Pathology Flashcards
Obstructive vs restrictive disease
Airway pathology - Obstructive
Lung pathology - Restrictive
Obstructive airway syndromes
Asthma, COPD, emphysema
What is ACOS
Asthma/COPD overlap syndrome, usually in smokers with reversible COPD and eosinophilia who are steroid responsive. Blood eosinophilia > 4%
What is the asthma triad
Reversible airflow obstruction, airway inflammation and airway hyperresponsiveness
How does asthma evolve
Bronchoconstriction - chronic airway inflammation - airway remodelling
Histological remodelling of basement membrane, submucosa and smooth muscles in asthma
Basement membrane - Thickening
Submucosa - Collagen deposit
Smooth muscles - Hypertrophy
Response of airway cells to allergen in asthma
Dendritic cells take up antigen and present it to naive T cells in the lymph nodes. This causes maturation to Th2 and B cell. Th2 cells release IL5 which stimulates eosinophils to secrete leukotrienes and cytokines. B cells secrete IgE. Mast cells have IgE receptors and degranulate releasing histamine causing bronchoconstriction. Basophils also bind to IgE and secrete Leukotriene D4 which increases mucus secretion. Mast cells release IL-4 which further causes B cells to release IgE.
How can airway inflammation be measured
Bronchoscope and bronchial biopsy
What predisposes patient to airway hyperresponsiveness in asthma
Desquamation due to eosinophil influx
What drugs can cause asthma symptoms
NSAIDS and B blockers
What happens to FEV1/FVC ratio in asthma
< 75% as FEV1 drops by FVC remains normal
Components of COPD
Muco-ciliary dysfunction, tissue damage and inflammation
Disease process in COPD
Irritants such as cigarette smoke activate macrophages and airway epithelial cells. This causes release of neutrophil chemotactic factors including IL 8 and leukotriene B4. Macrophage and neutrophils release proteases that break down connective tissue in lung (emphysema) and stimulate muscus hypersecretion. These are normally counteracted by antiproteases however in COPD, there’s an imbalance between proteases and antiprotease.
What does protease-antiprotease imbalance lead to
Alveolar destruction and emphysema
What are indicators of high risk in COPD
Two exacerbations or more within last year (or)
FEV1 < 50% predicted are indicators or high risk
General symptoms in COPD
Non-atopic, smoker, daily productive cough, progressive breathlessness, frequent infective exacerbations, chronic bronchitis - wheezing, emphysema causing reduced breath sounds
Non pharmacological management of COPD
Smoking caessation, immunisation for influenza/pneumococcal, physical activity oxygen
Smoking caessationg techniques
Nicotine replacement therapy, varenicline, bupropion
Main inflammatory cells in asthma vs COPD
Asthma - Eosinophils, COPD - Neutrophils
Asthma vs COPD cough
Asthma - Non-productive cough whereas COPD is productive
Asthma vs COPD diurnal variation
Asthma has diurnal variation whereas COPD doesn’t
Asthma vs COPD gas exchange
Normal gas exchange in asthma where it’s impaired in COPD
Thoracic restriction not due to lung causes
Skeletal - Kyphoscoliosis, ankylosing spondalitis, multiple rib fracture
Muscle weakness, obesity, ascites
Interstital lung disease are also known as
Diffuse parenchymal lung disease (DPLD)
Is CO2 elimination impaired in DPLD
No as expiration is determined by diaphragm and intercoastal movement
What can cause fluid in alveolar spaces
Cardiac pulmonary oedema - Due to raised pulmonary venous pressure, ex: left ventricular failure
Non-cardiac pulmonary oedema - Leaky pulmonary capillaries due to sepsis or trauma (acute respiratory distress syndrome -ARDS)
Aetiology of DPLD
Infective pneumonia, infarction, rheumatoid disease, drugs, cryptogenic, alveolitis, granulomatous-alveolitis, extrinsinc allergic alveolitis, sarcoidosis, drug induced (amiodarone, bleomycin, methotraxate, gold), toxic gas/fumes, pulmonary fibrosis (rheumatoid/idiopathic), autoimmune
What is pneumoconiosis
Occupational restrictive lung disease caused by inhalation of dust, often mines and agriculture.
What is commonly used to treat urinary tract infection
Nitrofurantoin
Clinical syndrome of DPLD
Breathless on exertion, cough, no wheeze, finger clubbing, lung crackles, central cyanosis (if hypoxaemic) and pulmonary fibrosis as end stage to chronic inflammation
Important questions for DPLD history
Pets, occupation, drugs, arthritis
Lung volumes in DPLD
Reduced FEV1 and FVC however FEV1/FVC > 75%
Reduced gas diffusion (DLCO) as well as reduced oxygen saturation (PaO2 and SaO2)
Transbronchial or thoracoscopic lung biopsy in DPLD
Rarely indicated
What is ground glass opactiy
Nonspecific finding on CT scan that indicates partial filling of air spaces in the lungs by exudate or transudate, as well as interstitial thickening or partial collapse of lung alveoli
First line treatment for DPLD
Oral corticosteroids such as Prednisolone as ICS aren’t effective
Second line treatment of DPLD
Azathioprine - Immunosuppression, by inhibiting purine synthesis, less DNA and RNA is produced for synthesis of white blood cells.
Treatment of interstitial pulmonary fibrosis (IPF)
Anti-fibrotic agents such as pirfenidone, nintedanib
What is erythema nodosum
Swollen patches of fat under the skin causing red bumps and patches. Due to sarcoidosis
What is desquamative interstitial pneumoniae (DIP)
Form of idiopathic interstital pneumoniae featuring elevated macrophage levels. It is believed that these macrophages were pneumocytes (alveolar cells) that desquamated. Usually history of smoking
What can be used to treat desquamative interstitial pneumoniae
Methylprednisolone - Corticosteroids
Obstruction of airway generally leads to
Pneumonia
Ulceration generally leads to
Haemoptysis
Common types of lung tumours
Adenocarcinoma, squamous carcinoma, small and large cell carcinoma
Serious complication following needle aspiration of metastasis
Implantation of malignant cells along needle tract
When is biopsy or needle aspiration of metastasis generally used
For specimen collection from mediastinal and supraclavicular lymph nodes
Which lung cancer type is sensitive to chemotherapy
Small cell lung carcinoma
What is used to treat non-small cell lung carcinoma (NSCLC)
Surgery with chemothereapy used pre and post operatively
Prognosis of different cancer types
Worse - Small cell > large cell > squamous > adenocarcinoma
Small cell cancers react to chemotherapy. Why do they have a worse prognosis
Small cell lung cancers divide rapidly. Hence, they also die fast. However some of them may become resistant to treatment and bounce back aggresively
What drug used to treat adenocarcinoma is contraindicated in squamous cell carcinoma
Pemetrexed
What immunohistochemistry factors do small cell carcinioma express
Antigen p63 and high molecular weight cytokeratins
What immunohistochemistry factors do adenocarcinomas express
Thyroid transcription factor (TTF) 1
Common oncogenes in lung cancer
MYC - regulatory gene that codes for a transcription factor that plays a role in cell cycle progression, apoptosis and cellular transformation
Common tumour suppressor genes in lung cancer
p53 and Rb
What epithelial growth factor is mutated in lung epithelium
MAPK/ERK pathway. Specific mutations render EGFR gene active in the absence of ligand (epidermal growth factor) binding.
What mutation is almost exclusively seen in non-smokers and asian populations with adenocarcinoma of lung
EGFR overexpression
What do EGFR overexpression tumours response to
Tyrosine kinase inhibitors such as erlotinib. Used for treatment of non-small cell lung carcinoma
EML4-ALK fusion oncogenic lung cancers are a target for?
Crizotinib, anti-cancer drug acting as an ALK and ROS1 inhibitor. Used for treatment of non-small cell lung carcinoma
What is atypical adenomatous hyperplasia (AAH)
Subtype of pneumocytic hyperplasia in the lung. Involves spread of neoplastic cells along alveolar walls (bronchioalveolar carcinoma) which can eventually become invasive adenocarcinoma
What are carcinoids
Neuroendocrine tumours arising in cells of neuroendocrine system
Where are bronchial gland neoplasms usually seen
In salivary glands -
Adenoid cystic carcinoma and Mucoepidermoid carcinoma
What are paraneoplastic features
Systemic effects from biologically active molecules released from tumour cells
Why is incidence of lung cancer high but prevalence low
As most patients diagnosed with lung cancer do no live long, 50% pass away within 6 months
General symptoms of lung cancer
Haemoptysis, recurrent pneumonia, stridor, dyspnoea, hoarse voice, pleural effusion, distended jugular vein
Why does lung with tumour tend to shrink as tumour becomes bigger
When a lobe is obstructed, all of the air beyond is absorbed and the lung shrinks down to a smaller size.
Difference in wheeze in lung cancer vs asthma and COPD
Asthma and COPD produce an expiratory wheeze whereas lung cancer can produce a stridor - inspiratory wheeze
What can lead to hoarseness of voice
Tumour pressing onto the recurrent laryngeal nerve
How can metastatic lung cancer affect cardiovascular system
Atrial fibrillation followed by pericardial effusion. Patient will have dyspnoea and trouble breathing
How can a pancoast tumour cause wasting of hand muscles
Pancoast tumour can erode through the ribs and into the lower part of brachial plexus. This can also lead to weakness in the hands
How does patient present with pain that is due to cancer eroding the ribs
Worse at night and on movement
Common metastases sites for lung cancer
Liver, brain, bone, adrenal, skin, lung
Cerebral metastases vs stroke
Stroke is acute and develops within minutes whereas cerebral metastases leaks to stroke like symptoms over days and weeks.
Cerebral metastases presents with symptoms that are worse when
When patient wakes up in the morning and improves as the day goes by
Liver function tests for liver metastases
Abnormal, especially alkaline phosphate (ALP)
Common presentation of bone metastases
Localised pain worse at night or fracture due to trivial mechanical stress
Adrenal metastases causes functional problems
Yes but very rarely, hormones are generally still produced
Common paraneoplastic symptoms
Finger clubbing, hypertrophic pulmonary osteoarthropathy, weight loss, thrombophlebitis, hypercalcaemia, hyponatraemia, muscular weakness - eaton lambert syndrome
What is hypertrophic pulmonary osteoarthropathy
Medical condition combining clubbing and periostitis of the small hand joints
What is the eaton lambert syndrome
Autoimmune disorder characterized by muscle weakness of limbs
Important follow up for pneumonia
Chest x-ray 6 week down
Why does thrombophlebitis occur in cancer patients
Due to increased coagulability of blood
Signs and symptoms of hypercalcaemia
Stones, bones, abdominal groans, thrones and psychiatric overtones. Also cardiac arrhythmias and left ventricular hypertrophy
Treatment of hypercalcaemia
Initial treatment if rehydration. If Ca2+ levels are very high then use IV Bisphosphonate. Treat underlying cancer
Usual cancer that causes hypercalcaemia
Squamous cell carcinoma
Syndrome of inappropriate anti diuretic hormone is generally caused by
Small cell lung cancer. It results in small cell lung cancer
What can be used in the treatment of syndrome of inappropriate anti-diuretic hormone
Demeclocycline
What can be administered by IV if calcium is very high
Bisphosphonate
Most smokers cough up clear sputum almost everyday and they think this is normal. Is it?
No, this is chronic bronchitis
What does stony dull percussion suggest
Pleural effusion
What does hyper-resonant percussion suggest
Pneumothorax
What does dull percussion suggest
Solid mass such as pulmonary consolidation
Why should sputum cytology not be asked for
As the end result (positive or negative) for sputum cytology is bronchoscopy and it’s a time consuming process. Ask for bronchoscopy instead
What is positron emission tomography (PET)
Scan to assess function rather than structure of lung. Tissues with high metabolic activity light up upon uptake of radioactive glucose
Can a bronchoscope investigate possible tumours in the periphery of lungs
No because you can’t inspect bronchial divisions smaller than the diameter of the bronchoscope
Differential diagnosis for smoker, haemoptysis and abnormal chest x-ray
Lung cancer, tuberculosis, vasculitis, pulmonary embolism, secondary cancer, lymphoma, brochiectasis
Breaking news of cancer to a patient
Bring a relative for the patient and an experienced nurse (if needed) to comfort the patient
Ask if the patient has an idea of what it might be
Make sure they understand
Tell their GP and arrange a follow up
When is surgery viable for cancer
When the cancer is recognised before it spreads beyond its primary site
Which has a higher survival rate, small vs non-small cell
Non-small cell
Treatment options for cancer
Surgery, radiotherapy, chemotherapy, palliative care
Options for considering surgery
Is the disease localised, will patient survive operation, can we cut it out
What is staging for surgery important
To make sure the cancer hasn’t metastasized and can be completely removed by surgery. Can use -
Bronchoscopy, CT scan of thorax, PET scan, CT scan of brain, mediastinoscopy
Role of PET staging
To ensure there’s no metastases present before undergoing surgery
Surgery options for lung cancer
Pneumonectomy or lobectomy, thoracotomy, minimal access video assisted thoracic surgery (VATS)
VATS vs pneumonectomy
Faster recovery time and less traumatic
Is small cell carcinoma suitable for surgery
No as it divides rapidly, it may metastasize easily making it hard to pinpoint the exact location of tumour to remove during surgery. Chemotherapy is a better alternative
What is the ECOG score used for
To assess how the disease impacts the patients daily living abilities
Side effects of chemotherapy
Targets rapidly diving cells, these types are also present in intestinal epithelium and bone marrow. Can lead to opportunistic infection and anaemia, nausea, vomiting, tiredness, hair loss and pulmonary fibrosis
2 uses of radiotherapy
Radical - Curative intent
Palliative - Delaying tactic useful for metastases
Disadvantages of radiotherapy
Collateral damage to spinal cord, oesophagitis and adjacent lung tissue (fibrosis)
It always goes only to where you point it to, not good for subclincal metastases
What is SABR
Stereotactic Ablation Radiotherapy - Fires more beams than radiotherapy but with less intensity which causes lesser collateral damage. 4D scanning required
What determines lung cancer treatment
Cell type, extent of disease, co-morbidity and patients wishes
Prognosis for lung cancer
Half dead within 6 months
1 in 20 survive more than 5 years
What is induration
Swelling or hardening of normally soft tissue
What is lobar pneumonia
Confluent consolidation involving a complete lobe. Most often due to Streptococcus pneumoniae
Is pneumonia always fatal
Usually self-limiting and solves by resolution. Can be fatal in immunocompromised or immune-deficient
What is bronchopnemonia
Infection starts in bronchi and spreads to adjacent lungs. More often with pre-existing conditions
What organism would you expect in a aspiration pneumonia
Staphylococcus aureus, coliforms and anaerobes as these are generally found in the gut
What can lung abscess be mistaken for
Lung cancer
When do you generally get lung abscess
Aspiration pneumonia
Hypersensitivity in tuberculosis
Generally type 4 hypersensitivity - Granulomas with necrosis
