Respi 6131 Flashcards
The respiratory tract is divided into the
upper and lower respiratory tract
extra thoracic airway passages above the neck
upper respiratory tract
airway passages and lung parenchyma below the pharynx
lower respiratory tract
reaches from the nostril or
mouth to the pharynx
upper
passage of URT
oronasal
functions of the URT
functions to conduct, heat,
humidify, filter, and chemosense incoming air.
Leaving the nasal passage, air is warmed to about ________ and humidified to about ___________%water saturation
33°C; 98%
In addition to conducting, conditioning, and filtering air to the lower respiratory tract, a major function of the oronasal passage is __________
chemosensory
Nasal epithelia can metabolize many foreign compounds by ______________ and other enzymes
cytochrome P450
Chemosensory function of the nasal passages is accomplished by a wide variety of specialized receptors in
major subtypes including:
- olfactory receptors
- trace amine–associated receptors (TAARs)
- membrane guanylyl cyclase GC-D receptors
- vomeronasal receptors
- formyl peptide receptors (FPRs)
The olfactory epithelium contains
specialized chemosensory olfactory
neurons located in the ________ portion of the nasal passage.
superior
Airflow in this region of the nasal passage
is typically _________, thus sniffing can increase perception.
(olfactory receptors)
low
_______ detect trace amines, with fishy or
putrid odor, that are found in foods and
can also be generated during
fermentation or decay.
TAARs
GC-D receptors are located in the cilia of
olfactory sensory neurons and detect the
natriuretic peptides, _________ (found in urine) and _________
uroguanylin and guanylin
In rodents, these receptors detect carbon
dioxide, which is odorless in humans and
other primates
membrane guanylyl cyclase GC-D receptors
_________ are separate from, but adjacent to, olfactory neurons.
vomeronasal receptors
They can detect higher molecular weight
stimuli, including nonvolatile chemicals.
vomeronasal receptors
are also a part of the vomeronasal
system and detect bacterial or
mitochondrial formylated peptides,
which are thought to identify pathogens
or pathogenic states.
formyl peptide receptors (FPRs)
In addition to the detection of odor, the detection of irritant chemicals, cold and hot temperatures, or mechanical stress
can be a protective mechanism that may limit exposure. Two protein families, the ____________ and the ____________, perform these functions in the upper respiratory tract
transient receptor potential (TRP)
channels and the taste (TAS) receptors
are ion channels that are permeable
to cations, including calcium, magnesium, and sodium. These receptors are sensitive to a variety of natural ingredients, pain stimuli, and heat.
TRP
Taste buds, which contain_______, determine salt, sour, sweet, umami (glutamate and nucleotides), and bitter.
TAS
LRT Airways
Conducting airways
At the beginning of the lower respiratory tract is the __________, which is responsible for speech (phonation).
larynx
The conducting airways of the lower respiratory tract can be
divided into:
proximal (trachea and bronchi) and distal
regions (bronchioles)
Conducting airways have a bifurcating structure, with successive airway generations containing about twice the
number of bronchi progressively ___________ in internal diameter.
decreasing
Eventually a ___________ zone is reached where cartilaginous bronchi give way to noncartilaginous bronchioles, which in turn give way to gas exchange regions, respiratory bronchioles, and alveoli.
(CONDUCTING AIRWAYS)
transition
In the bronchiolar epithelium, mucus-producing cells and glands give way to ___________
(CONDUCTING AIRWAYS)
bronchiolar secretoglobin cells (BSCs)
One way in which airflow is altered is by smooth muscle that surrounds the airways and is under autonomic innervation via the __________
(CONDUCTING AIRWAYS)
vagus nerve
Main function of conducting airways
mucociliary clearance and antimicrobial
In humans, the proximal airway and a portion of the nasal passage are covered by a ____________ that contains a number of specialized cells including ciliated, mucous, and basal cells.
(Mucociliary Clearance and Antimicrobial Functions)
pseudostratified respiratory epithelium
__________and_________ are needed to move fluid into the airway lumen and ______________ are needed to move water out of the lumen.
(Mucociliary Clearance and Antimicrobial Functions)
Chloride ion channels and the cystic fibrosis transmembrane regulator;
sodium channels
Ciliated cells have microtubule-based protrusions, cilia, of which there are two types:
(Mucociliary Clearance and Antimicrobial Functions)
motile and primary
exert mechanical force through
continuous motion to propel harmful inhaled material out of the nose and lung. ___________ also exhibit mechanosensory and chemosensory
functions and can respond to mechanical stress, heat, acidic pH, and endogenous and synthetic agonists.
(Mucociliary Clearance and Antimicrobial Functions)
Motile cilia
often serve as sensory organelles.
(Mucociliary Clearance and Antimicrobial Functions)
Primary cilia
Serous cells contain and secrete a less viscous fluid, and are also enriched in antimicrobial proteins including lysozyme and lactotransferin. These cells also contain the antimicrobial protein, ___________
(Mucociliary Clearance and Antimicrobial Functions)
BPIF2 (aka SPLUNC2)
__________ is a serine proteinase inhibitor that is produced locally in the lung by cells of the submucosal bronchial glands and by nonciliated epithelial cells. The main function of ________ is the inhibition of neutrophil elastase and other proteinases, and may also have
antimicrobial functions.
(Mucociliary Clearance and Antimicrobial Functions)
Secretory leukocyte proteinase inhibitor (SLPI)
Another airway secretory cell is the ____________ previously called the Clara cell
(Mucociliary Clearance and Antimicrobial Functions)
bronchiolar secretoglobin cell (BSC)
- they are known to inhibit
phospholipase A2 and limit inflammation - are found mainly in the distal
airways and can act as tissue stem cells
(Mucociliary Clearance and Antimicrobial Functions)
bronchiolar secretoglobin cell (BSC)
The gas exchange region consists of
- terminal bronchioles,
- respiratory bronchioles,
- alveolar ducts,
- alveoli,
- blood vessels,
- lung interstitium
Gas exchange occurs in the ________, which comprise ∼________% of the total parenchymal lung volume.
alveoli; 85%
The alveolar epithelium consists of two cells:
the alveolar type I and type II cell
cover ∼95% of the alveolar surface and therefore are susceptible to damage by noxious agents that penetrate to the alveolus
(Gas exchange)
Type I
attenuated cytoplasm to enhance gas exchange
(Gas exchange)
Type I cells
- produce and secrete surfactant, a mixture of lipids, and four surfactant
associated proteins - can undergo mitotic division and replace damaged type I cells
(Gas exchange)
Type II cells
surfactant associated proteins
(Gas exchange)
- A1
- A2
- B
- C
- D
are amphipathic and aid in spreading secreted lipids which form a monolayer that reduces surface tension
(Gas exchange)
B and C
are members of the subfamily of C-type lectins called collectins, which defend
against pathogens.
(Gas exchange)
A1, A2, and D
do not alter lipid structure but do bind lipopolysaccharides (LPS) and various microbial pathogens, enhancing their clearance from the lung
(Gas exchange)
A1 and A2
is also necessary in the suppression of
pulmonary inflammation and in host defense against viral, fungal, and bacterial pathogens.
(Gas exchange)
D
Principal functions of the lungs is gas exchange which consists of:
- diffusion
- ventilation
- perfusion
Lung function changes with age and disease and can be measured with a _________
spirometer
Test in which an individual inhales maximally and then as rapidly as possible
Spirometry
The total lung capacity (TLC) is the total volume of air in an inflated human lung,__________(women) and _________(men)
- 4 to 5 L W
- 6 to 7 L M
After a maximum expiration, the lung retains ______ (women) and
______ (men), which is the residual volume (RV).
-1.1 L W
-1.2 L M
The vital capacity is the air volume moved into and out of the lung during maximal inspiratory and expiratory movement and
typical is __________ (women) and ________ (men)
- 3.1 L W
- 4.8 L M
In resting humans, the TV (tidal volume) measures ________L with each breath.
∼0.5 L
The respiratory frequency is _________ (thus the resting ventilation is about 6–8 L/min).
12 to 20 breaths per minute
Total lung cytochrome P450 (CYP) activity is roughly one-tenth to one-third of that in the liver (t or f)
(BIOTRANSFORMATION IN THE RESPIRATORY TRACT)
T
The CYP monooxygenase system is concentrated into a few lung cells:
(BIOTRANSFORMATION IN THE RESPIRATORY TRACT)
- BSCs
- alveolar Type II cells
- macrophages
- endothelial cells
has the most CYP followed by the type II cells
(BIOTRANSFORMATION IN THE RESPIRATORY TRACT)
BSCs
Phase II enzyme inlcude
(BIOTRANSFORMATION IN THE RESPIRATORY TRACT)
- glutathione S-transferases (GSTs)
(alpha, mu,and pi), - glucuronosyl transferases, and
- sulfotransferases (SULTs)
play a major role in the modulation of both acute and chronic chemical toxicity in the lung
(BIOTRANSFORMATION IN THE RESPIRATORY TRACT)
glutathione S-transferases (GSTs) and glutathione
In inhalation toxicology, exposure is measured as a concentration (compound mass per unit of air). (t or f)
T
GENERAL PRINCIPLES IN THE PATHOGENESIS OF LUNG DAMAGE
CAUSED BY CHEMICALS
- Toxic inhalants, gases, and dosimetry
- regional particle deposition
- deposition mechanisms
- particle clearance
Typically highly toxic compounds can produce adverse effects in a concentration of:
(TOXIC INHALANTS, GASES, AND DOSIMETRY)
mg/m3 or μg/m3 (1m3=1000L)
For gases, concentration may also be expressed as volume to volume of air, that is, ___________ or ___________
(TOXIC INHALANTS, GASES, AND DOSIMETRY)
parts per million (ppm) or parts per billion (ppb)
critical factors in determining how deeply a given gas penetrates into the lung
(TOXIC INHALANTS, GASES, AND DOSIMETRY)
- solubility
- diffusivity
- metabolism/reactivity
- breathing rate
Highly soluble gases such as ________ or ________ do not penetrate farther than the nose (during nasal breathing) unless doses are very high, and are therefore relatively nontoxic to the lung of rats
(TOXIC INHALANTS, GASES, AND DOSIMETRY)
SO2 or formaldehyde
Relatively insoluble gases such as ________ and __________ penetrate deeply into the lung and reach the smallest airways and the alveoli (centriacinar region), where they can elicit toxic responses.
(TOXIC INHALANTS, GASES, AND DOSIMETRY)
ozone and NO2
Very insoluble gases such as _______ and ________ efficiently pass through the respiratory tract and are taken up by the pulmonary blood supply to be distributed
throughout the bod
(TOXIC INHALANTS, GASES, AND DOSIMETRY)
CO and H2S
is a critical factor in determining the region of the respiratory tract in which a particle will be deposited
particle size
In respiratory toxicology, aerosols include (solid or liquid particles dispersed into air)
dusts, fumes, smoke, mists, fog, or
smog
(ranging from ≥ 1.0 μm for dusts to ≥ 0.01–50 μm for smog)
The upper respiratory tract is very efficient in removing particles that are very large (> 10 μm) or very small (< 0.01 μm) (t or f)
T
During nasal breathing, _____ to _____ μm particles are usually deposited in the upper nasopharyngeal region or the first five generations of large conducting airways.
1 to 10 μm
Smaller particles (______to _____μm) can also be deposited in the tracheobronchial region
0.001–0.1 μm
Particles ranging from _____to______ μm can be transported to the smaller airways and deposited in the alveolar region
0.003 to 5 μm
Materials that are hygroscopic (i.e., those that readily absorb moisture), such as _____,__________, and_________, take on water and grow in size in the warm, saturated atmosphere of the upper and lower respiratory tract
sodium chloride, sulfuric acid, and glycerol
Deposition mechanisms
- impaction
- interception
- sedimentation
- diffusion
- electrostatic deposition (for positively charged particles only)
occurs in the upper respiratory tract and large proximal airways where the airflow is faster than in the small distal airways because the cumulative diameter is smaller than in the proximal airways.
(DEPOSITION MECHANISM)
impaction
In humans, most > 10 μm particles are deposited in the _________ or ________ and cannot penetrate tissues distal to the larynx.
(DEPOSITION MECHANISM)
nose or oral pharynx
For _______ to _________ μm particles, impaction continues to be the mechanism of deposition in the first generations of the tracheobronchial region
(DEPOSITION MECHANISM)
2.5 to 10 μm
occurs when the trajectory of a particle brings it near enough to a surface so that an edge of the particle contacts the airway surface.
(DEPOSITION MECHANISM)
interception
Although fiber diameter determines the probability of deposition by impaction and sedimentation, interception is dependent on _________
(DEPOSITION MECHANISM)
fiber length
a fiber with a diameter of 1 μm and
a length of 200 μm will be deposited in
the bronchial tree primarily by
________ rather than impaction.
(DEPOSITION MECHANISM)
interception
controls deposition in the smaller bronchi, the bronchioles, and the alveolar spaces, where the airways are
small and the velocity of airflow is low
(DEPOSITION MECHANISM)
sedimentation
Sedimentation is not a significant route of particle deposition when the aerodynamic diameter is ≤ ______ μm
(DEPOSITION MECHANISM)
≤ 0.5 μm
Sedimentation is dependent on the ________ a particle is in a compartment (i.e., an alveolus) and can be increased by breath holding
(DEPOSITION MECHANISM)
time
________ of a particle within the air is an important factor in the deposition of submicrometer particles
(DEPOSITION MECHANISM)
diffusion
Diffusion is an important deposition mechanism in the nose, airways, and alveoli for particles ≤ ____ μm
(DEPOSITION MECHANISM)
≤ 0.5 μm
__________ (0.1 μm and smaller) are also
trapped relatively efficiently in the upper airways by diffusion.
(DEPOSITION MECHANISM)
Nanometer particles
is a minor deposition mechanism for
positively charged particles
(DEPOSITION MECHANISM)
Electrostatic deposition
The ________ of the airways is negatively charged and attracts positively charged particles.
(DEPOSITION MECHANISM)
surface
Lung defense is dependent on ___________, wherein rapid removal lessens the time available to cause damage to
the pulmonary tissues or permit local absorption
particle clearance
particle clearance is equivalent to clearance from the body. (t or f)
F; Not equivalent
Types of particle clearance
- nasal clearance
- tracheobronchial clearance
- alveolar clearance
- Particles deposited in the anterior portion of the nose are removed by extrinsic actions such as wiping and blowing.
- Particles deposited in the posterior portion of the nose are removed by mucociliary clearance that propels mucus toward the glottis, after which the particles are swallowed.
- Soluble particles may dissolve and enter the epithelium and/or blood before they can be mechanically removed.
Nasal clearance
- Particles deposited in the tracheobronchial tree are also
removed by mucociliary clearance. - In addition to deposited particles, particle-laden macrophages are also moved upward to the oropharynx,
where they are swallowed.
Tracheobronchial clearance
- Particles deposited in the alveolar region are removed by specialized cells, the alveolar macrophage.
- Lung defense involve both the innate and adaptive and immune systems.
- Macrophages are the primary effector of innate lung immunity and their ability to accomplish phagocytosis depends on the recognition of foreign or damage cells by a variety of macrophage surface macromolecules and receptors.
-Phagocytosis requires
> particle binding
> receptor activation
> actin polymerization
> vesicular membrane closure
Alveolar clearance
ACUTE RESPONSES OF THE LUNG TO INJURY
- Trigeminally mediated airway reflexes
- Bronchoconstriction airways hyperreactivity, and neurogenic inflammation
- acute lung injury (pulmonary edema)
Certain gases and vapors stimulate nerve endings in the nose, particularly those of the _________
Trigeminal nerve
___________ may be activated by many irritants causing tickling, itching, and
painful nasal sensations
Transient receptor potential channel receptors
Subfamily A receptors are activated by several irritants including:
- acrolein,
- allyl isothiocyanate
(wabasi), - allicin (garlic),
- cinamaldehyde,
- chlorine,
- ozone,
- hydrogen peroxide
_______ causes a decrease in airway diameter and a corresponding increase in resistance to airflow
bronchoconstriction
Bronchoconstriction can be provoked by:
- acrolein
- cigarette smoke,
- air pollutants,
- cholinomimetic drugs (acetylcholine),
- histamine,
- various prostaglandins
- leukotrienes,
- substance P
- nitric oxide
Characteristic symptoms of bronchoconstriction
- wheezing
- coughing
- sensation of chest tightness
- dyspnea
___________ (adult or infant respiratory distress syndrome) is marked by alveolar epithelial and endothelial cell perturbation and inflammatory cell influx that leads to surfactant disruption, pulmonary edema, and atelectasis.
acute lung injury
may compromise alveolar barrier function several hours after exposure to low concentrations, and immediate alveolar damage and death with high concentrations
Acrolein, HCl, NO2, NH3
____________ represents an acute, exudative phase of lung injury that alters ventilation–perfusion relationships
and limits diffusive transfer of O2 and CO2 even in otherwise structurally normal alveoli.
toxic pulmonary edema
CHRONIC RESPONSES OF THE LUNG TO INJURY
- COPD
- Lung cancer
- Asthma
- Pulmonary fibrosis
- Very common
- Characterized by a progressive airflow obstruction, involves airway (bronchitis)
and alveolar pathology
COPD
is defined by the presence of sputum
production and cough for at least three months.
chronic bronchitis
destruction of the gas-exchanging surface
area results in a distended, hyperinflated lung that no longer effectively exchanges oxygen and carbon dioxide as a result of
both loss of tissue and air trapping
emphysema
The major cause of human emphysema is, by far, _________, although other toxicants also can elicit this response.
cigarette smoke inhalation
The pathogenesis of emphysema involves a _____________________ that leads to the remodeling of the supportive connective tissue in the parenchyma and separate
lesions that coalesce to destroy lung tissue.
proteinase–antiprotease imbalance
is one of the body’s main defenses against uncontrolled proteolytic
digestion by this class of elastolytic enzymes, which includes elastase.
Alpha1-antiprotease (also called alpha1-antitrypsin)
is now the leading cause of death from cancer among men and women.
lung cancer
Two major forms of lung cancer
- non-small lung cancer 85%
>carcinoma,
>adenocarcinoma,
>large-cell lung cancer - small lung cancer 15%
The potential mechanisms of lung carcinogenesis center on:
damage to DNA and/or active oxygen species
characterized clinically by attacks of shortness of breath, which is caused by narrowing of the large conducting
airways (bronchi).
asthma
The clinical hallmark of ________ is increased airway reactivity of the bronchial smooth muscle in response to
exposure to irritants
asthma
Fibrotic lungs from humans with acute or chronic pulmonary fibrosis contain increased amounts of __________
(PULMONARY FIBROSIS)
collagen
In lungs damaged by toxicants, the response resembles adult
or infant ______________
respiratory distress syndrome
Excess lung collagen is usually observed not only in the alveolar interstitium, but also throughout the __________
and _________________
alveolar ducts; respiratory bronchioles
Type ___ and ___ collagen are major interstitial components and
are found in an approximate ratio of 2:1
I and III
patients with idiopathic
pulmonary fibrosis and patients dying of acute respiratory distress syndrome.
increase in Type I collagen relative to Type III
Commonly used tests in human studies include:
measurement of FEV1, FVC, and
airway resistance
