Structure and function of the airways

Question 1

What is a major risk factor for COPD

Answer 1

Smoking

Question 2

Describe cartillage

Answer 2

C-Shaped- offset in places- more densely packed in some areas along the trachea to give a greater tensile strength

Question 3

Where is cartilage not found

Answer 3

Bronchioles or alveoli

Question 4

Describe the basic functions and anatomy of the lung

Answer 4

 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.

Question 5

Describe the basic functions of the airways

Answer 5

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’

Question 6

What is meant by calibre

Answer 6

how much the airways are contracted

Question 7

Describe the basic organisation of the airways

Answer 7

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!

Question 8

Describe where mucous is wafted to

Answer 8

Wafted towards back of throat- in mucocillliray transport

Question 9

Outline the organisation of the airways

Answer 9

 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.

Question 10

Describe the structure of the airway wall

Answer 10

Epitehlial lining
Cilia
mucous layer on top of wall

Question 11

Describe lining cells

Answer 11

Ciliated, intermediate, brush, basal

Question 12

Describe contractile cells

Answer 12

Smooth muscle (airway, vasculature)

Question 13

Describe secretory cells

Answer 13

Goblet (epithelium), mucous, serous (glands)

Question 14

Describe connective tissue

Answer 14

Fibroblast, interstitial cell

(elastin, collagen, cartilage)

Question 15

Describe neuroendocrine

Answer 15

Nerves, ganglia, neuroendocrine cells,

neuroepithelial bodies

Question 16

Describe vascular cells

Answer 16

Endothelial, pericyte, plasma cell

(+ smooth muscle)

Question 17

Describe immune cells

Answer 17

Mast cell, dendritic cell, lymphocyte,

eosinophil, macrophage, neutrophil

Question 18

What is present inside goblet cells

Answer 18

Mucin granules- which contain mucin in a hightail condensed form

Question 19

What is meant by acinus

Answer 19

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.

Question 20

Describe the airway submucosal glands ion the human bronchial gland

Answer 20

Mucous cells secrete mucus
  Serous cells secrete antibacterials
       (e.g. lysozyme)
  Glands also secrete water and salts
       (e.g. Na+ and Cl-)

Question 21

Describe the arrangement of the submucosal glands

Answer 21

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

Question 22

Describe ciliary structure

Answer 22

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)

Question 23

Summarise ciliary structure

Answer 23

 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.

Question 24

Describe ciliary beating

Answer 24

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

Question 25

What are the functions of the airway epithelium

Answer 25

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

Question 26

What may play a role in ciliary beating

Answer 26

NO- abundant in epithelia

Question 27

What may CO be designed for

Answer 27

to kill bacteria

Question 28

How do we visualise smooth muscle

Answer 28

actin fluorescence

Question 29

What are the functions of airway smooth muscle cells

Answer 29

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.

Question 30

What is seen in asthma

Answer 30

plasma exudation

Question 31

Describe the secretory function of smooth muscle in inflammation

Answer 31

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;

Question 32

How do humans differ from animals

Answer 32

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

Question 33

Outline the trachea-bronchial circulation

Answer 33

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

Question 34

How well perfused is the airway mucosa

Answer 34

 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.

Question 35

Describe the subepithelial microvascular network

Answer 35

plexuses of arteries, capillaries and veins supply airways

Question 36

What are the functions of the trachea-bronchial circulation

Answer 36

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

Question 37

What are airways distal to the terminal bronchiole supplied by

Answer 37

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

Question 38

Describe plasma exudation

Answer 38

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)

Question 39

Describe the mechanism of plasma exudation

Answer 39

 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.

Question 40

How does Evans blue dye appear with PAF

Answer 40

Evans blue dye autofluoresence (orange colour)- leaves with plasma exudate

Question 41

Summarise the controls of airway function

Answer 41

``` 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) ```

Question 42

Describe innervation of the airways

Answer 42

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

Question 43

Summarise the cholinergic mechanisms

Answer 43

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

Question 44

Describe the roles of the vagus nerve in airway function

Answer 44

 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

Question 45

List some regulatory inflammatory cells in the airways

Answer 45

``` Eosinophils Neutrophils Macrophages Mast cells T lymphocyte + ‘Structural’ cells (e.g. smooth muscle) ```

Question 46

List some inflammatory mediators

Answer 46

``` Histamine Serotonin Adenosine Prostaglandins Leukotrienes Thromboxane PAF Endothelin Cytokines Chemokines Growth factors Proteinases Reactive gas species ```

Question 47

List some effects of these inflammatory mediators

Answer 47

``` Smooth muscle (airway, vascular: contraction, relaxation) Secretion (mucins, water, etc) Plasma exudation Neural modulation Chemotaxis Remodelling ```

Question 48

What is key to remember about inflammatory mediators

Answer 48

Cells produce more than one mediator Mediators do more than one thing

Question 49

List some diseases associated with loss of airway control

Answer 49

Asthma, chronic obstructive pulmonary disease (COPD) | and cystic fibrosis (CF)

Question 50

Describe the epidemiology of these conditions

Answer 50

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

Question 51

What are these diseases caused by

Answer 51

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

Question 52

Describe asthma

Answer 52

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

Question 53

Describe the histology of asthma pathology: airway inflammation

Answer 53

``` ‘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 ```

Question 54

Describe the cellular infiltration in asthma

Answer 54

inflammatory cells in submucosa | eosinophil is the primary inflammatory cell

Question 55

What are antigens to asthmatics

Answer 55

Cold air, small molecular weight particles, emotions (laughing, crying)- generally inocuous thins

Question 56

Summarise the pathology of asthma

Answer 56

 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.

Question 57

outline the pathophysiology of asthma

Answer 57

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)

Question 58

How do animals and humans differ in airway innervation

Answer 58

Both have adrenaline to cause dilation We have motor nerves containing NO for dilation Animals have sympathetic innervation (cervical thoracic ganglion)