Structure and function of the airways Flashcards
What is a major risk factor for COPD
Smoking
Describe cartillage
C-Shaped- offset in places- more densely packed in some areas along the trachea to give a greater tensile strength
Where is cartilage not found
Bronchioles or alveoli
Describe the basic functions and anatomy of the lung
The branching of the lungs is dichotomous branching.
The c-rings of the bronchi and trachea are slightly offset from each other to give greater tensile strength.
Describe the basic functions of the airways
Conduit (‘pipes’) to:
conduct O2 to the alveoli
conduct CO2 out of the lung
- gas exchange
Facilitated by:
mechanical stability (cartilage)
control of calibre (smooth muscle)
protection and ‘cleansing’
What is meant by calibre
how much the airways are contracted
Describe the basic organisation of the airways
Cartilage: c-shaped and offset
Smooth muscle: to control calibre
Submucosal gland: tip embedded in smooth muscle, potentially to cause secretion upon contraction
Systemic circulation: tracheal/bronchial circulation
Basement membrane: separates muscle, vessels and glands from endothelium
Airway epithelium: mainly ciliated with few goblet cells
Mucous: small amount in healthy people (10ml) to trap pathogens - wafted towards back of throat
See diagram!
Describe where mucous is wafted to
Wafted towards back of throat- in mucocillliray transport
Outline the organisation of the airways
The c-rings aren’t complete as the are offset (at an angle).
Below cartilage is a layer of smooth muscle cells with submucosal glands embedded into (when smooth muscle contracts, it squeezes the mucosal glands).
~10mL mucous produced per day.
Goblet cells AND submucosal glands produce mucin.
Cilia beat METASYNCHRONOUSLY.
Describe the structure of the airway wall
Epitehlial lining
Cilia
mucous layer on top of wall
Describe lining cells
Ciliated, intermediate, brush, basal
Describe contractile cells
Smooth muscle (airway, vasculature)
Describe secretory cells
Goblet (epithelium), mucous, serous (glands)
Describe connective tissue
Fibroblast, interstitial cell
(elastin, collagen, cartilage)
Describe neuroendocrine
Nerves, ganglia, neuroendocrine cells,
neuroepithelial bodies
Describe vascular cells
Endothelial, pericyte, plasma cell
(+ smooth muscle)
Describe immune cells
Mast cell, dendritic cell, lymphocyte,
eosinophil, macrophage, neutrophil
What is present inside goblet cells
Mucin granules- which contain mucin in a hightail condensed form
What is meant by acinus
Part of the airway that is involved in gaseous exchange (passage of oxygen from the lungs to the blood and carbon dioxide from the blood to the lungs).
It begins with respiratory bronchioles and subsequent divisions of the airway and alveoli.
Describe the airway submucosal glands ion the human bronchial gland
Mucous cells secrete mucus
Serous cells secrete antibacterials
(e.g. lysozyme)
Glands also secrete water and salts
(e.g. Na+ and Cl-)Describe the arrangement of the submucosal glands
The arrangement of the human submucosal glands means that with serous cells on the outside, the watery substance that they secrete mixes with the innermost mucous and washes it into a collecting duct.
so the watery serous acini wash more viscous mucus to collecting duct upon contraction
Reducing the viscosity of the mucous is essential in allowing it to move across the cilia
Describe ciliary structure
9 pairs of microtubules around the outside- joined by next links
joined to central pari by radial spokes
all surrounded by a cell membrane
each pair of the peripheral microtubules has an outer and inner arm (dynein)
Summarise ciliary structure
Cilia beat in a METACHRONAL rhythm (like a wave).
The cilia waft the mucous up the respiratory tract using their apical hooks.
Each individual cilia displays a ‘9+2’ relationship with 9 filaments around 2 central filaments.
o The rods then slide over each other to simulate movement.
~200 cilia per cell.
In COPD patients, you would see a continuous sheet of mucous on the airway but normally, it’s flaked under microscope.
Describe ciliary beating
leading edge of mucous moved by cilia, before they move back to move next field of mucous - synchronised rhythm of beating to move mucous - metasychronal rhythm
What are the functions of the airway 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)
CO (by hemeoxygenase, HO)
Arachidonic acid metabolites, e.g. prostaglandins (COX)
Chemokines, e.g. interleukin (IL)-8
Cytokines, e.g. GM-CSF
Proteases
What may play a role in ciliary beating
NO- abundant in epithelia
What may CO be designed for
to kill bacteria
How do we visualise smooth muscle
actin fluorescence
What are the functions of airway smooth muscle cells
Regulates:
Tone- airways calibre (contraction and relaxation)
Secretion – Up-regulated a lot by inflammation. (Mediators
Cytokines
Chemokines)
Structure- hypertrophy and proliferation
With respiratory disease, more inflammation and smooth muscle hypertrophy/proliferation which increases contractile forces of smooth muscle meaning more secretions are made.
What is seen in asthma
plasma exudation
Describe the secretory function of smooth muscle in inflammation
Bacterial products and cytokines released from inflammation
undergoes hypertrophy and proliferation - may not contract harder but massive increase in secretion to produce mediators, cytokines and chemokines (recruit inflammatory cells); upregulate NOS and COX enzymes to produce NO and prostaglandins;
How do humans differ from animals
Humans have sensory nerves to open airways compared to the sympathetics of animals
NO producing pathway- vasorelaxtion- dilating the airways
Hormonal pathway from adrenaline too
One cell- produces a whole range of different mediators with a variety of effects, chemotaxis and neuronal modulation
histamine relaxes SM
Outline the trachea-bronchial circulation
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
Blood returns from tracheal circulation via systemic veins
Blood returns from bronchial circulation to both sides of
heart via bronchial and pulmonary veins
How well perfused is the airway mucosa
Blood flow to the airway mucosa = 100-150mL/min/100gTissue – The HIGHEST to any tissue.
o I.E. It’s VERY WELL perfused with blood.
Describe the subepithelial microvascular network
plexuses of arteries, capillaries and veins supply airways
What are the functions of the trachea-bronchial circulation
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
What are airways distal to the terminal bronchiole supplied by
Alveolar wall capillaries only
For this reason, a pulmonary embolus may result in infarction of the tissues supplied by the alveolar wall capillaries, shown as wedge-shaped opacity on the lung periphery of chest X-ray
Describe plasma exudation
post-capillary venules have gaps that leak plasma gently to bathe tissue; can be stimulated to leak more by inflammatory mediators (e.g. Histamine and platelet activating factors) and C-fibre nerves ( sensory nerve)
Describe the mechanism of plasma exudation
When the endothelial cells contract, they pull away from each other and form a gap which plasma leaks from.
This system can become exaggerated in disease.
The endothelial cells are served by (pseudo) sensory nerves (they also have MOTOR function).
In asthma for example, histamines and platelet activating factor (PAF) are produced which trigger the sensory nerves thus exaggerating the plasma exudation.
How does Evans blue dye appear with PAF
Evans blue dye
autofluoresence
(orange colour)- leaves with plasma exudate
Summarise the controls of airway function
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)Describe innervation of the airways
sensory vagus via nodose ganglion to brain stem
constriction- Parasympathetic
(cholinergic)
‘Motor’ pathway passes from brain stem (vagus)
NOT SNS nerves to open airways, instead nitric oxide producing pathway (due to vasorelaxant properties) to dilate airways; adrenal glands can produce adrenaline to induce relaxation
Summarise the cholinergic mechanisms
Irritants activate sensory nerves (via Vagus and nodose ganglion to CNS)
Central cholinergic reflex down Vagus PSNS nerve to PSNS ganglion
Postganglionic neurones lead to muscarinic receptors that:
Cause vasodilation
Cause airway constriction
Cause submucosal glands to secrete mucous
Describe the roles of the vagus nerve in airway function
Cholinergic Nerves are the most important pathways.
o The cholinergic reflex can trigger bronchoconstriction if an allergen is detected (e.g. peanut).
MOST animals have PNS pathways causing constriction and SNS causing relaxation but humans DON’T.
o CONSTRICTION via PNS nerves (the cholinergic reflex).
o DILATION via adrenaline from adrenal gland AND NO in nervous pathway – work together.
Note that the contraction and secretion is under the cholinergic reflex control (reacts in response to ACh
List some regulatory inflammatory cells in the airways
Eosinophils Neutrophils Macrophages Mast cells T lymphocyte \+ ‘Structural’ cells (e.g. smooth muscle)
List some inflammatory mediators
Histamine Serotonin Adenosine Prostaglandins Leukotrienes Thromboxane PAF Endothelin Cytokines Chemokines Growth factors Proteinases Reactive gas species
List some effects of these inflammatory mediators
Smooth muscle
(airway, vascular:
contraction, relaxation)
Secretion
(mucins, water, etc)
Plasma exudation
Neural modulation
Chemotaxis
RemodellingWhat is key to remember about inflammatory mediators
Cells produce more than
one mediator
Mediators do more than
one thing
List some diseases associated with loss of airway control
Asthma, chronic obstructive pulmonary disease (COPD)
and cystic fibrosis (CF)
Describe the epidemiology of these 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 are these diseases caused by
These common conditions are characterised by airway inflammation and airway obstruction due to airway remodelling- they are no longer fit for purpose
can also cause airway remodelling
Describe asthma
A clinical syndrome characterised by increased airway
responsiveness to a variety of stimuli
(→ airways obstruction)
Airflow obstruction varies over short periods of time
and is reversible
(spontaneously or with drugs)
Dyspnoea, wheezing and cough
(varying degrees - mild to severe)
Airway inflammation → re-modelling
Describe the histology of asthma pathology: airway inflammation
‘Mucus’ plug In lumen Basement membrane thickening Epithelial ‘fragility’ Cellular infiltration Vasodilation (‘congested’ vessels) Airway wall thrown into folds smooth muscle hypertrophy, increased gland size
Describe the cellular infiltration in asthma
inflammatory cells in submucosa
eosinophil is the primary inflammatory cell
What are antigens to asthmatics
Cold air, small molecular weight particles, emotions (laughing, crying)- generally inocuous thins
Summarise the pathology of asthma
Airway obstruction varies over short periods of time and is reversible (due to adrenaline).
Characterised by dyspnoea, wheezing and coughing.
Airway inflammation leads to remodelling.
EOSINOPHILS are the major player and act fast to form mucous plugs made of eosinophils.
HISTOLOGY: epithelial fragility, thickening of the basement membrane and prominent blood vessels.
Mucous plug combined with bronchoconstriction can cause full obstruction of breathing.
outline the pathophysiology of asthma
Epithelial fragility exposes sensory nerve- making it more sensitive to activation. Activation leads to bronchoconstriction (hypertrophy/hyperplasia of SMC), vasodilation and Mucus
hypersecretion
(Hypertrophy/
Hyperplasia).
Infiltration of inflammatory mediators- vast array of effects such as re-modelling of the airways with hypertrophied submucosal glands and airway smooth muscle and general inflammation
leads to plasma exudation, sub epithelial fibrosis and goblet cell hypertrophy
PAF causes plasma exudation.
ATP causes goblet cell exocytosis.
histamine (causes plasma exudation and airway constriction)
How do animals and humans differ in airway innervation
Both have adrenaline to cause dilation
We have motor nerves containing NO for dilation
Animals have sympathetic innervation (cervical thoracic ganglion)
