B2.059 Pathology of Tobacco Use

Question 1

what percentage of adults in the US are smokers?

Answer 1

20%

Question 2

how many years after smoking cessation do you see a reduction in mortality from CVD or cancer?

Answer 2

5 years

Question 3

how does nicotine work?

Answer 3

addictive
binds to nicotinic acetylcholine receptors in brain with release of catecholamines from sympathetic neurons
increased HR, BP, cardiac output

Question 4

what is the effect of carbon monoxide in cigarettes?

Answer 4

impaired oxygen transport and utilization

Question 5

what is the effect of formaldehyde and nitrogen oxides in cigarettes?

Answer 5

toxic to cilia, mucosal irritation

Question 6

what is the function of cilia?

Answer 6

help move toxins and bacteria from lungs to upper respiratory tract so that they can be expelled

Question 7

what are the 3 major effects of smoking on the lungs?

Answer 7

mucosal irritation
leukocyte recruitment
carcinogenic agents

Question 8

what is the effect of leukocyte recruitment in lungs?

Answer 8

tissue destruction by elastases

emphysema

Question 9

what are two ways that smoking has carcinogenic effects?

Answer 9

source of carcinogens

increases cancer risk from OTHER exposures by 10x (asbestos, uranium)

Question 10

what are effects of smoking on the cardiovascular system?

Answer 10

atherosclerosis
increased platelet aggregation
decreased oxygen supply
increased oxygen demand (myocardial work)

Question 11

what are some risks of smoking on maternal/fetal health?

Answer 11

increased risk of spontaneous abortions, preterm birth

intrauterine growth retardation

Question 12

what are some cancers linked to smoking?

Answer 12

lung, larynx
esophagus
pancreas
bladder
oral cavity

Question 13

how can second hand smoke exposure be measured?

Answer 13

blood levels of cotinine (nicotine metabolite)

Question 14

where is secondhand smoke exposure primarily a concern?

Answer 14

at home

Question 15

what is the primary chronic injury which leads to emphysema or chronic bronchitis?

Answer 15

smoking

Question 16

characterize chronic bronchitis

Answer 16

persistent cough with sputum production for at least 3 months in at least 2 consecutive years with no identifiable cause

Question 17

what is the pathogenesis of chronic bronchitis

Answer 17

damage to airway lining cells and interference with ciliary function

Question 18

what are the outcomes of mucous hypersecretion in chronic bronchitis?

Answer 18

protective response

contributes to obstruction in smaller, lower parts of airways

Question 19

what are the outcomes of inflammation in chronic bronchitis?

Answer 19

acute and chronic

damage>repair>increased collagen>less flexibility>obstruction of small airways

Question 20

characterize the risk of infection in chronic bronchitis

Answer 20

higher

easier for microbes to get into an area with excess damage/mucous

Question 21

what are other clinical feature of chronic bronchitis?

Answer 21

dyspnea on exertion
hypercapnia (elevated CO2), hypoxemia, mild cyanosis
blue bloater

Question 22

what are some complications associated with chronic bronchitis?

Answer 22

superimposed infections (most common)
pulmonary hypertension and cor pulmonale (compression on vasculature causes pressure backup on heart)

Question 23

characterize emphysema

Answer 23

irreversible enlargement of airspaces distal to the terminal bronchiole with destruction of airspace wall

Question 24

what makes up respiratory epithelium?

Answer 24

columnar and ciliary epithelium

Question 25

bronchi: epithelium type, muscle/support, function

Answer 25

respiratory prominent smooth muscle & cartilage conduct air

Question 26

bronchioles: epithelium type, muscle/support, function

Answer 26

simple ciliated cuboidal to columnar circular smooth muscle conduct air, regulate airway size

Question 27

terminal bronchioles: epithelium type, muscle/support, function

Answer 27

simple ciliated cuboidal thin smooth muscle conduct air

Question 28

respiratory bronchioles: epithelium type, muscle/support, function

Answer 28

simple ciliated cuboidal and alveoli few smooth muscle fibers conduct air and some gas exchange

Question 29

alveolar duct: epithelium type, muscle/support, function

Answer 29

simple cuboidal smooth muscle fibers around alveolar openings conducts air and a lot of gas exchange

Question 30

alveoli: epithelium type, muscle/support, function

Answer 30

``` alveolar cells (type 1 and 2 pneumocytes) no muscle gas exchange and surfactant production ```

Question 31

what are the 2 primary classes of emphysema?

Answer 31

centriacinar (centrilobular) | panacinar (panlobular)

Question 32

emphysema is also used as a descriptive term for lung disease w which 2 features

Answer 32

overinflation | bullae (dilated spaces)

Question 33

characterize overinflation

Answer 33

compensatory after removal of part of a lung obstructive, distal to the point of obstruction (backflow not possible)

Question 34

characterize bullous emphysema

Answer 34

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)

Question 35

characterize centriacinar (centrilobular) emphysema

Answer 35

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

Question 36

characterize paracinar (panlobular) emphysema

Answer 36

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

Question 37

what is the pathogenesis of emphysema?

Answer 37

inflammation and parenchymal destruction - inflammatory mediators and leukocytes - protease/antiprotease imbalance - oxidative stress - infection

Question 38

what can cause protease/antiprotease imbalance?

Answer 38

extra protease formation (in locations of injury) or alpha-1-antitrypsin deficiency (happens everywhere)

Question 39

what is alpha-1-antitrypsin

Answer 39

acts against proteases to limit tissue destrcution

Question 40

what is the result of protease/antiprotease imbalance?

Answer 40

connective tissue breakdown | loss of elastic recoil leading to collapse of respiratory bronchioles

Question 41

what is the pathogenesis of an obstruction in emphysema?

Answer 41

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

Question 42

what % of patients with emphysema have an A1AT deficiency?

Answer 42

1%

Question 43

where is A1AT synthesized and where is it located?

Answer 43

synthesized by hepatocytes | present in plasma, tissue fluid, and macrophages

Question 44

what is the wildtype A1AT gene?

Answer 44

PiMM

Question 45

what is the genotype associated with A1AT deficiency?

Answer 45

PiZZ

Question 46

characterize PiZZ protein

Answer 46

abnormally folded/polymerized defect in migration from ER to Golgi accumulates in hepatocytes in ER- can induce apoptosis decreases serum levels of A1AT

Question 47

besides emphysema, what is a clinical consequence of A1AT deficiency?

Answer 47

liver disease, seen in 10-15% of patients

Question 48

how can you recognize empysema due to A1AT deficiency?

Answer 48

younger age of onset panacinar distribution smoking markedly exacerbates consequences

Question 49

what are some clinical features associated w emphysema?

Answer 49

``` dyspnea wheezing weight bloss barrel chested appearance breathing through pursed lips overventilation with normal oxygen pink puffer ```

Question 50

what are some complications associated with empysema?

Answer 50

pneumothorax and collapse of lung respiratory failure pulmonary hypertension and cor pulmonale is uncommon and usually a terminal event