Respiratory cell biology

Question 1

What is the respiratory mucosa made up of?

Answer 1

Ciliated cells
Goblet cells
Submucosal glands

Question 2

What are submucosal glands?

Answer 2

Collecting ducts that drain produced mucous to the airways; mucous acini are closer to the ducts, producing mucus, with more distal serous acini that secrete antibacterials - ensures that watery serous acini wash the more viscous mucus to the collecting duct

Question 3

What are the functions of the respiratory mucosa?

Answer 3

Secretion of protective lining, antioxidant/antiprotease/lysozyme synthesis and release, xenobiotic metabolism

Question 4

Describe the structure of the cilia:

Answer 4

Actin polymers in a 9+2 arrangement, with 9 pairs around the outside, and one in the centre; dynein arms and ATPase allow the columns to slide over each other and bend the cilia

Question 5

Describe ciliary beating:

Answer 5

Cilia beat in a synchronised (metachronal rhythm) to move the leading edge of mucous before moving back to the next field

Question 6

What is the Muco-ciliary escalator?

Answer 6

Moves mucous containing irritants and microbes upwards to larger airways for clearance by coughing or ingestion - only about 10ml in healthy people

Question 7

Describe the actions of macrophages and neutrophils in the lungs:

Answer 7

Macrophages infiltrate alveoli and phagocytose inhaled microbes and toxins and degrade, while polymorphonuclear neutrophils produce inflammatory mediators

Question 8

What is the macrophage:neutrophil ratio in non-smokers and smokers?

Answer 8

70:30% in non-smokers (30:70% in smokers)

Question 9

What are the inflammatory mediators that neutrophils produce in the alveoli?

Answer 9

Serine proteinases and metalloproteinases that break down proteins, connective tissue, elastin and collagen when activated by toxins

Question 10

What is the effect of chronic smoking on neutrophils?

Answer 10

The number will increase by up to 30% and will secrete proteinases, oxidants and mediators to attract more inflammatory cells

Question 11

Describe the xenobiotic metabolism in the lungs:

Answer 11

Metabolism of foreign compounds deposited by inhalation performed by phase I and II enzymes secreted from TII cells and macrophages

Question 12

What are procarcinogens?

Answer 12

Molecules found in cigarette smoke which are converted to active compunds by phase I enzymes

Question 13

What happens to pro-carcinogens that are activated by phase I enzymes?

Answer 13

Phase II enzymes make them water soluble metabolites for excretion

Question 14

When can procarcinogens lead to cancer?

Answer 14

When there is overloading; leads to DNA binding and mutations

Question 15

How many main types of cell are present in the airways? Name them:

Answer 15

8
Epithelial cells
Goblet cells
TI Pneumocytes
TII Pneumocytes
Alveolar macrophages
Smooth-muscle cells
Interstitial cells
Clara/Club cells

Question 16

Describe the structure and location of airway epithelial cells:

Answer 16

Ciliated with many mitochondria

Line all airways and alveoli

Question 17

Describe the function of epithelial cells

Answer 17

Form continuous barrier to isolate host from external environment; produce secretions to facilitate clearance and maintain surface tension

Question 18

Describe the structure and location of goblet cells

Answer 18

Polarised columnar cells containing mucin granules

Large, central and small airways; surrounded by strat. squamous

Question 19

Describe the function of goblet cells

Answer 19

Synthesise mucous, store in mucin granules which use with apical surface to secrete to airways; enables clearance of irritants/microbes; occurs continuously but can be increased by toxins

Question 20

Describe the structure of TI and TII Pneumocytes

Answer 20

TI: Very thin cells
TII: Contain lamellar bodies storing surfactant

Question 21

Describe the function of smooth muscle cells in the airways

Answer 21

Can contract to constrict airways, providing structure and tone to the airways and controlling flow

Question 22

Describe the structure and location of interstitial cells in the airways

Answer 22

Myofibroblasts (stromal cells)

Subepithelially In mucosal surfaces

Question 23

What is the function of the interstitial cells?

Answer 23

Deposit the ECM that the cells sit on - made of collagen and elastin to give elasticity/compliance

Question 24

Describe the structure and location of Clara/Club cells:

Answer 24

Non-ciliated secretory cells with Granules containing detoxifying enzymes

Question 25

What is the function of Clara/Club cells?

Answer 25

Replace the damaged epithelium and produce secretions for xenobiotic metabolism

Question 26

What is the function of TI pneumocytes?

Answer 26

Thin enough to facilitate gas exchange in alveoli

Question 27

What is the function of TII pneumocytes?

Answer 27

When lung stretches, surfactant released to maintain surface tension and allow alveoli to expand

Question 28

Where are TI and TII pneumocytes located?

Answer 28

TI: Cover 95% of the alveolar surface, but make up 33% of alveolar epi. cell count

TII: Cover 5% of the alveolar surface, but make up 66% of alveolar epi. cell count

Question 29

Described as sensory innervation of the airways:

Answer 29

Vagus afferents that travel to the CNS via nodose ganglion (or to spinal cord using dorsal root ganglion)

Question 30

Describe the innervation of the constriction mechanisms of the airways:

Answer 30

Parasympathetic Vagus cholinergic efferents cause constriction of airway smooth muscle cells

Question 31

Describe the innervation of the relaxatory mechanisms of the airways:

Answer 31

Not sympathetic; nitric oxide producing pathways are activated that dilate airways

Question 32

What are the steps of the cholinergic mechanisms utilised in the airways?

Answer 32

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 33

What is the humoral control of the airways?

Answer 33

Adrenaline: produced by adrenal gland; causes airway relaxation

Nitric Oxide: present in excess in epithelium to cause airway dilation

Question 34

What are the effects of smoking on goblet cells?

Answer 34

Number at least doubles (hyperplasia), with increased volume and viscosity of secretions to trap cigarette particles - inadvertently trapping microbes and leading to infection

Question 35

What are the effects of smoking on ciliated cells?

Answer 35

Severely depleted and beat asynchronously, and begin to appear in bronchioles and smaller airways - can no longer clear thicker mucous so reduced

Question 36

What are the effects of smoking on the epithelial cells of the airways?

Answer 36

Fibrosis occurs and alveolar walls are destroyed, leading to airway collapse and stenosis that prevents distal gas exchange

Question 37

Which diseases cause a loss of airway control?

Answer 37

Include: Asthma, COPD and Cystic fibrosis

Question 38

What is the pathophysiology of asthma?

Answer 38

Airway epithelia become fragile, exposing sensory nerves, leading to increased airway responsiveness to stimuli; causes stimulation of sensory nerves that activate a cholinergic reflex; reflex causes bronchoconstriction and mucous secretion, with an influx of inflammatory cells producing mediators