what is emphysema?
destruction of airspaces distal to the terminal bronchioles = resulting in irreversible enlargement
what is centriacinar emphysema?
most common formrespiratory bronchioles are affected but the distal alveoli remain normal
what is the morphology of centriacinar emphysema
holes = seen in lung parenchyma = represent amphysematous air spaces (dilated bronchioles)
why do the holes appear black?
carbon pigment deposited from tar produced in smokers
are all alveoli destroyed?
no normal alveoli exist between ares of emphysema
explain how cigarette smoke causes emphysema
smoke produces oxidants causing accumulation of inflammatory cells in lungsoxidants and proteases released from inflammatory cells destroy elastic tissue in walls of air spacessmoking also impairs naturally occuring anti-protease
what are the main proteases, inflammatory cells and anti-proteases involved in this?
protease = elastaseinflam cells = neutrophilsprotease inhibitor = alpha-1 antitrypsin
what is the function of the elastic fibres and what does damage to them cause?
normal = during expiration, elastic fibres help prevent complete collapse of airways = helps air get outdestruction of them....increased mucusincreased fibrosislarger smooth muscle = to try force air outwhen air is ready to come out = collapse of vessels = leads to hyperinflation/air trapping ing the chest
Why are emphysema patients referred to as "pink puffers"?
airway collapses during expiration => patients purse their lips to prevent this from happening
why do emphysema patients develop dyspnea
difficulty breathing
is it normal for emphysema patients to have chornic bronchitis as well?
yes since both are caused by smoking
what makes an emphysema x-ray different
hyperinflated chest- flattened diaphragm- inflation of apex above clavicle- horizontal ribs = can't exhale properly- decreased bronchovascular lung markings (thread shadow of bronchial and vascular trees in normal lung)- overtaking of heart shadow by opacity of hyperinflated lungs
What is sputum?
mucus coughed up
what is chronic bronchitis defined as?
defined as persistent cough with sputum production
what is prominent in patient bronchi?
mucus hypersecretion, inflammation, recurrent infections and fibrosis
why are they called blue bloaters
patients become hypoxemic and cyanosed = oxygen deficiencyedema from right side o the heart failure potentially
what is the gross morphology of chronic bronchitis
lots of red inflammationmucus plugs within lumen of bronchusmooth muscle hypertrpohy from coughing
what is the pathogenesis of chronic bronchitis?
cigarette smoke triggers chronic inflammation in bronchi and bronchiolesinflammatory mediators and growth factors released => causes bronchial wall to undergo metaplasia and mucus gland hypertorphy and phyperplasia
what cells undergo metaplasia
surface lining epithelium change into goblet cells
what happens to the mucus secreting glands in submucosa?
hypertrophy and hyperplasia
what does this result in
mucus hypersecretion = protective measure against smokeeventually causes airway obstruction
what happens to the cilia?
smoke interferes with the movement of cilia = preventing clearance of mucus and infective organisms
what does perpetuate mean
to make permanent or long lasting
what does mucus obstruction perpetuate?
infection and chronic bronchitis
how does impaired phagocytosis occur in chronic bronchitis?
macrophages in alveoli are overwhelmed with bacteria and apoptotic cellsleads to increased bacterial colony and apoptotic bodies
what are the main differences between emphysema and bronchitis
...
what is the main risk factor for lung cancer
smoking
what is the pathogenesis of lung cancer
tobacco smoke:contains >70 casrcinogens = these cause mutations int he DNAif they cause mutations in oncogenes ad tumour suppression genes = carcinogenesis
what is carcinogenesis
process by which normal cells are transformed into cancer cells
explain the molecular pathogenesis of adenocarcinoma
tumour that forms glands and produces mucingain of function = oncogenes = EGFR and KRAS
what is mucin
a glycoprotein constituent of mucus
how common is adenocarcinomas?
40-50% patientsBUT least common in smokersmost cancers in non-smokers are adenocarcinomas
explain the molecular pathogenesis of squamous cell carcinoma
high frequency of loss function tumour suppresion genes = p53 + RB (fewer)
how common is squamous cell carcinoma
20-25% cases
explain the molecular pathogenesis of small cell carcinoma
highly malignantmutations of p53 and BCL2 (anti-apoptotic gene)i.e. tumour suppresion and a gene that prevents apoptotic bodies
which carcinomas have the strongest association with smoking
small cellsquamousthen adenocarcinomas
where do small-cell carcinomas come from?
neuroendocrine cellsin bronchial tree
where do squamous cell carcinomas come from?
basal cells in bronchial tree
Where do adenocarcinomas arise from?
type 2 alveolar cells in alveoli
explain how dysplasia is caused and how it can lead to a carcinoma in situ
#NAME?
what is it called when it invades basement membrane
invasive carcinoma
explain the morphology of normal tissue to adenocarcinoma
normal = large spacesatypical adenomatous hyperplasia = thickening of alveolar wallsadenocarcinoma in situ = cells are dysplastic but localisedlung carcinoma = extensive growth and invasion into surrounding tissue and gland formation
what happens in squamous cell carcinoma?
squamous metaplasia of bronchial epitheliumpseudostratified turns into squamous
explain the process of this occuring
goblet cell hyperplasiabasal cell hyperplasiasquamous metaplasiasquamous dysplasiacarcinoma in situinvasive squamous carcinoma
what do tumour cells look like in small cell carcinoma?
smallvery little cytoplasmdark nucleifinely granulated chromatin
what does the gross morphology of lung carcinoma look like
appears gray-whitetumour = firm consistencyblack pigmentsareas of hemorrhage or tissue necrosis within tissue
where can the tumours be located
in bronchi = squamous or small cellor peripheral under pleura
what are presenting symptoms of lung cancer
Non-specific (cough, weight loss, hemoptysis, postobstructive pneumonia)
what is a tissue biopsy of bronchial wall
lesion of bronchial wall by flexible bronchoscope
what is a cytology sample?
exfoliated or aspirated cells = not piece of tissue
how can lung cancer be treated?
Small cell: chemotherapy, radiation - usually metastatic at diagnosis = surgey cannot be perforemed. initially sensitive to radiation by it always relapsesNon-small cell (adeno + squamous) chemotherapy, radiation, surgery, laser therapy or stenting (for airway lesions)