Structure and Function of the Airways Flashcards
The Airways and Lungs
Each airways divides into two - this is called DICHOTOMOUS BRANCHING
As the airways branch, they get narrower and narrower until you get to the periphery
What keeps the airways open and what shape are they and why are they that shape?
The Airways and Lungs
Each airways divides into two - this is called DICHOTOMOUS BRANCHING
As the airways branch, they get narrower and narrower until you get to the periphery
These airways are held open because they have cartilage rings (C shaped so that it can allow food to pass down the oesophagus with ease)
The rings are slightly offset compared to each other which gives greater tensile strength to holding the airways open
The airways lead down to the alveolar region where gas exchange takes place
Basic Functions of the Airways
Conduit to:
Conduct O2 to the alveoli
Conduct CO2 out of the lungs
GAS EXCHANGE
Facilitated by:
Mechanical stability (cartilage)
Control of calibre (smooth muscle)
Protection and cleansing
Organisation of Airway Structures
This is a transverse section through the trachea
You wont see a complete C because they are ……………… - they are at an angle
Beneath the cartilage there is a layer of smooth muscle
……………… Glands secrete mucus onto the airway surface
The lower part of the submucosal gland is embedded in the smooth muscle - why?
The airway epithelium has ciliated cells and mucus producing ……………… cells
Organisation of Airway Structures
This is a transverse section through the trachea
You wont see a complete C because they are offset - they are at an angle
Beneath the cartilage there is a layer of smooth muscle
Submucosal Glands secrete mucus onto the airway surface
The lower part of the submucosal gland is embedded in the smooth muscle - when the smooth muscle contracts it squeezes the submucosal gland - they work in tandem
The airway epithelium has ciliated cells and mucus producing goblet cells
Structure of the Airway Wall
This is a longitudinal section
Mucus is there to trap the particles and microbes etc. that enter the airways
The beating cilia moves the microbes to the back of the throat so that we can swallow it
10 mL of mucus is produced per day
When diseased, you may produce a lot more mucus which you then cough up as sputum
Goblet cells and submucosal glands both produce mucus
Some of these structures have nervous control
Immune cells come and go depending on whether you are healthy, have an acute infection or a chronic infection
Human Airway Epithelium
The electron lucent granules are the mucus
There are lots of mitochondria because these cells are highly metabolically active so that they can keep pumping the cilia
Mucin secretion by guinea pig tracheal goblet cell
(expansion of intra-granular mucin upon secretion; to ATP, Real Time)
Mucin granules come to the apical surface and fuse with it
A little pore forms and water goes in through the pore
The very concentrated mucus becomes diluted and EXPANDS RAPIDLY
As the pore open more and more, the mucus pops out (like a jack in the box)
The concentrated mucus expands many hundred fold when the water enters
NOTE: these goblet cells aren’t goblet shaped any more because it is in vitro
The cell is in the middle and there is already a little globule of mucin around it
A massive amount of mucin comes out from a relatively tiny granule - each of these granules puts mucus out onto the airway surface
What do serous cells excrete?
LEFT - dog tracheal gland
Within the gland there are dark areas which are the functional units (……………)
These functional units (……………..) secrete mucus out into the collecting duct and this then moves to the ciliated duct and the cilia waft the mucus out of the gland
LEFT - dog tracheal gland
Within the gland there are dark areas which are the functional units (ACINI)
These functional units (ACINI) secrete mucus out into the collecting duct and this then moves to the ciliated duct and the cilia waft the mucus out of the gland
RIGHT - human bronchial gland
They have a particular arrangement - there are serous cells peripheral to the mucus cells
The serous cells produce a watery 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 secrete water - mucus, antibacterial enzymes, salt and water all come from these glands
Ciliary Structure (Human Cilium)
Why does the cilia beat?
Cilia have ………. within them
They have ………… ………… which, we believe, engages with the mucus to push it along more easily
If you cut the cilia in a transverse section, there is a ………. relationship (there are 9 around the outside and two in the middle
The rods slide over each other pushing the cilia one way or another - this is a highly energetic process
There are about 200 cilia per ciliated cell
Ciliary Structure (Human Cilium)
Cilia beat to waft the mucus
Cilia have rods within them
They have apical hooks which, we believe, engages with the mucus to push it along more easily
If you cut the cilia in a transverse section, there is a 9+2 relationship (there are 9 around the outside and two in the middle
The rods slide over each other pushing the cilia one way or another - this is a highly energetic process
There are about 200 cilia per ciliated cell
Pattern of beating of cilia
…………………… RHYTHM - one field of cilia beats and then the field behind it catches up and, in turn, the field behind that catches up and so on
Meanwhile, the one that beat first is on the backstroke, waiting to beat again
This ………………… rhythm allows the cilia to move the mucus sequentially along
As the movement of cilia is slightly out of sync, the mucus can be moved along
They have a leading stroke like a swimmer and then a weaker stroke back?
Pattern of beating of cilia
METACHRONAL RHYTHM - one field of cilia beats and then the field behind it catches up and, in turn, the field behind that catches up and so on
Meanwhile, the one that beat first is on the backstroke, waiting to beat again
This metachronal rhythm allows the cilia to move the mucus sequentially along
As the movement of cilia is slightly out of sync, the mucus can be moved along
Airway Epithelium: Functions
Secretion of …………, …………. and …………….(components of mucus (+plasma, mediators etc.))
Movement of ………………. by cilia - mucociliary clearance
Physical barrier against inhaled insult
Production of regulatory and inflammatory mediators:
……. (by nitric oxide synthase, NOS)
…….. (by hemeoxygenase, HO)
………….. ………..Metabolites (e.g. prostaglandins, COX)
………………….. (e.g. IL-8)
………………… (e.g. GM-CSF)
…………………
Airway Epithelium: Functions
Secretion of mucin, water and electrolytes (components of mucus (+plasma, mediators etc.))
Movement of mucus by cilia - mucociliary clearance
Physical barrier against inhaled insult
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. IL-8)
Cytokines (e.g. GM-CSF)
Proteases
What happens if you give NO donors to ciliated cells?
NOS Expression in Human Airway Epithelium
You can see where the nitric oxide synthase resides
There is a lot of NOS in the epithelium so a lot of NO gets produced in the epithelium
NO could be controlling the beating of the cilia - if you give NO donors to ciliated cells, the ciliary beats become faster
Airway Smooth Muscle: Functions
What is tone?
List 3 functions of airway smooth muscle cells?
Secretion = smooth muscle cells may produces small amounts of secretions
In respiratory disease of the airways (e.g. asthma) you get ……………….. and smooth muscle…………………… due to proliferation of smooth muscle cells
This increase in the mass of smooth muscle may mean that there is an increase in ……………… force of that muscle - you get a marked increase in the secretion of mediators
It produces lots of cytokines etc. and it changes in function and phenotype
Airway Smooth Muscle: Functions
Tone = how relaxed or contracted the airway is
Secretion = smooth muscle cells may produces small amounts of secretions
In respiratory disease of the airways (e.g. asthma) you get inflammation and smooth muscle hypertrophy due to proliferation of smooth muscle cells
This increase in the mass of smooth muscle may mean that there is an increase in contractile force of that muscle - you get a marked increase in the secretion of mediators
It produces lots of cytokines etc. and it changes in function and phenotype
Airway Smooth Muscle: Secretory Functions
In response to cytokines, ……… can get upregulated
COX enzymes produce more ………………………..
Chemokines lead to the recruitment of …………………… ………..
The smooth muscle then gets involved in the inflammatory process
Airway Smooth Muscle: Secretory Functions
In response to cytokines, NOS can get upregulated
COX enzymes produce more prostaglandins
Chemokines lead to the recruitment of inflammatory cells
The smooth muscle then gets involved in the inflammatory process
Airway Vasculature: Tracheo-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:
………….., ………………. …………… and others
Blood returns from tracheal circulation via …………….. …………
Blood returns from bronchial circulation to both sides of
heart via ……………..and ………………. veins
Airway Vasculature: Tracheo-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
Tracheo-bronchial Circulation: Functions
We don’t really know why it is so well perfused
The system is so rich in blood that you can get direct gas exchange between the tissues and the blood
Contributes to ………………. of inspired air
Contributes to……………………. of inspired air
Clears …………… .. ………….
Clears inhaled drugs (good/bad depending on the drug)
Supplies airway tissue and lumen with …………… ……………
Supplies airway tissues and lumen with …………… …………… (mechanism of plasma exudation)
Tracheo-bronchial Circulation: Functions
We don’t really know why it is so well perfused
The system is so rich in blood that you can get direct gas exchange between the tissues and the blood
Contributes to warming of inspired air
Contributes to humidification of inspired air
Clears nflammatory mediators
Clears inhaled drugs (good/bad depending on the drug)
Supplies airway tissue and lumen with inflammatory cells
Supplies airway tissues and lumen with proteinaceous plasma (mechanism of plasma exudation)
Mechanism of Plasma Exudation in the Airways
All tissue is bathed in plasma which leaks out of the ………… ………. ……………..
The post-capillary venules have these endothelial cells that will contract (they have actin and myosin)
When the endothelial cells contract, they pull away from each other a little and form a gap - ………………. leaks through this gap
Normally, this system is perfectly safe, however, the plasma exudation system can become exaggerated in disease (especially in something like ……………..)
The endothelial cells are served by ……………….. nerves (which are incorrectly named because though they look like sensory nerves, they have motor function as well and can make the endothelial cells contract)
………………… and ……………… …………….. ……………. are produced in something like asthma and these sensory nerves can become activated thus exaggerating the plasma exudation process
Mechanism of Plasma Exudation in the Airways
All tissue is bathed in plasma which leaks out of the post-capillary venules
The post-capillary venules have these endothelial cells that will contract (they have actin and myosin)
When the endothelial cells contract, they pull away from each other a little and form a gap - plasma leaks through this gap
Normally, this system is perfectly safe, however, the plasma exudation system can become exaggerated in disease (especially in something like asthma)
The endothelial cells are served by sensory nerves (which are incorrectly named because though they look like sensory nerves, they have motor function as well and can make the endothelial cells contract)
Histamines and platelet activating factor are produced in something like asthma and these sensory nerves can become activated thus exaggerating the plasma exudation process
Name 4 ways of controlling airway function?
Control of Airway Function
Nerves:
Parasympathetic (cholinergic)/Sympathetic (adrenergic?)/Sensory
Regulatory and Inflammatory Mechanisms
Histamine
Arachidonic Metabolites (prostaglandins and leukotrienes)
Cytokines
Chemokines
Proteinases
E.g. neutrophil elastase
Reactive Gas Species
E.g. O2-, NO
Innervation of the Airways
………… Nerves are the most important motor pathways in the airways
Some thing (like a peanut) can enter the airway and activate the sensory pathway
This message goes to the central systems and via a …………………. reflex you get some ……………………….. to stop the peanut from going down too far
Humans rely on …………………… from the adrenal gland - if you’re fighting or fleeing, you want to have your airways wide open so adrenaline ………….. the airways
We also have a neuronal pathway but it is NOT sympathetic
It is a different pathway that produces …………
……… is the neurotransmitter of the neuronal pathway that causes the opening up of the airways
So adrenaline and the neuronal pathway producing NO work to relax the airways
Innervation of the Airways
Cholinergic Nerves are the most important motor pathways in the airways
Some thing (like a peanut) can enter the airway and activate the sensory pathway
This message goes to the central systems and via a cholinergic reflex you get some BRONCHOCONSTRICTION to stop the peanut from going down too far
Humans rely on ADRENALINE from the adrenal gland - if you’re fighting or fleeing, you want to have your airways wide open so adrenaline relaxes the airways
We also have a neuronal pathway but it is NOT sympathetic
It is a different pathway that produces NO
NO is the neurotransmitter of the neuronal pathway that causes the opening up of the airways
So adrenaline and the neuronal pathway producing NO work to relax the airways
Cholinergic Mechanisms in the Airways
Irritants can cause an impulse to pass up the sensory fibre which causes a ……………………. REFLEX which contracts smooth muscle and causes secretion of mucus
You may also get a little bit of …………………
The contraction and secretion is under ……………….. control
There is smooth muscle around the airways which contracts in response to …………………
Cholinergic Mechanisms in the Airways
Irritants can cause an impulse to pass up the sensory fibre which causes a CHOLINERGIC REFLEX which contracts smooth muscle and causes secretion of mucus
You may also get a little bit of vasodilation
The contraction and secretion is under cholinergic control
There is smooth muscle around the airways which contracts in response to acetylcholine
Regulatory-Inflammatory Cells in Airways
On the left hand side there are a variety of inflammatory cells
These cells produce a variety of mediators and most cells produce more than one mediator - hence any of these cells can have a variety of consequences
Asthma: Definition and Characteristics
A clinical syndrome characterised by ……………… ……………… …………….. to a variety of stimuli (leads to airway obstruction)
Airway obstruction varies over short periods of time and is ………………… (because adrenaline causes the airways to reopen)
Dyspnoea, wheezing and cough
Airway inflammation leads to ………………………
Asthma: Definition and Characteristics
A clinical syndrome characterised by increased airway responsiveness to a variety of stimuli (leads to airway obstruction)
Airway obstruction varies over short periods of time and is REVERSIBLE (because adrenaline causes the airways to reopen)
Dyspnoea, wheezing and cough
Airway inflammation leads to remodelling
Asthma Pathology: Airway Inflammation
On the left is where the airway lumen should be - it would normally be a nice white colour
In this case, it is blocked by a MUCUS PLUG which has lots of eosinophils in it
Eosinophils are very aggressive and are involved in defence against large pathogens like nematode worms
You can see epithelial fragility
There is thickening of the basement membrane
The blood vessels become very prominent
In the submucosa there is massive infiltration of eosinophils
Asthma Pathology: Bronchoconstriction
This is the epithelium of a smallish airway of someone who died of asthma
It has become folded because the smooth muscle has contracted and the airway has shut down
The last bits of lumen that remained has become blocked by a mucus plug
This little bit of mucus would not normally cause any harm but when combined with bronchoconstriction, it can block up the airway
Asthma: Pathophysiology ‘Schema’
……………………………….. causes plasma exudation
…………. causes goblet cell exocytosis
We can put it together to understand the bigger picture
We have ……………….. ……………….. which exposes the sensory nerves which can respond to different mediators produced by inflammatory cells
This sets up a ……………….. ……………….. REFLEX
This ……………….. reflex causes smooth muscle ……………….. and shutting down of the airways
The ……………….. reflex will also cause ………………. …………………
This repeated ……………….. and ……………….. hypersecretion is associated with ……………….. of the smooth muscle and the glands
There is an increase in the number of……………….. cells
Chemical mediators are produced and released by these cells
Mast cells produce mediators which cause bronchoconstriction, mucus secretion etc.
Asthma: Pathophysiology ‘Schema’
PAF (platelet activating factor) causes plasma exudation
ATP causes goblet cell exocytosis
We can put it together to understand the bigger picture
We have epithelial fragility which exposes the sensory nerves which can respond to different mediators produced by inflammatory cells
This sets up a CENTRAL CHOLINERGIC REFLEX
This cholinergic reflex causes smooth muscle contraction and shutting down of the airways
The cholinergic reflex will also cause mucus secretion
This repeated bronchoconstriction and mucus hypersecretion is associated with hypertrophy of the smooth muscle and the glands
There is an increase in the number of goblet cells
Chemical mediators are produced and released by these cells
Mast cells produce mediators which cause bronchoconstriction, mucus secretion etc.
SUMMARY
