Respiratory medicine Flashcards
What areas of the CNS control breathing?
There is a voluntary aspect of breathing controlled by the cerebral brain cortex
The brainstem is responsible for generating automatic rhythm. It has different interconnected neurones situated in the pons and the medlla. These have synapses with the respiatory muscles.
What are the three different types of receptors in the lung that influence breathing patterns?
Slowly adapting receptors= stretch receptors, stimulated by stretching of airway walls- initiates expiration.
Rapidly Adapting receptors= irritant receptors, respond to chemicals eg smoke, initiates cough, bronchoconstriction and mucus production
Bronchial C-fibre endings are stimulated by increase interstitial fluid (oedem) and inflammatory mediators.
What are the different conditions relating to abnormal oxygen and carbon dioxide levels?
What are chemoreceptors and where are they located?
Chemoreceptors are sensors that detect changes in CO2, O2, and pH
What is COPD?
COPD patients find it hard to exhale due to blockages in their airways and decreased elastic recoil
COPD is when the lungs fail to ventilate adequately and this causes hypoxia and CO2 buildup, causing chronic hypercapnia and loss of sensitivity of central chemoreceptors.
A COPD patient’s drive to breathing is controlled by hypoxia and their drive abolished if the patient is given high inspired O2.
What happens to breathing patterns whilst sleeping?
During sleep…
- Respiratory drive decreases
- there is a reduction in metabolic rate
- there is reduced input from higher centres such as pons and cortex
- patients with impaired ventilation first develop respiratory failure during sleep
What is phasic and tonic activity in lung breathing patterns?
Tonic activity= continuous background activity which tends to maintain patients airways and varies with the state of alertness.
Phasic activity is contraction of upper airway muscles, which opens the upper airways and facilitates inward airflow.
What is obstructive sleep apnoea?
During sleep, there can be a loss of tonic activity to upper airways which can collapse to give cessation to breathing
Causes fragmented sleep and daytime sleepiness
Risk factors are alcohol, nasal obstruction and anatomical anomalies.
How is the pressure gradient formed between the lungs and the atmosphere?
Gas moves along a pressure gradient which is achieved due to the thoracic cage.
Tension between lung elastic recoil (inward) and chest wall elastic recoil (outwards) that creates the pressure gradient between the alveoli and the atmosphere.
How do we inspire and expire?
INSPIRATION= The brain influences the external intercostal muscles which pull ribs upwards. This causes pleural space pressure to decrease and therefore decreases the alveolar pressure.
EXPIRATION= doesn’t require activity from the brain, lungs move inwards due to elastic recoil.
FORCED EXPIRATION= diaphragm moves upwards due to abdominal muscles contracting, internal intercostal muscles contract resulting in the ribs moving downwards.
What is the carbon dioxide/bicarbonate buffering system?
Dissolved CO2 is in equilibrium with carbonic acid ionised to give bicarbonate, which acts as a buffer to regulate the hydrogen ion concentration.
Why do we need to carry out gas transport?
In Oxidative metabolism, dietary fuels provide energy through their oxidisation by O2 to CO2. This generates ATP.
What is Henry’s law?
The concentration of a dissolved gas is directly proportional to its partial pressure.
What factors influence how fast a gas diffuses through a membrane?
- Difference in concentration on either side of the membrane
- the molecular size of the gas
- the solubility in the hydrophobic interior of the membrane
- membrane area
- membrane thickness
What are the effects of atmospheric nitrogen?
It has high atmospheric content, but low solubility in water. It has no biological role in humans but can dissolve in blood.
This can be a problem for divers under high pressure, there can be high dissolved concentrations which has an anaesthetic effect known as ‘nitrogen narcosis’, results in confusion.
How much oxygen is dissolved in plasma in the blood?
Oxygen has a partial pressure of 13.3kPa
1.5% is dissolved in plasma, rest is bound by haemoglobin
What is the structure of haemoglobin?
It is a tetramer, it contains 4 subunits- 2 alpha and 2 beta.
Connected to an iron atom in the middle which is maintained in the ferrous state.
What is myoglobin?
It is the oxygen storing subunit in muscles which binds one molecule of oxygen
What is the Bohr effect?
In deoxygenation haemoglobin, binding of first oxygen molecule changes the conformation of the protein, and the other 3 subunits have a higher affinity for oxygen- called CO-OPERATIVITY
(Mb is myoglobin)
Produces a SIGMOID SATURATION CURVE
What are the Bohr, Haldane and 2,3-BPG effects?
Bohr= increased proton concentration favours oxygen dissociation
Haldane= CO2 promotes oxygen dissociation
2.3-bisphospholycerate is a metabolite which binds to oxyhaemoglobin and causes dissociation of oxygen (it lowers the affinity of Hb for oxygen, improving oxygen delivery)
What are the effects of anaemia and CO-poisoning on O2 delivery by Hb?
In an anaemic person, whilst they have 50% less Hb, the remaining Hb molecules can still deliver oxygen. In CO poisoned individuals the curve is shifted to left because CO locks the Hb into the oxy-conformation (high affinity) so it doesn’t release oxygen.
What is methaemoglobin?
When an electron is spilled from the ferrous atom, called methaemoglobin and is no longer capable of transporting O2.
There is a repair, however if there is a mutation if the repair system, can cause high levels of mHb.
How is CO2 transported around in the blood?
7% is dissolved, 70% is hydrated to carbonic acid and bicarbonate and 23% is combined as carbamino-Hb (bonded to the N-terminal groups of the chains)
How is CO2 hydrated to carbonic acid?
It is hydrated by reaction with water to carbonic acid by the enzyme carbonic anydrase in the red blood cell
This then ionises to bicarbonate.
The bicarbonate leaves the red blood cell through a transporter- the opposite happens at the lungs.
What does the drug Erythropoiten do?
Increases Hb- used to treat patients but also illegally in sports.
What is the allosteric effect?
The afinity of binding O2 increases with each successively bound O2 molcule.
What is a right shift in the Hb saturation curve and how can a right shift occur?
A right shift means there is less affinity for oxygen from Hb and it gives up oxygen more readily.
This can be cause by the following effects:
What are the different partial pressures of oxygen in air, the trachea, alevoli, arteries and veins?
Why is there not an equilibrium between alveolar and arterial partial pressure?
- There may be mixing of venous blood with arterial blood
- not all the blood that passes through the lungs gets oxygenated
- alveolar dead space where ventilation is not occuring.
When does hypoventilation occur and what are the effects of it?
Can occur in altitude, when there is a problem with the alveolar or capillary membrane or due to a miss-match of ventilation and perfusion.
It causes a lower partial pressure of O2 which results in lower blood oxygen content
What happens to the gas content of CO2 and O2 during hypoventilation and hyperventiliation ?
What is physiological dead space?
Physiological dead space = anatomical dead space + alveolar dead space
What is alveolar dead space?
Re[resents areas of insufficient blood supply for gas exchange
Increases with age and disease
What is respiratory failure and ventilatory failure?
Respiratory failure= failure to oxygenate properly leading to hypoxemia
Ventilatory failure= failure of the ventilatory pump mechanism leading to hypoxemia
Why do patients become hypoxic?
Hypoventilation and/or ventilation perfusion mismatch
How can you distinguish between type 1 and type 2 respiratory failure?
What are different causes of ventilatory failures?
Control failure (e.g. drug overdose effecting brain commands)
Peripheral mechanism failure- nerves, muscles, chest cannot move (scoliosis) or gas cannot get in or out (asthma)
What is type II respiratory failure?
There is a decrease in oxygen and an increase in CO2. Common causes are severe COPD, acute asthma and pulmonary oedema.
Uses due to hypoventilation
To treat, give the patient oxygen and treat the underlying cause to reverse hypoventilation
What causes ventilation-perfusion mismatch?
Lung diseases effecting the airways, lung infections such as pneumonia, bronchial narrowing (COPD/asthma) or acute lung injury
What happens to arterial CO2 in V/Q mismatch?
V/Q mimatch in one area of the lung will cause low O2 and high CO2 levels.
The high CO2 levels will increase ventilation in other areas of the lung with normal V/Q.
The increased ventilation rate allows more CO2 to leave, which means oxygen is not being taken up in this area.
This causes normal levels of CO2 but low levels of O2.
How does pulmonary embolism cause V/Q mismatch?
Emboli create areas of dead space where there is ventilation but no perfusion causing hypoxia.
How does asthma cause respiratory failure?
Bronchospasm, hyperventilation and mucous plugging causes ventilation defects and V/Q mismatch.
This causes type 2 respiratory failure.
How does COPD cause respiratory failure?
COPD is a mixture of chronic airway inflammation and narrowing as well as emphysema.
Causes hypoventilation and V/Q mismatch
Patients may have type 1 or type 2 respiratory failure.
How do you measure haemoglobin saturation?
Uses a pulseometer which can be placed on a finger. It uses absorption spectroscopy.
Easy to do at home, but assumes Hb levels are normal and nail polish effects results.
Where are arterial blood gases taken from?
The radial artery, but sometimes the femoral/ brachial artery.
What is measured in arterial blood gases?
- PaO2
- PaCO2
- Hydrogen ion concentration
- Bicarbonate concentration
- Sometimes electrolytes
- Sometimes Hb levels
- Carboyhaemoglobin (amount of Hb bound to CO to detect CO poisoning)
- Base excess
*
What does an increase in blood CO2 lead to?
Acidosis
What happens in CO poisoning?
Co binds to Hb in the place of oxygen to form carboxyhaemoglobin. Can cause death by asphyxia
What causes type 2 respiratory failure?
Low oxygen levels due to hypoventilation of lungs. High CO2 due to increased levels in alveolar space and less being removed from blood
What are the two types of acidosis and what causes them?
Respiratory acidosis= H+ is increased by an increase in PaCO2
Metabolic acidosis= H+ is increased by an increase in acid production or a decrease in excretion.
What will arterial blood gases look like for someone with acute type 2 respiratory failure?
ACUTE= have low O2, high CO2, high H+ and normal bicarbonate levels
What will arterial blood gases look like for someone with chronic type 2 respiratory failure?
Have low O2, high CO2, normal H+ but higher bicarbonate
This is becuase the acidosis has been controlled by metabolic compensation, where there is increased bicarbonate retention by the kidney.
Why should high concentration oxygen not be given to COPD patients?
They have chronic type 2 failure and are dependant on hypoxia to stimulate breathing.
Chronic high CO2 no longer stimulates breathing, so a suddent increase in PO2 with oxygen therapy can worsen hypoventilation
What are the ABG results of respiratory alkalosis and what causes it?
Caused by hyperventilation
Respiratory alkalosis is not associated with respiratory failure
Normal PO2, low PCO2, low H+, normal bicarbonate
What is metabolic acidosis?
Excess acid production by the body, e.g. diabetic ketoacidosis.
What is a classical clinical sign of acidosis?
Kussmal breathing (deep, rapid breathing pattern)
It is a compensatory mechanism to increase CO2 removal
What are the ABG results of metabolic acidosis?
PO2 levels normal
PCO2 levels are low
H+ level is high
Bicarbondate level low
What is the CO2 and Bicarbonate equasion?
What decreases and increases bicarbonate in the body?
HCO3 is increased by an increase in pCO2
HCO3 is decreased by an increase in acid production or decrease in excretion
Why are there two measures of bicarbonate?
Actual and standard
Acutual= calculated with actual H+ and pCO2
Standard= actual H+ and A NORMAL pCO2 level, show will show the metabolic effects
What is base excess?
The amount of base needed to be removed from a litre of blood at a normal pCO2 level in order to bring the H+ back to normal
A negative value indictaed metabolic acidosis
How do you interpret CO2 and H+ of blood gases?
Normal or low CO2= type 1 respiratory failure
High CO2= type 2 respiratory failure
High H+= acidosis
Low H+= alkalosis
How are the upper airways protected against pathogens?
Colonisation
Swallowing- into stomach acid
Lung anatomy- mucus and ciliated epithelium, cough reflex
Immune system
What are the most common viruses that cause respiratory tract infections?
Rhinovirus (common cold), influenza A or coronavirua
What are the symptoms of flu?
Temperature, headache, weakness, cough
What are the usual symptoms of pharyngitis?
Sore throat
Tender glands in neck
Large tonsils somtimes with exudate
Tender anterior cervical lympth nodes
What are the usual causes of pharyngitis?
Caused by virus or occasionally bacteria
If there is exudate on the tonsils hints to bacterial infection
What are the clinical symptoms of sinusitis?
Unilateral face pain (into ears and teeth)
Purulent nasal discharge
Fever
What are the symptoms of acute epiglottitis?
Sore throat and pain on swallowing
High pitched wheezing noise when breathing in (inspiratory stridor)
Fatigue
What are the symptoms of laryngo-tracheobronchitis?
A disease most common 3 months- 3 years
Barking cough and inspiratory stridor (high pitched wheezing noise)
What are the issues with premature babies and respiratory infections?
Babies born premature might not get sufficient trasfer of antibody from their mother.
What is bronchiolitis?
Inflammation of the bronchioles
What are the clinical features of bronchitis?
Cough- may be productive or not
Wheeze
May have fever but no systemic features of infection
What are the complications of bronchitis?
May cause acute exacerbations of COPD or asthma
What is the treatment for bronchitis?
Uusally none if viral, sometimes antimicrobials
Manage exacerbations of COPD/asthma with steroids and increased inhalers
What are the symptoms of bronchieactasis?
Have a chronic cough
Excessive sputum production
Recurrent pneumonia and weight loss
May develop clubbing and have chronuc crackles
What does this x-ray suggest
Dullness suggests inflammation
Pneumonia maybe
What are the most common causes of pneumonia?
Viruses (10%)
Streptococcus pneumoniae (40%)
Mycoplasma pneumoniae (10%)
Chlamdophila pneumoniae (10%)
What people are more at risk of developing pneumonia?
Infants, elderly, COPD, immunocompromised, patients with impaired swallow reflex, diabetes, alcoholics, drug users and congestive heart disease
What are the differences in the common types of pneumonia?
S. pneumoniae= extremes of ages, can be severely ill with respiratory failure
Mycoplasma pneumoniae= usually younger adult, mild illness
Chlamydophila pneumoniae= older age groups, prolonged wheezing
What is the treatment for pneumonia?
Has to be prompt and with antimicrobials
For mild give amoxicillin
For severe upto 10 days of intravenous antimicrobials
What is empyema?
Collection of pus in the pleural space
What are the clinical features of tuberculosis?
Cough, haemoptysis, breathlessness
Weight loss, fever and night sweats
Swollen lymph nodes
What suggests a patient has TB?
- Symptoms
- Upper lobe disease with cavities
- Pleural disease
- Multiple tiny nodules (growth of abnormal tissues
- Failure to resolve with antibiotics
How do you treat tuberculosis?
Have to treat with antimicrobials for 6 months or longer
Why are the smaller airways more prone to collapse?
They have no cartilage
What is the NANC nervous system?
Non‐adrenergic non‐cholinergic (NANC) transmission/mediators describes a part of the autonomic nervous system which does not use acetylcholine or noradrenaline as transmitters.
What factors of the autonomic nervous system can cause bronchoconstriction and bronchodilation of the airways?
Acetylcholine from vagus nerve acts on muscarinic receptors in the airway’s smooth muscle to cause constriction
Beta agonists in circulation on beta adrenergic receptors (e.g. adrenaline causes dilitation)
What NANC factors cause bronchodilitation and constriction?
Nitric oxide and Vastoactive internal peptide (VIP)= constriction
Neurokinins and substance P= dilation
What are asthma and COPD associated with?
Asthma tends to be more of an allergenic disease and is associated with the inflammatory cell known as the eosinophil- also associated with smooth muscle cell problems/hypertrophy. COPD is a disease generally caused my smoking and is associated with acutely aggressive immune cells such as neutrophils which can release proteases with causes lung destruction.
What is the main difference between asthma and COPD?
the presence of reversible airways obstruction
What is the pathology of asthma?
There is smooth muscle thickening due to inflammation and hypertrophy
There is also bronchoconstriction and mucous plugging
What is the pathology of COPD?
There is increased mucous production and destruction of alveoli and connective tissue leading to collapse of conducting airways.
There is also a loss of elastic natural support that keeps the airways open.
What are different methods of measuring airway obstruction?
Peak flow
Spirometery
Lung volume and flow
What is peak flow?
Peak expiratory flow measures the max speed of expiration.
Peak flow is worse in the morning for an asthma patient
What is spirometry?
Calculates FEV1/FVC
FEV1=how much a patient can exhale in 1 second
FVC= how much they can exhale altogether
What will FEV1 and FVC be for those with airway obstruction and severe COPD?
Airway obstruction (more mild)= FEV1 will be lower but FVC similar
Severe COPD= FEV1 and FVC will have decreased
What value of FEV1/FVC suggests an obstructive airways pathology?
0.7
What are the subdivisions of lung volume?
VC= the total volume of air that can be displaced from the lungs by maximal expiratory effort.
RV= the amount of air that remains in a person’s lungs after fully exhaling
IRV= the amount of air a person can inhale forcefully after normal tidal volume inspiration
Vt= the amount of air that moves in or out of the lungs with each respiratory cycle
How can you tell the difference between asthma and COPD in a spirometry test?
Do spriometry, then give the patient a bronchodilator
If the second test is better, is asthma, if no improvement is COPD
What are some localised airway obstruction causes?
- a lesion outside the wall squashing the airways e.g a large lympth node
- a lesion in the wall e.g. tumour
- a lesion in the lumen e.g. foreign body
What are the effects of localised airway obstruction?
Can cause distal collapse or over inflation
What is the clinical definition for chronic bronchitis?
Cough and sputum productive for 3 months in 2 consecutive years
What causes chronic bronchitis?
Pollution and smoking
What is the progression of chronic bronchitis?
Initially cough and sputum production
Then hypercapnia, hypoxia, pulmonary hypertension and right ventricular failure
(The hypertension places excess strain on the heart’s right ventricle as it works to pump blood through the lungs)
What is the anatomical definition of emphysema?
Irreversible dilation of acinar (portion of the lung distal to the terminal bronchiole) spaces with destruction of walls.
What are the different classifications of emphysema?
What are the clinical features of emphysema?
Hyperventilation, normal pCO2 and pO2. Weight loss and right ventricular failure.
What are the 5 different types of asthma?
- atopic (related to allergy)
- non-atopic
- aspirin-induced asthma
- occupational
- allergic bronchopulmonary aspergillosis
What is atopic asthma caused by?
Triggered by a variety of factors eg dust, pollen, house mites. In these patients bronchoconstriction is mediated by a type I hypersensitivity reaction (involves immunoglobulin E (IgE) mediated release of antibodies). Hypersensitivity leads bronchial obstruction and the symptoms of asthma
What are examples of beta-2-agonists?
Salbutamol
Ventolin
What is non-atopic asthma and how can this be distinguished from atopic?
Non-atopic is non allergic, is associated with recurrent infections and not immunologically mediated.
Skin tests are negative.
What is aspirin-induced asthma?
Aspirin (acetylsalicylic acid)-induced asthma (AIA) consists of the clinical triad of asthma, chronic rhinosinusitis with nasal polyps, and precipitation of asthma and rhinitis attacks in response to aspirin and other NSAIDs
What is occuopational asthma?
Hypersensitivity to an inhaled antigen that is related to an individuals occupation.
What is allergic bronchopulmonary aspergillosis?
A type of asthma that involves a specific allergic response to the spore of aspergillosis fumigatus
Mixed hypersensitivity reaction
Mucus plugs are common and it is associated with bronchiectasis
What is bronchiectasis?
Permament dilitation of bronchi and bronchioles
Due to a combination of obstruction and inflammation
What are the clinical features of bronchiectasis?
Chronic cough productive of copious sputum
Finger clubbing
Complications such as infection and respiratory failure
What is the parenchyma?
The part of the lungs involved in gas transfer, including the alveoli, interstitium, blood vessels, bronchi and bronchioles
What would a patient with crackles, a 3 day history of breathlessness, cough and haemoptysis and a chest x-ray belowmost likely have?
Pneumonia
What are the 5 key components of acute inflammation?
Heat, redness, swelling, pain and loss of function
Why do patient’s with pneumonia or other infections experiance pyrexia?
Fevers are caused by chemicals called pyrogens flowing in the bloodstream. Pyrogens make their way to the hypothalamus in the brain and bind there, increasing temperature
One common pyrogen is called Interleukin-1 (IL-1), which is produced by white blood cells called macrophages
What are symptoms of lobar pneumonia?
Rust coloured sputum
Consolidation of a large portion/entire lobe
Associated with S. Pneumonia
What is consolidation of the lung?
when the air that usually fills the small airways in your lungs is replaced with something else
What are the signs of bronchopneumonia?
Patchy consolidated areas of acute inflammation
Often in the elderly with risk factors such as heart failure, renal failure, stroke, COPD
What are the risk factors for pneumonia?
- Chronic diseases
- Immusuppressive agents
- Immunologic deficiency
- loss of cough reflex
- injury to cilia
What is cystic fibrosis?
A multi-system disorder effecting the lungs and GI tract
Cystic fibrosis is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein
Causes viscous mucus secretion
What is a granuloma?
A collection of immune cells known as macrophages. They form when the immune system attempts to wall off substances it perceives as foreign but is unable to eliminate.
What is secondary tuberculosis?
Reactivation of old, often subclinical infection
Causes more damage due to hypersensitivity
What is restrictive chronic lung disease?
It is a decrease in the total volume of air that the lungs are able to hold
Examples of conditions are pulmonary fibrosis and scoliosis
What is interstitial lung disease?
Interstitial lung disease (ILD) is an umbrella term used for a large group of diseases that cause scarring (fibrosis) of the lungs. The scarring causes stiffness in the lungs which makes it difficult to breathe and get oxygen to the bloodstream.
What are causes of interstitial lung disease?
Pulmonary fibrosis
Interstitial pneumonia
Respiratory bronchiolitis
How does fibrosis occur?
What is occupational lung disease?
Can be caused by asbestos which can be in shipyards or the building trade. Causes several diseases such as pleural plaques (benign), asbestosis (progressive fibrosis), mesothelioma and adenocarcinoma. Silica, coal dust and beryllium can cause lung diseases too.
What is the difference between obstructive and restrictive lung disease?
Obstructive disorder= in which the radius of an airway is narrowed, thus reducing airflow in and out of the lungs.
Restrictive disorder= prevents normal expansion of the lungs. They are diseases casuing increased fibrous tissue in the lung.
What are the two causes of restrictive lung diseases?
- Extra pulmonary disease such pleural space or chest wall disease
- Intra pulmonary disease such as parenchyma disease
What are examples of conditions that cause extra-pulmonary restrictive lung diseases?
Impaired neuromuscular junctions e.g. myasthenia gravis
Impaired muscles
Pleural thickening from abestos
Skeletal abnormalities e.g. scoliosis
What are examples of conditions that cause intra-pulmonary restrictive lung diseases?
Silicon gathering in a stone mason
Asbestosis
Drug induced lung fibrosis
Idiopathic pulmonary fibrosis
What is transpulmonary pressure?
The difference between the lung elastic recoil pressure and chest wall elastic recoil pressure
What does having a lung with low compliance mean?
Greater inflation pressure is required to inflate the lung, but deflation is easy
What does a lung with high compliance mean?
A lower inflation pressure is required to inflate the lungs but there is little elastic recoil and it does not deflate easily
What changes with compliance in a fibrotic lung?
There is decreased compliance and increased elastic recoil
(it is hard inflate but deflates easily)
What are the two pressures acting on the alveoli?
Inflation pressure
Surface tension pressure inside, caused by moisture
What reduces the surface tension in the alevoli?
Surfactant= surface active agent
It is comprised of lipids (mainly phospholipids) and proteins
What is a surfactant molecule made of?
A surfactant molecule has a hydrophobic end which is composed of fatty acids and a hydrophilic end composed of glycerol, phosphate and choline.
They only act to reduce surface tension only when they are close together.
What are conditions where there is little surfactant?
- respiratory stress syndrome of the new born, effects premature babies who do not produce enough surfactant
- pneumonia
- idiopathic pulmonary fibrosis
- lung transplant
Why is spirometry and lung volume measurements not a good option for diagnosing restrictive lung diseases?
The pattern between extra-pulmonary restriction and intra-pulmonary restrictions in spirometry and lung volume are very similar
What is measured in restrictive lung disease when coming to a diagnosis?
Gas exchange in the lung
Alveolar volume
What gases are used to measure alveolar volume and gas exchange?
Gas exchange= carbon monoxide
Alveolar volume= helium
How can you tell if the restrictive disease is extra-pulmonary or intra-pulmonary?
A subject breathes in and out a gas of known concentrations of helium and carbon monoxide. Use 10% helium and 0.3% CO.
Re-measure concentration of helium in the container. Reduction is volume of alveoli and tubing of container.
For CO, the reduction in concentration after reaching steady state gives us the number of CO molecules transported to the bloodstream.
What is a particulate?
this term relates to the exposure to a dry aerosol of separate particles which are themselves scientifically very small pieces of solid matter. Can be naturally occurring eg dust or man-made eg diesel exhaust.
What is particulate matter 10 (PM10)?
The mass of particles collected by a sampler with a convention that is 50% efficient for particles with an aerodynamic of 10micro m.
What are nanoparticles and what can they cause?
They are particles with one or more dimensions less than 100nm
They caused disease if exposed to alot/over time
What are the different places a particle can end up in the lung?
Sedimemtation- gathering of particlesw
Diffusion- in the alveloi
Interception- stuck on a corner
Impaction- stick in the wall by following original path instead of bending
Electrostatic deposition- charged particles attracts other charged particles
What is translocation of particles?
When particles relocated to another part of the body, e.g. the liver.
Either through coughing up mucus and swallowing it- digested or the tissues are being directly exposed.
What deals with particles in the lungs?
The cilia beat upwards to remove particles from the lung
In the alveolar space there is no cilia so the immune system, e.g. macrophages have to attack the particles
What are fibres?
Fibres are defined as having a length greater than 5 microns and a diameter of less than 3 microns. Naturally occurring fibres are asbestos, plant fibres (cotton). Man made fibres include insulation woods
What are the 3 factors that influence whether a fibre can cause disease?
- it must be thin enough to escape cilia
- it must be bio persistent (maintains its shape in lungs)
- it has to be long to stop macrophages from consuming them.
What adverse effects can macrophages have on the lungs?
When macrophages are too small to consume fibres it produces chemicals to dissolve this fibre, which leak out as the fibre is too big. These detrimental materials can have a profound effect on the surrounding tissue
What is a bronchodilator?
Bronchodilators relax the smooth muscle layer that surrounds the bronchi and bronchioles, increasing the diameter of the airway and reducing the resistance to airflow during episodes of bronchospasm.
What are examples of bronchodilators?
- Beta-2 agonists
- Antimuscarinic drugs
- Magnesium sulfate
- Phosphodiesterase inhibitors
What are examples of long-lasting and short-lasting beta-2 agonists?
Short acting= salbutamol and terbutaline
Long acting= salmeterol formoterol
How do beta-2 agonists cause bronchodilation?
Activate the beta-2 adrenoceptors that are the targets of circulating catecholamines
They up-regulate the production of the secondary messenger cyclic AMP ultimately leading to smooth muscle relaxation.
How do antimuscarinic drugs cause bronchodiltation?
Antagonists of muscarinic receptors that is normally activated by ACh from the parasympathetic fibres
These receptors promote smooth muscle contraction- stopped by anti-muscarinic drugs
What are short and long-acting drugs?
Short acting- ipratropium bromide
Long acting - tiotropium
How do methylxanthines cause bronchodilation?
Causes smooth muscle relaxation by inhibiting the degredation of cyclic AMP, increasing it’s availability
When is magnesium sulfate used?
Used as a bronchodilator in the emergency treatment of severe asthma
What are the classes of drugs with anti-inflammatory effects in the airway?
- Leukotriene receptor antagonists
- Corticosteroids
- Phosphodiesterase type-4 inhibitor
How do leukotriene receptor antagonists cause anti-inflammatory effects?
Inhibit the actions of leukotrienes, which are pro-inflammatory mediators
What are corticosteriods used for?
Reduce inflammation and prevent excerbations of asthma and COPD.
How does histamine cause worse asthma?
Histamine released from degranulating mast cells is known to be an important mediator that causes bronchospasm and promotes inflammation in people with asthma and other allergies
What two groups of drugs have effects on histamine?
Mast cell stabilising drugs
Histamine-1 receptor antagonists
What are mast cell stabilising drug examples and what are they used for?
Sodium cromoglicate
Used in eye drops to treat allergic rhinitis
Now used infrequently
How are beta-2 agonists, antimuscarinics, methylxanthines and corticosteroids administered?
B2A= inhalation
AM= inhalation
M= mouth
C= inhalation and mouth
What corticosteroids are taken by inhalation and mouth?
Oral= prednisolome
Inhalation= beclomatose
What are humanised monoclonal antibody drugs and what are examples?
New drugs that are being developed to target specific componenets of the immune response in inflammatory airways disease
- Omalizumab is a humanised monoclonal anti-IgE antibody that is effective at treating patients with allergic asthma
- Mepolizumab and reslizumab are humanised anti-interleukin-5 (anti-IL-5) monoclonal antibodies that reduce the production and survival of eosinophils.
What is angiodema?*
A condition characterised by excessive plasma leakage from capillaries leading to intermittent oedema of the skin/organs.
When it affects the throat and larnyx it may compromise breathing and obstruct the upper airway
What drugs are used to treat angioedema?*
Tranexamic acid
Danazol
What are drugs that can treat pulmonary fibrosis?
Mucolytic drugs help to break up the thick mucous- dornase alfa is an enzyme that breaks up DNA strands that contribute to mucus viscosity
Ivacaftor potentiates cholide ion transport through the defective CFTR channels
What is an example of a pulmonary surfactant?*
Beractant- mainly used in pre-term neonates
What are examples of anti-fibrotic drugs?*
Pirfenidone and nintedanib
What are respiratory stimulants and suppressants?*
Stimulates- stimulate the drive to breath, e.g. doxapram
Suppressants- depress respiration e.g. opioids such as codeine
What is the potential harm of using oxygen as a drug?
the potential to depress respiratory drive in patients with chronic obstructive pulmonary disease who also retain carbon dioxide. They depend on hypoxia for their respiratory drive and injudicious use of oxygen may suppress respiration and lead to carbon dioxide-induced narcosis and death.
What is the treatment pathway for chronic asthma?
What is the treatment pathway for acute asthma?
What is the treatment of chronic COPD?
What is the treatment pathway for an acute exacrbation of COPD?
What is the treatment pathway for acute anaphylaxis?
What are the 3 main mechanisms by which drugs can have an adverse effect on the respiratory system?
- bronchospasm
- pneumonitis and fibrosis
respiratory supression
How can drugs adversely affect respiratory function by bronchospasm?
Drugs can disrupt the balance between constriction and and relaxation of bronchial smooth muscle in favour of the former. Bronchospasm reduces the diameter of the airway lumen, increases the resistance to airflow, increases the work of breathing and potentially reduces the ventilation of the alveoli.
How can drugs cause an adverse affect on respiratory function through the mechanism of pneumonitis and fibrosis?
Drugs may cause an inflammatory reaction in the lungs (pneumonitis) which may progress to fibrotic scarring- this will reduce the number of alveoli, make it difficult to expand lungs and will harm gas exchange
How can drugs adversely affect the respiratory system through respiratory supression?
Drugs may supress the drive to breath or cough by inhibiting the respiratory centre in the CNS, or due to paralysis of the respiratory muscles.
What drugs cause bronchoconstriction?
Beta blockers (beta antagonists)- propranolol, atenolol, bisoprolol
NSAIDs can cause aspirin induced asthma with bronchospasm
Cholinesterase
What are beta blockers?
Antagonists at beta-adrenoceptors
These drugs were designed to be more selective for beta-1 receptors in the heart, they are not completely specific.
What are examples of non-selective and beta-1 selective beta blockers?
Non= propanolol
Beta-1= atenolol and bisoprolol
What is the pathogenesis of aspirin-induced asthma?
1/5 of asthmatic population is sensitive to aspirin and NSAIDs and may present with bronchospasm
NSAIDs inhibit the COX pathways, this reduces formation of protaglandins and diverts arachidonic acid metabolism towards the synthesis of cysteinyl leukotrienes, which may promote bronchoconstriction and inflammation.
What drugs are effective in blocking the bronchoconstriction provoked by aspirin?
Leukotriene antagonists e.g. montelukast
What does the enzyme cholinesterase do and what are cholinesterase inhibitors used to treat?
The enzyme cholinesterase breaks down acetylcholine around cholinergic receptors. Cholinesterase inhibitors (e.g. neostigmine) are used to treat conditions where the potentiation of cholinergic transmission might be beneficial such as myasthenia gravis
What is paradoxical bronchospasm?
PB is when a patient’s airways constrict instead of relax after using a bronchodilator
What drugs can cause pneumonitis and fibrosis?
Antibiotics e.g. nitrofurantoin
Anti-rheumatic drugs e.g. methotrexate
Biological agents e.g. adalimumab
Cancer chemotherapy e.g bleomycin
The anti-arrhythmic drug amiodarone
What factors predispose to drug-induced interstitial lung disease?
Patients at extreme ages
Genetic susceptibility
Dose related
Existing lung damage
What drugs are associated with central respiratory depression?
Opioid analgesics e.g. morphinen, oxycodone
Benzodiazepines e.g. diazepam
Barbiturates
Ethanol
Oxygen (in patients with chronic CO2 retention)
What is a hypnotic drug?
Hypno7c drugs are intended to promote sleep in people with short-term insomnia. Commonly-used drug classes are benzodiazepines (e.g. diazepam)
Barbituates are now rarely used
What are the methylxanthine class of drugs?
They are non-selective phosphodiesterase inhibitors
How do phosphdiesterase inhibitors cause bronchodilation?
They target the enzyme phosphodiesterase (PDE) that is responsible for the breakdown of cyclic adenosine monophosphate (cAMP), the secondary messenger for beta-2 adrenoceptors
What are examples of phosphodiesterase inhibitors?
Methylxanthines= aminophyllin, theophylline
Roflumilast
What is a metered-dose inhaler? (without spacer)
A valve delivers a dose of the drug in a fine mist from a small canister
Widely used due to small size and portability
Patients must have excellent co-ordination
What is a metered dose with a spacer?
A spacer device is a chamber that retains the aerosol, allowing more time for it to be consumed
Used when patient has poor coordination, high doses are required, and for younger children
What are dry powder inhalers?
A handheld device that does not require the same careful coordination associated with metered dose inhalers
What is the action duration of short lasting and long lasting beta-2 agonists
Short- 4-6 hours
Long- 12+ hours
What are examples of long acting and short acting beta-2 agonist drugs?
Short= salbutamol and terbutaline
Long= salmeterol and formoterol
What is the mechansim of action of beta-2 agonists?
Activate beta-2 adrenoceptors
Causes activation of adenylate cyclase which increases production of cAMP which in turn increases activity of proteins such as kinase A
This inhibits smooth muscle contraction
What are the clinical indictations for using beta-2 agonists?
Asthma and COPD
How are beta-2 agonists administered?
Usually by inhalation, typical dose of salbutamol is 100-200 mg
What are the predictable (type A) adverse effects of beta-2 agonists?
Tremor
Increased HR
Palpitations
Hypokalalaemia
Vasodilitation
What are the different time scales and examples of long and shorting bronchodilator drugs?
Short= 3-6 hours such as ipratropium bromide
Long= 12-24 hours= tiotropium, aclindinium bromide
What is the mechanism of action for antimuscarinic bronchodilators?
They antagonise muscarinic receptors on bronchial smooth muscle
These receptors normally respond to ACh released by postganglionic fibres
Antagonism of M3 receptors reduces the availability of calcium, which inhibits smooth muscle contraction causing bronchodilatation.
Also have use in drying up mucous secretions
What are the clinical indictations for using antimuscarinics?
Asthma and COPD
How are antimuscarinics usually administered?
Inhalation
What are the adverse effects of antimuscarinic drugs?
Dry mouth
Constipation
Tachyarrhythmias
Urinary retention
Glaucoma (damage to optic nerve)
What is the mechanism of action of phosphodiesterase inhibitors?
Traditionally attributed to inhibition of phosphodiesterase, leading to an increase in cAMP
Methylxanthines also activate the CNS and respiratory stimulation
What are the inications for prescribing methylxanthine phosphodiesterase inhibitors?
Chronic asthma
COPD
How are phosphodiesterase inhibitors administered?
Theophylline and aminophylline are normally administered by mouth twice daily.
Aminophylline is also able to be intravenously
What has to be watched with theophylline?
It has a narrow therapeutic range
Metabolised by the cytochrome P450 system in the liver and the rate of metabolism reduced in patients with heart failure/ liver disease but increased in smoking and regular alcohol consumption
Also interacts with other drugs that may cause toxicity
What are the adverse effects of phosphodiesterase inhibitors?
Heart- tachycardia, palpitations, arrhythmias
Dizziness
Hypotension
Tremor
Anxiety
What is the mechanism of action of leukotriene receptor antagonists and what are they used for?
Leukotrienes are inflammatory mediators that cause bronchoconstriction and promote further inflammatory action
LRA inhibit these actions and it is indicated for the prophylaxis of asthma in pa0ents who cannot be controlled by an inhaled corticosteroid and long-acting beta-2 agonist (LABA)
