RESPIRATORY III

Gas transport in blood

Regulation of respiration

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 GAS EXCHANGE
Atmosphere:
PO2 - 160 mmHg
PCO2 - 0.3 mmHg

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 OXYGEN TRANSPORT
• Oxygen transport in the blood is either
• bound to heme portions of the hemoglobin within the RBCs (98.5%)
• dissolved in the plasma (1.5%)

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 BOUND TO HEMOGLOBIN
• Loading and unloading of O 2 is given by a simple reversible equation:
HHb + O2  HbO2 + H+
deoxyhemoglobin oxyhemoglobin
• O2 binding is “cooperative”
• The binding of the 1st O2 molecule causes the Hb to change shape
which makes it easier for the 2nd O2 to bind. Binding of the 2 nd O2
makes it easier for the 3 rd.
• As O2 loading proceeds, the affinity of Hb for O 2 
• When Hb has 4 bound O2 molecules it is fully saturated. When it has 1,
2, or 3 it’s unsaturated
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 Hb-O2 dissociation curve

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 HEMOGLOBIN PROMOTES THE NET TRANSFER OF O 2 AT
BOTH THE ALVEOLAR AND TISSUE LEVELS

• At alveolar level, Hb removes O2

dissolved in plasma. Maintain PO 2
pressure gradient for diffusion

• At tissue level, O2 move out from

blood to tissue, the PO2
decreases, the Hb unload some
stored O2.

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 FACTORS PROMOTE UNLOADING OF O 2

1. Low pH
2. High PCO2
3. High temperature
4. High 2,3-diphosphoglycerate

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How much oxygen is in the blood? Ca O2
Need to know how much oxygen is dissolve in plasma (PaO2),
% bound to hemoglobin (SaO2) and total number of O2 binding sites

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 CARBON DIOXIDE TRANSPORT

• 7% is dissolved in plasma.
• 93% diffuse into RBC
• 23% is bound to globin portion
of Hb (carbaminohemoglobin)
• 70% is transported as HCO3-,
the bicarbonate ion.

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To maintain charge balance, a Cl- enters the RBC when the
HCO3- leaves. (through HCO3- -Cl- carrier)
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This is known as the chloride shift (Hamburger effect)
Tissues Lungs

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 QUIET RESPIRATION
• During quiet respiration, the
DRG is active for about 2
seconds (inspiration) and then is
inactive for 3 seconds
(expiration)
• DRG inspiratory neurons fire 
impulses travel down the
phrenic and intercostal nerves
(output)  contraction of
inspiratory muscles 
inspiration
• DRG inspiratory neurons cease
firing  inspiratory muscles
relax  expiration
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 FORCED RESPIRATION

• During forced respiration, the level

of DRG activity increases to where
it activates VRG neurons.
• Thus, normal inspiratory
muscles and accessory
inspiratory muscles are
activated.
• At the end of the active inspiration,
the VRG expiratory neurons initiate
active expiration.

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 PNEUMOTAXIC CENTER

• Located in the upper pons.

• The primary effect of this center is to control the duration of the
filling phase of the lung cycle.
• When the pneumotaxic signal is strong, inspiration might last for as
little as 0.5 sec, thus filling the lungs only slightly; when the
pneumotaxic signal is weak, inspiration might continue for > 5 sec,
thus filling the lungs with a great excess of air
• The function of the pneumotaxic center is primarily to limit
inspiration. This has a secondary effect of increasing the rate and
pattern of respiration.

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 APNEUSTIC CENTER

• Located in the lower pons

• The apneustic center sends signals to the DRG in the medulla to
delay the switched off signal provided by the pneumotaxic center
(regulate regular breathing rhythm)
• The apneustic center may prolong inspiration when your oxygen
requirements become elevated, as during exercise (control depth of
respiration)

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 Penumotaxic

-
Apneustic

+
DRG + VRG

Quiet breathing Forced breathing

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 REGULATION OF RESPIRATION
Main objective: To maintain normal levels of PO22, PCO22 and pH of
arterial blood

Central Medulla, pons,

controller cerebral cortex

Chemorecptors, Respiratory
mechananoceptors, Sensors Effectors muscles
proprioceptors

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 CENTRAL CHEMORECEPTORS
• 80% of respiratory drive for ventilation is a result
of its stimulation
• located in the ventrolateral surface of medulla,
near the point of exit of the IX and X nerves and
the medullary inspiratory center
• communicate directly with the respiratory center
• the most important for the minute-to-minute
control of respiration
• sensitive to changes in the pH of CSF
•  pH   ventilation
•  pH   ventilation

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 CENTRAL CHEMORECEPTORS
• Blood–brain barrier is relatively impermeable to H + and HCO3-
• CO2 is quite permeable across blood-brain barrier
• In the CSF, CO2 + H2O  H+ + HCO3-
• Central chemoreceptors detect the  pH  ventilation  more
CO2 will be exhaled and PaCO2 will  toward normal

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 PERIPHERAL CHEMORECEPTORS
• Carotid and aortic bodies located around
carotid sinus and aortic arch
• Its stimulation has both respiratory and
CVS effects (carotid bodies have greater
respiratory effect)
• Information about PaO2, PaCO2 and pH is
relayed to the medullary inspiratory center
via CN IX and X
•  PaO2 (< 60 mmHg),  PaCO2 and  pH
  ventilation
• Respond of these receptors are very fast
and oscillate within a respiratory cycle

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 HERING-BREUER REFLEX

• The Hering-Breuer reflex is important during deep breathing and

probably more important in newborn babies than it is in adults.
• Slowly adapting stretch receptors (located in the smooth muscle of
bronchial tree) send volume-related information via vagal afferent
fibers to inspiratory off-switch neurons. This signals the
termination of inspiration to prevent lungs overinflation.

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 MECHANORECEPTORS

• Irritant receptors are rapidly adapting receptors that are found

between the epithelial cells. They cause bronchoconstriction in
response to inhaled noxious stimuli or physical stimulation.
• Pulmonary C fiber endings such as juxtacapillary or‘J’ receptors
detect alveolar fluid imbalances (edema), injury, congestion and
large lung inflation. They cause a reflex increase in breathing
rate, and is also thought to be involved in the sensation of
dyspnea.

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 MUSCLE PROPRIOCEPTORS
• During exercise, the increase in ventilation often precedes the
actual increased oxygen requirement!!!
• There are probably at least 2 components to this increase in
respiration that precedes the increased oxygen requirement. 
• "anticipation of exercise" and may involve activation of the
sympathetic nervous system. 
• activation of stretch receptors in muscle spindles, tendon and
joints (proprioceptors) . Increased activity of proprioceptors is
detected by the medulla, and results in increased rate and
depth of respiration.
• The effect is very rapid, and shows an "added value" to stretching
before exercise

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 CEREBRAL CORTEX
• Commands from the cerebral cortex can temporarily override the
automatic (involuntary) respiratory centers.
• A person can voluntarily hyperventilate (i.e., increase breathing
frequency and volume). The consequence of hyperventilation is a
decrease in in PaCO2, which causes arterial pH to increase.
Hyperventilation is self-limiting because the decrease in PaCO 2 will
produce apnea vera to allow blood CO2 level to return to normal 
normal breathing pattern.
• A person may also voluntarily hypoventilate (i.e., breath-holding).
Hypoventilation causes a decrease in PaO 2 and an increase in PaCO 2,
both of which are strong drives for ventilation. A period of prior
hyperventilation can prolong the duration of breath-holding.

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 Basic breathing rhythm can be modified by
several control mechanisms

Vagus and
glossopharyngeal +
+
-+ Mainly Vagus nerve
nerves

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CLASSIFICATION OF RESPIRATORY
FAILURE

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 FUNCTIONS OF RESPIRATORY SYSTEM
1. Ventilation and blood oxygenation
2. Respiratory pump
3. Acid-base balance regulation
4. Defense mechanism: entrapped in mucus, digested by
macrophages, initiate immunological response
5. Thermoregulation: route for water loss and heat elimination
6. Metabolic functions: synthesize leukotrienes, convert
angiotensin I to II, degrade substance such as noradrenalin
and serotonin
7. Organ of speech, singing and vocalization
8. Organ of smell

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