RESPIRATORY Flashcards
What is Chronic Obstructive Pulmonary Disease (COPD)?
Progressive irreversible airway obstruction characterised by persistent airflow limitation caused by long term damage to lung tissue.
What are the conditions that are classed as COPD?
Chronic Bronchitis
Emphysema
What is the epidemiology of COPD?
1.2 million people with COPD in the UK
4th leading cause of death globally
Typically diagnosed >45 yrs
More common in males
Strongly related to Smoking.
What are the risk factors for COPD?
Cigarette smoking - MOST INPORTANT CAUSE
Air pollution - Exposure to air pollutants e.g. sulfur and nitrogen dioxide
Occupational exposure to dusts, chemical agents, and fumes, silica
A1AT deficiency - can lead to early onset COPD
Family history of chronic bronchitis
Spirometry recap
Define
FEV1
FVC
What is the normal FEV1/FVC ratio
FEV1 = volume of air that can be forcefully expired in 1 second
FVC = total volume of air that can be forcibly exhaled after maximum inhalation
The normal value for the FEV1/FVC ratio is 70% (and 65% in persons older than age 65).
What happens to the
FEV, FEV1, and FEV1/FVC, and TLC in Obstructive conditions like COPD and Asthma?
In COPD, the airways become obstructed and the lungs don’t empty properly which leaves air trapped inside the lungs.
- FVC (max air exhaled in one breath): lowered
- FEV1 (first second of air breathed out in a single breath): lowered, more than the FVC
- FEV1:FVC ratio: lowered
- TLC (total lung capacity): increased due to air trapping
Define Chronic Bronchitis?
Chronic Bronchitis is a clinical term relating to a chronic productive cough for at least 3 months over 2 consecutive years.
(Alternative explanations for the cough should also be excluded).
Normal physiology, layers of the respiratory tract -
What makes up the Mucosa?
Mucosa consists of Pseudostratified columnar epithelial cells, interspersed with goblet cells that secrete mucous
As well as the lamina Propria - Basement membrane and loose connective tissue
Normal physiology, layers of the respiratory tract -
What makes up the submucosa?
Submucosa - Smooth muscle and connective tissue, as well as Bronchial mucinous glands, that produce the mucus to be secreted by the goblet cells
Bronchi only is lined with cartilage, which stiffens and supports the bronchus
What is the pathophysiology behind chronic bronchitis
Hypertrophy and hyperplasia of bronchial mucinous glands and goblet cells. Also ciliary destruction. (ie due to cigarette smoke as main cause
More mucous in lumen - causes narrowing and obstruction,
epithelial layer may become ulcerated and undergoes metaplasia
Also, smoking makes the cilia short and less mobile, making it harder to move mucus up and out of bronchioles. A cough is sometimes the only way to clear this mucus.
What is the metaplasia seen in Chronic bronchitis? What is air trapping in the context of CB?
squamous epithelium replaces the columnar cells (squamous metaplasia), when ulcers heal
Bc bronchioles are small, a small amount of mucous can block them - leads to air trapping, where air can’t be exhaled - the majority of air trapping happens in the bronchioles
Pathophysiology of chronic bronchitis - why may patients with this go on to develop hypoxia and hypercapnia?
Mucus plugs block airflow, == high levels of CO2 and low levels of O2 in the lung
–> so less O2 moves into blood and less CO2 moves out of blood.
Blood vessels can then undergo vasoconstriction to shunt blood away from damaged tissue towards healthy lung tissue.
What are some signs and symptoms of chronic bronchitis?
- Wheeze: due to narrowing of the passageway available for air to move in and out
- Crackles or rales: caused by the popping open of small airways
-
Cyanosis (blue bloaters): if there is buildup of CO2 in blood
- Productive cough, lots of mucous
- Dyspnoea
- Signs of CO2retention
- Drowsy
- Asterixis
- Confusion
What is the cause of the barrel shaped chest in COPD?
Both chronic bronchitis and emphysema leads to air trapping within the Bronchi/acini.
This leads to Hyperinflation of the lungs giving a barrel chest appearance.
air trapping ===> Hyperinflation
What is Emphysema as a pathological Definition?
A lung disease characterised by dilatation and destruction of the lung tissue causing enlarged air spaces distal to the terminal bronchioles
Outline the pathophysiology behind emphysema.
Occurs in the ACINUS - (the respiratory bronchioles, alveolar ducts and alveolar sacs distal to a single terminal bronchiole)
Irritants/chemicals damage alvolar wall EG cigarette smoke
immune cell infiltration releasing Leukotriene B4, IL-8 and TNF-a, as well as Neutrophil Proteases (elastases and collagenases)
- Neutrophil proteases break down alveolar septa break down, REDUCES TOTAL SURFACE AREA -
Loss of elasticity in the airways means that the airways collapse upon exhalation causing air trapping distally.
How does the Bernoulli principle explain some of the pathophysiological changes that happen in emphysema?
(due to Bernoulli principle that means that high velocity exhaled air creates low pressure in airways - elastin normally stops airways collapsing under low pressure)
When elastin isn’t there, airways collapse
What are the different types of Emphysema?
Centriacinar Emphysema
Panacinar Emphysema:
Paraseptal Emphysema:
What is Centriacinar Emphysema? What is it commonly due to? Where does it commonly affect in the lungs?
Most common
Damage to central/proximal acini due to smoking
Typically affects upper lobes
What is Panacinar Emphysema? What is it commonly due to? Where does it commonly affect in the lungs?
Entire acinus affected
Due to A1AT Deficiency (protease inhibitor deficiency) cannot prevent breakdown.
Typically affects Lower lobes
What is Paraseptal Emphysema? What can if commonly lead to? Where does it commonly affect in the lungs?
distal alveoli of the acinus are most affected. Typically affects the lung tissue on the periphery of the lobules.
Peripheral ballooned alveoli can rupture causing pneumothorax
What are the pathological changes seen in emphysema?
Related to loss of Elastin:
Collapse: the alveoli are prone to collapse.
Dilation and bullae formation: alveoli dilate and may eventually join with neighbouring alveoli forming bullae
How is Chronic Bronchitis and Emphysema classified differently?
Chronic Bronchitis is defined by clinical features
Emphysema is defined by structural changes (enlarged alveoli)
What do you need to consider in spirometry testing for COPD?
FEV1/FVC ratio less than 0.7
Important to note that it does not show a dramatic response to reversibility testing with salbutamol (beta-2 agonist). If it does then consider asthma as a differential
Bronchodilator (salbutamol) will increase FEV1 by >12% in asthma, FEV1 would increase less than 12% or not at all in COPD
What are some signs and symptoms of emphysema
- Breathing with pursed lips (pink puffers): prevents alveolar collapse by increasing the positive end expiratory pressure
- Barrel shaped chest: due to air trapping and hyperinflation
- Loss of cardiac dullness:due to hyperexpansion of lungs from emphysema
- Dyspnoea
- Cough: could be productive
- Weight loss: due to energy expenditure while breathing
- Signs of CO2retention
- Drowsy
- Asterixis
- Confusion
What is the main test you would use to investigate COPD? What would you see in it?
Clinical Dx with Spirometry Test for confirmation
Spirometry shows Obstruction:
FEV1/FVC ration <0.7
Global Initiative for COPD (GOLD)
FEV1% - compared to predicted value
Stage 1 - > 80% (mild)
Stage 2 – 50-79% (moderate)
Stage 3 – 30-49% (severe)
Stage 4 - < 30% (very severe)
Multiple peak flow measurements to exclude asthma
What other tests may be done to look for the cause of COPD? on top of spirometry?
CXR:
DLCO (diffusing capacity of CO across lung):
Low in COPD, Normal in Asthma
Genetic testing for A1AT Def.
ABG - may show T2RF
ECG - heart function
CXR - flattened diaphragm
Bloods - anaemia
What would you see on a xray for someone with COPD
Hyperexpanded, enlarged lungs, air pockets (bullae) or a flattened diaphragm, and saber sheath trachea
Barrel shaped chest
What is the initial management for COPD?
STOP SMOKING
Annual flu vaccine and the pneumococcal vaccine (this is a one off vaccine)
What are the GOLD groups in COPD?
GOLD A= 1 or less exacerbations per year not requiring admission with mild symptoms
GOLD B= 1 or less exacerbations per year not requiring admission severe symptoms
GOLD C= 2 exacerbations per year or 1 per year requiring admission n with mild symptoms
GOLD D= 2 exacerbations per year or 1 per year requiring admission with severe symptoms
What are the different bronchodilators used to treat COPD?
SABA:short-acting beta-agonist (e.g. salbutamol)
SAMA: short-acting muscarinic antagonist (ipratropium)
LABA: long-acting beta-agonist (e.g. salmeterol)
LAMA: long-acting muscarinic antagonist (e.g. tiotropium)
COPD treatment - What is the Initial therapy?
Any short or long acting bronchodilator
SABA/SAMA
SABA - salbutamol
SAMA - ipratropium
What is the second line treatment for COPD, if they do not have asthmatic or steroid responsive features?
long acting beta agonist (LABA) plus a long acting muscarinic antagonist (LAMA) -
LABA: long-acting beta-agonist (e.g. salmeterol)
LAMA: long-acting muscarinic antagonist (e.g. tiotropium)
What is the second line treatment for COPD, if they DO have asthmatic or steroid responsive features?
combined long acting beta agonist (LABA) plus an inhaled corticosteroid (ICS)
LABA (i.e. salmeterol)
ICS (i.e. budesonide)
. If these don’t work then they can step up to a combination of a LABA, LAMA and ICS.
Other than bronchodilators, what other treatments can be given in COPD?
Nebulisers - eg Salbutamol
- Phosphodiesterase-4 inhibitors eg Roflumilast - (blocks the breakdown of cyclic adenosine monophosphate)
- Long-term oxygen therapy (LTOT)
How do LABAs and SABAs work?
b2-adrenoceptor agonists (beta agonists)
They act on b2-adrenoceptors to cause smooth
muscle relaxation and bronchodilation, by increasing cAMP . Also inhibit histamine release
from lung mast cell
How do LABAs take longer to work than SABAs?
LABAs possess adequate lipophilic properties to remain in the airway tissues as a depot in close vicinity to the beta2-receptor, explaining their long duration of effect.
How do LAMAs and SAMAs work
They are Anti-cholinergics
(long/short-acting muscarinic antagonist)– promotes cGMP degradation 🡪 smooth muscle relaxation
Muscarinic antagonists work by blocking the action of acetylcholine, a neurotransmitter that causes smooth muscle contraction in the airways, leading to bronchospasm and narrowing of the airways.
What is the method of action behind how inhaled corticosteroids work? (ICS)
Glucocorticoids reduce number of inflammatory cells in airways by:
- Suppress production of chemotaxic mediators
- Reduce Adhesion molecule expression
- inhibit inflammatory cell survival in the airway
ICS also suppress inflammatory gene expression in airway epithelial cells,
eg via IKB-ALPHA
What is an Exacerbation of COPD?
worsening of symptoms such as cough, shortness of breath, sputum production and wheeze. It is usually triggered by a viral or bacterial infection.
What are the main bacterial causes of an IECOPD?
What antbx would you use to treat these?
H.Influenzia
S.Pneumoniae
TREAT BOTH WITH AMOXICILLIN
What would an exacerbation look like on an ABG?
CO2 will make blood more acidotic. This will show as a type 2 respiratory acidosis high CO2 and low oxygen with low pH
If this chronic there will be some metabolic compensation by kidneys releasing more bicarbonate to try and neutralise pH
What is the treatment for an exacerbation of COPD where the patient is well enough to stay at home?
Prednisolone for 7-14 days
Regular inhalers or home nebulisers
Antibiotics if there is presence of infection
What is the treatment for an exacerbation of COPD where the patient is in hospital?
Nebulised bronchodilators (e.g. salbutamol 5mg/4h and ipratropium 500mcg/6h)
Steroids (e.g. 200mg hydrocortisone or 30-40mg oral prednisolone)
Antibiotics if evidence of infection
Physiotherapy can help clear sputum
What are the treatment options for an exacerbation of COPD not responding to treatment?
IV aminophylline
Non-invasive ventilation
Intubation and ventilation
-Doxapram can be used as a respiratory stimulant if ventilation not appropriate
Why do you have to be careful giving oxygen to someone with COPD and how would you manage this?
Too much oxygen in someone that is prone to retaining CO2 can depress their respiratory drive.
Venturi masks are designed to deliver specific percentage concentrations of oxygen
If retaining CO2 aim for oxygen saturations of 88-92% titrated by Venturi mask
If not retaining CO2 and their bicarbonate is normal (meaning they do not normally retain CO2) then give oxygen to aim for oxygen saturations > 94%
What is Tuberculosis? What is it characterised
An infectious disease caused by Mycobacteria characterised by caseating granulomas.
What causes Tuberculosis?
Caused by two species: Mycobacterium tuberculosis and Mycobacterium bovis.
Spread via airborne transmission
What is the morphology of M. TB?
Acid Fast Rod Bacilli
Non motile + non spore forming
Acid fast staining (Zeihl-Neelsen stain.) - Stains red
Doesn’t take up gram stain due to Mycolic acid capsule
Resistant to phagocytic killing.
Slow growing (15-20 hrs)
What are some risk factors for TB?
IVDU,
homeless,
immunosuppression
alcoholic,
close contact with infected patients - either as living with them or as healthcare worker
What is the epidemiology of TB?
1.7Bn people have latent TB
Top infectious killer in the world
Affects immunocompromised more
More common in South Asia (India, China, Pakistan) and Sub-Saharan Africa
How does TB lead to the formation of Ghon complexes? (Primary/active TB)
Macrophages struggle to clear TB due to its waxy mycolic acid capsule.
Instead of being broken down and cleared, A focal caseating granuloma typically forms in the lower lobe known as a Ghon focus.
The Ghon focus can then spread to the Hilar Lymph nodes in the lungs, which together form a ghon complex
These ghon complexes can under go fibrosis and calcification, leading to the appearance of ranke complexes on xray
What is latent TB?
- occurs after primary infection, immune system encapsulates sites of infection and stop the progression of the disease.
- Patients remain asymptomatic and the bacteria remains dormant, resulting innegative sputumcultures but apositive Mantoux test.
- These patients arenotinfectious.
- However, if patients areimmunocompromised, the disease can progress or reactivate at a later stage to becomeactive TB.
Outline what happen in secondary TB.
Where in the lung is it most likely to happen and why?
Immunocompromised patients may develop secondary TB when latent TB reactivates
- Patients are infectious.
- Reactivation typically occurs in thelung apexwhere pO2is highest, as mycobacteria are aerobic.
bacteria can spread locally, to form caseating granulomata, or systemically (miliary TB).
Outline what Miliary TB is, and what happens in it.
Miliary TB - Where immune system cannot control the infection and it becomes disseminated
Extrapulmonary TB - where TB infects other areas
What Extra-pulmonary sites can TB infect?
Lymph nodes
Pleura
Central nervous system
Pericardium
Gastrointestinal system
Genitourinary system
Bones and joints
Cutaneous TB affecting the skin
What are some general symptoms of active TB?
Systemic Sx:
Fatigue
Fever + night sweats + weight loss (characteristic of TB)
Lymphadenopathy
Wet Cough w/haemoptysis >3 weeks
Chest pain
Dyspnoea
Erythema Nodosum (swollen fat under the skin causing bumps and patches that look red or darker than surrounding skin.)
TB = Wet cough, Sarcoidosis - similar symptoms, but dry cough
What are some Extra-pulmonary manifestations of TB?
CNS - Meningism
Skin rash
Cardiac - TB pericarditis Sx
Bone - Join pain
Spinal Pain (spinal TB)
GU - Epididymitis, LUTS
Abdo - Ascites
What are some signs of TB? Why isn’t latent TB symptomatic
- Auscultation: often normal; crackles may be present
- Clubbing: if long-standing
as bacteria is contained within granuloma and causes no Sx
What are some screening Tests for TB/diagnosis of latent TB?
Latent Disease - Mantoux Test
Interferon Gamma release assay
Tests for TB - outline Interferon-gamma release assay(IGRA)
Take blood sample, mix it with TB antigens.
In a person that has had previous contact with TB the white blood cells have become sensitised to those antigens and will release interferon-gamma.
More sensitive than the Mantoux test - unlikely to be positive from the BCG vaccine
Tests for TB - outline the Mantoux test
indicates possible previous vaccination, latent or active TB.
0.1 ml of 1:1,000 of tuberculin is injected S/C, site is inspected 48-72 hours later
- This reaction is measured as a diameter ofindurationthat occurs across the forearm
- If positive, assess for active disease, greater than 5mm
What tests would you do for active TB?
Nucleic-Acid Amplification Test (NAAT): rapid diagnostic test conducted on sputum or urine
Microbiology:send three deep cough sputum samples; analyse with Ziehl-Neelsen stain (will turn red)
Chest Xray -
Latent disease may show Ghon complex
Reactivated TBmay show patchy or nodular consolidation with cavitation (gas filled spaces in the lungs)
what would DisseminatedMiliary TB look like on chest xray
Patchy Consolidation
Ghon Complex
Granulomatous Lesions
Hilar Lymphadenopathy - (enlargement)
Pleural Effusion
What is the management of latent TB?
Doesnt necessarily need Tx
If risk of reactivation then:
6 months of isoniazid with pyridoxine
or
3 months of isoniazid, pyridoxine and rifampicin
What is the Treatment for Active TB?
RIPE: Combination Abx for 6-12 months
R – Rifampicin for 6 months
I – Isoniazid for 6 months
P – Pyrazinamide for first 2 months
E – Ethambutol for first 2 months
Pyra zina mide
Etham but ol
Who is offered the BCG vaccine?
BCG vaccine is offered to patients that are at higher risk of contact with TB:
Neonates born in areas of the UK with high rates of TB
Neonates with relatives from countries with a high rate of TB
Neonates with a family history of TB
Unvaccinated older children and young adults (< 35) who have close contact with TB
Unvaccinated children or young adults that recently arrived from a country with a high rate of TB
Healthcare workers
What is Pneumonia?
Infection of the lung parenchyma leading to inflammation of the lung tissue and fluid exudation (sputum) collecting in the alveoli.
Can be seen as consolidation on a chest x-ray
What are the different types of pneumonia?
Community acquired
Hospital acquired if it occurs more than 48 hours after admission - (can be further classified into Elderly, Ventilator-associated, Post-op)
Aspiration pneumonia if it occurs after inhaling foreign material
What are the main causes of CAP?
Think - community, so more basic/simple bacteria
Streptococcus pneumonia (50%)
H. Influenzae (20%)
- Staphylococcus aureus
- Klebsiella pneumonia
Pseudomonas aeruginosa
Outline the classification/morphology of streptococcus pneumonia
Gram-positive cocci
Alpha haemolytic
Optochin sensitive
What are the location-based classification of pneumonia?
- Bronchopneumonia: infection can be throughout the lungs involving the bronchioles as well as the alveoli.
- Atypical or interstitial pneumonia: infection is mainly just outside the alveoli in the interstitium.
- Lobar pneumonia: infection causes complete consolidation of a whole lobe of the lung.
What are the main causes of HAP?
P.aeurginosa
E.coli
S.aureus
Klebsiella
These can cause CAPs as well, but just not as common
What is the most common cause of pneumonia
What about in COPD patients
What Pneumonia causing organism is often seen in alcoholics?
Streptococcus pneumoniae (pneumococcus) =Accounts for 80% of cases -Particularly associated with high fever, rapid onset and herpes labialis
A vaccine to pneumococcus is available
Haemophilus influenzae Particularly common in patients with COPD
Klebsiella pneumonia is classically seen in alcoholics
What pneuomia causing organism is often seen with Autoimmune haemolytic anaemia and erythema multiforme?
What pneuomia causing organism is often seen following a influenza infection
What pneuomia causing organism is often seen with hyponatraemia and lymphopenia?
Mycoplasma pneumoniae
Staphylococcus aureus
Legionella pneumophilia
What is the main cause of aspiration acquired pneumonia?
Klebsiella
What is the pathophysiology of pneumonia?
These microbes typically multiply and cross over from the airways into the lung tissue, creating an inflammatory response.
Pneumonia refers to any inflammatory reaction affecting the alveoli it is most commonly secondary to infection
The tissue fills with white blood cells as well as proteins, fluid, and red blood cells if a nearby capillary is damaged in the process.
What is atypical pneumonia?
How are they Tx?
pneumonia caused by an organism that cannot be cultured in the normal way or detected using a gram stain.
They dont respond to penicillins
Tx with Macrolides, Fluoroquinolones and tetracyclines.
What are the main causes of atypical pneumonia?
Legionella pneumophila (Legionnaires’ disease) infected water, causes Hyponatraemia
Mycoplasma pneumoniae. erythema multiforme, neuro signs
Chlamydophila pneumoniae school child
Coxiella burnetii AKA “Q fever” farmer
Chlamydia psittaci. - bird owner
TIP: You can remember the 5 causes of atypical pneumonia with the mnemonic: “Legions of psittaci MCQs”
M – mycoplasma pneumoniae
C – chlamydydophila pneumoniae
Qs – Q fever (coxiella burnetii)
Legionella pneumophila should be suspected in multiple otherwise fit patients who have developed pneumonia after air condition exposure. Hyponatraemia and lymphopenia are features associated with Legionella pneumophila .
What is the main cause of fungal pneumonia? How can you treat it?
Pneumocystis jiroveci (PCP)
Occurs in immunocompromised Px
AIDS defining illness
Co-trimoxazole
(combination of Trimethoprim and Sulphamethoxazole)
What are the risk factors for pneumonia?
Extremes of age
Preceding infection (viral)
Immunosuppressed
IVDU
Smoking
CO-Morbidities - DM, HIV
Respiratory conditions - asthma, COPD, CF
What are the symptoms of pneumonia?
Productive cough w/purulent sputum (rusty suggests S. pneumoniae)
Fever - due to infection
Pleuritic chest pain- pain worse on deep breathing (sandpaper on sandpaper)
Dyspnoea
Malaise
May cause confusion in elderly
Dry cough in atypical pneumonia
Classic symptoms
- Fever
Sweats
Rigors
What are the signs of pneumonia?
Reduced breath sounds
Bronchial Breathing w/ coarse crepitations
Crackles and Wheeze
Consolidation
Dull Percussion
Hypoxia
Tachycardia
Pyrexia
Confusion
Cyanosis
What are some differential diagnosis for pneumonia?
Heart Failure
PE
Pleural effusion
Bronchiectasis
Acute bronchitis
Drug-induced pneumonitis
Cancer
TB
Interstitial Lung Disease
Outline the effect of Pneumocystis jiroveci on healthy people.
Who are the kind of people that will develop Pneumocystis pneumonia (PCP) from it?
commonly found in the lungs of healthy people, not a cause for disease. source of opportunistic infection in immunocompromised people, eg HIV/AIDs, cancer, autoimmune or inflammatory conditions, and chronic lung disease
The risk of PCP increases when CD4-positive T-cell levels are less than 400 cells/μL
How is PCP treated?
Co-trimoxazole
(combination of Trimethoprim and Sulphamethoxazole)
How can you gauge the severity of pneumonia in
a) the hospital
b) the community
Give the values that lead to scoring
CRB-65 out of hospital and CURB-65 in hospital. The only difference is that out of hospital you do not count urea.
C – Confusion (new disorientation in person, place or time)
U – Urea > 7
R – Respiratory rate ≥ 30
B – Blood pressure < 90 systolic or ≤ 60 diastolic.
65 – Age ≥ 65
outline How does the scoring for CURB-65 dictate treatment and mortality, for dealing with pneumonia
Score 0/1: Consider treatment at home
Score ≥ 2: Consider hospital admission
Score ≥ 3: Consider intensive care assessment
0 = Low risk (<1% mortality)
1-2 = Intermediate risk (1-10% mortality)
3-4 = High Risk (>10% mortality)
What investigation would you do for a pneumonia?
1st Line:
- CXR:consolidation caused by inflammatory exudate within alveoli and bronchioles
- Atypical pneumoniacauses interstitial inflammation instead, so CXR may be normal
FBC - Raised WCC
U&E - urea
CRP - raised due to inflammation
Sputum culture:allows assessment of organism and antibiotic sensitivities
Urine culutres, for Legionella Urinary Antigen - Doesn’t respond well to Abx
What is consolidation? (seen on xray in lung infections) How does it occur
Consolidation - region of normally compressible lung tissue - filled with liquid instead of air
Happens as inflammatory fluid exudate accumilates in the alveoli and broncioles in acute inflammation
MUST BE PRESENT IN ORDER TO DIAGNOSE PNEUMONIA - IT IS MORE RADIO OPAQUE - WHITER THAN NORMAL LUNG TISSUE
What is the Initial treatment for pneumonia? What broad spectrum antbx would you give for mild severity?
Oxygen Saturation 94-98%
IV Fluids if dehydrated
Appropriate Analgesia - Paracetamol/NSAIDs
Mild severity – CURB65 0-1 (5 days)
Amoxicillin
Allergic? – clarithromycin or doxycycline
What anbtx would you give for moderate severity and severe severity Pneumonia? (What CURB scores would these equate to?)
Moderate severity – CURB65 2 (5 days)
Amoxicillin + clarithromycin
Severe CURB65 3-5 (>5 days, 14-21 if S. Aureus)
IV co-amoxiclav + clarithromycin
(btw Clarithromycin is a macrolide)
Anbtx treatment for pneumonia - once the causative organism is known to be Streptococcus Pneumoniae, what specific anbtx would you give?
S. Pneumoniae
Use amoxicillin, or cefuroxime (second gen Cephalosporin)
Anbtx treatment for pneumonia - once the causative organism is known to be H Influenziae, what specific anbtx would you give?
Amoxicillin + clavulanic acid - (Co-Amoxiclav)
Doxycycline
Anbtx treatment for pneumonia - once the causative organism is known to be Staphylococcus aureus, what specific anbtx would you give?
What do you give for MRSA?
Flucloxacillin
Cefuroxime
MRSA =
Vancomycin
Anbtx treatment for pneumonia - once the causative organism is known to be klebsiella pneumoniae, what specific anbtx would you give?
What about
P. Aeruginosa
Co-amoxiclav
Cephalosporins
P. Aeruginosa
Piperacillin-Tazobactam (Tazocin)
What do you give to treat atypical pneumonia?
Macrolides/Fluoroquinolones,tetracyclines.
What is asthma? What is it characterised by?
Asthma is a chronic inflammatory airway disease characterised by intermittent airway obstruction and hyper-reactivity, + inflammed bronchioles and mucous hypersecretion
What are the types of Asthma?
Eosinophilic (Allergic) (70%) - Extrinsic IgE mediated T1 Hypersensitivity
Non-Eosinophilic (Non Allergic) (30%) - Intrinsic non IgE mediated.
What is the prevalence of asthma?
What age does it tend to start?
What ages are its peak prevalence?
- Asthma is a common disease with a prevalence of almost 10% in the US
- Commonly starts in childhood between the ages 3-5 years and may either worsen or improve during adolescence
- Peak prevalence between 5-15 years
What are some risk factors for developing asthma?
- History of atopy: such as eczemaand allergic rhinitis (IgE-mediated atopic conditions)
- Family history
- Allergens: such as tobacco smoke, pets, outdoor air pollution, weeds, grass, mould pollen and dust mites
- Viral upper respiratory tract infection
- Other triggers: cold weather and exercise, medications e.g. beta blockers and aspirin
- Occupational exposure (10-15%): isocyanates are the most common cause ofoccupational asthma(e.g. spray painting)., or flour form baking
What genetics have been asossciated with asthma?
What is the hygiene hypothesis?
Genes controlling cytokines IL-3 -4 -5 -9 -13
ADAM33
states that early childhood exposure to particular microorganisms protects against allergic diseases by contributing to the development of the immune system.
Generally asthma before 12 is more genetic after this it is more environmental
Oultine the pathophysiology behind IgE Allergic type asthma that leads to activation of Mast cell and eosinophil activation
excessive reaction from Th2 cells against specific allergens.
Allergens from environmental triggers e.g. cigarette smoke, are picked up by dendritic cells and presented to Th2 cell
Cyotkines are produced - (IL-3, IL-4, IL-5, IL-10, IL-13)
This leads to the production of IgE antibodies which coat mast cells and stimulate them to release granules containing things e.g. histamines, leukotrienes and prostaglandins.
It also results in the activation of eosinophils which promote an immune response by releasing more cytokines and leukotrienes.
What pathophysiological changes to the bronchi is seen in asthma?
Smooth muscle spasm around bronchioles
Increased mucus secretion.
Airway wall oedema
There is also an increase in vascular permeability and recruitment of additional immune cells from the blood.
Initially these inflammatory changes are completely reversible but longer term leads to thickening of the epithelial basement membrane, which permanently reduces the airway diameter.
—> also in chronic asthma - see smooth muscle hypertrophy
What drugs can trigger asthma? How can they do this?
Beta blockers - (block adrenaline from binding) Blocking these receptors leads to smooth muscle contraction, narrowing airways and increasing blood pressure.
Aspirin inhibits COX1/2
leads to increase USE of LPOX pathway.
Produces leukotrienes (LTB4, 5, 6)
These are proinflammatory
What are the symptoms of asthma?
Chest tightness
Episodic Dyspnoea/SOB
Wheeze
Dry Cough (typically but can be wet)
What are the signs of asthma?
Diurnal PEFR variation
Dyspnoea and Expiratory Polyphonic wheeze
Samter’s Triad: Nasal polyps, Aspirin sensitivity, Asthma
Atopic Triad: Atopic Rhinitis, Asthma, Eczema
Hyper resonant Percussion
What may be found in sputum from an asthmatic?
Curschmann spirals:
Mucus plugs that look like casts of the small bronchi
Charcot-Leyden crystals:
From break down of eosiophils.
What are some primary investigations of asthma?
- Fractional exhaled nitric oxide (FeNO):>40 ppb is positive in adults
-
Spirometry:FEV1/FVC <70% suggests obstruction
if positive for obstruction, then carry out Bronchodilator reversibility (BDR) - Peak flow rate (PEFR):measured multiple times a day over 2-4 weeks. Variability of >20% is diagnostic
- Airway hyperreactivity testing: a histamine or methacholine direct bronchial challenge is performed if the investigations above are inconclusive
- Allergy testing: immunoassay for allergen-specific IgE or skin-prick testing
How does Peak flow measurements differ at different times of the day?
Morning lower, evening higher. Diurnal variation
What is the bronchodilator reversibility test? What values in this would be indicative of asthma?
Looks to see if bronchodilators can improve FEV1
In asthma, use of bronchodilators should lead to
improvement of FEV1 by ≥12%andincrease ≥200ml in volume post-bronchodilator
An improvement of less than 12% is indicative of COPD
What is the general 1st and 2nd line management of chronic, non exacerbatory asthma?
1st line - SAB2A, eg Salbutamol, PRN
2nd line - SABA; e.g. salbutamol + low dose ICSe.g. beclomethasone.
What is the general 3rd and 4th line management for chronic asthma?
3a. Before adding more drugs assess inhaler technique and compliance
3b. SABA + ICS + Leukotriene Receptor Antagonist (LTRA = montelukast)
4th - SABA + ICS + LABA (Salmeterol) +/- LTRA
after SABA, ICS, LABA, and LTRA for asthma what do you switch to?
SABA and MART(maintenance and reliever therapy); this is combined fast-acting LABA and ICS for symptomatic relief and maintenance in a single inhaler.
Can increase ICS dose!!!
ICS increase transcription of B2-receptor gene = more expression of it on cell surface receptors —> ICS help Beta Agonists to work
What is the presentation of an asthma attack?
Fast respiratory rate
Symmetrical wheeze
Tight sounding chest with reduced air entry
How tight is someone’s chest when they’re having an asthma attack?
Almost as tight as Abishek’s chest at miniNAMs when he wore a muscle fit top a good 3 sizes to small
#pecs #gainz #gymLAD
What is investigated in an asthma attack?
PEFR
ABG: patients will initially have respiratory alkalosis. Abnormal or high PCO2 is concerning as it implies the patient is tiring
What PEFR would be considered an moderate, severe, life threatening/fatal asthma attack?
Moderate - PEFR 50-75% of predicted
Acute Severe - PEFR 33-50%, Resp rate >25, HR >110, can’t complete sentences
Lifethreatening PEFR <33%, Sats <92%, Becoming tired, No wheeze,
What is the treatment for acute asthma attacks?
OSHITME:
O2 if oxygen sats are low
Saba (Salbutamol nebulised)
Hydrocortisone IV
Ipratropium bromide added to nebulizer remember, ipratropium is a SAMA
Theophyline IV - Bronchodilator
MgSO4 - Magnesium sulphate,
Escalate
What are some indicators of good asthma control?
- No night-time symptoms
● Inhaler used no more than three times per week
● No breathing difficulties, cough or wheeze on most days
● Able to exercise without symptoms
● Normal lung function test
What is cystic fibrosis?
Cystic fibrosis (CF) is an inherited, autosomal recessive, multi-system disease affecting mucus glands.
Respiratory problems most prominent, as well as pancreatic insufficiency.
What is epidemiology of Cystic fibrosis?
Cystic fibrosis is the most common inherited condition in the Caucasian population, affecting 1/2500 births, whilst 1/25 of the population are carriers
AUTOSOMMAL RECESSIVE
A mutation on what gene causes CF?
What does this mutation go on to cause?
cystic fibrosis transmembrane conductance regulatory gene on chromosome 7
Δ-F508 is the most common mutation, where the codon for phenylalanine (F) in the CFTR gene is deleted, resulting in proteolytic degradation.
Normal physiology - what does the CFTR gene do?
cystic fibrosis transmembrane conductance regulatory gene codes for a channel protein that pumps chloride ions into various secretions, those chloride ions help draw water into the secretions, which ends up thinning them out.
How does a mutation to the CFTR gene cause disease?
Misfolded CFTR protein can’t migrate from the endoplasmic reticulum to the cell membrane, meaning there’s a lack of CFTR protein on the epithelial surface
This means that it can’t pump chloride ions out, which means water doesn’t get drawn in, and the secretions are left overly thick.
What is the pathophysiology of a CFTR dysfunction in relation to the lungs?
CFTR mutation leads to thick mucus secretions.
This causes impaired mucociliary clearance as the mucus is extra thick.
This leads to stagnation of mucus that contains pathogens which leads to increased infection risk.
The thicker mucus causes difficulty breathing
Trapping of mucosal pathogens can cause a inflammatory reaction which leads to an increased risk of bronchiectasis
What are the main pathogens that can cause lung infections in people with cystic fibrosis? What anbtx would you give for these
- Low volume thick airway secretions that reduce airway clearance, resulting in bacterial colonisation and susceptibility to airway infections, especially with:
S. Aureus – flucloxacillin
H. influenzae – amoxicillin
Pseudomonas aeruginosa - ciprofloxacin
What is the pathophysiology of a CFTR dysfunction in relation to neonates?
Can lead to Meconium Ileus:
Stool becomes too thick to pass through the bowel leading to bowel obstruction. - Surgical emergency
Failure to thrive
What is the pathophysiology of a CFTR dysfunction in relation to the GI Tract?
Thick secretions from the pancreas can lead to pancreatic duct obstruction.
Pancreatic insufficiency and malabsorption of foods.
Pancreas enzymes can build up in pancreas and damage it, leading to pancreatitis and fibrosis
Bowel obstructions
Can also lead to endocrine dysfunction - insulin dependant diabetes
What is the pathophysiology of a CFTR dysfunction in relation to the Hepatobiliary system?
How can CF lead to male infertility?
Thicker biliary secretions leads to an increased risk of biliary obstruction.
Could lead to liver cirrhosis
CFTR mutation can cause atrophy of the vas deferens leading to infertility
What are the symptoms of CF?
Chronic cough w/Thick sputum production
Recurrent respiratory tract infections
Loose, greasy stools (steatorrhoea) due to a lack of fat digesting lipase enzymes
Abdominal pain and bloating
Most common cause of Meconium Ileus in infants
Parents may report the child tastes particularly salty when they kiss them, due to the concentrated salt in the sweat
Poor weight and height gain (failure to thrive)
What are some signs of CF?
- Low weight
- Nasal polyps
- Finger clubbing
- Crackles and wheezes
- Abdominal distension
When is CF most often diagnosed?
What does the test in question look for
- It is found during the heel-prick/Guthrie test which screens for CF in babies by looking for serum immunoreactivity trypsinogen
Immunoreactivity trypsinogen is an pancreatic enzyme that is released into the blood when the pancreas is damaged.
What other investigations can you do for CF? What is gold standard?
Other than heel-prick/Guthrie test (looks for serum IRT)
Sweat test:gold standard test; induce sweating (by placing electrodes on skin) followed by analysis of sweat to check Cl- concentration
A result of> 60 mmol/L (sweat chloride) is positive and requires referral to a cystic fibrosis specialist (normal value < 40 mmol/Ll)
Genetic testing:Genetic testing for CFTR gene mutation can be performed during pregnancy, via amniocentesis
- Lung function tests:obstructive pattern seen; and allows monitoring of treatment
-
Sputum sample:microbiological investigation during exacerbations
Faecal elastase:test for pancreatic insufficiency
Why are people with CF at a massively increased risk of recurrent respiratory tract infections?
Patients with cystic fibrosis struggle to clear the secretions in their airways.
This creates a perfect environment with plenty of moisture and oxygen for colonies of bacteria to live and replicate.
What are some first line treatments to help manage CF?
Exercise, no smoking!
- Airway clearance techniques:minimum 2 times per day. Chest physiotherapy and postural drainage.
- Bronchodilator: inhaledsalbutamolfor exacerbations
rhDNasee.g. dornase alfa - an enzyme that breaks down material in secretions, making them less viscous
- Nebulised hypertonic saline
what is the new miracle cure for CF?
personalised genetic treatments - targets specific mutation - F508 del,
Lumacaftor is a CFTR corrector, acts as a Pharmalogical chaperone to bring the F508 del CFTR protein to the cell membrane
Ivacaftor, a CFTR potentiator binds to channel directly, increases the chances of it opening. primarily the targets G551D mutation.
Can be used in combination with one another
What is bronchiectasis?
Bronchiectasis is the permanent dilation of bronchi due to the destruction of the elastic and muscular components of the bronchial wall.
It’s an obstructive airway disease
Name some diseases that can lead to Bronchiectasis
Primary ciliary dyskinesia: cilia don’t move normally which leaves mucus stuck in the airways. Bacteria trapped in mucus can lead to pneumonia and inflammation
Cystic fibrosis: mucus is sticky and therefore hard to sweep, can accumulate
Obstruction
Foreign body e.g. peanut
Post TB stenosis
Tumour
Thick mucus
AIDs, or immunoglobulin deficiency
Post-infections
Outline that pathophysiology that leads to bronchectasis.
Chronic inflammation 🡪 damage to airways 🡪 elastin destruction (lung dilates) and collagen deposition 🡪 stiff, large airways that are plugged with mucous, and and fibrosis of lung parenchyma (non-reversible)
What are some symptoms for bronchiectasis?
Chronic cough with expectoration of large quantities of foul-smelling sputum, sometimes it is flecked with blood (haemoptysis)
Haemoptysis
SOB/Dyspnoea
Wheeze
Chest pain
What are some investigations for bronchiectasis?
What specific sign do you see on the gold standard investigation
Lung function test – shows obstructive pattern, less lung capacity and less FEV1 - FEV1/FVC = <0.7
Chest xray - Dilated bronchi with thickened walls – tramline and ring shadows, Multiple cysts containing fluid showing up as cystic shadows
High resolution CT - gold standard - Thickened, dilated bronchi with cysts at end of bronchioles, Airways larger than associated blood vessels - Signet ring sign
Sputum culture – to see colonisation status and exclude non-tuberculous mycobacterial disease
How can bronchiectasis lead to heart failure
Airways that are full of mucous become hypoxic.
Widespread hypoxia leads to widespread vasoconstriction of the pulmonary blood vessels - leading to pulmonary hypertension
Pulmonary hypertension means that the right side of the heart will have to beat harder to get blood around pulmonary circulation - RV hypertrophy
Known as Cor pulmonale
Normal physiology - where is the pleural cavity found?
What are its functions?
Lungs covered by thin serious layer – visceral pleural
Reflected on chest wall and pericardium as parietal pleura
Pleural cavity is the thin space in-between this, and the fluid here is drained into lymphatic system
Allows movement of lung against chest wall
Coupling system between lungs and chest
Clearing fluid from pulmonary interstitium
What are the main pathology relating to a Exudative Pleural Effusion?
caused by inflammation, infection and malignancy. The inflammation results in protein e.g. LDH leaking out of the tissues and into the pleural space. - eg increased vascular permeability
What are the main pathology relating to a Lymphatic effusion (chylothorax)
-
Lymphatic effusion (chylothorax)
- The thoracic duct is disrupted so drainage is not efficient - lymphatic fluid accumulates in the pleural space.
Eg damage to duct during surgery or due to tumours
What are the signs of pleural effusion?
Reduced Chest expansion on affected side
Reduce breath sounds on affected side
Dull percussion (increased fluid)
Decreased tactile or vocal fremitus (reduced vibration of chest wall when speaking)
Pleural friction rub/bronchial breathing
Tracheal Deviation
What are the investigations for a pleural effusion
CXR:
Transudates usually bilateral (TB)
Exudates usually unilateral (EU)
Blunting of costophrenic angle
Thoracocentesis - aspirate some pleural fluid, just above the rib to avoid NV bundle
Transudate – clear
Exudate – cloudy
Lymphatic – looks like milk
Pleural effusion - outline lights criteria
The criteria state that an exudate is likely if one or moreof the following criteria are met:
- Pleural fluid protein divided by serum protein is> 0.5
- Pleural fluid LDH divided by serum LDH is> 0.6
- Pleural fluid LDH> 2/3the upper limits of normal serum LDH
Normal physiology - what creates the vacuum in the pleural space?
Vacuum in the pleural space created by
1. Tension of the diaphragm and Chest wall, to pull the thoracic cavity outwards
2. Elastic recoil of the lungs which pull the lungs inwards
- This pull creates a vacuum in the pleural space
Pleural space has a pressure of -5 centimetres of water relative to the pressure of 0 centimetres of water in both the thoracic cavity and the lungs
What is the Pathophysiology of a Pneumothorax?
Breach in the pleura (trauma/CT disorders)
Leads to air entry into pleural cavity
Elastic recoil of the lung causes it to deflate
eg. Subpleural bullae burst
eg. Abnormal connection between pleural space and airways (due to trauma)
What is a tension pneumothorax and what causes it?
Typical presentation: a ventilated patient suddenly becomes breathless and haemodynamically unstable. This is an emergency
Air is forced into the thoracic cavity without means of escape it is a one way valve.
What are the signs of a tension pneumothorax?
- Trachea will deviate away, due to the increased pressure “pushing” it over to the other side
- Hyper-resonant percussion because there is more air inside the chest
- Decreased tactile and vocal fremitus
What is the primary investigation for a pneumothorax?
- If tension pneumothorax is suspected, don’t wait for investigations!
-
Erect CXR:first-line investigation
- Demonstrates a visible visceral pleural edge with no lung markings peripheral to this line
- In atension pneumothorax, there is mediastinal shift and tracheal deviation contralaterally
CT chest:gold-standard due to accurate pneumothorax size estimation, - rarely done though
What is the management for spontaneous pneumothorax?
Rim of air <2cm and no SOB - can heal on its own
If SOB and/or a >2cm rim of air
- Aspiration is usually performed at the2nd intercostal space midclavicular lineon the affected side
- Chest drain is inserted at the5th intercostal space mid-axillaryline on the affected side within the ‘triangle of safety’
- High-flow oxygen if needed
- Repeat CXR
What is Empyema?
An infected Pleural Effusion (pus collects in pleural cavity)
Normal physiology - what do type 1 and type 2 pneumocytes do, and what is found in the lung interstitial tissue?
Type 1 - helps make up air barrier, long and thin
Type 2 - cuboidal, secrete surfactant
In-between these there is interstitial tissue, that contains macrophages and fibroblasts
Outline the pathophysiology behind idiopathic pulmonary fibrosis.
What is created and what do you see?
type II pneumocytes over-proliferate during the repair process = too many myofibroblasts, that don’t undergo apoptosis so collagen accumulates
interstitial layer thickens between the alveoli and the capillary ==> excess collagen also leads to the loss of alveoli
creating cysts, surrounded by thick walls in a pattern called “honeycombing”.
What can cause pulmonary fibrosis in the upper respiratory zones?
PSHCT
Pneumonoconiosis
Sarcoidosis + Silicosis
Hypersensitivity Pneumonitis
Cystic Fibrosis
Tuberculosis
What can cause Pulmonary Fibrosis in the Lower Respiratory Zones?
Idiopathic Pulmonary Fibrosis
Drug Induced PF
Connective tissue Disorders (SLE)
What are the diagnostic investigations for pulmonary fibrosis?
Spirometry: Restriction
CXR - non specific but can be used to exclude other DDx
Gold Standard:
High CT thorax to confirm diagnosis = Ground glass & Honeycombing
Lung biopsy if still unclear
What spirometry is indicative of a RESTRICTIVE pulmonary disease, like pulmonary fibrosis?
FVC reduced so FEV1/FVC ratio >0.8 predicted value e.g. pulmonary fibrosis
Decreased total lung capacity
FEV1 = volume of air that can be forcefully expired in 1 second
FVC = total volume of air that can be forcibly exhaled after maximum inhalation
Normal physiology recap- what is a granuloma?
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate.
Histiocytes (specifically macrophages) are the cells that define a granuloma.
The macrophages in granulomas are often referred to as “epithelioid”. This term refers to the vague resemblance of these macrophages to epithelial cells
Outline the pathophysiology behind sarcoidosis.
What is the specific type of cell that forms as a result?
A T-cell-mediated immune response to an unknown antigen attracts other immune cells, causes the formation of granulomas
The granulomas in sarcoidosis are non-caseating which means that there is no tissue necrosis at the centre of the granuloma.
The macrophages begin to release local mediators that result in inflammation, and can fuse together forming a single multi-nucleated cell called a Langhans cell,
It can involve nearly every organ, but they most often involves hilar lymph nodes which are lymph nodes that are near the point where the bronchi meets the lung.
What are the Chest symptoms of sarcoidosis?
How can you differentiate if from TB?
Dry cough - note TB has phlegm production!!**
Dyspnoea
Mediastinal lymphadenopathy
Constitutional Sx:
Weight loss, Fatigue and fever
What are the Common and Less common Extra-pulmonary symptoms of Sarcoidosis?
Common: (PESH)
Peripheral lymphadenopathy
Eye – anterior uveitis
Skin –Erythema nodosa, skin papule
Hepatosplenomegaly
Less common:
Bone
Heart – arrhythmias
CNS
Kidney
What is Lofgren’s Syndrome?
specific presentation of sarcoidosis. It is characteristic by a triad of:
Erythema nodosum
Bilateral hilar lymphadenopathy
Polyarthralgia (joint pain in multiple joints)
Heerfordt’s syndrome: causes facial nerve palsy, fever, uveitis and parotitis - see picture, also asossicated with sarcoidosis
What are some primary investigations for Sarcoidosis?
- Routine bloods:inflammatory markers may be raised, can screen for other organ involvement
- Serum calcium:hypercalcaemia (10%) (due to macrophages in non-caseating granulomas activating vitamin D)
- Angiotensin-converting enzyme (ACE):elevated (but with poor sensitivity (60%) and specificity (70%))
- CXR:first-line imaging; may show hilar lymphadenopathy or bilateral infiltrates
CT chest:shows hilar lymphadenopathy
What is the gold standard test for sarcoidosis? What would it shoe?
Tissue biopsy: usually done by doing bronchoscopy with ultrasound guided biopsy of mediastinal lymph nodes.
Shows characteristic non-caseating granulomas with epithelioid cells, as well as intracytoplasmic star-shaped or laminar calcified inclusions - (asteroid bodies, Schaumann bodies)
Outline to pathophysiology behind Hypersensitivity pneumonitis
TYPE 3 HYPERSENSITIVITY REACTION
Allergen is inhaled and picked up by alveolar macrophages which take it to the nearest lymph node., and antibodies against allergen (IgG) form autoantigens
These complexes get deposited in the lung tissues and alveoli.
Complement is activated which causes acute inflammation of the lung tissue causing pneumonitis
Chronically this can lead to pulmonary fibrosis
Can be acute or chronic
How is Hypersensitivity pneumonitis diagnosed?
Bronchoscopy with Bronchoalveolar lavage:
Biopsy shows raised T Lymphocytes and mast cells in bronchi, alveoli and non-caseating granulomas
High Res CT - Ground glass (upper lobes) and centrilobular nodules. Reticular opacity
Spirometry/ Pulmonary function test - Restrictive
Serology - Specific Igs
What is pulmonary hypertension?
Pulmonary hypertension is increased resistance and pressure of blood in the pulmonary arteries.
A mean pulmonary arterial pressure that is greater than 25 mmHg.
What diseases/conditions can lead to primary pulmonary hypertension? How do they do this?
SLE, infections e.g. HIV, thyroid disorders, and inherited genetic mutations.
Endothelial damage - release endothelin-1, serotonin, and thromboxane. These make the pulmonary arterioles constrict and cause hypertrophy of the smooth muscle surrounding them.
The damaged endothelial cells also produce less nitric oxide and prostacyclin (which, make the pulmonary arterioles dilate and inhibit smooth muscle hypertrophy)
How can left heart failure lead to pulmonary hypertension?
-usually due to myocardial infarction or systemic hypertension
Pulmonary blood vessels are normal and undamaged, but the left side of the heart is unable to pump efficiently. This causes a backup of blood in the pulmonary veins and capillary beds, which can increase the pressure in the pulmonary artery.
What is the first line and gold standard investigations for Pulmonary hypertension?
What would you see on an ECG for pulmonary hypertension?
1st Line: ECHO:
RV function, enlargement and Pressures
Gold Standard (diagnostic) Right heart Catheter
CXR - RVH, Enlarged proximal PA
ECG:
Right Ventricular Hypertrophy
Right axis deviation
Right bundle branch block
Recap - outline some normal cells found on the epithelium of the lungs, and their function
Ciliated Cells - to help waft pathogens out of lungs
Goblet Cells - to secrete mucin
Club Cells - help protect bronchiolar epithelium
Basal cells - immature cells that can differentiate into other cells
Neuroendocrine cells - that can secrete hormones into the blood
What are the different types of non - small cell lung cancer?
- Adenocarcinoma (40%)
- Squamous cell Carcinoma (20%)
- Large Cell Carcinoma (10%)
- Carcinoid/other (10%)
What are some general risk factors for lung cancer?
- Increasing age: adenocarcinomas are an exception, often occurring in younger patients.
- Smoking: tobacco smoking or environmental smoke exposure.
- Other environmental exposure: radon, asbestos, arsenic, chromium, air pollution and radiation.
- Family history: some gene mutations are known to be associated with an increased risk of lung cancer development.
Outline the pathophysiology of Small cell lung cancers -
Where are they often located?
What cells are they derived from?
- 15%of lung cancer cases
- Location: central lesion near the main bronchus, and commonly large
- Derived from neuroendocrine Kulchitsky cells
Associated with Smoking
What symptoms small cell lung cancers cause?
What is the prognosis for SCLC?
- Contain neurosecretory granules that can release neuroendocrine hormones. This makes SCLC responsible for multiple paraneoplastic syndromes:
- SIADH → hyponatraemia
- Ectopic ACTH→ Cushing’s syndrome
- Lambert-Eatonmyasthenic syndrome - releases antibodies that destroy neurons
- PTH-like substance 🡪 hypercalcaemia
- HCG or related hormones 🡪 gynecomastia (enlargement of male breast tissue)
- Rapid growth and patients usually present in an advanced stage, metastases early, often to mediastinum or distally.
What paraneoplastic syndromes are seen in squamous cell carcinomas? What symptoms would be seen with these?
Hypertrophic pulmonary osteoarthropathy: causes inflammation of the bones and joints in the wrists and ankles, and clubbing of the fingers and toes
PTHrP→ hypercalcaemia - - Fatigue, Bone pain, Headaches, Nausea and vomiting, Constipation., polyuria
Most present as obstructive lesion leading to infection
What is a Pancoast Tumour? What tumours can cause it?
A tumour in the lung apex/ upper lung that commonly metastasises to the necks sympathetic plexus and can press on the sympathetic ganglion
Can be caused by both squamous cell and adenocarcinomas
What is seen in a Pancoast tumour/what can it cause?
HORNERS Syndrome characterised by:
Ptosis - Droopy eyelids
Myosis - Excessive Pupil Constriction
Anhidrosis - Lack of sweating
What are the general Symptoms of Lung cancer?
Cough w/haemoptysis
Shortness of breath
Pleuritic Chest pain
Constitutional Sx of Cancer:
Fever
Night sweats
Weight loss
Loss of appetite
Signs of Paraneoplastic syndromes!
What are some investigations for lung cancer?
-
Chest X-ray: first-line
- Hilar enlargement
- Lung consolidation
- “Circular opacity” – a visible lesion in the lung field
- Pleural effusion – usually unilateral in cancer, and collpase
- CT chest with contrast:gold-standard imaging; requested if there is an abnormal CXRorpersistent symptoms with a normal CXR.
- PET-CT:if CT is suggestive of malignancy, patients should have a staging PET-CT, using 18-fluorodeoxygenase which is taken up by malignant tissue
Gold standard
Bronchoscopy + Biopsy
How are Lung Cancers Graded? outline the classification of T1-T4
TNM classification
Tumour – how big it is
T1 – <3cm
T2 - >3cm
T3 – invades chest wall, diaphragm and pericardium
T4 – invades mediastinum, heart, great vessels, trachea, oesophagus, vertebra, carina
TMN staging out line
N0 - N3
and M0 - M3
Nodes – how many and where they are
N0 - none
N1 – Hilar nodes
N2 – same side mediastinal nodes or subcarinal
N3 – contralateral mediastinum or supraclavicular
Metastases
0 - none
1a – tumour on same side
1b – tumour elsewhere
X - unknown
What are some local obstruction complications for lung cancer?
-
Local obstruction:
- Recurrent laryngeal nerve palsypresents with a hoarse voice. It is caused by the cancer pressing on the recurrent laryngeal nerve as it passes through the mediastinum.
- Phrenic nerve palsydue to nerve compression; causes diaphragm weakness and presents as shortness of breath.
- Superior vena cava obstruction caused by direct compression of the tumour on the superior vena cava. It presents with facial swelling, difficulty breathing and distended veins in the neck and upper chest. “Pemberton’s sign” is where raising the hands over the head causes facial congestion and cyanosis. This is a medical emergency.
- Horner’s syndromeis a triad of partial ptosis, anhidrosis and miosis. It is caused by aPancoast’s tumour(tumour in thepulmonary apex) pressing on thesympathetic ganglion.
Pneumothorax
What are the common causes of secondary lung cancer? What specific signs can you see on xray from them?
CRESP:
C = choriocarcinoma
R = renal cell carcinoma
E = endometrial carcinoma
S = Synovial sarcoma
P = Prostate carcinoma
These will often give rise to CANNONBALL metastases, or SNOWSTORM pattern
Cannonball- multiple large, well circumscribed round pulmonary metastases
Normal Physiology - what does a shift to the left of the O2 Hb disassociation curve mean? What can cause this curve to shift to the left?
Further left you go: <== More affinity to O2, picks up O2 easier, harder to dissociate O2
Factors that drive curve more left: (Haemoglobin has MORE AFFINTY FOR O2 - LEFT FOR LOCKS IN O2 more )
Higher pH (More alkaline),
Decrease in CO2,
Decrease in Temperature,
Foetal Haemoglobin,
Carbon Monoxide ,
methemoglobinemia = elevated methaemoglobin - (haemoglobin with iron in Fe3+ state, that cannot bind to O2 like normal Hb with Fe2+)
Normal Physiology - what does a shift to the right of the O2 Hb disassociation curve mean? What can cause this curve to shift to the right?
Further right you go ==> Less affinity for O2, dissociates more easily.
Factors that drive curve to the right: (Haemoglobin will have LESS AFFINITY FOR O2)
Decrease in pH (more acidic) , More CO2, Increase in Temperature
What is a Mesothelioma?
name some other parts of the body that have mesothelium
A malignant neoplasm of the mesothelial cells of the pleura
Other sites include mesothelial cells of peritoneum, pericardium and tunica vaginalis of testes
Briefly outline the pathophysiology behind mesotheliomas. What do these tumours express?
asbestos fibres make their way to the mesothelium and can get tangled up with the cell’s chromosome, causes DNA damage and modification in gene expression
Can also activate neutrophil and macrophages.
These growths start to express a lot of calretinin, a calcium-binding protein, involved in regulating calcium levels within the cell.
What are the signs and symptoms of Mesothelioma?
- Signs
- Finger clubbing
- Reduced breath sounds
- Stony dull percussion: suggests a pleural effusion
- Ascites: if peritoneal disease is present
- Signs of metastases: e.g. lymphadenopathy, hepatomegaly, bone pain/ tenderness, abdominal pain/obstruction
- Symptoms
- Shortness of breath
- Cough
- Pleuritic chest pain or chest wall pain
- Bloody sputum: if blood vessels are affected
-
Constitutional symptoms:
- Fatigue, fever, night sweats, weight loss
What investigations would do for a mesothelioma
- CXR:unilateral pleural effusion, reduced lung volumes, pleural thickening, lower zone interstitial fibrosis for asbestos
-
Contrast-enhanced CT chest:performed following a suspicious
CXR and may demonstrate**pleural thickening, pleural plaques and enlarged lymph nodes
Gold standard - biopsy
Stain with selective markers that are positive in mesotheliomas, such as calretinin - fried egg shape
What is the most common cause of Epiglottitis? What is its classificiation?
Haemophilus Influenza B - (gram-negative coccobacillus)
Other organisms have become more common in the developed world, such asStreptococcus pneumoniaeandStreptococcus pyogenes.
What are the risk factors for Epiglottitis?
Peak age 6-12 (can occur at any)
Male gender
Unvaccinated
Immunocompromised
now far less common due to the introduction of HiB vaccine
What are the symptoms and signs of Epiglottitis?
Rapid Onset:
Dysphagia
Dysphonia (stridor)
Drooling
Distress
Stridor
Tripod Position: A sign of respiratory Distress
Lean forward, mouth open, tongue out = max air in)
Pyrexia
What is the primary investigation of Epiglottitis?
If acutely unwell then NO Ix but immediate Tx
Laryngoscopy:diagnostic and will demonstrate swelling and inflammation of the epiglottis
Lateral neck radiograph:securing the airway is the priority but, once done, an x-ray can be performed looking for thethumb sign (soft tissue shadow that looks like a thumb pressed into the trachea);
Outline the pathophysiology behind Goodpastures - What antibodies bind to what in collagen? What does this do?
n Goodpasture syndrome, autoantibodies bind to a specific part of the α3 chain that is usually hidden deep within the folded triple helix of Type IV collagen. (makes the basement membrane if you can remember phase 1)
This is a type II hypersensitivity reaction - autoantibodies, usually IgG but rarely IgM or IgA, bind to the the α3 chain, and activate the complement system
Normal physiology - where is the middle ear, and what is found in it?
The middle ear is the space that sits between the tympanic membrane (ear drum) and the oval and round windows that connect to the inner ear.
Contains The 3 auditory ossicles, the malleus, incus and stapes, and its where the eustachian tube connects to the ear
It is a very common site of infection in children.
Side effects of TB medication - Give some side effects of
Rifampicin
Haematuria
Side effects of TB medication - Give some side effects of Isoniazid
What disease can it also trigger?
Peripheral Neuropahty,
Can also be a trigger for SLE
Side effects of TB medication - Give some side effects of Pyrazinamide
Hepatitis, Also gout, and joint pain
Side effects of TB medication - Give some side effects of Ethambutol
– Eye problems e.g. uveitis
What are the risk factors of a PE?
Anything affecting Virchow’s Triad:
Endothelial Injury:
Smoking, HTN, Trauma
Venous Stasis:
Immobility, Post surgery, AF, Obesity
Hypercoagulability - Oral contraceptive pill, Polycythaemia, Malignancy
What kind of things does the Wells score look at?
Active Cancer
paralysis/recent plaster immoblisation of leg
Recenlty bedridden or major surgery
Local tenderness along distribution of venous system
Entire leg swollen/calf swelling
Pitting oedma
Previous DVT
All of these score +1 point
Alternative diagnosis at least as likely as a DVT = -2 points
What would you see on an ECG for someonne with a PE?
ECG: S1Q3T3
Deep S waves in lead I
Deep Q waves in lead III
T waves inverted in Lead III
RBBB V1-3 & Sinus Tachycardia
