1

1.                            BIOMECHANICS OF RESPIRATORY ACT.

2.    VENTILATION OF LUNGS.

3.    TRANSPORT OF GASES

 

BIOMECHANICS OF RESPIRATORY ACT

 

video

Common characteristic of breathing. The respiratory system is divided into a respiratory zone, which is the site of gas exchange between air and blood, and a conducting zone, which conducts the air to the respiratory zone. The exchange of gases between air and blood occurs across the walls of tiny air sacs called alveoli, which are only a single cell layer thick to permit very rapid rates of gas diffusion.

 

 

 

The term respiration includes three separate but related functions:

(1) ventilation (breathing);

(2) gas exchange, which occurs between the air and blood in the lungs and between the blood and other tissues of the body; and

(3) oxygen utilization by the tissues in the energy – liberating reactions of cell respiration.

Video

 

Breathing Basics. With each breath, we bring oxygen into the lungs. When we exhale, we release carbon dioxide (CO2), water, and other gases from the lungs. The balance of CO2 and oxygen in the blood is very important to general health. By altering your breathing, you can change this balance and cause other physical and mental symptoms. Breathing engages various parts of the body to expand the lungs. The primary muscle of breathing is the diaphragm.6, 7 As the diaphragm flattens downward when you inhale (also known as inspiration), the chest cavity expands and air is drawn into the lungs.

 

Work of Breathing

Work = Pressure x Volume

Respiratory work at rest or during exercise is seldom responsible for more than 5% of the total body work. Most of this is used to overcome the lung and chest wall stiffness during inspiration. Work to overcome airway resistance is usually very small, except during exercise or in athsmatics.

Patients with most respiratory diseases have increased respiratory workloads, which may be due to high respiratory rates, stiff lungs, or high airway resistances. When the patient becomes so exhausted that they cao longer keep up the workload, respiratory failure ensues. Anaesthetic machine tubing, one-way valves, and ETTs all increase total resistance and respiratory work, while drugs will diminish respiratory effort, so that the patient with poor respiratory function usually requires ventilating both during and after the operation.

Ventilation and the exchange of gases (oxygen and carbon dioxide) between the air and blood are collectively called external respiration. Gas exchange between the blood and other tissues and oxygen utilization by the tissues are collectively known as internal respiration.

 

Ventilation is the mechanical process that moves air into and out of the lungs. Since the oxygen concentration of air is higher in the lungs than in the blood, oxygen diffuses from air to blood. Carbon dioxide conversely moves from the blood to the air within the lungs by diffusing down its concentration gradient. As a result of this gas exchange, the inspired air contains more oxygen and less carbon dioxide than the expired air. More importantly blood leaving the lungs (in the pulmonary veins) has a higher oxygen and lower carbon dioxide concentration than the blood delivered to the lungs in the pulmonary arteries. This result bring the fact that lungs function is to give gaseous equilibrium between blood and the air.

Main process of the external respiration. The passage air respiratory systems are divided into two functional zones. The respiratory zone is the region where gas exchange occurs, it includes the respiratory bronchioles (which contain separate outpouchings of alveoli) and the terminal cluster of alveolar sacs.

 

The conducting zone of the respiratory system, in summary, consists of the mouth, nose, pharynx, larynx, trachea, primary bronchi, and all successive branchings of the bronchioles up to and including the terminal bronchioles. In addition to conducting air into the respiratory zone, these structures serve additional functions: warming and humidification of the inspired air and filtration and cleaning. Regardless of the temperature and humidity of the ambient air, when the inspired air reaches the respiratory zone it is at a temperature of 37° C (body temperature), and it is saturated with water vapor as it flows over the warm, wet mucous membranes that line the respiratory airways. This ensures that a constant internal body temperature will be maintained and that delicate lung tissue will be protected from desiccation.

 

 

Gas exchange between the air and blood occurs entirely by diffusion through lung tissue. This diffusion occurs very rapid because there is a large surface area within the lungs and a very short diffusion distance between blood and air.

Phases of respiratory act. Inspiration & Expiration

Pulmonary ventilation consists of two phases: inspiration and expiration. Inspiration (inhalation) and expiration (exhalation) are accomplished by alternately increasing and decreasing the volume of the thorax and lungs.

The thorax must be sufficiently rigid so that it can protect vital organs and provide attachments for many short and powerful muscles. Breathing, or pulmonary ventilation, requires the flexibility of the thorax to function as a bellow during the ventilation cycle. The rigidity and the surfaces for muscle attachment are provided by the bony composition of the rib cage.

 

he rib cage is pliable, because the ribs are separate from one another and most of the ribs (upper ten of the twelve pairs) are attached to the sternum by resilient costal cartilages. The vertebral attachments also provide considerable mobility. The structure of the rib cage and associated cartilages provides continuous elastic tension, so that after stretched by muscle contraction during inspiration, the rib cage can return passively to its resting dimension when the muscles relax. This elastic recoil is greatly aided by the elasticity of the lungs.

 

Video

Respiratory muscles cause passage of air into the Lung. Between the bony portions of the rib cage are two layers of intercostals muscles: the external intercostal muscles and internal intercostal muscles. Between the costal cartilages, there is only one muscle layer, which its fibers oriented in the same manner to those of the internal intercostal muscle. These muscles may called as the interchondral part of the internal intercostal muscle or parasternal intercostal muscle.

 

 

An unforced, or quiet, inspiration primarily results from contraction of the dome– shaped diaphragm, which become lowered and flattened. This increases thoracic volume in a vertical direction. Inspiration is also aided by the parasternal and external intercostal muscles, which raise the ribs when they contract and increase thoracic volume laterally. Other thoracic muscles involved in forced (deep) inspiration. The most important of these is the scalenus muscle, followed by the pectoralis minor muscle, and in extreme cases the sternocleidomastoid muscle. Contraction of these muscles elevates the ribs in an anteroposterior direction; simultaneously, the upper rib cage is stabilized so that the intercostal muscles become more effective.

 

Mechanism of normal quiet inspiration and expiration. Quiet inspiration is an active process. The contraction of the inspiratory muscles and diaphragm increases intrathoracic volume. This stretch the thorax and lungs. Quiet expiration is a passive process. The thorax and lungs recoil when the respiratory muscles relax. due to their elastic tension

During quiet breathing, the intrapleural pressure, which is about – 2.5 mm Hg (relative to atmospheric) at the start of inspiration, decreases to about — 6 mm Hg, the lungs are pulled into a more expanded position. and the pressure in the airway becomes slightly negative, which cause the  air flows into the lungs. At the end of inspiration, the lung recoil pulls the chest back to the expiratory position, where the recoil pressures of the lungs and chest wall become balance. At this time, the pressure in the airway becomes slightly positive, and air flows out of the lungs. Expiration during quiet breathing is passive because no muscles contract which decrease intrathoracic volume. However, there is some contraction of the inspiratory muscles in the early part of expiration. This contraction exerts a braking action on the recoil forces and slows expiration.

 

Mechanism forced ventilation. Strong inspiratory efforts reduce the intrapleural pressure value as low as —30 mm Hg, producing correspondingly greater degrees of lung inflation. When forced ventilation is increased, the extent of lung deflation is also increased by active contraction of expiratory muscles that decrease intrathoracic volume.

Movement of the diaphragm accounts for 75% of the change in intrathoracic volume during quiet inspiration. This muscle attached around the bottom of the thoracic cage, and it arches over the liver and moves downward like a piston when it contracts.

 

 

Video

The other important inspiratory muscles are the external intercostals muscles, which run obliquely downward and forward from rib to rib. The ribs pivot as if hinged at the back, so that when the external intercostals contract they elevate the lower ribs. This pushes the sternum outward and increases the anteroposterior diameter of the chest. The transverse diameter is actually changed little if at all. Either the diaphragm or the external intercostals muscles alone can maintain adequate ventilation at rest. Transaction of the spinal cord above the third cervical segment cause fatal without artificial respiration, but transaction below the origin of the phrenic nerves that innervate the diaphragm (third to fifth cervical segments) is not fatal; conversely, in patients with bilateral phrenic nerve palsy, respiration is somewhat labored, but adequate to maintain life. The scalene and sternocleidomastoid muscles in the neck are accessory inspiratory muscles that they help to elevate the thoracic cage during deep labored respiration.

 

A decrease in intrathoracic volume and forced expiration result when the expiratory muscles contract. The internal intercostals have this action because they pass obliquely downward and posterior from rib to rib and therefore pull the rib cage downward when they contract. Contractions of the muscles of the anterior abdominal wall also aid expiration by pulling the rib cage downward and inward and by increasing the intraabdominal pressure, which pushes the diaphragm upward.

 

 

Change of pressure in pleural cavity in correlation from phases of respiratory act. The lungs and the chest wall are elastic structures. Normally, there is no more than a thin layer of fluid between the lungs and the chest wall. The lungs slide easily on the chest wall but resist being pulled away from it in the same way as 2 moist pieces of glass slide on each other but resist separation. The pressure in the “space” between the lungs and chest wall (intrapleural pressure) is sub atmospheric. The lungs are stretched when they are expanded at birth, and at the end of quiet expiration their tendency to recoil from the chest wall is just balanced by the tendency of the chest wall to recoil in the opposite direction. If the chest wall is opened, the lungs will collapse; and if the lungs lose their elasticity, the chest expands and becomes barrel-shaped.

Movement of blood on venous in correlation from phases of respiratory act.

Contraction of the diaphragm during inhalation also improves venous return. As the diaphragm contracts, it lowers to increase the thoracic volume and decrease the abdominal volume. This creates a partial vacuum in the thoracic cavity (negative intrathoracic pressure) and a higher pressure in the abdominal cavity. The pressure difference thus produced favors blood flow from abdominal to thoracic veins. 

Change of pressure in alveoli. The respiratory muscles cause pulmonary ventilation by alternatively compressing and distending the lungs, which in turn causes the pressure in the alveoli to rise and fall. During inspiration the intra-alveolar pressure becomes slightly negative with respect to atmospheric pressure, normally slightly less than -1 mm Hg, and this causes air to flow inward through the respiratory passageways. During normal expiration, on the other hand, the intra-alveolar pressure rises to slightly less than +1 mm Hg, which causes air to flow outward through the respiratory passageways. Note that, how little pressure is required to move the air into and out of the normal lung, though in most of the time, much pressure is required in some types of lung diseases.

During maximum expiratory effort (with the glottis closed )the intra-alveolar pressure can be increased to as much as 140 mm Hg in the strong, healthy man, and during maximum inspiratory effort it can be reduced to as low as -100 mm Hg.

 

Intra-alveolar pressure during inspiration & expiration

As the external intercostals & diaphragm contract, the lungs expand. The expansion of the lungs causes the pressure in the lungs (and alveoli) to become slightly negative relative to atmospheric pressure. As a result, air moves from an area of higher pressure (the air) to an area of lower pressure (our lungs & alveoli). During expiration, the respiration muscles relax & lung volume descreases. This causes pressure in the lungs (and alveoli) to become slight positive relative to atmospheric pressure. As a result, air leaves the lungs.

The visceral and parietal pleurae are normally flush against each other, so that the lungs are stuck to the chest wall in the same manner as two wet pieces of glass sticking to each other. The intrapleural space contains only a film of fluid secreted by the two membranes. The pleural cavity in a healthy person is thus potential rather than real; it can become real only in abnormal situations when air enters the intrapleural space. Since the lungs normally remain in contact with the chest wall, they expand and contract along with the thoracic cavity during respiratory movements.

Air enters the lungs during inspiration because the atmospheric pressure is greater than the intrapulmonary, or intraalveolar, pressure. Since the atmospheric pressure does not usually change, the intrapulmonary pressure must fall below atmospheric pressure to cause inspiration. A pressure below that of the atmosphere is called a subatmospheric pressure, or negative pressure. During quiet inspiration, for example, the intrapulmonary pressure may decrease to 3 mmHg below the pressure of the atmosphere. This subatmospheric pressure is shown as –3 mmHg. Expiration, conversely, occurs when the intrapulmonary pressure is greater than the atmospheric pressure. During quiet expiration, for example, the intrapulmonary pressure may rise to at least +3 mmHg over the atmospheric pressure.

The lack of air in the intrapleural space produces a subatmospheric intrapleural pressure that is lower than the intrapulmonary pressure . There is thus a pressure difference across the wall of the lung—called the transpulmonary (or transmural) pressure—which is the difference between the intrapulmonary pressure and the intrapleural pressure. Since the pressure within the lungs (intrapulmonary pressure) is greater than that outside the lungs (intrapleural pressure), the difference in pressure (transpulmonary pressure) keeps the lungs against the chest wall. Thus, the changes in lung volume parallel changes in thoracic volume during inspiration and expiration.

Recoil Tendency of the Lungs, and the Intrapleural Pressure. The lungs have a continual elastic tendency to collapse and therefore to pull away from the chest wall. This is called the recoil tendency of the lungs, and it is caused by two different factors. First, throughout the lungs are many elastic fibers that are stretched by lung inflation and therefore attempt to shorten. Second, and even more important, the surface tension of the fluid lining the alveoli also causes a continual elastic tendency for the alveoli to collapse. This effect is caused by intermolecular attraction between the surface molecules of the alveolar fluid. That is, each molecule pulls on the next one so that the whole lining sheet of fluid on the alveolar surfaces acts like many small elastic balloons continuously trying to collapse the lung.

Ordinarily, the elastic fibers in the lungs account for about one third of the recoil tendency, and the surface tension phenomenon accounts for about two thirds.

The total recoil tendency of the lungs can be measured by the amount of negative pressure in the pleural space required to prevent collapse of the lungs; this pressure is called the pleural pressure or, occasionally, the lung recoil pressure. It is normally about – 4 mm Hg. This negative pressure (-4 mm Hg) on the outer surfaces of the lungs is required to keep them expanded to normal size. When the lungs are stretched to very large size, such as at the end of deep inspiration, then the pleural pressure required may be as great as -12 to -18 mm Hg.

“Surfactant” in the alveoli, and its effect on the collapse tendency.

A lipoprotein mixture called “surfactant” is secreted by special surfactant-secreting cells (the “type II granular pneumocytes”) which are the component parts of the alveolar epithelium. This mixture, containing especially the phospholipids dipalmitoyl lecithin, decreases the surface tension of the alveolar fluid lining. In the absence of surfactant, lung expansion is extremely difficult, which often requires negative pleural pressures as low as – 20 to – 30 mm Hg to overcome the collapse tendency of the alveoli. This illustrates that surfactant is exceedingly important for minimizing the effect of surface tension which cause the collapse of the lungs.

Surfactant is produced by type II alveolar cells in late fetal life. Premature babies are sometimes born with lungs that lack sufficient surfactant, and their alveoli are collapsed as a result. This condition is called respiratory distress syndrome (RDS). Considering that a full-term pregnancy lasts 37 to 42 weeks, RDS occurs in about 60% of babies born at less than 28 weeks, 30% of babies born at 28 to 34 weeks, and less than 5% of babies born after 34 weeks of gestation. The risk of RDS can be assessed by analysis of amniotic fluid (surrounding the fetus), and mothers can be given exogenous corticosteroids to accelerate the maturation of their fetus’s lungs.

 

Control of Bronchial Tone

The walls of bronchi and bronchioles contain smooth muscle and they are innervated by the autonomic nervous system. In general, sympathetic discharge via Beta-2-adrenergic receptors causes the bronchi to dilate and parasympathetic discharge via the vagus nerves causes them to constrict.. It may be similar to the intrinsic enteric nervous system in the gastrointestinal tract and there is evidence that VIP (Vasoactive intestinal polypeptide) is the mediator secreted by its neurons.

The function of the bronchial muscles is still a matter of debate, but in general, they probably help to maintain an even distribution of ventilation. They also protect the bronchi during coughing. There is a circadian rhythm in bronchial tone, with maximal constriction at about 6 A.M and maximal dilatation at about 6 P.M. Thats why the asthma attacks are more severe in the late night and early morning hours, pi–stimulants such as isoproterenol are effective in asthma because they mimic the effects of sympathetic stimulation. Cooling the airways causes bronchoconstriction, and exercise triggers asthmatic attacks because it lowers airway temperature.

Lung Volumes. The amount of air that moves into the lungs with each inspiration (or the amount that moves out, with each expiration) is called the tidal volume. The air inspired with a maximal inspiratory effort in excess of the tidal volume is the inspiratory reserve volume. The volume expelled by an active expiration effort after passive expiration is the expiratory reserve volume, and the air left in the lungs after a maximal expiratory effort is the residual volume. Normal values for these lung volumes, and names applied to combinations of them.

 

 

1. Tidal volume (TV),

2. Inspiratory reserve volume (IRV).

3. Expiratory reserve volume (ERV).

4. Vital capacity (VC)

 

 

The space in the conducting zone of the airways occupied by gas that does not exchange with blood in the pulmonary vessels is the respiratory dead space. The vital capacity, the greatest amount of air that can be expired after a maximal inspiratory effort, is frequently measured clinically as an index of pulmonary function. The fraction of the vital capacity expired in 1 second (timed vital capacity; also called forced expired volume in 1 second, or FEV I”) gives additional valuable information. The vital capacity may be normal but the timed vital capacity can be greatly reduced in diseases such as asthma, in which the resistance of the airways is increased due to bronchial constriction. The amount of air inspired per minute (pulmonary ventilation, respiratory minute volume) is normally about 6 L (500 ml/breath x 12 breaths/min). The maximal voluntary ventilation (MVV), or, as it was formerly called, the maximal breathing capacity, is the largest volume of gas that can be moved into and out of the lungs in 1 minute by voluntary effort. The normal MVV is 125-170 L/min.

 

 

Spirograph

 

Effects of Gravity on the Lung. Because of gravitational forces,the pressure gradient present. Intrapleural pressure at the bases of the lungs is 5 mm Hg greater than at the apexes. Consequently, the transmural pressure (the difference between intrapulmonary and intrapleural pressure) may become negative at the end of forced expiration, causing airways to close. For the same reason, more of the gas inspired during the first part of inspiration goes to the apexes than to the bases.

Gravity also affects the pressure in the pulmonary blood vessels. Dead Space &Uneven Ventilation. Since gaseous exchange in the respiratory system occurs only in the terminal portions of the airways, the gas that occupies the rest of the respiratory system is not available for gas exchange with pulmonary capillary blood. Thus, in a man who weighs 68 kg, only the first 350 ml of the 500 ml inspired with each breath at rest goes through gaseous exchange in the alveoli. Conversely, with each expiration, the first 150 ml expired is the gas that occupied the dead space, and only the last 350 ml is from the alveoli.

It is wise to distinguish between the anatomic dead space (respiratory system volume exclusive of Alveoli) and the total (physiologic) dead space (volume of gas which do not equilibrate with blood and air, e.g waste ventilation). In health, the 2 dead spaces are identical. In disease states that may be no exchange of gas between the alveoli and the blood, and some of the alveoli may be overventilated.

 

The volume of gas in nonperfused alveoli and any volume of air in the alveoli in excess of that necessary to arterialize the b1ood in the alveolar capillaries is part of the dead space (no equilibrating) gas volume. The anatomy dead space can be measured by analysis of the single breath N₂ curves. From mid inspiration,the subject take a deep breath as possible of pure O₂, then exhales steadily while the N₂ content of the expired gas is continuously measured. The initial gas exhaled (phase I) is the gas that filled the dead space and that consequently contains no N₂.

 

Alveolar Ventilation. Because of the dead space, the amount of air reaching the alveoli (alveolar ventilation) at a respiratory minute volume of 6 L/min is 500 minus 150 ml times 12 breath/min, or 4.2 L/min. because of the dead space, rapid, shallow respiration produces much less alveolar ventilation than slow, deep respiration at the same respiratory minute volume (Table ).

 

Table . Effect of variations in respiratory rate and depth on alveolar ventilation.

 

 

 

 

TRANSPORT OF GASES.

 

Gas Exchange

 During respiration, air becomes saturated with water vapor by the time it enters the alveolar sac. In the alveolus, it also mixes with carbon dioxide.

 At the alveolar membrane, each gas diffuses in the direction where the partial pressure of that gas is less. In other words, oxygen diffuses towards the blood and is taken up by hemoglobin, and carbon dioxide diffuses towards the alveolus and mixes with the air. No “active process” is involved. Oxygen simply diffuses through the membrane and plasma, and is taken up by the red blood cells.

 Although the diffusion occurs very rapidly, the gases do not have time to totally equilibrate. There will be a small pressure difference across the alveolar membrane for each gas. That is, oxygen partial pressure will be somewhat higher in the alveolus than in the blood, and carbon dioxide pressure will be slightly higher in the blood than in the air in the alveolus. In the case of oxygen, this pressure difference is calculated for the lung as a whole as the “arterial-alveolar (Aa) gradient.”

 About 2% of the blood flow through the lungs bypasses the pulmonary capillaries. This blood is not oxygenated, and forms a “physiologic shunt.” Because of this blood that bypasses the alveoli, arterial blood will always contain less oxygen pressure than blood that has equilibrated with the oxygen in the lung alveoli. This “shunt” becomes part of the calculated “Aa gradient.”

 As blood circulates through the body, an opposite change occurs in the capillaries of the systemic circulation. Oxygen diffuses from the area of higher pressure — the blood — into the lower pressure of the cells. Carbon dioxide diffuses from the cells into the blood.

Gas exchange in the lungs occurs across an estimated 300 million tiny (0.25 to 0.50 mm in diameter) air sacs, known as alveoli. Their enormous number provides a large surface area (60 to 80 square meters, or about 760 square feet) for diffusion of gases. The diffusion rate is further increased by the fact that each alveolus is only one cell-layer thick, so that the total “air-blood barrier” is only two cells across (an alveolar cell and a capillary endothelial cell), or about 2 μm. This is an average distance because there are two types of cells in the alveolar wall, type I and type II, and the type II alveolar cells are thicker than the type I cells . Where the basement membranes of capillary endothelial

CO2 Elimination

Oxygen Transport

Effect of Shunts

Some venous blood passes through the lungs without equilibration with Alveolar gas. This “Venous Admixture” or “Shunt” subsequently mixes with oxygenated blood in the pulmonary veins, and has the effect of reducing PaO₂and elevating PaCO₂.

While the slight rise in PaCO₂can be overcome easily by increasing the ventilation to normal alveoli, the same is not true for PaO₂. Normal alveoli can blow off twice as much CO2as usual if ventilated twice as much normal, but never saturate the blood leaving them any more than 100%.

A pure shunt causes hypoxaemia that DOES NOT correct by increasing inspired oxygen.

A patient with a 50% shunt breathing 100% inspired oxygen will only get a PaO2 of about 60 mmHg, but doubling their ventilation will maintain normocarbia.

Low V/Q ratio

Areas of lung with lower-than-normal ventilation cause hypoxaemia. The blood leaving these areas is part-way between alveolar and mixed venous.

If we reduce the total ventilation of an otherwise normal lung by half, ie give it a global V/Q ratio of 0.5, CO₂levels will rise and eventually reach equilibrium at 80mmHg but the patient will become very hypoxic well before the CO₂ levels get high. Increasing inspired oxygen to as little as 30% will, however, completely correct the resulting hypoxaemia.

Thus hypoxaemia due to hypoventilation can be easily corrected with supplemental oxygen, whereas that due to true shunt will not correct no matter how much oxygen is administered.

 

 

cells fuse with those of type I alveolar cells, the diffusion distance can be as small as 0.3 μm , which is about 1/100th the width of a human hair. Alveoli are polyhedral in shape and are usually clustered, like the units of a honeycomb. Air within one member of a cluster can enter other members through tiny pores . These clusters of alveoli usually occur at the ends of respiratory bronchioles, the very thin air tubes that end blindly in alveolar sacs. Individual alveoli also occur as separate outpouchings along the length of respiratory bronchioles. Although the distance between each respiratory bronchiole and its terminal alveoli is only about 0.5 mm, these units together constitute most of the mass of the lungs.

The exchange of gases (O2 & CO2) between the alveoli & the blood occurs by simple diffusion: O2 diffusing from the alveoli into the blood & CO2 from the blood into the alveoli. Diffusion requires a concentration gradient. So, the concentration (or pressure) of O2 in the alveoli must be kept at a higher level than in the blood & the concentration (or pressure) of CO2 in the alveoli must be kept at a lower lever than in the blood. We do this, of course, by breathing – continuously bringing fresh air (with lots of O2 & little CO2) into the lungs & the alveoli.

Breathing is an active process – requiring the contraction of skeletal muscles. The primary muscles of respiration include the external intercostal muscles (located between the ribs) and the diaphragm (a sheet of muscle located between the thoracic & abdominal cavities).

Transport of Oxygen:

The exchange of oxygen and carbon dioxide takes place in between the lungs and blood. The greater part of oxygen diffuses into the blood and at the same time, carbon dioxide diffuses out. Here the question is where the oxygen would go.

The most part oxygen (about 97%) is now carried by the erythrocytes or R. B. Cs. In which it combines with the hemoglobin, the iron containing respiratory pigment under high concentration forming loose chemical compound the oxy-hemoglobin.

Hemoglobin is purple colored but oxy-hemoglobin is of bright red color. Along the blood stream during circulation, the oxy-hemoglobin reaches the tissues, breaks up releasing most of its oxygen, and regains its normal purple color as hemoglobin, there by the blood acts as an efficient oxygen carrier.

A small portion of oxygen (about 3%) also dissolves in the plasma and is carried in the form of solution to the tissues blood stream. Now this free oxygen, before entering into the tissue proper first passes into the tissue fluid and then enters the tissue by diffusion. In return, the carbon dioxide is given out by the tissues, dissolves in the tissue fluid and finally passes into the blood stream and conveyed of blood is 10 to 26 volumes of oxygen per 100 volumes of blood.

The oxygen transport from lungs to tissues is achieved because hemoglobin has the highest affinity for oxygen at 100 mm Hg PO2 (which is almost present in the alveolar air) and low affinity for oxygen at 40 mm Hg PO₂ which is prevalent in the tissues. So oxygen readily combines with the reduced hemoglobin of Venus blood in the lungs and it is readily given off to the tissues by the arterial blood. The release of oxygen from blood is further increased by the fall in pH increased CO₂tension, and rise in temperature etc.

Transport of Carbon Dioxide:

The resultant carbon dioxide, which is produced from metabolism and given out by the tissue, is passed into blood through the tissue fluid and conveyed back to the respiratory surfaces along with the blood stream. But by plasma and hemoglobin of blood. Blood transports carbon dioxide in three ways, namely:

(1) As carbonic acid

(2) As bicarbonates of sodium and potassium and

(3) As carbominohemoglobin

All these compounds are reversible compounds. About 10% of total carbon dioxide is carried by the blood in the dissolved state as carbonic acid (CO₂ + H₂O – H₂CO₃) but 80% of CO₂ as Sodium bicarbonate in the plasma and as potassium bicarbonate in the plasma and as potassium bicarbonate in the corpuscles and the remaining 10% as carbamino-hemoglobin (a loose compound formed by CO2 + hemoglobin).

Now the question is if they are conveyed in compound from but not in Free State how does it become free. In the blood there is an enzyme called carbonic anhydrase formed in the erythrocytes. This enzyme enhances the conversion of bicarbonates into carbonates, carbon dioxide and water by catalytic apart from this enzyme, oxy-hemoglobin also helps in releasing the carbon dioxide from various compounds. Because oxy-hemoglobin is strongly acidic and the acidity causes the release of carbon dioxide from bicarbonates, carbonic acid and carbamonohemoglobin.

Therefore, the carbon dioxide so formed is removed by diffusion before the blood leaves the lung. This transportation of gases also comes under external respiration.

In short: from tissue – diffuses into – tissue

(CO₂ high concentration)

From tissue fluid – diffuses into – blood

(Free CO₂)

(i) By blood plasma:

As physical solution:

10% CO₂ + H₂O – Carbonic anhydrase – H₂CO₃

(Carbon dioxide) (Water) enzyme (carbonic acid)

(ii) By R. B. C. Hemoglobin as Carbamino Compounds:

10% carbon dioxide + hemoglobin – carbamino hemoglobin

(iii) As Bicarbonate compounds: 80% carbon dioxide – in plasma as sodium bicarbonate

2Na HCO₃ – Na₂ CO₃ + H₂O + CO₂

(Sodium bicarbonate)

In corpuscles as potassium bicarbonate i.e. – 2 K. H.

(Potassium bicarbonate)

CO₃ – K2CO₂ + H₂O + CO₃

Release of CO2 at the Respiratory Surface:

Carbonic acid, bicarbonates of sodium and potassium and carbamino compounds are carried to the lungs where they breakdown under the influence of various factors and liberate free CO_2.

 

The influence of cutting of vagal nerves on breathing. Fix a narcotized rat on the operation table. Make a longitudinal incision of skin on middle neck line, preparation the vagal nerve. Record the pneumogramme before and after cutting one and than both of vagal nerves. Draw the results in your reports. In conclusion explain the changes.

 

 

Unlike liquids, gases expand to fill the volume available to them, and the volume occupied by a giveumber of gas molecules at a given temperature and pressure is (ideally) the same regardless of the composition of the gas.

Video

Therefore, the pressure exerted by any one gas in a mixture of gases (its partial pressure) is equal to the total pressure times the fraction of the total amount of gas it represents.

 

 

The composition of dry air is 20.98% O₂, 0.04 CO₂, 78.06% N₂, and 0.92% other inert constituent such as argon and helium. The barometric pressure (p_b) at sea level is 760 mm Hg (1 atmosphere). The partial pressure (indicated by the symbol P) of O₂ in dry air is therefore 0.21 x 760, or 160 mm Hg at sea level. The partial pressure of N₂ and the other inert gases is 0.79 x 760, or 600 mm Hg; and the P CO₂ is 0.0004 x 760, or 0.3 mm Hg. The water vapor in the air in most climates reduces these percentages, and therefore the partial pressures, to a slight degree. Air equilibrated with water is saturated with water vapor and inspired air is saturated by the time it reaches the lungs. The P.H₂O at body temperature (37 °C) is 47 mm Hg. Therefore, the partial pressures at sea level of the other gases in the air reaching the lungs are P O₂ , 14′ mm Hg; P CO₂ 0-3 mm Hg; and P.N₂ (including the other inert gases), 564 mm Hg.

 

Cell membranes are completely permeable to the passage of carbon dioxide and oxygen. On diffusing into the red blood cell these gases interact with other compounds. Once beyond the capillaries no further gain or loss of these gases can occur and the compounds involved reach an equilibrium.

While in the systemic capillaries, the RBCs are subjected to increasing levels of carbon dioxide and decreasing levels of oxygen. The opposite is the case in the pulmonary capillaries. The reactions are the same but in reverse directions in these two locations.

Gas diffuses from areas of high pressure to area of low pressure, the rate of diffusion depending upon the concentration gradient and the nature of the barrier: between the 2 areas. When a mixture of gases is in contact with and permitted to equilibrate with a liquid each gas in the mixture dissolves in the liquid to an extent determined by its partial pressure and its solubility in the fluid. The partial pressure of a gas in a liquid is that pressure which in the gaseous phase in equilibrium with the liquid would produce the concentration of gas molecules found in the liquid.

 

GAS EXCHANGE IN THE LUNG

Composition of Alveolar Air. Oxygen continuously diffuses out of the gas in the alveoli (alveolar gas) into the bloodstream, and C0₂ continuously diffuses into the alveoli from the blood. In the steady state, inspired air mixes with the alveolar gas, replacing the O₂ that has entered the blood and diluting the CO₂ that has entered the alveoli. Part of this mixture is expired. The O₂ content of the alveolar gas then falls and its CO₂ content rises until the next inspiration. Since the volume of gas in the alveoli is about 2 L at the end of expiration (functional residual capacity, each 350-ml increment of inspired and expired air has relatively little effect on the P.O₂ and P.CO₂. Indeed, the composition of alveolar gas remains remarkably constant, not only at rest but also under  a variety of other conditions

Sampling Alveolar Air . Theoretically, all but the first 150 ml expired with each expiration is alveolar air, but there is always some mixing at the interface between the dead space gas and the alveolar air. A later portion of expired air is therefore the portion taken for analysis. Using modern apparatus with a suitable automatic valve, it is possible to collect the last 10 ml expired during quiet breathing. The composition of alveolar gas is compared with that of inspired and expired air.

Video

Diffusion Capacity. Partial Pressures of O₂ and CO₂ in the body (normal, resting conditions): Alveoli: P.O₂ = 100 mm Hg; P.CO₂ = 40 mm Hg

Alveolar capillaries

Mechanics of Ventilation Air is delivered to alveoli as a consequence of respiratory muscle contraction. These muscles include the diaphragm and the external intercostal muscles of the rib cage and accessory inspiratory muscles (scalenes and sternocleidomastoids which are not active in eupnea). Contraction of these muscles enlarges the thoracic cavity, creating a subatmospheric pressure in the alveoli. Contraction of the diaphragm leads to downwards displacement of the thoracic cavity and contraction of external intercostals muscles leads to lifting of the thoracic cage leading to increase in the antero-posterior diameter.

As alveolar pressure declines, atmospheric air moves into the alveoli by bulk

flow until the pressure is equalized. The process of inflating the lung is called

inspiration. Expiration is usually passive, resulting from relaxation of the inspiratory muscles and powered by elastic recoil of lung tissue that is stretched during inspiration. With relaxation of the inspiratory muscles and lung deflation, alveolar pressure exceeds atmospheric pressure, so gases flow from the alveoli to the atmosphere by bulk flow. Active expiration is due to internal intercostals muscles and the abdominal recti muscles.

The Opposing Force of Pulmonary Elastance or Compliance

The lung is an elastic structure with an anatomical organization that promotes its collapse to essentially zero volume, much like an inflated balloon. The term elastic means a material deformed by a force tends to return to its initial shape or configuration when the force is removed. While the elastic properties of the

lung are important to bring about expiration, they also oppose lung inflation.

As a result, lung inflation depends upon contraction of the inspiratory muscles.

The resistance to deformation (inflation) is termed elastance. However, compliance is the preferred term to describe the elastic properties of the lung. Compliance, as the recripocal of elastance, is a measure of the ease of deformation (inflation).

Effect of ventilation perfusion ratio on alveolar gas concentration:

Ventilation-perfusion ratio (ranges from 0 to infinity):

– Alveolar Oxygen and Carbon Dioxide Partial Pressures when VA/Q Equals Zero, that is, without any alveolar ventilation-the air in the alveolus comes to equilibrium with the blood oxygen and carbon dioxide because these gases diffuse between the blood and the alveolar air. Because the blood that perfuses the capillaries is venous blood returning to the lungs from the systemic circulation, it is the gases in this blood with which the alveolar gases equilibrate. The normal venous blood has a PO2 of 40 mm Hg and a PCO2 of 45 mm Hg. Therefore, these are also the normal partial pressures of these two gases in alveoli that have blood flow but no ventilation.

– Alveolar Oxygen and Carbon Dioxide Partial Pressures when VA/Q Equals Infinity, there is no capillary blood flow to carry oxygen away or to bring carbon dioxide to the alveoli. Therefore, instead of the alveolar gases coming to equilibrium with the venous blood, the alveolar air becomes equal to the humidified inspired air. That is, the air that is inspired loses no oxygen to the blood and gains no carbon dioxide from the blood. And because normal inspired and humidified air has a PO2 of 149 mm Hg and a PCO2 of 0 mm Hg, these will be the partial pressures of these two gases in the alveoli.

– Gas Exchange and Alveolar Partial Pressures when VA/Q Is Normal, when there is both normal alveolar ventilation and normal alveolar capillary blood flow (normal alveolar perfusion), exchange of oxygen and carbon dioxide through the respiratory membrane is nearly optimal, and alveolar PO2 is normally at a level of 104 mm Hg, which lies between that of the inspired air (149 mm Hg) and that of venous blood (40 mm Hg). Likewise, alveolar PCO2 lies between two extremes; it is normally 40 mm Hg, in contrast to 45 mm Hg in venous blood and 0 mm Hg in inspired air. Thus, under normal conditions, the alveolar air Po2 averages 104 mm Hg and the Pco2 averages 40 mm Hg.

VA/Q = 0→ O2 = 40, CO2 = 45mmHg

VA/Q = infinity → O2 = 149, CO2 = 0mmHg

VA/Q = normal → O2 = 104, CO2 = 40mmHg

If less than normal then called physiological shunt If more thaormal then called physiological dead space

Normally at the tip of the lung, VA/Q is (2.5) times normal (phys. dead space), while at the base, it is (0.6) times normal (phys. shunt).

Normally, there are abnormal VA/Q ratios in the upper and lower portions of the lung. In the upper both ventilation and perfusion are low but VA is more than Q, so there is physiological dead space, but in the lower VA is less than Q, so there is physiological shunt.

 

Entering the alveolar capillaries P.O₂ = 40 mm Hg (relatively low because this blood has just returned from the systemic circulation and has lost much of its oxygen); PCO₂ = 46 mm Hg (relatively high because the blood returning from the systemic circulation has picked up carbon dioxide)

The exchange of oxygen and carbon dioxide takes place in between the lungs and blood. The greater part of oxygen diffuses into the blood and at the same time, carbon dioxide diffuses out. Here the question is where the oxygen would go.

The most part oxygen (about 97%) is now carried by the erythrocytes or R. B. Cs. In which it combines with the hemoglobin, the iron containing respiratory pigment under high concentration forming loose chemical compound the oxy-hemoglobin.

Hemoglobin is purple colored but oxy-hemoglobin is of bright red color. Along the blood stream during circulation, the oxy-hemoglobin reaches the tissues, breaks up releasing most of its oxygen, and regains its normal purple color as hemoglobin, there by the blood acts as an efficient oxygen carrier.

A small portion of oxygen (about 3%) also dissolves in the plasma and is carried in the form of solution to the tissues blood stream. Now this free oxygen, before entering into the tissue proper first passes into the tissue fluid and then enters the tissue by diffusion. In return, the carbon dioxide is given out by the tissues, dissolves in the tissue fluid and finally passes into the blood stream and conveyed of blood is 10 to 26 volumes of oxygen per 100 volumes of blood.

The oxygen transport from lungs to tissues is achieved because hemoglobin has the highest affinity for oxygen at 100 mm Hg PO2 (which is almost present in the alveolar air) and low affinity for oxygen at 40 mm Hg PO₂ which is prevalent in the tissues. So oxygen readily combines with the reduced hemoglobin of Venus blood in the lungs and it is readily given off to the tissues by the arterial blood. The release of oxygen from blood is further increased by the fall in pH increased CO₂ tension, and rise in temperature etc.

While in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from the alveoli into the blood & carbon dioxide from the blood into the alveoli.

Leaving the alveolar capillaries

§                                             PO2 = 100 mm Hg

§                                             PCO2 = 40 mm Hg

Blood leaving the alveolar capillaries returns to the left atrium & is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs.

Entering the systemic capillaries

§                                             PO2 = 100 mm Hg

§                                             PCO2 = 40 mm Hg

Body cells (resting conditions)

§                                             PO2 = 40 mm Hg

§                                             PCO2 = 45 mm Hg

Because of the differences in partial pressures of oxygen & carbon dioxide in the systemic capillaries & the body cells, oxygen diffuses from the blood & into the cells, while carbon dioxide diffuses from the cells into the blood.

Leaving the systemic capillaries

§                                             PO2 = 40 mm Hg

§                                             PCO2 = 45 mm Hg

Blood leaving the systemic capillaries returns to the heart (right atrium) via venules & veins (and no gas exchange occurs while blood is in venules & veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle.

Figure. Partial pressure and diffusion at the respiratory membrane.

While in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from the alveoli into the blood and carbon dioxide from the blood into the alveoli. Leaving the alveolar capillaries: PO₂ = 100 mm Hg; PCO₂ = 40 mm Hg.

Blood leaving the alveolar capillaries returns to the left atrium and is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs.

Entering the systemic capillaries: PO₂ = 100 mm Hg; PCO₂ = 40 mm Hg.

Body cells (resting conditions): PO₂ = 40 mm Hg; PCO₂ = 46 mm Hg. Because of the differences in partial pressures of oxygen and carbon dioxide in the systemic capillaries and the body cells, oxygen diffuses from the blood and into the cells, while carbon dioxide diffuses from the cells into the blood. Leaving the systemic capillaries: PO₂ = 40 mm Hg; PCO₂ = 46 mm Hg. Blood leaving the systemic capillaries returns to the heart (right atrium) via venules and veins (and no gas exchange occurs while blood is in venules and veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle.

Oxygen moves from the alveoli to the red blood cells along the short path. The PO₂ of alveolar air is 100 mm Hg, whereas that in the venous blood in the pulmonary artery is 40 mm Hg

There is no evidence that any process other than passive diffusion is involved in the movement of O₂; into the blood along this pressure gradient. O₂ dissolves in the plasma and enters the red blood cells, where it combines with hemoglobin. Diffusion into the blood must be very rapid, since the time for each milliliter of blood is in the capillaries is short. Nevertheless, O₂ diffusion is adequate in health to raise the PO₂; of the blood to 97 mm Hg, a value just under the alveolar PO₂. This falls to 95 mm Hg in the aorta because of the physiologic shunt.

 

 

The diffusion capacity of the lungs for O₂ is the amount of O₂ that crosses the alveolar membrane per minute per mm Hg difference in PO₂ between the alveolar gas and the blood in the pulmonary capillaries. Expressed in terms of STPD, it is normally about 20 ml/min/mm Hg at rest. As a result of capillary dilatation and an increase in the number of active capillaries, it rises to values of 65 or more during exercise. The diffusion capacity for O₂ is decreased in diseases such as sarcoidosis and beryllium poisoning (berylliosis) that cause fibrosis of the alveolar walls and produce alveolar-capillary block.

 

Figure . Summary of PO₂ and PCO₂ values in air, lungs, blood, and tissues, graphed to emphasize the fact that both O₂ and CO₂ diffuse “downhill” along gradients of decreasing partial pressure.

The P.CO₂ of venous blood is 46 mm Hg, whereas that of alveolar air is 40 mm Hg, and CO₂ diffuses from the blood into the alveoli along this gradient. The PCO₂ of blood leaving the lungs is 40 mm Hg. CO₂ passes through all biologic membranes with ease, and the pulmonary diffusion capacity for CO₂ is much greater than the capacity for O₂. It is for this reason that CO₂ retention is rarely a problem in patients with alveolar capillary block even when the reduction in diffusion capacity for O₂ is severe.

The partial pressure gradients for O₂ and CO₂ have been plotted in graphic form in Fig 44-3 to emphasize that they are the key to gas movement and that O₂ “flows downhill” from the air through the alveoli and blood into the tissues whereas CO₂ ”flows downhill” from the tissues to the alveoli.

However, the amount of both of these gases transported to and from the tissues would be grossly inadequate if it were not that about 99% O₂ which dissolves in the blood combines with the O₂ carrying protein hemoglobin and that about 94% of the CO₂ which dissolves enters into a series of reversible chemical reactions, which convert it into other compounds. The presence of hemoglobin increases the O₂ carrying capacity of the blood 70-fold, and the reactions of CO₂ increase the blood CO₂ content 17-fold (Table ).

Table . Gas content of blood.

 

Oxygen Delivery to the Tissues. The O₂ delivery system in the body consists of the lungs and the cardiovascular system. O₂ delivery to a particular tissue depends on the amount of O₂ entering the lungs, the adequacy of pulmonary gas exchange, the blood flow to the tissue, and the capacity of the blood to carry O₂. The blood flow depends on the degree of constriction of the vascular bed in the tissue and the cardiac output. The amount of O₂ in the blood is determined by the amount of dissolved O₂, the amount of hemoglobin in the blood, and the affinity of the hemoglobin for O₂.

OXYGEN TRANSPORT

How are oxygen & carbon dioxide transported in the blood?

·                     Oxygen is carried in blood:

1 – bound to hemoglobin (98.5% of all oxygen in the blood)

2 – dissolved in the plasma (1.5%)

Because almost all oxygen in the blood is transported by hemoglobin, the relationship between the concentration (partial pressure) of oxygen and hemoglobin saturation (the % of hemoglobin molecules carrying oxygen) is an important one.

Reaction of The relationship between oxygen levels and hemoglobin saturation is indicated by the oxygen-hemoglobin dissociation (saturation) curve(in the graph above). You can see that at high partial pressures of O2 (above about 40 mm Hg), hemoglobin saturation remains rather high (typically about 75 – 80%). This rather flat section of the oxygen-hemoglobin dissociation curve is called the ‘plateau.’

Recall that 40 mm Hg is the typical partial pressure of oxygen in the cells of the body. Examination of the oxygen-hemoglobin dissociation curve reveals that, under resting conditions, only about 20 – 25% of hemoglobin molecules give up oxygen in the systemic capillaries. This is significant (in other words, the ‘plateau’ is significant) because it means that you have a substantial reserve of oxygen. In other words, if you become more active, & your cells need more oxygen, the blood (hemoglobin molecules) has lots of oxygen to provide

When you do become more active, partial pressures of oxygen in your (active) cells may drop well below 40 mm Hg. A look at the oxygen-hemoglobin dissociation curve reveals that as oxygen levels decline, hemoglobin saturation also declines – and declines precipitously. This means that the blood (hemoglobin) ‘unloads’ lots of oxygen to active cells – cells that, of course, need more oxygen.

 Hemoglobin & Oxygen.

The dynamics of the reaction of hemoglobin with O₂ make it a particularly suitable O₂ carrier. Hemoglobin is a protein made up of 4 subunits, each of which contains a hem moiety attached to a polypeptide chain. Hem is a complex made up of porphyry and 1 atom of ferrous iron. Each of the 4 iron atoms can bind reversibly one O₂ molecule. The iron stays in the ferrous state, so that the reaction is an oxygenation, not an oxidation. When hemoglobin takes up a small amount of O₂, the R state is favored and additional uptake of O₂ is facilitated. This is why the oxygen hemoglobin dissociation curve, the curve relating percentage saturation of the O₂-carrying power of hemoglobin to the P.O₂, has a characteristic sigmoid shape. Combination of the first hem in the Hb molecule with O₂ increases the affinity of the second hem for O₂, and oxygenation of the second increases the affinity of the third, etc, so that the affinity of Hb for the fourth O₂ molecule is many times that for the first. When hemoglobin takes up O_2, the 2/3 chains move closer together; when O₂ is given up, they move further apart. This shift is essential for the shift in affinity for O₂ to occur. When blood is equilibrated with 100% O₂ (P.O₂ = 760 mm Hg), the normal hemoglobin becomes 100% saturated. When fully saturated, each gram of hemoglobin contains 1.34 ml of O₂. The hemoglobin concentration iormal blood is about 15 g/dl (14 g/dl in women and 16 g/dl in men). Therefore, 1 dl of blood contains 20.1 ml (1.34 ml x 15) of O₂ bound to hemoglobin when the hemoglobin is 100% saturated. The amount of dissolved O₂ is a linear function of the P.O₂ (0.003 ml/dl blood/mm Hg PO₂). In vivo, the hemoglobin in the blood at the ends of the pulmonary capillaries is about 97.5% saturated with O₂ (PO₂= 97 mm Hg). Because of a slight admixture with venous blood that bypasses the pulmonary capillary (“physiologic shunt”), the hemoglobin in systemic arterial blood is only 97% saturated. The arterial blood therefore contains a total of about 19.8 mL of O₂ per deciliter: 0.29 ml in solution and 19.5 ml bound to hemoglobin. In venous blood at rest, the hemoglobin is 75% saturated, and the total O₂ content is about 15.2 ml/dl.

Thus, at rest the tissues remove about 4.6 ml of O₂ from each deciliter of blood passing through them (Table 44-4); 0.17 ml of this total represents O₂ that was in solution in the blood, and the remainder represents O₂ that was liberated from hemoglobin. In this way, 250 ml of O₂ per minute is transported from the blood to the tissues at rest.

 

Figure. Oxygen hemoglobin dissociation curve pH 7,40. temperature 38⁰. 

Factors Affecting the Affinity of Hemoglobin for Oxygen. Three important conditions affect the oxygen hemoglobin dissociation curve: the pH, the temperature, and the concentration of 2,3-diphosphoglycerate (DPG; 2,3-DPG). A rise in temperature or a fall in pH shifts the curve to the right .

When the curve is shifted in this direction, a higher P.O₂; is required for hemoglobin to bind a given amount of O₂. Conversely, a fall in temperature or a rise in pH shifts the curve to the left, and a lower P O₂ is required to bind a given amount of O₂. A convenient index of such shifts is the P₅₀, the P O₂ at which the hemoglobin is half saturated with O₂; the higher the P₅₀, the lower the affinity of hemoglobin for O₂.

 

Figure. Effect temperature and pH on hemoglobin dissociation curve. 

 

The decrease in O₂ affinity of hemoglobin when the pH of blood falls is called the Bohr effect and is closely related to the fact that deoxyhemoglobin binds H⁺ more actively than does oxyhemoglobin.

 

 

 

 

 

The pH of blood falls as its CO₂ content increases , so that when the PCO₂ rises, the curve shifts to the right and the P₅₀ rises. Most of the unsaturation of hemoglobin that occurs in the tissues is secondary to the decline in the P O₂, but an extra 1-2% unsaturation is due to the rise in P.CO₂ and consequent shift of the dissociation curve to the right.

 

 

2,3-DPG is very plentiful in red cells. It is formed from 3-phosphoglyceraldehyde, which is a product of glycolysis via the Embden-Meyerhof pathway. It is a highly charged anion that binds to the Beta chains of deoxygenated hemoglobin but not to those of oxyhemoglobin. One mole of deoxygenated hemoglobin binds 1 mole of 2,3-DPG. In effect:

HbO₂ + 2,3-DPG =Hb-2,3-DPG + O₂

In this equilibrium, an increase in the concentration of 2,3-DPG shifts the reaction to the right, causing more O₂ to be liberated. ATP binds to deoxygenated hemoglobin to a lesser extent, and some other organic phosphates bind to a minor degree.

Factors affecting the concentration of 2,3-DPG in the red cells include pH. Because acidosis inhibits red cell glycolysis, the 2,3-DPG concentration falls when the pH is low. Thyroid hormones, growth hormone, and androgens increase the concentration of 2,3-DPG and the P₅₀.

 

 

Myoglobin. Myoglobin is an iron-containing pigment found in skeletal muscle. It resembles hemoglobin but binds one rather than 4 mol of O₂ per mole. Its dissociation curve is a rectangular hyperbola rather than a sigmoid curve. Because its curve is to the left of the hemoglobin curve (Fig), it takes up O₂ from hemoglobin in the blood.

 

It releases O₂ only at low P.O₂ values, but the P O₂ in exercising muscle is close to zero. The myoglobin content is greatest in muscles specialized for sustained contraction.

 

 

Figure . Dissociation curve of hemoglobin and myoglobin at 38⁰, pH 7,40.

Video

The muscle blood supply is compressed during such contractions, and myoglobin may provide O₂ when blood flow is cut off. There is also evidence that myoglobin facilitates the diffusion of O₂ from the blood to the mitochondria, where the oxidative reactions occur.

Carbon dioxide – transported from the body cells back to the lungs as:

1 – bicarbonate (HCO3) – 60%

formed when CO2 (released by cells making ATP) combines with H2O (due to the enzyme in red blood cells called carbonic anhydrase) as shown in the diagram below

2 – carbaminohemoglobin – 30%

formed when CO2 combines with hemoglobin (hemoglobin molecules that have given up their oxygen)

3 – dissolved in the plasma – 10%

The resultant carbon dioxide, which is produced from metabolism and given out by the tissue, is passed into blood through the tissue fluid and conveyed back to the respiratory surfaces along with the blood stream. But by plasma and hemoglobin of blood. Blood transports carbon dioxide in three ways, namely:

(1) As carbonic acid

(2) As bicarbonates of sodium and potassium and

(3) As carbominohemoglobin

All these compounds are reversible compounds. About 10% of total carbon dioxide is carried by the blood in the dissolved state as carbonic acid (CO₂ + H₂O – H₂CO₃) but 80% of CO₂ as Sodium bicarbonate in the plasma and as potassium bicarbonate in the plasma and as potassium bicarbonate in the corpuscles and the remaining 10% as carbamino-hemoglobin (a loose compound formed by CO2 + hemoglobin).

Now the question is if they are conveyed in compound from but not in Free State how does it become free. In the blood there is an enzyme called carbonic anhydrase formed in the erythrocytes. This enzyme enhances the conversion of bicarbonates into carbonates, carbon dioxide and water by catalytic apart from this enzyme, oxy-hemoglobin also helps in releasing the carbon dioxide from various compounds. Because oxy-hemoglobin is strongly acidic and the acidity causes the release of carbon dioxide from bicarbonates, carbonic acid and carbamonohemoglobin.

Therefore, the carbon dioxide so formed is removed by diffusion before the blood leaves the lung. This transportation of gases also comes under external respiration.

In short: from tissue – diffuses into – tissue

(CO₂ high concentration)

From tissue fluid – diffuses into – blood

(Free CO₂)

(i) By blood plasma:

As physical solution:

10% CO₂+ H₂O – Carbonic anhydrase – H₂CO₃

(Carbon dioxide) (Water) enzyme (carbonic acid)

(ii) By R. B. C. Hemoglobin as Carbamino Compounds:

10% carbon dioxide + hemoglobin – carbamino hemoglobin

(iii) As Bicarbonate compounds:80% carbon dioxide – in plasma as sodium bicarbonate

2Na HCO₃– Na₂CO₃+ H₂O + CO₂

(Sodium bicarbonate)

In corpuscles as potassium bicarbonate i.e. – 2 K. H.

(Potassium bicarbonate)

CO₃– K2CO₂+ H₂O + CO₃

Release of CO2 at the Respiratory Surface:

Carbonic acid, bicarbonates of sodium and potassium and carbamino compounds are carried to the lungs where they breakdown under the influence of various factors and liberate free CO_2.

Measuring of thorax sizes in different phases of breathing

1) Measure the sizes of thorax by means of tape-measure. Put it under the angles of scapulae and on the level of thoracic papilla. Measure:

a) During the deep inhalation;

b) During the deep exhalation.

Define the excursion of thorax (the difference between the sizes measured during the inhalation and exhalation).

Write down the results in to the table:

 

#	Sizes of thorax		Excursion of thorax
	During the deep inhalation	During the deep exhalation
1

 

2) Legs of compasses put the inferior margins of ribs arcs on the same level, as in the previous measuring (by means of metallic compasses). Define the changes of sizes of thorax in the frontal ltness during the deep inhalation and deep exhalation. Legs of compasses put to the inferior margin of breast bone and on the same level to the spine. Define the excursion of thorax in sagittal flatness during the deep inhalation and deep exhalation.

Write down the results in to the table:

 

In conclusion define whether the excursion of thorax corresponds to the physiologic norm; explain the mechanism of size changing of thorax in different phases of breathing.

Changes of pressure in pleural cavity and lungs during the modeled breathing

To demonstrate the changes that appeared in the thoracic cavity during the breathing use the model of Donders. Determine the pressure in the “ pleural cavity” and lungs during the inhalation and exhalation. Pay attention to the volume of lungs when the position of diaphragm is changed. Show graphically changes of lungs volume, pressure in lungs and pleural cavity in different phases of breathing.

In conclusion define the mechanism of pressure changes in “pleural cavity” and lungs during the modeled breathing.

Measuring of pressure in respiratory ways

Fix the narcotized rat on the table. Make a clit on the middle cervical line till the trachea. Introduce there an injective needle connected manometer. Register changes of pressure in respiratory ways during the inhalation and exhalation and show the results graphically.

In conclusion define whether the results correspond to the physiologic regularity changes of pressure in respiratory ways while breathing.

 

Spirometry

By dry spirometer

Put closely the desinfected glass tube on the input tube of the spirometer. Turning the cap, put the scale of the set in such a way that the arrow is in zero position. Breathing out into the spirometer tube, determine the respiratory volume, reserve volume of breath out and life capacity of the lungs.

The results must be given in the following way:

 

Spirography

The examinee should take into his mouth desinfected tube connected with the system of spirograph. Put the forceps on his nose. Then write the spirogram. Determine the breath frequency according to the time mark (interval between the waves is equal to 5 seconds), breath volume, reserve volume of breath in and breath out (1 mm of vertical mobilization of spirograph’s pinna is equal to 20 ml of air), life capacity of the lungs and breath minute volume. Draw the spirogram in your notebook and mark all the lungs’ volumes and capacities. In your conclusion pay atention to that whether these results are physiologically normal and evaluate the functional condition of external breathing of the examinee.

 

 

References:

 

1. Review of Medical Physiology // W.F.Ganong. – 24th edition, 2012.

2. Textbook of Medical Physiology // A.C.Guyton, J.E.Hall. – Eleventh edition, 2005.

3. The human organs by R.M.DeCoursey, NMcGraw-Hill book company.