Respiratory Medicine Flashcards
Small cell lung cancer paraneoplastic syndromes
ADH
ACTH - not typical, hypertension, hyperglycaemia, hypokalaemia, alkalosis and muscle weakness are more common than buffalo hump etc
Lambert-Eaton syndrome
Squamous cell lung cancer paraneoplastic syndromes
parathyroid hormone-related protein (PTH-rp) secretion causing hypercalcaemia
clubbing
hypertrophic pulmonary osteoarthropathy (HPOA)
hyperthyroidism due to ectopic TSH
Adenocarcinoma
lung cancer paraneoplastic syndromes
gynaecomastia
hypertrophic pulmonary osteoarthropathy (HPOA)
oxygen dissociation curve
Shifts to Left = Lower oxygen delivery
HbF, methaemoglobin, carboxyhaemoglobin Low [H+] (alkali) Low pCO2 Low 2,3-DPG Low temperature
oxygen dissociation curve
Shifts to Left = Lower oxygen delivery
What is the L rule
Low [H+] (alkali)
Low pCO2
Low 2,3-DPG
Low temperature
Shifts to L → Lower oxygen delivery, caused by
oxygen dissociation curve
Shifts to Right = Raised oxygen delivery
Raised [H+] (acidic)
Raised pCO2
Raised 2,3-DPG*
Raised temperature
‘CADET, face Right!’ for CO2, Acid, 2,3-DPG, Exercise and Temperature
What is transfer factor?
transfer factor describes the rate at which a gas will diffuse from alveoli into blood. Carbon monoxide is used to test the rate of diffusion. Results may be given as the total gas transfer (TLCO) or that corrected for lung volume (transfer coefficient, KCO)
Causes of a raised TLCO
asthma pulmonary haemorrhage (Wegener's, Goodpasture's) left-to-right cardiac shunts polycythaemia hyperkinetic states male gender, exercise
Causes of a lower TLCO
pulmonary fibrosis pneumonia pulmonary emboli pulmonary oedema emphysema anaemia low cardiac output
conditions may cause an increased KCO with a normal or reduced TLCO
pneumonectomy/lobectomy
scoliosis/kyphosis
neuromuscular weakness
ankylosis of costovertebral joints e.g. ankylosing spondylitis
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Eosinophilic granulomatosis with polyangiitis (EGPA) is now the preferred term for Churg-Strauss syndrome. It is an ANCA associated small-medium vessel vasculitis.
Features of Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
asthma blood eosinophilia (e.g. > 10%) paranasal sinusitis mononeuritis multiplex pANCA positive in 60%
Tidal volume
volume inspired or expired with each breath at rest
500ml in males, 350ml in females
Inspiratory reserve volume (IRV) = 2-3 L
maximum volume of air that can be inspired at the end of a normal tidal inspiration
inspiratory capacity = TV + IRV
Expiratory reserve volume (ERV) = 750ml
maximum volume of air that can be expired at the end of a normal tidal expiration
Residual volume (RV) = 1.2L
volume of air remaining after maximal expiration
increases with age
RV = FRC - ERV
Functional residual capacity (FRC)
the volume in the lungs at the end-expiratory position
FRC = ERV + RV
Vital capacity (VC) = 5L
maximum volume of air that can be expired after a maximal inspiration
4,500ml in males, 3,500 mls in females
decreases with age
VC = inspiratory capacity + ERV
Total lung capacity (TLC)
sum of the vital capacity + residual volume
Features of Cystic fibrosis
short stature diabetes mellitus delayed puberty rectal prolapse (due to bulky stools) nasal polyps male infertility, female subfertility
Causes of respiratory alkalosis
anxiety leading to hyperventilation pulmonary embolism salicylate poisoning* CNS disorders: stroke, subarachnoid haemorrhage, encephalitis altitude pregnancy
Features of allergic bronchopulmonary aspergillosis
bronchoconstriction: wheeze, cough, dyspnoea. Patients may have a previous label of asthma
bronchiectasis (proximal)
features of allergic bronchopulmonary aspergillosis
eosinophilia
flitting CXR changes
positive radioallergosorbent (RAST) test to Aspergillus
positive IgG precipitins (not as positive as in aspergilloma)
raised IgE
Management of allergic bronchopulmonary aspergillosis
oral glucocorticoids
itraconazole is sometimes introduced as a second-line agent
Features of moderate asthma
PEFR 50-75% best or predicted
Speech normal
RR < 25 / min
Pulse < 110 bpm
Features of severe asthma
PEFR 33 - 50% best or predicted
Can’t complete sentences
RR > 25/min
Pulse > 110 bpm
Features of life threatening asthma
PEFR < 33% best or predicted Oxygen sats < 92% Silent chest, cyanosis or feeble respiratory effort Bradycardia, dysrhythmia or hypotension Exhaustion, confusion or coma
Epidemiology of bronchiolitis
most common cause of a serious lower respiratory tract infection in < 1yr olds (90% are 1-9 months, with a peak incidence of 3-6 months). Maternal IgG provides protection to newborns against RSV
higher incidence in winter
Respiratory syncytial virus (RSV) is the pathogen in 75-80% of cases.
Basics of bronchiolitis
respiratory syncytial virus (RSV) is the pathogen in 75-80% of cases
other causes: mycoplasma, adenoviruses
may be secondary bacterial infection
more serious if bronchopulmonary dysplasia (e.g. Premature), congenital heart disease or cystic fibrosis
Features of bronchiolitis
coryzal symptoms (including mild fever) precede:
dry cough
increasing breathlessness
wheezing, fine inspiratory crackles (not always present)
feeding difficulties associated with increasing dyspnoea are often the reason for hospital admission
Bronchiolitis - referral to hospital
apnoea (observed or reported)
child looks seriously unwell to a healthcare professional
severe respiratory distress, for example grunting, marked chest recession, or a respiratory rate of over 70 breaths/minute
central cyanosis
persistent oxygen saturation of less than 92% when breathing air.
Bronchiolitis
consider referral to hospital
a respiratory rate of over 60 breaths/minute
difficulty with breastfeeding or inadequate oral fluid intake (50-75% of usual volume ‘taking account of risk factors and using clinical judgement’)
clinical dehydration.
Management of bronchiolitis
humidified oxygen is given via a head box and is typically recommended if the oxygen saturations are persistently < 92%
nasogastric feeding may be needed if children cannot take enough fluid/feed by mouth
suction is sometimes used for excessive upper airway secretions
Features of sarcoidosis
acute: erythema nodosum, bilateral hilar lymphadenopathy, swinging fever, polyarthralgia
insidious: dyspnoea, non-productive cough, malaise, weight loss
skin: lupus pernio
hypercalcaemia: macrophages inside the granulomas cause an increased conversion of vitamin D to its active form (1,25-dihydroxycholecalciferol)
Lofgren’s syndrome
Sarcoidosis
an acute form of the disease characterised by bilateral hilar lymphadenopathy (BHL), erythema nodosum, fever and polyarthralgia. It usually carries an excellent prognosis
Mikulicz syndrome
there is enlargement of the parotid and lacrimal glands due to sarcoidosis, tuberculosis or lymphoma
Heerfordt’s syndrome
(uveoparotid fever) there is parotid enlargement, fever and uveitis secondary to sarcoidosis
What is anti-alpha 1 trypsin deficiency
(A1AT) deficiency is a common inherited condition caused by a lack of a protease inhibitor (Pi) normally produced by the liver. The role of A1AT is to protect cells from enzymes such as neutrophil elastase. It classically causes emphysema (i.e. chronic obstructive pulmonary disease) in patients who are young and non-smokers.
Genetics of alpha 1 anti-trypsin deficiency
located on chromosome 14 inherited in an autosomal recessive / co-dominant fashion* alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow normal = PiMM homozygous PiSS (50% normal A1AT levels) homozygous PiZZ (10% normal A1AT levels)
Features of alpha 1 anti-trypsin deficiency
patients who manifest disease usually have PiZZ genotype
lungs: panacinar emphysema, most marked in lower lobes
liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in children
obstructive spirometry
Management of alpha 1 anti-trypsin deficiency
no smoking
supportive: bronchodilators, physiotherapy
intravenous alpha1-antitrypsin protein concentrates
surgery: lung volume reduction surgery, lung transplantation
Step 1 asthma management
Short-acting beta agonist (SABA)
Step 2 asthma management
SABA + low-dose inhaled corticosteroid (ICS)
Step 3 asthma management
SABA + low-dose ICS + leukotriene receptor antagonist (LTRA)
Step 4 asthma management
SABA + low-dose ICS + long-acting beta agonist (LABA)
Continue LTRA depending on patient’s response to LTRA
Step 5 asthma management
SABA +/- LTRA
Switch ICS/LABA for a maintenance and reliever therapy (MART), that includes a low-dose ICS
Step 6 asthma management
SABA +/- LTRA + medium-dose ICS MART
OR consider changing back to a fixed-dose of a moderate-dose ICS and a separate LABA
Step 7 asthma management
SABA +/- LTRA + one of the following options:
increase ICS to high-dose (only as part of a fixed-dose regime, not as a MART)
a trial of an additional drug (for example, a long-acting muscarinic receptor antagonist or theophylline)
seeking advice from a healthcare professional with expertise in asthma
Salbutamol mechanism of action
Beta receptor agonist
• Short-acting inhaled bronchodilator. Relaxes bronchial smooth muscle through effects on beta 2 receptors
• Used in asthma and chronic obstructive pulmonary disease (COPD).
• Salmeterol has similar effects but is long-acting
Corticosteroids mechanism of action
Anti-inflammatory • Inhaled corticosteroids are used as mainterance therapy
• Oral or intravenous corticosteroids are used following an acute exacerbation of asthma or COPD
Ipratropium mechanism of action
Blocks the muscarinic acetylcholine receptors • Short-acting inhaled bronchodilator. Relaxes bronchial smooth muscle
• Used primarily in COPD
• Tiotropium has similar effects but is long-acting
Methylxanthines (e.g. theophylline) mechanism of action
Non-specific inhibitor of phosphodiesterase resulting in an increase in cAMP • Given orally or intravenously
• Has a narrow therapeutic index
Montelukast mechanism of action
Blocks leukotriene receptors • Usually taken orally
• Useful in aspirin-induced asthma
Klebisella pneumoniae
is a Gram-negative rod that is part of the normal gut flora. It can cause a number of infections in humans including pneumonia (typically following aspiration) and urinary tract infections.
Features of Klebsiella pneumoniae
more common in alcoholic and diabetics
may occur following aspiration
‘red-currant jelly’ sputum
often affects upper lobes
Prognosis in Klebsiella pneuoniae
commonly causes lung abscess formation and empyema
mortality is 30-50%
Lower zone fibrosis
idiopathic pulmonary fibrosis
most connective tissue disorders (except ankylosing spondylitis) e.g. SLE
drug-induced: amiodarone, bleomycin, methotrexate
asbestosis
Upper zone fibrosis
hypersensitivity pneumonitis (also known as extrinsic allergic alveolitis)
coal worker’s pneumoconiosis/progressive massive fibrosis
silicosis
sarcoidosis
ankylosing spondylitis (rare)
histiocytosis
tuberculosis
Lambert eaton syndrome
Muscle weakness secondary to small cell lung cancer
The main symptoms are weakness in the legs, arms, neck and face, as well as problems with automatic body functions, such as controlling blood pressure.
Genetics of cystic fibrosis
due to a defect in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which codes a cAMP-regulated chloride channel
In the UK 80% of CF cases are due to delta F508 on the long arm of chromosome 7. Cystic fibrosis affects 1 per 2500 births, and the carrier rate is c. 1 in 25
Bacteria that colonise cystic fibrosis patients
Staphylococcus aureus
Pseudomonas aeruginosa
Burkholderia cepacia*
Aspergillus
Features of microscopic polyangitis
renal impairment: raised creatinine, haematuria, proteinuria
fever
other systemic symptoms: lethargy, myalgia, weight loss
rash: palpable purpura
cough, dyspnoea, haemoptysis
mononeuritis multiplex
Investigations of microscopic polyangitis
pANCA (against MPO) - positive in 50-75%
cANCA (against PR3) - positive in 40%
Varenicline
a nicotinic receptor partial agonist
should be started 1 week before the patients target date to stop
the recommended course of treatment is 12 weeks (but patients should be monitored regularly and treatment only continued if not smoking)
has been shown in studies to be more effective than bupropion
nausea is the most common adverse effect. Other common problems include headache, insomnia, abnormal dreams
varenicline should be used with caution in patients with a history of depression or self-harm. There are ongoing studies looking at the risk of suicidal behaviour in patients taking varenicline
contraindicated in pregnancy and breast feeding
Bupropion
a norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist
should be started 1 to 2 weeks before the patients target date to stop
small risk of seizures (1 in 1,000)
contraindicated in epilepsy, pregnancy and breast feeding. Having an eating disorder is a relative contraindication
Churg strauss vs granulomatosis with polyangititis
BOTH - vasculitis, sinusitis, dyspnoea
Churg-Strauss- asthma, eosinophilia, pANCA
Granulomatosis w/ polyangitis- renal failure, haemoptyisis, cANCA
Occupational Asthma causes
isocyanates - the most common cause example occupations include spray painting and foam moulding using adhesives platinum salts soldering flux resin glutaraldehyde flour epoxy resins proteolytic enzymes
Acute respiratory distress syndrome: summary
caused by the increased permeability of alveolar capillaries leading to fluid accumulation in the alveoli, i.e. non-cardiogenic pulmonary oedema. It is a serious condition that has a mortality of around 40% and is associated with significant morbidity in those who survive.
Causes of ARDS
infection: sepsis, pneumonia massive blood transfusion trauma smoke inhalation acute pancreatitis cardio-pulmonary bypass
Clinical features of ARDS
dyspnoea
elevated respiratory rate
bilateral lung crackles
low oxygen saturations
Criteria of ARDS diagnosis
acute onset (within 1 week of a known risk factor)
pulmonary oedema: bilateral infiltrates on chest x-ray (‘not fully explained by effusions, lobar/lung collapse or nodules)
non-cardiogenic (pulmonary artery wedge pressure needed if doubt)
pO2/FiO2 < 40kPa (200 mmHg)
Upper zone fibrosis causes
TB
Silicosis
Ankylosing spondylitis
Coal worker’s pneumoconiosis
Alpha-1 antitrypsin (A1AT) deficiency
common inherited condition caused by a lack of a protease inhibitor (Pi) normally produced by the liver. The role of A1AT is to protect cells from enzymes such as neutrophil elastase. It classically causes emphysema (i.e. chronic obstructive pulmonary disease) in patients who are young and non-smokers.
A1ATD Genetics
located on chromosome 14 inherited in an autosomal recessive / co-dominant fashion* alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow normal = PiMM homozygous PiSS (50% normal A1AT levels) homozygous PiZZ (10% normal A1AT levels)
Extrinsic Allergic alveolitis
caused by hypersensitivity induced lung damage due to a variety of inhaled organic particles. It is thought to be largely caused by immune-complex mediated tissue damage (type III hypersensitivity) although delayed hypersensitivity (type IV) is also thought to play a role in EAA, especially in the chronic phase.
Examples of extrinsic allergic alveolitis
bird fanciers’ lung: avian proteins from bird droppings
farmers lung: spores of Saccharopolyspora rectivirgula from wet hay (formerly Micropolyspora faeni)
malt workers’ lung: Aspergillus clavatus
mushroom workers’ lung: thermophilic actinomycetes
Surgical contraindications for non-small cell lung cancer
assess general health
stage IIIb or IV (i.e. metastases present)
FEV1 < 1.5 litres is considered a general cut-off point*
malignant pleural effusion
tumour near hilum
vocal cord paralysis
SVC obstruction
Paraneoplastic syndromes: squamous cell
PTHrp, clubbing, HPOA (hypertrophy pulmonary osteoarthropathy)
Paraneoplastic syndromes: small cell
ADH, ACTH, Lambert-Eaton syndrome
Lower zone fibrosis
idiopathic pulmonary fibrosis
most connective tissue disorders (except ankylosing spondylitis) e.g. SLE
drug-induced: amiodarone, bleomycin, methotrexate
asbestosis
symptoms of acute mountain sickness
headache
nausea
fatigue
Management of acute mountain sickness
the risk of AMS may actually be positively correlated to physical fitness
gain altitude at no more than 500 m per day
acetazolamide (a carbonic anhydrase inhibitor) is widely used to prevent AMS and has a supporting evidence base
treatment: descent
High altitude pulmonary oedema (HAPE) or high altitude cerebral oedema (HACE),
HAPE presents with classical pulmonary oedema features
HACE presents with headache, ataxia, papilloedema
Management of HAPE/HACE
Management of HACE
descent
dexamethasone
Management of HAPE
descent
nifedipine, dexamethasone, acetazolamide, phosphodiesterase type V inhibitors*
oxygen if available
Investigations of COPD
post-bronchodilator spirometry to demonstrate airflow obstruction: FEV1/FVC ratio less than 70%
chest x-ray: hyperinflation, bullae, flat hemidiaphragm. Also important to exclude lung cancer
full blood count: exclude secondary polycythaemia
body mass index (BMI) calculation
normal function of the cystic fibrosis transmembrane regulator
chloride channel, specifically a cyclic-AMP regulated chloride channel
Genetics of Cystic fibrosis
In the UK 80% of CF cases are due to delta F508 on the long arm of chromosome 7. Cystic fibrosis affects 1 per 2500 births, and the carrier rate is c. 1 in 25
Infective organisms in cystic fibrosis
Staphylococcus aureus
Pseudomonas aeruginosa
Burkholderia cepacia*
Aspergillus
Lofgren’s syndrome
acute form sarcoidosis characterised by bilateral hilar lymphadenopathy (BHL), erythema nodosum, fever and polyarthralgia.
Indications for steroids in sarcoidosis
patients with chest x-ray stage 2 or 3 disease who are symptomatic. Patients with asymptomatic and stable stage 2 or 3 disease who have only mildly abnormal lung function do not require treatment
hypercalcaemia
eye, heart or neuro involvement
Stages of sarcoidosis on CXR
1 = Bilateral Hilar Lymphadenopathy 2 = BHL + infiltrates 3 = infiltrates 4 = fibrosis
Poor Prognostic factors in Sarcoidosis
insidious onset, symptoms > 6 months absence of erythema nodosum extrapulmonary manifestations: e.g. lupus pernio, splenomegaly CXR: stage III-IV features black people
When to use NIV in COPD (pH)
pH in the range of 7.25-7.35 achieve the most benefit
When to admit to ITU - COPD pH
<7.25
A1ATD phenotypes
PiMM- no symptoms- normal alleles
PiMZ- MZ has one normal allele and one affected allele - unlikely to develop clinically significant symptoms but increased risk of lung and liver disease
PiZZ - will develop significant symptoms
PiSZ/PiSS - increased risk of developing symptoms over Mz
Bronchiolitis obliterans
an inflammatory condition that affects the bronchioles. In affected people, the bronchioles may become damaged and inflamed leading to extensive scarring that blocks the airways.
Causes of cavitating lung lesions
abscess (Staph aureus, Klebsiella and Pseudomonas)
squamous cell lung cancer
tuberculosis
Wegener’s granulomatosis
pulmonary embolism
rheumatoid arthritis
aspergillosis, histoplasmosis, coccidioidomycosis
Catamenial pneumothorax
Monthly chest pain associated with menstrual bleeding - caused by endometrial tissues and is generally encountered in reproductive women. The mean ages are between 32-35 years old.
hortness of breath or difficulty breathing, fatigue, and dry cough. It can produce monthly episodes of chest pain which may radiate to the shoulder.
Meigs syndrome
classical triad of ascites, pleural effusion, and benign ovarian tumour e.g. ovarian fibroma and usually resolves following resection of the tumour.
