Respiratory Pathology Flashcards
What is Asthma?
- Chronic inflammatory disorder of the airways
- Paroxysmal bronchospasm
- Wheeze
- Cough
- Variable bronchoconstriction that is at least partially reversible
- Mucosal inflammation & oedema of airways mucosa
- Hypertrophic mucous glands & mucus plugs in bronchi
- Hyperinflated lungs
- Clinicopathological classification
- Causes; Atopic , non-atopic, aspirin-induced, allergic bronchopulmonary aspergillosis (ABPA)- from aspergillus fungus
What is Atopic Asthma?
• Type I hypersensitivity reaction;
o Allergen- dust, pollen, animal products
o Cold, exercise, resp infecs
o Many diff cell types & inflamm mediators involved
o Degranulation of IgE bearing mast cells;
Histamine initiated bronchoconstriction & mucus prduc obstructing air flow
Eosinophil chemotaxis- lots of eosinophils inflamed
• Persistent/ irreversible changes
o Bronchiolar wall smooth muscle hypertrophy
o Mucus gland hyperplasia
o Respiratory bronchiolitis leading to centrilobular emphysema
Atopic Asthma- Clinical
• Children & young adults
• Common; 33.9% UK children 12-14yrs with ‘wheeze’ (2002), 1 in 10 UK kids diagnosed with asthma, 590,000 teens, 9-15% adult onset asthma is occupational (commonest occupational lung disease)
Atopic Asthma- At Autopsy
• Acute asthma- a mucus plugged small bronchus with eosinophils
• Airway occluded by mucus=death
• Cells- eosinophils
What is Obstructive Pulmonary Disease?
Localised or diffuse obstruction of air flow
• Localised;
o Tumour or foreign body
o Distal alveolar collapse (total) or over expansion (valvular obstruct
o Distal retention pneumonitis (endogenous lipid pneumonia- rec in alveoli) & bronchopneumonia
o Distal bronchiectasis (bronchial dilation- 1 bit of lung expands, compresses bit next to it)
What is Bronchiectatsis?
Bronchiectatsis
• Permanent dilation of bronchi & bronchioles caused by muscle destruct & elastic tissue
• Results from chronic necrotizing infection
• Rare ( for now…..)- due to antibiotics that work
• Site: bronchus/ bronchioles
• Cause: infections, predisposing conditions (so infecs can’t be cleared by antibiotics);
o Cystic fibrosis
o Primary ciliary dyskinesia (inherited- cilia don’t function properly), Kartagener syndrome (cilia affecetd)
o Bronchial obstruction: tumour, foreign body
o Lupus, rheumatoid arthritis, inflammatory bowel disease, GVHD
• Signs/Symptoms: long standing cough, intermittent fever, lots of foul smelling sputum
• May be localised- so can be resectable
• Complications- pneumonia, septicaemia, metastatic infec, amyloid
What is Chronic Obstructive Pulmonary Disease?
- Combination of chronic bronchitis & emphysema
- Cor pulmonale- R sided heart failure
- Blue bloater (hypoxic, large patient)
What is Chronic Bronchitis?
- Cough & sputum for 3 months in each of 2 consecutive years
- Site: bronchus
- Cause: chronic irritation, smoking & air pollution
- Middle aged & old
- 1 in 20 of >65yr consultant g.p. per year
- Pathology: Mucus gland hyperplasia & hypersecretion, 2ndry infec by low virulence bacteria (don’t kill you but hard to get rid of), chronic inflamm of small airways of lung cuases wall weakness & destrc = centrilobular emphysema
- Diff to asthma as has no acute component
What is Emphysema?
• Loss of elasticity of alveoli & abnormal enlargement of airspace vol in alveoli- caused by proteases (made by immune cells during inflamm) digesting the elastin
• Classification (& causes);
o Centrilobular (centiacinar- upper lung zones; focal enlargement & destruc of resp bronchiole, distal alveoli unaffected)- coal dust, smoking
o Panlobular (panacinar- destruc & enlargement of bronchioles & alveoli) - >80% a1 antitrypsin (an anti-protease) deficiency (rare, autosomal dominant- causes emphysema & liver disease) , severest in lower lobe bases
o Paraseptal (distal acinar- bronchioles unaffected but airspaces enlarged & alveoli destruc)- Upper lobe subpleural bullae adjacent to fibrosis. Pneumothorax if rupture
• Site: acinar (distal lung)
• Symptoms: dyspnoea (progressive & worsening)
What is Interstitial Lung Disease?
• Heterogenous group of diseases lumped together- usually diffuse (affect whole lung) & chronic
• Diseases of pulmonary connective tissue- mainly alveolar walls
• Restrictive rather than obstructive lung disease
• Causes: often unknown
• Pathological, radiological & clinically descriptions diff
• Pathology;
o Increased tissue in alveolar-capillary wall- increased gas diffusion distance
o Inflammation & fibrosis- decreased lung compliance
o Limited morphological patterns- differ with site & with time in any individual but with many causes & clinical associations
• Normal alveoli; thin walls
• Interstitial disease- expands interstitial space in alveolar walls (full of inflamm cells), gas exchange would be impaired
• More interstitium than gas- gas exchange effectively not going to occur
What is Acute Interstitial Lung Disease?
- Diffuse alveolar damage – exudate & death of type I pneumocytes form hyaline membs lining alveoli, followed by type II pneumocyte hyperplasia (line alveolar walls)
- Histologically called acute interstitial pneumonia
- Adult respiratory distress syndrome (shock lung) - shock, trauma, infecs, smoke, toxic gases, oxygen, paraquat poisonig (weed killer), narcotics, radiation, aspiration, DIC
What is Chronic Interstitial Lung Disease?
Presentation (gradual);
• Dyspnoea increasing for months to years
• Clubbing, fine crackles, dry cough
• Interstitial fibrosis & chronic inflamm with varying radiological & histological patterns
• Common end-stage fibrosed “honeycomb lung”
• Examples (diff types);
o idiopathic pulmonary fibrosis,
o many pneumoconioses (dust diseases)
o sarcoidosis,
o collagen vascular diseases-associated lung diseases
What is Idiopathic Pulmonary Fibrosis?
Idiopathic Pulmonary Fibrosis (/Cryptogenic Fibrosing Alveolitis)
• Alveoli become increasingly scarred- lungs become stiff & difficult to get oxygen into blood
• Bosselated (“cobblestone”) pleural surface due to contrac of interstitial fibrous tissue accentuates lobular architecture
What is Sarcoidosis?
- Lymph node enlargement & widespread granuloma appearance
- Non-caseating (non-necrotic) perilymphatic pulmonary granulomas, then fibrosis
- Hilar nodes usually involved
- Breathless- have x ray- hilar nodes
- Other organs may be affected- skin,heart, brain, kidneys
- Hypercalcaemia & elevated serum ACE
- Typically young adult females (20-40 yrs), aetiology unknown
What is Pneumoconioses?
• Originally- non neoplastic lung diseases due to inhalation of mineral dusts in the workplace
• Now also includes organic dusts, fumes and vapours
• Inhaled dusts;
o Chemically inert
o Fibrogenic reac
o allergenic
o oncogenic- lung carcinoma & pleural mesothelioma
• <3mm diameter to reach alveoli
• Often occupational
What is Coal Workers Pneumonconiosis (CWP)?
- Anthracosis- milder asymptomatic type of pneumoconiosis caused by carbon accumul in lungs due to repeated exposure to air pollution/ inhalation of smoke/ coal dust particles
- Simple (macular) CWP
- Can progress to Nodular CWP
- Progressive massive fibrosis
- COPD (‘chronic bronchitis & emphysema’) if >20yrs underground mining
- Don’t have to have COPD to have CWP- just need to have dust in lungs
- Black in lungs - inhaled coal dust
- Heterotrophy of R ventricle due to vascular resistance of affected lungs
What is Silicosis?
- Silica - sand & stone dust
- Kills phagocytosing macrophages (which eat it)
- Fibrosis & fibrous silicotic nodules, also in nodes
- Possible TB reactivation
- Increased risk of lung carcinoma with silicosis- prescribed occupational disease (gov recognises the association)
- Mixed dust pneumoconiosis – silica with exposure to other dusts
What is Hypersensitivity Pneumonitis?
Hypersensitivity Pneumonitis (/Extrinsic Allergic Alveolitis)
• Type III hypersensitivity reaction to organic dusts
• Farmers’ lung – exposed to actinomycetes in hay (develop hypersensitivity pneumonitis)
• Pigeon fanciers’ lung - pigeon antigens
• Peribronchiolar inflammation with poorly formed non-caseating granulomas extends alveolar walls
• Repeated episodes lead to chronic irreversible interstitial fibrosis
• These reversible in early stages
What is Cystic Fibrosis?
• Autosomal recessive inherited multi-organ disorder of epithelial cells- affects fluid secretion in exocrine glands & epithelial lining of resp, GI & reproductive organs
• Epidemiology: Incidence 0.4 per 1000 live births, mostly affects Caucasians
• Bronchioles distended with mucus
• Hyperplasia mucus secreting glands, bronchioles distended with mucus, mucus plugged exocrine glands
• Multiple repeated infections
• Severe chronic bronchitis and bronchiectasis
• Atrophy and fibrosis of gland
• Impaired fat absorption, enzyme secretion, vit deficiencies (as can’t absorb fat soluble vits pancreatic insufficiency)
• Small bowel: mucus plugging - meconium ileus
• Liver: plugging of bile cannaliculi = cirrhosis
• Salivary glands: Similar to pancreas: atrophy and fibrosis
• 95% of males are infertile
• Tests; part of newborn screening in UK, sweat test, genetic testing
• Median survival in UK 41 yrs
• Treatments;
o Physiotherapy
o Mucolytics (are inhaled- loosen mucous)
o Heart/lung transplants
o Why hasn’t gene therapy worked?- is a single gene disorder but gene therapy failed
o Orkambi (lumacaftor-ivacaftor) drug- prolong peoples lives (not on NHS as too expensive)
• Further reading- molecular basis of CF & it’s treatment;
o CTFR gene found at 508th position on chromosome- codes for protein ion channel that transports chloride & thiocyanate ions across membs
o Common mutation in CTFR gene- deltaF508 (deletion of 3 nucleotides causing a.a. phenylalanine loss at 508th position)
o Most affects lungs, liver, pancreas, intestine
o Abnormal sodium & chloride transport across epithelium
o Mucus sticky as not humidified enough- hard to remove form airway infecs
o Duct that leads from pancreas to gut blocked no pancreatic enzymes so can’t digest food properly= poor growth & diarrohea
o Treatment;
Lungs; antibiotics (prvent infecs), ivacaftor (reduce mucus), bronchodilators, steroids (treat nasal polyps)
Airway clearance techniques: e.g. active cycle of breathing tchniques (ACBT)
Dietary: digestive enzyme capsules
Lung capsules
For associated probs: bisphospahates- brittle bones, insulin- diabetes
What is Malignant Lung Pathology?
Definition- tumours in lung that possess potentially lethal abnormal characteristic that enables them to invade & metastasize to other tissues
- Primary- arise within the lungs (then can spread)
- 2ndry- originally elsewhere (e.g. kidneys) then metastisise to lungs
What are Primary Malignant Lung Tumours?
• Most common (>90%) are carcinomas- arise from epithelium
• The 4 major types of lung carcinomas, classified based on light microscopy (histology) are;
o Adenocarcinoma (30-40%)
o Squamous cell carcinoma (20-30%)
o Small cell carcinoma (15-20%)
o Large cell undifferentiated carcinoma (10-15%)
Other Primary Malignant Lung Tumours
• Carcinoid tumours– low grade malignant tumours, better survival (from neuroendocrine cells in lung)
• Malignant mesenchymal tumours – very rare, most common is synovial sarcoma
• Primary lung lymphomas – originate in lung lymphoid tissue, rare, can be seen in HIV/AIDS patients (treated by chemo so slightly better survival)
What are Secondary Lung Tumours?
- Very common, more common than primary tumours
- Usually present as multiple discrete nodules, can also be solitary nodule in lung (need to differentiate if it’s primary or come from elsewhere)
- Most common are carcinomas from various sites eg. Breast, GI tract, Kidney
- Sarcomas
- Melanomas e.g. from skin
- Lymphomas
What is the Epidemiology of Lung Cancer?
- Most common cause of cancer death in UK & worldwide (major public health prob)
- 45 000 new cases diagnosed each year and >30 000 deaths/year (UK)
- M > F, only slight
- Age usually between 40 and 70 yrs, rare in younger individuals
- Major risk factor- cigarette smoking; lung cancer incidence rise closely paralleled increase in cigarette smoking, incidence & mortality rates been decreasing due to decrease smoking rates.
- Overall prognosis is poor, 5 year survival is between 5 – 10%.
What is the Aetiology of Lung Cancer?
- Tobacco smoking
- Occupational/Industrial hazards, eg Asbestos, uranium, arsenic, nickel mines
- Radiation – mines where radon emitted (Japan- atomic bomb survivors after WWII- high lung cancer incidence)
- Pulmonary fibrosis patients have an increased lung cancer risk
- Genetic mutations- EGFR, KRAS, ALK mutations etc (usually in lung cancers of never smokers)
What is the Pathogenesis of Lung Cancer?
- Not very well understood
- Mutations in key genes regulating; cell prolif, DNA repair & apoptosis
- Squamous cell carcinoma- cigg smoking is irritant to bronchial epithelial cells (squamous metaplasia= dysplasia= carcinoma in-situ= frank squamous carcinoma)
What is a pack year?
- Major risk factor- tobacco smoke is a carcinogen
- Almost linear dose relationship between n.o. of ciggs smoked/ day & risk of developing lung cancer e.g. risk x10 higher if smoke 10 per day
- ‘Pack years’ quantifies; 1 pack year= 20cigarettes per day for 1yr e.g. 40 cigarettes/day for 6 mnths
- Passive smoking does increase risk for lung cancer
What are the Clinical Features of Lung Cancer?
- Local effects of tumour (symptoms related to tumour in chest)
- Distant metastases (symptoms related to metastasis)
- Non-specific features
- Asymtomatic, discovered incidentally (e.g. from a CT)
- As tumour grows= ulcerates= bleeds=cough up blood (haemoptysis) — presenting sign
- Distally develop consolidation
= pneumonia
• Pleural effusion=breathlessness
Non-Specific Features
• Usually metabolic effects- weight loss, lethargy
• Electrolytic disturbances, e.g. small cell carcinoma – hyponatraemia, hypokalaemia, hypercalcaemia
• Finger clubbing
• Can produce hormones e.g. ACTH
• CT saggital section of chest; lung lymphatics stuffed with tumour- Lymphangitis carcinomatosa
What are the Local Effects of Lung Cancer?
- Central tumours in proximal airways can ulcerate and bleed –haemoptysis.
- Tumour obstructing airways with distal collapse or consolidation – breathlessness or features of pneumonia.
- Tumour infiltrating into adjacent strucs, eg Pleura – pleural effusion presenting as breathlessness, can invade chest wall/ribs – chest pain
- Recurrent laryngeal nerve – hoarseness
- Horner’s syndrome – sympathetic chain, ptosis (eyelids drooping)
- Oesophagus - dysphagia
What are Distant Metastases of Lung Cancer?
- Can present with disseminated disease.
- Common sites – lymph nodes, pleura liver, bone, adrenal, brain
- Depending on site can present with pathological fractures (tumour from lung metastised e.g. to hip causing fracture), seizures, lumps in neck etc
What is Lung Cancer Management?
Lung Cancer Management (Primary)
• Small % of patients diagnosed with early stage (disease limited to lung/ extension into local nodes), offered Surgery or radical radiotherapy.
• Majority present with advanced disease – used to be limited to Chem or Palliative Radiotherapy.
• Only about 10% have surgery (early stage of surgery)- not all fit for surgery (e.g. have other conditions) even if have localised disease
• (Don’t operate on people with metastases)
• Recent advances in lung cancer treatment with advanced disease;
o Targeted/tailored therapy
o Based on tumour genomics eg EGFR mutations, ALK re-arrangements
o I.d. Immune checkpoint inhibitors eg PD-L1 receps in tumour (know they’ll respond to anti-PD-L1 drugs; makes their own immune system fight against tumour (isn’t chemo/ radio therapy))
o Send it for genomic studies- see mutations (may have drug against mutation)
What is Normal Mesothelium?
- Single layer of mesothelial cells lines pleural cavity
- They secrete hyaluronic acid rich mucinous pleural fluid- lubricates visceral & parietal pleural movement against each other during resp
What is Pleural Inflammation?
Causes
• Primary inflammatory diseases- collagen vascular diseases e.g. systemic lupus erythematosus & rheumatoid arthritis
• Infecs- usually 2ndry to pneumonias or pulmonary TB. Viral- primary Coxsackie B infec (Bornholm disease)
• Pulmonary infarction- usually 2ndry to pulmonary arterial thromboembolus
• Emphysema- 2ndry to ruptured bullae
• Neoplasms- primary or secondary pleural neoplasms
• Theraputic- pleurodesis usually with talc to treat recurrent pleural effusions/ recurrent pneumothoraxes
• Iatrogenic- radiotherapy to thorax, immune reacs to drugs (eosinophils- markers for this for pleura)
Diagnosis
• If there is no associated pleural effusion;
o Symptomatic- pleuritic chest pain (sharp localised pain exacerbated by breathing)
o Sign- auscultation of a pleural rub during breathing
Usually associated pleural effusion- excess fluid in pleural cavity
What is Pleural Fibrosis?
• Usually 2ndry to pleural inflamm;
o Uni or bilateral
o Localised or diffuse
• Asbestos associated pleural fibrosis;
o Parietal pleural fibrous plaques
o Diffuse pleural fibrous
Effects of Pleural Fibrosis
• Widespread thick fibrosis- prevent normal lung expansion during respiration causing breathlessness
• Fibrous adhesions- wholly/ partly obliterate pleural cavity
• Fibrous tissue removal (pleural decortication)- improve lung expansion & compression during resp
What is Parietal Pleural Fibrous Plaques?
- Associated with low level asbestos exposure
- Asymptomatic
- May be visibe on chest radiographs
- Dense poorly cellular collagen
- Not a UK Gov Prescribed Occupational Disease- doesn’t cause disability
What is Diffuse Pleural Fibrosis?
- Assocaited with high level asbestos exposure
- Usually bilateral
- Dense cellular collagen not extending into interlobar fissures
- Benign fibrosis doesn’t go into fissures (malignant do- how radiologists distinguish the two)
- Prevents normal expansion and compression of the lung during breathing causing breathlessness
- IS a UK Gov prescribed Occupational Disease for specified high exposure occupations eligible for Industrial Injuries Disablement Benefit
What are Pathological fluids in Pleural Cavity?
LIQUIDS;
• Serous fluid- pleural effusion (compresses lung so vol reduced- breathless)
• Pus- empyema or pyothorax (usually 2ndry to pneumonia)
• Blood- haemothorax (usually traumatic/ ruptured thoracic aortic aneurysm)
• Bile- chylothorax (usually traumatic)
GAS
• Air- pneumothorax
What are the different types of Pleural Effusion?
• TRANSUDATES
o Fluid pushed through capill due to high pressure in capill
o Low capill oncotic (colloid osmotic) pressure &/or high capill hydrostatic pressure
o Intact capillaries retain semipermeability
o Low protein (<2.5g/dL) & low lactate dehydrogenase
• EXUDATES
o Fluid leaks around cells of capills caused by inflamm
o Pathological capillaries loose semipermeability
o Normal capillary oncotic pressure and normal vascular hydrostatic pressure
o High protein (>2.9 g/dL) & high lactate dehydrogenase
What are the causes of Pleural Effusions?
Causes
• Nephrotic syndrome- protein leaks out, low serum albumin
Transudates
• High vascular hydrostatic pressure- left ventricular failure, renal failure
• Low capillary oncotic (colloid osmotic) pressure- hypoalbumenaemia (hepatic cirrhosis, nephrotic syndrome)
Exudates
• Inflammation with/without infection- an acute inflammatory effusion become an empyema when see lots of neutrophils it’s an empyema
• Neoplasms either primary or secondary
What are the signs and symptoms of Pleural Effusions?
• Symptoms;
o Breathlessness - effusion compresses the lung
o Little/no pleuritic pain – the visceral and parietal pleura are not in contact
• Signs;
o Percussion- dull (as fluid underneath)
o Auscultation- reduced breath sounds (as fluid)
• Investigations to support diagnosis; imaging (ultrasound, chest radiograph, CT)
What is the treatment of Pleural Effusions?
• Treat the breathlessness by removing the fluid
o Aspiration with a needle & syringe, ultrasound guided (so don’t cause a pneumothorax)
o Reaspirate if the fluid reaccumulates
o For recurrent effusions consider a temporary or permanent pleural drain
o For recurrent effusions when the lung expands after drainage and the underlying cause remains consider pleurodesis to obliterate the pleural cavity
• Identify and treat the underlying cause
• Local- pleural fluid for cytology, microbiology, & biochemistry, pleural biopsy
• Systemic – investigate the systemic causes of pleural effusions
What is a Pneumothorax ?
- Air in pleural cavity
* Common, occasionally fatal
What is a open Pneumothorax ?
o Chest wall perforation usually traumatic- ‘sucking shest wound’- connects body surface to pleural cavity
o External air drawn into pleural cavity during inspiration, reducing potential lung expansion
What is a closed Pneumothorax ?
o Not traumatic (e.g. ruptured bullae)
o Lung perforation- connects lung air spaces to pleural cavity
o Lung air drawn into pleural cavity during inspiration, reducing potential lung expansion
o Causes;
Ruptured emphysematous bullae
Common inflamm lung diseases; asthma, pneumonia, TB, cystic fibrosis
Traumatic- lung tears from fractured ribs
Iatrogenic- mechanical ventilation at high pressures, lung & pleural biopsy procedures
Some rare cystic lung diseases- Langerhans’ cell histiocytosis, lymphangioleiomyomatosis
Catamenial due to pleural endometriosis
What is a Tension Pneumothorax?
- Rupture forms a valve (closes)- air can’t get out
- Perforation into pleural cavity, in an open/closed pneumothorax can be valvular- allowing air into cavity during inspiration but not out during expiration
- Pressure in pneumothorax can rise above atmospheric pressure (think of blowing up a balloon)
- This can compress mediastinal strucs e.g. vena cavae & heart and move the mediastinum compressing the contralateral lung
- A tension pneumothorax is potentially fatal and requires urgent treatment
What are the signs and symptoms of a Pneumothorax?
Symptoms (small ones may be asymptomatic);
• Breathlessness
• Pleuritic chest pain
Signs;
• Cyanosis
• Tachycardia
• Contralateral tracheal deviation in tension pneumothorax
• Percussion – hyperresonant
• Auscultation – reduced breath sounds
Investigations to support diagnosis;
• Imaging – ultrasound, chest radiograph, CT
• Symptomatic pneumothoraces are often initially treated without further investigation
What is treatment of a Pneumothorax?
- May resolve spontaneously
- Tension pneumothorax- can be decompressed as an emergency procedure using a needle inserted via an intercostal space
- With open pneumothorax the penetrating chest wound causing it can be covered with an occlusive adhesive dressing that may incorporate a valve to allow air out but not in
- For any pneumothorax a chest drain tube can be inserted incorporating a valve to allow air out but not in while the pneumothorax resolves
- For recurrent pneumothoraces- pleurodesis considered
What are Pleural Neoplasms ?
Primary;
• Benign/ low grade malignant- uncommon/ rare e.g. low grade mesothelial tumours (cells lining pleural cavity)
• Malignant- e.g. malignant mesothelioma (common), others (uncommon/ rare)
Secondary Malignant;
• Carcinomas – breast, lung, others- common
• Others – lymphoma, melanoma, others
What is a Malignant Mesothelioma?
• Neoplasm of mesothelial cells that line serous cavities- pleura, peritoneum, pericardium, tunica vaginalis
• 92% pleural, 8% peritoneal
o Both commoner in men
o Peritoneal mesotheliomas affect a higher proportion of women, have a higher proportion of the low grade type & less strongly associated with asbestos exposure
• Tend not to metastasise widely
Mesothelioma- 17th most common cause of cancer deaths
In older people
Expecting to see a fall in the disease as asbestos banned
Low survival
What is a early Malignant Mesothelioma ?
- Breathlessness
- A small tumour can produce a large pleural effusion
- Tumour can be difficult to i.d. on imaging & so is difficult to target biopsies at it
- Can shed malignant cells into effusion so effusion cytology may allow early tissue diagnosis
What is an advanced Malignant Mesothelioma?
- If have biopsy- can go along needle tract to chest wall
- 1st spreads around lung
- Spreads into fissure
What is the Histology of a Malignant Mesothelioma ?
Malignant Mesothelioma Histology
• Mixed tubopapillary epithelioid & spindle cell sarcomatoid (soft tissue tumour) morphology
• Can be either type alone
• Can be poorly cellular- ‘desmoplatic’
• Main morphological differential diagnosis is malignant mesothelioma or non-small carcinoma
• In pic; tubules and solid aggregates of malignant mesothelial cells, morphological differential diagnosis is adenocarcinoma or epithelioid malignant mesothelioma
Malignant mesothelioma Immunostaining
• Uses antibodies linked to a dye to identify antigens is cells
• Mesothelial cells & epithelial cells express diff antigens- can be differentiated from each other
• There is some cross reaction therefore a panel of 4 or more antibodies is used
• Mesothelium-associated antigen stains in pics
o Top- cytoplasmic stain cytokeratin 5
o Middle- stained with Wilms tumour antigen
o Bottom- calretinin (stains cytoplasm & nucleus)
What are the causes of a Malignant Mesothelioma?
• Asbestos (80-90% of cases)
o Strong association with asbestos over general pop leve exposure but exposure can be quite low level
o Risk increases e.g. higher risk after 60 years than 15 years even if have same exposure
o Mesothelioma develops 15 years to over 60 years after exposure
o The risk increases with cumulative exposure level and time from exposure
o Is the background level safe? - Not certain but fairly safe
o Estimated 1 to 2 “spontaneous” cases per million persons per year
• Thoracic irradiation (theraputic)
• BAP1 (oncogene) (BRCA1- associated protein 1) mutations- germline mutations in a familial cancer syndrome with uveal melanomas and mesotheliomas
What is Asbestos?
• Fibrous metal silicates, 5-100μm x diameter 0.25-0.5μm
o Amphibole - blue asbestos (crocidolite), brown asbestos (amosite)
o Serpentine - white asbestos (chrysotile)
• When inhaled some become coated with mucopolysacharides containing iron- form asbestos bodies
• Can see asbestos bodies in tissue sections by light microscopy, brown when unstained or blue if iron is stained, and quantified – a cheap simple process
• Asbestos fibres can be quantified in lung extracts by electron microscopy – complex & expensive
Asbestos Use
• A fire-proof material in commercial & domestic buildings & in shipbuilding (1940s to the 1990s)
• 5.5 million tons of asbestos imported into the UK (1940-1998)
• Crocidolite & amosite imports banned in 1985 & all asbestos imports banned in 1999
• A lot is still in buildings- risk to those working in/near building maintenance & demolition processes
Asbestos caused about 5000 UK deaths in 2014
What is Asbestos Oncogenicity?
- Amphiboles particularly crocidolite- most oncogenic & persist in the lungs
- Chrysotile is less oncogenic and is more readily cleared from the lungs
- Erionite (fibrous zeolite mineral)- fibre struc similar to asbestos.
- Is used as a building material in areas of Cappadocia, Turkey- very high incidence of mesothelioma occurring in young people
Asbestos & Lung Carcinoma
• High level exposure to asbestos dust- independent risk factor for lung carcinomas of all types
• 2000-2500 UK carcinomas/yr mainly in men due to asbestos
• 5% of 46,403 cases diagnosed in 2014
• Lung carcinoma IS high exposure occupation in Gov Prescribed Occupational Disease
What is Asbestosis?
- Asbestosis- an usual interstitial pneumonia-like progressive pulmonary interstitial fibrosis caused by high level exposure to asbestos dust
- Fibrosis of alveolar walls impairs gas exchange & lung expansion & contraction during breathing
- Asbestosis associated with any occupation working with asbestos is a UK Gov Prescribed Occupational Disease that is eligible for Industrial Injuries Disablement Benefit
- Increasing in incidence & mortality
- 431 registered deaths in 2014,
- 985 new Industrial Injuries Disablement Benefit cases in 2014 & 1175 cases in 2015
Can see Asbestos corns – benign hyperkeratotic wart-like skin lesions
What are the Possible Causes of an Acute Sore Throat?
• History key points:
o Rapidity of onset of sore throat
o Difficulty breathing/speaking
o Ability to eat/drink/swallow
o Associated neck pain/swellings
o Symptoms of systemic infection e.g. fever, chills, rigors, general malaise
o Travel history
• Pharyngitis: inflamm of back of the throat (pharynx), resulting sore throat & fever (patient will say ‘I.ve got a sore throat’)= most common cause is viral
• Acute tonsillar pharyngitis: symmetrically inflamed tonsils and pharynx (+/- fever +/- headache) (Severe infec: patient has marked systemic symptoms of infec &/or unable to swallow).
• Consider infectious mononucleosis (EBV) (glandular fever): symmetrically inflamed tonsils/ soft palate inflamm & posterior cervical lymphadenopathy (don’t really need antibiotics)
• Suspect epiglottitis: sudden onset of severe sore throat, no inflammation of the tonsils and/or oropharynx & systemic symptoms/signs of infection- watch out for this, can make it worse when do throat exam!
What is the most common cause of a Sore Throat?
VIRUSES ACCOUNT FOR THE MOST COMMON SORE THROAT- EXAM Q!!! But in 1/3rd of ppl no cause can be found
What is are the causes of Pharyngitis & Tonsillar Pharyngitis?
VIRUSES ACCOUNT FOR THE MOST COMMON SORE THROAT- EXAM Q!!! But in 1/3rd of ppl no cause can be found
Common infectious causes;
• Viruses: Rhinovirus, Coronovirus, Parainfluenza, Influenza (A & B), Adenovirus etc. Viruses account for ~50% and are the most common cause of sore throat.
• Bacteria: Group A beta-haemolytic Streptococcus (GABHS) is the most common bacterial cause of sore throat. (15–30% of sore throats in children, and 10% in adults).
• Group A strep if in blood stream- life threatening
Rare causes:
• Neisseria gonorrhoeae (Gonococcal pharyngitis)- Gonorrhoae causes sore throat if infected in pharynx
• HIV-1 (can be the first presentation of HIV infection)
• Corynebacterium diphtheriae (Diptheria)
What is the Centor Criteria?
• Used by GP’s to clinically differentiate if something viral or bacterial
• Gives indication of likelihood sore throat a bacterial infec
• Criteria;
o Tonsillar exudate
o Tender anterior cervical lymphadenopathy
o Fever over 38°C
o Absence of cough
• If 3 or 4 of criteria met +ve predictor value 40-60% likely to have a bacterial infec
• Absence of 3 or 4 of criteria fairly high –ve predictive value of 80%- more likley to be viral
What are the investigations & management of a Acute sore throat?
• Outpatient/ambulatory investigation- usually clinical assessment no routine investigations unless infectious mononucleosis is suspected
• Inpatient (severe infec) investigation- (assume patient more unwell), Throat swab for culture, blood cultures, (blood tests: FBC, U&Es, liver function tests). If suspected infectious mononucleosis: blood sample for Monospot or EBV serology.
• Management;
o Oral analgesics (paracetamol, ibuprofen)- help bring temp down
o Most sore throats don’t need antibiotics as most NOT caused by bacteria, but if non severe acute tonsillar pharyngitis symptoms present for 1 week & getting worse may give antibiotics (non severe acute tonsillar pharyngitis if symptoms present for 1 week and getting worse)
What is Infectious Mononucleosis?
Infectious Mononucleosis/ Glandular Fever/ Kissing Disease
• Epstein-Barr virus (EBV)
• Teenagers. Often asymptomatic.
• Characterised by a triad of symptoms: fever, tonsillar pharyngitis, and cervical lymphadenopathy.
• Complications e.g. splenic rupture
• Avoid ampicillin (not an allergy, it reacts with EBV forming mac-pap rash)
• Blood for Monospot +/- EBV serology
What is Epiglottitis?
• Epiglottitis (supraglottitis): inflamm of strucs above glottis.
• Almost always caused by bacterial infec
• Haemophilus influenzae type b (Hib) was commonest cause in >90% of paediatric cases but Hib vaccine significantly reduced rate of Hib epiglottis. Still do see Hib cases in adults & rarely in children.
• Other causative organisms: Streptococcus pneumoniae & Group A Streptococcus.
• Investigations: Blood cultures & epiglottic swabs (examining throat may cause total airway obstruct- only do so when anaesthetic support present)
• Management: -
o Acute epiglottitis & associated upper airway obstruct- signif morbidity & mortality and may cause resp arrest & death within 24 hrs. Securing airway & oxygenation is a priority!
o IV antibiotics (usually 3rd generation cephalosporin)
o Analgesia
o Hib epiglottitis - Inform public health
o Secure airway & ensure patient has antibiotics
What is Otitis Externa?
• Ear canal- only skin-lined cul-de-sac in the body
• OE = inflammation of external ear canal presenting with a combination of: otalgia, pruritus and non mucoid ear discharge.
• Split into 2;
o Symptoms < 3/52 (less than 3 wks)= acute OE
o Symptoms >3/52 (over 3 wks)= chronic OE
• Risk factors; swimming (or other water exposure), trauma (e.g. ear scratching, cotton swabs), occlusive ear devices (e.g. hearing aids, ear phones), allergic contact dermatitis (e.g. due to shampoos, cosmetics) & dermatologic conditions (e.g. psoriasis).
• Pain, itchy ear
• Can have eczma & sirrhosis in ear canal- causes OE
What is Acute Otitis Externa?
• Acute OE range in severity mild/moderate/severe + necrotising (malignant) OE
• Unilateral
• 90% AOE bacterial (most common: Pseudomonas aeruginosa & Staphylococcus aureus), 2% fungal
• Chronic- bilateral
• Diagnosis: history & otoscopic examination
• Investigations: Ear swab or pus sample from ear for culture
• In necrotising otitis externa: CT temporal bone (& bone biopsy), blood cultures if systemically unwell
• Non-Antimicrobial Management;
o Remove/modify precipitating factors
o Remove pus and debris from ear canal (called ‘toileting’)
o Analgesia
• Antimicrobial management:
o Topical agents for mild-moderate
o Topical plus systemic antibiotic such as flucloxacillin for severe AOE
What is Malignant (Necrotising) External Otitis?
- Malignant (necrotising) external otitis- when external otitis spreads to skull base (soft tissue, cartilage, & bone of temporal region & skull).
- Can be life threatening
- Most commonly develops in elderly diabetic/ other immunocompromised patients
- Severe pain, otorrhoea, granulation tissue in canal floor, & cranial nerve palsies may be present.
- These patients should be promptly referred ENT
- Treat for a minimum of 6 weeks e.g. with iv ceftazidime then po ciprofloxacin
What is Chronic Otitis Externa?
- Symptoms over 3 wks
- Pruritus , mild discomfort, erythematous external canal that is usually devoid of wax.
- Often bilateral.
- White keratin debris may fill ear canal- over time canal wall skin thickens &narrows external ear canal
- A common cause- allergic contact dermatitis (e.g. from chemicals in cosmetics or shampoos)
- Generalised skin conditions e.g. atopic dermatitis or psoriasis can also predispose to chronic OE
- More likely to be caused by chemicals
- Treat underlying cause (often a skin condition)
What is Otitis Media?
- Middle ear inflamm (not canal)
- Pressure build up behind tympanic memb
- Fluid in middle ear
- V. common in children
- Uncomplicated acute OM is defined as: mild pain <72hrs duration & no severe systemic symptoms, with temp less than 39⁰C & no ear discharge
- Complicated acute OM defined as: severe pain, perforated eardrum &/or purulent discharge, bilateral infec, mastoiditis
- Organismsa: viruses, bacteria- streptococcus pneumoniae, Haemophilus influenza & Moraxella catarrhails
- Treatment: depending how severe e.g. if not too severe- GP can wash (but will need to follow up), if not unwell watch & treat symptomatically (analgesia, decongestant etc.) & review early. If unwell - amoxicillin
What is Mastoiditis?
- Infec spread to mastoid bone & air cells
- Most common AOM complication- incidence reduced if use antibiotics for OM
- Mastoiditis & other severe AOM complications of AOM rare in adults
- In <1 in 1000 children with untreated AOM
- Clinical features; fever, posterior ear pain &/or local erythema over mastoid bone, oedema of pinna, or a posteriorly & downward displaced auricle
- Always need CT scan
- Treatment: Analgesia, IV antibiotics +/- mastoidectomy
What is Pinna Cellulitis ?
- Pinna- bit on outside of ear
- Associated with trauma (including ear piercing & acupuncture), surgery or burns
- Perichondritis: complication of high ear piercing (puncture through cartilage of upper third of pinna)
- Swab area & blood cultures (if in secondary care) should be obtained prior to starting antibiotics
- Usual infective agent(s) in auricular perichondritis: Pseudomonas aeruginosa &/or Staphylococcus aureus
- Empirical treatment: ciprofloxacin + flucloxacillin (or vancomycin if penicillin allergy)
- Remove piercing & treat infec
What is Pneumonia? What are its anatomical patterns?
• Infec affecting the most distal airways & alveoli
• Formation of inflamm exudate
• 2 anatomical patterns;
o Bronchopneumonia- characteristic patchy distribution centred on inflamed bronchioles & bronchi then subsequent spread to surrounding alveoli
o Lobar pneumonia- affects a large part/ entirety of a lobe - 90% due to S.pneumoniae
What are the different types of Pneumonia?
• Community acquired pneumonia (CAP)
• Hospital acquired pneumonia (HAP)
o Pneumonia developing >48hrs after hospital admission
o Additional causative organisms to CAP, especially if >5days after admission: enterobacteriaceae
o In hospitals- have superbugs in env so have diff pop of organisms to think about , enterobacteriaceae (gut bacteria)
• Ventillator acquired pneumonia (VAP)
o Subgroup of hospital acquired
o Pneumonia developing >48hrs after ET intubation & ventilation
o Pseudomonas spp. may be implicated
o Some people have strep pnumoniae in their throat normally so if put a tube down will push this bacteria into lungs
• Aspiration pneumonia- e.g. in stroke patient
o Pneumonia resulting from abnormal entry of fluids e.g. food, drinks, stomach contents, etc. into lower resp tract
o Patient usually has impaired swallow mechanism
o Anaerobes may be implicated
What is Community Acquired Pneumonia?
Community Acquired Pneumonia (CAP) • Do HIV test in someone that presents with this- could be HIV presentation • From env- legionella pneumonia Epidemiology • Incidence: 1 per 1000 ppl/yr (common!) • 20-40% cases need hospital admission • Peak age 50-70 yrs • Peak onset midwinter- early spring • Acquisition of organisms; o Person-to-person or from a person’s existing commensals (S.pneumoniae, H.influenzae) o From the environment (L. pneumophilia) o From animals (C.psittaci)
What are the Causative Organisms of Community Acquired Pneumonia?
see table of typical and atypical bacteria.
Causative Organisms: CAP
• Bacterial causes often divided into ‘typical’ & ‘atypical’
• Aytypical pneumonia- described cases and no organism could be identified which failed to respond to penicillin (organisms with atypical or no cell wall))- caused by atypical organisms (clinical presentation & treatment slightly diff)
• Atypical- didn’t respond to penicllin, no causative organism found, now think of atypical pneumonia as if present unwell e.g. ; malaise, headache, diarrhoea (not as easy to identify)
What is the CURB score?
CRURB 65 score- for severity of Pneumonia
Confusion: No 0 Yes+1
Urea : > 7 mmol/L
Respiratory Rate ≥ 30 No 0 Yes+1
Systolic BP < 90 mmHg or Diastolic BP ≤ 60 mmHg
No0 Yes+1
Age ≥ 65
0/1=low 2 moderate 3-5= high severity§
What are the Investigations for Inpatients with Community Acquired Pneumonia?
• Chest x-ray- may be clinically resolve but chest x-ray findings take longer to resolve (up to 6wks +)
• Legionella- affected liver tests
• Recommended for all moderate- severe CAP based on CURB65 score >2;
o Sputum culture
o Blood culture
o Pneumococcal urinary antigen
o Legionella urinary antigen
o PCR or serology for:
Viral pathogens e.g. influenza (PCR of respiratory samples)
Mycoplasma pneumoniae (PCR of respiratory samples preferable, complement fixation: interpret with caution)
Chlamydophila sp. (complement fixation test most widely available – on blood)
What is the Management of CAP/HAP/VAP & Aspiration Pneumonia?
With any unwell/ septic patient;
• A= airway- ensure open, patent & maintained airway
• B= breathing- assess resp rate & saturations, provide supplemental oxygen to reach prescribed target
• C= circulation- assess BP & heart rate, gain iV access & give IV fluids if haemodynamically unstable, urinary catheter (monitor urine output)
Then PROMPT empirical antibiotic therapy
What are the complications of Pneumonia ?
• 3-5% Pleural effusion: – clear fluid +/- pus cells +/-organisms
• 1% Empyema: pus in the pleural space (-loculated)
• Lung abscess: – suppuration + destruction of lung parenchyma
o Single (aspiration) anaerobes, Pseudomonas
o Multiple (metastatic) Staphylococcus aureus
What is Influenza?
• Usually influenza causes uncomplicated disease; fever, headache, myalgia, dry cough/ clear sputum, sore throat- convalescence takes 2-3wks
• Primary viral pneumonia- more commonly in patients with pre-existing cardiac & lung disorders ;
o Cough, breathlessness, cyanosis
o 2ndry bacterial pneumonia then may develop after initial period of improvement- S.pneumoniae, H.influenzae, S.aureus
• Complication; 2ndry bacterial pneumonia
• Swab- test this for influenza
• Diagnosis: viral antigen detection in resp samples using PCR
What is VZV pneumonia?
- Complication of VZV (chicken pox) infec
- Rare in children, signif morbidity & mortality in adults with varicella
- Those at greatest risk; immunocompromised, adults with chronic lung disease, smokers & pregnant women (preg women not more at risk of getting virus but is more severe when they do get it (need supportive care; oxygen, fluids then give acyclovir))
- Insidious onset 1-6 days after rash with symptoms of progressive tachypnoea, dyspnoea & dry cough.
- Tests: Chest X-ray typically reveals diffuse bilateral infiltrates
- Treatment: Supportive & prompt administration of IV acyclovir
What is Rhinovirus?
- Responsible for most common colds
- Can cause LRTI & trigger exacerbations of asthma
- Tests: PCR on NPA/throat swab
- Treatment: supportive
What is CMV pneumonia?
- Rarely in immunocompetent hosts
- Can cause severe illness in transplant recipients & HIV patients (uncommon)
- Tests: Chest-Xray, Broncho-alveolar lavage (can put a scope down & get fluid from alveolus) & viral load PCR
- Treatment: supportive, anti-viral (e.g. ganciclovir) &; consider immunosuppression reduc (transplant pts).
What is a LRTI with Bronchiectasis?
• Acquired disorder of major bronchi & bronchioles- permanent abnormal dilatation & destruction of bronchial walls
• Chronic cough, mucopurulent sputum production & recurrent infecs (e.g. S.aureus, H.influenzea, Pseudomonas aeruginosa, viruses).
• Exacerbation investigations: SpO2, CXR, FBC, U&Es, LFTs, CRP, review previous sputum culture
• Antibiotics recommended for exacerbations with acute deterioration with worsening symptoms
• Non-Antimicrobial Management;
o Effective clearance of respiratory secretions e.g. physiotherapy, postural drainage
o Nutritional support
o Identification and treatment of underlying cause - Annual influenza vaccination
What is a LRTI with Cystic Fibrosis?
• CF- inherited disease caused by a genetic mutation on chromosome 7 causing abnormal produc & function of cystic fibrosis transmembrane conductance regulator (CFTR).
• Defective CFTR chloride channel function results in viscous secretions.
• Colonising organisms & resistance change over time:
o Staphylococcus aureus in childhood
o Pseudomonas aeruginosa in childhood/early adolescence (attempts will be made to eradicate)
o Burkholderia cepacia complex: very resistant & transmissible (need to avoid this in CF patients!)
o Non tuberculous mycobacteria & Fungi
• Acute exacerbations:
o Use most recent sputum culture results to guide treatment (often infected with normal flora)
o Prolonged antibiotic courses (3-4 weeks not uncommon)
o General measures: postural drainage, deep breathing, coughing, exercise, aerosolised DNAase etc+ Influenza and Pneumococcal vaccinations. Lung transplant.
• Colonising Organisms & resistance change over time- treated by diff antibiotics
What is the Prevention of LRTIs?
• Pneumococcal vaccination (S. pneumoniae);
o Patients with chronic heart, lung and kidney disease
o Patients with splenectomy
o Infant vaccination schedule
o May repeat after 5 years in certain populations
• Influenza vaccination for vulnerable groups (annually); 2- 17 year olds, Over 65s, chronic disease, multiple comorbidities
What is Aspergillosis?
- Immunocompromised- will get infec
- Aspergillosis is an infec caused by Aspergillus (mold- type of fungus) that lives indoors & outdoors
- Most people breathe in Aspergillus spores every day without getting sick
- Immunocompromised patients & those with lung disease at a higher risk of developing health probs due to Aspergillus
- Types of health problems caused by Aspergillus; allergic reacs, lung infecs, and infecs in other organs
What is Allergic Bronchopulmonary Aspergillosis?
- In people with a background of atopy, asthma & cystic fibrosis
- Presents with worsening asthma & lung function
- Diagnostic features; high total IgE, specific IgE to Aspergillus & positive serum IgG to Aspergillus
- CT imaging of the thorax may demonstrate central bronchiectasis
- Treatment: corticosteroids and antifungal therapy
What is Aspergilloma (pulmonary)?
- Compilation: massive haemotyptysis (blood loss if it goes through one of their vessels)
- Mobile mass (of Aspergillus) within a pre-exisiting lung cavity
- Old cavities left by previous TB or sarcoidosis become colonised with Aspergillusspp.
- Symptoms: cough, haemoptysis, weight loss, wheeze & clubbing. Some asymptomatic.
- Can be demonstrated on chest X-ray or CT thorax.
- Diagnosis can be confirmed by a positive test for Aspergillus IgG antibody
- Sputum culture may be positive for Aspergillusspp
- Complication: Massive haemoptysis
- Treatment: 10% cases resolve spontaneously, surgical resection, antifungals (injected into the cavity, or orally for symptom relief).
What is Pneumocystitis jiroveci pneumonia?
- Disease of immunosuppression e.g. in HIV patients
- Is a fungus but no ergosterol in its cell wall & not susceptible to a number of antifungals.
- Ubiquitous in the env
- Transmission: airborne route
- Pneumonia: insidious onset of fever, dyspnoea, non-productive cough & reduced exercise tolerance.
- Exercise induced hypoxia (shortness of breath on exercise)
- Specimens: rarely isolated from expectorated sputum, can be found in induced sputum, broncho-alveolar lavage increases the diagnostic rate.
- PCR to detect P.jiroveci DNA overtaken immunofluorescence techniques.
- Supportive care, antimicrobials (including co-trimoxazole) and steroids.
- Some at risk groups including HIV-infected patient with a CD4 count
What is Nocardia Asteroides?
- Genus of bacteria found in env
- Pulmonary nocardiasis acquired via inhalation of organism
- More common in immunosuppressed & those with pre-exisiting lung disease (esp. alveolar proteinosis)- but still rare
- Presentation & clinical;/ radiological findings variable- diagnosis difficult
- Lung abscesses can develop
- Suitable specimens; sputum, or broncho-alveolar lavage or biopsy
- Treatment: as with all pneumonic infections supportive Rx (ABC) & then antibiotics (several months). Co-trimoxazole most commonly used.
What is Mycobacterium Tuberculosis?
- Latent disease- interferon gamma
- Infects 1/3 of the world’s pop (most frequent infectious cause of death worldwide)
- Most cases occur in developing world (not limited to there)
- Infec acquired by inhalation of infected resp droplets, bacilli lodge in alveoli & multiply- formation of a Ghon focus
- Depending on host’s immune response infec either become quiescent or progress &/or disseminate
- 90% of primary infections are asymptomatic
- Risk of disease progression highest at extremes of age & in immunocompromised (inc. HIV)
- Reactivation of disease may occur later in life, particularly in the immunocompromised
- Pulmonary TB most common; chronic productive cough, haemoptysis, weight loss, fever, night sweats
- Can disseminate (milary TB) or affect almost any other organ
- Diagnosis: clinical features + supportive radiology + detection of acid-fast bacilli or culture of M. tuberculosis from clinical specimens (usually sputum).
- PCR-based tests may be used to detect MTB in clinical specimens.
- Interferon gamma release assays (IGRA) +/- Tuberculin skin test – Mantoux can be used (do not differentiate active from latent disease)
- Treatment: combined chemotherapy for several months (usually 6/12)
- Notifiable disease & contact tracing
- Prevention: BCG given to infants & children in high prevalence areas (or parents & grandparents from high prevalence area)
