INTRATHORACIC MALIGNANCIES + TB Flashcards
what is the leading cause of cancer mortality?
lung cancer
how many cases of lung cancer are caused by smoking?
> 70%
what are examples of carcinogens in cigarette smoke?
arsenic nickel cadmium chromium acetaldehyde phenol nitrous oxide formaldehyde hydrogen cyanise
outline the risk of lung cancer with passive smoking?
relative risk is 1.25 which is equivalent to smoking 1 cigarette per day
how much more likely are smokers to get lung cancer?
15-30 times more
what are some causes of lung cancer?
smoking
occupational exposure to carcinogens e.g. asbestos, chromates, chloromethyl, silica, nickel etc
radon - naturally occurs in soils and rocks
what are the signs and symptoms of lung cancer?
cough chest pain SOB wheezing haemoptysis fatigue weight loss hoarseness of voice increased sputum production dysphagia horners syndrome Superior vena cava syndrome
what causes the hoarseness of voice in lung cancer?
invasion of the tumour into the recurrent laryngeal nerve
why can lung cancer cause dysphagia?
as the tumour or lymph nodes can compress the oesophagus
what is superior vena cava syndrome?
a group of problems caused when blood flow through the superior vena cava (SVC) is slowed down - can be caused by lung cancer compressing the vessel
what are the sympotms of superior vena cava syndrome?
swelling of upper limbs, head, neck
shortness of breath or touble breathing
coughing
describe the link between horners syndrome and lung cancer?
Pancoast tumours can cause horners syndrome as it invades the sympathetic ganglia
what are the signs of horners syndrome?
miosis (constriction of the pupils), anhidrosis (lack of sweating) and ptosis (drooping of the eyelid)
why can we get diaphragm paralysis in lung cancer?
if there is invasion of the phrenic nerve
why can we get rib destruction in lung cancer?
due to chest wall invasion
what is a pancoast tumour?
a tumour at the apex of the lung
where does lung cancer typically metastasise to?
lymph nodes, bones, brain, liver, and adrenal glands
what are paraneoplastic syndromes?
a group of rare disorders caused by the presence of tumors in the body
what are the common paraneoplastic syndromes associated with lung cancer?
hypercalcaemia, cushings syndrome, hyponatremia, gynaecomastia, peripheral neuropathy, finger clubbing
Lambert-Eaton myaethenic syndrome
what are the 2 main categories of lung cancers?
non-small cell carcinoma
small cell carcinoma
which type of lung cancer is most common?
non-small cell carcinoma (specifically adenocarcinoma)
what are the 3 types of non-small cell carcinoma?
adenocarcinoma
squamous cell carcinoma
large cell carcinoma
which lung cancer is most closely associated with smoking?
squamous cell carcinoma
whats the most common type of lung cancer found in non-smokers?
adenocarcinoma
what cell type is affected in adenocarcinoma?
glandular epithelial cells
what cell type is affected in large cell carcinoma?
epithelial cells - msot often the ones on the periphery of the lungs
what cell type is affected in squamous cell carcinoma?
psuedostratified columnar colitaed epithelium mostly in the centre of the lungs
whats the difference between limited and extensive small cell carcinoma?
limited - in 1 lobe
extensive - in both
what is Lambert-Eaton myasthenic syndrome?
a condition in which the body’s immune system attacks the connections between nerves and muscles
what is the cause of Cushing’s syndrome?
too much cortisol
outline the stages of squamous cell carcinoma?
normal respiratory epithelium - pseudostratified columnar ciliated epithelium
metaplasia - replacing brochial epithelium by mature squamous epithelium caused by irritation by cigarette smoke
dysplasia - disordered cell growth, loss of normal architecture and uniformity of individual cells, increase in mutotic figures
malignancy - excessive growth of abnormal squamous cells
outline the steps of adenocarcinoma?
pneumocytes lining epthelia change from squamous cells to more cuboidal shaped cells = atypical adenomatous cell hyperplasia
eventually the tumour becomes invasive and infiltrates normal tissue. circular glandular structures form in the tissue lined by atypical columnar epithelial cells
what is atypical adenomatous hyperplasia?
a precursor of adenocarcinoma of the lung
how do we treat small cell carcinoma?
if its limited then we use radical chemo and radiotherapy
if its extensive then we give palliative chemo and radiotherapy
whats the medial survival time in small cell carcinoma?
7% reaching 5 year
how do we treat non-small cell carcinoma?
if its in stage 1 or 2 and hasnt spread to peripheral lymph nodes we do surgical resection or potentially radical radiotherpy
if its stages 3 or 4 we offer palliative chemo and radiotherapy
whats the survival rate of non-small cell carcinoma?
25% 5 year survival
what are some molecular targeted drugs for adenocarcinoma?
tyorisine kinase inhibits such as eriotinib of geftinib
ALK inhibits such as crizotnib
what is malignant mesothelioma?
a type of cancer that occurs in the mesothelium that is usually linked to asbestos
how do we diagnose lung cancer?
chest x-ray - coin lesion CT scan PET_CT scan to see where there are active cancer cells as it measures where ther eis higher glucose turnover bronchoscopy and biopsy fine needle aspirations
which type of lung tumour divides and spreads the fastest?
small cell carcinomas
outline the pathology of mesothelioma?
asbestos fibres are inhaled, phagoctic cells attempt to phagocytose the fibres but cant destroy them so they undergo apoptosis. This causes release of tumour promoting factors and the mesothelial cells of the pleura get inflamed. DNA damage leads to uncontrollable mesothelial cell division
what causes most pancoast tumours?
non-small cell lung tumours - adenocarcinoma and squamous cell carcinoma
what happens if a pancoast tumour compresses the brachial plexus?
ipsilateral paresthesia
where in the lungs does small cell lung cancer usually develop?
in the centre of the lungs
what cells are affected in small cell lung cancer?
small, immature neuroendorcine cells
where in the lungs does large cell lung cancer usually develop?
anywhere
Whats the differenc ebetween myasthenia gravis and Lambert-Eaton myasthenic syndrome?
the target of the attack is different in MG as the acetylcholine receptor on the nerve is affected, whereas in LEMS it’s the voltage-gated calcium channel on the nerve
also, in LEMS muscle weakness improves with use unlike in MG where it decreases with use
what paraneoplastic syndromes are associated with small cell cancers
small cell cancers are immature neuroendocrine cells so they ectopically produce hormones
We get hyponatremia and Cushing syndrome
they also cause Lambert-eaton myasthenic syndrome
can also cause production of antibodies against Hu-antigens on neurones - e.g. if cerebellar neurons are affected we get ataxia and nystagmus whilst if cerebral neurones are affected we get dementia and seizures
what paraneoplastic syndromes are associated with squamous cell lung cancers?
hypercalcemia as they sometimes produce parathyroid hormone related peptide
what paraneoplastic syndromes are adenocarcinomas associated with?
hypertrophic osteoarthropathy - fingernail clubbing, joing pain, proliferation of long bone periosteum causing femur and tibia pain
what paraneoplastic syndromes are large cell carcinomas associated with?
gynecomastia or galactorrhoea as they can produce the beta subunit of hCH
what does it mean if the chest xray shows evidence of pleural effusion?
you should do a diagnostic thoracentesis to obtain a sample of pleural fluid. if this fluid has malignant cells then the cancer has invaded the pleura - poor prognosis
how many people worldwide are infected with mycobacterium tuberculosis?
2 billion people
where are TB incidence rates the highest globally?
India leading the count, followed by China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa
whats the strongest risk factor for TB?
HIV
what are the tuberculosis risk factors?
being born in high prevalence areas i.e. India, pakistan, romania, Bangladesh, Somalia
being <5
being in prolonged close contact with someone who has TB
history of TB
comorbid contiiosn e.g. HIV, diabetes, chronic kidney disease
taking immunosuppressive drugs
under-served groups e.g. homeless, shelters, prison
history of excessive alcohol, IV drug users and smokers
how does tuberculsois spread?
through the air from one person to another
why can mycobacterium tuberculosis surive for months on dry surfaces?
as they have a waxy cell wall - also can resist weak disinfectants
outline the pathology of tuberculosis
you inhale M.TB, its taken up by alveolar macrophages and here they produce a protein (sulfatide) which inhibits the phagosome-lysosome fusion allowing M.TB to survive and proliferate = primary TB
what symptoms might you have in primary TB?
no symptoms or mild flu-like illness
what happens after primary TB infection?
3 weeks later, cell mediated immunity kicks in (triggered by TB cord factor) and immune cells suround the TB creating a granuloma, preventing its spread. The tissue inside dies due to caseous necrosis - Gohn focus. These areas undergo calcification and can be seen as scar tissue on xrays
outline how TB can become reactivated?
in some cases, even though M.TB are walled off in grnaulomatous tissue, they can remain viable also stay dormant until the host becomes compromised and then the disease can become reactivated
what is systemic miliary TB?
a potentially life-threatening type of tuberculosis that occurs when a large number of the bacteria travel through the bloodstream and spread throughout the body.
what makes up the Gohn complex?
the Gohn focus and infected hilar lymph nodes
what is extra pulmonary TB?
when any organ, other than the lungs is infected by M.TB
what organs are typically affected in extrapulmonary TB?
spine - Potts disease kidneys abdomen bone brain muscles retina lymph nodes
what is Pott’s disease also known as?
tuberculosis spondylitis
what are symptoms of TB?
productive, prolonged cough chest pain haemoptysis fever chills night sweats appetite loss weight loss fatigue
what conditions increase the risk of TB reactivation?
HIV silicosis diabetes mellitus chronic renal failure TNF alpha blocker therapy solid organ transplants
what is silicosis?
an interstitial lung disease caused by breathing in tiny bits of silica
how do we diagnose TB?
Mantoux test Interferon gamma release assay x-ray sputum smear and cultures PCR
what is the Mantoux test?
injecting a small amount of purified protein derivative tuberculin into the skin of the forearm - a type 4 hypersensitivity reaction will occur if you have an active or latent TB infection and a small, hard red bump will form at the injection site 48-72 hours after the test
how can we test for TB ensuring that a positive result is not because of the BCG vaccine?
using the interferon gamma release assay
what is the interferon gamma release assay?
whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis infection.
who should you treat for TB?
anyone with a positive AFB smear or anyone of high clinical suspicion e.g. history of cough, weight loss, emigration from high risk country
what tests should be done before starting TB treatment?
liver function tests and visual acuity and colour vision tests
what TB treatment can cause optic neuritis and how does it do this?
isoniazid by depleting B6 levels
what are the 1st line drugs for TB?
isoniazid
rifampicin
pyrazinamide
ethambutol
how does isoniazid work?
inhibts mycolic acid synthesis, an essential component of bacterial cell walls
how does rifampicin work?
inhibits DNA dependant RNA polymerase = suppression of RNA synthesis and cell death
how does ethambutol work?
thought to inhibit arabinosyl transferases which are involved in cell wall biosynthesus = increased cell wall permeability
what is standard TB treatment?
combination of rifampicin, isoniazid, pyrazinamide and ethambutol for 2 months followed by a combination of rifampicin and isoniazid for 4 more months
what is given throughout TB treatment to prevent optic neuritis?
pyridoxine
what is pyridoxine?
vitamin B6
what are the 2 categories of drug resistant strains of TB?
multidrug resistant Tb - reistsant to isoniazid and rifampicin
extremely drug reistaant TB
what is the breakthrough medication for XDR-TB?
pretomanid
what vaccine works against TB?
BCG
who is the BCG vaccine offered to?
babies who are likely to spend time with someone with TB - if they live in an area of high rates of TB or have parents/grandparents from a country with high rates of TB
Those in contact with someone who has active TB
may be given to adults at risk of TB through their world e.g. vet staff, healthcare workers or abattoir workers
outline the key facts about mycobacterium TB?
they are rod shaped gram positive bacteria that are strict aerobes and are particularly hardy due to theyr waxy cell wall (mycelia acid)
how do we stain mycobacterium TB?
using ziehl Nielsen stain as they are acid fast bacteria so will not gram stain
Why cant we gram stain acid fast bacteria?
Acid-fast organisms have a lipoid capsule that has a high molecular weight and is waxy at room temperature. This makes the organism impenetrable by aqueous-based staining solutions.
what is progressive primary tuberculosis?
in children and immune compromised individuals the Tb cannot be contained in granulomas so it is spread throughout the lungs, causing further damage
what is a Ranke complex?
a calcified Ghon complex
why are the upper lobes of the lung usually affected in secondary TB?
as oxygenation is greatest here, and Mycobacterium TB is a strict aerobe
what are some conditions caused by TB?
sterile pyuria meningitis Pott disease Addisons disease Hepatitis Lymphadenitis in neck mycobacterial arthritis osteomyelitis
why is the tuberculin/Mantoux test known as a screening not diagnostic test?
as it doesnt differentiate between active, passive or BCG
why can the tuberculin test cause false positives and false negatives?
it can cause false positives in those who are vaccinated against TB
it can cause false negatives in those whos immune systems are too impaired to react e.g. in AIDS
how does an interferon gamma release assay work?
measure amount of Interferon gamma released by T lymphocytes when exposed by antigens unique to M.tuberculosis
what is used as prophylaxis for those at risk of developing TB?
isoniazid for 9 months
