THE RESPIRATORY SYSTEM

I. Definitions
A. Respiration - O 2/CO 2 exchange between the body and the environment.
1. Pulmonary ventilation
2. Diffusion of O 2 and CO 2
3. Transport of gases to and from tissue

B. Breathing - The movement of gas in and out of the lungs.

C. Lungs - air/blood flow for O 2 and CO 2 exchange. Maintaining correct CO 2

partial pressure (P C O 2) is more important than P O 2 because of pH.

D. Perfusion (Q) - cardiac output

F . Partial pressure- How gases are measured.

E

II. Structural Basis of Breathing

A. Airw ays - structural/functional characteristics

Trachea cartilaginous support Have smooth muscle.

9 Can constrict airways
Bronchi esp. term. bronchioles
9 Have cilia; secrete mucus
Bronchioles conducting zone
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Terminal
bronchioles
9
Respiratory
bronchioles
9 Diameter depends on
Alveolar ducts "terminal respiratory lung volume
9 unit"; primary areas of
Alveoli gas exchange

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Alveoli have thin walls and a large
surface area.

B. Pulmonary capillaries - cover 70-80% of alveolar walls. Capillary volume can

increase through recruitment and distension.

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 C. Definitions
1. Inspiration - active phase of
b reathing. D i a p h r a g m a n d
external intercostal muscles.
2. Expiration - usually a passive
process. Abdominal muscles and
internal intercostal muscles can
participate.

D. Lung expansion and contraction -

1. Transpulmonary pressure - pressure difference between thoracic cavity and
alveoli.
2. Compliance - how easily lung expands.
Determined by:
a. elasticity of tissue
b. surface tension

Lung compliance measures the force that is needed to

expand the lungs, or the ease of expansion. A lung with a
high compliance is easy to expand, whereas a lung with a
low compliance is stiff and hard to expand. The opposing or
compressive forces are the lung elasticity and surface
tension.

Emphysema - loss of elastic fibers, so it

increases compliance and decreases
elastance.

Fibrosis decreases compliance, so lung is

harder to expand and collapses further when
exhaling.

Asthma - Increase in airway resistance due to

constriction of smooth muscles.

3. Surface tension - attraction of water molecules for each other at the

interface with air. This collapses alveoli.
4. Surfactant - Mixture of phospholipids, apoproteins and Ca2+ secreted by
type II alveolar cells. Decreases surface tension.
Neonatal respiratory distress syndrome

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III. Alveolar Ventilation -

A. Typical volumes and capacities:

V T = tidal volume = vol. of air in each breath.
< T = respiratory minute vol.= VT x freq. of breaths

NOTE: In these notes, < = “V dot” = vol/min

V A = vol. of fresh air that enters functional alveoli in each breath.
< A = Alveolar Ventilation (alveolar minute volum e) volume of fresh air
participating in gas exchange per unit time.
V D = physiological dead space = air that does not reach gas exchange areas.
Includes anatomical dead space and functional deadspace.
VA = VT - VD
< < <
A = T - D

B. Normal values: V T = 500 ml <

T = 6000 m l/min; minute ventilation
V D = 150 ml = <
1800 ml/min
<
D
V A = 350 ml A = 4200 m l/min; alveolar ventilation
f = 12 breaths/min A = alveolar

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C. Relationship between A and CO 2 : <
They are inversely related to each other.
Exhaled CO2 = metabolic CO 2 production.
Assuming constant CO 2 production,

< A (L/min) = < CO2 ml/min x K

P ACO2 (mm Hg) (K = cor rec tion fac tor = 863 m m Hg , at T b =33 o C,

barometric pressure = 760 mm Hg)

or P A C O 2. < /<
CO2 A

<
1) Increasing A decreases P A C O 2.
2) higher CO2 production shifts curve to
the right.

D. Relationship between A and O 2 <

<
1) Increasing A increases PA O 2.
2) Increased O2 consumption shifts the
curve to the right.

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 E. Alveolar Gas Equation - predicts P A O 2 based on P A C O 2.
P A O 2 . P O2 (air) - P A C O 2/R (R = Respiratory exchange ratio= CO2
production/O 2 consumption) Ideally, R = 0.8

R is related to metabolic rate, energy sources, activity, etc.

Use P A C O 2 to estimate PA O 2:

During exercise, R can decrease to 0.53. P A O 2 and P A C O 2 don’t change because

<
of the ventilation/perfusion ratio ( A /Q), which goes up during exercise.

At rest < A = 4.2 L/min and Q = 5 L/min, < /Q = 0.84.

A

During exercise, < A can be 26 L/min and Q can be 15 L/min, so < /Q = 1.7
A

Changes in R counteract changes in < /Q.

A

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IV. Ventilation/Perfusion Ratios ( < /Q) A

P a C O 2, P A O 2 , and < /Q are tightly related.

A

<
A. Mismatch in A and Q.
1. Wasted ventilation (high < /Q)- Ventilating alveoli receiving decreased
A
perfusion.

<
2. Physiological shunt (low A /Q)- Perfusion of areas not receiving
ventilation (or blood shunts around the capillary beds).

Normally, the upper lung has excess physiological dead space, while the
lower lung has excess physiological shunt.

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 Smoking leads to:
1) small bronchioles become obstructed, causing excessive physiological
shunt
2) alveolar walls become damaged causing excessive physiological dead
space. (wasted ventilation)
3) incr. compliance of lungs
4) increases in allergies and asthma

<
Matching Q and A ,
B. Control of Pulmonary flow (Q) to match A . <
1. Passive (local) regulation -Increase in pulmonary capillary volum e.
2. Active (local) regulation -increased smooth muscle tone due to:
alveolar oxygen tension P A O 2 -“hypoxic vasoconstriction”: low P A O 2
causes vascular muscle constriction so areas receiving low
ventilation will receive less perfusion.

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 <
V. Neural/Central regulation of A /Q - Control of breathing
A. Central organization "Breathing center" in the medulla:
1. Dorsal neuronal group in ‘nucleus of the solitary tract’ (NTS) Stimulates
inspiration. Can control breathing alone.
2. Ventral neuronal group in ‘nucleus ambiguous’ (NA) Normally inactive;
stimulates inspiration and expiration.
3. Pneumotaxic center - located in the pons. Stops inspiration by inhibiting
dorsal neuronal group. Increases breathing rate.
4. Apneustic center - in lower pons. Stimulates NTS; leads to prolonged
inspiration

These are influenced by:

a. reticular activating system associated with behavioral arousal.
b. peripheral and central chemoreceptors
c. Mechanoreceptors (stretch receptors) from smooth muscle along
airways and breathing muscles.
d. Voluntary control of breathing - via cortex. Can override brainstem.

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B. Spinal integration - mechanoreceptors in muscles stimulate spinal motor
neurons to inhibit their activity
C. Chemoreceptors - responsive to [H + ] and [CO 2 ].

i CO 2 + H 2 O W H 2 CO 3 W H + + HCO 3 - (bicarbonate) i
carbonic anhydrase

1. Central chemoreceptors - along surface of medulla; sensitive to[H + ].

2. Peripheral chem oreceptors - carotid bodies; sense P CO2 and P O 2

D. < as function of P a C O 2, P a O 2
< . This is modulated by:
A
An increase in P a C O 2 causes an increase in A

1. Arousal effects -

= asleep/anesthetized

= awake

= exercising

2. pH effects -

= high pH/high HCO3-

= normal pH

= low pH/low HCO3-

3. Oxygen effects -

= high O2

= normal O2

= low O2

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 Likewise, reduced P a O 2 6 8 < A via sensors in
carotid bodies.

Increasing Pa C O 2 shifts the curve up and to the right,

so at the same P a O 2, have higher A <

E. Mechanoreceptors
1. Receptors in lungs:
a. stretch receptors within smooth muscle. Promotes expiration.
b. irritant receptors around epithelial cells. Constricts airways and 8's
breathing rate.
c. c fibers in lung interstitial and alveolar walls. Causes rapid, shallow
breathing.
2. Receptors in chest wall:
Modify afferent m otor signals to minimize changes in ventilation.
Located in diaphragm, intercostals, and abdominal wall.

F. Sleep
1. General changes - Responses are reduced due to 9reticular activating
system stimulation.
2. Sleep apnea -
a. Central apnea - inhibition of central breathing centers.
b. Obstructive apnea - blockage of airways (associated with obesity).

G. Exercise
<
8 A , with little change in
Change in Va in response
P a C O 2. to a change in PCO2

= resting
Change in PCO2 in
response to a change in Va
= exercise

= change in
set point

<
Combination of 2 different plots of A vs. P C O 2. Changes causes both curves to
shift, creating a new point of equilibrium that maintains the correct P a C O 2.

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VI O 2 and CO 2 Transportation
A. O 2 Transportation - Reversible binding
of O 2 to Hb:
O 2 -Hem oglobin Equilibrium Curve:

1. O 2 is picked up in the lungs and

released in tissues
2. Hb buffers blood P O 2 from major
changes.

B. Factors affecting HbO 2 equilibrium curve

1. [H + ], P C O 2 - Bohr effect.
2. Incr. temp. or 2,3-diphosphoglycerate
3. CO - decreases O 2 binding capacity

C. CO 2 Transport
In the blood, CO 2 is transported as:
6 HCO 3 - (ionic form; 90% of CO 2 in blood)
6 protein bound (carbamino-CO 2 ; HbCO 2 )
6 40 ml/L dissolved in plasma as a gas

CO 2 + H 2 O W H 2 CO 3 W H + + HCO 3 -
8
Carbonic anhydrase

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In red blood cells this goes very rapidly. End products are eliminated by:
1. H + combining with Hb 6 HHb
2. HCO 3 - diffuses into plasma in exchange for Cl-.
3. HCO 3 - attaching to Hb 6 HbHCO 3

D. Modulation of CO 2 binding to Hb - Haldane effect

P O 2 decreasesCO 2 binding to Hb. This nearly doubles the CO2 exchange in
the lungs.

= tissue conditions

= alveolar capillaries CO2-

bound
= change going from Hb
tissue to alveoli

E. [H + ] Regulation - maintain pH 7.4, range 7.2-7.6; damaging beyond 6.7

and 7.8.

pH - log[HCO 3 -]
PC O 2

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 1. pH - P C O 2 - HCO 3 - relationship Bicarbonate is potent buffer;
8acids cause HCO 3 - to be converted to CO 2 and H 2 O:
carbonic anhydrase

H + + HCO 3 - 6 H 2 CO 3 W CO 2 + H 2 O

and CO 2 is eliminated in lungs. Hb acts as an additional buffer

if 8CO 2 6 8H +
if 8HCO 3 - 6 9H +

2. pH - bicarbonate diagram

At a given P C O 2, as you increase

pH, [HCO 3 -] goes up. If you
increase P C O 2, the curve shifts to
the left. The Buffer slope line
represents the buffering
capacity of the blood, especially available Hb.

During exercise, you get an8in acids.

i. Hb buffers some H + , so buffer slope line drops.
ii. HCO 3 - buffers some, so get 9[HCO 3 -].
iii. 8P C O 2 causes 8 ventilation; with over compensation you get 9P C O 2.

3. Physiologic factors controlling pH

a. respiratory control mechanisms:
b. renal mechanisms (discussed in upcoming lectures on Renal system)

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Nicotine in urine of smokers' babies
By LEE BOWMA N, Scripps Howard News Service
May 14, 2006

Scientists have found cancer-causing chemicals from tobacco smoke in the urine of nearly half the babies of
smoking parents they tested in a new study.
The study found "substantial uptake" of nicotine and the chemical NNAL in 67 of 144 infants, or 47 percent, and the
levels were directly related to how much their parents smoked around them in the home or car. NNAL is a byproduct
of a toxin in tobacco that's known to cause lung cancer.

"The take-home message is: Don't smoke around your kids," said Stephen Hecht, a cancer-prevention researcher at
the University of Minnesota Cancer Center who led the study, published Friday in the journal Cancer Epidemiology,
Biomarkers and Prevention.

Hecht and his team collected urine samples from the infants, 3-12 months, and interviewed parents about smoking
habits. Eighty-two percent of the babies' mothers were daily smokers and 72 percent had other family members,
including fathers, who smoked.

Parents or other family members of babies who had detectable levels of NNAL smoked an average of 76 cigarettes
a week in the home or car with the infants present. Children with undetectable levels of the chemical had family
members who smoked an average of 27 cigarettes near the babies each week. Nearly all the babies had detectable
levels of nicotine, as well as cotinine, the byproduct that's left as the body metabolizes nicotine.

However, Hecht said that the difference likely reflects the limits of the equipment used by the researchers. "With
more sensitive analytical equipment, the NNAL from urine of babies in lower-frequency smoking households would
most likely be detectable."

The infants' NNAL levels were higher than those seen in studies of adults exposed to secondhand smoke in the
home.

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