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CHAPTER 14:

Respiration
Lungs
•  Lungs
–  Pleurae – membranes that surround each lung; closed sac against which the lung grows
–  Visceral – side adjacent to lung; if your lung was a fist and the pleurae a deflated balloon,
this is the side touching your fist as you punch against it
–  Parietal – side away from lung; if your lung was a fist and the pleurae a deflated balloon,
this is the side opposite your first as you punch against it
–  Intrapleural space: space in between the visceral and parietal surfaces
Thoracic cavity
ext intercostals & contracts due to
diaphragm passive relaxation of
actively contract ext intercostals &
causing thoracic diaphragm
cavity to expand

INSPIRATION EXPIRATION

Normal Ventilation or Normal Breathing


Respiration
•  Ventilation
–  Mechanical movement of air in and out of lungs
•  Gas Exchange
–  Lungs: Between air and blood; occurs in the alveoli
and is a spontaneous process that occurs by
simple diffusion
–  Tissues: Between blood and cells
•  Oxygen utilization
–  Biochemical processes in cell
Air Passages
•  Conducting Zone
–  No gas exchange
–  Inspired air is humidified and filtered, mainly in the
nose
–  From external nares and mouth to beginning of
respiratory bronchioles
•  Upper airway: nose/mouth to beginning of trachea
•  Lower airway: beginning of trachea (larynx) to start of
respiratory bronchioles
•  Respiratory Zone
–  Gas exchange
–  Respiratory bronchioles and Alveoli
Lung Facts
• Lung size
• The right lung is slightly larger than the left lung – which is smaller to accommodate
the heart
• Lung lobes
• Upper and middle lobes are in the anterior, or front of the body
• Lower lobe is in the posterior, or back of the body
• Larynx
• Consists of cartilage, intrinsic and extrinsic muscles and a mucosal lining
• Laryngeal cartilage houses the vocal cords, or voice box
• The intrinsic muscles of the larynx alter the positions, shape and tension of the
vocal folds to allow for the production of various sounds
Conducting Zone

Know upper and lower airway


Conducting Zone

Larynx → trachea→Primary or mainstem bronchi→ → →


Conducting Zone
17 branches total, including alveoli
1 Larynx (1)

1 Trachea (1)

2 Primary or Mainstem Bronchi (2)

Bronchi
(>20 secondary and tertiary branches,)

Bronchioles
(>100,000)

Alveolar sacs
(8 million)

Alveoli
(many millions)
Zones

Conducting zone stops and respiratory zone begins with alveolus


Zones
Structure Glands Cell Type Support

Trachea Mucous Goblet and Ciliated Hyaline Cartilage


Cells
Bronchioles No glands Ciliated, Clara, Smooth muscles
Goblet cells
Respiratory No glands Clara and Type I Type III collagen
Bronchioles and II pneumocytes
Alveoli No glands Type I and II Type III collagen
pneumocytes

Clara cells: protect bronchial epithelium with their secretory products. They are never
seen in areas with mucous glands
normal breathing

Muscles of Ventilation hyperventilation

Contraction raises sternum


up and forward and also
raises ribs, increasing size of
thoracic cavity 

Contraction raises
Contraction lowers
ribs, increasing size ribs, decreasing size
of thoracic cavity of thoracic cavity

Contraction presses
viscera up against the
diaphragm further,
decreasing size of
thoracic cavity

Contraction flattens
or lowers the dome,
increasing size of
thoracic cavity

http://video.search.yahoo.com/search/video;_ylt=A0oG7mPdqZ1OQ10AsuhXNyoA?p=lung%20ventilation&fr2=piv-web
Normal inspiration: primarily driven by
diaphragmatic and external intercostal
contraction

Relaxing breathing requires the contraction of the


external intercostals and diaphragmatic muscles.
Expiration is simply releasing the muscles. active
However, ACTIVE breathing requires the external (contracted diaphragm flattens)
abdominals and internal intercostals during
expiration
Normal expiration: primarily driven by
diaphragmatic and external intercostal
relaxation (passive)

active
passive
(contracted diaphragm flattens)
(relaxed diaphragm)
Inspiration: Expiration:
Increase size of thoracic cavity
Decrease size of thoracic cavity to raise
which lowers pressure in thorax
pressure in thorax (raise intrapulmonary
(lower intrapulmonary pressure).
Goal pressure) which causes airway pressure
Room air pressure then exceeds
to exceed room air pressure and air flows
airway pressure and air flows into
out of lungs.
lungs.

Relaxation of diaphragm and external


Contraction of diaphragm and
intercostals coupled with elastic recoil
Normal external intercostals lowers
of lungs increases intrapulmonary
Breathing intrapulmonary to -3 mmHg.
pressure to +3mmHg.
(Active)
(Passive)

More forceful contraction of


Increased
Diaphragm/External Intercostals Graded contraction of Accessory Muscles
Ventilatory
plus graded recruitment of of Expiration (e.g., internal intercostals
Effort
Accessory Muscles of Inspiration and abdominal muscles); ~ +30mmHg
(Active)
(e.g., scalene muscle); ~ -20mmHg
Surface Tension
•  Water molecules lining the surface of
all airways are attracted to each other
–  This creates a force or pressure (P) that
tends to cause airways to close (“surface
tension;” attraction to collapse)
•  Tendency to collapse (no
exchange)
–  Solution: Surfactant (phospholipids)
•  type produced by type II alveolar cells
•  reduces surface tension
•  keeps small alveoli open
•  production starts late in gestation
–  Early birth: Respiratory Distress Syndrome
(RDS) due to alveolar collapse
Type 1 alveolar cells: the lining cells
for easy gas exchange
Type 2: produce surfactants
Lung volumes and capacities

Lung function test


using a spirometer
Lung volumes and capacities
Ventilation
•  Respiratory minute volume (or minute ventilation)
–  Volume of air inhaled in 1 minute (or exhaled, as the two are the same)
–  At rest, Minute Volume = tidal volume x respiratory rate (breaths/min)
–  Can be increased (hyperventilaton) or decreased (hypoventilation)
•  Respiratory rate and depth of respiration typically both change at same time in same
direction
•  Hyperventilation: increased rate and depth of ventilation
•  Hypoventilation: decreased rate and depth of ventilation
• Most important: alveolar air
measurements of CO2 and O2
• When breathing in, the inspired air is
only a fraction of the residual volume of
air (and its pressure) in the lungs Fully humidified air is known to have
a PH2O of 47 mmHg at body temp (37C)

Variable,
here assumed to be 0 Systemic Artery
PCO2 =40 mmHg

PO2 =100 mmHg

Clinical
indices of
lung function
*THIS IS IMPORTANT* 
Effects of respiratory minute
volume on PCO2 in arterial blood
Control of Ventilation
•  Respiratory Centers in brain stem
•  Rhythmicity Area drives automatic
breathing (cyclic contraction and
relaxation of diaphragm and external
intercostals)
–  Diaphragm innervated by phrenic nerve
which originates at the 6th cervical vertebra
•  spinal injuries above C6 are fatal without
immediate intervention
•  Ondine’s Curse: congenital or acquired
neurological disease leading to reduced function of
Rhythmicity Area
–  Solutions: tracheostomy or . . .

•  Multiple inputs to these centers adjust


ventilation to meet needs (will discuss)
• 
Control of Ventilation
Respiratory Centers in brain stem
•  Rhythmicity Area drives automatic breathing (cyclic contraction
and relaxation of diaphragm and external intercostals)
–  Diaphragm innervated by phrenic nerve which originates
at the 6th cervical vertebra
•  spinal injuries above C6 are fatal without
immediate intervention
•  Multiple inputs to these centers adjust ventilation to meet
needs (will discuss)
•  Some drugs depress this center, reducing respiration. Also
inhibit the cerebral cortex. Think: when you hold your breath,
you feel the need to breathe in. Inhibition of the cerebral cortex
will make it so you don’t feel any stimuli to breathe in.
–  Narcotics
–  Alcohol
–  Anesthetics (Propofol)
–  Reduce respiratory rate and tidal volume (can cause
apnea if overdosed)
•  Rhythmicity Area in
medulla oblongata
will produce an
automatic ‘normal
Medulla Oblongata
(Rhythmicity Area) breathing’ pattern of
ventilation in the
absence of any other
input that is often
irregular (which is
‘normal’ for it; check
tests)
•  *the aortic and
carotid bodies are
peripheral
chemoreceptors
•  Cerebral cortex can
voluntarily control
ventilation
–  you can “take a deep
Medulla Oblongata
(Rhythmicity Area) breath” while a physician
auscults your lung sounds
•  Cerebral cortical activity
also affects the activity
of the Rhythmicity Area
in a general way that is
not under voluntary
control
–  anxiety often leads to
hyperventilation
•  Apneustic Center
enhances and
prolongs inspiration
•  Pneumotaxic
Medulla Oblongata
(Rhythmicity Area) Center inhibits
inspiration
•  These 2 centers were
discovered in early
animal experiments.
•  Beyond the MCAT,
an important role for
these 2 centers in
health or disease of
people (or animals) is
not known.
Medullary Central Chemoreceptors;
more sensitive (80%)
-highly responsive to ↑CO2
-responsive to ↑ H+

Peripheral Chemoreceptors (20%)


-highly responsive to ↑CO2
-responsive to ↑ H+
-responsive to ↓↓O2
The important modifiers of ventilation:
Input to Rhythmicity Area in the medulla alters ventilation (rate and depth).

Drugs

-
↑ CO2 , ↑H+

↑ CO2 , ↑H+, ↓↓ O2)

Input to Rhythmicity Area


in the medulla alters
ventilation (rate and depth)
•  Chemoreceptors play
the critical role in
controlling ventilation
•  Central (80% of CO detection)
2

–  Medulla oblongata
–  Detect H+ (directly) and
Medulla Oblongata
(Rhythmicity Area)
CO2 (indirectly)
–  Brain tissue, CSF, and
blood perfusing the brain
•  Peripheral (20%)
–  Carotid and Aortic Bodies
–  Detect H+ (directly) and
CO2 (indirectly) in arterial
blood
A Key Respiratory Reaction

Carbonic
Anhydrase
Enzyme

Carbonic Proton Bicarbonate


Acid

•  Key Points:
–  Carbonic anhydrase is ubiquitous
–  Adding CO2 to this system will lead to ↑H+
Carbonic
Anhydrase
Enzyme

Carbonic Proton Bicarbonate


Acid
•  If CO2 builds up in blood:
–  Will get ↑H+ in blood by mass action of above reaction (same
thing occurs in carotid and aortic bodies).
–  Aortic and Carotid
•  ↑H+ Lowers the pH of the blood, which the aortic and carotid bodies are
sensitive to. Note: the aortic and carotid bodies are sensitive to the change in
pH, regardless of the change in CO2. So pH could drop but have nothing to
do with CO2 and the aortic and carotid bodies would still detect the shit out of
it.
•  Lowered O2 essentially causes the same response from the aortic and
carotid bodies as lowered pH does (increased ventilation), only it is even
greater. If blood O2 falls below 50mmHg, it can stimulate ventilation directly
–  Medullary
•  ↑H+ Also lowers the pH of the CSF, which the medullary chemoreceptors are
sensitive to. Blood pH isn’t detected by the medullary chemoreceptors
because the BBB prevents changes in pH for brain blood
–  Augments the central chemoreceptors response which is to
increase ventilation (increase frequency and depth of
ventilation)
***In health, CO2 levels control
ventilation.
(In disease, pH and O2 levels can have an
independent effect.)***

Know chart
At rest, tissues utilize more oxygen than can be carried as
dissolved in plasma making an additional oxygen carrier
(hemoglobin) essential for life.

Hemoglobin: 98% of blood’s oxygen carrying capacity


Fe+2

lungs
deoxyhemoglobin + O2 oxyhemoglobin
tissues
Oxygen and Hemoglobin
•  Systemic arterial blood (after lungs)
–  20 mL of O2/100 mL of blood
–  97% of hemoglobin binding for O2 are
occupied (97% saturation)
–  PO2 = 100 mmHg
•  Systemic venous blood (after tissues)
–  15 mL of O2/100 mL of blood
–  75% of hemoglobin binding for O2 are
occupied (75% saturation)
–  PO2 = 40 mmHg
Oxyhemoglobin Dissociation Curve
Bohr Effect
•  ↑H+ (↓pH) shifts curve to right (more O2 released to tissues)

Delivered:

5 mL O2

8 mL O2

veins arteries
Tissue Metabolism
•  Key metabolic processes:
–  Oxidative Phosphorylation
•  Required from blood (respiratory system):
–  O2
•  Wastes removed by blood (respiratory system):
–  CO2, H+
•  Increased metabolic activity means increased O2
requirement. What adaptations are present?
–  Bohr and Temperature effects
•  Increased [H+] and/or temperature shift curve to right (more
oxygen released to tissues)
Carbon dioxide transport
•  As with oxygen, solubility is limited
–  Not enough CO2 can be dissolved in plasma
to keep up with its production from normal
tissue metabolism
–  Solutions: transport CO2 in three forms
1.  Dissolved (10%)
2.  Bound to hemoglobin (Carbaminohemoglobin; 20%)
3.  As bicarbonate (HCO3- ; 70%)
1.  Causes an “alkaline tide,” increasing the pH slightly
Carbon dioxide transport
•  These numbers actually make a lot of fucking sense if you think about it:
–  1. 10% dissolved in blood: any more than this and the aortic, carotid and
medullary chemoreceptors are going to do their job and make you
hyperventilate all the fucking time. not cool
–  2. 20% bound to carbaminohemoglobin: So, systemic arterial blood (filled
with oxygen after a nice breath of spring air) has a 97% saturation rate
for hemoglobin. Systemic venous blood, which was just raped by
oxygen-deprived tissues carrying out oxidative phosphorylation, has a
saturation rate of 75%. So, from fresh air to being raped is a difference of
only 22%...thus there isn’t a whole lot of hemoglobin that are “empty” for
CO2.
–  3. Well, you gotta dissolve it somewhere.
CA

Similar to GLUT4 transporters in terms of removing


product to keep reaction moving to the right. This is
cool
CA

Read up on this
Ventilation and Acid-Base
Balance
•  [H+] is one of 3 control factors for
ventilation (CO2, H+, O2)
•  Acidosis: any process that leads to the
accumulation of H+ in the body
Ventilation and Acid-Base
Balance
•  Suppose H+ ions build-up in blood (blood pH
falls), what change occurs in ventilation
minute volume and how does this impact [H
+]?

–  pH stimulates peripheral chemoreceptors


(carotid and aortic bodies) → ↑increased rate
and depth of ventilation → ↑minute volume
–  Relies on peripheral chemoreceptors since H+
can’t get from blood to brain chemoreceptors
Respiratory response to acidosis

Carbonic
Anhydrase
Enzyme

Carbonic Proton Bicarbonate


↓ by hyperventilation Acid

•  Key Point:
–  Removing CO2 will shift curve to left by mass
action and this will ↓H+ (raise blood pH toward
normal)

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