Week 7 - Lung Cancer, Pulmonary Hypertension and VTE Flashcards
What type of tumour is a granuloma? Benign or malignant?
Benign
A granuloma is an area of tightly clustered immune cells, or inflammation, in your body. They form around an infection or foreign object in your body. They can form almost anywhere, but they’re most often found in your lungs. Granulomas can be a symptom of a chronic condition or an infection.
What types of malignant tumours can you get in the lung?
Primary lung cancers
Carcinoid tumours (neuroendocrine cause)
Secondary lung cancers - are metastases from other cancers
Where do 90% of malignant primary tumours arise from?
What are the two types of cancer that can arise from here?
The bronchial mucosa cells
Can cause
- Non-small cell lung cancer
- Small cell lung cancer
What is the difference between NSCLC and SCLC?
NSCLC = arises from epithelial and glandular cells
SCLC = arises from neuroendocrine cells
SCLC - is more aggressive and invasive than NSCLC and has a poorer prognosis
Where does adenocarcinoma in the lung arise from?
What percentage of lung cancers are of this origin?
The alveolar cells
5%
What malignancy can arise from the pleura of the lungs?
Mesothelioma
What is the epidemiology of lung cancer?
What can cause lung cancer?
What is the main risk factor for lung cancer?
Smoking (90% of lung cancers are related to smoking)
What is the latent period of asbestos exposure to the formation of lung cancer?
What can increase your risk of lung cancer following asbestos exposure?
About 30-40 years
Smoking at the same time - inc risk x100
How does bronchogenic lung cancer begin?
Carcinogens damage DNA in the mucosa of the bronchi => squamous metaplasia.
This can then progress to dysplasia. Dysplastic cells can then progress to become malignant cells.
What are common Sx of lung cancer?
Persistent cough
Breathlessness - can be progressively worsening
Chest pain
Haemoptysis
Also -
Monophonic wheeze (Monophonic wheezes are loud, continuous sounds occurring in inspiration, expiration or throughout the respiratory cycle)
Shoulder pain (if brachial plexus affected)
Hoarse voice (if left recurrent laryngeal nerve affected)
SVC obstruction
Enlarged lymph nodes
Skin nodules
What are the signs of lung cancer to look for on exam?
Cachexia
Clubbing (20%)
Hoarse voice
Horner’s syndrome
Cervical and supraclavicular lymphadenopathy
Trachial deviation
SVC Obstruction
Pleural effusion signs
What are the systemic Sx of lung cancer?
What are the signs of a pleural effusion?
↓ chest expansion
↓breath sounds
dullness on percussion
↓ TVF and ↓VR
What scale do we use to measure how sick a patient is?
WHO Performance Status
What imaging is done if lung cancer is suspected?
CXR
What other imaging can be done if lung cancer is identified on CXR?
Staging CT thorax and abdomen with contrast (highlights BVs – easier to see lymph nodes – can tell us what stage LC is at)
PET scan (used FDG which is taken up by rapidly metabolising cells)
Bone scan
CT brain
MRI scan of thorax
What blood test results can indicate the possibility of SCLC?
Hyponatremia
Hypercalcaemia
Hyponatremia = neuroendocrine cells can release ADH (makes more aquaporin channels appear in DCT - inc water reasborption) causing hyponatremia. Called syndrome of inappropriate ADH (SIADH).
Hypercalcaemia = PTH released in excess by the tumour cells => increases bone reabsorption (decreases formation) = increases serum calcium.
Rarely can get ectopic ACTH release -> raised cortisol and Cushing’s.
How can SVC obstruction present?
Headaches
Distended, engorged, pulseless neck veins
Collateral veins on arms and chest
Facial oedema
CXR - can show mass on RHS and widened mediastinum
How is SVC managed?
Dexamethosone
Metallic stent insertion
Anticoagulation if thrombus
Radio and chemo to reduce obstruction - but can take weeks to be effective
What blood tests should you for if you suspect LC?
What are the most common methods of obtaining a biopsy in LC?
Bronchoscopy
CT guided biopsy
What are the different subtypes of NSCLC?
Squamous cell - arises from squamous epithelial cells
Adenocarcinoma (from glandular epithelium)
Large cell lung cancer (from undifferentiated cells)
Malignant carcinoid
Others
What percentage of lung cancers are NSCLC and SCLC?
NSCLC = 80%
SCLC = 20%
What is the TNM staging of lung cancer?
What factors determine how a lung cancer is managed?
Histology result
Staging
WHO Performance status
Lung function
Co-morbidities
Patient’s wishes
What is the difference between limited and extensive lung cancer?
Limited = confined to the thorax
Extensive = spread outside the thorax
Which treatments are deemed to be an attempt at curative procedures?
Surgery
Radiotherapy
Which treatments are used for palliation?
Chemo
Immunotherapy
Radio
Sx control
What are the terms for
- removal of a lung lobe
- removal of a lung
- removal of part of a lobe
Lobectomy
Pneumonectomy
Wedge resection
What are the survival rates for lung cancer?
1 year survival = 30% M and 35% F
5 year = 9.5%
What is the difference between a provoked and unprovoked DVT?
Provoked VTE (venous thromboembolism) = clear cause from Hx or tests
Unprovoked = no clear cause
What is the disorder called when blood clots more easily than it should?
Thrombophilia
What is a low platelet count called?
Thrombocytopenia
What are the reasons that a VTE occurs?
Virchow’s triad
- Hypercoagulability
- Statsis
- Endothelial injury
What can cause circulatory stasis?
What can cause a hypercoagulable state?
What is the most common inherited thrombophilia?
What does this do to the blood?
Factor V Leiden deficiency – mutation of F5 gene – fairly common (5% of pop) but only around 10% will have thrombosis.
What is the second most commonly inherited thrombophilia?
Prothrombin thrombophilia (Factor II)
When should you test for inherited thrombophilias?
- Unprovoked DVT/PE & have 1st degree relative who has also had a DVT/PE
AND they want to stop Rx
What is the commonest acquired thrombophilia?
Why does this cause thrombi?
Antiphospholipid syndrome
In APLS, the immune system produces abnormal antibodies called antiphospholipid antibodies.
These target proteins attached to fat molecules (phospholipids), which makes the blood more likely to clot.
Which disease to 10-15% of Ps with antiphospholipid syndrome also have?
SLE
What is the second commonest acquire thrombophilia?
What can cause this disease?
Acquired Dysfibrinogenaemia (dysfunctional fibrinogen)
Caused by
- severe liver disease (commonest)
- AI disease
- Plasma cell disorders
- Certain cancers (e.g. cervical)
In summary - what are the four main causes of thrombophilia?
Factor V Leiden
Prothrombin thrombophilia
Antiphospholipid syndrome
Acquired dysfibrinogenaemia
What are the most common causes of vascular injury in Virchow’s triad?
What is May Thurner syndrome?
Narrowed left iliac common vein due to pressure from right common iliac artery.
DVTs can occur in any vein - where are the most common places for them to occur?
Calf (popliteal / tibial vein), thigh (femoral and iliac veins). Arm = rare.
What are the clinical signs of a DVT?
Unilateral calf swelling
Heat
Pain
Redness
Hardness
- But can be asymptomatic
What are the DDs for DVT?
Baker’s cyst
Cellulitis
Muscular pain
Lymphodema
Chronic venous insufficiency
Superficial thrombophlebitis
What is the best investigation for a suspected DVT?
Doppler USS
What is D-dimer?
It is a breakdown product from fibrin - only present when the coagulation system has been activated
What is the D-dimer test used for?
Used to RULE OUT DVT - if a low score then is a low probability of DVT.
A positive test is not specific as it can be caused by lots of different things - therefore it cannot confirm a DVT
How is DVT in the calf treated?
Analgesia and sometimes blood thinners, repeat US in 7 days to ensure no progression, individual risk assessment.
If a DVT is large or above the knee, how is this treated?
Anticoag w/DOAC (Rivaroxaban, Dabigatran) – 3-6m if 1st, lifelong if 2nd.
If P has renal dysfunction use warfarin.
How are PEs categorised?
By size - is a spectrum.
- Microemboli (asymptomatic)
- Small, peripheral (pleural pain, breathlessness, haemoptysis)
- Large, central – in major artery (chest pain, breathless, hypoxia)
- Massive (syncope, shock, tachycardia, death)
What are the signs of PE?
Low O2
Low PaO2
Sinus tachycardia + S1 Q3 T3
ECG = right heart strain
What is S1 Q3 T3?
Prominent S wave in lead I.
Large Q wave in lead III. ST depression with an ascent to the T-wave in lead II (red arrows).
T wave inversion in lead III (blue arrows).
What investigations should be done to diagnose PE?
When should a CTPA be done?
Wells score >4 + Positive D-Dimer
Which score is used to determine your risk of DVT?
Wells score
When should a VQ scan be done?
If CTPA is contraindicated
How are large and small PEs treated?
Assess bleeding risk with HASBLED score
Large PE - start on LMWH (Enoxaparin) - then convert to Warfarin or DOAC for 3-6m (if first PE) or lifelong (if 2nd)
Small PE - skip LMWH and go straight to DOAC
How should you treat a massive PE?
IV fluids
IV heparin
Consider if thrombolysis suitable (does P have shock +/- R heart strain)
Options - surgical embolectomy, catheter fragmentation
What is the mortality of a PE if
- untreated
- treated
Untreated = 30%
Treated = 5%
What is the number 1 cause of preventable hospital deaths?
VTE
What measures can you employ to prevent VTE?
Prophylactic LMWH - SC
Stockings
Early mobilisation
Hydration
What can Ps sometimes confuse haemoptysis for?
Haematemesis
Epistaxis
Gum bleeding
What Qs do you need to ask Ps about haemoptysis?
Fresh, red or dark, altered blood?
When
How often
Volume
Mixed with sputum?
Associated Sx = chest pain, breathlessness, weight loss
How is haemoptysis classified?
Massive (over 250mls in 24 hours)
Or non-massive
What is the best way to define whether haemoptysis is massive or not?
Best to define with functionality - amount is difficult to define.
- i.e. look at physiological effect = being unwell, feeling weak, anaemic
and haemodynamic instability (tachycardia, low BP)
Where do the lungs derive their blood supply from?
The pulmonary arteries and the bronchial arteries
The pulmonary arteries carry deoxygenated blood at low pressure. They supply 99% of the blood flow to the lungs and participate in gas exchange at the al- veolar capillary membrane. The bronchial arteries carry oxygenated blood to the lungs at a pressure six times that of the pulmonary arteries
Where does 5% of haemoptysis originate from?
The pulmonary arterial system
Where do the bronchial arteries originate from?
The descending aorta
Where do pulmonary arteries terminate?
In the capillary beds of the lungs
What can cause bleeding in the lungs?
Inflammation from infection –> proliferation and hypertrophy of the bronchial arteries = they are unstable and can erode and bleed
Dont need to know slide in detail
What sieve can be used to determine the cause of bleeding the lungs?
IITTV
Infection - MTB, aspergilloma, BET, RTI
Inflammation - SLE
Trauma
Tumour
Vascular - PE, clotting disorders
What is a fungal ball in the lungs called?
Aspergilloma
What investigations can be done for haemoptysis?
CXR
CTPA (if suspected PE)
Staging CT (LC)
HRCT (BET)
Bloods - FBC, D-dimer, clotting, CRP
Sputum - cytology, MC&S, AAFB
Bronchoscopy
How is minor haemoptysis treated?
Oral tranexamic acid
After biopsy - give topical adrenaline
How is severe haemoptysis treated?
IV fluids, bloods and IV tranexamic acid
How is life threatening haemoptysis treated?
IV fluid, bloods, FFP and clotting factors
Urgent CTPA
Bronchoscopy + topical adrenaline + embolisation if possible
Really bad - surgical resection
What is radiotherapy used for in lung cancer?
Radical and palliative procedures
Can also be used prior to surgery to reduce tumour size
Can be used post surgery to improve survival rate
What are the possible SEs of radiotherapy on
- lungs
- heart
- oesophagus
But modern radiotherapy techniques is more targeted to the lungs now and reduces the exposure of other organs.
What is chemotherapy used for in LC
Rarely curative - used to prolong life and provide symptom relief
Can also be used prior to surgery to reduce tumour size
Can be used post surgery to improve survival rate
What are the common targets of immunotherapy in lung cancer?
EGFR inhibitor
VEGF
PDL-1 Inhibitors
Also
Tyrosine Kinase
Anaplastic lymphoma kinase
Checkpoint inhibitors
What is the difference between a thrombus and an embolus?
What percentage of deaths in hospital are attributable to PE?
10%
What is the leading cause of death during pregnancy puerperium in the UK?
PE
What is it called when a large embolus blocks the bifurcation of the main pulmonary artery and extends into the right and left pulmonary arteries?
Saddle embolus
What symptoms should make you suspect PE?
Pleuritic chest pain
Breathlessness
Haemoptysis
What are the DDs for a PE?
Pneumothorax
Acute MI
Exacerbation of asthma
CAP
LV failure
Costochondritis
What are the clinical symptoms and signs of a PE?
What can an echocardiogram show in acute severe PE?
Right ventricular dilation + pulmonary hypertension
What things other than a PE can increase D-dimer levels?
Acute illness
Pregnancy
Age
CKD
How should the Wells score be utilised?
What is the investigation of choice in suspected PE?
CTPA
What is the difference between a CTPA and a pulmonary angiogram?
CTPA is used to examine blood vessels all over — from your brain to your legs — while a pulmonary angiogram focuses on the lungs.
What should you do if clinical suspicion of a PE is high but the CTPA is negative?
Pulmonary angiogram
When should you do a VQ scan?
When the CTPA is contraindicated
When is a VQ contraindicated?
When there is chronic lung disease = COPD or fibrosis - VQ scan is not suitable as many areas are not ventilated due to the disease.
Lungs will divert blood away from these areas - therefore not helpful to diagnose PE in these Ps.
If you cannot determine the cause of a VTE - what investigation should you do?
Exclude malignancy
Do thrombophilia screen
Which score is used to calculate the severity of a PE?
PESI score
What causes a VTE in pregnancy?
Is a hypercoaguable state + occlusion of pelvic veins by large uterus
What treatment can be given to pregnant women with a VTE?
LMWH or UFH
Warfarin = tetraogenic
DOAC crosses the placenta
How long should anticoagulation be given in Ps with a VTE?
Unprovoked or thrombophilia = lifetime
Provoked = 3-6m then review
What can be considered for recurrent PEs despite anticoagulation or CI to anticoag?
IVC Filter - traps emboli travelling from veins to the lungs
What percentage of hospitalised Ps develop PE?
How is this preventable?
1%
By use of LMWH and TED stockings
What are potential complications of DVT?
Post-thrombotic syndrome (40%) = pain, swelling, heaviness, venous claudication, itching, skin hyperpigmentation
What are the potential complications of PE?
Chronic thromboembolic pulmonary hypertension (CTEPH)
How should acute PE be managed?
What is pulmonary hypertension defined as?
Pulmonary artery pressure >25mmHg (3.3kPa) at rest
OR
>30mmHg (>4kPa) when exercising
What is the difference between primary and secondary pulmonary hypertension?
Primary = idiopathic cause - diagnosis of exclusion
Secondary = secondary to a disease process
Which protein receptor may be altered in familial primary pulmonary hypertension?
BMPR2
Bone Morphogenetic Protein Receptor 2
What is the pathophysiology behind pulmonary hypertension?
Endothelial injury results in release of cytokines which are vasoconstrictors - these cause smooth muscle hyperplanea, medial hypertrophy, intimal thickening of the pulmonary arterioles. Over time = vascular remodelling & inc in pulmonary resistance.
What type of cytokine group do these belong to?
Endothelin
Thromboxane
Endothelin-derived contracting factor
Vasoconstrictors
What type of cytokine group do these belong to?
Oxygen
Prostacyclin
NO
Adenosine
Endothelin-derived relaxing factor
Endothelin-derived hyperpolarizing factor
Vasodilators
How are SSRIs linked with pulmonary hypertension?
Can worsen existing pulmonary hypertension in adults.
If taken when pregnant - they may cause pulmonary hypertension of the newborn.
Which connective tissue disorders are linked to pulmonary hypertension?
RA
SLE
Both cause pul HT secondary to interstitial lung disease
What is the commonest cause of pul art HT worldwide?
Schistosomiasis - the eggs embolise to the lungs and cause a granulomatous reaction in the pulmonary arterioles.
On average how long does it take from onset of Sx for a diagnosis of PHT to be reached?
> 2years
What are the Sx of PHT?
Dyspnoea
Which grading classification is used to determine the severity of PHT Sx?
NYHA Functional Class
What are the physical examination findings in Ps with PHT?
What can an ECG show in pul HT?
Right axis deviation
RV hypertrophy
What can you see in a CXR in PHT?
Prominent of main pulmonary arteries
Enlargement of hilar vessels
Peripheral pruning
RV enlargement
What ratio between the pulmonary artery and ascending aorta on CT can indicate pulmonary HT?
Ratio >1
Can a trans-thoracic echocardiogram detect PHT?
May not detect mild PHT.
At what pressures is pulmonary hypertension regarded to be
= mild
= moderate
= severe?
Mild = 26-25 mmHg
Moderate = 36-45 mmHg
Severe = >45 mmHg
What happens to the heart in severe pul HT?
Get
= abnormal RV size and function
= paradoxical septal motion
= Abnormal pulmonic valve motion
What is the gold standard for diagnosing pul HT?
Right heart catheterisation
Should Ps with pul HT get pregnant?
No - avoid pregnancy if possible. Mortality is high - 30-50%
What medical Rx can be given for pul HT?
Oxygen
Anticoagulants
Vasodilators - Ca Channel blockers
Prostacyclin
Endothelin 1 antagonist - Bosentan
Phosphodiesterase 5 Inhibitor - Viagra
What surgical procedures can be done for pulmonary hypertension?
What is the prognosis of living with pul HT?
Much better - survival is now 7-10 years
