1. Physiology of Respiration Dr. Hiwa S. Namiq 17-2-2019

2. Pulmonary Ventilation
Major functions of respiration are 4: (1) Pulmonary ventilation, which means the inflow and outflow of air between the atmosphere and the lung alveoli (2) Diffusion of oxygen and carbon dioxide between the alveoli and the blood (3) Transport of oxygen and carbon dioxide in the blood and body fluids to and from the body’s cells (4) Regulation of ventilation

3. Mechanics of Pulmonary Ventilation
The lungs can be expanded and contracted in two ways:
1-by downward and upward movement of the diaphragm to lengthen or shorten the chest cavity.
2- by elevation and depression of the ribs to increase and decrease the antero-posterior diameter of the chest cavity
Muscles that raise the rib cage during inspiration:
External intercostals
Sternocleidomastoid muscles (lifts sternum)
Anterior serrati (lifts many ribs)
Scaleni (lifts first two ribs).
Muscles that pull the rib cage downward during expiration:
Internal intercostals.
Abdominal recti (pull downward on the lower ribs and compress the abdominal contents upward against the diaphragm)

5. Pleural versus Alveolar pressure:*
Pleural pressure is the pressure of the fluid in the thin space between the lung pleura and the chest wall pleura.
The normal pleural pressure at the beginning of inspiration is about –5 centimeters of water (±2.5).
Alveolar pressure is the pressure of the air inside the lung alveoli.
When the glottis is open and no air is flowing into or out of the lungs, the alveolar P. is equal to atmospheric pressure (0 centimeters water pressure). It fluctuates between -1 and +1 during inspiration and expiration.

6. Compliance of the Lungs
lung compliance is defined as the extent to which the lungs will expand for each unit increase in transpulmonary pressure (difference between pleural and alveolar pressure).
The total compliance of both lungs is about 200 ml of air per cm water of transpulmonary pressure
The compliance diagram are determined by two elastic forces:
Elastic forces of the lung tissue itself
(2) Forces caused by surface tension of the fluid that lines the inside walls of the alveoli
the tissue elastic forces tending to cause collapse of the air- filled lung represent only about one third of the total lung elasticity, whereas the fluid-air surface tension forces in the alveoli represent about two thirds

7. Compliance diagram of lungs in a healthy person.

8. Surfactant and its function
The fluid-air surface tension that lines the alveoli tends to collapse the alveoli during expiration.
When water forms a surface with air, the water molecules on the surface of the water have an especially strong attraction for one another.
As a result, the water surface is always attempting to contract thus trying to collapse the alveoli (called surface tension elastic force).

9. This collapse is normally prevented by the presence of a substance called surfactant which is secreted by the type II alveolar cells.
It is composed of a mixture of phospholipids, proteins and ions. The most important component responsible for reducing the surface tension is a phospholipid called dipalmitoylphosphatidylcholine.

10. Functions of the Respiratory Passageways
Trachea, Bronchi, and Bronchioles
Multiple cartilage rings keep trachea from collapsing.
Less extensive cartilage plates in bronchi also maintain rigidity yet allow sufficient motion for the lungs to expand
Bronchioles (diameters less than 1.5 millimeters) lack such cartilage but still kept expanded mainly by the same transpulmonary pressures that expand the alveoli
Intermittent between the cartilaginous rings of trachea and bronchi are smooth muscles (wall of bronchioles is entirely smooth m. except the respiratory bronchiole, which is mainly pulmonary epithelium and underlying fibrous tissue )
Many obstructive diseases of the lung result from narrowing of the smaller bronchi and bronchioles due to excessive smooth muscle contraction of their wall.

11. Control of bronchiolar musculature
Sympathetic Dilation of the Bronchioles
Direct control is less effective
Sympathetic stimulation from the adrenal medullae (norepinephrine and epinephrine on beta Rc-dilation)
Parasympathetic Constriction of the Bronchioles
Parasympathetic fibers secret acetylcholine and cause mild to moderate constriction of the bronchioles.
Parasympathetic worsens the condition of Asthma
Effects of local substances secreted by the lungs:
Histamine and slow reactive substance of anaphylaxis (released in the lung tissues by mast cells during allergic reactions-pollen in the air- cause airway obstruction during allergic asthma
Smoke, dust, sulfur dioxide and acidic elements in smog initiate local parasympathetic reflex and cause airway obstruction.

12. Pressures in the Pulmonary System
Systolic pressure in the right ventricle - about 25 mm Hg
Diastolic pressure- about 0 to 1 mm Hg
Systolic pulmonary artery pressure is essentially equal to the pressure in the right ventricle
Diastolic pulmonary arterial pressure is about 8 mm Hg, and the mean pulmonary arterial pressure is 15 mm Hg.
Pressure pulse contours in the right ventricle, pulmonary artery and aorta.

13. Left Atrial and Pulmonary Venous Pressures.
The mean pressure in the left atrium and the major pulmonary veins averages about 2 mm Hg (varying from 1 to 5 mm Hg)
Blood Volume of the Lungs
The blood volume of the lungs is about 450 milliliters, about 9 per cent of the total blood volume of the entire circulatory system
the quantity of blood in the lungs can vary from as little as one half normal up to twice normal- e.g. when blowing a trumpet about 250 ml of blood can be expelled from the pulmonary into the systemic circulation.

14. Blood Flow Through the Lungs and Its Distribution
The amount of blood flowing to the lungs is essentially equal to CO therefore similar peripheral factors affect both.
Adequate blood distribution is important for sufficient aeration of well-oxygenated alveoli.
Automatic Control of Pulmonary Blood Flow Distribution
When the concentration of oxygen in the air of the alveoli decreases below normal the adjacent blood vessels constrict, an effect opposite to what is observed in systemic vessels.
This is to distribute blood flow where it is most effective.

15. Pulmonary Capillary Dynamics
mmHg

16. Pulmonary Edema Most common causes of PE:
Pulmonary edema occurs in the same way that edema develops elsewhere in the body (rise in the negative interstitial fluid pressure toward positive).
Most common causes of PE:
Left-sided heart failure or mitral valve disease
Damage to the pulmonary blood capillary membranes caused by infections (pneumonia) or by breathing noxious substances (chlorine or sulfur gases)

17. Physical Principles of Gas Exchange
After the alveoli are ventilated with fresh air, diffusion of oxygen occurs from the alveoli into the pulmonary blood and carbon dioxide in the opposite direction.
All respiratory gases are simple molecules that are free to move among one another- a process called Diffusion (kinetic motion)
The rate of diffusion of each gas is directly proportional to the pressure caused by that gas alone (partial pressure of the gas)
The air has an approximate composition of 79 per cent nitrogen and 21 per cent oxygen (with small amount of CO2, Helium and water vapor)

19. Thickness of the membrane. Surface area of the membrane.
Diffusion of oxygen from one end of a chamber (A) to the other (B). The difference between the lengths of the arrows represents net diffusion.
Factors Affecting the Rate of Gas Diffusion Through the Respiratory Membrane
Thickness of the membrane.
Surface area of the membrane.
Pressure difference of the gas between the two sides of the membrane.
Diffusion coefficient of the gas in the membrane.

20. Rate at Which Alveolar Air Is Renewed by Atmospheric Air
Expiration of a gas with successive breaths
Rate at Which Alveolar Air Is Renewed by Atmospheric Air

21. Normal VR is 4.2 L/min
Effect of alveolar ventilation on the alveolar PO2 at two rates of oxygen absorption from the alveoli—250 ml/min and 1000 ml/min. Point A is the normal operating point.

22. Effect of alveolar ventilation on the alveolar PCO2 at two rates of
carbon dioxide excretion from the blood—800 ml/min and 200 ml/min. Point A is the normal operating point.

23. Diffusion of Gases Through the Respiratory Membrane
A respiratory unit is composed of a respiratory bronchiole, alveolar ducts, atria, and alveoli
The alveolar walls are extremely thin, and capillaries are arranged as an interconnecting network.
Gas exchange between the alveolar air and the pulmonary blood occurs through the respiratory membrane

25. Respiratory Membrane
(Pulmonary membrane)

26. Diffusing Capacity of the Respiratory Membrane
It is the volume of a gas that diffuses through the respiratory membrane each minute for a partial pressure difference of 1 mmHg.
Diffusing Capacity for Oxygen.
In the average young man, the diffusing capacity for oxygen under resting conditions averages 21 ml/min/mm Hg. With a mean O2 pressure difference of 11 (11×21), it is equal to 230 ml O2 (amount of O2 that diffuses through respiratory membrane each minute)
Diffusing Capacity for Carbon Dioxide
CO2 diffuses through the respiratory membrane so rapidly (average PCo2 difference between pulmonary cap. and alveoli is less than 1mm Hg)
Also diffusion coefficient of CO2 is about 20 times that of oxygen and thus diffusing capacity for carbon dioxide under resting conditions is about 400 to 450 ml/min/ mm Hg

27. VA/Q Where VA = alveolar ventilation
Effect of the Ventilation-Perfusion Ratio on Alveolar Gas Concentration
Normally to some extent, some areas of the lungs are well ventilated but have almost no blood flow, whereas other areas may have excellent blood flow but little or no ventilation
The ratio between alveolar ventilation and alveolar blood flow is called the ventilation-perfusion ratio.
This is expressed as follow:
VA/Q Where VA = alveolar ventilation
Q = blood flow
When both are normal for a given alveolus, the ratio is also normal.
When ventilation is zero but perfusion normal, the ratio=zero (shunted blood-physiologic shunt)
When ventilation is normal but no perfusion, the ratio is infinity
(Physiologic dead space)
At both extremity, there is no gas exchange at the alveoli

28. Diffusion of Oxygen from the Alveoli to the Pulmonary Capillary Blood
Uptake of oxygen by the pulmonary capillary blood

29. venous admixture of blood
with a PO2=95
Changes in PO2 in the pulmonary capillary blood, systemic arterial blood, and systemic capillary blood, demonstrating the effect of “venous admixture.”

30. Oxygen diffuses from the alveoli into the pulmonary capillary blood because the oxygen partial pressure in the alveoli (Po2 = 104 mm Hg ) is greater than the Po2 in the pulmonary capillary blood (40 mm Hg).
In the other tissues of the body, a higher Po2 in the capillary blood (95 mm Hg) than in the tissues (40 mm Hg) causes oxygen to diffuse into the surrounding cells.
Diffusion of oxygen from a tissue capillary to the cells

31. Diffusion of Carbon Dioxide from the Peripheral Tissue Cells into the Capillaries and from the Pulmonary Capillaries into the Alveoli
Uptake of carbon dioxide by the blood in the tissue capillaries
Diffusion of carbon dioxide from the pulmonary blood into the alveolus

32. Role of Hemoglobin in Oxygen Transport
Normally, about 97% of the oxygen is transported from the lungs to the tissues in reversible chemical combination with hemoglobin (when PO2 is high oxygen binds with the hemoglobin, but when PO2 is low, oxygen is released from the hemoglobin) .
The remaining 3 per cent is transported in the dissolved state in the water of the plasma and blood cells.
Oxygen-Hemoglobin Dissociation Curve
Oxygen-hemoglobin dissociation curve shows the percentage of hemoglobin bound with oxygen.
The blood that leaves the lungs and enters the systemic arteries has a PO2 of about 95 mm Hg and oxygen saturation of systemic arterial blood averages 97 per cent.
While venous blood returning from the peripheral tissues has a PO2 of about 40 mm Hg and the saturation of hemoglobin averages 75 per cent.

33. Oxygen-hemoglobin dissociation curve

34. Factors that shift the oxygen- hemoglobin dissociation curve

35. Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids
Once oxygen has diffused from the alveoli into the pulmonary blood, it is transported to the peripheral tissue capillaries almost entirely in combination with hemoglobin.
The presence of hemoglobin in the red blood cells allows the blood to transport 30 to 100 times as much oxygen as could be transported in the form of dissolved oxygen in the water of the blood

36. Transport of Carbon Dioxide in the Blood
In the body’s tissue cells, oxygen reacts with various foodstuffs to form large quantities of carbon dioxide. This carbon dioxide enters the tissue capillaries and is transported back to the lungs.
Most of the carbon dioxide (about 70 per cent) is transported in the form of (Bicarbonate ions) after CO2 combines with water on the surface of RBC to form carbonic acid, which then dissociate to give HCO3- and H+. This reaction is accelerated by the enzyme carbonic anhydrase on the red cell membrane.
Also about 23% of CO2 is transported in form of carbaminohemoglobin (Hb-CO2)
Normally, the rest of all the carbon dioxide (7%) is transported in a dissolved state to the lungs.

37. Chloride shift
Transport of carbon dioxide in the blood

38. Regulation of Respiration
Neural control of respiration:
Respiratory Center. The respiratory center is composed of groups of neurons located bilaterally in the medulla oblongata and pons of the brain stem.
It is divided into three groups of neurons:
Dorsal respiratory group which mainly causes inspiration.
Ventral respiratory group which mainly causes expiration.
Pneumotaxic center which mainly controls rate and depth of breathing.

40. Dorsal Respiratory Group of Neurons—Its Control of Inspiration and of Respiratory Rhythm
Most of the neurons of DRG are located within the nucleus of the tractus solitaries in the medulla of brain stem.
This nucleus is the sensory termination of both the vagal and the glossopharyngeal nerves that transmit sensory signals from:
Chemoreceptors
Baroreceptors
Receptors in the lungs
The DRG generates rhythmical inspiratory discharges to the inspiratory muscles (mainly diaphragm) in a ramp manner (2 by 3 seconds).

41. Features of this group of neurons:
Ventral Respiratory Group of Neurons—Functions in Both Inspiration and Expiration
Features of this group of neurons:
Remain almost inactive during normal quiet respiration and not participate in basic rhythm of respiration.
Operates as an overdrive mechanism when only high levels of pulmonary ventilation are required (e.g. in heavy exercise) via powerful expiratory signals to abdominal muscles

42. PNEUMOTAXIC CENTER
A pneumotaxic center, located dorsally in the nucleus parabrachialis of the upper pons, transmits signals to the inspiratory area. The primary effect of this center is to control the “switch-off” point of the inspiratory ramp, thus controlling the duration of the filling phase of the lung cycle. When the pneumotaxic signal is strong, inspiration might last for as little as 0.5 second, thus filling the lungs only slightly; when the pneumotaxic signal is weak, inspiration might continue for 5 or more seconds, thus filling the lungs with a great excess of air.

43. Lung Inflation Signals Limit Inspiration—The Hering-Breuer Inflation Reflex
In addition to the CNS control of respiration, sensory nerve signals from the lungs also contribute to this control.
Stretch receptors found in muscular walls of bronchi and bronchioles transmit signals through the vagi into the DRG when the lungs become overstretched (TV = 3×).
These receptors activate a feedback response that “switches off” the inspiratory ramp and thus stops further inspiration (Hering- Breuer inflation reflex).

44. Chemical Control of Respiration
Excess carbon dioxide or excess hydrogen ions in the blood mainly act directly to stimulate the respiratory center. But oxygen does not have a significant direct effect on the respiratory center. Instead it acts almost entirely on peripheral chemoreceptors.
Chemosensitive Area of the Respiratory Center
None of the 3 neuron groups which control respiration is affected directly by changes in blood carbon dioxide concentration or hydrogen ion concentration.
A Chemosensitive area is highly sensitive to changes in either blood Pco2 or hydrogen ion concentration, and it in turn excites the other portions of the respiratory center.

45. Stimulation of brain stem inspiratory area by signals from the Chemosensitive area. Note that carbon dioxide in the fluid gives rise to most of the hydrogen ions (Q/ Which one have greater effect? H+ or CO2 or O2)

46. Effects of increased arterial blood PCO2 and decreased arterial pH (increased hydrogen ion concentration) on the rate of alveolar ventilation.

47. Peripheral Chemoreceptor System for Control of Respiratory Activity
Chemoreceptors, are located in several areas outside the brain,
They are especially important for detecting changes in oxygen in the blood and to a lesser extent to changes in carbon dioxide and hydrogen ion concentrations
Most of the chemoreceptors are in the carotid bodies (few are also in the aortic bodies)
Respiratory control by peripheral chemoreceptors (carotid and aortic bodies)

48. Other Factors That Affect Respiration
Voluntary control of respiration.
Effect of irritant receptors in the airways.
Effect of brain edema.
Anesthesia.

49. Chronic Pulmonary Emphysema
Pulmonary Emphysema describes a complex obstructive and destructive process of the lungs caused by many years of smoking
Chronic infection, caused by inhaling smoke that irritate the bronchi and bronchioles with partial paralysis of the cilia of the respiratory epithelium (nicotine effect), as a result mucus cannot be moved easily out of the passageways
The infection, excess mucus, and inflammatory edema of the bronchiolar epithelium together cause chronic obstruction of many of the smaller airways.
The obstruction of the airways causes entrapment of air in the alveoli and this combined with the lung infection, causes marked destruction of as much as 50 to 80 per cent of the alveolar walls

50. Contrast of emphysematous lung with extensive alveolar destruction
Normal Lung

51. Asthma
Asthma is characterized by spastic contraction of the smooth muscle surrounding the bronchioles, which causes extremely difficult breathing.
The usual cause of asthma is contractile hypersensitivity of the bronchioles in response to foreign substances in the air like pollen or smog.
The typical allergic person has a tendency to form abnormally large amounts of IgE antibodies which cause allergic reactions when they react with the specific antigens. The antibodies are attached to the mast cells in the pulmonary interstitium.

52. The antigen-antibody complex causes the mast cells to secret histamine, slow-reacting substance of anaphylaxis, eosinophilic chemotactic factor and bradykinin. These substances produce a localized pulmonary edema and spasm of the bronchiolar smooth muscle.
Sever obstruction occurs during expiration as the bronchioles are already partially occluded. Thus the investigations shows reduced timed expiratory volume but increased functional residual capacity and residual volume.