1. The Respiratory System: Physiology
Chapter 23
The Respiratory
System:
Physiology

2. Respiratory System Anatomy
Functionally, the respiratory system is divided into the conducting zone and the respiratory zone.
The conducting zone - nose, pharynx, larynx, trachea, bronchi, bronchioles and terminal bronchioles.
The respiratory zone is the main site of gas exchange and consists of the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli.

3. Functions of Respiratory System
The respiratory system functions to supply the body with oxygen and dispose off carbon dioxide
Four processes accomplish this:
Pulmonary ventilation – moving air into and out of the lungs
External respiration – gas exchange between the lungs and the blood
Internal respiration – gas exchange between blood and tissues
Transport of oxygen and carbon dioxide between the lungs and tissues- by blood

4. Pulmonary ventilation
Pulmonary ventilation is the movement of air between the atmosphere and the alveoli
Inspiration – air flows into the lungs
Expiration – air flows out of the lungs

5. Pressure Relationships in the Thoracic Cavity
Respiratory pressures are described relative to atmospheric pressure
Atmospheric pressure
Pressure exerted by the air surrounding the body
At sea level the atmospheric pressure is 760mmHg= 1atm

6. Pressure Relationships in the Thoracic Cavity
Intrapulmonary pressure– pressure within the alveoli
Intrapulmonary rises & falls with the phases of breathing, but always equalizes itself with atmospheric pressure- 760mmHg

7. Pressure Relationships in the Thoracic Cavity
Intrapleural pressure– pressure within the pleural cavity
Intrapleural pressure is less than intrapulmonary pressure= 756mmHg

8. Pulmonary Ventilation
A mechanical process that depends on volume changes in the thoracic cavity
Volume changes lead to pressure changes, which lead to the flow of gases to equalize pressure
Boyle’s law – the pressure of a gas varies inversely with its volume
The larger the volume the lesser the pressure- V ∝ 1/P
Volume = 1 liter
Pressure = 1 atm
Volume = 1/2 liter
Pressure = 2 atm

9. Pulmonary Ventilation
Muscles of inspiration ( inhalation):
Diaphragm ( primary muscle of inspiration)
External intercostals
Normal expiration is a passive process
Muscles of forced expiration (exhalation):
Internal intercostals
Abdominal muscles

10. The recruitment of accessory muscles depends on whether the respiratory movements are quiet (normal), or forced

11. Inspiration
Inspiratory muscles contract: diaphragm descends, rib cage rises
Thoracic cavity volume increases
Lungs stretched- intrapulmonary volume increases
Intrapulmonary pressure drops by 2mmHg
Air flows into lungs down the pressure gradient, till intrapulmonary pressure equalizes atmospheric pressure

12. Expiration
Inspiratory muscles relax; diaphragm rises, rib cage descends
Thoracic cavity volume decreases
Elastic lungs recoil passively
Intrapulmonary volume decreases
Intrapulmonary pressure rises by 2mmHg
Air flows out of the lungs, down the pressure gradient, till intrapulmonary pressure equalizes atmospheric pressure

13. Factors affecting Pulmonary Ventilation
3 factors affect the ease with which we ventilate:
Surface tension of alveolar fluid
Lung compliance
Airway resistance

14. Factors affecting Pulmonary Ventilation
The surface tension of alveolar fluid causes the alveoli to assume the smallest possible diameter
The alveoli would collapse each expiration
Surfactant reduces tension- prevents the collapse of alveoli
Clinical connection: Infant respiratory
distress syndrome ( IRDS) .

15. Factors affecting Pulmonary Ventilation
Lung compliance means the ease with which lungs and chest wall expand.
Related to two main factors
Elasticity of the lung tissue
Surface tension of the alveoli
Lungs of healthy people have a high compliance
Compliance is decreased in:
Lung fibrosis, IRDS, intercostal muscle paralysis, emphysema

16. Factors affecting Pulmonary Ventilation
3. Airway resistance
Gas flow is inversely proportional to resistance (friction)- mainly determined by diameter of airways
The smaller the diameter the more the resistance
Sympathetic stimulation dilates bronchi & decreases resistance
Airway resistance increases in:
Asthma attacks, chronic bronchitis-when bronchioles are constricted -decreases ventilation

17. Old and new spirometers used to measure ventilation.
Measuring Ventilation- Ventilation can be measured using spirometry. Lung volumes and Capacities can be measured
Old and new spirometers used to measure ventilation.

18. Lung Volumes
Tidal Volume (VT) is the volume of air inspired (or expired) during normal quiet breathing (500 ml).
Inspiratory Reserve Volume (IRV) is the volume inspired during a very forced inhalation (3100 ml – height and gender dependent).

19. Lung Volumes
Expiratory Reserve Volume (ERV) is the volume expired during a forced exhalation (1200 ml).
Residual Volume (RV) is the air still present in the lungs after a force exhalation (1200 ml).
The RV is a reserve for mixing of gases but is not available to move in or out of the lungs.

20. Lung Capacities
Inspiratory capacity: Is the total volume of air that can be inspired after a tidal expiration
IC=TV+IRV
Functional residual capacity: Is the volume of air that remains in the lungs at the end of normal tidal expiration
FRC= RV+ ERV
Vital Capacity (VC) : the total amount of exchangeable air
Is all the air that can be exhaled after maximum inspiration.
It is the sum of the inspiratory reserve + tidal volume + expiratory reserve (4800 ml)
Total lung capacity- Is the sum of all lung volumes-6000ml
Minimal Volume (MV) is the air still present in lung tissue after the thoracic cavity has been opened (480 ml)

21. A graph of spirometer volumes and capacities

22. Forced vital capacity (FVC)– the volume of air forcibly & rapidly expelled after taking a deep breath
Forced expiratory volume (FEV1) – the volume of air expelled during 1sec (healthy person can expel 80% of FVC in 1sec) in the FVC test
COPD decreases FEV1, because it increases resistance to flow of air

23. Only about 350 ml of the tidal volume reaches the respiratory zone – the 150ml remains in the conducting zone (called the anatomic dead space).
If a single VT breath = 500 ml, only 350 ml will exchange gases at the alveoli.
With a respiratory rate of 12/min, the minute ventilation rate= 12 x 500 = 6000 ml/min.
The alveolar ventilation rate(volume of air/min that actually reaches the alveoli) = 12 x 350 = 4200ml/min.

24. Respiration Respiration is the exchange of gases.
External respiration (pulmonary) is gas exchange between the alveoli and the blood.
Internal respiration (tissue) is gas exchange between the systemic capillaries and the tissues of the body.

25. Exchange of O2 and CO2
The respiratory system depends on the medium of the earth’s atmosphere to extract the oxygen necessary for life.
The atmosphere is composed of these gases:
Nitrogen (N2) 79%
Oxygen (O2) 21%
Carbon Dioxide (CO2) 0.04%
Water Vapor variable, but on average around 1%

26. Exchange of O2 and CO2
Using gas laws we can understand the principals of respiration
Dalton’s Law states that each gas in a mixture of gases exerts its own pressure- its partial pressure Pp.
Total pressure is the sum of all the partial pressures.
The partial pressure of each gas is directly proportional to its percentage in the mixture

27. Exchange of O2 and CO2
The partial pressures determine the direction of movement of gases
Each gas diffuses across a permeable membrane from high to low partial pressure
There is a higher PO2 in the alveoli than in the pulmonary capillaries O2 moves from the alveoli into the blood.
Since there is a higher PCO2 in the pulmonary capillaries CO2 moves into the alveoli

28. Exchange of O2 and CO2 Henry’s law deals with gases and solutions:
The quantity of a gas that will dissolve in a liquid is proportional to the partial pressures of the gas and its solubility.
Increasing the partial pressure of a gas in contact with a solution will result in more gas dissolving into the solution
How much it dissolves also depends on solubility
CO2 is 24 times more soluble in blood (and soda !) than O2

29. Clinical connections
Hyperbaric oxygen- high pressures of O2 are used to treat anaerobic bacterial infections such as tetanus, gangrene
Decompression sickness (“the bends”)
Air is mostly N2, but very little dissolves in blood due to its low solubility
Insoluble N2 is forced to dissolve into the blood and tissues because of breathing compressed air in scuba diving
By ascending too rapidly, the N2 bubbles out of the tissues and blood

30. Alveolar air is different in composition from Atmospheric air
The atmosphere is mostly oxygen and nitrogen, while alveoli contain in comparison more carbon dioxide and less oxygen
These differences result from:
Gas exchanges in the lungs
Mixing of alveolar air that remains, with newly inspired air
Atmospheric air: Alveolar air:
PO2 = 159 mmHg PO2 = 105 mmHg
PCO2 = 0.3 mmHg PCO2 = 40 mmHg

31. External Respiration (Pulmonary gas exchange)
O2 diffuses down its steep PO2 gradient in the alveoli (105mmHg) to pulmonary capillary blood (40mmHg)
CO2 diffuses down its gentler PCO2 gradient from pulmonary capillary blood ( 45mmHg) to alveoli (40mmHg)- exhaled
Blood in the pulmonary veins entering the left atrium has:
PCO2 40mmHg
PO2 100mmHg (due to mixing of blood from bronchial veins)

32. Internal Respiration
As in gas exchange between blood & alveoli, the gas exchange between blood & tissue cells occurs by simple diffusion, driven by partial pressure gradients
Tissue cells constantly use O2 & produce CO2
PO2 in tissue is 40mmHg- O2 moves into tissues from blood capillaries
PCO2 is 45 mm Hg in tissues- CO2 moves into blood
PO2 of venous blood draining tissues is 40 mm Hg and PCO2 is 45 mm Hg

33. Systemic tissue cells:
Atmospheric air:
PO2 = 159 mmHg
PCO2 = 0.3 mmHg
CO2 exhaled
O2 inhaled
Alveolar air:
PO2 = 105 mmHg
PCO2 = 40 mmHg
Alveoli
CO2 O2
Pulmonary capillaries
(a) External respiration:
pulmonary gas
exchange
To lungs
To left atrium
Deoxygenated blood:
PO2 = 40 mmHg
PCO2 = 45 mmHg
Oxygenated blood:
PO2 = 100 mmHg
PCO2 = 40 mmHg
To right atrium
To tissue cells
(b) Internal respiration:
systemic gas
exchange
Systemic capillaries
CO2 O2
Systemic tissue cells:
PO2 = 40 mmHg
PCO2 = 45 mmHg

34. Factors affecting gas exchange
Factors influencing the movement of oxygen and carbon dioxide across the respiratory membrane
Partial pressure gradients and gas solubilities
Surface area for gas exchange & thickness of the respiratory membrane
Matching of alveolar ventilation (airflow) to alveoli and pulmonary perfusion (blood flow)

35. Partial pressure gradients and gas solubility
The more the partial pressure differences, the more is the rate of gas diffusion
During exercise greater differences in PCO2 and PO2 between alveolar air and pulmonary blood- greater rate of gas diffusion
Decreased alveolar PO2 at high altitudes – decreases oxygen diffusion
Solubility:
CO2 diffuses out faster compared to O2 diffusing in

36. Surface area & respiratory membrane
Respiratory membranes are only 0.5 to 1 m thick- allows efficient gas exchange
Thicken in pulmonary edema- gas exchange is inadequate
The greater is the surface area, the more gases can be exchanged- normally huge
Decrease in surface area:
emphysema, when walls of adjacent alveoli break
mucus, tumors block gas flow into alveoli

37. Ventilation-Perfusion Matching
Ventilation and perfusion must be matched for efficient gas exchange
In the lungs, pulmonary vasoconstriction occurring in response to hypoxia diverts pulmonary blood from poorly ventilated areas of the lungs to well-ventilated regions
pulmonary vasodilation in response to increased ventilation

38. Transport of O2
In the blood, some O2 is dissolved in the plasma as a gas (only about 1.5%)
Most O2 (about 98.5%) is carried attached to Hb.
Oxygenated Hb is called oxyhemoglobin (Hb-O2)

39. Transport of O2
The amount of Hb saturated with O2 is called percent saturation of hemoglobin
Each Hb molecule can carry 1 to 4 molecules of O2. Blood leaving the lungs has Hb that is almost fully saturated-
the percent saturation is close to 98%
Partially saturated hemoglobin –
when 1-3 heme groups are bound to oxygen

40. Factors affecting saturation of Hb
Most important factor is PO2
The relationship between the amount of PO2 in plasma and the saturation of Hb is called the oxygen-hemoglobin dissociation curve.
The higher the PO2 dissolved in
the plasma, the higher the Hb.
saturation
With PO2 100mmHg in
arterial blood saturation is 98%

41. PO2 and percent saturation contd.
In the venous blood at PO2 40mmHg
-percent saturation is 75%
- only 25% has O2
been unloaded to tissues
With PO2 between mmHg, Hb is
90% or more saturated with oxygen
So even with PO2 as low as 65mmHg
Hb saturation is not so low-
(important for those with lung diseases
or living at high altitudes

42. PO2 and percent saturation contd.
Between 40 and 20mmHg a small decrease in PO2
causes a large drop in Hb saturation -with release of oxygen
In actively contracting muscles PO2 may drop to 20mmHg – saturation 35%- with oxygen release to muscles

43. Transport of O2
Measuring hemoglobin saturation is common in clinical practice- done by Pulse oximeters
3660 Group,
Inc/NewsCom

44. Factors influencing the affinity of Hb binding with O2 -Affect percent saturation of Hb

45. Bohr Effect Metabolically active tissues produce H+
H+ bind to Hb- change its shape- decreasing affinity of Hb for oxygen- enhancing unloading of O2 to tissues
The pH decrease shifts the O2–Hb saturation curve “to the right”
This is called the Bohr effect

46. Transport of CO2
CO2 is transported in the blood in three different forms:
7% is dissolved in the plasma, as a gas.
70% is transported as bicarbonate ions (HCO3–) through the action of an enzyme called carbonic anhydrase.
CO2 + H2O H2CO H+ + HCO3-
23% is attached to Hb (to the amino acids) as carbaminohemoglobin( HbCO2)

47. Transport of CO2
At the level of tissues: Carbon dioxide diffuses into RBCs, combines with water to form H2CO3, (catalyzed by carbonic anhydrase), which quickly dissociates into hydrogen ions and bicarbonate ions
Cl–)
Bicarbonate diffuses from RBCs into the plasma
The chloride shift – to balance the outrush of negative bicarbonate ions from the RBCs, chloride ions (Cl–) move into the erythrocytes

48. Transport of CO2
At the lungs, these processes are reversed
Cl–)

49. Control of Respiration- Respiratory Center
The medullary rhythmicity area, has centers that control basic respiratory rythm
The inspiratory center
stimulates the diaphragm
via the phrenic nerve, and
the external intercostal
muscles via intercostal nerves.
Inspiration normally lasts about 2s.

50. Control of Respiration-Respiratory Center
Expiration is a passive process- nerve impulses cease for about 3 sec, causing relaxation of inspiratory myscles
The expiratory center is inactive during quiet breathing
During forced exhalation,
however, impulses from this
center stimulate the internal
intercostal and abdominal
muscles

51. Control of Respiration
Other sites in the pons help the medullary centers
The pneumotaxic center limits inspiration to prevent hyperexpansion of lungs
The apneustic center prolongs
inhalation
The pneumotaxic center does use reverberating circuits (cooperation between the pneumotaxic and apneustic centers) whereas the Herring Breuer reflex uses stretch receptors.
69. To prevent over-inflation, the pneumotaxic center uses:
A. reverberating circuits
B. diverging circuits
C. stretch receptors
D. chemoreceptors
ans: A
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70. The Hering-Breuer reflex uses:
A. reverberating circuits to regulate O₂ levels
B. diverging circuits to regulate O₂ levels
C. stretch receptors to prevent overinflation
D. O₂ receptors to control internal respiration
E. CO₂ receptors to control internal respiration
ans: C

52. Chemoreceptor Regulation of Respiration:
Central chemoreceptors in medulla only sensitive to PCO2
Peripheral chemoreceptors sensitive to PCO2, PO2, arterial pH
PCO2 levels rise (hypercapnia) stimulate both the central & peripheral chemoreceptors
Respiratory center stimulated
Hyperventilation – increased rate and depth of breathing occurs in response to hypercapnia- CO2 flushed out

53. Chemoreceptors Peripheral Chemoreceptors
Medulla oblongata Central chemoreceptors
Internal carotid
artery
glossopharyngeal nerve
(cranial nerve IX)
Carotid body
Carotid sinus
vagus nerve
(cranial nerve X)
Peripheral Chemoreceptors
Arch of aorta
Aortic bodies
Heart

54. Chemoreceptor Regulation of Respiration
Fall in pH:
Acidosis may occur due to:
Carbon dioxide retention, other metabolic conditions e.g. accumulation of lactic acid
Increased ventilation in response to falling pH is mediated by peripheral chemoreceptors

55. Chemoreceptor Regulation of Respiration
Arterial PO2 levels are monitored by the aortic and carotid body peripheral chemoreceptors
Substantial drops in arterial PO2 (to 60 mm Hg) are needed before oxygen levels become a major stimulus to increase ventilation (hypoxic drive)

56. Chemoreceptor Regulation of Respiration

57. Control of Respiration
Other brain areas also play a role in respiration:
The cerebral cortex has influence over breathing.
Stretch receptors in lungs sense overinflation-
inhibitory signals are sent to the medullary inspiration center to end inhalation and allow expiration (Herring Breuer reflex)
Emotions (limbic system) affect respiration.
Plus hypercarbia (elevated PCO2) and acidosis (a low pH ) stimulate more rapid breathing through the brainstem breathing centers

58. Diseases
Asthma is a disease of hyper-reactive airways (the major abnormality is constriction of smooth muscle in the bronchioles
It presents as attacks of wheezing, coughing, and excess mucus production.
It typically occurs in response to allergens
Bronchodilators and anti-
inflammatory corticosteroids
are mainstays of treatment.
Pulse Picture Library/CMP mages /Phototake

59. Diseases Chronic Obstructive Pulmonary Diseases
They are diseases caused by cigarette smoking
Chronic bronchitis is caused by chronic irritation and inflammation
Patients have cough with sputum
Emphysema : destruction of elastic tissue
with enlargement of air spaces