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Human Organs and Tissues > Airway Host Defence > Flashcards

Airway Host Defence Flashcards

1
Q

What are the 3 broad defense mechanisms and some examples of each?

A
  1. PHYSICAL
    Cough
    Barrier function Mucociliary Clearance
  2. CHEMICAL
    Mucus composition and viscocity
    Antimicrobial peptides
  3. CELLULAR
    Phagocytosis by macrophages Immune response
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2
Q

What are the 3 major atmospheric polutants?

A
  1. carbon monoxide
  2. Nitrogen oxides
  3. Sulphur oxides
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3
Q

What causes production of CO?

A

incomplete combustion of carbon in fuels

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4
Q

What is the danger of CO?

A

binds hemoglobin with 200x affinity of oxygen

can impair mental skills

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5
Q

What produces NO?

A

burning of fossil fuels at high temps in power stations and cars

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6
Q

What does NO cause?

A

inflammation of eyes and upper respiratory tract at low concentrations

High concentrations can cause acute trachetis, acute bronchitis, and pulmonary edema

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7
Q

What produces sulphur oxides?

A

burning of sulphur containing fossil fuels

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8
Q

What does exposure to sulphur oxides cause?

A

Inflammation of mucous membranes, eyes,
upper respiratory tract and bronchial mucosa
•Short term exposure to high concs can cause edema

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9
Q

What is the largest pollutant by weight?

A

CO

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10
Q

What in cigarettes is responsible for the high risk of bronchial carcinomas?

A

Tar and largely aromatic hydrocarbons

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11
Q

What are the 3 mechanisms of clearing inhaled materials?

A
  1. Impaction
  2. Sedimentation
  3. Diffusion
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12
Q

How does impaction work? What kind of particles does this get rid of?

A

largest particles fail to turn at the corners of the respiratory tract. Particle hits wet surface and sticks. 95% particles > 5 m filtered by nose

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13
Q

How does sedimentation work? where is this mechanism most important?

A

gradual settling of particles due to their weight. Mechanism dominates in small airways

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14
Q

How does diffusion work to clear particles?

A

random movement of particles as result of their continuous bombardment by gas molecules. Only
for smallest particles (<0.1 m)

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15
Q

What kind of protective process is coughing?

A

a very non-specific protective reflex

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16
Q

When does the cough reflex develop?

A

about one month after birth

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17
Q

What initiates coughing?

A

A variety of irritants triggering specialized cough receptors in/under the airway epithelium

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18
Q

What are the 4 phases of the cough?

A
  1. Deep and rapid respiratory effort
  2. Compression due to closing of the glottis, activation of the diaphagm, and chest wall muscles
  3. Sudden opening of glottis and high expiratory airflow
  4. Relaxation of muscles and reversal of pressures
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19
Q

What kind of epithelial cells are in bronchial epithelia?

A

Ciliated, pseudostratified, columnar epithelium

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20
Q

What are 3 functions of tight junctions?

A
  1. structural support
  2. barrier
  3. separate apical and basolateral domains
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21
Q

the mucous layer in the respiratory system is subdivided into two layers, what are they?

A

Gel layer: top, stickier layer

Sol layer: less viscous

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22
Q

What two factors need to be controlled in order to have effective movement of the mucous blanket?

A

the length of the cilia (between 5-7 µm in the trachea and become shorter) and the height of the sol layer

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23
Q

What is the end point for the mucous? which way does it travel?

A

Moves upwards from the lungs towards the epiglottis

End point is the pharynx where it is swallowed

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24
Q

Cilia are found down to about which bronchial division?

A

the 16th

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25
Q

Ciliated epithelia line which 8 structures of the respiratory and associated systems?

A

bronchi, bronchioles of lungs plus nasal cavity, paranasal sinuses, eustachian tubes, middle ear, pharynx, trachea

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26
Q

Whats the basic structure of cilia?

A

9+2 arrangement

  • ATPase or dynein arms on subfibre (complete) A
  • Nexin links connecting doublets
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27
Q

What is the recovery stroke for cilia movement? How much cycle time does this account for?

A

From rest position, cilia bend sideways and back

Takes place near cell surface and accounts for 3/4 of cycle time

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28
Q

What comes after the recovery stroke?

A

Effective stroke - cilia moving perpendicular to the cell surface

claws on the tip of cilia engage with overlying mucous and sweep it towards the head
- this is the only time the cilia engage with the mucous

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29
Q

What factor will inhibit ciliary beating frequency (CBF)? How?

A

neuropeptide Y

by reducing intracellular calcium

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30
Q

Increases in intracellular calcium will…

A

increase CBF

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31
Q

What do mechanoreceptors int he epithelium do with regards to cilia?

A

Increase CBF in response to mechanical stimulation

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32
Q

What 5 factors affect mucocillary host defense in healthy people?

A
  1. Age: CBF is higher in neonates and teens, lower in adults
  2. Sex: Clearance slower in males than females
  3. Sleep: Clearance is decreased during sleep
  4. Exercise: Strenuous exercise increases MCC (no effect of gentle exercise)
  5. Gravity: No effect on heathy individuals really, but postural drainage may assist in CF
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33
Q

What are 3 diseases that affect mucociliary clearance?

A
  1. Primary ciliary dyskinesia
    - aka immotile cilia syndrome
  2. Bronchiectasis
  3. Cystic Fibrosis
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34
Q

What is Primary Ciliary Dyskinesia?

A

Impaired ciliary action usually due to absence of dynein arms or radial spokes (sometimes) in cilia

Ciliary motion is abnormal and not coordinated

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35
Q

What are the results of having primary ciliary dyskinesia?

A

Incidence of resp. infection high.
- Bronchitis, rhinitis, sinusitis, otitis media (middle ear infection), obstructive lung disease.

Males usually sterile due to sperm immobility.

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36
Q

What is bronchiectasis?

A

abnormal widening of the bronchi

37
Q

What is thought to cause defective MCC in bronchiectasis?

A

local damage to the respiratory tract epithelium due to infection

38
Q

How are particles cleared in the alveoli?

A

No mucous or cilia

Particles engulfed by macrophages

39
Q

How do macrophages kill and remove foreign bacteria/particles?

A

Phagocytose foreign particles: migrate to small airways to load on mucociliary escalator OR
leave via lymphatics
Contain lysozyme so can directly kill bacteria

40
Q

What can impair macrophage activity ?

A

Cigarette smoke,

alcohol, alveolar hypoxia, ozone, radiation

41
Q

the principal mononuclear phagocyte of the alveolar surface is…

A

the alveolar macrophage!

42
Q

Where are alveolar macrophages derived from?

A

circulating blood monocytes

43
Q

What is the composition of respiratory mucous?

A

Water with high molecular mass + cross-linked glycoproteins + serum and cellular proteins

44
Q

What two elements of respiratory mucous give it the viscoelastic properties?

A

Glycoproteins and water

45
Q

What are mucins and what is their role in mucous?

A

gigantic biopolymers of glycoproteins characterized by presence of one or more large region rich in serine and threonine.

Amino acids covalently attached via linkage sugar NAG

Role:

  1. provide structural framework of defense barrier,
  2. prevent barrier dehydration,
  3. present carbohydrate sites which pathogens attach to
46
Q

Human resp mucous is a mixture of what two kinds of mucous?

A

MUC5AC (goblet cells)
- main one

MUC5B (mucous cells in submucosa)

47
Q

Airway mucous is a mixture of products from which 4 places?

A
  1. Alveolar liquid
  2. Secretory products from cells lining the surface epithelium
  3. Submucosal gland products
  4. Serum transudate
48
Q

What type of cells can transform into goblet cells in disease?

A

clara cells

49
Q

How much larger volume wise are submucosal glands compared to goblet cells?

A

about 40 times

50
Q

What happens when a secretory granule docks with the plasma membrane of a SMG? What happens to the mucin polymers

A

a secretory pore forms.

The pore has a high ionic conductance and Ca2+ inside the granule is exchanged for extracellular Na+. This Na+/ Ca2+ exchange triggers a polymer-gel phase transition, when the mucin polymer matrix undergoes extensive swelling and switched from condensed to hydrated state

51
Q

What kind of material is mucous? What kind of flow properties does it have?

A

Viscoelastic material characterized by nonlinear (non Newtonian viscosity) and time-dependent flow (thixotropic) properties

52
Q

What are viscosity and elasticity? In terms of rheology?

A

Viscosity = resistance to flow and is the capacity of a material to absorb energy when moving
- extent to which it resists the tendency to flow

Elasticity = capacity of a material to store energy used to move or deform it
- tendency to recover its original shape

53
Q

What happens to the viscosity of mucous as the applied force increases?

A

the viscosity decreases

54
Q

What is rheology?

A

the characterization of the physical properties of mucous

55
Q

What is phelgm? What does it contain?

A

purulent secretion that is a product of airway inflammation, Containing breakdown products of inflammatory and epithelial cells; including DNA and actin fragments, bacteria, cell debris and mucins

56
Q

What is sputum?

A

Phlegm that has been expectorated

57
Q

What is the sol layer or pericilliary liquid layer like?

A

low viscosity medium

about 7 µm deep

58
Q

What factors are contained in the sol layer? What does this acheive?

A

Antibacterial factors
- lysozyme, lactoferrin…

Broad antibacterial spectrum against S. aureus and P. aeruginosa

59
Q

What is responsible for the hydration of mucous and the depth of the sol layer?

A

The transepithelial movement of ions and water

60
Q

How is the periciliary liquid layer (PCL) controlled ?

A
  1. When excess PCL is present, Na+ absorption via epithelial Na channels (ENaC) is dominant. Cl- is absorbed passively via the paracellular pathway
  2. When PCL volume if low, ENaC is inhibited which makes the apical membrane potential more negative, so generating a driving force for Cl- secretion.
61
Q

What do epithelial cells lining the airways express as part of innate host defence mechanisms?

A

Antimicrobial peptides

62
Q

AMPs are generally… which allows them to bind to prokaryotic cell membranes

A

cationic

63
Q

high levels of what 2 things can inhibits the functioning of AMPs?

A

salt or serum proteins

64
Q

What 2 small AMPs are found in the human airway?

A
  1. Defensins

2. Cathellcidins

65
Q

What are 2 examples of large AMPs? What do they do?

A
  1. Lysozyme
    - induces lysis of gram positive bacteria
  2. Lactoferrin
    - sequesters iron from bacteria
66
Q

What does Coal Workers Pneumoconisis + Silicosis (CWP) refer to?

A

Interstitial disease of the lung resulting from chronic exposure to coal dust

Silicosis is due to the inhalation of dust containing silica (quartz)

67
Q

What is the latency period for CWP and Silicosis?

A

long, like 20 years

68
Q

What occurs to the lung tissue in CWP?

A

formation of lesions called coal dust macules

coal-dust laden macrophages within the walls of the respiratory bronchioles and adjacent alveoli. Often emphysema surrounding macule. In advanced disease, condensed masses of black fibrous tissue seen called nodules

69
Q

What occurs in the lung tissue in Siliciosis?

A
  1. Infiltration of the alveolar walls with plasma cells, lymphocytes and fibroblasts, with some collagen deposition.
  2. Alveoli fill with eosinophils.
  3. Widening of alveolar walls with collagen and clusters of type II cells.
    - Nodules rare
70
Q

What are 3 asbestos related diseases ?

A
  1. Asbestosis
  2. Bronchial carcinoma
  3. Pleural disease
71
Q

What causes asbestosis?

A

Asbestos fibres depositing at branch points in the airways.

Cascade of inflammatory activation which results in a fibroblast proliferation and extracellular matrix deposition in interstitial space

72
Q

Pleural disease may occur after even….

A

trivial exposure to asbestos

73
Q

What is pleural disease?

A

formation of pleural plaques or thickening which results in restriction and reduced compliance?

74
Q

What is a severe complication that may develop from pleural disease?

A

Malignant mesothelioma

75
Q

What is occupational asthma?

A

Variable airflow obstruction or bronchial hyper-responsiveness from conditions in a particular working environment

76
Q

What are the two forms of occupational asthma?

A
  1. Immunologically mediated

2. Non-immunologically mediated

77
Q

What is characteristic of immunologically mediated OA compared to the N-I mediated?

A

Latency period necessary to acquire sensitization

78
Q

What is thought to be the cause of Non-immunologically mediated OA?

A

maybe extensive denudation of epithelium results in airway inflammation and hyper-responsiveness due to loss of epithelium-derived relaxing factors, exposure of nerve endings to neurogenic inflammation and non-specific activation of mast cells, with release of mediators and cytokines

79
Q

Epithelial cells of the lungs are exposed to oxidants in which two ways?

A
  1. Internally from normal metabolic processes

2. Externally from environmental pollutants

80
Q

What are examples of enzymatic and non-enzymatic antioxidant defenses against oxidants?

A
  1. non enzymatic: glutathione, vitamins C+D…

2. Enzymatic: superoxide dismutases, catalases, and peroxidases

81
Q

Oxidative stress has been implicated in the pathogenesis and progression of many pulmonary diseases including….

A

asthma, cystic fibrosis, idiopathic pulmonary fibrosis and COPD, plus effects of environmental
pollutants

82
Q

What is a free radical?

A

Any species that contains one or more unpaired electrons

83
Q

What are 5 important ROS?

A
  1. Superoxide anion
  2. Nitric oxide
  3. Peroxynitrite
  4. Hydroxyl radical
  5. Hydrogen peroxide
84
Q

What are the 2 primary ROS produced in vivo?

A

O2- and H2O2

85
Q

What is the most harmful ROS?

A

OH-

86
Q

What is the pathophysiology of oxidant stress in asthma?

A

there are more inflammatory cells than controls which results in more ROS being produced

airway antigen challenge + asthma attack = immediate formation of O2

87
Q

deficiency in superoxide dismutases in asthma results in…

A

lower levels of epithelial lining fluid

Exposure to ROS results in apoptosis of epithelial cells

88
Q

What is responsible for keeping the alveoli sterile?

A

alveolar macrophages

Human Organs and Tissues (16 decks)

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