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Infect & Immune 2 MW, NJH & AB > MW L1 Asthma introduction > Flashcards

MW L1 Asthma introduction Flashcards

1
Q

What percentages of deaths from asthma are preventable?

A

90%

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2
Q

Definition of asthma

A

chronic inflammatory condition of the airways,

  • associated with VARIABLE airway obstruction
  • increase in airway response to variety of stimuli
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3
Q

Asthma is associated with …… airway obstruction which is often ………..

A 
variable
reversible (with treatment of spontaneously)
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4
Q

PEFR is

A

peak expiratory flow rate

blow as fast as you can into the tube

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5
Q

FEV1 is

A

forced expiratory volume

integrates the PEFR over 1 second

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6
Q

Lung function test eg (2)

A

PEFR and FEV1

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7
Q

What does lung funct measure

A

They are both measures of EXPRIRATION

Asthmatics have trouble with them. Expiration is usually a passive process.

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8
Q

Step 1 Asthma attack

A

Early bronchoconstriction
Over mins - hours function falls.
Largely due to contraction of smooth muscle.

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9
Q

Step 2 Asthma attack

A

Pt feels fine for some hours.

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10
Q

Step 3 Asthma attack

A

Hours later wheezing occurs, associated with inflammation.
Oedema.
Interstitial connective tissue becomes spongy.
Excess secretions.

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11
Q

Which part of an asthma attack is caused by bronchoconsriction and which by oedema, secretion and inflammation

A

Bronchoconstriction - early stage

Oedema, secretions and inflammation - late stage

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12
Q

Asthma patients show increased ……(2)……… when exposed to something causing brconchoconstriciton

A

Increased maximum response and sensitivity

compared to healthy person

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13
Q

4 mechanisms of hyperresponsiveness

A

1 Increased smooth muscle contractility
2 Increased excitatory nerve actitivty
3 Decreased bronchililator activity
4 Inflammation

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14
Q

Mechanism of hyperresponsiveness:
1. Increased smooth muscle contractility
What happens? (2)

A

Hyperplasia & hypertrophy

- therefore muscles contract more

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15
Q

Mechanism of hyperresponsiveness:
1. Increased smooth muscle contractility
Hyperplasia means

A

more muscle cells

-this means they can develop tension and constrict harder

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16
Q

Mechanism of hyperresponsiveness:
1. Increased smooth muscle contractility
Hypertrophy means

A

bigger muscle cells

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17
Q

Mechanism of hyperresponsiveness:
1. Increased smooth muscle contractility
Smooth muscle growth regulators (2 main categories):

A

Mitogens (cause cell growth) and modulators (switch off growth)

18
Q

Mechanism of hyperresponsiveness:
1. Increased smooth muscle contractility
4 examples of mitogens

A 
Platelet derived growth factor
Endothelin
Cytokines
Histamine
(cells growth happens over weeks and months not just hours)
19
Q

Mechanism of hyperresponsiveness:
1. Increased smooth muscle contractility
3 examples of modulators

A

Heparin
Nitric oxide
Prostaglandin E2
(switch off smooth muscle growth so may be beneficial)

20
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
Airway is innervated by which nerves?

A

The vagus

21
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
What type of nerves innervate the airways?
(….. acting on …. receptors)

A

Cholingergic

ACh acting on M3 receptors

22
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
Appart from ACh what other neurotransmitters cause contractile response

A

Excitatory non-adrenergic non-cholinergic transmitters (eNANC)

23
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
eNANC acts on

A

neurokinin receptors, (these are peptides)

24
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
3 examples of eNANC

A

substance P
neurokinin A
neurokinin B

25
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
Both Cholinergic nerves and eNANC stimulate…….. causing bronchiconstriction

A

stimulate GPCR leading to elevation of intracellular free Ca

26
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
How do cholinergic nerves cause bronchoconstriction?

A

release ACh, acts on M3 receptors (Gq)
PLC hydrolysis membrane IP3
Intracellular Ca released into cytoplasm

27
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
How does increased Ca cause bronchoconstriction?

A

Ca binds to calmodulin and activates MLCK - causes contraciton

(myosin light chain kinase)

28
Q

What does myosin light chain kinase do?

A

phosphorlylates MLC to MLC-P

MLC-P causes contraction

29
Q

Mechanism of hyperresponsiveness:
2 Increased excitatory nerve actitivty
Negative feedback system for ACh causing smooth muscle contraction?

A

ACh acts back on M2 receptors in the parasympathetic nerve terminal.
M2 reduces the levels of ACh being released.

30
Q

Mechanism of hyperresponsiveness:
3 Decreased bronchililator activity
Main categories of bronchodilators (2)

A
  • Circulating adrenaline

- Inhibitory non-adrenergic non-cholinergic transmitters (iNANC)

31
Q

Mechanism of hyperresponsiveness:
3 Decreased bronchililator activity
How does circulating adrenaline cause bronchodilation?

A

acts on beta-adrenoreceptors on airway smooth muscle

32
Q

There are more para or symp nerves in the airways?

A

Parasympathetic. - causing constriciton

most dilation comes from adrenaline

33
Q

Mechanism of hyperresponsiveness:
3 Decreased bronchililator activity
Two main iNANC?

A

Neuronally-derived NO

Dilator neuropeptides

34
Q

Neuronally derived NO acts on… to cause…

A

soluble guanylate cyclase to cause bronchodilation

35
Q

name 2 dilator neuropeptides

act on…. to cause….

A

CGRP (calcitonin-gene related peptide)
VIP (vasoactive intestinal polypeptide)
activate adenylyl cyclase to cause bronchodilation

36
Q

Mechanism of hyperresponsiveness:
3 Decreased bronchililator activity
Main’classical’ pathway that beta2 adrenoreceptor activation causes bronchodilation?

A

activaition causes GPCR to convert ATP into cAMP.
cAMP activates PKA.
PKA inactivates MLCK.

37
Q

Mechanism of hyperresponsiveness:
3 Decreased bronchililator activity

Beta2 adrenoreceptors activates PKA. How can PKA cause bronchodilation? (3) + (1)

A
  • inactivates MLCK (‘classical’ pathway)
  • opens K+ channels, becomes hyperpolarised and harder to electrically activate
  • Calcium sequestration

-Beta2 also activates MLC phosphotase

38
Q 
Mechanism of hyperresponsiveness:
4 Inflammation
Main mechanisms (2)
A
  • epithelial damage and exposure of sensory nerves

- oedema leading to decreased luminal diameter

39
Q

Why is mucus white?

A

lots of WBC

40
Q

severe asthma what becomes a problem?

A

scarring of the airway

41
Q

5 Evolving concepts in asthma pathogenisis?

A
  1. primary abnormality of airway-myocyte hyperresponsiveness
    2 autonomic dysfuntion with exagerated activity of chilinergic or tacykinnin pathways
  2. IgE mediated mast cell/ basophil degranulation
  3. Complex T lymphocyte mediated airway inflammation
  4. airway remodelling

Infect & Immune 2 MW, NJH & AB (12 decks)

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