Lecture to first year medical student LNU-FQD College of Medicine (medical physiology).

1. FUNCTIONAL ANATOMY
MECHANICS OF RESPIRATION
RodolfoT. Rafael,MD., DPAFP

2. PHYSIOLOGY OF
RESPIRATION
Exchange and Transport of Respiratory
Gases
Respiratory Exchange Ratio
2
RodolfoT. Rafael,M.D., DPAFP

3. PHYSIOLOGY OF RESPIRATION
• Regulation of Respiration
RodolfoT. Rafael, M.D., DPAFP

4. Structure and Function of the
Respiratory System
 gas exchange
 host defense
 metabolic organ

5. LUNG ANATOMY
 contained in a space 4L- surface area for gas
exchange (∼85 m2)
 demonstrate functional unity- similar to
kidney
 Weight 1 kg
 60% tissue
 Alveolar spaces
 lung volume
 interstitium- collagen, potential space for fluid
and cells to accumulate

6. Upper Airways-Nose, Sinuses,
Larynx
 Nose---> distal alveolus
 nasal cavity, posterior pharynx, glottis, vocal
cords, trachea, tracheobronchial tree.
 Upper airway
 nose -------- > vocal cords
 Lower airways
 trachea ------- > alveoli

7. Upper Airways
 condition inspired air
 nose
 filter entrap, clear particles
> 10μm, and provides the
sense of smell
 20ml
 surface area increase by
the nasal turbinates

8. Upper Airways
 10,000 to 15,000 L/day
 Nasal resistance
 50% nose
 8cm H2O/L/sec
 viral infections, exercise
 high mouth breathing
 Interior of the nose - respiratory epithelium-
surface secretory cells
 immunoglobulins, inflammatory mediators, and
interferons.

9. Upper Airways
 The paranasal sinuses (frontal sinuses, maxillary
sinus, sphenoid sinus, ethmoid sinus)
 ciliated epithelium ?
 The sinuses have two major functions-
 they lighten the skull
 they offer resonance to the voice.
 They may also protect the brain during frontal trauma.
 In some sinuses (e.g., the maxillary sinus), the opening
(ostium) is at the upper edge- retention of mucus.
 Sinusitis-obstructed ostia
 nasal edema retention of secretions

10. Upper Airways
 The major structures of the larynx include the
 epiglottis
 arytenoids
 vocal cords
 infectionsedematous airflow resistance.
 The epiglottis and arytenoids "hood" or cover the
vocal cords during swallowing.
 The act of swallowing food after mastication
(chewing) usually occurs within 2 seconds, and it
is closely synchronized with muscle reflexes that
coordinate opening and closing of the airway.

11. Lower Airways-Trachea, Bronchi,
Bronchioles, Respiratory Unit
 The right lung, located in the right
hemithorax
 divided into three lobes (upper, middle, and
lower) by two interlobular fissures (oblique,
horizontal)
 Left lung, located in the left hemithorax
 is divided into two lobes (upper, including the
lingula, and lower) by an oblique fissure

13. Lower Airways
 Visceral pleura
 Parietal pleura
 The interface of these two pleuras allows for
smooth gliding of the lung as it expands in the
chest and produces a potential space.
 Air – pneumothorax
 Fluid- pleural effusion empyema

14. Lower Airways
 The trachea bifurcates (branches) into two
main stem bronchi
 main stem bronchi lobar bronchi (one for each
lobe) segmental bronchi bronchioles
alveolus

17. Lower Airways
 lung supplied by a segmental bronchus - functional
anatomic unit of the lung.
 Bronchi and bronchioles differ
 size
 cartilage
 type of epithelium
 blood supply
 dichotomous or asymmetric branching pattern- terminal
bronchioles
 respiratory bronchioles results in decreased diameter * the
total surface area for that generation increases in size and
number until the respiratory bronchiole terminates in an
opening to a group of alveoli

19. Lower Airways
 The alveoli
 polygonal in shape and about 250 μm in diameter.
 5 × 108 alveoli
 Type I and type II epithelial cells
 1:1 ratio.

20.  The type I cell
 occupies 96% to 98% of the surface area of the
alveolus
 the primary site for gas exchange.
 the basement membrane of type I cells and the
capillary endothelium are fused
 The type II epithelial cell
 small and cuboidal and is usually found in the
"corners" of the alveolus
 occupies 2% to 4% of its surface area
 synthesize pulmonary surfactant

21. Lower Airways
 Alveolar-capillary network
 Gas exchange occurs
 1 to 2 μm in thickness
 type I alveolar epithelial cells, capillary endothelial cells, and
basement membranes.
 < 1 second
 Injury and type I cell deaththe type II cell replicates and
differentiates into type I cells to restore normal alveolar
architecture
 Phylogeny
 recapitulating ontogeny- embryonic development the epithelium
of the alveolus- composed of type II cells

22. Lung Interstitium
 Composed of connective tissue, smooth muscle,
lymphatics, capillaries, and a variety of other
cells.
 Fibroblasts are prominent cells in the
interstitium of the lung
 collagen and elastin
 Collagen is the major structural component of the
lung that limits lung distensibility.
 Elastin is the major contributor to elastic recoil of the
lung.
 Cartilage
 Kultschitzky cells- neuroendocrine cells-
biogenic amines- fetus- bronchial carcinoid

23. BLOOD SUPPLY TO THE LUNG-PULMONARY AND
BRONCHIAL CIRCULATIONS
 The lung has two separate blood supplies.
 The pulmonary circulation
 deoxygenated blood- right ventricle to the gas-
exchanging units for removal of CO2 and
oxygenation.
 The bronchial circulation
 arises from the aorta- nourishment to the lung
parenchyma.

24. Pulmonary Circulation
 The pulmonary
capillary bed
 largest in the body
 surface area of 70 to 80
m2
 The network of
capillaries is so dense
that it might be
considered to be a
sheet of blood
interrupted by small
vertical supporting
posts

25. Pulmonary Circulation
 The capillary volume in the lung at rest is
 70 mL.
 During exercise- volume increases
 200 mL.
 Increase?
 The pulmonary veins
 return blood to the left atrium - supernumerary
conventional branches
 provide a large reservoir for blood, and they can either
increase or decrease their capacitance to provide constant
left ventricular output in the face of variable pulmonary
arterial flow.
 Pulmonary arteries and veins with diameters larger
than 50 μm contain smooth muscle.

26. Bronchial Circulation
 The bronchial
arteries
 three in number
 provide a source of
oxygenated,
systemic blood to the
lungs
 accompany the
bronchial tree and
divide with it

27. Bronchial Circulation
 bronchi, bronchioles, blood vessels, and nerves
 perfuse the lymph nodes and visceral pleura.
 1/3 of the blood returns to the right atrium- bronchial
veins
 2/3 drains into the left atrium- pulmonary veins.
 Cystic fibrosis, the bronchial arteries, which normally
receive only 1% to 2% of cardiac output, increase in
size (hypertrophy) and receive as much as 10% to
20% of cardiac output.
 The erosion of inflamed tissue into these vessels
secondary to bacterial infection- hemoptysis

28. INNERVATION
 Breathing is automatic - central nervous system
(CNS).
 The peripheral nervous system (PNS) includes
both sensory and motor components.
 conveys and integrates signals from the environment
to the CNS.
 Sensory and motor neurons of the PNS transmit
signals from the periphery to the CNS.
 Somatic motor neurons- skeletal muscles
 Autonomic neurons- smooth muscle, cardiac
muscle, and glands.
 The lung- autonomic nervous system of the PNS,
which is under CNS control

30. INNERVATION
 There are four distinct components of the
autonomic nervous system:
 parasympathetic (constriction)
 sympathetic (relaxation)
 nonadrenergic noncholinergic inhibitory (relaxation)
 nonadrenergic noncholinergic stimulatory
(constriction).
 (+) parasympathetic system leads to airway
constriction, blood vessel dilation, and increased
glandular secretion.
 (+) sympathetic system causes airway relaxation,
blood vessel constriction, and inhibition of
glandular secretion

32. INNERVATION
 As with most organ systems, the CNS and
PNS work in cohort to maintain homeostasis.
 Lungs
 no voluntary motor
 no pain fibers
 Pain fibers

33. INNERVATION
 The parasympathetic innervation - medulla in
the brainstem (cranial nerve X, the vagus).
 Preganglionic fibers - vagal nuclei  vagus
nerve  ganglia adjacent to airways and blood
vessels in the lung.
 Postganglionic fibers – ganglia smooth
muscle cells, blood vessels, and bronchial
epithelial cells (including goblet cells and
submucosal glands).
 Both preganglionic and postganglionic fibers
contain excitatory (cholinergic) and inhibitory
(nonadrenergic) motor neurons.
 Acetylcholine and substance P
 dynorphin and vasoactive intestinal peptide

34. INNERVATION
 Parasympathetic
 (+) vagus nerve--> slight constriction of smooth
muscle tone in the normal resting lung.
 bronchial glands--> increase the synthesis of
mucus glycoprotein, raises the viscosity of mucus.
 greater larger airways, and it diminishes toward
the smaller conducting airways in the periphery.
 Response of the parasympathetic nervous
system very specific and local
 Response of the sympathetic nervous system
more general.

35. INNERVATION
 Sympathetic Nervous System
 Mucous glands and blood vessels
 mucous glands increases water secretion.
 Upsets the balanced response of increased
water and increased viscosity between the
sympathetic and parasympathetic pathways

36. Central Control of
Respiration
 Breathing is an automatic, rhythmic, and
centrally regulated process with voluntary
control.
 brainstem- main control center for respiration
 Regulation of respiration requires
 generation and maintenance of a respiratory rhythm
 modulation of this rhythm by sensory feedback loops
and reflexes that allow adaptation to various
conditions while minimizing energy costs
 recruitment of respiratory muscles that can contract
appropriately for gas exchange.

38. MUSCLES OF RESPIRATION-DIAPHRAGM,
EXTERNAL INTERCOSTALS, SCALENE
 The major muscles of respiration include the
 diaphragm
 the external intercostals
 scalene
 Skeletal muscles
 provide the driving force for ventilation
 the force of contraction increases when they are stretched
and decreases when they shorten.
 The force of contraction of respiratory muscles
increases at larger lung volumes.
 The process of respiration or gas exchange begins
with the act of inspiration, which is initiated by
contraction of the diaphragm.

39. Diaphragm
 Contraction
 protrudes into the abdominal cavity
 decrease chest pressure
 inspiration
 Relaxation
 exhalation
 increase chest pressure
 Major muscle of respiration
 Divides the thoracic cavity from the abdominal
cavity
 airway pressure= 150-200 cmH2O
 Quiet breathing- 1 cm
 Deep-Breathing= 10 cm
 R and L phrenic nerves

40. FLUIDS LINE THE LUNG EPITHELIUM AND
PLAY IMPORTANT PHYSIOLOGICAL ROLES
 The respiratory system is lined with three fluids:
 periciliary fluid
 mucus
 surfactant
 Periciliary fluid and mucus
 components of the mucociliary clearance system and line the
epithelium of the conducting airways from the trachea to the
terminal bronchioles.
 they form the basis for the mucociliary clearance system, which
aids in the removal of particulates (e.g., bacteria, viruses, toxins)
from the lung
 Surfactant
 lines the epithelium of the alveolus and provides an "antistick"
function that decreases surface tension in the alveolus

41. Cells of the Mucociliary
Clearance System
 The respiratory tract to the level of the
bronchioles is lined by a pseudostratified, ciliated
columnar epithelium
 maintain the level of periciliary fluid
 5-μm layer of water and electrolytes in which cilia and the
mucociliary transport system function.
 depth is maintained by the movement of various ions-
chloride secretion and sodium absorption
 Mucus and inhaled particles - rhythmic beating of
the cilia on the top of the pseudostratified,
columnar epithelium.
 Each epithelial cell contains about 250 cilia.

43. Cells Regulating Mucus Production
 Goblet or surface secretory cells
 produce mucus
 increase in number in response to chronic cigarette smoke (and
environmental pollutants) increased mucus and airway obstruction in
smokers.
 Submucosal tracheobronchial glands * cartilage in the
tracheobronchial tree.
 empty to the surface epithelium through a ciliated duct, and they are
lined by mucus-secreting mucous and serous cells
 increase in number and size in chronic bronchitis, and they extend down
to the level of the bronchioles in pulmonary disease.
 Clara cells are found at the level of the bronchioles- the goblet cells
and submucosal glands have disappeared.
 granules with nonmucinous material and may have a secretory function.
 play a role in epithelial regeneration after injury.

44. Surfactant and Surface
Tension
 The alveoli are lined with surfactant.
 Surface tension
 force caused by water molecules at the air-liquid
interface that tends to minimize surface area, thereby
making it more difficult to inflate the lung.
 The effect of surface tension on lung inflation is
illustrated by comparing the volume-pressure curves
of a saline-filled versus an air-filled lung.
 Higher pressure is required to fully inflate the lung
with air than with saline because of the higher surface
tension forces in air-filled versus saline-filled lungs.

45. Surfactant and Surface
Tension
 Surface tension is a measure of the attractive force of the
surface molecules per unit length of material to which
they are attached.
 The units of surface tension are those of a force applied
per unit length.
 For a sphere (such as an alveolus), the relationship
between the pressure within the sphere (Ps) and the
tension in the wall is described by the law of Laplace:

47. Surfactant and Surface
Tension
 In the absence of surfactant
 the surface tension at the air-liquid interface would remain
constant and the transmural (transalveolar) pressure needed to
keep it at that volume would be greater at lower lung (alveolar)
volumes
 Thus, greater transmural pressure would be required to produce
a given increase in alveolar volume at lower lung volumes than at
higher lung volumes.
 Surfactant stabilizes the inflation of alveoli because it
allows the surface tension to decrease as the alveoli
become larger
 As a result, the transmural pressure required to keep an alveolus
inflated increases as lung volume (and transpulmonary pressure)
increases, and it decreases as lung volume decreases.

50. Surfactant and Surface
Tension
 “Interdependence”
 Alveoli surrounded by other alveoli.
 The tendency of one alveolus to collapse is opposed
by the traction exerted by the surrounding alveoli.
 collapse of a single alveolus stretches and distorts the
surrounding alveoli, which in turn are connected to other
alveoli.
 pores of Kohn
 canals of Lambert
 The pores of Kohn and the canals of Lambert provide
collateral ventilation and prevent alveolar collapse
(atelectasis).

52. Composition and Function of
Surfactant
 phospholipids, neutral lipids, fatty acids, and proteins.
 85% to 90% lipids, predominantly phospholipids, 10% to
15% proteins.
 The major phospholipid- phosphatidylcholine, 75% of
dipalmitoyl phosphatidylcholine (DPPC).
 major surface-active component in surfactant.
 2nd phosphatidylglycerol (PG)1% to 10% of total surfactant.
 important in the spreading of surfactant over a large surface area.
 Surfactant is secreted by type II cells
 Cholesterol and cholesterol esters account for the majority
of the neutral lipids; their precise functional role is not yet
fully understood, but they may aid in stabilizing the lipid
structure.

53. Composition and Function of
Surfactant
 Four specific surfactant proteins
 (SP-A, SP-B, SP-C, SP-D)
 make up 2% to 5% of the weight of surfactant
 SP-A
 most studied
 which is expressed in alveolar type II cells and in Clara cells in the lung.
 involved in the regulation of surfactant turnover, in immune regulation within the
lung, and in the formation of tubular myelin.
 Two hydrophobic surfactant-specific proteins are SP-B and SP-C.
 SP-B
 involved in tubular myelin formation and the surface activity (i.e., surface tension,
spreading ability) of surfactant, and it may increase the intermolecular and
intramolecular order of the phospholipid bilayer.
 SP-C
 involved in the spreading ability and surface tension activity of surfactant.
 The function of SP-D is unknown at this time.

54. Composition and Function of
Surfactant
 Secretion of surfactant  via exocytosis of the lamellar
body .
 β-adrenergic agonists, activators of protein kinaseC,
leukotrienes, and purinergic agonists
 The major routes of clearance of pulmonary surfactant
within the lung are
 reuptake by type II cells, absorption into the lymphatics,
 clearance by alveolar macrophages
 Pulmonary surfactant serves several physiological roles,
including
 (1) reducing the work of breathing by decreasing surface tension
forces
 (2) preventing collapse and sticking of alveoli on expiration
 (3) stabilizing alveoli, especially those that tend to deflate at low
surface tension.

55. THE LYMPHATIC SYSTEM
 Major functions of the lymphatic network in the lung
 Host defense
 removal of lymph fluid from the lung
 The lymphatic capillaries are highly specialized to allow the
transfer of fluid from the interstitial spaces into the
lymphatic capillaries.
 Although the lymphatic capillaries are somewhat similar to
blood capillaries, they have several distinct features that
aid in fluid movement and clearance:
 (1) there are no tight junctions between endothelial cells
 (2) fine filaments anchor the lymph vessels to adjacent
connective tissue such that with each muscle contraction the
endothelial junctions open to allow fluid movement
 (3) valves enhance lymph flow in one direction.

56. STATIC LUNG MECHANICS

57. Lung Volumes
Total lung capacity (TLC), the total volume of air that can be contained in the
lung. Lung volumes are reported in liters either as volumes or as capacities.

58. Lung Volumes
(tidal volume [VT]) that is moved with each quiet breath is measured.

59. Lung Volumes
Vital capacity (VC)- The total volume of exhaled air, from a maximal inspiration to
a maximal exhalation
Residual volume (RV) is the air remaining in the lung after a complete exhalation.
Functional residual capacity (FRC) is the volume of air in the lung at the end of
exhalation during quiet breathing and is also called the resting volume of the lung.
FRC is composed of RV and the expiratory reserve volume (ERV; the volume of air
that can be exhaled from FRC to RV).

60. Lung Volumes
The ratio of RV toTLC (RV/TLC ratio)
 is used to distinguish different types of pulmonary disease.
 In normal individuals, this ratio is usually less than 0.25.
 An elevated RV/TLC ratio, secondary to an increase in RV out of proportion
to any increase inTLC, is seen in diseases associated with airway obstruction,
known as obstructive pulmonary diseases.
 An elevated RV/TLC ratio can also be caused by a decrease inTLC, which
occurs in individuals with restrictive lung diseases.

61. Determinants of Lung Volume
 What determines the volume of air in the
lung atTLC or at RV?
 The answer lies in the properties of the lung
parenchyma and in the interaction between the
lungs and the chest wall.
 The lungs and chest wall always move
together in healthy individuals.

62. Measurement of Lung Volumes
 RV andTLC can be measured in two ways:
 helium dilution
 body plethysmography.
 Both are used clinically and provide valuable
information about lung function and lung disease.

63. Lung Compliance (CL)
 is a measure of the elastic properties of the lung.
 It is a measure of how easily the lung is
distended.
 is defined as the change in lung volume resulting
from a 1-cm H2O change in the distending
pressure of the lung.
 The units of compliance are mL (or L)/cm H2O.
 High lung compliance refers to a lung that is
readily distended.
 Low lung compliance, or a "stiff" lung, is a lung
that is not easily distended.

64. Pressure-Volume Relationships
 Air flows into and out of the airways from areas of higher
pressure to areas of lower pressure.
 In the absence of a pressure gradient, there is no airflow.
 Minute ventilation is the volume of gas that is moved per unit
of time.
 It is equal to the volume of gas moved with each breath times
the number of breaths per minute:
VE=VT X f
whereVE is minute ventilation in mL or L/min,VT is tidal volume in mL or L,
and f is the frequency or number of breaths per minute.

65. DYNAMIC LUNG MECHANICS

66. Airflow in Airways
 Air flows through the airways when there is a pressure
difference at the two ends of the airway.
 During inspiration, the diaphragm contracts, pleural
pressure becomes more negative (relative to atmospheric
pressure), and gas flows into the lung (from the higher to
the lower pressure).
 Gas exchange to meet the changing metabolic needs of the
body depends on the speed at which fresh gas is brought to
the alveoli and the rapidity with which the metabolic
products of respiration (i.e., CO2) are removed.
 Two major factors determine the speed at which gas flows
into the airways for a given pressure change:
 the pattern of gas flow
 resistance to airflow by the airways

67. Airflow in Airways
 There are two major patterns of gas flow in
the airways-laminar and turbulent flow.
 Laminar flow is parallel to the airway walls and is
present at low flow rates.
 As the flow rate increases and particularly as the
airways divide, the flow stream becomes unsteady
and small swirls occur.
 At higher flow rates, the flow stream is
disorganized and turbulence occurs.
French physician Poiseuille

69. Airway Resistance
 Airflow resistance is the second major factor that
determines rates of airflow in the airways.
 Airflow resistance in the airways (Raw) differs in
airways of different size.
 In moving from the trachea toward the alveolus,
individual airways become smaller while the number
of airway branches increases dramatically.
 Raw is equal to the sum of the resistance of each of
these airways (i.e., Raw = Rlarge + Rmedium + Rsmall).
 The major site of resistance along the bronchial tree is the
large bronchi.
 The smallest airways contribute very little to the overall
total resistance of the bronchial tree

70. In a normal lung, most of the resistance to airflow occurs in the
first eight airway generations

71. Factors That Contribute to
Airway Resistance
 In healthy individuals, airway resistance is approximately 1 cm
H2O/L · sec.
 One of the most important factors affecting resistance is lung
volume.
 Increasing lung volume increases the caliber of the airways.
 resistance to airflow decreases with increasing lung volume, and it
increases with decreasing lung volume.
 Airway mucus, edema, and contraction of bronchial smooth
muscle, all of which decrease the caliber of the airways.
 The density and viscosity of the inspired gas also affect airway
resistance.
 Breathing a low-density gas such as an oxygen-helium mixture results in
a decrease in airway resistance

73. Neurohumoral Regulation of Airway Resistance
 Stimulation of efferent vagal fibers, either directly or reflexively,
 increases airway resistance and decreases anatomic dead space secondary to
airway constriction (recall that the vagus nerve innervates airway smooth
muscle).
 Stimulation of the sympathetic nerves and release of the postganglionic
neurotransmitter norepinephrine
 inhibit airway constriction.
 Reflex stimulation of the vagus nerve by the inhalation of smoke, dust,
cold air, or other irritants
 result in airway constriction and coughing.
 Agents such as histamine, acetylcholine, thromboxane A2,
prostaglandin F2, and leukotrienes (LTB4, LTC4, and LTD4) are released
by resident (e.g., mast cells and airway epithelial cells) and recruited
(e.g., neutrophils and eosinophils) airway cells in response to various
triggers, such as allergens and viral infections.
 act directly on airway smooth muscle to cause constriction and an increase in
airway resistance.
 Inhalation of methacholine, a derivative of acetylcholine
 used to diagnose airway hyperresponsiveness, which is one of the cardinal
features of asthma.

74. The Spirogram
 A spirogram displays the volume of gas
exhaled against time
 four major test results:
 (1) forced vital capacity (FVC)
 (2) forced expiratory volume in 1 second (FEV1)
 (3) the ratio of FEV1 to FVC (FEV1/FVC)
 (4) the average midmaximal expiratory flow
(FEF25-75).

76. Flow-Volume Loop
 A newer way of measuring lung function
clinically is the flow-volume curve or loop.
 A flow-volume curve or loop is created by
displaying the instantaneous flow rate during
a forced maneuver as a function of the
volume of gas.
 This instantaneous flow rate can be displayed
both during exhalation (expiratory flow-
volume curve) and during inspiration
(inspiratory flow-volume curve)

78. END

79. Quiz
1. Contraction of diaphragm create______ pressure inside the chest.
2. Relaxation of diaphragm create______ pressure inside the chest.
3. ____________ the total volume of air that can be contained in the lung.
Lung volumes are reported in liters either as volumes or as capacities.
4. _________________The total volume of exhaled air, from a maximal
inspiration to a maximal exhalation
5. __________________is the air remaining in the lung after a complete
exhalation.
6. ____________________is the volume of air in the lung at the end of
exhalation during quiet breathing and is also called the resting volume of
the lung.
7. The ratio of ____________________ is used to distinguish different types
of pulmonary disease.
8. During inspiration, the diaphragm _____________, pleural pressure
becomes more __________ (relative to atmospheric pressure), and gas
flows into the lung.
9. ______ an instrument displays the volume of gas exhaled against time
10. Function of the respiratory system