath epithelium) which secrete matrix and reorder/remodel matrix
- Epithelial also signals to alveolar macrophages
- Signal to CTLs which cause secretion of proteases
- Matrix metalloproteases: cut down matrix
- Alveolar macrophages also secrete metalloproteases and chemotactic factors
- Lots of inflammatory macrophages, but can’t
differentiate so just sit there recruiting more
macrophages - Less anti-inflammatory macrophages
- Lots of inflammatory macrophages, but can’t
- Reruit neutrophils which release neutrophil elastace and matrix metalloproteinasas (MMPs)
- Mass damage to mitochondria – dysfunction
- Release lots of superoxide further causing genetic
damage (may give antioxidants to treat) - Lots of proteins and irritants in the lumen causes mucus hypersecretion
- Due to cell population changes and decreased lumen size mucus cannot be cleared forming plug
What is a lavage?
Way of washing lung
What are protease inhibotrs?
- inhibit proteases (alpha 1 AT, TIMPs) – if downregulated proteases secreted causing mass amounts of tissue damage
When is COPD detected usually?
around age of 40
Symptoms increase by stage 3 and become disabled
Why do the small airways collapse, become obstructed and stenosed?
Loss of alveolar attahcments, mucus wall thickening, inflammation
