What is Hypoxia?
[*] a fall in alveolar, thus arterial pO2. pO2 may vary over quite a range around the normal value of 13.3 kPA without any alteration in the degree of saturation of the pigment
Explain about Hypocapnia and Hypercapnia
[*] Hypercapnia: a rise in alveolar, and hence arterial pCO2
[*] Hypocapnia: a fall in alveolar, and hence arterial pCO2
- The alveolar pCO2 has a very important role as CO2 forms part of the principal system controlling acid base balance.
- The pH of hydrogen carbonate/dissolved CO2 solution is determined by the Henderson-Hesselbalch equation: pH = pK + log ([HCO3-]/(pCO2 x 0.23))
- pCO2 x 0.23 = [dissolved CO2] when pCO2 is in kPa
- [Dissolved CO2] is therefore determined by the partial pressure of CO2, as the solubility is fixed
- Crucially therefore the pH is determined by the ratio of [HCO3-] to pCO2 which is normally about 20:1 – not on their absolute values
- Changes in pCO2 therefore affect pH of arterial blood.
- Changes in pCO2 may be used to compensate for changes in pH consequent upon alteration of [HCO3-] (e.g. if metabolic acid is buffer). pCO2 therefore needs to be controlled to keep pH stable, but may itself be used to control pH changes brought about in other ways.
- The kidneys also control [HCO3-} by variable excretion and synthesis so they may compensate for persisting changes in pCO2 by altering [HCO3-]
Describe hypoventilation and hyperventilation
[*] Hypoventilation: removal of CO2 from lungs is less rapid than its production – the inability to normally ventilate the lung; ventilation decreases with no change in metabolism (breathing less than you actually have to)
[*] Hyperventilation: removal of CO2 from lungs is more rapid than its production; ventilation increases with no change in metabolism (breathing more than you actually have to)
NB: in exercise, ventilation increases because metabolism increases (not hyperventilation)
Describe the effects of plasma pH on hyper- and hypo- ventilation
[*] pCO2 affects plasma pH (Henderson-Hasselbach): pH = 6.1 + log ([HCO3-] / (pCO2 x 0.23))
[*] Hyperventilation: pCO2 decreases, (pO2 increases), pH increases
[*] Hypoventilation: pCO2 increases, pH decreases
Describe the general effects of acute hypo- and hyper-ventilation
[*] Acute hypoventilation
- Hypercapnia and Respiratory Acidosis
- pH falls below 7.0
- Enzymes become lethally denatured
[*] Acute hyperventilation
- Hypocapnia and Respiratory Alkalosis
- pH rises above 7.6
- Free calcium concentration falls enough to produce fatal tetany. Ca2+ is only soluble in acid, so when pH rises, Ca2+ cannot stay in the blood. Nerves become hyper-excitable
- Voluntary hyperventilation (panic attack) is very common – twitches, tremors, can be dangerous
Define the terms ‘Respiratory Acidosis’, ‘Respiratory Alkalosis’, ‘Compensated Respiratory Acidosis’ and ‘Compensated Respiratory Alkalosis’
[*] Respiratory Acidosis: hypoventilation (CO2 is produced more rapidly than it is removed by the lungs) can lead to alveolar pCO2 rising (hypercapnia) so [dissolved CO2] rises more than [HCO3-} producing a fall in plasma pH.
[*] Compensated Respiratory Acidosis: if respiratory acidosis persist, the kidneys respond to low pH by reducing excretion of HCO3- restoring the ratio [Dissolved CO2]/[HCO3-], and the pH, near to normal. This takes 2-3 days.
[*] Respiratory Alkalosis: hyperventilation (CO2 is removed from alveoli more rapidly than it is produced) can lead to alveolar pCO2 falling, disturbing the ratio of [Dissolved CO2] to [HCO3-] so plasma pH rises.
[*] Compensated Respiratory Alkalosis: If respiratory alkalosis persist, the kidneys respond to the high pH by excreting HCO3- so the ratio [Dissolved CO2]/[HCO3-] returns near to normal, and therefore pH is restored, but buffer base concentration is reduced. This takes 2-3 days
Define the terms ‘Metabolic Acidosis’, ‘Metabolic Alkalosis’, ‘Compensated Metabolic Acidosis’, ‘Compensated Metabolic Alkalosis’
[*] Metabolic Acidosis: metabolic production of acid by the tissues => hydrogen carbonate is displaced from plasma as the acid is buffered therefore the pH of blood falls. This is a reduction of buffer base – metabolic acidosis.
Acid normally reacts with HCO3- in capillaries => breathed out
[*] Compensated Metabolic Acidosis: the ratio [Dissolved CO2]/[HCO3-] may be restored near the normal by lowering pCO2 (increased ventilation by the lungs), correcting pH, but the depletion of buffer base remains, until corrected by the kidney
[*] Metabolic Alkalosis: metabolic production of hydrogen carbonate => hydrogen carbonate is retained in the plasma therefore the pH of blood rises e.g. after vomiting
[*] Compensated Metabolic Alkalosis: the ratio [Dissolved CO2/HCO3-} may be restored near the normal by increasing pCO2 (decreased ventilation by the lungs), correcting pH but the alkalosis (excess of buffer base) is corrected by the kidney
Decreased ventilation generates a problem itself as it is reducing our oxygen intake
Describe the acute effects of falling inspired pO2
- Alveolar pO2 may vary considerably without affecting oxygen transport, though if it falls a great deal serious problems occur. We do not need to control pO2 precisely but must keep it above 8kPa
- Inspired pO2 is an insignificant influence upon respiration until it has fallen significantly but only small increases in inspired pCO2 produce large increases in ventilation rate
- The falling arterial pO2 is detected by Peripheral Chemoreceptors located in the Carotid and Aortic bodies
- The carotid and aortic bodies are stimulated by a decrease in oxygen supply relative to their own oxygen usage which is small. They only respond to large drops in O2.
- Stimulation of the receptors:
- Increases the tidal volume and rate of respiration (increased breathing)
- Changes in circulation directing more blood to the brain and kidneys
- Increased pumping of blood by the heart (increased heart rate)
Describe the acute effects of increasing inspired pCO2
[*] We need to control pCO2 precisely to avoid acid base problems. The alveolar pCO2 markedly affects plasma pH and disturbances of pH arising from persisting alterations of pCO2 are slowly corrected by the kidneys (through reduced/increased excretion of HCO3-)
[*] Sometimes ventilation is changed to correct metabolic disturbances of pH.
[*] Changes in pH following metabolic production of acid or alkali may be corrected by alteration of alveolar pCO2
- The peripheral chemoreceptors in the carotid and aortic bodies also detect changes in pCO2 but are insensitive
- Central chemoreceptors in the medulla of the brain are much more sensitive, altering breathing on a second to second basis.
- Central chemoreceptors detect changes in arterial pCO2
- Small rise in pCO2 would increase ventilation
- Small fall in pCO2 would decrease ventilation
- Are the basis of negative feedback control of breathing
Describe the acute effects of falling arterial plasma pH
- Metabolic Acidosis: metabolic production of acid displaces HCO3- from plasma as the acid is buffered; therefore the pH of blood falls.
- Compensated Metabolic Acidosis: the rate of [Dissolved CO2] to [HCO3-] may be restored to near normal by lowering pCO2 through increasing ventilation to correct pH.
Describe the location and function of the peripheral chemoreceptors and their role in the ventilator and other responses to Hypoxia
[*] The arterial pO2 must be detected by chemoreceptors. Receptors sensitive to falling pO2 are located in the carotid bodies and aortic bodies
[*] The carotid and aortic bodies are stimulated by a decrease in oxygen supply relative to their own oxygen usage which is small.
[*] A high rate of blood flow through the structures ensures that they do not normally change their response until the pO2 is low. They only respond to large drops in O2.
[*] Stimulation of the receptors has a variety of effects
- Increase in tidal volume and rate of respiration
- Changes in circulation directing more blood to brain and kidneys
- Increased pumping of blood by the heart
[*] They have slight tonic (continuous) activity and only respond to large falls in pO2 but they do not adapt.
[*] There is a respiratory drive as long as pO2 is low.
Describe the location and function of the central chemoreceptors
[*] Chemoreceptors sensitive to raised pCO2 are located both in the carotid and aortic bodies – the peripheral chemoreceptors, as well as in the medulla – the central chemoreceptors.
[*] Peripheral chemoreceptors are not particularly sensitive, needing a rise of 1.3kPA in pCO2 to stimulate them, whereas the whole animal responds to a rise of 0.3kPa. They are not crucial for the precise regulation of respiration but do respond QUICKLY to large changes in pCO2. Central Chemoreceptors are much more sensitive, altering breathing on a second to second basis
- Small rise in pCO2 leads to increased ventilation
- Small falls in pCO2 lead to decreased ventilation
[*] Central Chemoreceptors are located on the ventral surface of the medulla and exposed to the cerebro-spinal fluid. They respond to a fall in CSF pH.
Describe the central chemoreceptors' role in the ventilatory respiratory to changes in arterial pCO2 and the roles of the cerebro-spinal fluid, blood brain barrier and choroid plexus in that response
- The CSF is separated from the blood by the Blood Brain Barrier, which allows free passage of CO2 but not HCO3- or H+.
- The pH of the CSF is determined by its own hydrogen carbonate / carbonic acid buffer system.
- No haemoglobin in CSF
- CSF [HCO3-] is determined by the activity of choroid plexus cells which pump HCO3- into and out of the CSF and is largely independent of plasma [HCO3-]
- CSF [Dissolved CO2] is determined by plasma pCO2 although rapid changes in plasma pCO2 take time to influence CSF [Dissolved CO2]
- Just as in plasma, therefore, CSF pH and thus the stimulus to the chemoreceptors is determined by the ratio of [HCo3-] to [Dissolved CO2]
- [*] If arterial pCO2 changes, then after a short delay, CSF pCO2 will follow. This leads to changes in CSF pH which are sensed by central chemoreceptors => normally producing changes in breathing which tend to restore CSF pH (i.e. if pCO2 rises, ventilation increases to lower pCO2 again). This negative feedback is the principal means by which ventilation is controlled.
What happens if this negative feedback doesn't occur?
[*] If the negative feedback doesn’t occur e.g. due to an additional stimulus to ventilation from hypoxia, or because of disease of the lung, persisting changes in CSF pH stimulate the choroid plexus cells to pump more or less hydrogen carbonate into the CSF and change [HCO3-] to bring the ratio [HCO3-]/[Dissolved CO2] back towards normal.
Why is CSF pH corrected more quickly than blood pH?
[*] CSF is corrected much more quickly than blood pH because of its small volume. As CSF pH is corrected, changes in ventilation driven by alteration of pCO2 disappear and the control system is ‘reset’ to operate around a different pCO2.
- In the short term, [HCO3-} is fixed (cannot cross BBB) so falls in pCO2 lead to increased pH and rises in pCO2 lead to lower pH.
- If pCO2 remains altered for any length of time, the activity of the choroid plexus cells serves to ‘reset’ the system to control around a different pCO2: as long as CSF returns to normal, you stop feeling breathless – central chemoreceptors are happy. Over a slightly longer time scale, kidneys change [HCO3-] so you can live with higher plasma CO2 in the long term (but body does not tolerate short term variations)
- Long term changes: persisting hypercapnia, persisting hypoxia
Describe hypoxia (think about the oxygen transport chain, the carbon dioxide transport chain etc)
[*] The steps in the chain of oxygen supply: air => airways => alveolar gas => alveolar membrane => arterial blood => regional arteries => capillary blood => tissues
- The oxygen content of arterial blood depends on the pO2 and the Hb content of blood
- The delivery of oxygen to the tissues depends on the cardiac output and a normal vascular system permitting normal perfusion of tissues.
- The steps in the carbon dioxide transport chain: Tissues => Capillary blood => Region veins => Venous blood => Alveolar membrane => Alveolar gas => Airways => Air
Describe ventilation and gas exchange briefly
[*] NB: there are no exhaust valves so the values of pO2 and pCO2 are different in air and atmospheric air because of inspired and expired gases mixing in the same tube – ventilation is not 100% efficient.
[*] Gas exchange in normally 100% efficient so same values for alveolar air and arterial blood.
What could hypoxia be caused by?
- Poor ventilation and perfusion matching (V/Q mismatch)
- Diffusion impairment
- Low inspired pO2: this occurs in people acutely exposed to high altitudes where the atmospheric pressure is less than 101 kPa as would occur if a passenger airplane cabin becomes depressurised or in acute mountain sickness. People who live at high altitudes have numerous physiological adaptations to survive in these conditions such as polycythaemia (increased Hb), increased red cell 2-3 DPG and increased capillary density in tissues
- Right to left shunts (revise CVS!!)
Describe Types 1 and 2 Respiratory Failure
[*] Respiratory failure is usually said to exist when the arterial pO2 falls below 8kPa (60 mmHg) when breathing air at sea level
- Not enough oxygen enters the blood
- Not enough CO2 leaves the blood
- Do not necessarily occur together
[*] Type 1 Respiratory failure: low pO2 (<8kPa) with a normal or low pCO2 (CO2 removal not compromised but not enough oxygen enters the blood)
- Breathlessness, exercise intolerance, central cyanosis (of the tongue, mucous membranes – in mouth)
- Daily tasks e.g. getting out of bed can be challenging, very disabling
- May not be able to walk very far
[*] Type 2 Respiratory failure: low pO2 (<8kPa) with a high pCo2 of > 6.7 kPa (50 mmHg) (not enough oxygen enters the blood, not enough CO2 leaves it)
What could cause hypoventilation?
[*] The muscles of respiration’s movement is involuntary and depends on impulses which originate in the respiratory centre in the brain stem, and travels via the spinal cord, spinal and peripheral nerves and the neuromuscular junction to reach these muscles.
[*] Causes of hypoventilation – ineffective respiratory effort:
- Respiratory centre depression; e.g. Head injury, drug overdose (narcotics – opioid analgesics – adverse drug reaction)
- Respiratory muscle weakness due to damage/disease of any part of nerve pathways from the respiratory centre to the muscles of respiration (e.g. brain stem / spinal cord/ intercostal nerves/ phrenic nerve / neuromuscular junction / muscle disease)
- Chest wall problems (mechanical problems) e.g. scoliosis /kyphosis, morbid obesity, rib fractures, pneumothroax
- Hard to ventilate lungs due to severe lung fibrosis or widespread severe airway obstruction (life threatening asthma, late stages of COPD)
What could cause ventilation/perfusion mismatch?
Ventilation /perfusion mismatch (Type 1 respiratory failure – pCO2 is low/normal)
- Reduced ventilation of some alveoli: lobar pneumonia
- Reduced perfusion of some alveoli: pulmonary embolism
[*] Reduced ventilation causes a drop in alveolar pO2 due to low ventilation (V): perfusion (Q) ratio (low V/Q ratio) of these alveoli. The blood draining these alveoli is poorly oxygenated, causing a low pO2 in the blood reaching the left side of the heart.
[*] Causes of reduced ventilation:
Early stages of Acute Severe Asthma
Respiratory distress syndrome of newborn (collapse of some alveoli due to lack of surfactant)
[*] Reduced perfusion of some alveoli, usually due to pulmonary embolism, causes diversion of blood to other parts of the pulmonary circulation.
The extra blood flow (increased perfusion Q) is not matched by the ventilation (V) of these alveoli. The reduced V/Q ratio causes the alveolar pO2 to fall and the blood draining these alveoli is poorly oxygenated, causing a low pO2 in the blood reaching the left side of the heart.
Poor O2 uptake in some alveoli cannot be compensated by increased uptake in others (the other alveoli are already working at full saturation – 100% efficiency)
[*] In either situation, the drop in pO2 in areas with a low V/Q ratio cannot be compensated by extra oxygen uptake by blood at better ventilated alveoli with a high V/Q ratio, due to nature of the oxygen Hb dissociation curve which means that blood (Hb) becomes fully saturated with O2 at a pO2 of 13.3 kPa and cannot further increase its O2 content despite exposure to higher alveolar pO2 levels.
Poor O2 uptake in some alveoli cannot be compensated by increased uptake in others, whereas low pCO2 removal in some alveoli can be compensated by increased CO2 washout in other alveoli, as CO2 easily diffuses across alveolar capillary membrane and pCo2 removal is not limited. Hence ventilation-perfusion mismatch causes Type 1 Respiratory failure
What could cause diffusion impairment?
- Diffusion impairment (Type 1 respiratory failure – pCO2 is low/normal): O2 diffuses much less readily than CO2 so is always affected first
- Structural changes: lung fibrosis causing thickening of alveolar capillary membrane. Lung fibrosis could be due to fibrosing alveolitis, extrinsic allergic alveoltis, pneumoconiosis (disease of coal miners), asbestosis
- Increased path length: pulmonary oedema
- Total area for diffusion reduced: emphysema
- Normally involves most of the alveoli
- The barrier to diffusion between alveolar air and pulmonary capillary blood is normally very small (<1 micron).
- Diffusion may be impaired if the barrier is thicker (as in lung fibrosis) or the diffusion pathway lengthens as in pulmonary oedema where the extra layer fluid increases the distance across which gases have to diffuse.
- Diffusion may also be impaired if the total area available for diffusion is reduced (even though the barrier itself is normal) as happens in emphysema
- O2 diffuses much less readily than CO2 and so it is always affected more by any change to the diffusion barrier. Therefore diffusion impairment causes Type 1 Respiratory failure with hypoxia with a normal or low pCO2.
Describe the normal ventilation-perfusion ratio in the lung
- Ideal ratio should be 1
- At the apex of the lung, ratio is 3.3 which indicates ventilation is too much for perfusion - blood flow is low partly due to upright posture (effect of gravity)
- For most of the lung, ideal ratio is 1
Describe measurement of oxygen saturation and blood gas analaysis
[*] Oxygen Saturation of haemoglobin in arterial blood (SaO2) can be measured by a pulse oximeter
- Device uses infrared light to measure amount of oxygenated haemoglobin
- SaO2 > 95% (97% is normal)
- Very useful for monitoring patients
[*] Blood Gas Analysis
- Arterial blood sample obtained by arterial stab radial artery usually used)
- Sample put through a blood gas analyser
- Blood has to be heparinised or treated with some other anti-clotting agent to prevent blood clotting
- Blood must be sealed properly to prevent gas mixing with atmosphere.
- Normally stored in ice cold water to limit gas diffusion
Describe how hypoventilation results in type 2 respiratory failure
[*] Hypoventilation leads to hypoxia and hypercapnia, as the movement of both O2 into and CO2 out of lungs is affected => hence causes Type 2 Respiratory failure.
[*] Acute (or acute on chronic) Type 2 Respiratory Failure: develops over hours, days, or weeks, usually requires urgent ventilator support as the hypoxia and hypercapnia are life threatening
[*] Chronic Type 2 Respiratory Failure: develops very gradually over a long period of time (e.g. COPD worsening over years), allows time for some compensatory mechanisms to develop which allows the hypoxia and hypercapnia to be tolerated better.
- These patients manage without ventilation initially (though often needing ventilation to tide over acute complications such as lung infections), BUT as the disease progresses they too eventually require ventilatory support
- They show features of chronic CO2 retention and chronic hypoxia
What is Chronic CO2 Retention and Chronic Hypoxia?
[*] Chronic CO2 retention: in persistent hypercapnia, the choroid plexus imports HCO3- into the CSF which restores the CSF pH to normal and results in the central chemoreceptors being ‘reset’ (adapted to the higher CO2 level) so they become unresponsive to the current level of CO2.
- The hypoxic stimulus persists and respiration is now driven by hypoxia (via peripheral chemoreceptors)
- This is clinically important, as oxygen therapy which corrects the hypoxia, removes the stimulus for respiration and may lead to respiratory depression with a reduction in the rate and depth of respiration. Therefore these patients should receive 24% or 28% oxygen if required, and their condition monitored for respiratory depression
- Features of CO2 retention include warm hands and a bounding pulse, due to vasodilatation and flapping tremors.
[*] Chronic hypoxia leads to polycythaemia (increased Hb level) due to increased erythropoietin secretion and an increase in red cell 23 DPG (allows better unloading of O2)
- Also leads to hypoxia induced vasoconstriction of pulmonary arterioles which eventually leads to pulmonary hypertension and right heart failure (cor pulmonale)
- Also leads to increased ventilation and renal correction of acid-base balance (increased anaerobic acid – lactate acid production over time)
Chronic Respiratory failure is severely disabling
Briefly describe Emphysema
- Destruction of lung tissue (alpha1-antitrypsin)
- Changes in compliance – lungs become more elastic
- Ventilation perfusion mismatch
- Affects oxygen supply
- Type 1 failure initially – as it progresses, it becomes more Type 2
Interpret uncomplicated blood gas abnormalities
[*] Type 1 Respiratory Failure:
- Respiratory rate increases
- pO2 decreases
- CO2 stays the same or decreases
[*] Type 2 Respiratory Failure:
- Respiratory rate increases
- pO2 decreases
- CO2 increases
[*] Type 2 respiratory failure (low pO2 and a high pCO2 on Arterial Blood Gas analysis) indicates the presence of hypoventilation and should always prompt the question of whether urgent ventilator support is needed
Define asthma and describe the nature of the airflow obstruction in asthma
[*] Asthma is a chronic inflammatory disorder of the airways, particularly affecting the smooth muscle layer. In susceptible individuals, inflammatory symptoms are usually associated with widespread but variable airflow obstruction and an increase in airway responsiveness to a variety of stimuli. Obstruction is often reversible, either spontaneously or with treatment.
[*] 5 Defining Characteristics:
- Chronic inflammatory process (airway wall inflammation and remodelling)
- Variable airflow obstruction
- Airway hyper-responsiveness to a variety of stimuli
[*] Airways in asthma have thickened smooth muscle and basement membranes
[*] Triggers cause the airway smooth muscle to contract, reducing airway radius, increasing resistance and reducing airflow
[*] NB: airways obstruction is a feature of both Asthma and Chronic Obstructive Pulmonary Disease (COPD). The main difference is that the airway obstruction is often reversible in asthma (>15% improvement either spontaneously or with bronchodilators or steroids) and not fully reversible in COPD (<15% improvement with treatment)
Describe, in outline, the pathophysiology of asthma
[*] Chronic inflammatory process driven by TH2 cells
[*] Macrophages process and present antigens to T lymphocytes, activating T cells with TH2 cells being preferentially activated
[*] TH2 cells release cytokines which attract and activate inflammatory cells, including mast cells and eosinophils. TH2 cells also activate B cells, which produce IgE.
[*] Typically for a sensitized atopic asthmatic, exposure to antigen results in a 2 phase response consisting of an immediate response (reaching maximum in about 20 minutes) followed by a late phase response (3-12 hours later)
- The immediate response is an example of type 1 hypersensitivity. It is caused by interaction of the allergen and specific IgE antibodies, leading to mast cells degranulation and release of mediators (histamine, tryptase, prostaglandin D2 and leukotriene) which cause bronchial smooth muscle contraction => bronchoconstriction
- The late phase response is an example of type IV hypersensitivity. It is complex, involving the full spectrum of inflammatory cells, including eosinophils, mast cells, lymphocytes and neutrophils which release an array of mediator and cytokines, which cause airway inflammation.
The eosinophils release Leukotriene C4 and other mediators, some of which are toxic to epithelial cells, and causes shedding of epithelial cells.
Eosinophils are very sensitive to steroid therapy
What is airway narrowing due to?
[*] The airway inflammation causes reduced airway calibre (airway narrowing) due to:
- Mucosal swelling (oedema) due to vascular leak
- Thickening of bronchial walls due to infiltration of inflammatory cells
- Mucus overproduction; the mucus is also abnormal – thick, tenacious and slow moving. The cough is therefore usually dry or only productive of scanty, white sputum. In severe cases many airways are occluded by mucus plugs.
- Smooth muscle contraction
- The epithelium is shed and is incorporated into the thick mucus
- The inflammation also causes hyper-responsiveness of airways to nonspecific stimuli.
What could long term poorly controlled asthma lead to?
[*] Long term poorly controlled asthma can lead to airway remodelling, some of which may not be fully reversible. The changes include:
Hypertrophy and hyperplasia of smooth muscle
Hypertrophy of mucus glands
Thickening of the basement membrane
What are the effects of airway narrowing? (Including effects on gas exchange)
- Causes wheezing and other clinical features of asthma
- Results in an obstructive pattern on spirometry (decreases FEV/FVC ratio <70%) and typical flow volume loops; which shows reversibility with bronchodilators or over a period of time.
- Air trapping with increased residual volume
[*] Effect on gas exchange:
- Airway narrowing leads to reduced ventilation of the affected alveoli => this causes a ventilation/perfusion mismatch in the affected area
- Hyperventilation of better ventilated areas of the lung cannot compensate for the hypoxia, but can compensate for CO2 retention by increased breathing out of CO2.
- In mild to moderate asthma, you get decreased pCO2 and decreased O2 = type 1 respiratory failure
- In severe attacks (extensive involvement of airways; fewer unaffected areas where hyperventilation wash out CO2), and exhaustion (which limits respiratory effort), limits the amount of CO2 which can be breathed out, leading to a rise in CO2. Thus the blood gas analysis reveals increased pCo2 and decreased pO2 = type 2 respiratory failure
Therefore increasing pCO2 is a sign of life threatening asthma (Disease is severe and extensive and patient is exhausted – these patients often require assisted ventilation).
Describe the epidemiology of asthma
- Increasing in prevalence
- More common in the developed world
- Increasing in populations who move from developing to developed countries
[*] 5.4 million people in the UK currently receive treatment: 1.1 million children and 4.3 million adults
[*] Genetic risk
[*] Sensitisation to airborne allergens
- House dust mite
- Air pollution
- Tobacco smoke (pre-/post natal exposure, active)
- Hygiene hypothesis
What are the types of asthma?
- Allergic asthma: eosinophils, mast cells & IgE
- Viral-induced wheeze (most common in children under 5) (e.g. asthma symptoms with colds)
- “Aspirin-sensitive” asthma – adults only (aspirin are COX inhibitors – decreasing prostaglandin production, leading to overproduction of leukotrienes)
- Occupational Asthma (e.g. welders, farmers, bakers)
What are the triggers of an asthma attack?
[*] Triggers of an attack (airway wall smooth muscle contraction) include:
- Cold air
- Allergens – pollen, animals (animal hair / dander), house dust mite faeces
- Emotional distress
- Fumes – car exhaust, cigarette smoke, perfumes
- Chemicals – isocyanates and acid anhydrides (varnish/paint)
- Drugs – NSAIDS and beta blockers
- Because of airway hyper-responsiveness, non-allergic stimuli like cold air and fumes can also trigger attacks
- Arachadonic acid metabolites e.g. prostaglandins, Leukotrienes
[*] Although they may occur spontaneously, asthma exacerbations are most commonly caused by:
- Lack of treatment adherence
- Respiratory Virus infections associated with the common cold
- Exposure to allergen or triggering drug (e.g. NSAID)
How would you diagnose asthma? Describe the symptoms
[*] The diagnosis of asthma is a clinical one. There is no standard definition of the type, severity or frequency of symptoms, not of the findings on investigation.
[*] Asthma is defined as more than one of the following recurring symptoms:
- High pitched, expiratory, musical sound
- Wheeze originates in airways which have been narrowed by compression or obstruction
- In asthma the wheeze is of variable intensity and tone (polyphonic). Wheeze is bilateral.
- The wheeze changes; when there is severe constriction, you almost lose the wheeze. When the airways open up, wheeze gets louder
- Often worse at night (lack of sleep, poor performance at school)
- Exercise induced (decreased participation in activities)
- Dry cough (wet cough indicates infection or COPD)
- ? sputum production
- With exercise
- Objective assessment: tachypnoea, recession, tracheal tug
- Prolonged expiratory phase +/- wheeze
Variable Airflow Obstruction
[*] Airway hyper-responsiveness and airway inflammation are components of the disease and their assessment aids diagnosos
Describe the History of an Asthmatic
- Onset and pattern of symptoms including disturbance to everyday life, schooling etc, precipitating factors (cold air, exercise, laughing)
- Past medical history: hay-fever, eczema, birth, pre-natal smoke exposure, food allergies e.g. peanuts
- Family history: asthma, other atopic diseases, smoking
- Occupational history, home (farms, wood or coal-burning fires)
- Non-asthma drug history
- Previous treatment: appropriateness, compliance, technique, response
Describe the examination of asthma
- Scars, deformities
- Hyper-expansion (Barrel chest)
- Eczema, hay-fever
- Can they speak?
- Charts (look for trends)
- Polyphonic wheeze
Describe the cells involved in inflammation and what happens in remodelling
- Mast cells: increased in asthma, release prostaglandins, histamine etc
- Eosinophils: large numbers in the bronchial walls and secretions of asthmatics
- Dendritic cells and lymphocytes:
Dendritic cells have a role in the initial uptake and presentation of allergens to lymphocytes
T-Helper lymphocytes (CD4) release cytokines that play a key part in the activation of mast cells
TH2 phenotype favour the production of antibody production by B lymphocytes to IgE
[*] Airway remodelling
- Epithelium: stressed and damaged with a loss of ciliated columnar cells
- Basement membrane: deposition of collagens, causing it to thicken
- Smooth muscle: hyperplasia causing thickening of the muscle
Describe the tests used to assess the condition of a patient suspected of asthma, and how they are interpreted
[*] Spirometry – flow volume loop
- Low PEFR (peak expiratory flow rate)
- Low FEV1/FVC Ratio
- >12% increase in FEV1 following salbutamol
[*] Allergy Testing
- Skin prick to aero-allergens e.g. cat, dog, HDM
- Blood IgE levels to specific aero-allergens
[*] Chest X-Rays
- Performed to exclude other diseases/inhalation of foreign body / pneumothorax during severe acute exacerbations
- Generally normal in the chronic situation.
Describe patient education and primary prevention
[*] Patient education: educate patients to correctly recognise their symptoms, to use their medication timely, to use services appropriately and to develop their own Personal Asthma Action Plan
[*] Education of professionals: appropriate medication, concordance with treatment plans
[*] Primary Prevention
- Stop smoking (including parents)
- Fresh air
- Reduce exposure to allergens/triggers
- Weight loss (if overweight)
Explain about drug treatment in asthma
[*] important classes of drugs used in treatment, and inhalers are used to deliver the drugs in an aerosol form.
Airway relaxants (‘Reliever’ therapies – management of symptoms)
- B2 agonists (short and logn acting)
- Muscarinic antagonists
- Theophylline /Aminophylline
Anti-inflammatory agents (‘Preventer’ therapies – management of symptoms)
- Leukotriene Receptor antagonist
- To give patients opportunities e.g. being able to sleep through the night without coughing etc
Explain about the BTS Guidelines and why it's important to identify patients with acute severe asthma
[*] BTS Guidelines: A Stepwise Approach
- Start treatment at the step most appropriate to initial severity
- Achieve early control
- Maintain control by stepping up and stepping down treatment as necessary
- Before initiating any new drug, check compliance and technique
[*] It is vital to assess patients for features of acute severe asthma, which requires immediate treatment and hospitalisation. Treatment of acute severe asthma includes nebulised β2 agonists and ipratropium delivered in oxygen and intravenous steroids followed by a short course of high dose oral prednisolone. Other drugs such as magnesium sulphate and aminophylline may also be required.
- B2-adrenoagonists are muscarinic antagonists and provide short term relief e.g. Salbutamol
- Anti-inflammatory agents e.g. corticosteroids, preventer therapies
Explain about life-threatening asthma
[*] Patients with features of life threatening asthma need ITU management and may require ventilation.
- Saturations <92% in oxygen / cyanosis
- Silent chest / poor respiratory effort
- Altered consciousness / hyper-aggressive
- PEFR <35% of predicted
- Rising or ‘normal’ pCO2
- Poor asthma teaching is a common cause of death – patients haven’t had the education
What is the Acute Asthma Management Plan?
A – Oxygen
B – Continuous salbutamol and atrovent nebulisers
C – IV access
Intubate and ventilate
How can PEFR be used in diagnosis of asthma
Peak Expiratory Flow Rate
- Effort dependent, difficult to incentivise
- Ask patient to take a deep breath, close lips firmly around the mouthpiece and then blow out as hard as possible
- Takes <5 minutes
- Better for monitoring then diagnosing asthma
- Wide range of “normal values”
- No correction for ethnicity
- Less reproducible than FEV1
- Airway constriction => decreased PEFR
- NB: asthmatics typically show diurnal variation
How can spirometry be used in the diagnosis of asthma?
- Incentive Spirometry – Effort depedent
- Incentivised by (i) trained professional encouraging breaths (ii) visual cues
- 2 or 3 tidal breaths with lips around spirometer, deep breath to Total Lung Capacity and then …blow out hard as possible
- Repeat 3 or more times to achieve maximum of 5% variation from largest Full Vital Capacity
- Repeat post bronchodilator => bedside test of reversibility (15% improvement)
- Takes 5-30 mintues
- Normal FEVA/FVC values and spirometry does not exclude asthma – need to check reversibility
How can Airway Hyper-responsiveness be used in the diagnosis of asthma?
[*] BHR: Airway Hyper-Responsiveness: Exercise-induced Bronchoconstriction
- Perform pre-exercise spirometry
- Exercise 6-8 minutes, monitoring O2 and Heart rate
- Perform spirometry 1,5,10, and 15 minutes post exercise
- Repeat post bronchodilator
- Takes at least an hour to complete and another 15-30 minutes to output and interpret data
How can FENO be used in the diagnosis of asthma?
[*] FENO: enhaled NO
- Nice recommends FeNO testing as option to help diagnose asthma and should be done in combination with other diagnostic options according to the BTS.
- Further investigation is recommended for people whose FeNO test result is negative because a negative result does not exclude asthma.
- Takes 5 minutes
- Relatively expensive
NB: Sputum could also be used in the diagnosis of asthma
What are the diagnostic pillars?