BHS 116- Physiology
Notetaker: Stephanie Cullen
Date: 10/9/12, 1st hour
Page: 1
FINAL EXAM INCLUDES: 21 old lectures, 9 new lectures
- 60-66% of the final is new material on lectures 26-34
- 34-40% of the final is old material excluding lectures 1,2,3, and 12
Lecture 30
Chronic Obstructive Pulmonary Disease (COPD)
- 3 primary diseases:
o Chronic bronchitis
 Disease of the bronchi
o Asthma
 Disease of the bronchi
o Emphysema
 Disease of alveoli
- All 3: More difficulty with expiration than with inspiration
- Smoking is a big culprit, especially in emphysema and bronchitis
- Normal spirogram vs one from someone with COPD
o Increase RV, decrease normal VC, normal to increased TLC
(emphysema)
 Can inspire a normal amount of air then gradually build
up the amount of air staying in the lungs (RV) since
we can’t expire all the air we take in
 Usually the TLC remains somewhat normal
(bronchitis, asthma)
Objective: Describe the pathophysiology, pathogenesis, and symptoms of
emphysema.
Emphysema
- Abnormal permanent enlargement of the airways distal to the terminal bronchiole
o Acinus: Respiratory bronchiole, alveolar duct, and alveolus
- Accompanied by irreversible destruction of the alveolar wall without fibrosis
- 2 most common types based on anatomical location are Centriacinar (Centrilobular) and
Panacinar
o Based on where in that acinus the damage is occurring
- Symptoms:
o Dyspnea (breathlessness)
o Weight loss
o Patients can be barrel-chested because of the air building up
inside the lungs (thoracic cavity is expanded)
- Histology
o Emphysema: expanded air spaces
o Normal lung at the bottom
Objective: Describe the differences between centrilobar and panacinar
emphysema.
BHS 116- Physiology
Notetaker: Stephanie Cullen
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Date: 10/9/12, 1st hour
Page: 2
Centriacinar Emphysema
o Disease of the respiratory bronchioles
o Respiratory bronchioles are affected
 First place that exchange can occur with the blood vessels (usually doesn’t
because most blood vessels are in close proximity to the terminal alveoli
where most exchange occurs)
o Distal alveoli are spared (until disease becomes severe)
o Predominately in heavy smokers
o Most common
o This the first region that smoke gets to and affects when
smoking
 First place cells are damaged (toxins have the greatest
effect)
 Sparing of other 2 regions
Panacinar Emphysema
o Respiratory bronchioles through the alveoli are uniformly enlarged
 Entire acinus is susceptible to damage
 Damage and enlargement in all 3 regions
o Associated with α 1-antitrypsin (α1-AT) deficiency
 Mutation in this enzyme that is a protease inhibitor
(breaks down trypsin normally)
 Defense against trypsin proteases
 Without this gene, trypsin can chop up other proteins
 Inherited disorder
o Less common
Pathohistology
o Centriacinar
 Both diseased and normal airspaces exist within the same
acinus since respiratory bronchioles are diseased but the
alveoli and alveolar ducts are normal
 Some large air spaces are seen and some normal sized air
spaces are seen
o Panacinar
 Entire acinus is diseased thus no normal tissue
 More enlarged air spaces seen throughout
o Distinguish between the 2 by the amount of enlarged air spaces
seen
Pathophysiology of Emphysema
o Total lung capacity is increased due to difficulty in expiration
 Due to the extra air in the lungs
o There is a further increase in chest pressure when trying to blow air
out that causes closing of some of the airways
 Could collapse the respiratory/terminal bronchioles
o Residual volume of the lungs is also increased due to difficulty in
expiration
BHS 116- Physiology
Notetaker: Stephanie Cullen
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Date: 10/9/12, 1st hour
Page: 3
This is because all the air cannot be blown out during expiration
Normally it is about 1.2 L left but it can triple to almost 3 or 3.5 L of air
left in the lungs
o Maximal expiratory flow rate is reduced
 This is due to both the collapse of airways (from the
increase amount of air) and the obstruction of airways due
to alveolar tissue destruction (decreased recoil)
 Normally 400-500 range but it cut in half with emphysema
Forced Expiratory Vital Capacity
o Test: total amount of air we can expire forcefully in a given amount
of time
o After maximal inspiration, individual exhales as fast and hard as
they can
 Usually within 4-5 sec, you can get out all of the air you
inspired
o Over 1 sec we get the FEV1 (forced expiratory volume)
 80% of air we take in is expired in the first second in a
normal lung (FEV1/FVC)
o In the first second of exhaling, there is a great difference in volume
expired between a normal individual and an individual with emphysema or
asthma
 45-50% in a person with COPD
 Start with a smaller forced vital capacity and less air is expired in the first
second due to the disease and takes longer to expire the air taken in (up to
7 sec or longer)
Pathogenesis of Emphysema
o Chronic infection- chronic inflammation
o Smoking
 Most common cause of emphysema
o Oxidant-antioxidant imbalance
o Protease-antiprotease mechanism
 Alveolar wall is destroyed because of imbalance of proteases and their
inhibitors (proteases are winning)
 Break down elastic tissue- can’t recoil
 Collapsing pressure is reduced by 1/3
 Recoil is part of the reason you can’t get air out
o Probably more due to the protease-antiprotease imbalance with influence from the
oxidant-antioxidant imbalance
o Last 2 systems are disrupted with smoking being a major trigger of disruption
Why is Smoking BAD for Emphysema?
o Increased number of neutrophil and macrophages in alveoli
 Possibly due to chemoattractive properties of nicotine
 Nicotine is drawing neutrophils and macrophages to those sites in alveoli
and these and the macrophages already in the lungs can become activated
by the chemicals in cigarette smoke
o Stimulates release of proteases from neutrophils and macrophages
BHS 116- Physiology
Notetaker: Stephanie Cullen
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Date: 10/9/12, 1st hour
Page: 4
 Normally the lung has anti-proteases that can neutralize these
o Oxidants in cigarette smoke and oxygen free radicals secreted by neutrophils
inhibit protease inhibitor α1-AT
 Proteases take over and break down the alveolar wall
Pathogenesis
o Nicotine draws neutrophils to the site (already have macrophages there)
o Reactive oxygen species (oxidants) in the smoke help to neutralize the antiproteases
o Centrilobular
 Proteases break down alveolar wall
 Additionally, the macrophages inside the alveoli
are releasing their proteases which are breaking
down the alveolar wall as well
o Panacinar: deficiency in the α1-AT
 Can’t inhibit proteases (trypsin)
 Proteases take over
Objective: Describe the pathophysiology, pathogenesis, and symptoms of asthma (intrinsic vs
extrinsic).
Asthma
- Chronic relapsing inflammatory disorder characterized by hyperreactive airways
o Reversible bronchoconstriction
o Chronic airway inflammation in the walls of the bronchi (leading to
bronchoconstriction)
 Extrinsic (allergic or atopic)
 Acute (immediate upon exposure to allergen) and late (chronic)
(4-8 hours after activation) phases
 More common
 Intrinsic (non-allergic or non-atopic)
 Non-immune mechanism
- Symptoms
o Episodic wheezing
o Cough
o Dyspnea
o Laboring to get air into lungs and greater difficulty expiring
 Again, primarily an expiration problem
- Pathogenesis
o Extrinsic (allergic)
 Initial sensitization to inhaled antigen (allergen like
pollen) stimulate T-lymphocyte sub class (Th2) to
stimulate IgE production by B-lymphocytes
 No asthmatic symptoms upon 1st exposure
 IgE bound by mast cells and primes them
BHS 116- Physiology
Notetaker: Stephanie Cullen
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Date: 10/9/12, 1st hour
Page: 5
o Mast cells are coated with IgE so that IgE can bind the
allergen when it is inhaled again
 Actue Phase (minutes)
 Allergen is inhaled
 Allergen (immediately) binds to primed mast cells which release
mediators (histamine, leukotrienes, and prostaglandins)
o Histamine: leads to vasodilation and increased permeability
of the vessels in the bronchial wall
o Prostaglandins and leukotrienes:
 Opening of mucosal tight junctions (mucosal lining
becomes more permeable)
 Edema and mucus secretion
 Because of increased permeability of the
vasculature
 Fluid can flow into the lamina propria
causing thickening of the lamina propria
which constricts the bronchi
 Activation of goblet cells to secrete
excess mucus
 Direct stimulation of subepithelial vagal
receptors provoke bronchoconstriction
(smooth muscle contracts)
 Late Phase (hours)
 Continued bronchoconstriction and inflammation mediated
by eosinophils
o Intrinsic
 Stimulated by inhaled air pollutants
 Virus provoked (most common)
 IgE levels are normal
o Not immune related
 Virus induced inflammation of mucosa lowers
the threshold of the subepithelial vagal
receptor to irritants
 Bronchoconstriction
 Edema and mucus secretion
 Presence of eosinophils
Increase in the amount of mucus
o Due to: more goblet cells and more submucosal mucus
glands
 More goblet cells and more goblet cells stimulated
making even more mucus
 Submucosal glands also producing mucus (don’t normally see a lot of
these)
Increase in the amount of chronic inflammatory cells: macrophages and eosinophils
o In the mucus layer (bronchial lumen) and the lamina propria
BHS 116- Physiology
Notetaker: Stephanie Cullen
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Date: 10/9/12, 1st hour
Page: 6
Increase in the thickness of the basement membrane and number of smooth muscle cells
(layer is also thicker)
o Increased thickness in lamina propria due to edema and increased number of cells
Treatment
o Bronchodilators
 Act on smooth muscle of the bronchi
 Long-term β-agonists like Advair (agonist and anti-inflammatory)
 Short-term β-agonists like albuterol
o Corticosteroids
 Decrease inflammatory reaction
Objective: Describe the pathogenesis, symptoms, and forms of chronic bronchitis.
Chronic Bronchitis
- Common among smokers and big city dwellers (smog and pollution)
- Persistent productive cough for at least 3 consecutive months in at least 2 consecutive
years
o Don’t have to have it constantly
o Can go away for an extended period of time
- Earliest feature of bronchitis is hypersecretion of mucous in the large airways (trachea
and bronchi) due to hypertrophy of the mucous glands
o No eosinophils present in the mucous layer
o Can differentiate between bronchitis and asthma by eosinophils present/absent in
the mucus
- Irritant eventually leads to inflammation, fibrosis (if irritant persists), and narrowing of
the bronchioles
- At this firbrotic stage, the damage is irreversible
o Asthmas is reversible if allergen goes away- everything goes back to normal
o Chronic bronchitis can lead to fibrosis which is irreversible damage
- There are several forms of bronchitis:
o Simple chronic bronchitis
 Most common
 A lot of mucus production but no airflow obstruction
o Chronic mucopurulent bronchitis
 Secondary infection causes pus in mucous
o Chronic asthmatic bronchitis
 Intermittent episodes of asthma
o Chronic obstructive bronchitis
 Chronic outflow obstruction (expiratory problem)
Objective: Describe COPD.
Chronic Obstructive Pulmonary Disease
- Anatomic distribution of chronic bronchitis (bronchi disease,
inflammatory reaction, hyperproduction of mucus) and emphysema
(destruction of alveolar wall reducing their recoil)
BHS 116- Physiology
Notetaker: Stephanie Cullen
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Date: 10/9/12, 1st hour
Page: 7
o Both cause problems with expiration through different mechanisms
When bronchitis is accompanied by moderate to severe airflow obstruction, it can lead to
or be confused with emphysema
o Heavy smokers tend to have both diseases
o Start with different originations
 Bronchitis: bronchial injury due to an irritant/infection,
starts as reversible process but if it persists, get fibrosis
and turns into an irreversible process
 Emphysema: destruction of alveolar walls
o Over time with either of these, can start getting affects of other
system
 Can get to a point where one can’t be differentiated from
the other (COPD)
 Treat the combination of the 2
Average patient with COPD, will have some mix of bronchitis and some mix of
emphysema
o Can have either/or but called COPD unless there is obviously only
1 of the 2
o Patients with emphysema have primarily destruction of alveoli and
a little bronchiole inflammation
o Patients with bronchitis have primarily bronchial inflammation and
a little alveolar destruction
Clicker Question: In which of the following would you expect to see eosinophils
in the mucus?
a. Emphysema
b. Asthma
c. Chronic bronchitis