Respiratory pathology Flashcards
Symptoms of lung cancer
- Haemoptysis
- cough
- dyspnoea
- chest/shoulder pain
- finger clubbing
- weight loss
- hoarseness
- recurrent infections
- –> if more than 3 weeks –> imaging
Often symptoms only long after a tumor developed
Tumor staging
TNM
T= Tumor
- Size (<1cm = T1, > 3mm =T2)etc.
- Location: Invasion of surrounding tissue (chest wall, heart), compromising of major vessels (aorta, vena cava)
N= Lymph Nodes
- No invasion of lymph nodes
- Invasion of lymph nodes
M= Metastasis
- No metastases,
- Mentalities
Pathogenesis of lung cancer (brief summary) + riks factors
- inactivation of tumor suppressor genes (p53, box (cofactor fo p53)
- activation of oncogenes
–> Smoking, Radiation, Asbestos and genetics are risk factors that influence pathogenesis (turn of tumor suppressor genes, activate oncogenes)
Way of imaging/diagnosis in Lung cancer
- Chest X Ray: Shaddows in lung can be seen –> if abnormal:
- Chest CT(sometimes: –> trans-thoracic CT Biopsy –> biopsy via needle, CT lead
- Bronchoscopy/Endoscopy –> tumor can be seen + probe can be taken for further diagnosis
3b: Endobronchial ultrasound
PET scan –> highly metabolic active tissues: marked glucose in scan (tumor = highly active)(additional testing required)
–> Always attempt to do diagnosis and staging together (e.g. via biopsy from lymph node)
Paraneoplastic syndrome
Systemic effects of the tumor due to abnormal expression of things
–> would not normally be expressed by this tissue
- Endocrine–> Hormones expressed by tumor tissue e.g. Syndrome of inappropriate ADH –> hyponatremia (small cell carcinomas)
- Non-endocrine e.g. factors –> coagulation defect
Local and systemic complications of lung tumors
Local
Problems with breathing, pain
local invasion and obstruction of tissues–> esophagus, pericardium, pleura, chest wall, branch, airway, major vessels
Systemic:
Spread of metastases
Paraneoplastic syndrome
In which two big groups are Lung cancers classified (+ most important characteristics)
Most are carcinomas
- Non-small cell carcinomas (+3 subtypes)
less agressive, slowlier devinding
- Small cell carcinomas
very agressive, rapid deviding
What are the subclassifications of Non-small cell Carcinomas? (without characteristics) + What is treatment and prognosis
- Squamous cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
Often surgery possible, less chemosensitive
Prognosis: Early stage 60% 5Y survival
Late Stage: 5% 5Y survival
Squamous cell carcinoma
sub-type of non-small cell carcinoma
smoking –> irritation of epithelium –> metaplasia to more resistant epithelium –> Malignant tumor
often central (bronchial epithelium but recently: also peripheral)
local spread, late metastasis
Adenocarcinoma
peripheral, terminal airways and multicentric
more common in female, far east and non-smokers
often EGFR mutation (–> possible target with tyrosine kinase inhibitors) + ALK mutation(young patients)
Large cell carcinomas
uncommon
large cells, poorly differentiated
poor prognosis
Small cell carcinomas
- central, near bronchi
- smoking
- late diagnosis –> 80% w advanced disease
Treatment: Chemotherapy and radiotherapy (–> very responsive)
Prognosis 2-4 month untreated, 10-20 month treated
–> often paraneoplastic effects
Allergy
exaggerated immunological response to a foreign substance (allergen) which is either inhaled, swallowed, injected, or comes in contact with skin/eye.
o Allergy is a MECHANISM, not a disease.
Hypersensitivity
exaggerated response.
Intolerance
(Non-immunological hypersensitivity)
inability to consume or absorb/metabolize nutrients.
Atopy
Atopy – the genetic tendency to develop allergic diseases.
How do hypersensitivity, allergy, atopy and intolerance relate?
What is neurophysiology?
When CNS creates a sensory impression
What is behavioral psychology?
Interpretation of sensory information by the brain leading to sensation
Why do we cough? (causes of cough)
- defense mechanism
- additional to mucociliary clearing
- expulsive phase of cough –> high-velocity air flow
Where are cough receptors located?
within airway epithelium
the posterior wall of the trachea
pharynx
larynx
What kind of sensory receptors in the lung are there?
What are their characteristics?
Where are they located?
1. C-fibre receptor
- –Larynx, trachea, bronchi, lungs
- “free” nerve endings
- release signals after chemical stimulation
2. Rapidly adapting stretch receptors
- nasopharynx, larynx, trachea, bronchi,
- small, myelinated fibers
- Mechanical, chemical irritant stimuli, inflammatory mediators
3. Slowly adapting stretch receptors
- airway SM
- Mechanoreceptor –> respond to inflation
Which nerve do all sensory receptor of the lung and airway pass through?
Vagus nerve (X)
Afferent neural pathway for cough
Efferent neural pahtway for cough
What are the three main phases of cough?
- inspiratory phase
- Glottic closure
- Expiratory phase
How long is acute cough?
What is a typical cause?
less than 3w
Most typical cause is a common cold
When can you speak of chronic cough?
What are the 4 most common reasons?
Persistent cough longer than 3weeks
- Asthma and eosinophilic-associated (25%)
- Gastro-oesophageal reflux (25%)
- Rhinosinusitis (postnasal drip) (20%)
- Idiopathic (10%)
Chronic hypersensitivity syndrome –> increased sensitivity of cough receptors
What is emphysema?
Damage start in centre of alveoli sac
–> Destruction –> Try to repair with fibrotic tissue –>Emphysema (holes in lung tissue)
How does alveolar fibrosis occur?
- Type II cells divide in an attempt to repair but they don’t differentiate into Type I cells
- Fibroblast increase collagen production and
- Signal Type II cells not to differentiate into Type I cells
Which local effects does lung cancer have?
It can invate lung tissue and adjacent structures
–> e.g. CVS system
Which systemic effects can lung cancer have?
Metastasis can spread distantly
Paraneoplastic effecty –> Effects of hormones that are not meant to be expressed by that tissue
Endocrine: Hormones e.g. ADH in small cell carcinoma
Non-endocrine: coagulation
Which risk factors are associated with pneumonia?
Age (young and old)
Smoking
Excess alcohol consumption
How can you decide, wheater you would admit someone with pneumonia to the hospital or not?
Which factors influence, wheater pneumonia/ lung infection has a severe or a mild outcome?
What causes severe flu (over a mild form)?
- Highly pathogenic strains (zoonotic)
- Absence of prior immunity
Innate immunodeficiency (e.g. IFITM3 gene variant)
B cells (antibody- presumably local)
T cells (correlate with peripheral levels?)
- Predisposing illness/conditions
Frail elderly
COPD/asthma
Diabetes, obesity, pregnancy etc.
How does influenza influence Pneumonia?
An influenza infection predisposes to an bacterial pneumonia
Which nerves sense pain in the respiratory apparatus?
Where do they senses it from?
Trigeminal from Nose
Vagus senses most pain from nose, pharynx, larynx (very little) lung
Spinal nerves –> chest wall
How would you treat breathlessness?
If possible: Treatment of the course:
But if not:
- Bronchodilators
- suppression of breathing center
- Lun resection
- pulmonary rehabilitation (increase wellbeing, fitness etc.)
What are the three pathogens, that are responsible for most hospital-aquired pneumonias?
- Staphylococcus aureus(28%)
- Pseudomonas aeruginosa(21.8%)
- Klebsiella species(9.8%)
Which pathogens cause the most Community-aquired pneumonias?
What is special about this?
Most of the times not a single pathogen responsible but many infections leading to pneumonia:
- Strep. Pneumoniae
- Myxoplasmapneumoniae
- Staph. Aureus
- Chlamydophilapneumoniae
- Haemophilus influenzae
What is an atypical pneumonia?
What is its significance?
Atypical pathogens in pneumonia
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Legionella pneumophilia
Atypical bacteria are not covered by penicillinsand requireadditional agents (e.g. macrolides).
How could you diagnose a pneumonia?
- Acute lower respiratory tract symptoms
- New focal chest signs and, if in hospital, new CXR changes
- >1 systemic feature (fever, shivers, aches and pains, temperature >380C)
- No other explanation for illness
When should someone who is suspected to have a pneumonia be admitted to hospital?
How should pneumonia be treted?
- Antibiotics –> as fast as possible
- O2 (for hypoxia)
- Fluid (for dehydration)
- Analgesia (for pain)
How would a child with RS V (respiratory syncytial virus) present?
Who is at risk of RSV infection?
RSV= respiratory syncytial virus
Children
Elderly: might lead to winter death
What might be the consequence of a viral infection regarding pneumonia?
Sometimes a viral infection may make it easier for bacterial pneumonia to show up
–> virus weakens immune system and make tissue more prospone to infection
Is Allergy a disease?
No, it is a mechanism (immunological hypersenstitivity), not a disease
Explain the development of seasonal allergic rhinitis
- Sensation of Antigen –> First exposure
- Hypersensitivity + exaggerated resonse to antigen at 2nd contact –> Increased IL-4, IL-5, Eosinophils
What are teh immediate and late response cells that are involved in allergy?
Immediate: Mast cells and Basophils
Late response: Eosinophils
How can you treat seasonal allergic rhinitis?
What are the common causes/triggers for allergic asthma or rhinitis?
Pollen but also:
How does Allergy and Atopy relate to one another?
You can be atopic = have IgE against different things but don’t have to be allergic (no allergic response triggered)
Which cells are important in medating Atopic responses?
Th2 cells are important (–> secrete L4,L5,L13, Eosinophils)
Which airways are affected by astma?
It is basically an allergic response in the lower airways
What is the main immunological cell associated with asthma?
Eosinophils (but there are different types)
What are the advantages and disadvantages of Immunotherapy in alltergy?
Advantages
- Effective
- Produces long lasting immunity
Disadvantages
- Occasional severe allergic reaction
- Time consuming
- Standardisation problems
Summarise the steps in treatment of an allergic airway disease
- Avoid Allergen
- Anti-allergic medication
- Anti-histamines
- Nasal Steroids
- Allergen-specific immunotherapy
- subcutanous
- sublingual
Summarise the mechanism of action of immunotherapy on allergic airway disease
- Dendritic cells produce other mediators –> Has several effects
- Shift from Th2 to Th1 response
- Treg cells expressed (regulate and secrete IL-35)
- IL-35 induces IL-10 release which has many functions:
What is Extrinsic allergic alveolitis?
Explain its mechanism
small antigens get immunologically activated in alveoli
–> Triggers different immunological activation
e.g. Farmers lung etc.
What happens when there are cilia mutations in the airway?
No mucus clearing: often cilia can’t move
–> more prone to severe infections and respiratory failure
Which cartilage defects can occur in lung development?
What are their effects?
- Complete, round cartilage –> Narrowing of airway, might be so narrow that ventilation required
- Malacic “floppy” cartilage –> airway collaps very easily –> respiratory distress
What is agenesis of a lung?
Complete absence of a lung –> no lung or vessels
What is aplasia of a lung?
Blind ending bronchus –> no lungs or vessels (but still bronchus)
What is a hypoplasia in lung development?
Why does this occur
- Bronchi and rudimentary lung are present but
- Reduced size and number
Because of reduced space in the pulmonary cavity (e.g. diaphragmatic cysts, heart defects etc.)
What is Cystic Pulmonary Airway Malformation
CPAM?
abnormal differentiation of tissue caulses multiple small cysts
–> often several recurrent pneumonias and infections
What is an Intralobar Sequestration?
Segments of lung have normal blood supply but no ventilation in segments
–> can get infected
What is
Congenital Lobar Emphysema
Congenital Large HyperlucentLobe (CLHL)
- Progressive lobar overexpansion (one lobe too big, compresses everything around in pleural cavity)
- Underlying cause
- –Weak cartilage
- –Extrinsic compression
- –One way valve effect
- –Alveoli expand (not disrupted)
What level of the respiratory tract is affected by COPD?
Which condition does it affect?
Bronchi: Chronic bronchitis
Small airway (<2mm): Small airway fibrosis
Emphysema: Alveoli
What happens to the structure of the lung during emphysema?
Break down of elastic tissue part of alveoli —> Damage of alveoli (increased air space, decreased tissue (often also by oxidantsn metalloproteases)
Why do the small airways collapse, become obstructed and stenosed in COPD?
Which signal/factor is involved in this?
Because of small airway fibrosis
–> not functional repair of small chronic inflammation
What are the changes in epithelial cell profile and secretions during bronchitis?
- Hypersecretion of mucus
- More goblet cells
- more squamous endothelium
- hypertrophy of submucosal glands
Why would a protease inhibitor help treat COPD?
It would
- reduce inflammation and activation of goblet cells (Chronic bronchitis)
- stop the formation of new emphysema
- stop some of the repair process (by reduction of Signaling molecules) (fibrosis of small airway)
Why don’t endogenous inhibitors /regulatory proteases work in the regulation of COPD?
Because they are broken down by metalloproteases
Which substances to Neutrophils and Macrophages secrete that are important in the formation of COPD?
What are its effects?
Neutrophils: Elsastases
Macrophages: Metalloproteases + Oxidants
–> Lead to inflammation, emphysema, and triggering of repair mechanism leading to fibrosis
Which nerve supplies the larynx and the vocal cords?
Superior Laryngeal Nerve
