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Zagazig University

Faculty of Pharmacy The pulmonary (respiratory)

Dept. of Pharmacology
system is composed of:
- lungs,
- conducting airways,
y gy
- parts
t off the
th CNS,
CNS andd
- chest wall.

Dr Waleed Barakat
1 2

The chest wall consists of the

muscles of respiration such as:
- diaphragm,
- intercostal muscles (2 adjacent
ribs are bound by internal and external
intercostal muscle),

- abdominal muscles and

- rib cage.
3 4

The muscles of respiration and the The CNS & the Neural Pathways
chest wall are essential components Each breath is initiated in the brain,
of the respiratory system. and this message is carried to the
respiratory muscles via the spinal cord
The lungs are not capable of inflating and nerves to the respiratory muscles.
h l the
h force
f f this
for hi inflation
i fl i Functions of respiratory system
must be supplied by the muscles of • gas exchange,
respiration, acting on commands • acid-base balance,
initiated by CNS. • phonation,
• pulmonary defense and metabolism &
5 • the handling of bioactive materials. 6

Acid-Base Balance
In the body, increases in CO2 lead to
increases in H+ concentration The production of sounds by the
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- movement of air through the vocal
The respiratory system can therefore cords.
participate in acid-base balance by Sounds are produced by the actions
removing CO2 from the body. of the CNS controllers on the muscles
The CNS has sensors for the CO2 and of respiration, causing air to flow
H+ levels in the arterial blood and in the through the vocal cords and the
CSF that send information to the mouth.
controllers of breathing. 7 8

Pulmonary Defense Mechanisms Pulmonary Metabolism.

Each breath brings into the lungs a The cells of the lung must metabolize
small sample of the local atmospheric substrates to supply energy and
environment (bacteria, dust, toxic nutrients for their own maintenance.
gases and smoke).
smoke) In addition,
addition the pulmonary capillary
endothelium contains a great number
of enzymes that can produce,
metabolize, or modify naturally
occurring vasoactive substances.
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Gas Exchange - Air enters the respiratory system

through the nose or mouth.
To obtain O2 from the external
environment and supply it to the cells - Air entering through the nose is
(to produce energy for their normal filtered, heated to body temperature,
g) and to remove CO2 and humidified.
produced by - It then passes through the
tracheobronchial tree, the conducting
metabolism. airways, and the alveoli.
- It comes into contact with venous
blood in pulmonary capillaries.
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At the same time, venous blood (high
CO2 and low O2) returning from the
various body tissues is pumped into the
lungs by the right ventricle of the heart.

IIn the
th pulmonary
l capillaries,
ill i CO2 is
exchanged for O2. The blood leaving
the lungs (high O2 and low CO2
content), is distributed to the tissues of
the body by the left side of the heart.
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The Alveolar-Capillary Unit Gas transport properties of blood

(the site of gas exchange in the lung). Transport of O2
Oxygenated blood contains:
-The alveoli (about 300 million) are
0.3 ml dissolved O2 and
enveloped in pulmonary capillaries.
20.1 ml bound to Hemoglobin
g ((oxyHb)
y )
- This provides huge area of contact Blood (15 % Hb, each gm Hb binds 1.34
(about 50 to 100 m2) for gas exchange ml O2) so more Hb means more O2
by diffusion. Transport) and vice versa (Hb anemia
causes cellular hypoxia).
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Transport of CO2 Mechanisms of breathing

10 % CO2 dissolved Ventillation:
20 % CO2 bound to hemoglobin movement of air in the respiratory tract
(carbaminoHb) (inspiration and expiration).
70 % as bicarbonate (HCO3-)
mediated by expansion & contraction
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
of the chest (lungs follow passively)
Air flows over pressure gradient
(atmosphere to lung).
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If PB is defined as zero, the alveolar
Pressure differences between the
pressure is negative during inspiration
alveoli and the environment are the
and positive during expiration.
driving “forces” for the exchange of
gases that occurs during ventilation. These pressure differences are created
Alveolar pressure (PA) must be lower through coordinated movement of the
than the barometric pressure (PB) during diaphragm and chest (thorax), resulting
inspiration (breathing in) & higher during in an increase in lung volume during
expiration (breathing out). inspiration and a decrease during
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Inspiration Muscles of inspiration

• Active process. Diaphragm: contracts pushing down
• Contraction of diaphragm abdominal contents and ribs are lifted
(increase thorax length) upwards and outwards.
• Contraction
C t ti off external
t l intercostal
i t t l
muscles causing elevation of ribs External intercostals and accessory
(increase thorax diameter) muscles: used during exercise and
respiratory distress.

21 22

Expiration Muscles of expiration

• Passive process (normally). Used during exercise or disease

• Retraction of the lung elastic fibers. (expiration is normally passive).
Abdominal muscles:
• During
D i fforced d expiration:
i ti compress abdominal cavity,
¾ Contraction of internal intercostals push the diaphragm up
¾ Contraction of abdominal muscles push air out of the lungs
(elevation of diaphragm).
Internal intercostal muscles:
push ribs downwards and inwards.

Pulmonary volumes Residual Volume (RV)
Tidal Volume (TV) Volume of air that can not be forcibly
Volume of air normally exhaled after a expired (1200 ml).
typical inspiration (500 ml) Vital capacity (VC)
p y Reserve Volume ((ERV)) The largest volume of air that can be moved
i and
in d outt off the
th lungs.
Volume of air that can be forcibly
VC = IRV + TV + ERV.
expired after TV (1000-1200 ml). Total Lung Capacity (TLC)
Inspiratory Reserve Volume (IRV) Total volume of air that a lung can hold
Volume of air that can be forcibly (volume in the lungs after a maximal inspiration).
TLC = IRV + ERV + RV + TV.
inspired over and above TV (3300 ml). 25 (5700 – 6200 ml) 26

Pulmonary gas exchange

O2 diffusion into blood depends on:
Gas exchange in the lungs
Two way exchange of gases between - O2 pressure gradient
the alveolar air & venous blood (Alveolar PO2 – blood PO2)
g to the p
pressure g
gradient - Volume of air inspired
p per minute
(Alveolar air has more PO2 while, venous (Respiratory minute volume)
blood has more PCO2) - Alveolar ventilation
So O2 diffuses from alveolei into blood (volume of air reaching alveoli)
and CO2 diffuses from blood to
alveolei. (deoxygenated blood is converted
to oxygenated blood) 27 28

Structural factors facilitating O2 Systemic gas exchange

Two way exchange of gases between
¾ Very thin alveolar & capillary walls. the cells & arterial blood capillaries
¾ Very large surface area. according to the pressure gradient

¾ Blood supply to lungs (4L/min). O2 diffuses from blood to tissues

CO2 diffuses from tissues to blood
¾ Blood passes as very thin layer in
capillaries (each cell comes close to
alveolar air).
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O2 CO2
- As cells consume O2, - Catabolism produces excess CO2 in
- interstitial & intracellular PO2 decreases, cells.
- O2 pressure gradient between blood - Interstitial & intracellular PCO2
capillaries and tissues increases increases
- CO2 pressure gradient between tissues
- dissolved O2 diffuses from blood to
and blood increases
- CO2 diffuses from tissues to blood
- oxyhemoglobin dissociates to release
where it associates to hemoglobin
forming carbaminohb
HbO2 Hb + O2 31 32

Types of breathing Hyperventilation

Eupenia Pulmonary ventilation is increased more
Normal quiet breathing, than O2 demand
May be voluntary or psychogenic
Spontaneous ventilation & gas exchange
Alveolar PCO2 decreases & PO2 increases
Hyperpnea (ex.
(ex Exercise)
Increased breathing to meet increased Hypoventilation
O2 demand Slow shallow respiration
Pulmonary ventilation is increased, PCO2 increases and PO2 decreases
Tidal Volume is increased and
Breathing frequency may be increased 33 34

Dyspnea Regulation of breathing

Difficult breathing
Respiratory homeostasis to adjust
Associated with hyperventilation
ventilation (and hence arterial blood PO2,
Polypnea PCO2 and pH) to metabolic situation.
Increased breathing rate
Orthopnea Respiratory control centers
Difficult breathing while lying down Located in brain stem (pons and medulla)
Associated with heart disease
Cessation of breathing
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Centers in the medulla Centers in the pons
Inspiratory (stimulate inspiration)
Expiratory (stimulate expiration) Apneustic center
It causes sustained inspiration (apneusis)
Bilateral connection so stimulation at
one side of the brain affects both sides Pneumotaxic center
of respiratory system A as a modulating
Act d l i feed
f d back
b k control,l
when stimulated by apneustic center it
Reciprocal interaction: inhibits the apneustic and inspiratory
Stimulation of the inspiratory center center
inhibits expiratory center and vice
versa 37 38

Genesis of rhythmic respiration Signal through vagus nerve to inhibit

apneustic and inspiratory center and
Signal originate from apneustic center
activate expiratory center expiration
Stimulation of inspiratory center
g from inspiratory
p y center to called Herring Breuer reflex
respiratory muscles Stretch receptor signal stops
Expansion of chest and inflation of lungs Apneustic center is active again
Stimulation of stretch receptors on alveoli The cycle is repeated

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Arterial blood pH
Factors that influence breathing
Acidity of blood stimulates
Partial CO2 pressure
chemoreceptors & increases respiration
Normal PCO2 stimulates chemoreceptors Arterial blood PO2
causing faster breathing When decreased,, stimulates
Decreased PCO2 inhibits chemoreceptors & increases respiration
chemoreceptors and slows breathing However, when decreased below a
Very low PCO2 stops breathing shortly critical level, respiration decreases or
(apnea) stops due to hypoxia of neurons of the
respiratory centers (cannot respond). 42

Arterial blood pressure Miscellaneous factors
Sudden rise causes slowing in respiration Sudden painful stimulation causes apnea
Continued pain causes fast deep respiration
Sudden drop increases respiration Sudden cold stimulation causes apnea
rate and depth
called pressure reflex mechanism Chocking reflex (irritating stimulation of
pharynx or larynx) causes apnea to
prevent aspiration of food or liquids
during swallowing.

43 44

Thank You

Good Luck