Respiratory Systems 4 & 5 - Structure and Function of the Airways Flashcards
List the basic functions of the airways, and describe how these functions are facilitated
- The airways are condiut to conduct O2 to the alveoli, and conduct CO2 out of the lung
- This is facilitated by mechanical stability, control of calibre, protection and cleansing
- Mechanical stability is produced by cartilage
- Control of calibre is due to smooth muscle
Describe the organisation of the airway structure in the trachea, in a transverse section
- Outside - cartilage, which is in rings that are non-centred and C-shaped
- Smooth muscle
- Blood vessel
- Submucosal glands
- Ciliated cells covered with mucous and goblet cells
- Airway lumen
Which cell types in the airway are lining cells?
- Ciliated
- Intermediate
- Brush
- Basal
Which cells types in the airway are contractile cells?
Smooth muscle
Which cell types in the airway are secretory cells?
- Goblet
- Mucous
- Serous (glands)
Which cells types in the airways are connective tissue?
- FIbroblasts and intersitial cells
- Produce elastin, collagen, and cartilage
Which cell types in the airways are neuroendocrine?
- Nerves
- Ganglia
- Neuroepithelial bodies
Which cell types in the airways are vascular cells?
- Endothelial
- Pericyte
- Plasma cells
Which cell types in the airways are immune cells?
- Mast cells
- Dendritic cells
- Lymphocytes
- Eosinophil
- Macrophage
- Neutrophil
What do mucin granules contain?
Mucin (glycsylated proteins) in a highly condensed form
What do the submucosal glands produce?
- Mucous cells secrete mucus
- Serous cells secrete antibacterials
- Glands secrete water and salts too
- Secreted from acini
What is the difference between mucous and mucus?
- Mucous is the adjective (eg. mucous membrane)
- Mucus is the noun
Describe the structure of cilia
- Apical hooks engage with mucus
- Covered with cell membrane
- Made of microtubules in a 9+2 formation
- 200 per ciliated cell
Describe how cilia beat.
- Metachronal fashion
- Synchronised, like wind blowing over a field of wheat
List the functions of the airway epithelium
- Secrete mucus, water and electrolytes
- Move mucus by cilia (mucociliary clearance)
- Physical barrier
- Produce regulatory and inflammatory mediators
- Triggers lung repair
- Metabolises foreign and host derived compounds
List the regulatory and inflammatory mediators produced by the airway epithelium, and what enzyme they are produced by
- NO (by nitric oxide synthase, NOS)
- CO (by hemeoxygenase, HO)
- Arachidonic acid metabolites, e.g. prostaglandins (COX)
- Chemokines, e.g. interleukin (IL)-8
- Cytokines, e.g. GM-CSF
- Proteases
List the three functions of airway smooth muscle in inflammation
- Hypertrophy and proliferation
- Tone
- Secretion of mediators, cytokines, adhesion molecules and chemokines
Briefly describe the tracheo-bronchial circulation
- Bronchial arteries arise from the aorta, intercostal arteries and others
- Blood returns from the trachea via systemic veins
- Blood returns from te bronchi to both sides of the heart via bronchial and pulmonary veins
List the functions of the tracheo-bronchial circulation
- Good gas exchange
- Contributes to warming of inspired air
- Contributes to humidification of inspired air
- Clears inflammatory mediators
- Clears inhaled drugs
- Supplies the airway tissue with inflammatory cells and proteinaceous plasma
Describe the control of plasma exudation in airways.
- C-fibre nerves stimulate increased plasma to leave the blood
- Also stimulated by inflammatory mediators, such as histamine, and platelet activating factor
List the controls of the airway function
- Nerves (parasympathetic cholinergic and sympathetic adrenergic sensory)
- Regulatory and inflammatory mediators (histamine, arachidonic acid metabolites, cytokines and chemokines)
- Proteinases
- Reactive gas species
Describe the innervation of the airways
- To shut the airway, sensory nerve fibres relay up to the brain and there is a parasympathetic response (acetylcholine) to close the airway and secrete a small amount of mucous
- The airway afterwards is opened by sympathetic nerves and noradrenaline in other animals, while humans use an NO producing pathway, which speeds up cilia and is a vasodilator/dilates the airways
- The adrenal gland also produces adrenaline to open the airways
List the regulatory and inflammatory cells in the airways
- Eosinophils
- Neutrophils
- Macrophage
- Mast cell
- T lymphocyte
Give some examples of respiratory diseases with loss of airway control
- Asthma
- COPD
- Cystic FIbrosis
Define asthma and list the characteristics
- A clinical syndrome characterised by increased airway responsiveness to a variety of stimuli
- Airflow obstruction varies over short periods of time
- Dyspnoea, wheezing and cough
- Chronic inflammation and remodelling
Explain the pathophysiology of asthma
- Sensory nerves are activated, casing a cholinergic reflex resulting in bronchoconstriction and mucus hypersecretion
- This is accompanied by goblet cell hyperplasia, and hypertrophy
- Increase inflammatory mediators and growth factors
- Vasodilation
- Plasma leak and oedema
- Subendothelial fibrosis
Describe how the human airway epithelium looks in patients with COPD
- Increased goblet cell numbers and increased mucous secretion
- This is to defend against smoke
How do goblet cells change in smokers?
- Goblet cell number doubles (20% of epithelial cells in healthy people)
- Secretions increase
- Secretions are more viscoelastic
How do ciliated cells change in smokers?
- Severely depleted (usually 60-80% of epithelial cells in healthy people)
- Beat asynchronously
- Found in bronchioles
- Unable to transport thickened mucus
Describe the formation of stenotic bronchiolar airways in COPD
- In healthy people, intact alveolar walls hold the airway open, as there is no cartilaginous material in small airways
- In COPD patients, the walls of alveoli are disrupted so the airway doesnt open when you breathe in
- This results in blockage of the small airways
What is the function of club cells?
- Only present in the small airways of humans
- Previously were called CLARA cells
- 20% of epithelial cells, less in smokers
- Secretory cells, involved in detoxification and act as repair/progenitor cells.
What can smoking cause in the exchange surfaces of the alveoli?
HOLES
What is emphysema?
- A type of COPD where the breathing tubes are narrowed and the alveoli are damaged.
- Pulmonary fibrosis - increased synthesis of ECM makes the lungs rigid and unable to move
- Caused by smoking
What is the ratio of type 1 to type 2, and compare this with the percentage coverage of alveolar surface?
- Ratio of type 1 to type 2 is 1:2
- However, type 1 cells are thinner and more spread out, so take up 95% of the alveolar surface
Describe the function of epithelial type 2 cells
- Contain lamellar bosies which store surfactant prior to release onto the air-liquid interface
- Prevent alveolar collapse on expiration
- Precursor of type 1 cells
- Repair/progenitor cells
Describe the function of type 1 epithelial cells
Facilitate gas exchange and transport
Describe the function of stromal myofibroblasts in the alveoli
- Make ECM
- Collagen and elastin give elasticity and compliance
- They divide to repair
Describe the appearance of cells in alveolar fibrosis
- Increased type 2 cells
- Increased fibroblasts
- Increased collagen deposition
Describe the normal pathway of lung repair, and compare with the abnormal pathway
- Type 1 cell death is followed by growth factors stimulating type 2 cells to become type 1 cells
- Orchestrated by myofibroblasts
- In abnormal repair, there are elevated growth factors so type 2 proliferation occurs with no differentiation
List the functions of secretory epithelial cells
- Includes goblet, club and type II cells
- Secrete a protective layer to trap particles (surfactant/mucus)
- Synthesise and release antioxidants and antiproteinases
- Release lysosyme
- Carry out xenobiotic metabolism (process and detoxify foreign compunds)
- Contain cytochrome P450 and phase I/II enzymes
Why do neutrophils and macrophages increase in smokers?
- Increase by 10 fold
- Undergo phagocytosis, antimicrobial defence, xenobiotic metabolism, synthesise antioxidants
How does the macrophage:neutrophil ratio change in COPD patients?
Usually 70:30 in non-smokers
30:70 in COPD patients (as neutrophils increase by a lot more than macrophages)
What do neutrophils and macrophages do in the airways?
- Neutrophils produce serine proteinases
- Macrophages produce metalloproteinases
- Substrates: proteins, connective tissue, elastin, collagen
- Generate peroxides, interact with proteins and lipids, inactivates alpha-1-antitrypsin
- Produces growth factors
What are contained in club cells, type II cells and macrophages?
- Phase I and phase II enzymes
- These are involed in xenobiotic metabolism (foreign compounds)
How do phase I and phase II enzymes affect cigarette smoke?
- Phase I enzymes are involved in production of the active compound/carcinogen
- Phase II enzymes cause normal metabolism to water soluble metabolites
- Absence of phase II enzymes results in DNA binding, adduct formation and mutation
