chronic inflammatory condition of the airways, - associated with VARIABLE airway obstruction - increase in airway response to variety of stimuli

MW L1 Asthma introduction Flashcards by Alethea Charlton

What percentages of deaths from asthma are preventable?

90%

How well did you know this?

Not at all

Perfectly

Definition of asthma

chronic inflammatory condition of the airways,

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

How well did you know this?

Not at all

Perfectly

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

variable
reversible (with treatment of spontaneously)

How well did you know this?

Not at all

Perfectly

PEFR is

peak expiratory flow rate

blow as fast as you can into the tube

How well did you know this?

Not at all

Perfectly

FEV1 is

forced expiratory volume

integrates the PEFR over 1 second

How well did you know this?

Not at all

Perfectly

Lung function test eg (2)

PEFR and FEV1

How well did you know this?

Not at all

Perfectly

What does lung funct measure

They are both measures of EXPRIRATION

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

How well did you know this?

Not at all

Perfectly

Step 1 Asthma attack

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

How well did you know this?

Not at all

Perfectly

Step 2 Asthma attack

Pt feels fine for some hours.

How well did you know this?

Not at all

Perfectly

Step 3 Asthma attack

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

How well did you know this?

Not at all

Perfectly

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

Bronchoconstriction - early stage

Oedema, secretions and inflammation - late stage

How well did you know this?

Not at all

Perfectly

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

Increased maximum response and sensitivity

compared to healthy person

How well did you know this?

Not at all

Perfectly

4 mechanisms of hyperresponsiveness

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

How well did you know this?

Not at all

Perfectly

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

Hyperplasia & hypertrophy

- therefore muscles contract more

How well did you know this?

Not at all

Perfectly

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

more muscle cells

-this means they can develop tension and constrict harder

How well did you know this?

Not at all

Perfectly

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

bigger muscle cells

How well did you know this?

Not at all

Perfectly

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

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

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

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

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

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

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

The vagus

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

Cholingergic

ACh acting on M3 receptors

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

Excitatory non-adrenergic non-cholinergic transmitters (eNANC)

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

neurokinin receptors, (these are peptides)

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

substance P
neurokinin A
neurokinin B

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

stimulate GPCR leading to elevation of intracellular free Ca

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

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

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

Ca binds to calmodulin and activates MLCK - causes contraciton (myosin light chain kinase)

What does myosin light chain kinase do?

phosphorlylates MLC to MLC-P MLC-P causes contraction

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

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

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

- Circulating adrenaline | - Inhibitory non-adrenergic non-cholinergic transmitters (iNANC)

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

acts on beta-adrenoreceptors on airway smooth muscle

There are more para or symp nerves in the airways?

Parasympathetic. - causing constriciton | most dilation comes from adrenaline

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

Neuronally-derived NO | Dilator neuropeptides

Neuronally derived NO acts on... to cause...

soluble guanylate cyclase to cause bronchodilation

name 2 dilator neuropeptides | act on.... to cause....

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

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

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

Mechanism of hyperresponsiveness: 3 Decreased bronchililator activity Beta2 adrenoreceptors activates PKA. How can PKA cause bronchodilation? (3) + (1)

- inactivates MLCK ('classical' pathway) - opens K+ channels, becomes hyperpolarised and harder to electrically activate - Calcium sequestration -Beta2 also activates MLC phosphotase

``` Mechanism of hyperresponsiveness: 4 Inflammation Main mechanisms (2) ```

- epithelial damage and exposure of sensory nerves | - oedema leading to decreased luminal diameter

Why is mucus white?

lots of WBC

severe asthma what becomes a problem?

scarring of the airway

5 Evolving concepts in asthma pathogenisis?

1. primary abnormality of airway-myocyte hyperresponsiveness 2 autonomic dysfuntion with exagerated activity of chilinergic or tacykinnin pathways 3. IgE mediated mast cell/ basophil degranulation 4. Complex T lymphocyte mediated airway inflammation 5. airway remodelling