Case 2 Flashcards
what is bronchial asthma
a disease characterised by widespread narrowing of the peripheral airways varying in severity over short periods of time either spontaneously or in response to treatment
childhood asthma is:
extrinsic, atopic and mediated by antigens
adult asthma is:
intrinsic, idiosyncratic and mediated by neurological reflexes
some specific triggers of asthma are:
- excreta of house dust mites
- pollens
- exercise or emotion
- cold air
- animal fur
- respiratory tract infections
features of an asthmatic airway
- hypertrophy and hyperplasia of smooth muscle
- absence of ciliated epithelium
- thickened basal membrane
- mucus plug
what is there almost a complete loss of in airways of asthmatic patients
epithelium
first part of the role of a leucocyte:
- allergen attaches to macrophage (antigen presenting cell)
- then activates CD4+, Th2 lymphocyte
the pathway from activated lymphocyte IL4
- interleukin 4
- b lymphocyte then differentiates into a plasma cell
- secretes the IgE antibody
pathway from lymphocyte to IL5
- IL5 activates eosinophils and mast cells with IgE antibody
allergen induced release of mediators from sensitised mast cells
- the mast cell bears the IgE antibody
- there is a release of early mediators including eosinophil chemotactic factor
- released of later mediators (synthesised de novo)
allergen induced release of mediators from sensitised eosinophils
- eosinophil bearing the IgE antibody
- it releases the major basic protein
- leads to epithelial desquamation
what are the pre-formed mediators of a mast cell
- histamine
- proteases
- proteoglycans
- chemotactic factors
what are the later mediators of a mast cell derived from membrane lipids
- leukotrienes
- prostaglandins
- thromboxanes
- prostacyclin
effect of histamine on bronchial asthma
contraction of airways smooth muscle, increases vascular permeability and increased bronchial secretions
effect of chemotactic factors on bronchial asthma
- infiltration of airway wall by neutrophils and eosinophils
effects of leukotriene, C4, D4, E4 and prostaglandin D2
- contraction of airways smooth ,muscle, increased permeability and increased bronchial secretions
- major basic protein from eosinophils: epithelial desquamations
- B-cell activating factor: much later mediator
efficacy
efficacy is the tendency of the drug to activate the receptor. drugs with maximum efficacy are termed as full agonists. antagonists on the other hand have zero efficacy. when they bind, they do not active the receptor they just simply block the activity of an agonist
is efficacy released to affinity
no. affinity tells us how tightly something binds, and both agonists and antagonists have affinity
what does the Functional Gaddum Equation do
describes the effect produced by agonist D in the precedes of a competitive antagonists 1
what is a partial agonist
is a drug that cannot fully activate a receptor, even when all the receptors in a system are occupied.
how do partial agonists differ from full agonists
they have lower efficacy. not related to potency.
what is a superagonist
simply a drug who’s efficacy exceeds that of a full agonist (natural)
what is conformational selection
when a receptor visits the active site in the presence of a full agonist, the agonist binds and ‘locks’ it in the active state.
action of antagonists
they bind equally as tight to the inactive and active states. this prevents activation by agonists because of competition but the ramifications are a bit deeper.
what is a partial agonists
molecule that binds tighter to the active state than the inactive, but does not select between the two states as much as a full agonist does. the efficacy of a partial agonist depends on the ratio of inactive/active
what kind of control are smooth muscle conducting airways under
autonomic control
innervation of the diaphragm
phrenic nerve, cervical plexus (C3-C5)
Innervation of intercostal muscles
innervation of intercostal muscles
T1-T12
innervation of abdominal muscles
thoracic and lumbar
automatic respiratory rhythm generation model
- respiratory pacemaker in the medulla - will generate a respiratory rhythm in isolation, with no input
- pacemaker -> ‘pattern generation’ -> output to pump muscles and upper airways
what is the pacemaker region
pre-botzinger
sensory inputs to the respiratory centres
- peripheral chemoreceptors
- carotid bodies and aortic arch
- arterial stimulus
other sensory inputs to the respiratory centre
central chemoreceptors
- located on the surface of the medulla
sensory input from lungs, airways and chest wall
- nose - trigeminal (V)
- pharynx - glossopharyngeal (IX) and vagus (X)
- lungs - vagus (X)
- chest wall - spinal nerves
stretch receptors
predominantly in the trachea and main bronchi
- repsond to lung inflation
irritant receptors
- naso-pharync, larynx, bronchi and trachea
- mechanical, chemical irritant stimuli and inflammatory mediators
C-fibres
- receptors ‘free’ nerve endings
- larynx, trachea, bronchi , lungs (J-receptors)
- chemical irritant stimuli, inflammatory mediators and lung oedema (J-receptors)
normal range of values of blood gases while breathing air
Hb - 23.3-17.7 g/dl
pH - 7.37 - 7.45 units
PCO2 - 4.7-6.4 kPa
PO2 - over 10.7 kPa
calculated base excess values:
-2 to +2 mmol.l-1
acidosis
Respiratory: increased PCO2
Metabolic: decreased HCO3-
alkalosis
respiratory: deceased PCO2
metabolic: increased HC03-
Type 1 respiratory failure
- hypoxaemic failure
- low PaO2
- normal or low PaC02
- disturbance of the relationship of ventilation to perfusion
- mismatch of regional perfusion and ventilation
type II respiratory failure
- ventilatory failure
- low Pa02 and raised PaC02
- alveolar ventilation is reduced
- if type I and II are present together this is known as mixed respiratory failure
which genes are associated with asthma
- ADAM33 gene is associated with airway hyper-responsiveness and airway remodelling
- PHF11 gene is associated with increased IgE production
effect of cold air and exercise
- these both dry out the mucosa of the lung
- makes the lining hypersomolar
- causes mast cells to release histamine and prostaglandins, thus causing inflammation
Peak Expiratory Flow
- most useful test in asthma. patients should take two readings per day, to show the variability of the disease. in patients with suspected asthma, you should get them to take two weeks worth of measurements whilst at work, and 2 weeks whilst at home to prove the cause of the disease.
spirometry
you can show the presence of asthma by demonstrating 15% improvement in FEV1 or PEF
exercise tests
often used to diagnose asthma in children. run on a treadmill for max. 6mins and increase heart rate to over 160bpm. test peak flow before and after looking for a 15% difference
four principles of motivation interviewing
- express empathy
- develop discrepancy
- roll with resistance
- supporting self efficacy
what is self efficacy
a concept that refers to an individuals belief in their capacity to execute behaviours necessary to produce specific performance attainments. self efficacy effects every area of human endeavour. confidence in your own ability.
what is the major basic protein secreted by
IgE activated eosinophils and stimulates epithelial desquamation
what is the most common side effect of using the beta2 agonist inhaler
tremors
what is the Henderson hasselbalch equation used for
to calculate blood pH and estimated HCO3- concentration
what is the DRG inhibited by
signals from the pneumotacix centre
what are the stimuli that the central chemoreceptors in the ventral side of the medulla respond to
H+ increase
what is trans pulmonary pressure
measurement of the strength of the elastic forces in the lungs
the cellular levels of what is measured to aid in the diagnosis of asthma
eosinophils
how many people die from asthma every year
500,000
what happens in extrinsic asthma
allergens bind to IgE causing a reaction
what inhibits leukocyte infiltration
beclomethasone
what kind of antagonist is Ipratropium
muscarinic receptor antagonist
what is the risk ratio in meta analyses
the probability of an event occurring in the treatment group compared to the probability in the control
allergic asthma
- when a person is first exposed to an allergen it interacts with B lymphocytes
- these cells respond to the allergen by making immunoglobulin E
- releases into the circulation
- the response also involves tissue mast cells which are present in the lungs
- these are a type of granulocyte secreting cells which are rich in inflammatory mediators
- mast cells also have Fce receptors on cell surface
- these receptors have a high affinity binding site for IgE
- the circulation IgE made by the B cells can bind to these receptors
- the interaction is irreversible to when mast cell is next exposed to the allergen, it reacts
- by binding to the Fc receptors, the allergen crosslinks them, causing them to activate and trigger the degranulation of the mast cell
mediators released from mast cells
- chemokine: attract inflammatory cells to the area
- bronchoconstrictors: contract the airways and limit airflow
what do bronchodilators do
drugs that relax the smooth muscle, causing the lumen of the bronchiole to open. they are used as relievers to reverse bronchocontriction during an acute asthma attack
beta2 adrenergic receptor agonists
- bind to and activate the beta2 subtype of adrenoceptor
- their main effect on these receptors in smooth muscle cells is to evoke muscle relaxation
where are beta2 adrenergic receptors found
on mucous glands in the bronchiole walls and on ciliated epithelial cells that line the lumen of the bronchioles
what is the tidal volume
the volume of air displaced between normal inspiration and expiration, around 500ml
what is the inspiratory reserve volume
the extra volume of air that can be inspired over and about the normal tidal volume the. a person inspires with full force, around 3000ml
what is the expiratory reserve volume
maximum extra volume of air that can be expired by forceful expiration after the end of a normal tidal expiration, around 1100ml
what is the residual volume
the volume of air remaining in the lungs after the most forceful expiration, around 1200ml
what is the maximum volume
tidal volume + inspiratory reserve volume + expiratory reserve volume + residual volume
equation of the inspiratory capacity
tidal volume + inspiratory reserve volume
equation of the functional residual capacity
expiratory reserve volume + residual volume
equation of the vital capacity
inspiratory reserve volume + tidal volume + expiratory reserve volume
equation for the total lung capacity
inspiratory reserve volume + tidal volume + expiratory reserve volume + residual volume
what is the rate of diffusion of a gas directly proportional to
the pressure caused by that gas alone, the partial pressure
what is Henry’s Lae for partial pressure
the concentration of dissolved gas over the solubility coefficient
what are the different layers In a respiratory membrane
- layer of fluid lining the alveolus and containing surfactant
- the alveolar epithelium composed of thin epithelial cells
- an epithelial basement membrane
- thin interstitial space
- capillary endothelial membrane
factors that affect rate of diffusion though the respiratory membrane
- the thickness of the membrane
- the surface area of the membrane
- the diffusion coefficient of the gas in the substance of the membrane
- the partial pressure difference of the gas between the two sides of the membrane
what is the diffusion rate
(partial pressure difference x cross sectional area x solubility) / (distance x /molecular weight)
what is the diffusing capacity for oxygen in a man
21ml/min/mmHg
what is ventilation
aeration of the lungs
what is perfusion
blood flow to the lungs
how is the ventilation/perfusion ratio expressed
Va/Q
normal venous blood gases
PO2 - 40mmHg
PCO2 - 45mmHg
alveolar blood gas values
PO2 - 104mmHg
PCO2 - 40mmHg
what causes vasoconstriction at the start of exercise
sympathetic nervous system
conditions when exercise starts and continues
starts of as anaerobic and then with sufficient oxygen levels the condition become aerobic
what is the shunt flow
the small amount of blood in the bronchial circulation, that supplies the lungs with blood and isn’t exposed to air
what is the upper limit to which PO2 can rise in tissues
95mmHg
carbon dioxide can diffuse how much more rapidly than oxygen
20 times
how much oxygen is carried in chemical combination with haemoglobin in arterial blood
97%
which part of haemoglobin does oxygen combine with
haem
how is carbon dioxide usually transported
as carbonic acid
what is the Bohr effect
an increase in carbon dioxide in the blood causes oxygen to be displaced from the haemoglobin
what is hypercapnia
excess carbon dioxide in the body fluids
what happens if the base excess is out of the normal range
the condition is metabolic and not respiratory
three characteristics of asthma
- airflow limitation
- bronchial hyper-responsivness
- inflammation of the bronchi
how does aspirin trigger asthma
inhibits the cyclooxyrgenase pathway of arachidonic acid metabolism without affecting the lipoxgenase route, thus tipping the balance toward elaboration of the bronchoconstrictor leukotriene
how does propranolol trigger an asthma attack
it is a sympatholytic non-selective beta blocker. it inhibits postganglionic functioning of the sympathetic nervous system. in this case it is achieved through blocking beta adrenergic receptors.
early phase reaction of asthma
- the initial sensitisation to inhaled allergens stimulates the induction of the Th2 cells
- Th2 cells secrete cytokines that promote allergic inflammation and stimulate B cells to produce IgE and other antibodies.
how long does the sensitisation phase take
10-15 of IgE loading
what do mast cells secrete during degranulation
histamine, proteases, neutrophil chemotactic factor and eosinophil chemotactic factor
why are cytokines secondary mediators
they are not preformed
what is eotaxin
produced by airway epithelial cells, potent chemoattractant and activator of eosinophils
what are spiral shaped mucus plugs called
Curschmann Spirale
how many hospital addmitances are due to non-adherence
10-25%
when is it likely that a patient with adhere to treatment
when they understand what they are being asked to do and why
when are patients most likely to adhere to a drug PtII
when they remember what they are being asked to do if they are to act on it later and also satisfaction with the doctor and the consultation makes adherence more likely
systemic biases in risk perception
- compression: overestimate low risks, underestimate high ones
- miscalibration: overestimate accuracy of own knowledge
- availability: overestimate notorious risks
- optimism: underestimate a person’s susceptibility
what is theory of planned behaviour affected by
- attitude towards a behaviour
- subjective norm
- perceived behavioural control
if an inhaler is used correctly how much of the dose will be deposited in the lung
10%
