B2.059 Pathology of Tobacco Use Flashcards
what percentage of adults in the US are smokers?
20%
how many years after smoking cessation do you see a reduction in mortality from CVD or cancer?
5 years
how does nicotine work?
addictive
binds to nicotinic acetylcholine receptors in brain with release of catecholamines from sympathetic neurons
increased HR, BP, cardiac output
what is the effect of carbon monoxide in cigarettes?
impaired oxygen transport and utilization
what is the effect of formaldehyde and nitrogen oxides in cigarettes?
toxic to cilia, mucosal irritation
what is the function of cilia?
help move toxins and bacteria from lungs to upper respiratory tract so that they can be expelled
what are the 3 major effects of smoking on the lungs?
mucosal irritation
leukocyte recruitment
carcinogenic agents
what is the effect of leukocyte recruitment in lungs?
tissue destruction by elastases
emphysema
what are two ways that smoking has carcinogenic effects?
source of carcinogens
increases cancer risk from OTHER exposures by 10x (asbestos, uranium)
what are effects of smoking on the cardiovascular system?
atherosclerosis
increased platelet aggregation
decreased oxygen supply
increased oxygen demand (myocardial work)
what are some risks of smoking on maternal/fetal health?
increased risk of spontaneous abortions, preterm birth
intrauterine growth retardation
what are some cancers linked to smoking?
lung, larynx esophagus pancreas bladder oral cavity
how can second hand smoke exposure be measured?
blood levels of cotinine (nicotine metabolite)
where is secondhand smoke exposure primarily a concern?
at home
what is the primary chronic injury which leads to emphysema or chronic bronchitis?
smoking
characterize chronic bronchitis
persistent cough with sputum production for at least 3 months in at least 2 consecutive years with no identifiable cause
what is the pathogenesis of chronic bronchitis
damage to airway lining cells and interference with ciliary function
what are the outcomes of mucous hypersecretion in chronic bronchitis?
protective response
contributes to obstruction in smaller, lower parts of airways
what are the outcomes of inflammation in chronic bronchitis?
acute and chronic
damage>repair>increased collagen>less flexibility>obstruction of small airways
characterize the risk of infection in chronic bronchitis
higher
easier for microbes to get into an area with excess damage/mucous
what are other clinical feature of chronic bronchitis?
dyspnea on exertion
hypercapnia (elevated CO2), hypoxemia, mild cyanosis
blue bloater
what are some complications associated with chronic bronchitis?
superimposed infections (most common) pulmonary hypertension and cor pulmonale (compression on vasculature causes pressure backup on heart)
characterize emphysema
irreversible enlargement of airspaces distal to the terminal bronchiole with destruction of airspace wall
what makes up respiratory epithelium?
columnar and ciliary epithelium
bronchi: epithelium type, muscle/support, function
respiratory
prominent smooth muscle & cartilage
conduct air
bronchioles: epithelium type, muscle/support, function
simple ciliated cuboidal to columnar
circular smooth muscle
conduct air, regulate airway size
terminal bronchioles: epithelium type, muscle/support, function
simple ciliated cuboidal
thin smooth muscle
conduct air
respiratory bronchioles: epithelium type, muscle/support, function
simple ciliated cuboidal and alveoli
few smooth muscle fibers
conduct air and some gas exchange
alveolar duct: epithelium type, muscle/support, function
simple cuboidal
smooth muscle fibers around alveolar openings
conducts air and a lot of gas exchange
alveoli: epithelium type, muscle/support, function
alveolar cells (type 1 and 2 pneumocytes) no muscle gas exchange and surfactant production
what are the 2 primary classes of emphysema?
centriacinar (centrilobular)
panacinar (panlobular)
emphysema is also used as a descriptive term for lung disease w which 2 features
overinflation
bullae (dilated spaces)
characterize overinflation
compensatory
after removal of part of a lung
obstructive, distal to the point of obstruction (backflow not possible)
characterize bullous emphysema
large subpleural bullae >1 cm from a variety of causes
risk for rupture and pneumothorax
DOES NOT necessarily indicate emphysema is present throughout the lung (can occur on its own)
characterize centriacinar (centrilobular) emphysema
95% of clinically significant cases
affects proximal/central portion of acini (respiratory bronchiole), sparing distal alveoli
dilated and normal airspaces co-exist in the same acinus
more common/severe in upper lobes
inflammation of bronchi/bronchioles
characterize paracinar (panlobular) emphysema
clinically significant
affects entire acini from respiratory bronchiole to the distal alveoli
more common/severe in lower lobes
seen primarily in alpha-1-antitrypsin deficiency
what is the pathogenesis of emphysema?
inflammation and parenchymal destruction
- inflammatory mediators and leukocytes
- protease/antiprotease imbalance
- oxidative stress
- infection
what can cause protease/antiprotease imbalance?
extra protease formation (in locations of injury) or alpha-1-antitrypsin deficiency (happens everywhere)
what is alpha-1-antitrypsin
acts against proteases to limit tissue destrcution
what is the result of protease/antiprotease imbalance?
connective tissue breakdown
loss of elastic recoil leading to collapse of respiratory bronchioles
what is the pathogenesis of an obstruction in emphysema?
loss of elastic recoil leading to collapse of respiratory bronchioles
small airway inflammation- mucous hypersecretion and plugging OR narrowing of lumen of bronchioles due to inflammatory infiltrates, smooth muscle hyperplasia, and fibrosis
what % of patients with emphysema have an A1AT deficiency?
1%
where is A1AT synthesized and where is it located?
synthesized by hepatocytes
present in plasma, tissue fluid, and macrophages
what is the wildtype A1AT gene?
PiMM
what is the genotype associated with A1AT deficiency?
PiZZ
characterize PiZZ protein
abnormally folded/polymerized
defect in migration from ER to Golgi
accumulates in hepatocytes in ER- can induce apoptosis
decreases serum levels of A1AT
besides emphysema, what is a clinical consequence of A1AT deficiency?
liver disease, seen in 10-15% of patients
how can you recognize empysema due to A1AT deficiency?
younger age of onset
panacinar distribution
smoking markedly exacerbates consequences
what are some clinical features associated w emphysema?
dyspnea wheezing weight bloss barrel chested appearance breathing through pursed lips overventilation with normal oxygen pink puffer
what are some complications associated with empysema?
pneumothorax and collapse of lung
respiratory failure
pulmonary hypertension and cor pulmonale is uncommon and usually a terminal event
