L11.2 Smooth muscles in the respiratory system Flashcards Preview

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Flashcards in L11.2 Smooth muscles in the respiratory system Deck (21)
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1

How many generation of branches of airways are there?

  • 23 generations of airway, doubles at each branching
    • gen 0 = trachea
    • gen 1 = 2 main bronchi
    • gen 2-4 = large bronchi
    • gen 5-11 = small bronchi
    • gen 12-23 = bronchioles

2

How are the number of airways determined?

  • # of airway = 2generations

3

Movement of air through the airways

  • Conducting airway → air diiffusion at exchange
  • Parenchyma → gas movement by bulk

4

Resistance of airways

  • 50% resides in nose, pharynx, larynx
  • Nose
    • resistance 2x higher than mouth → reflex switch breathing through mouth in exercise
  • Vocal folds of larynx
    • Come tgt to form "expiratory brake" to prevent too-rapid collapse of lungs by maintaining intramural pressure
  • ↓cross sectional area → ↑resistance
    • ∴trachea and bronchi (low generation of branches) → ↑resistance
    • Resistance increases till 3rd generation, then starts decreasing (due to increase SA)

5

Why/how do you cough?

  • S.M in airways facilitate coughing → to remove foreign object obstructing the airways by coughing

6

Resistance of small bronchi/bronchioles

  • Generation 7-14 → small cross-sectional area, some contribution to resistance
  • Resistance is variable
    • No support of cartilage, and with presence of SM

7

Resistance beyond 16 generation 

  • Rapid ↑ in airway numbers → ↑x-sectional area → ↓resistance

8

Airway smooth muscles 

  • More prominent in lower airways
  • No cartilage in small airways → SM contraction → collapses small airways
    • Tube narrows and shortens

9

Silent zone of airways

  • FEV1.0 used to measure airflow through airways
    • Contributed to by LARGE airways ONLY
    • Drug which treats smaller airways will not see change in FEV1.0
  • COPD is a silent disease because it is not picked up by such measures and largely affects the smaller airways

10

 ASM morphology

  • Cytosol rich in contractile myofilament
  • Actin-myosin of SM show great plasticity
  • When ASM contracts, ASM shortens in a way that doesn't lose volume, just becomes squat

11

ASM of asthmatic patients

  • More prominent SM
  • More mediators activating SM
  • Muscles acts on mucus gland → excessive mucus which contributes to further narrowing of airway
    • ↑globet cell (secrete mucus)
    • ↑mucosal vascularity

12

Bronchial thermoplasty

  • kills SM for severe asthmatics

13

Effectiveness of b-agonists on asthma

  • b-agonist → treats spasms BUT vascular inflammation and mucus obstruction not treated

14

ASM dysfunction

  • Contributes to wall vol in airway remodelling and inflammation
    • Prolif and migrate SM
    • Secretion of cytokines, extracellular matrix proteins (i.e. collagen)

15

Do ASM matter?

  • Asthmatic patients have more SM mass, but SM proliferation is not increased
  • SM secretes cytokines and is proinflammatory
    • ↓Cytokine mediators after thermoplasty → removing SM
    • Removal of SM → improves asthma (in initial trials)

16

Neural mechanism of muscles

  • Contractile tone depends on:
    • PNS, vagal efferents
    • Excitatory NANC efferents
  • Relaxation depends on
    • SNS
    • Inhibitory NANC efferents

17

Inflammatory mechanism

  1. Mast cells activated
  2. Mast cells release mediators that activate ASM (LT most important)
  3. Over time → other cells activated
    • Communicate via cytokines (e.g. T cells prod GM-CSF → ↑eosinophils survival)

18

Actions of important agonists

  • LTD/E4 are potent contractile agents in SM (much more significant than histamine)
    • Causes persistent activation of SM in airways

19

Contractile agonists increases Ca oscillation 

  • Gq → PLC → IP3 acts on RyR → oppose Ca uptake and release ↑Ca
  • Ca binds to calmodulin → MLCK → contraction
    • Process controlled by MLCP (turns process off)

20

Contractile agonists increasing Ca sensitivity

  • Gq → PKC → ROCK → inhibits MLCP → ↑sensitivity

21

b-agonists on Ca activity

  • Inhibit Ca oscillations → inhibit IP3 R sensitivity
  • Inhibit Ca sensitivity → MLCP activation
  • ↑PKA → inhibit Ca channels