PATH 201 - LECTURE 11

where are the more severe respiratory diseases seen

in the lower respriatory tract

what makes up the lower respiratory tract

trachea

primary bronchi

lungs

what are the 3 main etiologies of common lung pathology’s

• inhalation of toxic smoke

• inhalation of infectious agents

• inhalation of allergens

what are some examples of toxic smoke/noxious agents that are inhaled and commonly cause lung pathologies

• tobacco smoke

• asbestos

• dust

• silica

• coal

what are the common lung pathologies that are caused by inhalation of toxic substance

• chronic bronchitis

• emphysema

• lung cancer

what are some examples of infectious agents that cause common lung pathologies

bacteria

virus

what are some examples of common lung pathologies caused by inhalation of infectious agents

• tubercolosis

• pneumonia

• influenza

what is an example of pathology due to inhalation of allergens

asthma

what pathologies fall under chronic obstructive pulmonary disease (COPD)

• emphysema

• chronic bronchitis

• they often coexist

what is emphysema

• the destruction of the airspace distal to the terminal bronchioles which results in irreversible enlargment

what causes emphysema

causes due to tobacco smoke and the toxins within it breaking down the elastin fibres in the membranes that allow the lungs to expand and contract

what is the most common form of emphysema

centriacinar emphysema

describe centriacinar emphsyema

• Respiratory bronchioles are dilated but the distal alveoli remain normal

what is parynchema

lung tissue

what are emphysematous air spaces

dilated respiratory bronchioles

what is anthracosis

• holes in the lung parenchyma filled with carbon pigment deposisition due to the tar in cigarrette appear black

what does a centriacinar pattern mean

• nromal alveoli exist between areas of emphysema

how does cigarrette smoke cause emphysema

• cigarrete smoking produces oxidants whcihc cause accumulation of inflammatory cells

• inflammatory cells release oxidants and proteases which destroy the elastic tissue in the walls of airspace

• smoking also impairs the acitivty of the antiprotease

what is the naturally occuring antiprotease in lungs that is inhibited by smoking

• alpha 1 antitrypsin

what are the main inflammatory cells seen with cigarrete smoke

neutrophils

what are the main proteases released by inflammatory cells that cause emphysema

elastases

why do patients with emphysema have expanded chests

• elastin not only allows for stretching, but it keeps the airways patent when we exhale

• without it, airways collapse and air gets trapped

• trapped air = expanded chest

what is wrong here

• emphysema

• flattened diaphragm

• inflaltion of the apex above the clav

• ribs horizontal

• decreased bronchovascular markings

why do people with emphysema purse their lips

• to prevent airways collapsing during exhalation

what is barrel chest

• hyperinflated chest due to trapped air

what do most patients with emphysema also have

some degree of chronic bronchitis since they are both caused by some degree of smoking

how is chronic bronchitis clinically defined

• persistent cough with sputum production for east 3 months in atleast 2 consecutive years

what are the symptoms of bronchitis

• mucus hypersecretion

• inflammation

• recurrent infections

• fibrosis

what eventually happens to patients with chronic bronchitis

• hypoxemia + cyanoses

• edema from right heart failure

describe the pathogenesis of chronic bronchitis

• cigarrette smoke triggers constant inflammation (chronic)

• inflammatory mediators and growth factors change the composition of the bronchus

• this results in mucus hypersecretion which causes airway obstruction

• movement of cillia is also affected; mucus cannot be cleared

describe the changes in the bronchus wall due to chronic inflammation (chronic bronchitis)

• metaplasia of the surface lining > more goblet cells

• hypertrophy and hyperplasia of mucus secreting glands in the submucosa > bigger more active glands

what causes fibrosis due to chronic bronchitis

• excess mucus causes blockages which means more infections

• more inflammation

• leads to fibrosis

describe impaired phagocytosis as a consequence of chronic bronchitis

• alveolar macrophages start to change their activity

• no longer able to effectivley phaocytose bacteria and apoptopic cells

• leads to further inflammation>repeat cycle

describe the pathogenesis of lung cancer (from cigarrete smoke)

• tobacco smoke contains carcingoens that cause DNA mutations that accumulate

• and then induce an inflammtory response

what genes do mutations that cause cancer affect

• oncogenes and tumour suppressor genes

what can accumulation of mutations in oncogenes and tumour suppressor genes lead to

• dysplasia and carcinogenesis

what is carcinogenesis

process by which normal cells turn into cancer cells

what does the inflammatory response induced by tobacco smoke that leads to cancer contribute to

• tumour growth

• immune system suprpession

what are the microscopic variants of lung cancer

adenocarcinoma

squamous cell carcinoma

small cell carcinoma

large cell carcinoma (others)

which microscopic lung cancer variant is most strongly assoicated with smoking

small cell carcinoma

which microscopic lung cancer variant is least assoicated with smoking

adenocarcinoma

which microscopic lung cancer variant occurs most commonly in women

• adenocarcinoma

what differs between the microscopic lung cancer variants

• the cell of origin

where is adenocarcinoma normally seen (in the lungs)

in the respiratory airway in type II alveolar cells

where does small cell carcinoma normally seen/originated

in th conducting airways in neuroendocrine cells

where is squamous cell carcinoma normally seen/originates

• in the conducting airways in basal cells

what is dysplasia

• Normal cells begin to change in type and number and then we see disordered growth - dysplasia

• this is normally driven by genetic mutations due to the carcinogens in tobacco smoke as well as other things

what is carcinoma in situ

• when the entire thickness of an epithelium is dysplastic but not yet invaded the basement memrbane

describe the morphology of adenocarcinoma

• tumour tissue shows malignant irregular shaped glands surrounded by fibrous tissue

what is desmoplastic storma

• the fibrous tissue that surrounds tumourous tissue in adenocarcinoma

describe the genetic mechanism of adencarcinoma

• gain of function mutations in EGFR and KRAS

• oncogenes

what kind of

describe the morphology of squamous cell carcinoma

• squamous dysplasia of bronchial epeithelium

describe the genetic mechanism of squamous cell carcinoma

• loss of funciton mutations of tumour suppressor p52 and RB

describe the morphology of small cell carcinoma

small tumour cells

• little cytoplasm

• dark hyperchromatic nuclei

• finely granular chromatin

describe the genetic mechanism of small cell carcinoma

mutations of p53 and BCL2 anti-apoptopic genes

describe the gross morphology of lung carcinoma

• gray white colour

• hard tumour consistency

• anthracosis

• heamorrhage and tissue necrosis

what cancer normally has tumours that are hilar/central

squamous or small cell

what cancer normally has tumours that are peripheral and under the pleura

adenocarcinomas

what does lung cancer normally present as

• cough

• hemoptysis (blood in sputum)

• chest pain

• dyspnea

• weight loss

how is lung cancer investigated

chest x ray

sputum sample examination

CT/MRI

bronchoscopy

tumour biopsy

what is enobronchial biosy

• tissue biopsy from a lesion in the bronchial wall or lumen through a bronchoscope

what are some traditional lung cancer therapies

surgery

chemo

radiation

what are some novel therapies for lung cancer

• immunotherapy

• mutated EGFR inhibitors

in terms of treatment how are lung cancers classified

• small cell

• non small cell

describe why lung cancer is classified as SCLC and NSCLC

• non small cell lung cancer can be localised on diagnosis and surgically cured

• SCLC is usually metastatic and usually relapses post radiation and chemo

what is indicated by the red arrows and what else can be interpreted

• emphysematous air spaces (dilated respiratory bronchioles due to emphysema)

• anthracosis

• centriacinar pattern- normal alveoli still exits in between areas of emphysema

what can be seen

• this is a nornal lung

• R is the respiratory bronchi

• AD is alveolar duct

• A is alveolus

• V is blood vessel

• AS is alveolar sac

• T is terminal bronchiole

what can be seen

• centriacinar emphysema

• red is dilated respiratory bronchiles

• green is anthracosis

• black is normal surrounding alveolar spaces

what can be seen

• chronic bronchitis

what can be seen

• normal bronchus

• top arrow is repiratory epithelium (pseudostratified colunar ciliated epithelium)

• second arrow is smooth muscle

• third is mucous and serous glands in the submucosa

• bottom is cartilage

what am i seeing from top to bottom

chronic bronchitis

• goblet cell metaplasia on lining epithelium

• smooth muscle hypertrophy from chronic copughing

• hyperplasia and hypertrophy of mucus glands

what can be seen

adenocarcinoma

• arrows are showing tumour tissue with irregular sized and shaped glands

describe A. B, C, D

• A is normal alveolar tissue

• B is atypical adenomatous hyperplasia

• C is adenocarcinoma in situ

• D is lung adenocarcinoma (invasion)

what can be seen

squamous cell carcinoma

• The left arrow is pseudostratified coloumnar epithelum

• the right arrow is squamous epithelium

what is A, B, C, D, E, F

squamous cell carcinoma

A. goblet cell hyperplasia

B. basal cell hyperplasia

C. squamous metaplasia

D. squamous dysplasia

E. carcinoma in situ

F. invasive squamous carcinoma

what is this

small cell carcinoma

what is this

squamous cell carcinoma

what is this

small cell carcinoma