6.5 - Structure and Function of the Airways

Question 1

Describe the overall branching of the lungs

Answer 1

trachea –> primary bronchi –> secondary bronchi –> tertiary bronchi –> bronchioles –> alveoli

Question 2

What kind of branching does the lung/airways have?

Answer 2

• dichotomous branching - every tube splits into two
• gradual dichotomous branching leads to alveolar region (where gas exchange takes place)

Question 3

What does the cartilage do?

Answer 3

• provides mechanical stability
• helps hold the airways open

Question 4

Why does the back of the trachea not have cartilage (why is the cartilage C-shaped instead of going all the way around)?

Answer 4

To allow the oesophagus to run down the back so we can swallow food

Question 5

What do type I cells in an alveolus do?

Answer 5

• very thin and flat, forming a delicate barrier
• they facilitate gas exchange
• incredible thin and cover 95% of alveolar surface
• flat and spread out over epithelium
• bumps and grooves can be seen in electron micrograph due to underlying capillaries (cells so thin you can see these)

Question 6

What do type II cells in an alveolus do?

Answer 6

• replicate to replace type I cells
• secrete surfactant (reduces surface tension in alveoli) and antiproteases
• xenobiotic metabolism - breakdown of drugs and noxious chemicals that enter the alveoli
• greater numbers than type I cells but only cover 5% of alveolar surface

Question 7

What do the macrophages in an alveolus do?

Answer 7

Go around cleaning up debris, viruses etc that we inhale into alveoli

Question 8

What do the fibroblasts in an alveolus do?

Answer 8

Produces collagen / the ECM that holds the structure together

Question 9

What are the basic functions of the respiratory airways?

Answer 9

• getting air efficiently to the gas exchange region and keeping the pipework clear
• conduit (pipes) to conduct O2 to the alveoli and conduct CO2 out of the lung (gas exchange)
• facilitated by cartilage providing mechanical stability, control of diameter by smooth muscle, and protection and cleansing mechanisms

Question 10

What are the features of the nasal passages?

Answer 10

• conchae - highly vascular, contribute to warming and humidification of intra-nasally-inhaled air
• nasal hairs filter out large particles
• pharynx - common passageway for food, liquids and air (nasopharynx –> oropharynx –> laryngopharynx)

Question 11

What features does a transverse section of a lower airway have?

Answer 11

• airways are highly vascular
• submucosal glands and goblet cells produce mucus (protect airways)
• cartilage
• smooth muscle (tracheal/bronchial) - contract to prevent food going down the wrong way

Question 12

What is the arrangement of the airway wall?

Answer 12

• mucus layer –> cilia –> epithelial cells
• cilia - middle ones are curved, side ones are backwards
• inhaled particles get trapped in mucus layer and are wafted by cilia, and are swallowed

Question 13

What are examples of airway cell types?

Answer 13

• lining cells - ciliated, intermediate, brush, basal
• contractile cells - smooth muscle (airway, vasculature)
• secretory cells - goblet (epithelium), mucous, serous (glands)
• connective tissue - fibroblast, interstitial cell (elastin, collagen, cartilage)
• neuroendocrine - nerves, ganglia, neuroendocrine cells, neuroepithelial bodies
• vascular cells - endothelial, pericyte, plasma cell (+ smooth muscle)
• immune cells - mast cell, dendritic cell, lymphocyte, eosinophil, macrophage, neutrophil

Question 14

What are mucin granules?

Answer 14

• found in goblet cells
• contain mucin in highly condensed form
• if mucus is needed to be produced, mucin granules come to apical surface of cell and fuse with it to make an ‘omega profile’
• airway liquid enters the granule so the condensed mucin takes up the liquid (hydrates mucus) and is quickly released into airway surface
• occurs quickly –> each cell produces its own mass in mucus quickly

Question 15

Why do the epithelial cells have so many mitochondria?

Answer 15

Cilia need energy to move and waft mucus along the surface

Question 16

What are acini in a human bronchial submucosal gland?

Answer 16

• acini are mucous-producing units
• mucous acini secrete mucus (more viscous?)
• serous acini secrete anti-bacterial enzymes e.g. lysozyme (more watery mucus?)
• glands also secrete water and salts e.g. Na+ and Cl-
• serous acini are more outward than mucous acini
• mucus produced –> collecting duct –> ciliated duct (waft it away)

Question 17

What do the microtubules do and what is the 9+2 arrangement?

Answer 17

• slide over one another in cilium to move it one way or another (axoneme = microtubules)
• 9+2 is the arrangement of microtubules in cilia - 9 doublets on outside and 2 singlets in the middle

Question 18

What is the rhythm of ciliary beating?

Answer 18

Metachronal - different lines of ciliary hair move at different times to waft mucus down the back of the throat

Question 19

In a human airway, what does mucus appear as on cilia?

Answer 19

• flakes
• likely due to fixation

Question 20

What are the functions of airway epithelium?

Answer 20

• secretion of mucins, water and electrolytes (components of mucus + plasma, mediators etc)
• movement of mucus by cilia - mucociliary clearance
• physical barrier
• produces regulatory and inflammatory mediators

Question 21

What are examples of regulatory and inflammatory mediators produced by airway epithelium?

Answer 21

• nitric oxide (NO) - via nitric oxide synthase (NOS) - thought to control frequency of ciliary beat but unsure - majority of cells produce NO so function must be important
• carbon monoxide (CO) - via hemeoxygenase (HO)
• arachidonic acid metabolites (e.g. protaglandins via COX)
• chemokines (e.g. IL-8)
• cytokines (e.g. GM-CSF)
• proteases

Question 22

What are the functions of airway smooth muscle cells?

Answer 22

• structure of airway
• tone (airway diameter) - by contraction and relaxation
• secretion of mediators, cytokines and chemokines - usually only little secreted

Question 23

How do the functions of airway smooth muscle cells change under inflammation?

Answer 23

• structure - contribute more towards structure via hypertrophy and proliferation e.g. in asthma
• still contribute to tone
• secrete more mediators, cytokines and chemokines
• produce prostaglandins, adhesion and NO molecules
• inflammatory cell recruitment

Question 24

What is the tracheo-bronchial circulation (systemic)?

Answer 24

• 1-5% of cardiac output goes to it
• blood flow to airway mucosa = 100-150 mL/min/100g tissue - among 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 the heart via bronchial and pulmonary veins
• subepithelium vascular network is a massive plexus

Question 25

What are the functions of the tracheo-bronchial circulation?

Answer 25

• good gas exchange (directly between airway tissues and blood)
• contributes to warming and humidification of inspired air
• clears inflammatory mediators
• clears inhaled drugs (this can be good or bad)
• supplies airway tissue and lumen with inflammatory cells and proteinaceous plasma (called plasma exudation)

Question 26

What different types of nerves control airway function?

Answer 26

• parasympathetic - cholinergic
• nitrous oxide sympathetic adrenergic pathway
• sensory nerves

Question 27

Nerve pathways between airway and CNS - peanut example

Answer 27

• peanut goes down airway, detected by sensory nerves which send AP up vagus nerve through nodose ganglion into brainstem
• this sets up cholinergic parasympathetic reflex - ACh comes out of nerve onto smooth muscle which contracts, stopping the peanut from going down airway any further
• to relax the muscle once the peanut is coughed up, the adrenal gland secretes adrenaline which acts on smooth muscle to relax it and open up airway
• we don’t have a sympathetic nervous relaxant pathway which releases NA, instead we have NO secreting nerves which cause airway smooth muscle to relax

Question 28

Which inflammatory and regulatory mediators control airway function?

Answer 28

• histamine
• arachidonic acid metabolites e.g. prostaglandins, leukotrienes
• cytokines
• chemokines
• different immune cells will produce a range of these e.g. mast cells, eosinophils, neutrophils, macrophages, T cells produce a range
• these mediators do more than one thing e.g. smooth muscle contraction/relaxation, secretion of mucins/water, plasma exudation, chemotaxis, neural modulation, remodelling
• proteinases/proteases (e.g. neutrophil elastase)
• reactive gas species e.g. O2, NO

Question 29

What respiratory diseases are associated with loss of airway control?

Answer 29

• asthma (5% of population)
• chronic obstructive pulmonary disease (COPD) - 4th cause of death in UK and USA
• cystic fibrosis (CF) - lethal autosomal recessive gene defect
• all are common conditions caused by airway inflammation and obstruction - caused by airway remodelling