1. The Respiratory System

2. Functions
Exchange of gases (O2 & CO2) between environment and tissues.
It plays a role in the regulation of pH of the extracellular fluid.

3. Mechanics of breathing
Anatomical consideration:
The lungs
Thoracic cage (muscles, ribs and vertebrae)
Diaphragm
Pleural space (visceral and parietal pleurae)

4. Chest movement: Inspiration:
External intercostal muscle ( anteroposterior diameter)
Internal intercostal muscle ( anteroposterior diameter)
Diaphragm ( vertical diameter)
Inspiration:
Active process
 volume of thoracic cavity  lower the intrapleural pressure
The lungs expand  lowers the intra-alveolar pressure  draw air into the lungs
Quiet breathing: 1/10th of inspiratory muscles are active
Deep breathing: increased in pulmonary ventilation 10 folds (60L/min)

5. Accessory muscles of respiration:
Expiration:
Passive
Relaxation of muscles of inspiration
Recoil of chest wall  rises of intrapleural pressure
Elastic recoil of the lungs  rises of intra-alveolar pressure  forced air out of the lungs
Accessory muscles of respiration:
Accessory muscle of inspiration: sternocleidomastoid, anterior serrati and the scaleni
Accessory muscle of expiration: the internal intercostal muscles and abdominal recti.

6. Intrapleural pressure:
Negative pressure vary between -2mmHg at the end of expiration to –6mmHg during inspiration.

7. Causes of the negative intrapleural pressure
1. The lungs
Elastic recoil of the lungs  tends to collapse in an inward direction
The surface tension of the fluid lining the alveoli
Surfactant normally reduced this surface tension
It’s a lipoprotein substance secreted by type II alveolar epithelium
Decrease surfactant in the newborn causes hyaline membrane disease of the newborn or (respiratory distress syndrome)
2. The chest wall
Tends to recoil outward
At equilibrium, there are two opposing forces lead to a negative pressure in the pleural cavity

8. 3. Pleural capillaries and lymphatics
The intrapleural space is rich in blood capillaries and lymphatics, which tend to absorb fluid from the pleural cavity  adds to the negativity of intrapleural pressure
Intra-alveolar (intrapulmonary) pressure
Pressure within the alveoli of the lungs varies with different stages of respiratory cycle
During inspiration: quiet inspiration, the pressure falls to –1mmHg but with forcible inspiration it falls to about –70mmHg
During expiration: in quiet expiration, it rises to 1mmHg but during forcible expiration it rises to 100mmHg (Valsalva manoeuver)

9. Lung Volumes and Capacities

10. Respiratory minute volume or (pulmonary ventilation):
Tidal volume:
Is the volume of air inspired or expired at each breath. 500mL in normal quiet breathing (0.5L).
Respiratory minute volume or (pulmonary ventilation):
Is the volume of air breathed in or out of the lungs each minute.
500 (tidal volume) x 12 (respiratory rate) = 6000mL/min.
Inspiratory reserve volume:
The volume of air inspired by a maximal inspiratory effort after normal inspiration (3.3L).
Inspiratory capacity:
The volume of air inspired by a maximal inspiratory effort after normal expiration. Equal to the tidal volume plus the inspiratory reserve volume (3.8L).
Expiratory reserve volume:
The volume of air expired by a maximal expiratory effort after normal expiration (1L).

11. Functional residual capacity (FRC):
Vital capacity:
The volume expired by a maximal expiratory effort after maximal inspiration. Equal to the tidal volume plus inspiratory reserve volume plus expiratory reserve volume (4.8L).
Residual volume:
The volume of air that remains in the lung after maximal expiration. Cannot be measured by spirometer or gas meter. Increased by age and lung disease (1.2L).
Functional residual capacity (FRC):
The volume of air that remains in the lung after normal expiration. Cannot be measured by spirometer (2.2L).

12. Total lung capacity:
The maximal volume of air that can be accommodated in the lungs. Equal to tidal volume plus inspiratory reserve volume plus expiratory reserve volume plus residual volume (6L).
Both residual volume and functional residual capacity  by age while vital capacity  by age.
The lung volumes and capacities are lower in females (20 – 25%) than in the male.

13. Distribution of pulmonary ventilation
Definitions
Ventilation: is the process dealing with the air movement between the lung and atmospheric air
Pulmonary ventilation: is the volume of air breathed in or out per minute
Inspired air is distributed to distinct spaces in the lungs

14. Anatomical dead space:-
Occupies the air-conducting system down to the terminal bronchioles
No gas exchange
Volume  150ml
Respiratory zone:-
Occupies the space distal to the terminal bronchioles down to the alveolar sacs
Gas exchange takes place
Volume  350ml/min
Gas exchange in the lungs (Diffusion)
Exchange of gases (O2 and CO2) between the alveoli and blood

15. Factors affecting the rate of diffusion
1. Alveolar capillary membrane (ACM):
Semipermeable membrane
Separates alveolar air from pulmonary capillary blood
Formed of several layers:
Fluid film lining the alveoli
Alveolar membrane
Interstitial fluid
Capillary wall
Change in the thickness of alveolar capillary membrane will affect the rate of gas diffusion
In pulmonary edema  thickness of the ACM   rate of diffusion
During exercise  thickness of ACM   rate of diffusion

16. 2. Partial pressure gradient of gases across the alveolar capillary membrane:
Partial pressure of O2 in mixed venous blood 40mmHg, the P–P of O2 in alveolar air is 100mmHg. So O2 diffuses from the alveolar space to the capillary blood along partial pressure gradient of about 60mmHg
P–P of CO2 in venous blood is 46mmHg, while in the alveolar air is 40mmHg, so CO2 diffuses from the capillary to the alveolar space along partial pressure gradient of about 6mmHg
3. Physical properties of gases:
Solubility and M-W of gases affect the rate of diffusion
CO2 is 20 times more soluble than O2
Diffusion failure affects O2 before CO2 is affected

17. 4. Surface area:
As the surface of the alveolar capillary membrane increases, the total volume of gas exchanged will be increased. The surface area of ACM = 70m2 in adult male
5. Ventilation/blood flow ratio:
Ventilation/blood flow ratio = alveolar ventilation/ blood flow = 4/5 = 0.8
The bases of the lung perfused more than the apices
6. Temperature:
The rate of diffusion of gases is normally dependent on temperature

18. 7. Chemical reactions:
Each 1 gram of Hb, when fully saturated, combines with 1.34ml of O2 at STP (at partial pressure of O2 of 100mmHg)
O2 dissolved in 100mL of blood at O2 partial pressure of 100mmHg is x 100 = 0.3mL
8. Diffusion capacity:
CO2 has greater diffusion capacity than O2 about 20 times more (CO2 has greater solubility than O2)

19. Transport of Oxygen O2 is transported in the blood in two forces:-
Oxyhaemoglobin > 98%
Dissolved oxygen < 2%
In arterial blood x 100 = 0.3mL of O2
In venous blood x 40 = 0.12mL of O2

20. Oxyhaemoglobin
Hb has great affinity for O2. It combines loosely, fast and reversibly with O2
It is the function of the P–P of O2 in relation with saturation of Hb with O2 (oxyhaemoglobin dissociation curve)

21. Oxygen-Haemoglobin dissociation curve:
The percentage saturation of Hb with O2 against partial pressure of O2
Sigmoid in shape (S-shaped)
Hb has 4 haem units attached to polypeptide chains
Oxygenation of one haem unit leads to changes in the configuration of the Hb molecule which increase the affinity of the 2nd unit and so on
Steep rise in the percentage saturation of Hb between PO2 of 0mmHg and 75mmHg, then slow rise in the curve, becoming more or less flat at PO2 of 80mmHg or above

22. Depends on PO2 and independent on Hb concentration
At zero P–P of O2  %saturation is zero
At PO2 100mmHg (arterial blood)  %saturation  97%
At PO2 40mmHg (venous blood)  %saturation  75%
It is used for measurement of O2 content in venous and arterial blood

23. When 1gm of Hb is fully saturated with O2  it binds up to 1
When 1gm of Hb is fully saturated with O2  it binds up to 1.34mL of O2
If Hb concentration = 150gm/L blood
O2 content of arterial blood (97% saturation) = 1.34 x 150 x 97/100 = 195mL/L of blood
O2 content of venous blood (75% saturation) = 1.34 x 150 x 75/100 = 150mL/L blood
O2 uptake by tissues = arterio-venous difference = 195 – 150 = 45mL/L of blood

24. Factors affecting O2-Hb dissociation curve:
Shift to the right indicate lower affinity of Hb for O2
Shift to the left indicate increased affinity of Hb for O2

25. 1. Partial pressure of carbon dioxide:
 PCO2   affinity of Hb for O2 and shifts the curve to the right (Bohr effect)
PCO2 is high in the tissues, while it is lower in the lung
2. pH:
 pH ( H+ concentration)   Hb affinity to O2 and shifts the curve to the right

26. 4. 2,3-diphosphoglycerate (2,3-DPG):
3. Temperature:
Rise of temperature also shifts the curve to the right
In active tissues, heat is generated mainly due to oxidation
4. 2,3-diphosphoglycerate (2,3-DPG):
2,3-DPG is found in RBCs bound to Hb
 2,3-DPG   Hb affinity to O2 and shifts the curve to the right
It helps the release of O2 from the tissue ( in hypoxia at high altitude)

27. Dissolved oxygen Less than 2%
It is at equilibrium with the O2 combined with Hb
The dissolved O2 transferred to tissues than replaced from O2 carried by Hb
It is essential for tissues that don’t have blood supply, like the cornea and cartilage

28. Can be increased by breathing pure or hyperbaric O2
O2 is poorly soluble in blood
In 100mL blood at body temperature, 0.003mL O2 dissolved at PO2 1mmHg
In arterial blood  0.3mL/100mL O2 is dissolved
In venous blood  0.12mL/100mL

29. Transport of CO2
CO2 produced by active cells diffuses by concentration gradient into the tissue fluid to reach the plasma

30. CO2 is transported by:
The plasma (this reaction proceed very slowly due to the absence of carbonic anhydrase enzyme)
The red blood cells (this reaction proceed very quickly due to presence of carbonic anhydrase enzyme)
In 3 forms:
Dissolved  10% (0.4mL)
Bicarbonate  70% (2.8mL)
Carbamino compounds  20% (0.8mL)

31. Control of Ventilation
Several mechanisms are involved which can be grouped into two main categories which are closely integrated:-
Nervous control mechanism
Chemical control mechanism

32. The Respiratory Center
Composed of several groups of neurons
Located in the entire length of the medulla and pons
Can be divided into four major groups of neurons:-
Dorsal respiratory group
Ventral respiratory group
The apneustic center
The pneumotoxic center

33. 1. The dorsal respiratory group –
located in the entire length of the dorsal aspect of the medulla. It comprises inspiratory neurons which discharge rhythmically during resting and forced inspiration, so that it is called the rhythmicity center. They are almost responsible for inspiration.

34. 2. The ventral respiratory group – lies ventrolateral to the dorsal respiratory group along the entire length of the medulla. They are inactive during quiet breathing but they are activated during forced breathing as in exercise and they are mainly expiratory neurons with some inspiratory neurons. They are inactive at rest or passive expiration and they become activated when expiration is on active process.

35. 3. The apneustic center – it is situated in the lower pons
3. The apneustic center – it is situated in the lower pons. It sends excitatory impulses to the dorsal respiratory groups to potentiate the inspiratory drive. It receives inhibitory impulses from the sensory vagal fibers of the Hering-Breuer inflation reflex and inhibitory impulses from the pneumotaxic center.

36. Midpontine section will abolite both sensory vagal and inhibitory impulses from the pneumotaxic center and result in apneustic breathing (prolonged inspiration), while section between the medulla and pons will remove the inspiratory drive of the apneustic center resulting in gasping breathing, i.e., shallow inspiration and followed by a prolonged period of expiration.

37. 4. The pneumotaxic center – located in the upper pons
4. The pneumotaxic center – located in the upper pons. It transmits inhibitory impulses to the apneustic center and to the inspiratory area to switch off inspiration.

39. Nervous Control of Ventilation
The rhythmicity center received impulses from:
Higher brain centers
Centers in the brain stem (medulla and pons)
Special receptors (respiratory reflexes)
The rhythmicity center sends excitatory impulses via the intercostal and phrenic nerves to the external intercostal muscles and diaphragm

41. Chemical Control of Ventilation
The rhythmicity center is affected by chemical changes in the blood via two types of chemoreceptors:-
Peripheral chemoreceptors
Central chemoreceptors

42. Peripheral Chemoreceptors

43. Located mainly in the carotid and aortic bodies, but may be found anywhere in the circulatory system
When stimulated, send excitatory impulses to the rhythmicity center (via glossopharyngeal and vagus nerves)
Highly sensitive to changes in arterial PO2 and to a lesser extent to PCO2 and pH
Fall of PO2, rise in PCO2 and fall of pH, stimulate the chemoreceptors to increase ventilation

44. Normal PO2, PCO2 and pH, low grade of tonic activity in the nerves
 PCO2 and  pH causes low tonic activity   ventilation
In metabolic acidosis  pH causes  ventilation to wash out CO2 and to bring pH to normal
In metabolic alkalosis  pH causes  ventilation, CO2 retained in the blood to compensate

45. Central Chemoreceptors
Most probably located on the ventrolateral surface of medulla oblongata (which is bathed with cerebrospinal fluid)
Highly sensitive to the hydrogen ion concentration of the CSF evoked by arterial PCO2 (CO2 can freely cross the blood-brain barrier into CSF, while BBB is relatively impermeable to H+ and HCO-3 ions)