Respiratory

Question 1

How does a virus affect different parts of the respiratory system?

Answer 1

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

Question 2

Who is RSV most dangerous for?

Answer 2

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.

Question 3

What is the influenza virus?

Answer 3

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.

Question 4

Where are the antigenic sites on the virus?

Answer 4

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.

Question 5

How is Influenza A categorised?

Answer 5

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

Question 6

Which viral antigens are found in humans?

Answer 6

H1-3 and N1-2 have evolved and adapted so that they can be transmitted between humans.

Question 7

How does the influenza virus change?

Answer 7

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.

Question 8

What’s the difference between influenza A, B and C?

Answer 8

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

Question 9

How is influenza transmitted?

Answer 9

Transmission mainly via aerosols generated by coughs and sneezes. However, also possible via hand-to-hand contact, other personal contact or fomites.

Question 10

How does influenza present?

Answer 10

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

Question 11

Who is at risk of mortality from influenza?

Answer 11

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

Question 12

What are the treatment options for influenza?

Answer 12

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

Question 13

What are the features of the seasonal flu?

Answer 13

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.

Question 14

What are the features of the pandemic flu?

Answer 14

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…

Question 15

What are the consequences of pandemic flu?

Answer 15

High morbidity
Excess mortality
Social disruption
Economic disruption

Question 16

What are the features of the spanish flu?

Answer 16

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.

Question 17

What is the timeline in pandemic flu?

Answer 17

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

Question 18

What is the overall case fatality rate and the clinical attack rate?

Answer 18

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

Question 19

Will we get more pandemics?

Answer 19

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?

Question 20

What is the Avian Flu?

Answer 20

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

Question 21

Why was avian flu prevalent in SE Asia?

Answer 21

Close proximity of poultry and people.

50 – 80% of poultry in small rural households

Question 22

How to control Avian flu?

Answer 22

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

Question 23

How were people prepared for swine flu?

Answer 23

International surveillance
Virus research
Vaccine research
Stock piling of drugs - 30 million courses of Oseltamivir
Plans written – strategic
Preparation of information – public and professional

Question 24

What are the features of swine flu?

Answer 24

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

Question 25

What are the phases of the pandemic?

Answer 25

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

Question 26

What are the rules of infection control?

Answer 26

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

Question 27

How to manage cases in a pandemic?

Answer 27

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

Question 28

What are antivirals?

Answer 28

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...)

Question 29

What are the issues with antivirals?

Answer 29

What happens if the virus develops resistance? What about side effects? Who do we give them to? How do we distribute them?

Question 30

When are face masks useful in a infection?

Answer 30

``` Worn correctly Changed frequently Removed properly Disposed of safely Used in combination with good universal hygiene practice ```

Question 31

What is the impact of a pandemic on the health service staff?

Answer 31

``` 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 ```

Question 32

What is the impact of a pandemic on schools?

Answer 32

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

Question 33

What's the hope of vaccines in a pandemic?

Answer 33

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

Question 34

What are the possible population-wide interventions that need to be taken in the face of a pandemic?

Answer 34

``` 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 ```

Question 35

What is MERS?

Answer 35

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

Question 36

What are the normal oxygen values for arterial blood?

Answer 36

Arterial blood: PaO2 90 -110 mm Hg (12.14.6 kPa) | Note PaO2 ~6 mm Hg (0.8kPa) lower in supine position

Question 37

What are the normal carbon dioxide values for arterial blood?

Answer 37

Blood PCO2 34-46 mm Hg (4.6-6.1 kPa) | Hyper/hypocapnia - Blood PCO2 outwith this range

Question 38

What are the different types of hypoxia?

Answer 38

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

Question 39

What is type 1 respiratory failure?

Answer 39

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)

Question 40

What is type 2 respiratory failure?

Answer 40

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

Question 41

What is the function of the nasal conchae?

Answer 41

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

Question 42

What is Stridor?

Answer 42

Upper airway block Prominent sound on inspiration Seen in children with coup

Question 43

What are the features of the broncioles?

Answer 43

``` Smooth muscle Mucous glands Cilia - Muco-ciliary staircase - Remove debris ```

Question 44

What happens at the alveolar epithelium?

Answer 44

Metabolic function Site of ACE – important for regulating salt balance Coverts Angiotensin 1 to Angiotensin 2

Question 45

What are the two zones of the bronchial tree?

Answer 45

``` 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 ```

Question 46

What is tidal volume?

Answer 46

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

Question 47

What is the minute volume?

Answer 47

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

Question 48

What are the features of the lung mechanics?

Answer 48

Elastic lungs Moveable ribs Muscles - external intercostals and diagphragm

Question 49

What are the elastic properties of lung tissue?

Answer 49

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

Question 50

Why are newborn/premature babies at risk of lung collapse?

Answer 50

Smaller the alveoli, the greater the surface tension | Babies don’t have much surfactant and have very tiny alveoli – high surface tension

Question 51

What are the mechanics of lung inhalation?

Answer 51

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.

Question 52

What does the surface tension do?

Answer 52

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.

Question 53

What is a flail chest?

Answer 53

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

Question 54

What is a pneumothorax?

Answer 54

Intra-pleural pressure equilibrates to atmospheric pressure “Vacuum” lost Lung collapses

Question 55

What can cause a pneumothorax?

Answer 55

Thoracic trauma - Blunt or penetrating | Spontaneous - ruptured bullae

Question 56

What is a bulla in the lung?

Answer 56

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.

Question 57

What are the treatment options for a pneumothorax?

Answer 57

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)

Question 58

How to treat a Persistent Spontaneous Pneumothorax?

Answer 58

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.

Question 59

What is Spirometry?

Answer 59

``` 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. ```

Question 60

What do all the lung volumes mean?

Answer 60

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

Question 61

What do all the lung capacities mean?

Answer 61

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)

Question 62

How does being pregnant affect the the capacities and volumes of the lungs?

Answer 62

Reduced inspiratory reserve volume Increased tidal volume Reduced expiratory reserve volume Reduced residual volume Reduced total lung capacity Reduced functional residual capacity

Question 63

What can spirometry be used for in the clinic?

Answer 63

Differentiate between Obstructive (COPD, asthma, CF) - obstructs the patient from exhaling Restrictive (fibrosis, oedema) - impinges on inhalation, stops people from filling their lungs

Question 64

What is FEV1 and FVC?

Answer 64

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

Question 65

What is normal FEV1 and FVC?

Answer 65

FEV1: >80% predicted FVC: >80% predicted FEV1/FVC ratio: >0.7

Question 66

How does airway resistance change in disease?

Answer 66

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

Question 67

What is lung compliance?

Answer 67

Extent to which lungs will expand for a given increase in trans-pulmonary pressure Lung vol. change / unit of transpulmonary pressure

Question 68

What are the different pressures in the lung?

Answer 68

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

Question 69

What is inspiratory and expiratory compliance in the lung?

Answer 69

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

Question 70

What happens when there is reduced lung compliance?

Answer 70

“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)

Question 71

What happens when there is high lung compliance?

Answer 71

``` Elastic fibres degraded means there is low elastic recoil Difficulty exhaling Difficulty inhaling Collapsed alveoli Increased work of breathing Occurs during Emphysema and COPD ```

Question 72

What is the pathophysiology of asthma?

Answer 72

``` 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 ```

Question 73

What is the pathophysiology of COPD/em

Answer 73

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

Question 74

Why can giving a COPD patient supplemental oxygen be dangerous?

Answer 74

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

Question 75

What is the neurological control of ventilation?

Answer 75

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

Question 76

What do the different respiratory centres do?

Answer 76

``` 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 ```

Question 77

What nerves are required for the neurological control of ventilation?

Answer 77

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

Question 78

What are the central and peripheral chemoreceptors?

Answer 78

``` 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

Question 79

How does the body respond to an increased carbon dioxide?

Answer 79

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

Question 80

What are the general arterial blood gas values?

Answer 80

pH 7.35 - 7.45 HCO3-- 24-28mmol/L pCO2 35-45 mHhg paO2 75-100mmHg (on air)

Question 81

How does the kidney react to increased H+ (acidosis)?

Answer 81

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

Question 82

How does the kidney react to increased HCO3- (alkalosis)?

Answer 82

Excess filtered HCO3- Not titrated by H+ Excreted in urine Decrease resp rate (minor)

Question 83

What's the difference between the pulmonary and circulatory circulation?

Answer 83

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

Question 84

What is the bronchial circulation?

Answer 84

Part of the systemic circulation Supplies lung parenchyma Returns via pulmonary veins

Question 85

How do the alveolar and extra-alveolar vessels differ?

Answer 85

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)

Question 86

Why is there an uneven distribution of pulmonary blood?

Answer 86

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

Question 87

What is the Ventilation:Perfusion Ratio?

Answer 87

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

Question 88

What happens when there is a ventilation:perfusion mismatch?

Answer 88

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

Question 89

What is Hypoxic Pulmonary Vasoconstriction?

Answer 89

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)?

Question 90

What determines whether gas exchange occurs?

Answer 90

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)

Question 91

What is pulse oximetry?

Answer 91

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.

Question 92

What anatomical changes mean that a pregnant woman's respiratory volumes and capacities are different?

Answer 92

Diaphragmatic elevation (~4cm) Increased sub-costal angle Increased thoracic circumference Decreased chest compliance but lung compliance unchanged Progesterone-induced tracheo-bronchial smooth muscle relaxation

Question 93

Why do pregnant women experience dyspnoea?

Answer 93

Increased tidal vol causes increased minute volume | ~70% women experience subjective dyspnoea

Question 94

Why is it important that there is a CO2 gradient between the mother and baby?

Answer 94

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

Question 95

How does the kidney compensate for respiratory alkalosis in pregancy?

Answer 95

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.

Question 96

How common is asthma?

Answer 96

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

Question 97

What is the pathology of asthma?

Answer 97

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

Question 98

What are the two types of asthma?

Answer 98

Eosinophilic - can be associated with allergy or not, the non-allergy variant is usually seen in adulthood. Non-eosinophilic

Question 99

What is atopic asthma?

Answer 99

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.

Question 100

What is Eosinophilic asthma?

Answer 100

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.

Question 101

What causes Atopic eosinophilic asthma?

Answer 101

Atopic eosinophilic asthma can be associated with fungal allergy, common aeroallergens (cat, dog, house, house dust mite) and occupation, pets, exposures.

Question 102

What Non-eosinophilic asthma?

Answer 102

``` No eosinophils present, instead the presence of neutrophils. Not very well understood. Divided into: Obesity-related Smoking-related Non-smoking, non-eosinophilic ```

Question 103

What is the overlap between asthma and COPD?

Answer 103

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

Question 104

How does Asthma present?

Answer 104

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

Question 105

What is cough-variant asthma?

Answer 105

A type of asthma in which the main symptom is a dry, non-productive cough.

Question 106

What factors may indicate the severity of asthma?

Answer 106

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

Question 107

What may suggest asthma that is poorly controlled?

Answer 107

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.

Question 108

What needs to be included when you're taking a history of an potential asthmatic?

Answer 108

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?

Question 109

What are the associated symptoms with asthma?

Answer 109

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

Question 110

What do you need to ask about a potential asthmatic's past medical history?

Answer 110

Always a vital part of the history Previous pneumonias (bronchiectasis?) Neurological/renal problems (vasculitis)

Question 111

What do you need to ask about a potential asthmatic's drug history?

Answer 111

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

Question 112

What do you need to ask about a potential asthmatic's social and family history?

Answer 112

``` 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 ```

Question 113

What do you need to ask about a potential asthmatic's occupation?

Answer 113

Exposure to dusts, fumes, allergens Lab workers, veterinary staff, animal breeders Paint sprayers Bakers Is your asthma better on holiday? Worse at work?

Question 114

How would you distinguish COPD from asthma?

Answer 114

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

Question 115

What would you see in an physical examination for asthma?

Answer 115

May be normal Wheeze, polyphonic, expiratory, widespread Absence of crackles, sputum and other signs

Question 116

What tests would you to look for asthma?

Answer 116

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

Question 117

What would you notice in an asthmatic in a lung function test?

Answer 117

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)

Question 118

What is reversibility testing?

Answer 118

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

Question 119

What are the specific tests for airway inflammation?

Answer 119

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

Question 120

How to diagnose asthma in the light of a high or low probability?

Answer 120

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

Question 121

What is severe asthma?

Answer 121

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

Question 122

Who is at risk of an asthma death?

Answer 122

``` >3 classes of treatment Recent admission/frequent attender Previous near-fatal disease Brittle disease Psychosocial factors ```

Question 123

What are the differential diagnoses of asthma?

Answer 123

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

Question 124

What's the aim of asthma treatment?

Answer 124

Most patients have poor control Aim to improve control Address important issues for patients (exercise for example) Maximum symptoms for minimum side-effects

Question 125

What's the treatment of asthma?

Answer 125

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

Question 126

Why do we need steroids to asthmatics?

Answer 126

Bronchodilators treat the symptoms, not the disease | We need steroids to reduce airway inflammation and decrease mortality risks

Question 127

What are the side effects of steroids?

Answer 127

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

Question 128

What are the delivery devices for asthmatic treatment?

Answer 128

Multiple different delivery devices: MDIs, dry powder | Use of a spacer to improve delivery and minimise side effects

Question 129

What are the NICE treatment steps for asthma?

Answer 129

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.

Question 130

What do we do if the asthma drugs aren't working?

Answer 130

Revisit the basics, particularly technique and adherence Investigate and treat Second line immunosuppression Phenotype-specific management

Question 131

What's the treatment for severe eosinophilic asthma?

Answer 131

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

Question 132

What's the treatment for non-eosinophilic asthma?

Answer 132

Maintain appropriate level of steroid therapy Focus on more bronchodilator treatment (same inhalers) Consider bronchial thermoplasty

Question 133

What happens to asthma in pregnancy?

Answer 133

⅓ gets worse ⅓ stays the same ⅓ gets better Most standard asthma treatments are safe in pregnancy

Question 134

How to recognise an severe asthma attack?

Answer 134

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

Question 135

What are the markers of an moderate asthma attack?

Answer 135

``` UNCONTROLLED/MODERATE PEFR >50% RR <25 Pulse <110 Normal speech, no other severe markers ```

Question 136

What are the markers of a severe asthma attack?

Answer 136

``` SEVERE (any one of…) PEFR 33-50% predicted RR >25 HR >110 Inability to complete sentences ```

Question 137

What are the markers of a life-threatening asthma attack?

Answer 137

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.

Question 138

What are the markers of a near fatal asthma attack?

Answer 138

NEAR FATAL | Raised PaCO2 and/or requiring ventilation with raised airway pressures.

Question 139

What is the immediate treatment for an asthma attack?

Answer 139

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)

Question 140

How would you monitor a patient who has just had an asthma attack?

Answer 140

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

Question 141

What would you do before the discharge of a patient who has had an asthma attack?

Answer 141

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)

Question 142

What are the different infections you can get in the respiratory tract?

Answer 142

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

Question 143

Why are there so many infections in the respiratory tract?

Answer 143

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.

Question 144

What are the lung immune defences against pathogens in the respiratory tract?

Answer 144

- 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

Question 145

What are the commensal flora present in the respiratory tract?

Answer 145

Sinuses - sterile Nares - Staphylococcus epidermidis and corynebacterium Teeth - Streptococci, lactobacilli Mucous - membranes streptococci and lactic acid bacteria Pharynx - Streptococci, gram neg rods and cocci

Question 146

Who is at greater risk of a respiratory tract infection?

Answer 146

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

Question 147

How common is pneumonia?

Answer 147

Very common (1 in 300) 20-50% hospitalised, 5-10% ITU Average 6-8 days Mortality: 1% community, 10% hospital, 30% ITU

Question 148

Who is at risk of pneumonia?

Answer 148

``` 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 ```

Question 149

What is the pathology of pneumonia?

Answer 149

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.

Question 150

What are the symptoms of pneumonia?

Answer 150

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

Question 151

What are the signs of pneumonia?

Answer 151

``` Raised heart rate Raised respiratory rate Low blood pressure Fever Dehydration The more present, the more severe the illness. ```

Question 152

What are the signs of lung consolidation on percussion and auscultation?

Answer 152

``` 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 ```

Question 153

What are the investigative tests for pneumonia?

Answer 153

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

Question 154

What can a chest x-ray tell you in a patient with pneumonia?

Answer 154

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

Question 155

What are some indicators of severity and a significant infection in pneumonia?

Answer 155

``` Pro-inflammatory cytokines Vasodilation Impaired cardiac contractility Reduced blood pressure Impaired organ perfusion Tissue hypoxia ```

Question 156

What are the warning signs of sepsis in a patient with pneumonia?

Answer 156

Signs of delirium/confusion, renal impairment due to the urea rise, increased oxygen demand (high RR, lactic acid production), systolic and diastolic BP drop.

Question 157

What is CURB65?

Answer 157

``` 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% ```

Question 158

What are the indications for the results of CURB65?

Answer 158

``` 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).

Question 159

What's the different between broad and narrow spectrum antibiotics?

Answer 159

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

Question 160

Give some examples of the type of bacteria that can case pneumonia?

Answer 160

``` S.pneumoniae 40% Mycoplasma 11% C.pneumoniae 13% Legionella sp. 4% H. influenzae 5% Viruses 13% No diagnosis 31% ```

Question 161

What are the features of S.pneumoniae and how do you treat the pneumonia caused by it?

Answer 161

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

Question 162

What are the features of H.influenzae and how do you treat the pneumonia caused by it?

Answer 162

``` Gram negative coccobacilli Encapsulated - has vaccine Unencapsulated ‘non-typable’ Antibiotics: B-lactam antibiotic - Amoxicillin + clavulanic acid ‘co-amoxiclav’ Tetracyclines - doxycycline NOT macrolides ```

Question 163

What are the features of Staph. Aureus and how do you treat the pneumonia caused by it?

Answer 163

May complicate recent influenza Ventilator-associated pneumonia too Antibiotics: B-lactam antibiotic - Flucloxacillin, Cefuroxime If resistant (MRSA) - vancomycin, linezolid

Question 164

What are the features of Klebsiella pneumoniae and how do you treat the pneumonia caused by it?

Answer 164

``` Gram negative bacilli Enterobacteriaceae Normal flora of the mouth and intestines Homeless, alcoholic, hospital-associated Antibiotics: B-lactam antibiotic - Co-amoxiclav, Cephalosporins ```

Question 165

What are some atypical pathogens that can cause pneumonia?

Answer 165

``` Legionella pneumophila Mycoplasma pneumoniae Chlamydophila pneumoniae Chlamydophila psittaci Coxiella burnetii ```

Question 166

Why are the atypical pathogens that cause pneumonia so sneaky?

Answer 166

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).

Question 167

What are the features of Mycoplasma pneumoniae?

Answer 167

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

Question 168

What are the features of Legionella spp.?

Answer 168

``` 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 ```

Question 169

What are the features of Chlamydophila pneumoniae?

Answer 169

Like M.pneumoniae but more likely in older groups, more prolonged wheezing Often older adults, sometimes closed outbreaks, longer duration of symptoms

Question 170

How do you get Chlamydophila psittaci?

Answer 170

Contact with sick birds (parrots), poultry workers

Question 171

How do you get Coxiella burnetii (Q fever)?

Answer 171

Exposure to pregnant animals in labour, especially sheep

Question 172

What are the microbiology tests for pneumonia?

Answer 172

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.

Question 173

How do you treat pneumonia with antibiotics?

Answer 173

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

Question 174

How long does a pneumonia patient need to take antibiotics?

Answer 174

5 days for mild-moderate, may extend >5 days if severe | 14-21 days for S.aureus, gram negative bacteria and Legionella spp.

Question 175

What are the special cases of pneumonia and how are they treated?

Answer 175

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

Question 176

What is PVL?

Answer 176

PVL = Panton-Valentine Leukocidin is a cytotoxin produced by some aggressive strains of S.aureus that cause a fulminant necrotising pneumonia.

Question 177

What vaccines are available to seek to prevent pneumonia?

Answer 177

Polysaccharide Pneumococcal Vaccine (protects against 23 serotypes) Indications: >65 years, immunocompromised, splenic dysfunction, chronic medical condition: chronic heart, lung, kidney, liver, kidney disease or diabetes Protects against invasive pneumococcal disease (IPD, bacteraemia, meningitis) but not pneumonia. Influenza vaccine is given to those who are >65 years old, immunocompromised or have medical comorbidities. Smoking cessation Pneumococcal conjugate vaccine (13 serotypes) in children has reduced pneumonia in children and IPD in adults.

Question 178

What is Parapneumonic effusion and empyema?

Answer 178

Parapneumonic effusion in 36-57% of CAP - a cause of failure to settle and source of complications e.g. empyema Empyema (~1% of CAP) - a collection of pus in the pleural cavity Failure of fever or markers of inflammation (WBC/CRP) to settle on antibiotics. Pain on deep inspiration. Signs of pleural collection (stony dull to percussion, reduced air entry)

Question 179

What can thoracocentesis tell us?

Answer 179

Parapneumonic effusion requires thoracocentesis (removed with a small needle with ultrasound guidance and sent to the lab) - to identify markers that suggest effusion will fail to resolve - is it just reactive fluid or does it need to be drained? ``` Markers on thoracocentesis suggesting effusion needs drainage: pH <7.2 Glucose <3.3 mmol/L LDH >1,000iu or pH <7 Positive gram stain or culture Pus or thick fluid Suggests empyema ```

Question 180

How would you treat paraneumonic effusions and empyema?

Answer 180

Empyema or complicated parapneumonic effusions require drainage by chest tube placement or cardio-thoracic surgery or decortication (e.g. if it is lobulated) Antimicrobials: Co-amoxiclav, Piperacillin-tazobactam or Meropenem (need to include anaerobic coverage) x <3 weeks

Question 181

What causes a lung abscess?

Answer 181

Seen in aspiration, alcoholics and those with poor dentition Organisms: Streptococcus milleri, anaerobes, klebsiella pneumoniae and other gram neg bacteria Or can be metastatic infection from the right heart and venous system e.g. IVDU, Lemierre’s Organisms: S.aureus, fusobacteria Prolonged antibiotics for up to 6 weeks May need surgical drainage

Question 182

When and in whom does a hospital acquired pneumonia occur?

Answer 182

Acquired at least 48 hours after hospital admission Elderly Ventilator-assisted Post operative

Question 183

What are the diagnostic signs of a hospital acquired pneumonia?

Answer 183

``` New fever Purulent secretions New radiological infiltrates New leukocytosis/CRP increase Plus increased O2 requirements ```

Question 184

How would you treat a hospital acquired pneumonia?

Answer 184

General principle: start broad and then focus treatment after some results Regimen influenced by: Time of HAP Patient factors Likelihood of exposure to resistant microorganisms

Question 185

What causes early-onset hospital acquired pneumonia?

Answer 185

Early onset <5 days of hospital visit Organisms similar to CAP and also anaerobes Antibiotics for anaerobes: Metronidazole or use a B-lactam with inhibitor of B-lactamase: Co-amoxiclav or Piperacillin-tazobactam

Question 186

What causes late-onset hospital acquired pneumonia?

Answer 186

``` Late onset >5 days S.aureus including MRSA Pseudomonas aeruginosa Acinetobacter baumannii Klebsiella pneumoniae ```

Question 187

How to treat hospital acquired pneumonia?

Answer 187

Piperacillin-tazobactam 4.5g qid or Meropenam 1g tid or Ceftazidime 2g tid May need Linezolid or Vancomycin for MRSA IV Colistin for multidrug resistant gram negatives (MDR)

Question 188

What causes pneumonia in immunocompromised patients?

Answer 188

``` Bacterial - all the common cases but may be atypical presentations Pseudomonas aeruginosa Fungal - Pneumocystis pneumonia (PSP) Moulds e.g. Aspergillus spp. Viruses Cytomegalovirus Adenovirus Respiratory syncytial virus (RSV) ```

Question 189

What causes chronic types of pneumonia?

Answer 189

Bacterial - Nocardia spp (immunocompromised), Burkholderia pseudomallei (SE Asia, N Australia), Non-tuberculous mycobacteria Fungal - Histoplasma capsulatum and other dimorphic fungi (americas and other regions), Moulds e.g. Aspergillus spp (patients with hematological malignancy) Parasites - Echinococcus granulosus (dog tapeworm) Non-infectious: malignancy, vasculitis, chronic interstitial pneumonia, drugs, eosinophils, organising pneumonias

Question 190

What is Bronchiolitis?

Answer 190

Infections due to Respiratory Syncytial virus - rarely other viruses, accounts for 80% Inflammation of the bronchioles and mucus production cause airway obstruction

Question 191

What are the different types of emerging respiratory virus infections?

Answer 191

SARS (severe acute respiratory syndrome) Outbreak from China in 2002 Severe respiratory illness with respiratory failure MERS-nCV Middle east respiratory syndrome novel coronavirus Individual cases spread from the middle east in 2012 Similar to SARS but low person to person spread ``` Avian influenza Novel forms of influenza A virus Occasional human cases with severe illness South-east Asia Associated with exposure to poultry Low person to person spread to date ```

Question 192

What is Bronchitis?

Answer 192

Self-limiting inflammation of the epithelia of the bronchi due to upper airway infection Generally results in cough +/- phlegm and breathlessness Acute bronchitis should be differentiated from chronic bronchitis, a condition in patients with COPD distinguished by a cough for at least 3 months in each of two consecutive years. Majority are viral Bacteria are rarely a cause in healthy adults Unless endotracheal tract or tracheostomy then similar bacteria to community acquired pneumonia.

Question 193

What are that the clinical features of Bronchitis?

Answer 193

Cough may be productive or non-productive, lasting more than 5 days (typically 1 to 3 weeks) SOB and often wheeze, but no signs of focal consolidation Fever and systemic features of infection unusual and suggest influenza or pneumonia

Question 194

What investigations would you do for Bronchitis?

Answer 194

Chest X-ray shows no features of pneumonia Viral and bacterial throat swabs Serology for Mycoplasma and Chlamydia

Question 195

What is the treatment for Bronchitis?

Answer 195

Usually none especially if viral | Little evidence for antimicrobials being helpful (unless pertussis)

Question 196

What viruses cause upper respiratory tract illness?

Answer 196

``` Rhinoviruses Influenza A virus - particularly causes systemic symptoms Coronaviruses Adenoviruses Parainfluenza viruses Respiratory syncytial viruses ```

Question 197

Are upper respiratory tract illnesses serious?

Answer 197

Usually transient Complications - sinusitis, pharyngitis, otitis media, bronchitis, rarely pneumonia May lead to a bacterial superinfection

Question 198

What are the treatments for the flu?

Answer 198

Tamiflu is a neuraminidase inhibitor which prevents the virus from budding out of the cell it's been made in. Reserved for people in an ‘at-risk’ group: chronic respiratory disease (including asthma and COPD), heart disease, kidney disease, liver disease, neurological conditions, diabetes mellitus. Start treatment within 48 hours (36 hours for Zanamivir in children) of the first symptoms.

Question 199

Is Tamiflu effective?

Answer 199

Shortens illness from 7 days to 61/2 days. No reliable evidence for reducing the risk of being admitted to hospital or developing pneumonia, bronchitis, sinusitis or otitis media.

Question 200

What causes pharyngitis?

Answer 200

Viral (70-80%) - rhinovirus, adenovirus etc Other viral: glandular fever, Epstein Barr virus, acute HIV infection Bacteria

Question 201

What are the bacterial causes of pharyngitis?

Answer 201

GABHS (Group A beta-hemolytic streptococcal) - Streptococcus pyogenes GABHS is important because it can be associated with scarlet fever, PSGN, rheumatic fever - carditis, arthritis, chorea, erythema, marginatum and subcutaneous nodules Other streptococci Mycoplasma pneumoniae (3-14%) - like a nasty cold with associated headache/congestion, occurs in epidemics Neisseria gonorrhoeae and other sexually transmitted diseases Fusobacterium necrophorum - Lemierre’s disease

Question 202

What are the major features of Asthma?

Answer 202

Increased irritability of bronchi causing spasm Produces paroxysmal attacks Macroscopically overdistended lungs Mucus plugs in bronchi Enlarged bronchial mucous glands with excess secretions

Question 203

What are the clinical categories of Asthma?

Answer 203

Extrinsic Atopic = IgE / Type 1 hypersensitivity Occupational = Type 3 hypersensitivity Allergic bronchopulmonary aspergillosis Intrinsic Aspirin, cold, infection, stress, exercise, SO2, pollutants etc - induced

Question 204

What are the causes of extrinsic asthma?

Answer 204

Enviromental agents like dust, pollens, foods, animal dusts etc. Family history often present - other atopic disorders (hay fever, eczema) Exposure produces the effect via cross- linked IgE on mast cells, causing histamine release

Question 205

What are the changes to the lungs that occur in asthma?

Answer 205

Bronchial obstruction with distal overinflation or atelectasis Mucus plugging of bronchi Bronchial inflammation (mixed) Seromucinous gland hypertrophy Bronchial wall smooth muscle hypertrophy Thickening of bronchial basement membrane

Question 206

What causes intrinsic asthma?

Answer 206

Associated with reccurent chest infections Not immune-mediated Possibly just unusually hyper-reactive airways

Question 207

What causes occupational asthma?

Answer 207

Work-associated inhaled agent This acts either as non-specific stimulus precipitating asthma in people with hypersensitive airways or capable of inducing airway hyper-reactivity. Combination of type I and III types of hypersensitivity

Question 208

What is allergic bronchopulmonary aspergillosis?

Answer 208

Driven by infection in lungs with Aspergillus fumigatus | Induces both immediate type I reaction and delayed immune complex type III hypersensitivity reaction.

Question 209

What is acute localised obstruction of the lungs?

Answer 209

Obstruction by tumour or foreign body Causes distal collapse (atelectasis) or over expansion (valve effect) Later may be complicated by secretions leading to distal lipid or infective pneumonia Usually show normal pulmonary function tests

Question 210

What are the 3 forms of chronic obstruction of the lungs?

Answer 210

Chronic bronchitis and/or emphysema Asthma Bronchiectasis

Question 211

What is chronic obstruction of the lungs?

Answer 211

Chronic Reversible (often variable) and intermittent Centered on bronchi or bronchioles ‘Obstructive’ pulmonary function tests Usually many airways involved = diffuse process

Question 212

What are the clinical features of chronic bronchitis?

Answer 212

Productive cough (cough and sputum) for 3 months over 2 consecutive years Mucus hypersecretion with bronchial mucus gland hypertrophy Respiratory bronchiolitis Some asthma effects

Question 213

What causes chronic bronchitis?

Answer 213

Affects middle aged heavy smokers Some following pollution chronically Recurrent low grade bronchial infections Organisms: Haemophilus influenzae, Streptococcus pneumoniae, viruses (respiratory syncytial virus, adenovirus)

Question 214

What are the features of severe chronic bronchitis?

Answer 214

Often starts mild but may progress to severe Hypercapnia Hypoxaemia Cyanosis (so-called ‘blue bloaters’) coupled with (so-called ‘pink puffers’ = coexisting emphysema) Produces right heart failure and/or respiratory failure

Question 215

What are the morphological changes in chronic bronchitis?

Answer 215

Mucus hypersecretion | Chronic inflammation leading to squamous metaplasia

Question 216

What is Emphysema?

Answer 216

Permanent enlargement of alveolar airspaces distal to terminal bronchioles due to destruction of elastin in walls Frequent association with chronic bronchitis Predominantly due to cigarette smoking

Question 217

What are the consequences of emphysema?

Answer 217

Gas trapping effect from emphysema prevents full exhalation of air, particularly if large air sacs (known as bullae). This causes: Pulmonary hypertension Poor oxygen delivery to tissues

Question 218

What causes Emphysema?

Answer 218

Smoking Alpha-1-antitrypsin deficiency Coal dust exposure Cadmium toxicity

Question 219

What is the pathology of emphysema?

Answer 219

Pathogenesis probably revolves around the recruitment of neutrophils in response to free oxygen radicals with release of IL8, LTB4 and TNF. Destructive enzymes e.g. neutrophil elastase are also released. All results in tissue damage.

Question 220

What are the clinical features of emphysema?

Answer 220

One third of lung capacity is destroyed before symptoms ‘Pure’ emphysema appears with reduced PaCO2 and normal PaO2 at rest due to overventillation (so-called‘pink puffers’) This leads to: Weight loss due to metabolic demands Right heart failure Overinflated chest Poor oxygen delivery to tissues

Question 221

What is Bronchiectasis?

Answer 221

This is the permanent dilatation of bronchi and bronchioles due to obstruction and/or severe inflammation.

Question 222

What are the symptoms of Bronchiesctasis?

Answer 222

Usually the lower lobes are affected Leads to pooling of secretions with further infection Symptoms: chronic cough with expectoration of large quantities of foul- smelling sputum, flecked with blood sometimes.

Question 223

How does the morphology of the lung change in Bronchiesctasis?

Answer 223

Dilation of bronchi and bronchioles Inflammation during acute exacerbations Inflammation and fibrosis extend into adjacent lung tissue

Question 224

What are the complications of Bronchiesctasis?

Answer 224

Pneumonia, recurrent Fungal colonization…asthma Emphysema Septicaemia Meningitis Metastatic abscesses (sepsis via blood stream to brain, heart) Amyloid formation (chronic effect) Further necrosis and destruction of lung tissue leading to pulmonary fibrosis Cor pulmonale (long term cardiovascular failure due to lung disease)

Question 225

What are Interstitial lung diseases?

Answer 225

Increased amount of lung tissue Increased stiffness and decreased compliance Restrictive lung defect of the pulmonary function Reduced Tco, VC, FEV1 Relatively normal FEV1/FVC ratio and PEFR

Question 226

What are the features of interstitial lung diseases?

Answer 226

Alveolar-capillary wall is the site of the lesion Acute or chronic clinical picture Numerous different causes giving similar but all have the ultimate pathology - non-compliant lung with loss alveolar surface Many diseases show their own characteristics allowing the specific aetiology to be identified Treatment often very limited effect because you cannot reverse the fibrosis.

Question 227

What are the causes of Adult respiratory distress syndrome?

Answer 227

``` Drug and toxin reactions Gastric aspiration Radiation pneumonitis Diffuse intrapulmonary haemorrhage Shock Trauma, direct pulmonary or multisystem trauma Infections (often severe viral or bacterial) Gas inhalation (NO2, SO2, smoke, Cl2) Narcotic abuse ```

Question 228

What is Adult respiratory distress syndrome?

Answer 228

Diffuse alveolar damage with hyaline membranes formed Many different clinical conditions all associated with severe injury to alveolar –capillary walls Fatal in many cases Causes acute respiratory distress with tachypnoea, dyspnoea, pulmonary oedema and arterial hypoxaemia refractory to O2 therapy

Question 229

What is the pathology of Adult respiratory distress syndrome?

Answer 229

Massive insult to the alveoli & capillaries May be related to O2 toxicity (free radicals) Polymorphs releasing enzymes and activating complement

Question 230

How can drugs and toxins cause damage to the lungs?

Answer 230

Cytotoxic drugs (Busulphan, bleomycin) lead to low grade alveolitis with healing interstitial fibrosis. Seen in novel immunotherapy for cancers Paraquat (potent herbicide) acts by release of hydrogen peroxide and the superoxide free radical. It remains in high concentrations in the lungs after ingestion.

Question 231

How can radiation cause pneumonitis?

Answer 231

Depends on the dose given, the lung volume irradiated and the length of treatment Changes vary from DAD (ARDS) to progressive pulmonary fibrosis

Question 232

What are the types of Chronic interstitial diseases?

Answer 232

Many types: Fibrosing alveolitis (aka CFA, UIP) Pneumoconioses Sarcoidosis Diffuse malignancies Rheumatoid diseases Pulmonary Langerhans cell histiocytosis (LCH) Lymphangioleiomyomatosis (LAM)

Question 233

What is Fibrosing Alveolitis?

Answer 233

AKA Idiopathic Pulmonary Fibrosis Pathologically defined as Usual Interstitial Pneumonia Unknown cause, likely autoimmune Abnormally large irregular spaces separated by thick fibrous septa (honeycomb lung) with inspissated secretions The subpleural regions are predominantly affected Histology shows patchy zones of inflammation and fibroplasia within normal lung Finger and toe clubbing Results in an end-stage fibrosis (honeycomb lung) as end point May progress to Cor pulmonale

Question 234

What is Pneumoconiosis?

Answer 234

Lung disease caused by inhaled dust Organic or inorganic dust (mineral) Reaction varies: inert, fibrous, allergic or neoplastic Co-existing disease may aggravate the lung debility

Question 235

What are the different reaction types in Pneumoconiosis?

Answer 235

The lung exposed to dust can respond in different ways: Minimal reaction: coal worker’s pneumoconiosis Fibrosis: progressive massive fibrosis, asbestosis and silicosis Allergic: extrinsic allergic alveolitis Neoplastic: mesothelioma, lung cancer

Question 236

What is Coal workers’ pneumoconiosis?

Answer 236

Coal dust inspired is ingested by alveolar macrophages (dust cells) They aggregate around bronchioles The consequences vary from trivial to lethal

Question 237

What are the different types of Coal workers’ pneumoconiosis?

Answer 237

Anthracosis: the presence of coal dust pigment in the lung, with no reaction or fibrosis Macular CWP: small aggregates of dust laden macrophages with no significant scarring Nodular CWP : fibrotic nodules (>10mm) in a background of extensive macular CWP, with no significant diffuse scarring

Question 238

What might Coal workers’ pneumoconiosis progress to?

Answer 238

Progressive massive fibrosis (PMF) which is where fusion of nodules creates a large zone of dense scarred and black lung Emphysema - same as for smoking May rarely progress to lung fibrosis Caplan’s syndrome is Rheumatoid Arthritis nodularity in association with CWP)

Question 239

What is Silicosis?

Answer 239

Silicates are inorganic minerals abundant in stone and sand The crystals (generally) 2µm fibres are toxic to macrophages, leading to their death with release of proteolytic enzymes. The causes local lung tissue destruction and fibrosis Nodules are formed after many years of exposure Progressing slowly towards diffuse interstitial fibrosis (There is a raised incidence of TB in silicotic cases)

Question 240

What is Asbestos disease?

Answer 240

Asbestos is an inconsumable silicate Used for its fire resistance for centuries, commonly causing benign pleural plaques (non-pathological) The non-neoplastic diseases include diffuse pulmonary fibrosis (asbestosis). Less common effects are diffuse pleural fibrosis and persistent pleural effusion.

Question 241

What is Extrinsic allergic alveolitis?

Answer 241

AKA Hypersensitivity pneumonitis Type 3 hypersensitivity causing bronchiolitis Later leads to chronic inflammation and granulomas These may resolve or lead to progressive fibrosis Classic types = Bird fancier’s lung or Farmer’s lung

Question 242

How is Rheumatoid disease linked to lung disease?

Answer 242

Many patients with connective tissue disorders have lung involvement. The lungs may show diffuse fibrosis, rheumatoid nodules and if coal worker’s pneumoconiosis present they may feature Caplan’s nodules. The pleura often shows fibrosis and lymphocytic aggregates.

Question 243

What is Diffuse malignancy?

Answer 243

These are neoplastic conditions that can look like diffuse non-neoplastic lung fibrosis on radiology. - Lymphangitis (carcinomatosa) is a process with diffuse permeation of the lung by malignant cells. - Lepidic carcinoma, is a lung cancer that spreads along lung alveolar surfaces with some fibrosis

Question 244

How common is lung cancer?

Answer 244

Common neoplasm affecting humans Male : Female = 2 : 1 ratio One third of all cancer deaths Despite improvements in therapy there is still a poor survival rate over five years in UK

Question 245

What are the causes of lung cancer?

Answer 245

Cigarettes (MOSTLY) Passive smoking Occupational risk factors – asbestos, radon, nickel, chromate, arsenic, uranium…. Lung fibrosis

Question 246

What are the symptoms of lung cancer?

Answer 246

``` Cough Recurrent chest infections Haemoptysis Increasing shortness of breath Extra-pulmonary changes (directly/ indirectly due to the cancer) General malaise Weight loss ```

Question 247

What are some of the paraneoplastic changes caused by lung cancer?

Answer 247

Secretion of PTH Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Secretion of ACTH and other hormones Hypertrophic pulmonary osteo-arthropathy (HPOA) Myasthenic syndrome (Eaton Lambert) Finger Clubbing Migratory thrombophlebitis Non-infective endocarditis (Libman Sacks) Disseminated intravascular coagulation (DIC)

Question 248

What are the different types of lung cancers?

Answer 248

``` Primary lung carcinomas (most common) Bronchial gland neoplasia Pleural neoplasia Soft tissue sarcoma/benign tumours Lymphomas Hamartomas Thoracic neoplasia - Majority are carcinomas (90%) Metastatic carcinoma is more common than primary lung carcinoma ```

Question 249

What are the different types of primary lung carcinomas?

Answer 249

Squamous cell carcinoma (25%) Adenocarcinoma (35%) Large (non small) cell undifferentiated carcinoma (10%) Small cell lung carcinoma (20%) Carcinoid tumours and neuroendocrine tumours (5-10%)

Question 250

How are lung cancers classified?

Answer 250

Divided broadly into small cell lung carcinoma and non-small cell lung carcinoma. Can also be classified based on hisotology, presentation, prognosis and response to chemo/radiotherapy.

Question 251

What is a small cell lung carcinoma?

Answer 251

A high grade epithelial neoplasm with strong cigarette smoking association. Has usually spread beyond chest by presentation Chemotherapy is primary/ standard treatment

Question 252

What is non-small cell lung carcinoma?

Answer 252

A variable grade/type epithelial neoplasm with a cigarette smoking association. May have metastasised by presentation/diagnosis Chemotherapy may be offered, along with new gene-based chemotherapy but surgery and radiotherapy may be mainstay of treatment.

Question 253

What do the new treatments for non-small cell lung carcinomas target?

Answer 253

``` New drugs currently being tested for tumour therapy by means of tissue sections EGFR ALK1 ROS1 PDL1 ```

Question 254

What is a Carcinoid?

Answer 254

A slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome.

Question 255

What is the TNM classification?

Answer 255

``` T = 1-4 worse for bigger tumours N = 0, 1, 2 worse for those with metastases M = 0 or 1 (a/b/c) if metastasis ```

Question 256

How is metastasis classified in lung tumours?

Answer 256

[M0] Absent [M1a] Contralateral lung pleural or pericardial effusion/nodule [M1b] Distant spread outside chest [MX] not known

Question 257

Give some examples of some rare tumours that can occur in the lung?

Answer 257

Non-Hodgkin lymphoma | Hodgkin lymphoma

Question 258

Give some examples of some benign tumours that occur in the lung?

Answer 258

TB and other infections Lymph nodes Benign neoplasia >> Hamartoma Hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended from a single mutated cell.

Question 259

What are the different types of Pleural neoplasia?

Answer 259

There are two main primary tumours affecting the pleura, as well as metastatic disease. Pleural fibroma - mostly benign, small amount are malignant. Localized fibrous tumors of the pleura or benign mesothelioma, are rare tumors that arise from the pleura. Although, most patients are asymptomatic, they can develop symptoms like cough or chest pain, especially if the tumor is large. Malignant mesothelioma - a cancer of the thin tissue (mesothelium) that lines the lung, chest wall, and abdomen. The major risk factor for mesothelioma is asbestos exposure. High grade pleural malignancy.

Question 260

What is the prognosis of malignant mesothelioma?

Answer 260

Average duration diagnosis to death for mesothelioma 8-12 months Limited benefit of surgery, chemotherapy, radiotherapy

Question 261

How are precision medicines being used to treat respiratory conditions?

Answer 261

``` Precision medicines (part of personalised medicine) - highly targeted medicines specified to a particular genotype of a particular person. Recent introduction of drugs for idiopathic pulmonary fibrosis - nintedanib and pirfenidone, which used to be very difficult to treat. Monoclonal antibodies for asthma - mepolizumab and reslizumab (very expensive) ```

Question 262

What do the endings of respiratory pharmacology drugs tell us about the type of drug it is?

Answer 262

``` Ends in -ab: monoclonal antibodies Ends in -sone: corticosteroid Ends in -tersol: bronchodilators Ends in -lone: corticosteroid Ends in -nib: kinase inhibitor ```

Question 263

What are the two major regions of the lung?

Answer 263

The human respiratory system is a complex organ system and the lung is composed of more than 40 different cells. The system is mainly composed of two vital regions: The conducting airways The respiratory region The respiratory region consists of respiratory bronchioles, alveolar ducts and alveolar sacs.

Question 264

What are the major lung diseases?

Answer 264

``` Pneumonia (alveoli fill with thick fluid making gas exchange difficult) Pulmonary fibrosis (fibrosis connective tissue builds up in lungs reducing their elasticity) Pulmonary tuberculosis (tubercles encapsulate bacteria and elasticity of the lung is reduced) Emphysema (alveoli burst and fuse into enlarged air spaces, surface area for gas exchange is reduced) Asthma (airways are inflamed due to irritation and bronchioles constrict due to muscle spasm) Bronchitis (airways are inflamed due to infection (acute) or an irritant (chronic), coughing brings up more mucus and pus) ```

Question 265

What are the components of respiratory disease that respiratory drugs seek to target?

Answer 265

``` Fibrosis Inflammation Infection Cough Allergy Bronchiectasis Bronchoconstriction Malignancy These components overlap in different lung diseases. ```

Question 266

What are inhaled pharmacologics?

Answer 266

Inhaled medicines are delivered directly to the lungs via the oral or nasal route. Inhaler devices allow drugs to penetrate deep into the lung and achieve the correct dose e.g. inhaler dry powder formulation (most common device) Nebulisers deliver medication in the form of aerosols

Question 267

How do the regions of the lungs differ in the way the transport drugs?

Answer 267

The transepithelial transport of drugs along the respiratory epithelium from the conducting airways and the respiratory region is significantly different. Conducting airways: smaller surface area and lower regional blood flow Higher filtering capacity (mucus, cilia) - removes up to 90% of delivered drug particles. Respiratory region: accounts for more than 95% of the lung’s surface area and is directly connected to the systemic circulation via the pulmonary circulation.

Question 268

What are the principles of inhaled medicines?

Answer 268

Rapid absorption: small hydrophobic molecules are thought to be rapidly absorbed (within seconds) throughout the lungs by passive diffusion through the epithelial cell plasma membrane Consider particle size: aerosol clouds with optimal properties should contain particles that are neither too small (these risk exhalation), nor too large (these deposit primarily in the upper airways, mouth and throat) Route of administration is important: Intranasal administration has anatomical limitation (narrower airway lumen) Oral inhalation administration far better as it allows administration of very small particles Inhalation technique is important - if patients inhale too forcefully from an inhaler, particle deposition in the upper airways, mouth and throat is dominant and lung deposition falls. Lots of it ends up in the gut

Question 269

What are the different delivery systems for inhaled drugs?

Answer 269

Pressurised metered-dose inhalers (PMDIs) - the device is activated by the user pressing down on the top of the container, resulting in the release of a fine spray containing propellent and drug. Spacer devices - slow down the particles of the drug and allow more time for evaporation of the propellant so that more of the drug can be inhaled. Dry powder inhalers (DIPs) - DPIs do not have a propellant, instead, on activation the device releases a small amount of drug in powder form which is then inhaled (this requires the person to have sufficient inspiratory effort to breathe in the powder. Nebulizers - Nebulizers work by dispersing a liquid into a fine mist which can be inhaled through a mask or mouthpiece. Their main advantage is that no coordination is required by the user and high doses of drugs can be delivered to the airways.

Question 270

How long are drugs retained for in the lung?

Answer 270

Drugs can be absorbed and cleared from the blood so quickly that their local efficacy in the lung/circulation is short Ideal to have a drug that is inhaled only once or twice a day. Absorption of therapeutic agents from the lungs can be prolonged by a variety of mechanisms.

Question 271

What factors should you consider when choosing a drug for respiratory pharmacology?

Answer 271

Solubility of the drug - presently some of the least-soluble drugs administered by inhalation are inhaled corticosteroids (ICS) for asthma, such as beclomethasone dipropionate (BDP) and fluticasone propionate (FP). Charge and tissue retention - (lung tissue binding) this can present absorption and increase half life. Encapsulation - allows controlled release by use of excipients (molecules that modify properties of medicines e.g. improves its solubility and dispersion, masks taste etc)

Question 272

What are the advantages of inhaled drugs?

Answer 272

Lungs are robust and are able to safely handle repeated exposure to therapeutics Inhaled medicines can act directly on the lung or enter the systemic circulation (fastest systemic uptake route other than IV) Very rapid absorption Lungs are naturally permeable to peptides (via epithelial cells) Large surface area (alveolar space is about 75m2) Fewer drug metabolising enzymes in the lung than in the blood/liver Non-invasive port of entry into the systemic circulation Potentially fewer side-effects

Question 273

What happens in bronchoconstriction?

Answer 273

Constriction of the airways due to tightening of the airway smooth muscle (ASM), luminal occlusion by mucus and plasma and airway wall thickening. Leads to airway flow obstruction. Most commonly seen in asthma and COPD. Can be reversible or non-reversible. In asthma, ASM is primed to contract and resistant to relaxation.

Question 274

What are the different types of bronchodilators?

Answer 274

Divided into two main categories: Adrenergic (sympathetic) - bronchodilation Anticholinergic (parasympathetic) - block bronchoconstriction

Question 275

What are B2 adrenergic agonists?

Answer 275

B2 adrenergic agonists act on B2-adrenoreceptors to cause smooth muscle relaxation and bronchodilation. Also inhibit histamine release from lung mast cells.

Question 276

What are the different types of B2 adrenergic agonists?

Answer 276

- Short-acting B2-adrenoceptor agonists (SABA) e.g. Salbutamol - Long-acting B2-adrenoceptor agonists (LABA) e.g. Formoterol and Salmeterol - Ultra LABAs - allow for once daily dosing e.g. Indacaterol, Oldodaterol - Inhaled medicines either aerosolized or as dry powder. LABAs are often combined with inhaled corticosteroids for the treatment of asthma and with an inhaled long-acting antimuscarinic agent (LAMA) for treating COPD patients.

Question 277

What are anticholinergics?

Answer 277

Acetylcholine contracts ASM by activating muscarinic receptors on smooth muscle cells. Antagonists (anticholinergics) block ACh binding to muscarinic receptors, preventing bronchoconstriction. Anticholinergic compounds block muscarinic receptors (M1-M5) on airway smooth muscle, glands and nerves to prevent muscle contraction, gland secretion and enhance neurotransmitter release.

Question 278

Give some examples of anticholinergics?

Answer 278

Atropine is a naturally occuring anticholinergic found in deadly nightshade. Atropine reverses bronchoconstriction caused by parasympathetic nerve stimulation. Ipratropium bromide and tiotropium bromide are newer synthetic derivatives of atropine with fewer side effects. Anticholinergic drugs are often used in combination with anti-inflammatory steroids in the treatment of asthma and COPD.

Question 279

Why does inflammation cause problems in lung disease?

Answer 279

Inflammation is central to a number of lung diseases. Inflammatory cells such as neutrophils and eosinophils inappropriately persist in the airway and lead to direct tissue damage and perpetuation of inflammation. Chronic vs acute exacerbation - has different treatment approaches.

Question 280

How does inflammation cause problems in lung disease?

Answer 280

Within the alveolar space, there is an epithelium lining and macrophages present in the middle. Upon infection, allergy or inhalation of noxious particles macrophages and epithelial cells send signals in the blood to cause chemotaxis, bringing more monocytes, more neutrophils, eosinophils and even mast cells from the blood and into the alveolar space. Mast cells release histamine, neutrophils release reactive oxygen intermediates and proteases. This causes physical damage and increased inflammatory signals from the epithelial cells.

Question 281

What are glucocorticoids and how do they help?

Answer 281

Glucocorticoids (aka corticosteroids) suppress inflammation via several mechanisms. Most effective in anti-inflammatory asthma. Inhaled corticosteroids: - Improve quality of life of patients with asthma - Improve lung function - Reduce frequency of exacerbations - Can prevent irreversible airway changes Relatively ineffective in COPD, CF, IPF. Severe asthmatics can become resistant.

Question 282

Which inhaled corticosteroids are used commonly in the UK?

Answer 282

``` Beclomethasone dipropionate (PMDI and DPI) Budesonide (PMDI, DPI and single dose units for nebulisation) Ciclesonide (PMDI) Fluticasone propionate (DPI, PMDI and single dose units for nebulisation) Mometasone furoate (DPI) ```

Question 283

How do ICS reduce inflammation?

Answer 283

At a cellular level glucocorticoids reduce the numbers of inflammatory cells in the airways. Suppress the production of chemotaxic mediators Reduce adhesion molecule expression Inhibit inflammatory cell survival in the airway ICS suppress inflammatory gene expression in airway epithelial cells - anti-inflammatory genes being turned on (IκBα the inhibitor of NF-κB transcription).

Question 284

What are the side effects of ICS?

Answer 284

Titrating to lowest effective dose reduces side effects High dose ICS are often used in COPD. This overuse of glucocorticoids is likely to produce several long-term side effects including: - Loss of bone density - Adrenal suppression - Cataracts, glaucoma

Question 285

What is Corticosteroid resistance?

Answer 285

Common in COPD, less common in Asthma. Asthma: approximately 10% of patients require maximal dose and 1% require regular oral corticosteroids. Small numbers are completely unresponsive to ICS. Resistance is usually linked to non-eosinophilic asthma (typically neutrophilic). COPD: most patients are resistant to ICS. Responsive patients are thought to have concomitant asthma which may explain the element of sensitivity to ICS.

Question 286

Why might patients become resistant to corticosteroids?

Answer 286

Possible genetic causes - could this allow us to predict which patients will be resistant? Poor GR binding and nuclear translocation Reduced downstream cellular signalling following corticosteroid:GR binding

Question 287

Why are B2 agonists and ICS used together?

Answer 287

Inhaled B2 agonists and glucocorticoids are frequently used together (usually as a fixed combined inhaler containing a glucocorticoid with a LABA) in the control of asthma. Important molecular interaction between these two classes of drug. Glucocorticoids increase the transcription of the B2-receptor gene, resulting in increased expression of cell surface receptors. LABA increases the translocation of GR from the cytoplasm to the nucleus after activation by glucocorticoids.

Question 288

How do new monoclonal antibody therapies target inflammation in asthma?

Answer 288

Inflammation in asthma is largely driven by eosinophils and lymphocytes. Latest mAbs target IL-5 driven inflammation by rendering IL-5 inactive.

Question 289

What is Bronchiectasis?

Answer 289

Obstructive lung disease Abnormal dilation of the bronchi - excessive sputum production, chest pain Permits infection Associated with cystic fibrosis Non-CF bronchiectasis is common (mainly associated with chronic infection) but less well understood. Some overlap with COPD and asthma. Influx of inflammatory cells into the wall of the airways. Pathophysiology of the bronchiectasis is thought to be due to excessive and persistent inflammation in the lung.

Question 290

How would you treat Bronchiectasis?

Answer 290

Very challenging Antibiotics treat infective elements of bronchiectasis Physical therapy clears airways Surgery and transplantation for severe disease

Question 291

What treatment would you use to treat the symptoms of Bronchiectasis?

Answer 291

Strategies used to treat symptoms rather than the underlying cause of disease Mucolytics treat hypersecretion B2 agonists are most useful in COPD/asthma/bronchiectasis overlap syndromes Anticholinergics have limited effect ICS have limited effect

Question 292

What is fibrosis?

Answer 292

Excessive fibrous connective tissue that leads to permanent scarring, airway wall thickening and breathing difficulties. A common end-stage of a number of heterogeneous conditions. Hallmark of the interstitial lung diseases.

Question 293

What is the interstitium of the lung?

Answer 293

The interstitium of the lung is a lace-like network of tissue that extends throughout the lungs and provides support to the air sacs (alveoli). Tiny blood vessels traverse the interstitium and facilitate gas exchange between the blood and the air.

Question 294

What are interstitial lung diseases?

Answer 294

Interstitial lung disease is a category of disorders that includes many different conditions, all of which affect the interstitium in various ways, including with increased inflammation, oedema and/or fibrosis. These disorders - which include idiopathic pulmonary fibrosis, other interstitial pneumonia and hypersensitivity pneumonitis - generally cause thickening of the interstitium and impair gas exchange. The conditions generally present with cough and/or breathlessness on exertion. Some interstitial lung diseases are acute, whereas others are chronic, progressive and irreversible.

Question 295

What is idiopathic pulmonary fibrosis?

Answer 295

Progressive and irreversible For many years IPF was considered a principally inflammatory disease due to increases in inflammatory cells in the lungs. However, a growing body of evidence indicates that IPF is an epithelial-driven disease whereby an aberrantly activated lung epithelium produces mediators of fibroblast migration, proliferation and differentiation into active myofibroblasts. These myofibroblasts secrete exaggerated amounts of extracellular matrix that subsequently remodel the lung architecture.

Question 296

How would you treat idiopathic pulmonary fibrosis?

Answer 296

Treatment options are limited (particularly for idiopathic pulmonary fibrosis) and transplantation is the best option for severe cases. Some forms of fibrosis respond to corticosteroids. Until recently the treatment strategy was amelioration of symptoms/preserving lung function - pirfenidone and nintedanib are new drugs that significantly slow the rate of disease progression in IPF.

Question 297

What is Pirfenidone?

Answer 297

A new and commonly used antifibrotic in IPF Has antifibrotic, anti-inflammatory and antioxidant properties but we don’t yet know the cellular target. Reduces: - Fibroblast proliferation - Collagen production - Production of fibrogenic mediators Orally administered

Question 298

What is Nintedanib?

Answer 298

Tyrosine kinase inhibitor Inhibits VEGFR (vascular endothelial growth factor receptor) and other growth factor receptors which are some of the drivers of the fibrotic process. Orally administered.

Question 299

What is respiratory failure?

Answer 299

Inability of the lungs to adequately oxygenated arterial blood supply (type 1) and/or eliminate CO2 from venous supply (type 2). Type 1: PaO2 <8 kPa (low or normal PaCO2) - lung failure Type 2: PaCO2 >6.0kPa - pump failure

Question 300

What causes respiratory drive?

Answer 300

Hypercapnia stimulates you to start breathing, to clear the excess CO2.

Question 301

How is breathing regulated?

Answer 301

NEURAL CONTROLS Cerebral cortex - conscious control of breathing Medulla oblongata - breathing centre CHEMICAL CONTROLS Medulla oblongata - chemoreceptors respond to rising blood level of carbon dioxide (increased acidity H) and lowered blood level of oxygen Carotid bodies - chemoreceptors respond to rising blood level of carbon dioxide and low blood level of oxygen Aortic bodies - chemoreceptors respond to rising blood level of carbon dioxide and low blood level of oxygen

Question 302

What causes respiratory failure?

Answer 302

Reduced FiO2 (concentration of oxygen that a person inhales) Ventilation/Perfusion mismatch (most commonly) Increased shunt Diffusion impairment - difficult for oxygen to transfuse across the lung parenchyma Alveolar hypoventilation First 4 tend to cause Type 1, alveolar hypoventilation can cause Type 1 or Type 2.

Question 303

What is a V/Q mismatch?

Answer 303

Commonest cause of hypoxaemia Imbalance between ventilation (airflow, V) and perfusion (blood flow, Q) Normal V/Q = 0.8 L/min Types of V/Q mismatch Ventilation of under-perfused alveoli (dead space) Perfusion of under-ventilated alveoli (shunt)

Question 304

What causes diffusion impairment?

Answer 304

Diffusion impairment occurs in emphysema, interstitial lung disease and pulmonary oedema.

Question 305

What are the signs of type 1 respiratory failure?

Answer 305

``` Cyanosis Increased respiratory rate (tachypnoea) Accessory muscle use Tachycardia Signs of underlying disease Confusion ```

Question 306

What is Alveolar hyperventilation?

Answer 306

Usually in the alveoli, the CO2-rich blood flows in, and the CO2 diffuses into the alveoli to be breathed out. The O2 from the O2 rich air diffuses into the blood and it flows to the rest of the body. But if there is a blockage in the alveoli, the CO2 cannot escape and eventually diffuses back into the blood and CO2 rises in the arterial system.

Question 307

When does alveolar hyperventilation occur?

Answer 307

``` Airway obstruction (COPD, asthma) Airway secretions (CF, bronchiectasis) Obesity hypoventilation/obstructive sleep apnea Neuromuscular disorders (GBS, drug overdose) Central sleep apnea ```

Question 308

What is Obstructive sleep apnea?

Answer 308

Usually seen in overweight/obese patients Relaxation of the pharynx during sleep Occlusion causes stimulation and wakening

Question 309

What are the signs of type 2 respiratory failure (hypercapnia)?

Answer 309

``` Bounding pulse Flapping tremor Confusion Drowsiness Reduced consciousness ```

Question 310

How would you treat type 1 respiratory failure?

Answer 310

Oxygen - aim for 94-98% Treat underlying cause e.g. bronchodilators to treat asthma, antibiotics to treat infections If unable to maintain adequate oxygen, use CPAP

Question 311

What is CPAP?

Answer 311

Continuous positive airway pressure (CPAP) is a form of positive airway pressure ventilator, which applies mild air pressure on a continuous basis. It keeps the airways continuously open in people who are able to breathe spontaneously on their own, but need help keeping their airway unobstructed. - Improves oxygenation by improving ventilation and improving VQ ratio - Prevents airway collapse - Decreases work of breathing

Question 312

What are the different delivery methods for oxygen?

Answer 312

``` Nasal cannulae (up to 4L/min) Simple face mask (can’t tell how much the patient is actually inspiring) Venturi mask - change the attachment based on how much oxygen you want to deliver Non-rebreathe mask - can deliver up to 80% FiO2 ```

Question 313

How would you treat type 2 respiratory failure?

Answer 313

Oxygen (cautious) - aim for 88-92% Treat underlying cause, usually 1 hour of ‘medical treatment’ e,g, bronchodilators, nebulisers, antibiotics, steroids (take longer than an hour) Check ABGs before and after medical treatment If unable to maintain adequate oxygenation/removal of CO2, treat with non-invasive ventilation (NIV)

Question 314

What is NIV?

Answer 314

Non-invasive ventilation Termed "non-invasive" because it is delivered with a mask that is tightly fitted to the face, but without a need for tracheal intubation (a tube through the mouth into the windpipe). Bi-phasic positive airways pressure (i.e. two levels) - The airflow is strongest when you breathe in, to help you take in as much air as possible. Airflow pressure is lower when you breathe out - IPAP and EPAP (inspiratory and expiratory) Aids alveolar ventilation Increases alveolar PO2 Decreases alveolar PCO2

Question 315

What are the BTS oxygen guidlines?

Answer 315

Recommended target saturation for acutely ill patients 94-98% For patients with known COPD or risk factors for hypercapnic respiratory failure, target 88-92% Most breathless patients who are not hypoxaemic do not benefit from O2 but reduction of >3% should prompt assessment Hypoxaemic patients should generally maintain an upright posture

Question 316

What is the normal pH, paO2 and paCO2 on an ABG?

Answer 316

pH: 7.35–7.45 PaO2 80–100mmHg PaCO2 35–45 mmHg

Question 317

What is tuberculosis?

Answer 317

Disease predominantly of the chest, that causes a prolonged cough, often with blood in the sputum. Caused by Mycobacterium tuberculosis. It is treatable and curable but diagnosis is difficult.

Question 318

Why is TB very common in poor countries?

Answer 318

Disease of poverty, industrialization, population increase and overcrowding. Malnourishment makes people more susceptible to the disease.

Question 319

How would you test for TB?

Answer 319

Sputum sample. The detection rate of TB in one sputum sample is not brilliant so better to have 3 samples over a day or so - increases sensitivity. Looking for pink acid fast bacilli.

Question 320

What are the features of Mycobacterium tuberculosis?

Answer 320

High lipid content with mycolic acids in the cell wall makes Mycobacterium resistant to Gram stain. Slightly curved, beaded bacilli. Ziehl-Neelsen stain for acid fast bacilli - Carbol fuchsin - Acid alcohol (AFB are resistant to de-staining) - Methylene blue Need 10,000 AFB per ml sputum to visualise Fluorochrome stains e.g. auramine phenol aid screening at lower power objective.

Question 321

What are the risk factors for TB?

Answer 321

``` Born in a high prevalence area - certain cities based on immigration rates Intravenous Drug User (IVDU) Homeless Alcoholic Prisons HIV+ ```

Question 322

How do you catch TB?

Answer 322

Spread in aerosol from infected individual’s lung to another lung via spitting or sneezing on plates or hands. Aerosol droplets of about 5 microns contain a few bacilli and lodge in alveolae or small airways. Unlikely to catch TB from someone on the street or on the bus. Tends to cluster in households. You can also catch bovine TB by drinking the milk of an infected cow.

Question 323

How likely is it that household contacts will contract TB?

Answer 323

If smear (from testing sputum) from an infected person is positive for TB, then 27-50% of household contacts will become infected. If smear is negative, this is <5% (much less infectious).

Question 324

How can TB patients be asymptomatic?

Answer 324

Majority of people mount an effective immune response that encapsulates and contains the organism forever. >95% do not have any disease. Bacteria reaches the lung and settles in the lung apex (more air and less blood supply/immune cells). Macrophages and lymphocytes seal in and contain the majority of infecting bacilli.

Question 325

What is the pathology of TB?

Answer 325

Some TB bacteria is better adapted to survive in the phagolysosome. So the macrophages may control the TB but won’t be able to kill all of it. The macrophages will recruit cell-mediated immune cells to form a granuloma to contain the bacteria, and here the story often ends. However, sometimes this process is not enough to contain it. 2-5% develop clinically evident primary pulmonary disease. Bacilli and macrophages coalesce to form a granuloma, this is called the Primary (Ghon) focus. Inflammation, damage and pus in the lung (but this process is much slower than it is in pneumonia). The granuloma slowly enlarges to keep up and the middle becomes necrotic. As it enlarges like this it becomes a cavity.

Question 326

How does TB infection spread from the lungs?

Answer 326

The bacilli are then taken up into lymphatics via the hilar lymph nodes and the lymph nodes get larger as they react with an immune response. Primary focus with the mediastinal lymph nodes = Ghon complex (can be seen on a chest X-ray - primary complex) The cavity can invade and communicate with one of the major airways, which means that as it is irritated the TB bacilli are expelled from the lungs through coughing.

Question 327

What are the symptoms and signs of TB?

Answer 327

``` Weight loss* Low grade fever Anorexia Night sweats* Malaise *Most predictive of TB ```

Question 328

What are the pulmonary features of TB?

Answer 328

Cough >3/52 (most other causes resolve by then) Chest pain Breathlessness Haemoptysis ``` May also be associated with: Consolidation Collapse of the lung Pleural effusion Pericardial effusion Depending on the site of granuloma/lymph node and subsequent rupture. ```

Question 329

How can TB cause a pleural effusion?

Answer 329

If the cavity is near the lining of the lung (rather than a major airway) then the infection can then spill out into the pleural cavity which can cause a pleural effusion.

Question 330

How can TB causes a pericardial effusion?

Answer 330

Erosion into bronchus inhalation and areas of tuberculous bronchopneumonia. If there is erosion from the lymph node into the pericardium, you can get a pericardial effusion.

Question 331

How can TB cause lung collapse?

Answer 331

If there is blockage of an airway, then any area of lung distal to that part may collapse.

Question 332

How can TB cause non-pulmonary disease?

Answer 332

If it is not contained within the lung, there is haematogenous dissemination which often leads to serious non-pulmonary disease. This may happen after primary infection or after reactivation. TB meningitis, miliary TB, pleural TB, bone and joint TB, genito-urinary TB.

Question 333

What is latent TB?

Answer 333

``` First exposure (primary infection) Within 2 years, may develop primary or progressive primary disease. But if they do not and the bacteria are still present, they are said to have latent TB. Latent TB in 90% of people will not do anything. But in 10% the TB will reactivate and they will have post primary disease and this will occur wherever the dormant bacilli happen to be hiding, usually the lung. It is also possible to be re-infected at some point later in life, and the same processes can occur. ```

Question 334

What are the extrapulmonary signs of TB?

Answer 334

Lymph node TB - swelling +/- discharge Miliary TB Bone TB - pain or swelling of joint, Potts disease with spinal cord lesion Abdominal TB - ascites, abdominal lymph nodes, ileal malabsorption Genito-urinary TB - epididymitis, frequency, dysuria and haematuria CNS TB - meningitis and CN palsy, tuberculoma

Question 335

What is TB osteomyelitis?

Answer 335

Occurs secondary to lymphohematogenous spread of Mycobacterium tuberculosis from a pulmonary focus. Clinical symptoms are very nonspecific and can include insidious onset of pain, swelling, decreased range of motion and difficulty ambulating.

Question 336

What is Pott's disease?

Answer 336

Pott disease is tuberculosis of the spine, usually due to haematogenous spread from other sites, often the lungs. The lower thoracic and upper lumbar vertebrae are the areas of the spine most often affected. It causes a kind of tuberculous arthritis of the intervertebral joints.

Question 337

How would you diagnose active TB?

Answer 337

Non-specific - signs and symptoms of catabolism caused by the prolonged inflammatory response Suggestive - changes in the cellular makeup seen in histopathology, visualisation of caseating granuloma on ZN stain Definitive - microbiology and microscopy AFB, PCR, culture

Question 338

What are some of the non-specific signs that could be related to TB?

Answer 338

``` Normochromic normocytic anaemia Thrombocytosis Raised ESR/CRP Hypoalbuminemia Hypergammaglobulinemia Hypercalcaemia Sterile pyuria (white cells in renal tract TB) ```

Question 339

What investigations would you do to come to a definitive diagnosis of TB?

Answer 339

``` Sputum Urine CSF Pleural fluid Biopsy specimen - bone, brain and any lymph nodes: cervical, axillary, inguinal, mediastinal, abdominal ```

Question 340

Can we diagnose a patient with latent TB?

Answer 340

It is not possible to find the ‘dormant’ bacteria. They are metabolically inactive. So instead an indirect measurement is used to detect an immune memory response to the organism. This can only answer the question whether the person has been exposed to TB before. If the answer is yes and the patient is clearly not suffering from active TB, we assume that they harbor dormant bacteria with the potential to reactive in the future.

Question 341

What is the Tuberculin skin test ‘Mantoux’?

Answer 341

Protein derived from organism Injected intradermally (technically difficult) Stimulates type 4 delayed hypersensitivity reaction Not sensitive - immunosuppressed or miliary TB won’t react (false negatives) Only moderate specific (false positives from vaccine) Won’t easily distinguish infection from disease Cannot tell you if you’ve got latent TB

Question 342

What is a Interferon gamma release assay (IGRAs)?

Answer 342

Separate out the white cells into tubes, first tube you do nothing, second tube you put in proteins from TB, other tube you put in something you know will react with it Use antigens specific to M.tuberculosis e.g. ESAT-6 and CFP10 Able to distinguish BCG (Bacille-Calmette-Guerin) used in vaccination or environmental mycobacteria and TB exposure - Quantiferon TB measures IFN-y released by cells - T-SPOT test measures IFN-y producing T cells in an enzyme linked immunospot (ELLISPOT) assay IGRAs demonstrate exposure to M. tuberculosis but NOT active infection

Question 343

What is the treatment for active TB?

Answer 343

TB is curable Treat with at least 4 drugs for at least 6 months Standard treatment in the UK - Rifampicin (6m) - Isoniazid (6m) - Pyrazinamide (first 2m) - Ethambutol (first 2m) Compliance is critical to reduce relapse and resistance Community TB nursing team ‘Directly observed therapy’ DOTS - given meds in a supervised fashion 3 or more times a week

Question 344

What are the requirements for TB therapy?

Answer 344

We need drugs that work in several different ways and drugs which will work in the extreme environment of the granuloma and for them to exist there for a prolonged amount of time. These drugs are uniquely used for TB. Side effects - low-level GI nausea, rashes, joint pains. If you’ve got CNS TB - you need treatment for 12 months.

Question 345

What is the action of the TB drugs?

Answer 345

- Rifampicin - Bactericidal, blocks protein synthesis, effective throughout the treatment course. SE include red urine, hepatitis, drug interactions (metabolise drugs faster meaning that they won’t work so well e.g. oral contraceptive pill) - Isoniazid - bactericidal for rapidly growing bacilli (blocks cell wall synthesis), most effective in initial stages). SE include hepatitis, peripheral neuropathy. - Pyrazinamide - Bactericidal initially, less effective later. SE include hepatitis, arthralgia/gout, rash. - Ethambutol - Bacteriostatic, blocks cell wall synthesis. SE include optic neuritis.

Question 346

Why is TB treatment so long?

Answer 346

Early killing of active bacteria occurs in the first weeks. Drugs need to be taken for a long time so that any dormant bacteria reactivation is controlled and stopped over the months following the start of the treatment.

Question 347

What is drug-resistant TB?

Answer 347

There are drug-resistant TB - can be one of the drugs, two drugs, or multidrug resistance (R and I). Most commonly to I (7%). Increased risk if the patient has had previous treatment, in a high risk area, contact of resistant TB or poor response to therapy. More difficult to treat - drugs with more side effects that are less effective. IV/IM >20 months Increased relapse rate Now present in many countries - very difficult to treat, high mortality.

Question 348

How can we prevent TB?

Answer 348

Active case finding - reduce infectivity Detection and treatment of latent TB - community TB nursing team using Mantoux Vaccination: Neonatal BCG - Limited efficacy, but does protect vs disseminated TB/TBM - Gives false positive Mantoux tests - Previously routine in UK teenagers, now just for neonates from high risk groups - No other vaccine currently available

Question 349

Who is at risk of latent TB?

Answer 349

Recent infection Healthcare worker Immunocompromised

Question 350

How would you diagnose and treat latent TB?

Answer 350

``` Diagnosis by mantoux test or IGRA Treatment: 6 months Isoniazid 3 months Rifampicin and Isoniazid Reduces risk of development of active TB by ⅔ ```

Question 351

How would you define the severity of COPD?

Answer 351

``` Severity based on FEV1: >80% Mild 50-79% Moderate 30-49% Severe <30% Very severe ```

Question 352

What are the mechanisms underlying airflow obstruction in COPD?

Answer 352

Small airways disease - airway inflammation, airway fibrosis, luminal plugs, increased airway resistance, narrowing due to oedema and mucus Parenchymal destruction - loss of alveolar attachments due to ruptured alveolar wall, decrease of elastic recoil, collapse of the airways Both contribute to airway limitation

Question 353

What are the airway changes in a COPD patient?

Answer 353

In COPD, the maximum amount of air they can breath out has been reduced so they can’t generate a normal minute volume. The only way they can do this is to breathe in more deeply on average, which is uncomfortable and mechanically disadvantaged. In exercise, they can’t increase their flow rate either (dynamic airflow obstruction) - this limits what the patient can do day-to-day.

Question 354

What are the vascular changes in a COPD patient?

Answer 354

As well as the airway changes, you also get vascular changes. Poor V/Q match Low PaO2 Poor ventilation may give high CO2 Obliteration and vasoconstriction gives pulmonary hypertension

Question 355

What are the signs and symptoms of COPD?

Answer 355

``` Shortage of breath Cough, phlegm Wheeze Raised respiratory rate Hyperexpansion/barrel shaped chest Cyanosis Weight loss Breathlessness after eating ‘Cor pulmonale’ - heart failure, raised jugular venous pressure, swelling of ankles but cardiac output maintained ```

Question 356

Who is the average COPD patient?

Answer 356

Tend to see it in older patients, smokers, male predominance.

Question 357

What are the classical phenotypes of COPD?

Answer 357

Pink puffer - weight loss, breathless, emphysematous, maintained O2 Blue bloater - cough, phlegm, cor pulmonale, respiratory failure Most people are somewhere on a spectrum in between

Question 358

What are the risk factors for COPD?

Answer 358

Cigarette smoke Occupational dust and chemicals Environmental tobacco smoke (ETS) - passive smoking Indoor and outdoor air pollution Genes (60%) Infections - particularly childhood infections Socio-economic status of the patient and their patients (in-utero development - low birthweight infant with poorly developed lungs) Aging

Question 359

How do you characterize dyspnoea?

Answer 359

1) SOB marked exertion 2) SOB on hills 3) Slow or stop on flat (at a normal speed) 4) Exercise tolerance 100-200 yards on flat 5) Housebound/SOB on minor tasks

Question 360

What is the CAT?

Answer 360

``` COPD assessment test Questions scored 0-5 A score out of 40 An idea of quality of life Can be used to compare an individual over different timepoints (not good for comparing person to person) ```

Question 361

What are the factors that contribute to a decline in quality of life for a COPD patient?

Answer 361

Lung disease leads to breathlessness, which limits the amount of exercise you can do. This may lead to muscle wasting and disability. This combined with the patient’s personality and environment may lead to increasing risk of anxiety and depression.

Question 362

What are the differential diagnoses of COPD?

Answer 362

``` Other causes of SOB Heart failure (common) Pulmonary embolism Pneumonia Lung cancer Asthma (common) Bronchiectasis (common) ```

Question 363

How does spirometry differ between COPD and asthma?

Answer 363

COPD Always abnormal spirometry Minimal variation in serial PEF Reversibility usually <15% Asthma Spirometry may be normal Day-to-day and diurnal variation in serial PEF Reversibility usually >15% You can get the patient to do peak flow during the day. You can see whether bronchodilators make any difference.

Question 364

What are the classical pathological differences between COPD and asthma?

Answer 364

Asthma - lots of inflammation, smooth muscle hypertrophy, basement membrane thickening, very little fibrosis or alveolar disruption COPD - lots of inflammation, fibrosis and alveolar disruption, very little smooth muscle hypertrophy and basement membrane thickening

Question 365

What are the classical cellular differences between COPD and asthma?

Answer 365

Asthma - eosinophilic inflammatory response, mast cells and CD4 T cells present with very few macrophages COPD - neutrophilic inflammatory response, CD8 T cells and lots of macrophages present There are people who have COPD but have eosinophilic presentation - require different treatment.

Question 366

How can you visualise the effects of COPD?

Answer 366

You can see the hyperexpansion in COPD on the X-ray but it is mainly used to look for cancer, pulmonary fibrosis, pneumonia. MRI can be used to look for emphysema.

Question 367

What is the Combined assessment of COPD?

Answer 367

``` Breathlessness score using MRC score Quality of life score using CAT Risk assessment based on previous exacerbation history/hospital admissions A - low risk, low symptoms B - low risk, high symptoms C - high risk, low symptoms D - high risk, high symptoms ```

Question 368

Why should you assess comorbidity in COPD patients?

Answer 368

COPD is often found with other diseases More common than you would expect even allowing for smoking impact Cardiac disease, cancer, renal failure, diabetes, weight loss, depression, anxiety, osteoporosis May be a genetic link

Question 369

What are the first therapeutic options for COPD patients?

Answer 369

Smoking cessation has the greatest capacity to influence the natural history of COPD. Healthcare providers should encourage all patients who smoke to quit. Pharmacology and nicotine replacements reliably increase long-term smoking abstinence All COPD patients benefit from regular physical activity and should be repeatedly encouraged to remain active.

Question 370

Why is rehabilitation important in COPD patients?

Answer 370

All COPD patients benefit from exercise training programs with improvements in exercise tolerance and symptoms of dyspnoea and fatigue Although an effective pulmonary rehabilitation program is 6 weeks, the longer the program continues, the more effective the results If exercise training is maintained at home, the patient’s health status remains above pre-rehabilitation levels

Question 371

Are there useful pharmcological treatments for COPD?

Answer 371

Appropriate pharmacologic therapy can reduce COPD symptoms, reduce the frequency and severity of exacerbations and improve health status and exercise tolerance. None of the existing medications for COPD have been shown conclusively to modify the long-term decline in lung function Influenza and pneumococcal vaccination should be offered depending on local guidelines

Question 372

What are the drug options for COPD patients?

Answer 372

``` B2 agonists - short and long acting Anticholinergics - short and long acting Inhaled corticosteroids Combinations: SABA with anticholinergic, LABA with anticholinergic, LABA with ICS Phosphodiesterase-4 inhibitors ```

Question 373

What are the goals of COPD therapy?

Answer 373

Reduce symptoms: Relieve symptoms Improve exercise tolerance Improve health status Reduce risk: Prevent disease progression Prevent and treat exacerbations Reduce mortality

Question 374

What are the consequences of COPD exacerbations?

Answer 374

Negative impact on quality life - over the whole time, not just at the time of the exacerbations Impacts on symptoms and lung function Increased economic costs Increased mortality - more dangerous in hospital and once you’ve gone home, chance of a cardiac event is raised for 90 days after an exacerbation of COPD Accelerated lung function decline

Question 375

Why are bronchodilators important for COPD management?

Answer 375

Central for COPD management Prescribed on an as-needed or regular basis to prevent or reduce symptoms Principle treatments are B2-agonists, anticholinergics, theophylline or combination therapy Almost always choosing a long-acting agent Choice of treatment depends on the availability of medications and each patient’s individual’s response in terms of symptoms relief and side effects

Question 376

Why are inhaled corticosteroids important for COPD management?

Answer 376

Regular treatment with inhaled corticosteroids improves symptoms, lung function and quality of life and reduces frequency of exacerbations for COPD patients with an FEV1 < 60% predicted Inhaled corticosteroid therapy is associated with an increased risk of pneumonia Withdrawal from treatment with inhaled corticosteroids may lead to exacerbations in some patients

Question 377

Why are combination treatments important for COPD?

Answer 377

An inhaled corticosteroid combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in moderate to very severe COPD Addition of a long acting B2 agonist/ICS to an anticholinergic (tiotropium) appears to provide additional benefits Combination therapy is associated with an increased risk of pneumonia

Question 378

Should COPD patients be given systemic corticosteroids?

Answer 378

Chronic treatment with systemic corticosteroids should be avoided because of its unfavourable benefit-to-risk ratio.

Question 379

Other than pharmacological treatments, what other treatments are there for COPD patients?

Answer 379

Oxygen therapy - long term administration of oxygen (>15 hours per day) to patients with chronic respiratory failure has been shown to increase survival in patients with severe, resting hypoxemia Ventilatory support - combination of non-invasive ventilation with long-term oxygen therapy may be of some use in a selected subset of patients, particularly in those with pronounced daytime hypercapnia. Surgery

Question 380

What are the surgical treatments for COPD patients?

Answer 380

Lung volume reduction surgery (LVRS) is more efficacious than medical therapy among patients with upper-lobe predominant emphysema and low exercise capacity. LVRS is costly relative to health-care programs not involving surgery. In appropriately selected patients with very severe COPD, lung transplantation has been shown to improve quality of life and functional capacity.

Question 381

What is palliative care?

Answer 381

Palliative care improves the quality of life of patients and families who face life-threatening illness, by providing pain and symptom relief, spiritual and psychosocial support from diagnosis to the end of life and bereavement.

Question 382

Who provides specialist palliative care?

Answer 382

Health professionals who specialise in palliative care and work within a multi-disciplinary specialist care team e.g. Consultants in palliative medicine Clinical nurse specialists Hospice nurses, Specialist social workers, dietitians, chaplains, physiotherapists

Question 383

Who provides generalist palliative care?

Answer 383

``` Health professionals who have not received accredited levels of training in palliative care provision and thus are not deemed ‘specialists’, but who routinely provide health care for patients at the end of their lives. e.g. GPs and hospital doctors & nurses District nurses, community matrons, Nursing home staff, social workers COPD nurses ```

Question 384

What are the features of palliative care?

Answer 384

Holistic / humanistic Individualised Patient and carer / family are clients Multidisciplinary approach

Question 385

What's the link between older people and chronic illness?

Answer 385

Two thirds of over 75s have at least one self-reported chronic illness One half of over 75s report a lifestyle limited by chronic illness Increasing age = increasing co-morbid conditions

Question 386

What are the care needs of older patients?

Answer 386

Multiple co-morbidities leading to greater impairment and need for care Greater risk of impairment from treatment complications (adverse drug reactions) Increased psychological distress Increased social isolation and economic hardship

Question 387

What's the link between chronic illness and social inequalities?

Answer 387

People with lower socio-economic status have higher incidence of chronic illness Poverty and poor living conditions increase with age Most severe deprivation experienced by pensioners living alone Britain has the highest proportion of winter deaths (from cold-related illnesses) in Europe

Question 388

What are gerontological care and palliative care concerned with?

Answer 388

Promoting quality of life Promoting dignity and autonomy Placing importance on controlling symptoms whilst avoiding the use of medical investigations and aggressive treatment

Question 389

How does palliative care differ between old and young people?

Answer 389

Older people are … less likely to be admitted to a hospice … less likely to die in their place of preference … less likely to receive proper preventative planning … more likely to experience repeated hospital admissions … less likely to be involved in discussions concerning options available to them at the end of life (advanced care planning)

Question 390

How is COPD classified?

Answer 390

Mild: characterised by mild airflow restriction FEV1 50-70% of predicted. Moderate: characterised by moderate airflow restriction, symptom progression, some restriction of activity FEV1 30-50% of predicted. Severe: severe airflow obstruction, reduced quality of life, exacerbations may be life threatening FEV1 <30%.

Question 391

What are the characteristics of COPD patients?

Answer 391

COPD predominantly affects the older population, slightly more common in men. Many patients have additional co-morbidities e.g. heart disease, diabetes, arthritis. Smoking is the predominant cause in approx 80% of cases, other risk factors include occupational exposure to various chemicals, air pollution, and genetic factors (alpha 1 antitrypsin deficiency).

Question 392

What are the major difficulties with COPD?

Answer 392

Unpredictable illness trajectory Difficulties with prognostication Poor patient understanding Limited access to specialist palliative care

Question 393

What is the prognosis of COPD?

Answer 393

COPD associated with poor prognosis Hospital based study identified that 50% of people died within 2 years of admission for an acute exacerbation Five year survival in the UK estimated at 72-78% for patients with mild COPD but 24-30% for patients with acute disease

Question 394

Why is it so difficult to give a COPD patient a prognosis?

Answer 394

Difficult to provide an accurate prognosis when illness trajectory is so unpredictable The majority of health professionals agree that discussions on prognosis are necessary, and they have an important role. However, the majority acknowledge they discuss prognosis badly.

Question 395

How does COPD compare with lung cancer?

Answer 395

Patients with COPD report worse activities of daily living than LC patients. 92% of COPD patients reported to suffer from depression vs 52% of LC patients. LC patients received more visits from district nursing teams LC patients more likely to know they might die. No difference in visits to GP but COPD patients more likely to visit intensive care units. 30% of LC patients received support from specialist palliative care compared to 0% of COPD patients

Question 396

Why do COPD patients end up dying in hospital?

Answer 396

Uncertainty about prognosis and whether all options exhausted Communication; death not discussed or anticipated No proactive management strategies Carers (including GP) exhausted Co-morbidity Unresolved anxiety

Question 397

What are the difficulties associated with access to specialist palliative care for COPD patietnts?

Answer 397

Palliative care was developed around a cancer model. Most people who receive specialist palliative care still have a diagnosis of cancer. 75% of deaths are from non-cancer conditions COPD patients are far less likely to receive palliative care than are cancer patients and less likely to receive specialist care. Specialist palliative care funding: cancer charities etc. Expertise of specialist palliative care teams: cancer focus. Differing patient needs COPD vs cancer Stigma (smoking)

Question 398

What is occupational health?

Answer 398

Occupational medicine - branch of medicine concerned with the interaction between work and health. Individual workers Groups of workers Workplace effects on surrounding populations (emissions to air, water, land) Health of employers’ customers or clients (e.g. patients)

Question 399

What are the common work-related ill-health cases in the UK today?

Answer 399

``` Stress, depression, anxiety (very common) Musculoskeletal disorders (very common) Lung disease Cancer Noise-induced hearing loss Hand-arm vibration ```

Question 400

How do we establish the extent of the problem in occupational health?

Answer 400

``` Case counts (medicolegal and reporting processes) are based on a traditional occupational disease concept Self-report implies much higher numbers affected by work (some can underestimate) Attributable or etiological fractions are a statistical method of assessing the fraction of cases that are attributable to work ```

Question 401

What are some sources of occupational illness data?

Answer 401

Labour force survey Death certificate Disablement benefit Surveillance schemes

Question 402

How would you calculate attributable risk?

Answer 402

Attributable risk is mostly calculated in cohort studies where individuals are assembled based on exposure status and followed over a period of time.

Question 403

How can the effects of work on health be classified?

Answer 403

- Acute - Cumulative e.g. dermatitis, COPD - Progressive (disease progression after exposure ceases) - Disease with latencies e.g. asbestosis There is a bit of overlap.

Question 404

How would you classify potential work hazards?

Answer 404

``` Mechanical Physical Chemical Biological Psychosocial ```

Question 405

What's the difference between hazard and risk?

Answer 405

``` Hazard = potentially harmful Risk = probability of harm ```

Question 406

What impact does employment and unemployment have?

Answer 406

Can depend on the nature of work Work to unemployment - negative effect on mental and physical health Unemployment to reemployment - positive effect on mental health and wellbeing School leavers to first job - often deemed to be an unsatisfactory employment so has a negative effect Work to retirement is a positive thing if voluntary, but a negative thing if forced.

Question 407

What are the features of 'good work'?

Answer 407

``` Should feel stable and safe Should have individual control, part of decision-making Appropriate quantity of work demands Fair salary Opportunities for training and promotion Prevents social isolation, discrimination and violence A place where you can share information Good work/life balance Reintegrates sick or disabled people Promotes health and well being ```

Question 408

When should you suspect a work-related illness?

Answer 408

If an illness fails to respond to standard treatment, does not fit the typical demographic profile or is of unknown cause, it should raise suspicion of occupational etiology.

Question 409

What are the screening questions for occupational health?

Answer 409

What type of work do you do? Do you think your health problem might be related to your work? Are your symptoms different at work and at home? Are you exposed to chemicals, dust, metals, radiation, noise or repetitive work? Have you been exposed to chemical, dust, metals, radiation, noise or repetitive work in the past? Are any of your co-workers experiencing similar symptoms? If the answer to any one of these questions suggest that the patient’s symptoms are job-related or that the patient has been exposed to hazardous material, a comprehensive occupational history should be obtained.

Question 410

What are the features of an occupational health history?

Answer 410

``` Current job, employer, duration Tasks as well as job title Past employers and jobs A brief exposure can be enough External and internal exposure Hobbies? (DIY, pets, gardening, chemicals) ```

Question 411

What is the GP's role in occupational health?

Answer 411

Able to give a sickness certificate ‘fit note’ Requires GPs to state if they have advised patients that they are not fit for work or may be fit for work, and whether the patient may benefit from a phased return to work, amended duties, altered hours or workplace adaptations. Need to spend more time finding out what the patient’s work actually entails Requires knowledge and understanding of a range of workplaces and possible adaptations Research shows that many do not have the knowledge required to understand the working lives of all their patients.

Question 412

What is the danger of long-term worklessness?

Answer 412

``` Greater risk than many ‘killer diseases’ Greater risk than most dangerous jobs Increased risk of poor mental and physical health Loss of fitness and wellbeing Social exclusion and poverty Trapped on benefits until retirement ```

Question 413

What are the inequalities evident in occupational health?

Answer 413

Greater risk in some jobs than others Some jobs have greater physical demands than others Impacts at transition points - harder to find work, harder to return to work from sickness absence, harder to find good work, less likely to remain in work

Question 414

What are health inequalities?

Answer 414

Health inequalities result from social inequalities in the conditions in which people are born, grow, live, work and age. Action to reduce health inequalities will have economic benefits in reducing losses from illness associated with health inequalities.

Question 415

What is the definition of a disability?

Answer 415

``` A physical or mental impairment, which has a substantial long-term adverse effect on a person’s ability to carry out normal activities. Type of impairment is broadly defined Substantial adverse effect Long-term Normal activities ```

Question 416

What are the adjustments that employers should be willing to make in response to work-related ill-health?

Answer 416

Altering the person’s work hours Allowing absences during work hours for medical treatment Given additional training Getting special equipment or modifying existing equipment Changing instructions or reference manuals Changing to an open plan working policy to accomodate someone with an anxiety condition or autism Providing additional supervision or support Making adjustments to premises

Question 417

What are the primary, secondary, tertiary aspects of the population approach to occupational health?

Answer 417

Primary (monitor risk, controlling hazards, promotion) Secondary (screening, early detection, task modification) Tertiary (rehabilitation, support)

Question 418

Why is work is important?

Answer 418

Means of obtaining adequate economic resources which are essential for material well-being and full participation in today’s society Meets important psychosocial needs Central to an individual’s identity, social roles and social status Main drivers of social gradients in physical and mental health and mortality

Question 419

What is occupational lung disease?

Answer 419

Occupational lung diseases represent a wide-range of respiratory conditions caused by inhaling a harmful substance in the workplace. In addition, a wide range of workplace exposures may aggravate the symptoms of pre-existing lung disease. Caused by inhalable particles, gases and vapours are generated from a wide range of industrial processes.

Question 420

What are the types of dust?

Answer 420

Inhalable - airborne dust less than 100 microns are termed ‘inhalable’ as they can enter the respiratory tract Respirable - airborne dust less than 10 microns are termed ‘respirable’ as they can penetrate to an alveolar level

Question 421

What are fumes?

Answer 421

Fumes are smaller (less than 1 micron) solid particles suspended in the air

Question 422

What are mists?

Answer 422

Mists are liquid particles suspended in the air

Question 423

What are vapours?

Answer 423

Vapours are the gaseous state of a substance which is liquid at 25°C.

Question 424

What affects a worker’s response to a workplace exposure?

Answer 424

A worker’s response to a workplace exposure is very variable and dependent on a range of factors: The physical and chemical nature of the agent The duration and dose of exposure Individual susceptibility

Question 425

What's the difference between immediate effect and repeated exposure in work-related ill-health?

Answer 425

Immediate effect E.g. A high dose exposure to chlorine gas, resulting in an acute airway injury and chronic asthma (acute irritant induced asthma) Repeated exposure These diseases develop after an asymptomatic or ‘latent’ period Shorter latency (months or a few years) commonly present whilst an individual worker is still exposed to a harmful material in the workplace Longer latency (often decades) commonly present close to or after retirement

Question 426

What questions should you be asking in light of a short latency lung disease?

Answer 426

What condition does the patient have? Is their job making their co-incidental disease worse or is it causing them to have a disease that they would not otherwise have? Is it safe for them to continue their job? Are other workers at risk of becoming ill?

Question 427

What questions should you be asking in light of a long latency lung disease?

Answer 427

Did your patient’s job give them this illness? Are there other contributing factors? What are the possible implications of that?

Question 428

What are the common occupational lung diseases?

Answer 428

Asbestos related Mesothelioma Pneumoconiosis Asthma

Question 429

What causes occupational asthma?

Answer 429

``` Spray paint Animals Metalwork Latex gloves Cleaning solutions Soldering Work cutting Bakery ```

Question 430

How common is occupational asthma?

Answer 430

15% of all adult onset asthma 90% asthma is induced by sensitisation to an agent inhaled at work 10% asthma is induced by a massive accidental irritant exposure at work (direct airway injury)

Question 431

What is OASYS?

Answer 431

OASYS - plots and interprets serial peak expiratory flow (PEF) readings of patients suspected as having occupational asthma or work-related asthma.

Question 432

What are the major features of occupational asthma?

Answer 432

``` Latent period Deteriorating symptoms Gradual improvement Can occur in most jobs - think about wood, floor, metal working fluids, isocyanate paint Can cause depression Destroys lives ```

Question 433

What is Extrinsic Allergic Alveolitis aka Hypersensitivity Pneumonitis?

Answer 433

Caused by metalwork fluids, mouldy hay, chickens, swimming pools. Allergic sensitisation (combined type III/IV) Occupational or environmental Acute (self-limiting febrile response) Sub-acute Chronic (irreversible pulmonary fibrosis) More common in non-smokers than smokers.

Question 434

What is Pneumoconiosis?

Answer 434

``` Lung disease caused by inhalation of mineral dust Asbestosis Coal worker’s pneumonia Silicosis Other unspecified pneumoconiosis ```

Question 435

What are Pleural plaques?

Answer 435

``` Layers of collagen, often calcified Harmless marker of exposure Not pre-malignant Aetiology unclear Doesn’t cause symptoms ```

Question 436

What are Diffuse pleural thickenings?

Answer 436

``` Follows benign effusion Obliteration of costophrenic angle Lung expansion restricted by thickened pleura No effective treatment May progress slowly ```

Question 437

What is Asbestosis?

Answer 437

``` Interstitial lung fibrosis Long latency (decades) History of heavy exposure No effective treatment May progress slowly (without further exposure) Progressive breathlessness ```

Question 438

What is Mesothelioma?

Answer 438

Rapidly progressive and incurable pleural cancer-encasing lung with tumour Often presents as unexplained pleural effusion Progressive breathlessness, chest pain, weight loss Average survival 8-14 months

Question 439

What happens post-diagnosis of occupational lung disease?

Answer 439

``` Unemployment (up to one third) Loss of earnings Chronic respiratory ill health Depression Loss of self worth Breakdown of relationships Compensation ```

Question 440

How do you prevent occupational lung disease?

Answer 440

Legal requirement Risk assessment Prevent or minimise exposure to harmful substances - Elimination (asbestos) - Substitution (latex to nitrile gloves) - Engineering controls (exhaust ventilation) - RPE (masks and respirators)

Question 441

How do you recognise occupational lung disease early?

Answer 441

If residual risk, monitor workers health (surveillance). Identify health problems early - Annual health questionnaire and spirometry for asthma - Questionnaire, spirometry and chest x-ray for silicosis - Prevent further harm by reducing/preventing exposure - Review control measures to protect other workers