Repiration

The respiratory system

 Regulation of breathing
(local , Nervous and Chemical)

1- Local (the lungs): Alveoli, alveolar

capillaries and bronchioles
a- lung perfusion - adjustments to blood
flow
b- alveolar ventilation – delivery of oxygen
to alveoli
a- lung perfusion (blood flow)

b) Alveolar ventilation
Local control via alveolar ventilation ensures optimum
conditions for gas exchange
2- Nervous control
Respiration is controlled by these areas of the
brain that stimulate the contraction of the
diaphragm and the intercostal muscles. These
areas, collectively called respiratory centers, are
summarized here:

a) The Medulla Oblongata, the medullary

inspiratory center, located in the medulla
oblongata, generates rhythmic nerve impulses
that stimulate contraction of the inspiratory
muscles (diaphragm and external intercostal
muscles).
Normally, expiration occurs when these muscles
relax, but when breathing is rapid, the inspiratory
center facilitates expiration by stimulating the
expiratory muscles (internal intercostal muscles
and abdominal muscles).
b) The Pons, The pheumotaxic area, located in
the pons, inhibits the inspiratory center, limiting
the contraction of the inspiratory muscles, and
preventing the lungs from overinflating.
The apneustic area, also located in the pons,
stimulates the inspiratory center, prolonging the
contraction of inspiratory muscles.
The respiratory centers are influenced by stimuli
received from the following three groups of
sensory neurons of chemoreceptors:

a) Central chemoreceptors (nerves of the

central nervous system), located in the medulla
oblongata, monitor the chemistry of cerebrospinal
fluid. When CO2 from the plasma enters the
cerebrospinal fluid, it forms HCO3– and H+, and the
pH of the fluid drops (becomes more acidic). In
response to the decrease in pH, the central
chemoreceptors stimulate the respiratory center to
increase the inspiratory rate.

b) Peripheral chemoreceptors (nerves of the

peripheral nervous system), located in aortic
bodies in the wall of the aortic arch and in carotid
bodies in the walls of the carotid arteries, monitor
the chemistry of the blood. An increase in pH or
pCO2, or a decrease in pO2, causes these receptors
to stimulate the respiratory center.

c) Stretch receptors in the walls of bronchi and

bronchioles are activated when the lungs expand
to their physical limit. These receptors signal the
respiratory center to discontinue stimulation of the
inspiratory muscles, allowing expiration to begin.
This response is called the inflation (Hering‐
Breur) reflex.
 Transport of Oxygen
Oxygen is transported in the blood in two ways:
1-Dissolved in the blood (1.5%)
2-Bound to haemoglobin (98.5%)
Bound to Haemoglobin
Once oxygen has entered the blood from the lungs,
it can be bound by haemoglobin (Hb) in the red
blood cells.
Structure of Haemoglobin

Haemoglobin is a protein comprised of four

subunits: in Adult, two alpha subunits and two
beta subunits. In Fetal (HbF) composed of two
alpha and two gamma subunits. Each subunit has
a haem group in the center that contains iron and
binds one oxygen molecule. This means each
haemoglobin molecule can bind four oxygen
molecules, forming oxyhaemoglobin. Haemoglobin
molecules with a greater number of oxygen
molecules bound are brighter red. This is why
oxygenated arterial blood is brighter red and
deoxygenated venous blood is darker red.
The binding of haemoglobin with oxygen is
reversible. This relation can be represented by the
Oxygen-haemoglobin dissociation curve

The dissociation curve indicates the oxygen

saturation and partial pressure of oxygen in the
blood. The binding of the first molecule is difficult.
As the first oxygen molecule binds to haemoglobin,
it increases the affinity of the haemoglobin
molecules for the second molecule of oxygen to
bind. Subsequently, haemoglobin attracts more
oxygen (this is known as cooperativity) and hence,
the curve is sigmoid shape or S-shape. p50 is the
oxygen tension when hemoglobin is 50 %
saturated with oxygen. When hemoglobin-oxygen
affinity increases, the oxyhemoglobin dissociation
curve shifts to the left and decreases p50. When
hemoglobin-oxygen affinity decreases, the
oxyhemoglobin dissociation curve shifts to the
right and increases p5
Oxygen Delivery at Tissues
When P O2 is high (P O2=104 mmHg) hemoglobin
binds with large amounts of oxygen & is almost
100% saturated & 100 ml of systemic arterial
blood contains about 20 ml of oxygen.
In contrast, when PO2 is low, hemoglobin is only
partially saturated. In other words, the greater the
PO2, the more O2 will bind to hemoglobin, until all
the available hemoglobin molecules are saturated.
Therefore, in pulmonary capillaries, where PO2 is
high, a lot of oxygen binds to hemoglobin. In
tissue capillaries, where the PO2 is lower,
hemoglobin does not hold as much O2, & the
dissolved O2 is unloaded via diffusion into tissue
cells. Thus as arterial blood flows through the
systemic capillaries about 5 ml of O2/100 ml of
blood is released & still Hb is 75% saturated with
O2 at 40 mm Hg in venous blood. The graph shows
that only 25% of the available O2 unloads from
Hb & is used by tissue cells under resting
condition.

During vigorous muscle activity, oxygen tension

drops to very low levels in the tissues (between 40
& 20 mmHg). As a result, large amounts of O2 are
released from hemoglobin and the oxygen
saturation of hemoglobin drops to 35% at 20
mmHg and much more oxygen can dissociate from
hemoglobin to be used by the tissue cells without
requiring an increase in respiratory rate or cardiac
output.
Factors Affecting Oxygen Affinity
Various factors can affect the affinity of
haemoglobin for oxygen:

1) pH/pCO2 – When H+/pCO2 increases and pH

decreases, Hb affinity for oxygen decreases. This is
known as the Bohr effect. Inversely, when
H+/pCO2 decreases and pH increases, the affinity
of haemoglobin for oxygen increases.
2) 2,3-diphosphoglycerate (2,3-DPG) – 2,3-DPG is
a chemical found in red blood cells. It is a product
from the glucose metabolic pathway. 2,3-DPG
binds to the beta chains of haemoglobin, so
increased 2,3-DPG levels results in it binding to
haemoglobin, decreasing the affinity of
haemoglobin for oxygen. Conversely, when there
are decreased 2,3-DPG levels there are fewer 2,3-
DPG molecules to bind to haemoglobin. This means
there are more opportunities for it to bind and
therefore it has a higher affinity for oxygen.
3) Temperature – At increased temperatures, for
example in active muscles, there is an increase in
heat production which decreases the affinity of
haemoglobin for oxygen. At decreased
temperatures, e.g. decreased metabolic states, the
reduced heat production means the affinity of
haemoglobin for oxygen increases.
The affinity of haemoglobin for oxygen also results
in a shift in the oxygen-haemoglobin dissociation
curve. An increase in oxygen affinity results in the
curve shifting to the left, whereas a decrease in
oxygen affinity results in the curve shifting to the
right.

Control Temp 2,3 DPG PO2 Acidity H+

factors
Change ↑ ↑ ↑ ↑
Shift of → → → →
curve
Change ↓ ↓ ↓ ↓
Shift of ← ← ← ←
curve
 Fetal hemoglobin

Fetal hemoglobin saturation curve

Fetal hemoglobin saturation curve

As mentioned above, Fetal hemoglobin (HbF) is
structurally different from normal adult hemoglobin
(HbA), giving HbF a higher affinity for oxygen than
HbA. HbF is composed of two alpha and two
gamma chains whereas. The fetal dissociation
curve is shifted to the left relative to the curve for
the normal adult because of these structural
differences.
Typically, fetal arterial oxygen pressures are lower
than adult arterial oxygen pressures. Hence higher
affinity to bind oxygen is required at lower levels of
partial pressure in the fetus to allow diffusion of
oxygen across the placenta. At the placenta of the
mother, there is a higher concentration of 2,3-BPG
formed, and 2,3-BPG binds readily to beta chains
rather than to alpha chains. As a result, 2,3-BPG
binds more strongly to adult hemoglobin, causing
mother Hb to release more oxygen for uptake by
the fetus. HbF then delivers that bound oxygen to
tissues that have even lower partial pressures
where it can be released.

Whales show an exceptionally wide range of diving

capabilities and many express high amounts of the
O2 carrier protein myoglobin (Mb) in their muscle
tissues, which increases their aerobic diving
capacity
Carbon dioxide transport