Respiratory Flashcards
How does a virus affect different parts of the respiratory system?
Depending on which part of the respiratory tract the virus attacks, you get different symptoms Upper respiratory (mouth to trachea): runny nose, blocked sinuses, sore throat, painful swollen tonsils Lower respiratory (vocal cords to alveoli): upper – barking cough, lower –pneumonic symptoms
Who is RSV most dangerous for?
Respiratory syncytial virus (RSV) – common in children but can be lethal in premature babies. Under 18 months can develop bronchiolitis which may mean they need oxygen or ventilation.
What is the influenza virus?
Influenza or ‘flu’ is an acute respiratory illness caused by infection with influenza viruses.
Member of the Orthomyxoviridae family, with 3 separate genera: influenza A, B and C.
Where are the antigenic sites on the virus?
Genetic material in the middle
Glycoprotein shell with hemagglutinin and neuraminidase present on the surface. These are the antigenic sites. They can be used to classify the virus.
How is Influenza A categorised?
Influenza A viruses further subdivided by 2 key surface antigens:
Haemagglutinin (15 subtypes)
Virus binding and entry to cells: i.e. the “Grappling Hook” for getting in
Immunity confers protection but only to specific subtype
Neuraminidase (9 subtypes)
The “Bolt Cutters” for getting out; cuts newly formed virus loose from infected cells and prevents it clumping together
Immunity to subtype reduces amount of virus released from cells resulting in a less severe disease
Which viral antigens are found in humans?
H1-3 and N1-2 have evolved and adapted so that they can be transmitted between humans.
How does the influenza virus change?
Influenza A and B are the main human pathogens
Viral genome consists of 8 single-stranded RNA segments.
Because the genome is segmented, gene re-assortment can occur in infections.
Genes swapping can occur during co-infection with human and avian flu virus
Also, no proof reading mechanism when it replicates so very prone to mutation.
Minor antigenic variation (antigenic drift) causes seasonal epidemics
Gene re-assortment & major antigenic variation (antigenic shift) may be associated with pandemics.
What’s the difference between influenza A, B and C?
Influenza A
“Sloppy, capricious, promiscuous”: can infect pigs, cats, horses, birds and sea mammals
Causes the severe and extensive outbreaks and pandemics.
Influenza B
Like Influenza A, also prone to mutation but tend to cause sporadic outbreaks (e.g. schools, care homes, garrisons) that are less severe.
More often seen in children
Influenza C
Relatively minor disease: mild symptoms or even asymptomatic
How is influenza transmitted?
Transmission mainly via aerosols generated by coughs and sneezes. However, also possible via hand-to-hand contact, other personal contact or fomites.
How does influenza present?
Influenza characterised by upper and/or lower respiratory tract symptoms, as well as fever, headache, myalgia and weakness.
Complications include bacterial pneumonia, and can be life threatening
Who is at risk of mortality from influenza?
Mortality risk higher in persons with underlying medical conditions:
Chronic cardiac and pulmonary diseases – asthma/COPD
Old age
Chronic metabolic diseases
Chronic renal disease
Immunosuppressed – cancer, medication, born with immunodeficiency
What are the treatment options for influenza?
Supportive care’ Oxygenation Hydration / nutrition Maintain homeostasis Prevent / treat secondary infections e.g. bacterial pneumonia
Role of antiviral medication e.g. Tamiflu reduces duration by one day
Reduce risk of transmission to others
Reduce severity and duration of symptoms
What are the features of the seasonal flu?
Every year the virus changes a little bit (‘Antigenic Drift’)
Means it can infect some people who were immune to last year’s variant.
Changes derived from mutation within the people it infects.
Influenza occurs most often in the winter months and usually peaks between December and March in the northern hemisphere.
Illnesses resembling influenza may occur in the summer months but they are usually due to other viruses.
Annual flu vaccination of at risk groups and children offers some protection against infection.
What are the features of the pandemic flu?
Virus mutates markedly (‘Antigenic shift’)
Large proportion of the population is susceptible.
Often created by the strain “jumping” from another species e.g. Flu virus found in ducks, chickens, horses, pigs, whales, seals…
What are the consequences of pandemic flu?
High morbidity
Excess mortality
Social disruption
Economic disruption
What are the features of the spanish flu?
H1N1 flu subtype, derived from an avian source
Killed between 50 and 100 million people worldwide, with about 40% of the world’s population becoming ill.
Of those who died, many felt ill in the morning and were dead by nightfall. It killed more people than WWI.
Believed that the movement of soldiers helped to spread the virus further afield.
It killed mostly young people (between 20 and 40 years) because the older population had been infected by a variant 40 years earlier leaving them with a residual immunity. Impacted greatly on future generations because these were the people of working (tax-paying) and child-bearing age.
What is the timeline in pandemic flu?
Incubation period 1-4 days
Infectious from onset of symptoms to 4-5 days after,
10% infectious before symptom onset.
2-4 weeks from first case to first introduction to UK
First wave last 3-5 months. Subsequent waves may be worse
What age groups will be affected? Depends if there is any residual immunity
Will take 4 – 6 months (or more) before vaccine available – time for development and manufacture
Potential effectiveness of current anti-virals
What is the overall case fatality rate and the clinical attack rate?
Overall case fatality rate – the proportion of people who die as a result of the infection
Clinical attack rate – the proportion of people who develop the disease out of those who are exposed
Will we get more pandemics?
More travel More people Intensive farming - more animal contacts with people, factory farming breeding grounds for viruses BUT on the plus side - Better nutrition, overall healthier population - Better supportive care options - Vaccination - Antivirals?
What is the Avian Flu?
Before 1997, H5N1 flu virus started circulating in SE Asia
Mild disease in birds (ruffled feathers and depression)
Mutation to highly pathogenic form → 100% mortality
First human cases: Hong Kong 1997
Strictly an avian pathogen but has the documented ability to pass from birds to humans
Most seasonal influenza get secondary bacterial pneumonia, whereas H5N1 causes a primary viral pneumonia
Why was avian flu prevalent in SE Asia?
Close proximity of poultry and people.
50 – 80% of poultry in small rural households
How to control Avian flu?
Cull affected birds Biosecurity and quarantine Disinfecting farms Control poultry movement Vaccinate workers – seasonal influenza vaccine to try and prevent a new mutant version emerging Antivirals for poultry workers Personal Protective Equipment (PPE) Try to reduce chance of co-infection
How were people prepared for swine flu?
International surveillance
Virus research
Vaccine research
Stock piling of drugs - 30 million courses of Oseltamivir
Plans written – strategic
Preparation of information – public and professional
What are the features of swine flu?
Reassortment of swine, avian and human flu virus
Novel virus substantially different from human H1N1 virus; many people susceptible
Human to human transmission
Sensitive to Oseltamivir and Zanamivir (at the moment)
Seasonal influenza vaccine not effective
Greater mortality in younger populations
People over 40 year have some immunity
What are the phases of the pandemic?
Containment Phase
Identification of cases – swabs (couriers),
Treatment of cases
Contact tracing – family, airline passengers
Large scale prophylaxis (anti-virals)
Treatment Phase
Treat symptomatic cases only
National Flu Pandemic Service
What are the rules of infection control?
Hand hygiene, cough etiquette
Universal precautions and PPE (mask, apron, gown, gloves)
Surgical masks OK for non aerosol generating procedures
Segregation of patients
Reduce social contact – 2m
Flu surgeries
Environmental cleaning
How to manage cases in a pandemic?
Call centres
Non medical staff manage cases according to an algorithm
Patient or relative collects antivirals
Home delivery of anti virals for some
Clinical staff free to treat high risk and severely ill people
Hospital admission criteria
What are antivirals?
UK stockpiled 30 million courses
Would cover a 50% attack rate
Mostly Tamiflu, with some Relenza
Tamiflu needs to be given with 24-48 hours of contact to have maximum effect
Evidence from seasonal flu is that it reduces hospitalisation by 50% and duration of disease by approximately 24hours (drug company studies…)
What are the issues with antivirals?
What happens if the virus develops resistance?
What about side effects?
Who do we give them to?
How do we distribute them?
When are face masks useful in a infection?
Worn correctly Changed frequently Removed properly Disposed of safely Used in combination with good universal hygiene practice
What is the impact of a pandemic on the health service staff?
STAFF ISSUES Anxiety/unwilling to work Adequate protection Access to antivirals Risk to family Child care Segregation of staff Redeployment of retired staff Recycling of staff Organisations sharing staff
What is the impact of a pandemic on schools?
Likely to spread rapidly in schools and other closed communities
What happens to NHS staffing levels if schools close down?
Impact on all services including police, fire, the military, fuel supply, food production, distribution and transport, prisons, education and business
What’s the hope of vaccines in a pandemic?
Developed in the past but not used - capacity issues and too late
Could take 6 -10 months, hopefully quicker
When to switch from producing normal seasonal flu vaccine to the pandemic strain?
Capacity:
- will take time to manufacture
- who do you allocate it to first?
May require two doses for at risk groups
What are the possible population-wide interventions that need to be taken in the face of a pandemic?
Travel restrictions Restrictions of mass public gatherings Schools closure Voluntary home isolation of cases Voluntary quarantine of contacts of known cases Screening of people entering UK ports
What is MERS?
Middle East respiratory syndrome-related coronavirus is a species of coronavirus which infects humans, bats, and camels.
It was first reported in Saudi Arabia in 2012 and has since spread to several other countries
What are the normal oxygen values for arterial blood?
Arterial blood: PaO2 90 -110 mm Hg (12.14.6 kPa)
Note PaO2 ~6 mm Hg (0.8kPa) lower in supine position
What are the normal carbon dioxide values for arterial blood?
Blood PCO2 34-46 mm Hg (4.6-6.1 kPa)
Hyper/hypocapnia - Blood PCO2 outwith this range
What are the different types of hypoxia?
Hypoxia is when oxygen supplies can’t meet oxygen demands of a given tissue.
Four sub-divisions:
- Hypoxaemic hypoxia
Low PaO2 (<94, <92, <90 %,<60 mm Hg/8 kPa)
- Anaemic: Reduced Hb
- Stagnant:Poor perfusion of the tissue
- Histiotoxic: cells can’t use oxygen – CN poisoning
Only Hypoxaemic hypoxia can be corrected by supplementary oxygen
What is type 1 respiratory failure?
Defined as:
PaO2<60 mm Hg (equivalent to SaO2 of ∼90%) with a normal or low PaCO2 level.
Factors influencing oxygenation
Due to hypoxaemic hypoxia.
High altitude
Ventilation-Perfusion mismatch (ok ventilation but poor perfusion – pulmonary embolism; shunt)
Diffusion problem (Pneumonia)
What is type 2 respiratory failure?
Defined as:
PaO2<60 mm Hg (equivalent to SaO2 of ∼90%) with hypercapnia, PaCO2 >50 mm Hg.
Due to inadequate alveolar ventilation
Increased airway resistance – COPD, asthma
Reduced breathing effort
Reduced gas exchange surface area (chronic bronchitis)
Deformities in the spine preventing expansion of the chest wall (kyphoscoliosis) or damaged (flail) chest wall
What is the function of the nasal conchae?
Warms, humidifies, filters inspired air
~160 cm2
“Turbinate precipitation” – causes it to change direction quickly, bigger particulates are filtered out because they can’t change direction quick enough
Mucous collects debris
What is Stridor?
Upper airway block
Prominent sound on inspiration
Seen in children with coup
What are the features of the broncioles?
Smooth muscle Mucous glands Cilia - Muco-ciliary staircase - Remove debris
What happens at the alveolar epithelium?
Metabolic function
Site of ACE – important for regulating salt balance
Coverts Angiotensin 1 to Angiotensin 2
What are the two zones of the bronchial tree?
Conductive zone: ~16 divisions Trachea – terminal bronchiole No alveoli – no gas exchange Anatomical deadspace (~150 ml)
Respiratory zone: Gas exchange in alveolated areas ~3 L volume ~50-100m2 surface area “sheet of blood” as a support structure around the alveoli
What is tidal volume?
the lung volume representing the normal volume of air displaced between normal inhalation and exhalation when extra effort is not applied. In a healthy, young human adult, tidal volume is approximately 500 mL per inspiration
What is the minute volume?
Respiratory minute volume (or minute ventilation or minute volume) is the volume of gas inhaled (inhaled minute volume) or exhaled (exhaled minute volume) from a person’s lungs per minute.
~15 breath/min
500 mL per inspiration
~7,500 ml/min
What are the features of the lung mechanics?
Elastic lungs
Moveable ribs
Muscles - external intercostals and diagphragm
What are the elastic properties of lung tissue?
Elastic fibres in lung parenchyma – need just the right number
Alveolar surface tension – lining of fluid in the alveoli which on its own would cause lung collapse, surfactant reduces the surface tension so that the lungs don’t collapse
Lungs collapse without ribs
Why are newborn/premature babies at risk of lung collapse?
Smaller the alveoli, the greater the surface tension
Babies don’t have much surfactant and have very tiny alveoli – high surface tension
What are the mechanics of lung inhalation?
Rib cage moves upwards and outwards
Increases thoracic volume with help from external intercostals, sternocleidomastoids, anterior serrati, scaleni.
Diaphragm contracts, flattening the abdominal contents to further expand the chest volume.
This decreases the intrathoracic air pressure creating a small vacuum that draws air in.
What does the surface tension do?
Pleural membranes are held together by pleural fluid which creates a surface tension to adhere them together.
Develops sub-atmospheric intra-pleural “pressure” (~ -5mm Hg) and prevents lung collapse.
What is a flail chest?
Occurs when two or more ribs broken in two or more places.
Causes paradoxical breathing
Chest “fragment” moves in opposite direction during respiratory cycle, it is sucked back into the chest because the transpulmonary pressure is so strong
What is a pneumothorax?
Intra-pleural pressure equilibrates to atmospheric pressure
“Vacuum” lost
Lung collapses
What can cause a pneumothorax?
Thoracic trauma - Blunt or penetrating
Spontaneous - ruptured bullae
What is a bulla in the lung?
A bulla is a permanent, air-filled space within the lung parenchyma that is at least 1 cm in size and has a thin or poorly defined wall; it is bordered only by remnants of alveolar septae and/or pleura.
What are the treatment options for a pneumothorax?
Aim: Re-establish sub-atmospheric intra-pleural pressure
Acute – emergency thoracocentesis
(needle decompression, 14G cannula, 2nd intercostal space; may fail.)
Longer term – tube thoracostomy (chest drain, 5th intercostal space)
How to treat a Persistent Spontaneous Pneumothorax?
Pleurodosis:
“Tyre-weld” - autologous blood patch
Using n-butyl-2-cyanoacrylate as a tissue glue
Talc or bleomycin - painful
Seals and sticks the pleura back together to re-establish sub-atmospheric intra-pleural pressure.
What is Spirometry?
A method to determine lung function Four volumes (Inspiratory Reserve volume, Tidal volume, Expiratory Reserve volume, Residual volume) Four capacities (collection of volumes) - Total Lung Capacity, Inspiratory Capacity, Vital Capacity, Functional Residual capacity.
What do all the lung volumes mean?
Inspiratory reserve volume - the additional amount of air that can be inhaled after a normal inspiration (tidal volume)
Tidal volume - the normal volume of air displaced between normal inhalation and exhalation when extra effort is not applied
Expiratory reserve volume - the amount of extra air, above anormal breath, exhaled during a forceful breath out.
Residual volume - the amount of air that remains in a person’s lungs after fully exhaling
What do all the lung capacities mean?
Total lung capacity - sum of all volume compartments or volume of air in lungs after maximum inspiration (usually about 4-6L
Inspiratory capacity - the additional amount of air that can be inhaled after a normal inhalation (IC = TV + IRC)
Vital capacity - the maximum amount of air a person can expel from the lungs after a maximum inhalation (VC = TV + IRC + ERV)
Functional residual capacity -the volume of air present in the lungs at the end of passive expiration (FRC = ERV+RV)
How does being pregnant affect the the capacities and volumes of the lungs?
Reduced inspiratory reserve volume
Increased tidal volume
Reduced expiratory reserve volume
Reduced residual volume
Reduced total lung capacity
Reduced functional residual capacity
What can spirometry be used for in the clinic?
Differentiate between
Obstructive (COPD, asthma, CF) - obstructs the patient from exhaling
Restrictive (fibrosis, oedema) - impinges on inhalation, stops people from filling their lungs
What is FEV1 and FVC?
Forced expiratory volume in 1s (FEV1): volume exhaled in first second after deep inspiration and forced expiration
Forced vital capacity (FVC): total volume of air patient can forcibly exhale in one breath
FEV1/FVC – the ratio of FEV1 to FVC expressed as a percentage
What is normal FEV1 and FVC?
FEV1: >80% predicted
FVC: >80% predicted
FEV1/FVC ratio: >0.7
How does airway resistance change in disease?
Healthy adult: main airway resistance: 4th - 8th airway generations (in the middle)
Few larger bronchi vs many smaller terminal bronchioles
Disease: greater resistance from smaller bronchioles due to:
- Muscular wall contraction
- Oedema
- Luminal mucus
What is lung compliance?
Extent to which lungs will expand for a given increase in trans-pulmonary pressure
Lung vol. change / unit of transpulmonary pressure
What are the different pressures in the lung?
Alveolar pressure: pressure inside alveoli ~ atmospheric pressure (~760 mm Hg). Convention dictates it is 0 mm Hg
Pleural pressure: pressure of pleural fluid. Negative with respect to alveolar pressure
Trans-pulmonary pressure: pressure difference between alveolar pressure and pleural pressure
What is inspiratory and expiratory compliance in the lung?
Inspiratory compliance: Less compliant due to parenchymal elastic and collagen fibres at apex
and surface tension reduced by surfactant at the base
Expiratory compliance: Greater uniformity due to elastic recoil
What happens when there is reduced lung compliance?
“Stiff” lungs means that there is inelastic scar tissue
It is difficult to stretch/inflate
Accumulation of fibrous tissue
Greater pressure change needed for same lung vol change
Occurs during pulmonary fibrosis; alveolar oedema; lack of surfactant (premature babies)
What happens when there is high lung compliance?
Elastic fibres degraded means there is low elastic recoil Difficulty exhaling Difficulty inhaling Collapsed alveoli Increased work of breathing Occurs during Emphysema and COPD
What is the pathophysiology of asthma?
Inflammation/irritation causes ontraction of bronchiolar smooth muscle (parasympathetic nerves) Narrow airways increased resistance Ventilation/Perfusion mismatch Increased work of breathing Muco-ciliary clearance reduced Wheeze
What is the pathophysiology of COPD/em
Chronic inflammation/infection blocks bronchioles
Air is entrapped; alveoli enlarge and rupture
Respiratory membrane destroyed
Reduced surface area for gas exchange
Increased airway resistance; increased work of breathing (require accessory muscles even in ‘relaxed’ breathing)
Ventilation/Perfusion mismatch (Shunt and deadspace)
Hypercapnia – new elevated “baseline” level of CO2 - “less sensitive” to hypercapnia
Why can giving a COPD patient supplemental oxygen be dangerous?
COPD patients may rely on hypoxic response to stimulate breathing (already baseline hypercapnic)
Hyper-oxygenation may removes hypoxic drive that they rely on
So the aim is to maintain SaO2 ~90% (88-92% accepted range) to minimise the risk of exacerbating hypercapnia
What is the neurological control of ventilation?
Central control region – medullary respiratory centres
Integrates/coordinate all information from sensors
Sensors – chemoreceptors
Gather information about system
Effectors – muscles (intercostals, diaphragm…)
Alter the system
What do the different respiratory centres do?
PONS * Apneustic centre: Stimulates inspiratory centre Sustained inhalation if not stopped * Pneumotaxic centre: Switches off inspiratory ramp Limits inspiratory cycle Increases resp rate MEDULLA * Inspiratory centre (Dorsal Respiratory Group; DRG): Key regulator of respiration Receives sensory info from CN IX, X Repetitive inspiratory drive “ramp” signals to muscles ~2secs 3 secs silence – muscles relax * Expiratory centre (Ventral Respiratory Group; VRG) : Gives extra respiratory drive Active on forced exhalation Stimulates abdominal muscles
What nerves are required for the neurological control of ventilation?
CN IX - Glossopharyngeal (Hering’s nerve; carotid bodies)
CN X – Vagus (aortic bodies)
Phrenic nerve root – diaphragm (C3-C5 keeps the diaphragm alive)
Intercostal nerves – intercostal muscles
What are the central and peripheral chemoreceptors?
ACT AS SENSORS Central Chemoreceptors Ventral surface of medulla Sensitive to CO2 and H+ ions O2 - little direct influence
Peripheral Chemoreceptors
Aortic bodies, Carotid bodies - decreased PO2, decreased pH, increased PCO2
Stretch receptors - prevent over-stretching
Irritant receptors
How does the body respond to an increased carbon dioxide?
Acute elevation – increased H+: respiratory compensation – increased resp rate.
Renal Involvement
Adjustment of H+ to normal levels over 1-2 days
Increased plasma HCO3- (renal synthesis)
HCO3- leaks into CSF – mops up excess H+
Potent acute effect on respiratory control; weak chronic effect
What are the general arterial blood gas values?
pH 7.35 - 7.45
HCO3– 24-28mmol/L
pCO2 35-45 mHhg
paO2 75-100mmHg (on air)
How does the kidney react to increased H+ (acidosis)?
Reabsorb all filtered HCO3-
Secrete H+
Synthesise new HCO3-
Phosphate Buffers - Major role in buffering renal tubular [H+]
Ammonia - Major role in buffering H+ in chronic acidosis
How does the kidney react to increased HCO3- (alkalosis)?
Excess filtered HCO3-
Not titrated by H+
Excreted in urine
Decrease resp rate (minor)
What’s the difference between the pulmonary and circulatory circulation?
Pulmonary circulation - low pressure, small difference in pressure from inlet to outlet, thin-walled arteries (little smooth muscle), receives all cardiac output all the time, rarely re-directs blood flow except in alveolar hypoxia
Systemic circulation - high pressure, big difference in pressure from inlet to outlet, thick-walled arteries (lots of smooth muscle), cardiac output is variable, regularly redistributes blood
What is the bronchial circulation?
Part of the systemic circulation
Supplies lung parenchyma
Returns via pulmonary veins
How do the alveolar and extra-alveolar vessels differ?
Alveolar vessels:
Capillaries and slightly larger vessels
Calibre determined by alveolar pressure vs luminal pressure.
Extra- alveolar vessels :
Arteries and veins in lung parenchyma
Calibre determined by lung volume (tissues stretched)
Why is there an uneven distribution of pulmonary blood?
Zone 1 (Apex): Alveolar pressure > arterial pressure
Capillaries squashed – no blood flow
Zone 2 (Middle): Arterial pressure > alveolar pressure > venous pressure
Intermittent capillary flow – systole not diastole
More like zone 3 in exercise
Zone 3 (Base): Arterial pressure > venous pressure > alveolar pressure
Continuous capillary flow
Describes most lung blood flow
What is the Ventilation:Perfusion Ratio?
Ventilation: Volume of gas/unit time (flow)
Perfusion: Volume of blood/unit time (flow)
When alveolar ventilation and perfusion are normal, there is productive gas exchange
What happens when there is a ventilation:perfusion mismatch?
Alveolar ventilation – absent due to airway obstruction, high altitude
Alveolar perfusion – normal (but wasted)
Therefore alveolar PO2 and PCO2 equilibrate to venous blood levels.
Alveolar ventilation – normal (but wasted)
Alveolar perfusion – absent due to pulmonary embolism.
Therefore alveolar PO2 and PCO2 equilibrate to inspired air.
Both cases - no gas exchange
What is Hypoxic Pulmonary Vasoconstriction?
Decreased alveolar PO2 (<73 mmHg) causes local vasoconstriction of the small pulmonary arteries.
Increased pulmonary resistance (~5X)
Shunts blood to better ventilated areas
Role in High altitude pulmonary oedema (HAPE)?
What determines whether gas exchange occurs?
Pressure and Partial pressure of gases within inspired air.
This affects the plasma solubility of those gases.
Oxygen: Poor plasma solubility - ~3% is dissolved
~97% carried via Haemoglobin (Hb)
Carbon Dioxide: Greater plasma solubility – but only ~2.7 ml/100ml blood
~7% is dissolved
~23% carried via Haemoglobin (carbamino-Hb)
What is pulse oximetry?
Pulse oximetry is a noninvasive method for monitoring a person’s oxygen saturation (SO2). It is a reading of peripheral oxygen saturation (SpO2) but is not always identical to the more desirable reading of arterial oxygen saturation (SaO2) from arterial blood gas analysis.
What anatomical changes mean that a pregnant woman’s respiratory volumes and capacities are different?
Diaphragmatic elevation (~4cm)
Increased sub-costal angle
Increased thoracic circumference
Decreased chest compliance but lung compliance unchanged
Progesterone-induced tracheo-bronchial smooth muscle relaxation
Why do pregnant women experience dyspnoea?
Increased tidal vol causes increased minute volume
~70% women experience subjective dyspnoea
Why is it important that there is a CO2 gradient between the mother and baby?
Maternal: Gradient between venous blood and alveolar air, CO2 excreted
CO2 must diffuse to maternal venous blood before alveolar excretion
Fetal:maternal CO2 gradient must be created
Decreased chemoreceptor sensitivity facilitates this
How does the kidney compensate for respiratory alkalosis in pregancy?
Potential for respiratory alkalosis due to excess [HCO3-]ECF.
But in the proximal renal tubule excess filtered HCO3- i not titrated by H+ and is excreted in the urine.
Reduced HCO3- as part of these compensatory mechanisms.
How common is asthma?
5.4 million in the UK receiving treatment
60% asthmatics with persistent symptom burden despite effective treatment available (potential risk of undertreated mild asthma)
65% asthmatics with asthma attacks
What is the pathology of asthma?
Bronchial hyperresponsiveness - airways get swollen and twitching
Increase in smooth muscle cells - in number and size (hypertrophy)
This narrows the diameter of the airway lumen
They constrict, which narrows the diameter of the lumen further
Swelling and inflammation also contributes to further narrowing
Mucous production also contributes to airway obstruction
What are the two types of asthma?
Eosinophilic - can be associated with allergy or not, the non-allergy variant is usually seen in adulthood.
Non-eosinophilic
What is atopic asthma?
Allergic inflammation is characterised by the recruitment of eosinophils.
Atopic asthma: atopy is the tendency to develop IgE-mediated reactions to common aeroallergens.
25% of the population are atopic, but only half of those people develop disease associated with this. So you can be atopic and healthy or atopic with an atopic disease.
What is Eosinophilic asthma?
Allergy-associated immune cells (Th2 cells) call in the eosinophils by cytokines which damage the epithelium and shredding of it, as well as mucous production and narrowing and damage of the airway.
What causes Atopic eosinophilic asthma?
Atopic eosinophilic asthma can be associated with fungal allergy, common aeroallergens (cat, dog, house, house dust mite) and occupation, pets, exposures.
What Non-eosinophilic asthma?
No eosinophils present, instead the presence of neutrophils. Not very well understood. Divided into: Obesity-related Smoking-related Non-smoking, non-eosinophilic
What is the overlap between asthma and COPD?
Common but not talked about much, difficult to define
Variable airflow obstruction, but not completely reversible
Smoke exposure (passive, active), asthma, infections
More symptomatic, greater healthcare burden
Target eosinophils with steroids, use bronchodilators
How does Asthma present?
Episodic wheeze - comes and goes over time
Cough, breathlessness
Diurnal variation - often worse at 3/4/5am (may be due to dip in adrenaline)
Brittle asthma (type 1, chronic severe, type 2 sudden dips) - known as unstable or unpredictable asthma because it can suddenly develop into a life-threatening attack.
Provoking factors: allergens, infections, menstrual cycle, exercise, cold air, laughter/emotion
What is cough-variant asthma?
A type of asthma in which the main symptom is a dry, non-productive cough.
What factors may indicate the severity of asthma?
Level of treatment required (number of inhalers)
A&E attendances, admissions, HDU/ITU care ventilation (how long?)
Attendance at GP for courses of antibiotics and steroids
What may suggest asthma that is poorly controlled?
Recent nocturnal waking?
Usual asthma symptoms in the day?
Interference with activities of daily living?
Positive to one or more suggests poor control of asthma.
What needs to be included when you’re taking a history of an potential asthmatic?
Age of onset (did it get any better at any point?)
Childhood ventilation/respiratory disease
The march of allergies
Any particular unusual features at the start (e.g. sudden onset, weight loss)
Obvious causes? Chlorine exposure? Occupation?
What are the associated symptoms with asthma?
Eczema, hay fever
Nasal polyp disease: samter’s triad (a chronic condition defined by asthma, sinus inflammation with recurring nasal polyps, and aspirin sensitivity), relevant re rare differentials such as Eosinophilic Granulomatosis with Polyangiitis (EGPA)
Other food allergies, drug allergies
Reflux disease
What do you need to ask about a potential asthmatic’s past medical history?
Always a vital part of the history
Previous pneumonias (bronchiectasis?)
Neurological/renal problems (vasculitis)
What do you need to ask about a potential asthmatic’s drug history?
What are they supposed to be taking?
What do they actually take?
Are they taking beta blockers orally or topically?
Are they sensitive to NSAIDs or aspirin?
Drugs with potential interactions: theophyllines
What do you need to ask about a potential asthmatic’s social and family history?
Do they smoke? Atopy is an inherited tendency Family history of asthma, eczema and hayfever Are there pets in the home? Psychological and psychiatric history
What do you need to ask about a potential asthmatic’s occupation?
Exposure to dusts, fumes, allergens
Lab workers, veterinary staff, animal breeders
Paint sprayers
Bakers
Is your asthma better on holiday? Worse at work?
How would you distinguish COPD from asthma?
COPD is a later disease dominantly of smokers
More of a relentless progressive SOB with wheeze as part of the symptom complex
Less diurnal variation, less day-to-day variation
Winter symptoms, sputum production
Overlap occurs
What would you see in an physical examination for asthma?
May be normal
Wheeze, polyphonic, expiratory, widespread
Absence of crackles, sputum and other signs
What tests would you to look for asthma?
Blood count: eosinophils
Test for atopy and allergy: skin prick tests (SPTs) and radioallergosorbent test (RAST)
Chest X-ray often useful to rule out lung cancer and COPD
Oxygen saturations
What would you notice in an asthmatic in a lung function test?
Airways obstruction may be present (reduced FEV1, reduced FEV1/FVC ratio)
PEFR reductions from percent predicted, variability (>20% predicted 3/7 days)
Increased responsiveness to challenge agents (mannitol, methacholine)
What is reversibility testing?
The test is carried out using a machine called a spirometer which measures how well your lungs work. Reversibility testing involves performing spirometry before and after you have taken medication and is sometimes done to investigate a diagnosis of asthma, or when diagnosis is not clear.
Increase in lung capacity with bronchodilators or anti-inflammatory treatment
Increase of 12% in FEV1 together with an increase of 200ml in volume is positive >400ml increase makes asthma highly likely
20% variability in PEFTR also suggests asthma
What are the specific tests for airway inflammation?
Becoming more common
Exhaled nitric oxide (FeNO), a marker of eosinophilic inflammation - but not specific, suppressed in smokers, elevated with viral infections and rhinitis
Direct measurement of cells in the airways can reliably guide treatment
How to diagnose asthma in the light of a high or low probability?
High probability of asthma - code as suspected asthma, initiation of treatment an assess response
Good response: Asthma, adjust maintenance dose
Poor response: intermediate probability of asthma, test for airway obstruction
Low probability of asthma - investigate/treat for a more likely diagnosis
What is severe asthma?
One major and two minor characteristics
MAJOR
Treatment with continuous oral steroids
Requirement for high dose inhaled steroids
MINOR
Additional daily reliever medication (beta agonists, theophylline, LTRA)
Symptoms needing reliever medication on a daily or near daily basis
Persistent airway obstruction (FEV1<80%, diurnal variation PEFR >20%)
>1 emergency visits p.a.
>3 steroid courses p.a.
Prompt deterioration with <25% reduction in oral or inhaled steroid dose
Near-fatal event in the past
Who is at risk of an asthma death?
>3 classes of treatment Recent admission/frequent attender Previous near-fatal disease Brittle disease Psychosocial factors
What are the differential diagnoses of asthma?
Bronchiolitis
Bronchiectasis (often complicates co-existing asthma)
CF
PE
Cancer
Cryptogenic fibrosing alveolitis
Hyperventilation (often complicates co-existing asthma)
Bronchial obstruction (foreign body, tumour etc)
Vocal cord dysfunction (often complicates co-existing asthma)
Aspiration
Congestive heart failure
COPD
What’s the aim of asthma treatment?
Most patients have poor control
Aim to improve control
Address important issues for patients (exercise for example)
Maximum symptoms for minimum side-effects
What’s the treatment of asthma?
Avoidance of triggers: allergen avoidance, occupational issues
Classes of drugs available:
Bronchodilators: beta agonists, leukotriene, receptor antagonists, theophyllines, long acting beta agonists, anticholinergics
Anti-inflammatory drugs: steroids
New biologics: omalizumab, mepolizumab
Why do we need steroids to asthmatics?
Bronchodilators treat the symptoms, not the disease
We need steroids to reduce airway inflammation and decrease mortality risks
What are the side effects of steroids?
Systemic: diabetes, cataracts, osteoporosis, hypertension, skin thinning, easy bruising, growth retardation, osteonecrosis of the femoral head
Topical: hoarse voice, oral candida, skin thinning, easy bruising, cataracts (in high dose)
Adrenal suppression
What are the delivery devices for asthmatic treatment?
Multiple different delivery devices: MDIs, dry powder
Use of a spacer to improve delivery and minimise side effects
What are the NICE treatment steps for asthma?
Diagnosis and assessment - consider monitor initiation of treatment with low dose inhaled corticosteroids
STEP 1: Regular preventer: Low dose inhaled corticosteroids
STEP 2: Initial add-on therapy: Add inhaled LABA to ICS (usually a combined inhaler)
STEP 3: Additional add-on therapy: if no response to LABA, stop LABA and consider increased dose of ICS.
If LABA is beneficial but still inadequate, continue LABA but increase ICS to a medium dose.
If LABA is beneficial but still inadequate, continue LABA and ICS and consider trial of other therapy - LTRA, S-R theophylline, LAMA
STEP 4: Consider trials of increasing ICS up to high dose or addition of a fourth drug e.g. LTRA, S-R theophylline, beta agonist tablet, LAMA. Refer patient for specialist care.
STEP 5: Use daily steroid tablet in the lowest dose providing adequate control. Maintain high dose ICS. Consider other treatments to minimize use of steroid tablets.
What do we do if the asthma drugs aren’t working?
Revisit the basics, particularly technique and adherence
Investigate and treat
Second line immunosuppression
Phenotype-specific management
What’s the treatment for severe eosinophilic asthma?
Anti-IgE (omalizumab) for atopic allergic disease - removes Ig-E from the blood
Anti-IL-5 (mepolizumab) - removes IL-5 from the blood
Oral steroids, additional immunosuppressants (guided by overall atopic disease burden
What’s the treatment for non-eosinophilic asthma?
Maintain appropriate level of steroid therapy
Focus on more bronchodilator treatment (same inhalers)
Consider bronchial thermoplasty
What happens to asthma in pregnancy?
⅓ gets worse
⅓ stays the same
⅓ gets better
Most standard asthma treatments are safe in pregnancy
How to recognise an severe asthma attack?
Do PEFR, full clinical assessment
Do oximetry
Gases of acute severe or low saturations (<92% on air, or needing O2)
CXR if suspect pneumothorax, consolidation, life threatening asthma, failure to respond
What are the markers of an moderate asthma attack?
UNCONTROLLED/MODERATE PEFR >50% RR <25 Pulse <110 Normal speech, no other severe markers
What are the markers of a severe asthma attack?
SEVERE (any one of…) PEFR 33-50% predicted RR >25 HR >110 Inability to complete sentences
What are the markers of a life-threatening asthma attack?
LIFE-THREATENING (any one of…)
PEFR <33%
SaO2 <92% or PaO2 <8kPa
Normal PaCO2 4.6-6 kPa (in early asthma you tend to hyperventilate so it is low but just before you expire you return to a normal CO2)
Altered consciousness, exhaustion, arrhythmia, hypotension, silent chest, poor effort, cyanosis.
What are the markers of a near fatal asthma attack?
NEAR FATAL
Raised PaCO2 and/or requiring ventilation with raised airway pressures.
What is the immediate treatment for an asthma attack?
Oxygen 40-60% (CO2 retention not usually a problem)
Salbutamol neb 5mg (+ipratropium neb 0.5mg if life threatening) - repeated/IV infusion
Prednisolone 30-60mg (+/- hydrocortisone 200mg IV)
Consider magnesium or aminophylline IV (bolus/load)
ABGs
CXR if suspect pneumothorax, consolidation or fails to respond to treatment (or is very severe)
How would you monitor a patient who has just had an asthma attack?
PEFR check within 15-30mins/regularly
Oximetry to maintain SaO2 >92%
Repeat ABG within 2 hours if severe attack or patient deteriorating
If deteriorating despite maximal treatment with worsening hypoxia, hypercapnia or coma/exhaustion - ITU transfer
Watch K, glucose
Consider rehydration
What would you do before the discharge of a patient who has had an asthma attack?
Opportunity to educate and prevent readmissions
Achieve PEFR >75% and <25% variability
Prednisolone for minimum 7-14 days (never decrease until improving)
Step up treatment
Asthma action plan
Nurse-led follow-up
Early clinical review (48 hours at GP surgery)
What are the different infections you can get in the respiratory tract?
Sinusitis
Tonsillitis - infection of the tonsils
Pharyngitis - ‘sore throat’ infection of the pharynx
Laryngitis - infection of the larynx
Tracheitis - infection of the trachea
Bronchiolitis - infection of the bronchioles
Pleurisy - inflammation of the pleura often caused by an infection
Bronchitis - infection of the bronchi
Pneumonia - infection of the alveoli and surrounding lung
Why are there so many infections in the respiratory tract?
Skin is a good barrier to infection - keeps everything out, is waterproof and also keeps everything in except sweat
Urinary system is sterile and flow is outwards
Intestine has acidic stomach/enzymes/commensal bacteria/thick mucosal barrier/mucosal immune system, Gut-associated lymphoid tissue (GALT).
Vagina has acidic pH/commensal bacteria/thick mucosal barrier/mucosal immune system
In the lungs, air has to go in and out and cross a very thin membrane (cannot have a massive barrier), there is a huge surface area.
What are the lung immune defences against pathogens in the respiratory tract?
- Commensal flora - colonisation resistance
- Swallowing - normal swallowing reflex using the epiglottis, neurological and anatomical factors
- Lung anatomy - mucus and ciliated epithelium ‘mucociliary escalator’ and barrier to some extent (moves things along) - can be damaged by viral infection - then micro aspiration from colonised URT increases risk of bacterial infection
- Cough reflex and sneezing
- Innate and adaptive immunity - soluble factors (IgA, defensins, collectins, lysozyme), alveolar macrophages, B and T cells, neutrophils if required
What are the commensal flora present in the respiratory tract?
Sinuses - sterile
Nares - Staphylococcus epidermidis and corynebacterium
Teeth - Streptococci, lactobacilli
Mucous - membranes streptococci and lactic acid bacteria
Pharynx - Streptococci, gram neg rods and cocci
Who is at greater risk of a respiratory tract infection?
Problems with swallowing - stroke, MND, tumour, surgery
Altered lung physiology - CF, bronchiectasis, emphysema, ILD (intrinsic), spinal disease, weakness, obesity, surgery (extrinsic)
Colonisation of the upper airways
Immune dysfunction - primary immunodeficiency, complement deficiencies, HIV, immunosuppressant therapy
Comorbidities
How common is pneumonia?
Very common (1 in 300)
20-50% hospitalised, 5-10% ITU
Average 6-8 days
Mortality: 1% community, 10% hospital, 30% ITU
Who is at risk of pneumonia?
Infants and elderly COPD and other chronic lung diseases Immunocompromised Nursing home residents Impaired swallow (neurological conditions etc.) Diabetes Congestive heart disease Alcoholics and intravenous drug users
What is the pathology of pneumonia?
Bacteria that have arrived quickly or have colonised for a while get micro-aspirated into the lower lung, they translocate to the normally sterile distal airway.
Macrophages see the bacteria and eat up the bacteria in a phagolysosome.
But it can get overwhelmed if there is too much bacteria or the patient is immunosuppressed. In this case, it brings in neutrophils through gaps in the endothelium.
Pus forms due to the excess fluid, antibodies, dead neutrophils.
Pus in the alveolus inhibits gas exchange.
‘Resolution phase’ is when the bacteria are cleared - inflammatory cells are removed by apoptosis. Resolution phase leads to complete recovery.
Severe disease if excessive inflammation, lung injury and/or failure to resolve without lung damage.
What are the symptoms of pneumonia?
Fevers, sweats, rigors (generic infection response)
Cough - classically rusty sputum suggests S. pneumoniae, but may be none, particularly with organisms such as Mycoplasma, Chlamydophila and Legionella (atypical pathogens)
Short of breath
Pleuritic chest pain (pain worse on deep breathing) particularly S.pneumoniae
Systemic features including weakness and malaise
Extrapulmonary features such as neurological or gastrointestinal with Legionella sp. Or a rash with mycoplasma
What are the signs of pneumonia?
Raised heart rate Raised respiratory rate Low blood pressure Fever Dehydration The more present, the more severe the illness.
What are the signs of lung consolidation on percussion and auscultation?
Dull to percussion Decreased air entry Bronchial breath sounds Crackles +/- wheeze Increased vocal resonance \+/- Hypoxia and signs of respiratory failure especially if chronic lung disease or severe pneumonia
What are the investigative tests for pneumonia?
Chest X-ray
Full blood count - WBC aids diagnosis and helpful as a marker of severity
Biochemistry - for urea and electrolytes and liver function tests (renal function required to assess severity, other tests for complications)
C-reactive protein - helps with diagnosis, assessment of severity and recovery
Pulse oximetry - assess severity and if required arterial blood gas define respiratory failure
Microbiological tests
What can a chest x-ray tell you in a patient with pneumonia?
Look for ‘air bronchogram’ in consolidated area
Multi-lobar suggestive of S.pneumoniae, S.aureus, Legionella sp.
Multiple abscesses or pneumatoceles of S.aureus
Air fluid level in abscess
Upper lobe cavity K. pneumoniae
Interstitial or diffuse shadowing more suggestive of viral or Pneumocystis pneumonia (PCP) in HIV or immunocompromised
Pleural collections - require aspiration and management to avoid emphysema
Look for features suggestive of alternative diagnosis - TB, lung cancer
What are some indicators of severity and a significant infection in pneumonia?
Pro-inflammatory cytokines Vasodilation Impaired cardiac contractility Reduced blood pressure Impaired organ perfusion Tissue hypoxia
What are the warning signs of sepsis in a patient with pneumonia?
Signs of delirium/confusion, renal impairment due to the urea rise, increased oxygen demand (high RR, lactic acid production), systolic and diastolic BP drop.
What is CURB65?
Signs of pneumonia Confusion Urea >7mmol/L Respiratory rate >30/min Blood pressure; low systolic <90mmHg or diastolic <60mmHg Age >65
One point for each. Predicts mortality. 0 = 0.7% 1 = 2.1% 3 = 9.2% 4-5 = 15-40%
What are the indications for the results of CURB65?
0-1 = mild, only admit if social circumstances or single worrying feature 2 = moderate, admit to hospital 3-5 = admit and closely monitor 4-5 = consider admission to critical care unit
In the community you can use this score (without the urea result).
What’s the different between broad and narrow spectrum antibiotics?
Broad spectrum - will work (for now), but is expensive, may have adverse effects, harder to give, promotes resistance
Narrow - Might miss, more tolerable, saves other choices, cheaper
Give some examples of the type of bacteria that can case pneumonia?
S.pneumoniae 40% Mycoplasma 11% C.pneumoniae 13% Legionella sp. 4% H. influenzae 5% Viruses 13% No diagnosis 31%
What are the features of S.pneumoniae and how do you treat the pneumonia caused by it?
Gram positive cocci
Alpha hemolytic, optochin sensitive
>90 serotypes
Any age but more likely at extremes of age
Can be severely ill with respiratory failure or sepsis
‘Invasive pneumococcal disease’
Antibiotics: B-lactam antibiotic e.g. Amoxicillin, Cefuroxime, Cefotaxime
Alternatives: Macrolides:Clarithromycin, Fluoroquinolones, Ciprofloxacin
What are the features of H.influenzae and how do you treat the pneumonia caused by it?
Gram negative coccobacilli Encapsulated - has vaccine Unencapsulated ‘non-typable’ Antibiotics: B-lactam antibiotic - Amoxicillin + clavulanic acid ‘co-amoxiclav’ Tetracyclines - doxycycline NOT macrolides
What are the features of Staph. Aureus and how do you treat the pneumonia caused by it?
May complicate recent influenza
Ventilator-associated pneumonia too
Antibiotics: B-lactam antibiotic - Flucloxacillin, Cefuroxime
If resistant (MRSA) - vancomycin, linezolid
What are the features of Klebsiella pneumoniae and how do you treat the pneumonia caused by it?
Gram negative bacilli Enterobacteriaceae Normal flora of the mouth and intestines Homeless, alcoholic, hospital-associated Antibiotics: B-lactam antibiotic - Co-amoxiclav, Cephalosporins
What are some atypical pathogens that can cause pneumonia?
Legionella pneumophila Mycoplasma pneumoniae Chlamydophila pneumoniae Chlamydophila psittaci Coxiella burnetii
Why are the atypical pathogens that cause pneumonia so sneaky?
They are intracellular pathogens that are difficult to detect and don’t grow in standard agar. Need different detection methods - need antibody/serology testing.
Don’t respond to B-lactams or penicillins.
Require ‘special’ antibiotics - macrolides (erythromycin/clarithromycin) or fluoroquinolones (ciprofloxacin) or tetracyclines (doxycycline).
What are the features of Mycoplasma pneumoniae?
Epidemics every 4 years
Usually in younger adults, milder illness
May have extrapulmonary features:
Haemolytic anemia (cold agglutinins)
Raynaud’s (cold agglutinins) erythema multiforme
Bullous myringitis (blisters on tympanic membrane)
Encephalitis
What are the features of Legionella spp.?
Lives in free living amoeba - like warm water Clusters of cases related to water cooling towers, showers, air conditioning, travel Severe illness, respiratory failure May be elderly, immunocompromised Extrapulmonary features: - Diarrhoea - Abnormal liver function tests - Hyponatremia - Myalgia, raised creatinine levels - Interstitial nephritis - Encephalitis, confusion
What are the features of Chlamydophila pneumoniae?
Like M.pneumoniae but more likely in older groups, more prolonged wheezing
Often older adults, sometimes closed outbreaks, longer duration of symptoms
How do you get Chlamydophila psittaci?
Contact with sick birds (parrots), poultry workers
How do you get Coxiella burnetii (Q fever)?
Exposure to pregnant animals in labour, especially sheep
What are the microbiology tests for pneumonia?
Sputum culture and sensitivity +/- Gram stain
Blood culture (low sensitivity)
Serology (acute and convalescent) - for viruses and atypical organisms
Urinary antigen - Legionella spp. (if history suggests risks or severe) or S.pneumoniae where available
PCR (only in outbreaks or specific patients) - viruses, Mycoplasma pneumonia
Remember to consider acid fast bacilli stain and culture for TB if the epidemiology or clinical features are suggestive.
How do you treat pneumonia with antibiotics?
Antimicrobial stewardship: use the narrowest spectrum of antibiotics as possible to reduce antibiotic resistance, side effects e.g. antibiotic-associated diarrhoea
Mild severity pneumonia in community (CRB65 0-1)
Amoxicillin 500mg tid (3x a day) PO
Penicillin allergic? Use Clarithromycin 500mg bd or Doxycycline 200mg load and then 500mg od PO
Moderate severity (CRB65 2) Amoxicillin plus Clarithromycin PO
Severe (CRB65 3-5)
IV Co-amoxiclav 1.2g tid and Clarithromycin 500mg bd
Alternatives - Cefuroxime 1.5mg and Clarithromycin 500mg bd
How long does a pneumonia patient need to take antibiotics?
5 days for mild-moderate, may extend >5 days if severe
14-21 days for S.aureus, gram negative bacteria and Legionella spp.
What are the special cases of pneumonia and how are they treated?
Legionella spp - ensure fluoroquinolone in regimen either alone or with clarithromycin
Necrotising pneumonia or other features of Panton-Valentine Leukocidin producing S.aureus infection - IV Linezolid 600mg bd or IV Clindamycin 1.2g qid
Pseudomonas aeruginosa - IV Ceftazidime 3g tid or Piperacillin-tazobactam 4.5g tid. With Gentamicin/Tobramycin or Ciprofloxacin 400mg bd
What is PVL?
PVL = Panton-Valentine Leukocidin is a cytotoxin produced by some aggressive strains of S.aureus that cause a fulminant necrotising pneumonia.
