Structure and function of the airways Flashcards
What is the branching the airways?
dichotomous branching
Where does the mechanical stability come from?
cartilage
What are type 1 cells in the alveolar regions?
- incredibly thin (like fried eggs) -cover ~95% of alveolar surface
- delicate barrier
- Facilitate gas exchange
What are type II cells?
- Replicate to replace type 1 ells
- release surfactant (reduces surface tension), antiproteases
- Xenobiotic metabolism
- Type II cells – greater numbers than Type I cells, but only cover ~5% of surface
What is the basic function of the respiratory airways?
Getting air efficiently to the gas exchange region. Keeping the pipework clear
What are the airways conduit to?
Conduit (‘pipes’) to:
- conduct O2 to the alveoli
- conduct CO2 out of the lung
- gas exchange
What are the airways facilitated by?
Facilitated by:
- mechanical stability (cartilage)
- control of calibre (smooth muscle)
- protection and ‘cleansing’
What does the pharynx do?
a common passageway for food, liquids and air.
What do the conchae do?
highly vascular – contribute to warming and ‘humidification’ of intra-nasally-inhaled air
What do the nasal hairs do?
Nasal hairs filter out large particles
What cell type are lining cells in the airway?
- Ciliated
- Intermediate
- Brush
- Basal
What cell type are contractile cells in the airway?
-Smooth muscle (airway, vasculature)
What cell type are secretory cells in the airway?
- Goblet (epithelium)
- mucous
- serous (glands)
What cell type are connective tissue in the airway?
-Fibroblast
-interstitial cell
(elastin, collagen, cartilage)
What cell type are neuroendocrine cells in the airway?
- Nerves
- Ganglia
- Neuroendocrine cells
- Neuroepithelial bodies
What cell type are vascular cells in the airway?
- Endothelial
- Pericyte
- Plasma cell (+smooth muscle)
What cell type are immune cells in the airway?
- Mast cell
- Dentritic cell
- Lymphocyte
- Eosinphil
- Macrophage
- Neutrophil
How is mucin secreted?
Mucin secretion by guinea pig tracheal goblet cell
expansion of intra-granular mucin upon secretion; to ATP, Real Time
What are the airway submucosal glands?
- Mucous cells secrete mucus
- Serous cells secrete anti-bacterial enzymes (e.g. lysozyme)
- Glands also secrete water and salts (e.g. Na+ and Cl-)
What is the function of airway epithelium?
- Secretion of mucins, water and electrolytes
- components of ‘mucus’ (+ plasma, mediators etc)
- Movement of mucus by cilia – mucociliary clearance
- Physical barrier
What is produced by airway epithelium?
-Production of regulatory and inflammatory mediators:
1. Nitric oxide (NO - via nitric oxide synthase, NOS)
2. Carbon monoxide (CO - via hemeoxygenase, HO)
3. Arachidonic acid metabolites (e.g. prostaglandins – via COX)
Chemokines (e.g. interleukin (IL)-8)
4. Cytokines (e.g. GM-CSF)
5. Proteases
How is NOS in airways?
- NOS expression in human airway epithelium
- Brown staining = nitric pride synthase (NOS) - produces nitric oxide (NO)
How does airway smooth muscle function in inflammation?
- Structure:
- Hypertrophy
- Proliferation - Tone: airway caliber (with or without inflammation)
- Contraction
- Relaxation - Secretion: (with or without inflammation but increase if inflammation)
- Mediators
- Cytokines
- Chemokines
What are the secretory functions in airway smooth muscle with Inflammation or exposure to bacterial products or cytokines?
-Activates NOS -> NO
-Activates COX -> Prostaglandins
-Increase prod Cytokines
-Increase prod Chemokines
-Increase prod adhesion molecules
>Last three used in inflammatory cell recruitment
What is the airway vasculature like?
- Tracheo-bronchial circulation (systemic)
- 1-5% of cardiac output
-Blood flow to airway mucosa = 100-150 mL/min/100g tissue (amongst the highest to any tissue) - Bronchial arteries arise from many sites on
aorta, intercostal arteries and others
How does blood return from trachea circulation?
Blood returns from tracheal circulation via systemic veins
How does blood return from bronchial circulation?
Blood returns from bronchial circulation to both sides of heart via bronchial and pulmonary veins
What is the function of the tracheo-bronchial circulation?
- Good gas exchange (directly between 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 (termed ‘plasma exudation’)
What are the nerves in the control of airway function?
-Nerves:
parasympathetic (cholinergic)
-LACK of sympathetic
-sensory
What are the regulatory and inflammatory mediators in the airway?
- histamine
- arachidonic acid metabolites (e.g. prostaglandins, leukotrienes)
- cytokines
- chemokines
- Proteinases/proteases (e.g. neutrophil elastase)
- Reactive gas species (e.g. O2-, NO)
What are some respiratory disease with loss if airway ‘control’?
- Asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF)
- All are common conditions:
Asthma – ~5% of population (industrialised countries)
COPD – 4th cause of death in UK and USA
CF – lethal autosomal recessive gene defect (~1:20 gene frequency; affects ~1:2000 Caucasians): CFTR
What is asthma?
-A clinical syndrome characterised by increased airway ‘responsiveness’ to a variety of stimuli (® airways obstruction)
What are the characteristics of asthma?
1. Airflow obstruction varies over short periods of time and is reversible (spontaneously or with drugs) 2. Dyspnoea, wheezing and cough (varying degrees - mild to severe) 3.. -Airway inflammation -> re-modelling
How is airway controlled?
- Parasympathetic Cholinergic nerves induce contraction airway smooth muscle (airway constriction) and mucus secretion (glands) - ACh neurotransmitter
- Airway relaxation (humans) via NOS-containing nerves and adrenaline (adrenal glands)
- Different inflammatory cells and mediators in airways
- Cells produce more than one mediator; mediators do more than one thing - Use Nitric oxide producing nerves for relaxation airway smooth muscle
What do submucosal glands secrete?
mucus, water, salts and anti-bacterials
What do cilia do?
Cilia (ciliated cells) beat metachronally for effective mucociliary clearance
What do airway epithelium produce?
Airway epithelium produces nitric oxide (NO) – control of ciliary beat?
What do airway smooth muscles have?
Airway smooth muscle cells have contractile and secretory functions
When do respiratory diseases occur?
Loss of homeostatic ‘control’ leads to respiratory disease
What is involved in the airway pathophysiology of asthma?
The airway pathophysiology of asthma involves the lumen, epithelium, basement membrane, submucosal structures (e.g. submucosal glands), vasculature and smooth muscle
What does NOS and COX do for inflammation?
- NOS causes release of NO for vasodilation
- COX causes prostaglandin release that is pro-inflammatory
- Cytokine//chemokine//adhesion molecule release all help to chemoattract other cells (cell recruitment) to the site of inflammation
What is the tracheo bronchial circulation?
- 1-5% CO
- Tracheal circulation return via systemic veins
- Bronchial circulation returns via bronchial and pulmonary veins to both sides of the heart
What is the function of the tracheo bronchial circulation?
Good gas-exchange Warming Humidifying Clearing mediators of inflammation Clear drugs Supply tissues with cells Supply tissue with plasma
What is the PNS control of the airway?
- PNS – ACh on muscarinic receptors
1. Mucus secretion
2. Bronchoconstriction
3. BV dilation
What is the SNS control of the airway?
- SNS – NA/A on adrenergic receptors via cervical thoracic ganglion
1. Bronchodilation
2. Adrenaline release from adrenals relaxes
What are inflammatory mediators?
Histamine
PG and LT
Cytokines
Chemokines
What is the asthma pathology?
- Epithelial fragility
- Basement membrane thickening
- Mucus plug in lumen
- Vasodialtion
- Cellular infiltration
