6.5 - Structure and Function of the Airways Flashcards
Describe the overall branching of the lungs
trachea –> primary bronchi –> secondary bronchi –> tertiary bronchi –> bronchioles –> alveoli
What kind of branching does the lung/airways have?
- dichotomous branching - every tube splits into two
- gradual dichotomous branching leads to alveolar region (where gas exchange takes place)
What does the cartilage do?
- provides mechanical stability
- helps hold the airways open
Why does the back of the trachea not have cartilage (why is the cartilage C-shaped instead of going all the way around)?
To allow the oesophagus to run down the back so we can swallow food
What do type I cells in an alveolus do?
- 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)
What do type II cells in an alveolus do?
- 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
What do the macrophages in an alveolus do?
Go around cleaning up debris, viruses etc that we inhale into alveoli
What do the fibroblasts in an alveolus do?
Produces collagen / the ECM that holds the structure together
What are the basic functions of the respiratory airways?
- 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
What are the features of the nasal passages?
- 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)
What features does a transverse section of a lower airway have?
- 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
What is the arrangement of the airway wall?
- 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
What are examples of airway cell types?
- 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
What are mucin granules?
- 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
Why do the epithelial cells have so many mitochondria?
Cilia need energy to move and waft mucus along the surface
What are acini in a human bronchial submucosal gland?
- 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)
What do the microtubules do and what is the 9+2 arrangement?
- 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
What is the rhythm of ciliary beating?
Metachronal - different lines of ciliary hair move at different times to waft mucus down the back of the throat
In a human airway, what does mucus appear as on cilia?
- flakes
- likely due to fixation
What are the functions of airway epithelium?
- 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
What are examples of regulatory and inflammatory mediators produced by airway epithelium?
- 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
What are the functions of airway smooth muscle cells?
- structure of airway
- tone (airway diameter) - by contraction and relaxation
- secretion of mediators, cytokines and chemokines - usually only little secreted
How do the functions of airway smooth muscle cells change under inflammation?
- 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
What is the tracheo-bronchial circulation (systemic)?
- 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
What are the functions of the tracheo-bronchial circulation?
- 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)
What different types of nerves control airway function?
- parasympathetic - cholinergic
- nitrous oxide sympathetic adrenergic pathway
- sensory nerves
Nerve pathways between airway and CNS - peanut example
- 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
Which inflammatory and regulatory mediators control airway function?
- 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
What respiratory diseases are associated with loss of airway control?
- 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
