Physiology of Respiration Flashcards
Where is the respiratory centre in the brain?
Medulla
Which chemoreceptors control the partial pressure of CO2 on arterial blood?
Medullary chemoreceptors
Which chemoreceptors control the partial pressure of oxygen in arterial blood?
Carotid body chemoreceptors
Which efferent pathways control airways?
- Cholinergic parasympathetic nerves
- Non-noradrenergic non-cholinergic (NANC) inhibitory nerves
(inflammatory mediators and other bronchoconstrictors also have a role in diseased airways
What is FEV1 and PEFR?
FEV1- forced expiratory volume in 1 second
PEFR- Peak expiratory flow rate- maximal flow (l/min) after a full inhalation
The bronchial smooth muscle is predominantly innervated by which autonomic innervation?
Parasympathetic- ganglia are embedded in the walls of the bronchi and bronchioles
Postganglionic fibres innervate airway smooth muscle, vascular smooth muscle and glands
Types of M receptors and which type of Muscarinic receptors are pharmacologically more important?
M3-found on bronchial smooth muscle and glands- mediate bronchoconstriction and mucus secretion
- M1- localised in ganglia and on postsynaptic cells and facilitate nicotinic neurotransmission
- M2- Inhibitory autoreceptors mediating negative feedback on Ach
Bronchodilators released by NANC
VIP and Nitric oxide
Which parts of the lung do sympathetic nerves innervate?
Tracheobronchial blood vessels and glands but not human airway smooth muscle
Which B adrenoceptors are in the airways
B2- beta agonists relax bronchial smooth muscle and inhibit mediator release from mast cells- increases mucociliary clearance
Location and myelination factor of irritant fibres and C fibres
Irritant fibres- myelinated- Upper airways
C fibres- unmyelinated- low airways
Which tachykinins are released with the excitation of sensory nerves?
Substance P and neurokinin A
Name two drugs used to treat other conditions which affect the lung and can cause fibrosis
Amiodarone- class III antiarrhythmic drug- potassium channel blocker Methotrexate- chemotherapy agent and immunosuppressant
What is asthma?
It is an inflammatory condition in which there is recurrent reversible airway obstruction in response to irritant stimuli that are too weak to effect non-asthmatic subjects- causes wheezes and needs treatment
Characteristics of asthma
- Inflammation of the airway
- Bronchial hyperreactivity
- reversible airways obstruction
Intermittent attacks of wheezing, shortness of breath and sometimes cough
Acute asthma causes hypoxaemia
Pathogenesis of asthma
Exposure of genetically disposed individuals to allergens: activation of Th2 lymphocytes and cytokine generation promotes:
- differentiation and activation of eosinophils
IgE production and release
- Expression of IgE receptors on mast cells and eosinophils
Characteristics of the immediate phase of an asthma attack
Abrupt
- spasm of the bronchial smooth muscle
- allergen interaction with mast cell-fixed IgE causes release of histamine, leukotriene B4 and Prostaglandin D2.
Characteristics of the late phase
Late phase or delayed response and may be nocturnal.
Progressing inflammatory reaction, initiation, of which occurred during the first phase, influx of Th2 lymphocytes
Two categories of antiasthma drugs
Bronchodilators and anti-inflammatory agents
5 steps of treatment
1- mild - salbutamol
2- add ICS
3- uncontrolled add LABA- salmeterol or formoterol- minimises the need for increased doses of inhaled corticosteroid
4- Theophylline and leukotriene antagonists- montelukast- coticosteroid sparring effect
5- prednisolone in addition to oral corticosteroid
Bronchodilators other than B2- adrenoceptor agonists
Theophylline, cysteiny leukotriene receptor antagonists and muscarinic receptor antagonists
How are B2 adrenoceptor agonists usually given
Inhalation of aerosol, powder or nebulised solution
SABA and LABA examples
SABA- Salbutamol - inhalation- max effect within 30 min and duration of action 3-5h
LABA- Salmeterol and formoterol- inhalation- duration of action is 8-12 hours
Theophylline characteristics
- Methylxanthine
- Inhibits phosphodiesterase and blocks adenosine receptors
- Narrow therapeutic window
- Antibiotics increase half-life, anti-convulsants
Which drugs are third line for asthma?
Cysteinyl leukotriene receptor antagonists
Commonest adverse effect of B2 adrenoceptor agonist
Tremor- tachycardia and cardiac arrhythmias
Unwanted side effects of Theophyllines
Insomnia, nervousness, seizures - it has a very narrow therapeutic index
Main SAMA
Ipratropium bromide- quaternary derivative of atropine
Route of administration of ipratropium?
Aerosol inhalation
30min after inhalation- max effect can be felt
Main LAMA used
Tiotropium
TWO LTRAs
Montelukast, zafirlukast
Which drugs are used for anti-inflammatory action in asthma?
Glucocorticoids
MOA of glucocorticoids
Restrain clonal proliferation of Th cells- reduce transcription of gene for IL2 and decrease formation of cytokines (Th2 cytokines that recruit and activate eosinophils and are responsible for production fo IGE)
Main compounds of corticosteroids used
Beclomethazone, budesonice, fluticasone (potent), mometasone, ciclesonide- given by inhalation with metered dose or dry powder inhaler
Example of higher potency glucocorticoids
Budesonise and fluticasone
Glucocorticoids given to patients who have acute exacerbations of asthma
Oral prednisolone and IV hydrocortisone
Treatment for acute asthma
- Oxygen >/ 60%
- Inhalation of nebulised salbutamol
- IV hydrocortisone followed by oral prednisolone
- IV magnesium 1.2-2mg for 20 mins
- IV theophyliine
COPD clinical features
PROGRESSIVE BREATHLESSNESS
cough- becomes chronic
Pulmonary hypertension- late feature
Pathogenesis of COPD
- Fibrosis of small airways
- Obstruction/destruction of alveoli and elastin fibres
- Emphysema causes resp failure- destroys alveoli- impairs gas transfer
Treatment of COPD
Stop smoking LABA- modest benefit Combat mucous hypersecretion Look at chest disease lecture LABA and LAMA+ ICS
