Non-respiratory functions of the Lungs Flashcards

1
Q

Describe the different types of epithelium found throughout the airway?

A

Pseudostratified ciliated columnar epithelium: Found in the nose, pharynx and trachea.

Ciliated columnar epithelium in a bronchus: Located in the bronchi.

Cuboidal epithelial cells: Located in the bronchioles. As the merge with the alveoli, they begin to flatten.

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2
Q

Explain how inspired air is heated and humidified?

A

During inspiration, cold air passes through the warmer airway lined fluid, the air is warmed via conduction.

The air gets **humidified by vaporisation of water from the mucosal layer **lining the epithelium. As water vaporises which cools the airways due to latent heat of vaporisation.

During expiration warm air condenses returning mositure to the mucosa and heat as latent heat of condensation.

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3
Q

How can the efficiency of warming and humidification be maximised?

A

Breathing at rest allows more time for warming and humidification.

Nasal breathing:
The nasal turbinates encourage turbulent flow which increases contact with the nasal mucosa and slows flow allowing more time for warming and humidification.

With nasal breathing there is also a longer distance at which gas has to travel again increasing the opportunity for humidification and warming.

WIth nasal breathing at rest 100% humidifcation and warming to ambient temperature occurs by the time the air has reached the trachea.

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4
Q

What are the 2 layers of the airway lined fluid and where are they produced?

A
  1. Mucous ‘gel’ layer: Secreted by goblet cells in response to irritation or infection. It contains several very large, viscoelastic proteins called mucins, which are sticky that forms a flexible gel which can retain large amounts of water. Only occurs in large airways and exists as ‘islands’ in distal airways.
  2. Periciliary ‘sol’ layer: Produced by ciliated epithelial cells through active secretion of sodium and chloride and passive osmosis of water (mutation in cystic fibrosis disrupts this)
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5
Q

Why is the depth of the percillary layer of importance?

A

The periciliary layer must remain at the correct depth to allow cilia to beat efficiently.

The depth is controlled by the active transport of ions by epithelial cells, the passive movement of water between the mucous and periciliary layers and evaporation.

Normal conditions: Tips of the cilia are brushing the mucous layer

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5
Q

Why is the depth of the percillary layer of importance?

A

The periciliary layer must remain at the correct depth to allow cilia to beat efficiently.

The depth is controlled by the active transport of ions by epithelial cells, the passive movement of water between the mucous and periciliary layers and evaporation.

Normal conditions: Tips of the cilia are brushing the mucous layer

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5
Q

Why is the depth of the percillary layer of importance?

A

The periciliary layer must remain at the correct depth to allow cilia to beat efficiently.

The depth is controlled by the active transport of ions by epithelial cells, the passive movement of water between the mucous and periciliary layers and evaporation.

Normal conditions: Tips of the cilia are brushing the mucous layer

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6
Q

What issues can occur with the mucous layer?

A

Build up of mucous layer: Occurs with convergence of multiple distal airways to the larger airway (plugging off bronchioles) and in smoking or infection. Excess water is all held in the mucous layer

Water Depletion: Caused by systemic dehydration or increased evaporative losses from a warm atmosphere. Water is donated to the periciliary layer by the mucous layer through osmosis until the depth of the mucous layer is reduced by up to 70%

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7
Q

How are inhaled particles removed from the lung?

A

Mucociliary Escalator:
Particles get trapped in the mucous layer. The mucous layer is propelled cephalad by beating cilia at 12-14x/s.The mucous velocity averages at 4 mm/min at a steady rate.

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8
Q

Describe the phases of cillia beating?

A
  1. **Recovery Stroke **which occupies 75% of the cycle time. Slow movement away from the resting position by sideways action of cilium.
  2. Effective Stroke: Cilia grip the underside of the mucous layer and propel it forward. It then releases to prepare for the recovery stroke. This is coordinated with the cilia adjacent to it for more effective movement.
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9
Q

What can affect cilliary function?

A

Tabacco smoke
Inhaled polutants
Anaesthetic agents
Infection

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10
Q

What is inertial impaction?

A

Inertial impaction refers to the particle’s inability to follow sudden change in gas flow direction such as in the upper airway and at airway bifurcations.

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11
Q

How does particulate size effect deposition in the respiratory tract?

A
  • Large particles (>10 μm) are deposited in the nose and pharynx and rarely pass beyond this
  • Smaller particles (3-10 μm) penetrate further into the respiratory tract
  • Sedimentation occurs with slow gas velocity and deposition on the airway lined fluid. This occurs in the small airways or alveoli and the particles are 1-3μm in size. Breath-holding following inspiration encourages this process. Fine particulate air pollution (PM2.5) causes inflammation of the lung and elsewhere in the body.
  • Diffusion occurs with particles <1μm in size and have minimal contact with the airway or alveolar walls. I.e. in smoking where most is exhaled.
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12
Q

Describe the methods of chemical inactivation of particles which bypass the mucocilliary escalator

A

Particles in the alveoli can be cleared by alveolar macrophages which are activated to different extents according to the particle type.

Chemical inactivation is a key defence system caused by:
* Lysozymes: destroys gram-positive bacterial cell walls excreted by neutrophils
* Defensins: Produced by epithelial cells and defend by direct bacterial cell wall damage or through attraction of other immune cells through acting as a chemokine.
* Surfactant Protein A: Acts as a chemokine through bacterial recognition in the alveoli.

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13
Q

Explain the role of the protease/antiprotease system within the lung?

A

Protease enzymes i.e. elastase or metalloproteinases are released in the lung in response to pathogens or tobacco smoke.

Whilst they are powerful antimicrobials, they may also damage lung tissue but two mechanisms help prevent this:
1. They are confined to the mucous layer which avoids close contact with the epithelial cells
2. Anti-protease enzymes exist to inactivate it through conjugation e.g. α-1-antitrypsin

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14
Q

Describe the humoral defence of the lung?

A

Humoral Immunity
Large amounts of immunoglobulin is present in the airway lining fluid.

The most abundant of which is immunoglobulin A and acts by preventing bacterial binding to the mucosa. IgG predominates deeper in the respiratory tract.

15
Q

Describe the cellular immunity of the lung?

A

Epithelial cells are immunologically active supported by macrophages.

Neutrophils multiply in COPD and eosinophils and mast cells in asthma.

Once the epithelial cells are activated they use a range of molecules to induce an inflammatory response and tissue healing:
* Adhesion molecules i.e. ICAM-1 in pulmonary capillaries for inflammatory cells
* Chemokines i.e. IL-8 recruit inflammatory cells to lung tissue
* Cytokines i.e. IL-1,6 & TNF amplifies the inflammatory response
* Growth factors i.e. TGF-β, EGF to stimulate cells responsible for repair i.e. fibroblasts
* ECM proteins i.e. collagen, hyalouronan to begin tissue repair.

16
Q

How can the lungs cellular immunity become pathological?

A
  1. Growth factors i.e. TGF-β, EGF to stimulate cells responsible for repair i.e. fibroblasts
  2. ECM proteins i.e. collagen, hyalouronan to begin tissue repair.

These mechanisms may become overactive in prolonged/severe inflammation leading to remodelling of pulmonary blood vessels. This can cause pulmonary HTN or excessive deposition of collagen can cause irreversible pulmonary fibrosis.

17
Q

What is the surface area of the endothelium that interface with the alveoli?

A

The endothelial surface contains multiple invaginations and projections and contain numerous vesicles that abut against the cell surface (caveolae) which increases the surface area further to 126 m2.

18
Q

Which molecules become activated when passing through the pulmonary circulation?

A

Angiotensin I

Arachidonic Acid

Cortisone

19
Q

Think of them in groups (6): Amines/Peptides/Arachidonic Acid etc

Which molecules become inactivated when passing through the pulmonary circulation?

A

Amines:
* 5-hydroxytryptamine
* Noradrenaline

Peptides:
* Bradykinin
* Endothelins

Arachidonic Acid Derivatives:
* PGD2 (PG=prostoglandin)
* PGE2
* PGF2α
* Leukotrienes

Purine Derivatives:
* Adenosine
* ATP
* ADP
* AMP

Steroids:
* Progesterone
* Beclometasone

Basic drugs:
* Fentanyl
* Lidocaine
* Propranolol

20
Q

What are the 2 groups of enzymes which exist on the pulmonary endothelial cells and what are their roles?

A

1. Membrane bound– responsible for Angiotensin I conversion to Angiotensin II. Also for the inactivation of bradykinin and adenosine

2. Cytoplasmic – involved in metabolism of arachidonic acid products, degradation of prostaglandins and breakdown of 5-HT and other amines

21
Q

What is the role of Monoamine oxidase and catechol-O-methyl transferase in pulmonary metabolism?

A

They are responsible for the metabolism of catecholamines. They are found extensively in the cytoplasm.

1/3 Noradrenaline and 98% of seretonin (5-HT) are removed. Adrenaline and dopamine are not effected as they are not taken up by the cell membrane.

22
Q

Which type of drug tends to be bound by the pulmonary circulation?

A

Basic drugs (pKa > 8) and lipophilic drugs tend to be bound by the pulmonary circulation while acidic drugs preferentially bind to plasma proteins

23
Q

What sort of molecule is ACE and where is it located?

A

ACE is a Zinc containing carboxypeptidase with two active sites.

It is located on the surface of endothelial cells lining the inside of the caveola extending to the luminal projections.

80% of Angiotensin I is converted in one pass through the pulmonary circulation. ACE also effectively removes bradykinin.