Respiratory_2

Report
PowerPoint® Lecture Slides
prepared by Vince Austin,
Bluegrass Technical
and Community College
CHAPTER
Elaine N. Marieb
Katja Hoehn
22
PART B
Human
Anatomy
& Physiology
SEVENTH EDITION
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The
Respiratory
System
External Respiration versus Internal Respiration

External Respiration is the exchange of gases
between the outside atmosphere and the blood
(from outside air into pulmonary capillaries)

Internal Respiration is the exchange of gases
between the blood and the tissue cells (from
capillaries into tissue cells)
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External Respiration
----------------------------------------------------------------------------
Internal Respiration
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Figure 22.17

PATM – Partial Pressure of Gas in Atmosphere

PA – Partial Pressure of alveolar gas

Pa – Partial Pressure of arterial gas

Pv – Partial Pressure of venous gas

PATMO2 – 159 mmHg

PaO2 - 104 mmHg PvO2 – 40 mmHg
PAO2 – 104 mmHg
_________________________________

PATM CO2 – 0.3 mmHg PACO2 – 40 mmHg

PaCO2 - 40 mmHg PvCO2 – 45 mmHg
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Composition of Alveolar Gas
 The atmosphere is mostly oxygen and nitrogen,
while alveoli contain more carbon dioxide and
water vapor

These differences result from:

Nitrogen has a poor solubility coefficient – thus
does not want to mix with blood easily

Carbon Dioxide has an excellent solubility
coefficient

Humidification (watering the air) of air by
conducting passages – airways have water on the
surfaces.
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External Respiration: Pulmonary Gas
Exchange

Factors influencing the movement of oxygen and
carbon dioxide across the respiratory membrane
1. Partial pressure gradients and gas solubilities
2. Matching of alveolar ventilation and pulmonary
blood perfusion
3. Structural characteristics of the respiratory
membrane
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Discussion of Oxygen Transport
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Partial Pressure Gradients and Gas
Solubilities
 The partial pressure oxygen (PO2) of venous blood
is 40 mm Hg; the partial pressure in the alveoli is
104 mm Hg

This steep gradient allows oxygen partial
pressures to rapidly reach equilibrium (in 0.25
seconds), and thus blood can move three times as
quickly (0.75 seconds) through the pulmonary
capillary and still be adequately oxygenated
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Oxygenation of Blood
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Figure 22.18
Partial Pressure Gradients and Gas
Solubilities
 Although carbon dioxide has a lower partial
pressure gradient:

It is 20 times more soluble in plasma than oxygen

It diffuses in equal amounts with oxygen

Oxygen --- 0.024

Carbon Dioxide - 0.57 (likes to dissolve in water the
best)

Nitrogen – 0.012

Carbon Monoxide – 0.018
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Formulas of Importance
Diffusion – net movement of certain particles from a region of high
concentration of those certain particles to region of low
concentration of those certain particles
D = A x Dc /t (Co – Ci)

A is the area of the membrane being diffused through, Dc is the
diffusion coefficient, t- is the thickness of the membrane being
diffused through, Co – Ci is the concentration difference between
the o (outside) and I (inside) of the container

The diffusion coefficient = solubility coefficient divided by the
square root of the molecular weight of the substance diffusing
(this applies more to gases)
Analysis- the greater the area and/or diffusion coefficient – the faster
the rate of diffusion. The more the concentration difference the
faster the rate of diffusion. However, the thicker the membrane to
diffuse through the slower the rate of diffusion.
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
Henry’s Law
 The amount of gas that will dissolve in a liquid
depends on the partial pressure of the gas above the
liquid (push down force) and the solubility
coefficient of the gas for the liquid (pull down force).
Solubility Coefficients of Gases in H2O
(Determination of how much a certain gas likes a certain liquid)

Oxygen --- 0.024

Carbon Dioxide - 0.57 (likes to dissolve in water the best)

Nitrogen – 0.012

Carbon Monoxide – 0.018
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The pp of CO2
in tissue cells
is generally
46 mmHg
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The pp of O2
in tissue cells ranges
from 5mm Hg to
40 mmHg with an
average of 23 mm Hg.
A tissue cell generally
needs only 1 – 3mmHg
to fully support all of
its oxygen requiring
chemical processes
Figure 22.17
A tissue cell should ideally be
20 – 30 micromillimeters from
a capillary and at absolute maximum
100 micromillimeters.
The intracellular oxygen partial pressure averages 23 mm Hg and the
interstitial fluid oxygen partial pressure averages 40 mm Hg.. Thus
oxygen can easily diffuse down this steep concentration gradient from the
95Copyright
– 104
mm Hg in the arterial end of the capillary to the 23 mm Hg in the
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The intracellular carbon dioxide partial
pressure averages 46 mm Hg and the
interstitial fluid oxygen partial
pressure averages 45 mm Hg. With the
arterial end of the capillary having a
partial pressure of 40 mmHg. Thus
carbon dioxide has less of
concentration gradient difference
than oxygen. However, its diffusion is
as good as oxygen due to its excellent
solubility coefficients for both water
(blood) and lipids (cell membranes).
cell.
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Oxygen Delivery
 Oxygen in the atmosphere is 20.84% with a partial
pressure of 159 mm Hg.

When air enters the airways the water vapor
concentration increases from 0.50% (pp of 3.7 %)
in the atmosphere to 6.2 % (pp 47) in the mouth
and respiratory pipes thus squeezing down the
percentage of O2 to 9.6% (pp of 149.3 mm Hg).

When air enters the alveolus the O2 percentage
drops even more due to increased partial pressure
of CO2 in the alveolus. This squeezes the partial
pressure of O2 to 104 mm Hg.
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
O2 diffuses (pp 104 mm Hg) across the exchange
membranes – then into the capillaries – where the
O2 partial pressure is 40 mm Hg.
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Oxygen Loading into the blood

Oxygen is carried in the blood in two ways 97% 98% is carried on Hemoglobin and 2% – 3% is
dissolved in the plasma

Oxygen in hemoglobin is carried on the iron as
long as the iron is in the +2 oxidation state (Fe ++
ferrous) – but if it is oxidized to the + 3 oxidation
state (ferric) Fe +++ it will not carry oxygen

Amount of Oxygen carried on a gram of hemoglobin is
between 1.32 to 1.39 ml.
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Oxygen Transport: Role of Hemoglobin

Each Hb molecule binds four oxygen atoms in a
rapid and reversible process

The hemoglobin-oxygen combination is called
oxyhemoglobin (HbO2)

Hemoglobin that has released oxygen is called
reduced hemoglobin (HHb)
Lungs
HbO2 + H+
HHb + O2
Tissues
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Hemoglobin (Hb)



Saturated hemoglobin – when all four hemes of the
molecule are bound to oxygen
Partially saturated hemoglobin – when one to three
hemes are bound to oxygen
The rate that hemoglobin binds and releases
oxygen is regulated by:

PO2, temperature, blood pH, PCO2, and the
concentration of BPG (an organic chemical)

These factors ensure adequate delivery of
oxygen to tissue cells
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Influence of PO2 on Hemoglobin Saturation
 Hemoglobin saturation plotted against PO2
produces a oxygen-hemoglobin dissociation
curve

98% saturated arterial blood contains 20 ml oxygen
per 100 ml blood (20 vol %) – 19.6 ml. bound to
Hgb and .04 ml dissolved in the plasma (14.6 grams
of Hgb/dl x 1.34 ml of O2 per gram)

As arterial blood flows through capillaries, 5 ml
oxygen are released

The saturation of hemoglobin in arterial blood
explains why breathing deeply increases the PO2 but
has little effect on oxygen saturation in hemoglobin
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Hemoglobin O2 Association/ Dissociation Curve
Loading
Unloading
Allosteric Effect of
Hgb.
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Explanation of
the
dynamics of O2
carriage on Hgb
Figure 22.20
Hemoglobin Association/Dissociation
(Saturation) Curve

Hemoglobin is almost completely saturated at a
PO2 of 70 mm Hg

Further increases in PO2 produce only small
increases in oxygen binding

Oxygen loading and delivery to tissue is adequate
when PO2 is below normal levels
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Hemoglobin Association/Dissociation
(Saturation) Curve
 Only 20–25% of bound oxygen is unloaded during
one systemic circulation

If oxygen levels in tissues drop:

More oxygen dissociates from hemoglobin and is
used by cells

Respiratory rate or cardiac output need not increase
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Hemoglobin O2 Association/ Dissociation Curve
Loading
Unloading
Explanation of
the
dynamics of O2
carriage on Hgb
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Figure 22.20
Structure of Hemoglobin
O2 locations
Allosteric explanation
When O2 loads or unloads on one heme (iron)– due to the structure
of Hgb -it slightly twists the molecule affecting the other hemes.
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Figure 17.4
Shifting of The Curve

Certain factors (pH change, Temp change, 2,3 BPG
concentration change, PaCO2 change) can cause the Oxygen
Association/Dissociation Curve to shift to the right or left

If the curve shifts to the right
it means that
hemoglobin has a decreased affinity for O2- thus O2 will
unload (dissociate) easier from Hgb. This shift is termed the
Bohr shift (Christian Bohr, Danish physiologist father of Niels Bohr, famous
physicist).

If the curve shifts to the left
it means that hemoglobin
has an increased affinity for O2- thus O2 will load easier onto
Hgb and be held onto tighter by Hgb.
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Explanation of Curve Shift (use p50 value)
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The red curve (more leftward)
represents a higher O2/Hgb
affinity. Notice that even if the
partial pressure of O2 around
Hgb is down as low as a partial
pressure of 8 mm Hg – only 50%
of the oxygen molecules on Hgb
will unload (2 out of 4). However
the blue curve (more rightward)
represents a lower O2/Hgb
affinity. Notice that at a
higher (30 mm hg) partial pressure
of O2 around Hgb – the Hgb is
willing to unload 50% of its
oxygen. Thus it is not holding
onto O2 as tightly.

Right Shift (less affinity shift) factors (Bohr Shift)

1. Increase in PaCO2

2. Increase in [2,3 BPG]

3. Increase in [H+] – thus more acidic pH

4. Increase in Temp – some suggest that an increased temp increases
the 2,3 BPG concentration

Left Shift (Increased affinity shift) factors

1. Decrease in PaCO2

2. Decrease in [2,3 BPG]

3. Decrease in [H+ ] – thus more acidic pH

4. Decrease in Temp – some suggest that a decreased temp decreases
the 2,3 BPG concentration
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Factors Shifting the Curve
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Figure 22.21

2,3-Bisphosphoglycerate (2,3-BPG, also known as 2,3diphosphoglycerate or 2,3-DPG) is a three-carbon isomer
of the glycolytic intermediate 1,3-bisphosphoglycerate.
2,3-BPG is present in human red blood cells (RBC;
erythrocyte) at approximately 5 mmol/L. It binds with
greater affinity to deoxygenated hemoglobin (e.g.,
when the red cell is near respiring tissue) than it does to
oxygenated hemoglobin (e.g., in the lungs). In binding to
partially deoxygenated hemoglobin, it allosterically upregulates the release of the remaining oxygen molecules
bound to the hemoglobin, thus enhancing the ability of
RBCs to release oxygen near tissues that need it most.
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
2,3-BPG is formed from 1,3-BPG by an
enzyme called bisphosphoglycerate mutase. It
is broken down by a phosphatase to form 3phosphoglycerate. Its synthesis and breakdown
are, therefore, a way around a step of
glycolysis.

glycolysis 1,3-BPG ------------> 2, 3-PG
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2,3 BPG
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Questions
1.
Where would you position the fetal
hemoglobin curve – A. to the right of the adult
curve B. to the left of the adult curve C.
superimposed on top of the adult curve
2.
Where would you position the myoglobin
curve (red chemical in muscle that holds
reserve oxygen) - A. to the right of the adult
curve B. to the left of the adult curve C.
superimposed on top of the adult curve
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Internal Respiration (Unloading) O2 to the tissues

O2 is delivered to tissue cells – some from the dissolved form in
the plasma and some from the Hgb.

The partial pressure in the tissue cells is generally around 40
mm Hg (Krebs cycle use of O2).

The partial pressure of O2 in the arteriole end of the capillary
(PaO2) is around 104 mm Hg. Thus O2 diffuses from the blood
into the interstitial fluids then into the tissue cells.

Under normal conditions only 1 out of 4 O2 molecules will
diffuse from Hgb in the capillaries if the tissue (interstitial fluid)
partial pressure is 40 mm Hg. However, if the tissue (interstitial
fluid) partial pressure of O2 is lower than 40 mm Hg more O2
molecules will dissociate off the Hgb – and dissociate quicker
(shown by the parabolic nature of the O2 curve.
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Tissue Cell Pressures of O2 - 23 mm Hg
Interstitial Fluid pp of 40 mm Hg
Arteriole Pressures
Arteriole PP of O2 – 104 mm Hg
Oxygen diffuses into tissue cells due to the difference in partial
pressures
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Hemoglobin O2 Association/ Dissociation Curve
75%
Unloading
Utilization Coefficient
How many unload
divided by how many
present
= 1/4
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Only 1 O2
dissociates
from Hgb if
the partial
pressure of
the tissues is
40 mm Hg. If
lower more
will unload
and quicker
Figure 22.20
Reason why unloading needs to be faster if 1 O2 molecule
unloaded did not bring tissue cells partial pressures to 40
mm Hg
 Blood in a capillary is only there for less than a second (around
.75 seconds or less). Capillaries are only 0.25 μm – 1 μm in
length.


When hemoglobin has unloaded one O2 molecule – it is a third
of the way in the capillary – if this one O2 did not return the
tissue O2 partial pressures to the physiologic level of 40 mm Hg
– then another O2 must be loaded and if still not enough another
one. Each must be unloaded quicker than the previous one –
since the blood is constantly reaching the end of the capillary
where no further diffusion can occur.
Thus the downward slope (dissociation direction) of the O2
curve must get steeper (rate getting faster) as O2 molecules are
released from Hgb into the tissues.
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Hemoglobin O2 Association/ Dissociation Curve
75%
Unloading
Steeper slope down after
one O2 unloaded
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Only 1 O2
dissociates
from Hgb if
the partial
pressure of
the tissues is
40 mm Hg. If
lower more
will unload
and quicker
Figure 22.20
Unloading of Oxygen into Tissues
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Figure 22.22a

Pa – Partial Pressure of arterial gas

PaO2 - 104 mmHg (clinical range 80 – 100)

Hypoxia – too low oxygen in the tissues

Hypoxemia – too low oxygen in the blood

Normoxia – normal oxygen level in the tissues

Hyperoxia – too high oxygen concentration in the
tissues – can cause bronchopulmonary dysplasia
and/or be a contributing cause of retrolental
fibroplasia in the newborn.
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Types of Hypoxia
 Anemic Hypoxia – not enough hemoglobin to
properly carry oxygen



Ischemic (stagnant) Hypoxia – some blockage in
the circulation to an area
Histologic Hypoxia – the oxygen is getting to the
tissues but cannot be utilized. Examples are
poisons such as cyanide.
Hypoxemic Hypoxia – something causing the
blood not be able to pick up enough oxygen from
the atmosphere (in a low oxygen environment,
suffocation, CO poisoning, etc.)
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Histologic Hypoxia



The oxygen gets to the tissues – but cannot be
utilized
1. Mitochondrial Diseases – mitochondria which
have their own DNA provided by the individuals
mother has some genetic defect disallowing proper
usage of oxygen in the electron transport chain
2. Cyanide Poisoning - The cyanide ion halts
cellular respiration by inhibiting an enzyme in
mitochondria called cytochrome c oxidase. This
enzyme is needed to transfer electrons so as to
make ATP.
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
Cytochrome C oxidase is the last enzyme in the respiratory
electron transport chain of mitochondria located in the
mitochondrial membrane. It receives an electron from each of
four cytochrome c molecules, and transfers them to one oxygen
molecule. In this complex hydrogens are transported to oxygen
making water (H2O).
Cytochrome Oxidase
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Carbon Monoxide Poisoning

The affinity between hemoglobin and carbon monoxide is
approximately 230 times stronger than the affinity between
hemoglobin and oxygen so carbon monoxide binds to
hemoglobin in preference to oxygen.

Carbon monoxide can also bind to a myoglobin. It has a high
affinity for myoglobin, about 60 times greater than that of
oxygen. Carbon monoxide bound to myoglobin may impair its
ability to utilize oxygen.

Carbon monoxide can also bind to Cytochrome oxidase
disturbing its function in the mitochondria in the production of
ATP.
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Carbon Monoxide

Hemoglobin is a tetramer with four oxygen binding sites. The
binding of carbon monoxide at one of these sites increases the
oxygen affinity of the remaining three sites, which causes the
hemoglobin molecule to retain oxygen that would otherwise be
delivered to the tissue. This situation is described as carbon
monoxide shifting the oxygen dissociation curve to the left.
Because of the increased affinity between hemoglobin and
oxygen during carbon monoxide poisoning, the blood oxygen
content is increased. But because all the oxygen stays in the
hemoglobin, none is delivered to the tissues. This causes
hypoxic tissue injury.

Carbon monoxide bound to hemoglobin make the hemoglobin
look redder – thus the patient may have a cherry red
appearance.
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Hyperoxia conditions

Bronchopulmonary dysplasia (BPD; formerly Chronic Lung
Disease of Infancy) is a chronic lung disorder that is most
common among children who were born prematurely, with low
birth weights and who received prolonged mechanical
ventilation to treat respiratory distress syndrome. BPD is
clinically defined as oxygen dependence at 36 weeks'
postmenstrual age.

BPD is characterized by inflammation and scarring in the lungs.
More specifically, the high pressures of oxygen delivery result
in necrotizing bronchiolitis and alveolar septal injury, further
compromising oxygenation of blood.
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Hyperoxia conditions

Retinopathy of prematurity (ROP), previously
known as retrolental fibroplasia (RLF), is an eye
disease that affects prematurely born babies. It is
thought to be caused by disorganized growth of retinal
blood vessels which may result in scarring and retinal
detachment. ROP can be mild and may resolve
spontaneously, but may lead to blindness in serious
cases. As such, all preterm babies are at risk for ROP,
and very low birth weight is an additional risk factor.
Both oxygen toxicity and relative hypoxia can
contribute to the development of ROP.
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Retinopathy

Normally, maturation of the retina proceeds in-utero and at
term, the mature infant has fully vascularized retina. However,
in preterm infants, the retina is often not fully vascularized.
ROP occurs when the development of the retinal vasculature is
arrested and then proceeds abnormally. The key disease element
is fibrovascular proliferation. Associated with the growth of
these new vessels is fibrous tissue (scar tissue) that may
contract to cause retinal detachment. Supplemental oxygen
exposure, while a risk factor, is not the main risk factor for
development of this disease. Restricting supplemental oxygen
use does not necessarily reduce the rate of ROP, and may raise
the risk of other hypoxia-related systemic complications.
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Discussion of Nitric Oxide (NO) as it Relates to
Hemoglobin
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Hemoglobin-Nitric Oxide Partnership



Nitric oxide (NO) also known as endothelial derived relaxing
factor (EDRF) is a vasodilator synthesized by the endothelial
cells from L-arginine and oxygen by various nitric oxide
synthase enzymes.
Nitric oxide lasts only a few seconds – let diffuses freely from
the endothelial cells to relax the smooth muscles of the blood
vessel walls – resulting in vasodilation. Thus it plays a role in
blood pressure regulation
Nitric oxide (NO) also contributes to vessel homeostasis by
inhibiting platelet aggregation, and leukocyte adhesion to the
endothelium.
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

Some special NO (termed SNO for S-nitrous thiols) is produced
in the lung. This NO is attached to a cysteine amino acid on
globin. Cysteine has a sulfhydryl R-group – thus it is called a
thiol.
O = N – S – R (amino acid cysteine)

The NO attached to cysteine is protected from hemoglobin
which gobbles up free NO produced by endothelial cells.

When Hemoglobin unloads O2 in the tissues it also unloads
SNO and picks up free NO made by the local endothelial cells
as well as CO2. The picked up NO is carried on the Heme
attached to the iron – this NO is not active thus cannot maintain
vasodilation. However the SNO left behind maintains adequate
vasodilation. But it has a short life – thus new NO needs to be
produced in order to maintain the vasodilation. The excess NO
carried on hemoglobin is taken to the lungs for exhalation.
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Discussion of Carbon Dioxide Transport
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CO2 Transport
CO2 transport originates in internal respiration (product of the
Krebs cycle) – whereas O2 transport originated in external
respiration – acquisition of O2 from the atmosphere.
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
CO2 diffuses from the tissue cells (CO2 formed in Krebs Cycle) that
generally have an intracellular partial pressure of 45 mmHg.

The CO2 then diffuses down its concentration first into the interstitial
fluids – then into the capillaries (that under usual circumstances has a
partial pressure of 40 mm Hg).

Note: the partial pressure differences between CO2 is lower (45 mm
Hg to 40 mm Hg) than that of O2 (104 mm Hg to 40 mm Hg) yet it
can diffuse just as quickly. Why? Because CO2 has a much better
solubility coefficient than O2 – thus water and lipid membranes likes
it better.

Solubility coefficient of Oxygen --- 0.024 versus Carbon Dioxide 0.57
D = A x Dc /t (Co – Ci)
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CO2 entrance into the blood

Once carbon dioxide enters the bloodstream it is
carried in three forms
1. Dissolved in plasma – 7 to 10%
2. Chemically bound to hemoglobin – 20% - 23% is
carried in RBCs as carbaminohemoglobin
3.Bicarbonate ion in plasma – 70% is transported as
bicarbonate (HCO3–)
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Transport and Exchange of Carbon Dioxide
3
2
1
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Figure 22.22a
Transport and Exchange of Carbon Dioxide

Most (70%) of the carbon dioxide diffuses into RBCs and combines
with water to form carbonic acid (H2CO3), which quickly dissociates
into hydrogen ions and bicarbonate ions –

In RBCs, carbonic anhydrase (enzyme produced in RBCs)
reversibly catalyzes the conversion of carbon dioxide and water to
carbonic acid
CO2
Carbon
dioxide

+
H2 O
 Water

H2CO3
Carbonic
acid

H+
Hydrogen
ion
+
HCO3–
Bicarbonate
ion
NOTE: The reason so much CO2 is carried in the bicarbonate form
is that while it is being carried it can act as a pH buffer – thus two
tasks are accomplished at the same time – 1.eliminating CO2 and
2. assisting in pH balance of the blood (discussed later)
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Chloride Shift

In order to maintain the balance of charges (Bulk
Electro neutrality) in the RBC – when the
negatively charged bicarbonate (HCO3- ) molecule
moves out of the RBC into the plasma so as to
assist in pH buffering the blood – the negatively
charged chloride (Cl- ) ion enters into the RBC
through a special integral protein in the RBC
membrane known as the chloride transporter

This action is termed the chloride shift (Hamburger
shift) – named after Hartog Jakob Hamburger
(1859–1924), a Dutch physiologist
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Carbon dioxide carriage on Hemoglobin

Oxygen is carried on the heme portion of
hemoglobin attached to iron in the +2 (ferrous)
oxidation state.

Carbon dioxide is carried on the protein globin
component of hemoglobin. Carbon dioxide can
bind to amino groups, creating carbamino
compounds. Amino groups are available for
binding at the N-terminals and at side-chains of
arginine and lysine residues in hemoglobin. This
forms carbaminohemoglobin.
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CO2 Association/Dissociation Curve
Not as
curved
(parabolic) as
the O2 curve
Not as much
allosteric
effect
with Hgb
Oxygen Curve
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Haldane Effect (Shifting of the CO2 curve)


At the tissues, as more carbon dioxide enters the
blood:

More oxygen dissociates from hemoglobin (Bohr
effect) rightward shift of the oxygen dissociation
curve – partly caused by the allosteric effect caused
by increased amounts of CO2 loading onto Hgb on
globin – pushing off some O2 on the heme.

This increased affinity of CO2 for globin on Hgb
pushes the CO2 curve to the left – Haldane shift.
This situation is reversed in pulmonary circulation
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Haldane Effect The decreased saturation of Hgb by
O2 leads to an increased affinity of Hgb
for CO2 (Haldane Shift) – leftward shift
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Figure 22.23
Haldane Shift
Bohr Shift
The Haldane Shift is the leftward shift of the CO2 dissociation curve –
which signifies increased affinity of Hgb for CO2. The rightward shift
of the oxygen dissociation curve is the Bohr shift which signifies
decreased affinity of Hgb for O2.
Combining the curves together shows the allosteric effect of CO2 on
O2 in Hgb and vice-versa the effect of O2 on CO2. In an environment
where CO2 concentration predominates it pushes the O2 curve to the right
and the CO2 curve to the left and vice versa where O2 concentration
dominates.
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External Respiration of Carbon Dioxide

At the lungs, these processes are reversed

Bicarbonate ions move into the RBCs and bind
with hydrogen ions to re-form carbonic acid. In
exchange for the negatively bicarbonate moving in
the negatively charged chloride moves out (reverse
the chloride shift)

Carbonic acid is then split by carbonic anhydrase
to release carbon dioxide and water

Carbon dioxide then diffuses from the blood into
the alveoli (plasma unloading of CO2 into alveoli)
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External Respiration of Carbon Dioxide

The CO2 dissolved in the plasma diffuses from the
venous blood (45 mm Hg) into the alveolus (40
mm Hg)

The CO2 attached to the globin portion of Hgb
detaches from the Hgb and diffuses into the
alveolus
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Transport and Exchange of Carbon Dioxide
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Figure 22.22b
What controls Respiration
1. Discuss Reticular Activating Formation
2. Brain Centers (VRG, DRG, Pneumotaxic, Apneustic)
3. Central and Peripheral Chemoreceptors
4. Cortical Control
5. Limbic Control
6. Lung Stretch Receptors
7. Irritant Gases
8. Pain
9. Muscle stretch receptors
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Reticular System in CNS

The reticular formation is a part of the brain that is involved in
actions such as awaking/sleeping cycle, and filtering incoming
stimuli to discriminate irrelevant background stimuli. It is
essential for governing some of the basic functions of higher
organisms, and is one of the phylogenetically oldest portions of
the brain.

The reticular formation is a poorly-differentiated area of the
brain stem, centered roughly in the pons. The reticular formation
is the core of the brainstem running through the mid-brain, pons
and medulla. The ascending reticular activating system
connects to areas in the thalamus, hypothalamus, and cortex,
while the descending reticular activating system connects to
the cerebellum and sensory nerves. The reticular activating
system is a portion of the reticular formation – concerned with
sleep/wake, arousal and alertness.
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Reticular System (Functions)

1. Somatic motor control - Some motor neurons
send their axons to the reticular formation nuclei,
giving rise to the reticulospinal tracts of the spinal
cord. These tracts function in maintaining tone,
balance, and posture--especially during body
movements.

Other motor nuclei include gaze centers, which
enable the eyes to track and fixate objects, and
central pattern generators, which produce rhythmic
signals to the muscles of breathing and
swallowing
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Reticular System (Functions)

2. Cardiovascular control - The reticular formation includes
the cardiac and vasomotor centers of the medulla oblongata.

3. Pain modulation - The reticular formation is one means by
which pain signals from the lower body reach the cerebral
cortex. It is also the origin of the descending analgesic
pathways. The nerve fibers in these pathways act in the spinal
cord to block the transmission of some pain signals to the brain.

4. Sleep and consciousness - The reticular formation has
projections to the thalamus and cerebral cortex that allow it to
exert some control over which sensory signals reach the
cerebrum and come to our conscious attention. It plays a central
role in states of consciousness like alertness and sleep. Injury to
the reticular formation can result in irreversible coma.
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Reticular System (Functions)

5. Habituation - This is a process in which the
brain learns to ignore repetitive, meaningless
stimuli while remaining sensitive to others. A good
example of this is when a person can sleep through
loud traffic in a large city, but is awakened
promptly due to the sound of an alarm or crying
baby. Reticular formation nuclei that modulate
activity of the cerebral cortex are called the
reticular activating system or extrathalamic control
modulatory system.
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Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Brain Centers that Control of Respiration

Breathing is a somatic motor controlled action.
There are nuclei in the brain that control the
respiration – known as the respiratory centers.

Medullary Centers
1.DRG (Dorsal Respiratory Group)
2.VRG (Ventral Respiratory Group)

Pontine Centers
3. Pneumotaxic Center
4. Apneustic Center
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Dorsal Respiratory Group (Controversy)

The dorsal respiratory group (DRG) is located in the dorsomedial
region of the medulla, and is composed of cells in the solitary tract
nucleus.

The DRG is considered by most researchers to be involved in the
generation of respiratory rhythm, and is primarily responsible for the
generation of inspiration. However, there is some controversy now
as to whether the VRG (Ventral Respiratory Group) initiates
most of the signaling for inspiration.

Newer thoughts state that the DRG receives the inputs from the
peripheral stretch receptors and chemoreceptors and communicate this
information to the VRG.
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Ventral Respiratory Group

The ventral respiratory group (VRG) is a column of neurons
located in the ventrolateral region of the medulla The four cell
groups of the VRG are the rostral nucleus retrofacialis, caudal
nucleus retroambiguus, nucleus para-ambiguus, and the preBötzinger complex.

The VRG contains both inspiratory and expiratory neurons.
Most researchers feel that the VRG is secondarily responsible
for initiation of inspiratory activity, after the dorsal respiratory
group. New thought is that the VRG may be the primary rhythm
–generating and integrative center.
New theory feels that the cyclic on/off switch between the
inspiratory and expiratory neurons in the VRG – produce
inhalation and exhalation – also setting the frequency at 12 –
15 breaths per minute – inspiration 2 seconds and expiration 3
seconds.
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

Which ever nuclei that initiates inspiration (VRG or
DRG) – its actions are a steady increase in action
firing frequency, leading to contraction of the
respiratory muscles. The impulses travel down the
phrenic and intercostal nerves to stimulate the
diaphragm and external intercostal muscles.

The rhythmic intermittent spontaneous firing of the
DRG (or VRG) produces a normal respiratory rate of
12-16 - breaths per minute in humans. Inspiration
usually lasts approximately 2 seconds, and expiration
lasts about 3 seconds (I/E ratio earlier discussed) . The
normal inspiration rate and rhythm is called eupnea.
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Pneumotaxic Center

The pneumotaxic center, also known as the
pontine respiratory group (PRG), is a network of
neurons in the rostral dorsal lateral pons.

The PRG antagonizes the DRG and VRG
cyclically inhibiting the depth of inspiration. The
PRG limits the burst of action potentials in the
phrenic nerve, effectively decreasing the tidal
volume and regulating the respiratory rate.
Absence of the PRG results in an increase in depth
of respiration and a decrease in respiratory rate.
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Apneustic Center

Controversy as to if it exists in the human – if it
does it is located in the lower pons as appears to
promote inspiration by stimulation of the neurons
in the medulla oblongata – (VRG and DRG).
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Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 22.24
Control of Respiratory Rhythm


According to recent research – the VRG (earlier thought was
the DRG) has pacemaker cells that spontaneously but
intermittently fire a cluster of action potentials initiating
inspiration. However, if these neurons are suppressed – that
does not abolish breathing – thus it is felt that normal
respiratory rhythm is a result of reciprocal inhibition of the
interconnected neuronal networks in the medulla
Other theories include

Inspiratory neurons are pacemakers and have intrinsic
automaticity and rhythmicity

Stretch receptors in the lungs establish respiratory rhythm
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Intercostal nerves
Phrenic Nerve
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Figure 22.24
Chemoreceptors affecting Breathing



Central – located 1mm below the ventral
medullary surface
Peripheral – located in the aorta (aortic body) and
the carotids (carotid body)
Sensory input from aortic body via cranial nerve X
(Vagus) goes into breathing centers (DRG) ;
sensory input from the carotids travel via cranial
nerve IX (glossopharyngeal) goes into same areas
in the brain
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
Central chemoreceptors of the central nervous system, located on the
ventrolateral medullary surface, are sensitive to the pH of their
environment.

These act to detect a change in pH of the cerebral spinal fluid (CSF)
that are indicative of a change in oxygen or carbon dioxide
concentration available to brain tissues. An increase in carbon dioxide
tension of the arteries, often resulting from increased CO2 intake
(hypercapnia) indirectly cause the blood to become more acidic;
the cerebral spinal fluid pH is closely comparable to the plasma pH, as
carbon dioxide easily diffuses across the blood/brain barrier.

However, a change in plasma pH will not stimulate central
chemoreceptors as H+ will not be able to diffuse into the CSF. Only
CO2 levels affect this as it can diffuse across into the CSF, forming H+
and decreasing pH. Central chemoreception remains, in this way,
distinct from peripheral chemoreceptors.
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
Central chemoreceptors are most sensitive to H+
but it has trouble going across the blood-brain
barrier. CO2 easily transverses the BBB – then
gets into CSF and interstitial fluids converting to
carbonic acid which dissociates to H+ and HCO3-.
Thus the H+ gets in indirectly based on the
concentration of CO2. Thus CO2 is the main
stimulus for breathing – except in those with
longstanding Chronic Obstructive Pulmonary
Disease (COPD) where O2 is the main stimulus for
breathing. With constant high levels of CO2 the
chemoreceptors decrease sensitivity to CO2.
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Depth and Rate of Breathing

Inspiratory depth is determined by how actively
the respiratory center stimulates the respiratory
muscles

Rate of respiration is determined by how long the
inspiratory center is active

Respiratory centers in the pons and medulla are
sensitive to both excitatory and inhibitory stimuli
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Sensory Inputs that affect Breathing
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Figure 22.25
Depth and Rate of Breathing: Reflexes



1. Pulmonary irritant reflexes – irritants promote
reflexive constriction of air passages (via Vagus)
2. Inflation reflex (Hering-Breuer) – stretch
receptors in the lungs are stimulated by lung
inflation
Upon inflation, inhibitory signals are sent to the
medullary inspiration center to end inhalation and
allow expiration
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Depth and Rate of Breathing: Higher Brain
Centers (Non-homeostatic)
 Hypothalamic (Emotional) controls act through
the limbic system to modify rate and depth of
respiration

Example: breath holding that occurs in anger

A rise in body temperature acts to increase
respiratory rate

Cortical controls are direct signals from the
cerebral motor cortex that bypass medullary
controls

Examples: voluntary breath holding, taking a deep
breath
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Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 22.26
Hyperventilation
 Hyperventilation – increased depth and rate of
breathing that results in drop in the PaCO2:

Quickly flushes carbon dioxide from the blood

Can physiologically occur in in response to
hypercapnia

Though a rise CO2 acts as the original stimulus,
control of breathing at rest is regulated by the
hydrogen ion concentration in the brain

A dramatic non-physiologic (anxiety) drop in
PaCO2 can cause vasoconstriction in the brain –
thus fainting (re-breath through paper bag)
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Depth and Rate of Breathing: PCO2

Hypoventilation – slow and shallow breathing due
to abnormally low PCO2 levels

Apnea (breathing cessation) may occur until PCO2
levels rise
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Depth and Rate of Breathing: PCO2

Arterial oxygen levels are monitored by the aortic
and carotid bodies

Substantial drops in arterial PO2 (to 60 mm Hg)
are needed before oxygen levels become a major
stimulus for increased ventilation

If carbon dioxide is not removed (e.g., as in
emphysema and chronic bronchitis),
chemoreceptors become unresponsive to PCO2
chemical stimuli

In such cases, PO2 levels become the principal
respiratory stimulus (hypoxic drive)
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Depth and Rate of Breathing: Arterial pH

Changes in arterial pH can modify respiratory rate
even if carbon dioxide and oxygen levels are
normal

Increased ventilation in response to falling pH is
mediated by peripheral chemoreceptors
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Peripheral Chemoreceptors
act most importantly to detect variation of
the oxygen in the arterial blood, in
addition to detecting arterial carbon
dioxide and pH.
These nodes, called the aortic body and
carotid body, are located on the arch of
the aorta and on the common carotid
artery, respectively. The carotids bodies
are most sensitive to changes in partial
pressure of arterial oxygen and pH. The
aortic bodies are most sensitive to the
content of arterial oxygen.
A continual signal is sent, via cranial
nerves IX and X, from the peripheral
chemoreceptors
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Figure 22.27
See Acid Base PowerPoint
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Respiratory Adjustments: Exercise
 Respiratory adjustments are geared to both the
intensity and duration of exercise


During vigorous exercise:

Ventilation can increase 20 fold

Breathing becomes deeper and more vigorous, but
respiratory rate may not be significantly changed
(hyperpnea)
Exercise-enhanced breathing is not prompted by an
increase in PCO2 or a decrease in PO2 or pH

These levels remain surprisingly constant during
exercise – PaCO2 may even decrease and PaO2
increase
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Respiratory Adjustments: Exercise

As exercise begins:


Ventilation increases abruptly, rises slowly, and
reaches a steady state
When exercise stops:

Ventilation declines suddenly, then gradually
decreases to normal
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Respiratory Adjustments: Exercise

Neural factors bring about the above changes,
including:

Psychic stimuli

Cortical motor activation

Excitatory impulses from proprioceptors in
muscles
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Post - Exercise

It appears that the blood gases are normal post
exercise along with ventilatory functions

It appears that the lactic acid buildup in muscles is
not due to failure to get enough oxygen into the
blood – but (1) inadequate cardiac output to pump
the blood at the higher exercise rate and (2)
inadequate vasculature in the skeletal muscles.

Thus increasing the intake of O2 as seen by
athletes after performance does not do anything
since the blood is already saturated with enough
oxygen.
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Respiratory Adjustments: High Altitude

The body responds to quick movement to high
altitude (above 8000 ft) with symptoms of acute
mountain sickness – headache, shortness of breath,
nausea, and dizziness
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Respiratory Adjustments: High Altitude

Acclimatization – respiratory and hematopoietic
adjustments to altitude include:

Increased ventilation – 2-3 L/min higher than at sea
level

Chemoreceptors become more responsive to PCO2

Substantial decline in PO2 stimulates peripheral
chemoreceptors
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See Respiratory Diseases PowerPoint
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Chronic Obstructive Pulmonary Disease
(COPD)
 Exemplified by chronic bronchitis and obstructive
emphysema


Patients have a history of:

Smoking

Dyspnea, where labored breathing occurs and gets
progressively worse

Coughing and frequent pulmonary infections
COPD victims develop respiratory failure
accompanied by hypoxemia, carbon dioxide
retention, and respiratory acidosis
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Pathogenesis of COPD
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Figure 22.28
Asthma

Characterized by dyspnea, wheezing, and chest
tightness

Active inflammation of the airways precedes
bronchospasms

Airway inflammation is an immune response
caused by release of IL-4 and IL-5, which
stimulate IgE and recruit inflammatory cells

Airways thickened with inflammatory exudates
magnify the effect of bronchospasms
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Tuberculosis

Infectious disease caused by the bacterium
Mycobacterium tuberculosis

Symptoms include fever, night sweats, weight loss,
a racking cough, and splitting headache

Treatment entails a 12-month course of antibiotics
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Lung Cancer

Accounts for 1/3 of all cancer deaths in the U.S.

90% of all patients with lung cancer were smokers

The three most common types are:

Squamous cell carcinoma (20-40% of cases) arises
in bronchial epithelium

Adenocarcinoma (25-35% of cases) originates in
peripheral lung area

Small cell carcinoma (20-25% of cases) contains
lymphocyte-like cells that originate in the primary
bronchi and subsequently metastasize
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Developmental Aspects

Olfactory placodes invaginate into olfactory pits
by the 4th week

Laryngotracheal buds are present by the 5th week

Mucosae of the bronchi and lung alveoli are
present by the 8th week
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Developmental Aspects

By the 28th week, a baby born prematurely can
breathe on its own

During fetal life, the lungs are filled with fluid and
blood bypasses the lungs

Gas exchange takes place via the placenta
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Respiratory System Development
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Figure 22.29
Developmental Aspects

At birth, respiratory centers are activated, alveoli
inflate, and lungs begin to function

Respiratory rate is highest in newborns and slows
until adulthood

Lungs continue to mature and more alveoli are
formed until young adulthood

Respiratory efficiency decreases in old age
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