Physiology of respiration exam

Mechanism of pulmonary ventilation (summary)

- Inspiration: • Active process • Contraction of the inspiratory respiration muscles: - Diaphragm which accounts for 60 - 75% of the tidal volume - External intercostal muscles - Auxiliary muscles - SCM and scalene mm. - Expiration: • In quiet breathing it is a passive mechanisms, but in forced expiration the expiratory respiratory muscles help it. - Internal and innermost intercostal muscles - Muscles of the anterior abdominal wall

Functions of pulmonary surfactant

- Mechanical stabilisation of alveoli and small airways by decreasing the surface tension at the air-liquid interphase • LaPlace's law - As air enters the smaller bubbles, the surface tension increases, and the smaller bubbles have a higher tendency to collapse compared to the larger ones • Keep surface tension low when the alveoli become smaller during expiration. • Surfactant increases the lung compliance and decreases work of breathing - Prevention of pulmonary oedema (without it, water would be drawn into the lungs due to an unopposed tension of 20mmHg in the lungs and this would draw fluid from the blood into the alveoli) • The decrease tension diminishes a negative force for transduction of fluid into the interstitum or alveoli - Defence system of the lung • Positive chemotactic effect for macrophage • SF increases phagocytosis • Prevents adhesions of microorganisms - via a decrease of surface tension of the pathogenic microbes • Transports solid inhaled particles or damaged cells from alveolar compartment into the wall of the alveoli => pulmonary macrophages - Facilitation of the free airflow and low resistance in the airways • Facilitates mucociliary transport and airflow through terminal bronchioles

Pulmonary ventilation

- Movement of air into and out of the lungs per unit time. The difference in pressures drives pulmonary ventilation because air flows down a pressure gradient, that is, air flows from an area of higher pressure to an area of lower pressure - Usually expressed as minute ventilation (MV) and is tidal volume + frequency. - Maximum voluntary ventilation (MVV): 120-180 L/min, using force - If there is an increase in the alveolar ventilation, which goes above the metabolic requirements, there will be hyperventilation. This results in a decreased PCO2 and an increased PO2 and the result is hypocapnia and respiratory alkalosis. - In an opposite reaction: hypoventilation - hypercapnia, respiratory acidosis.

The quality of respiration processes depends upon several factors including

- Pulmonary ventilation: inflow and outflow of air between atmosphere and lung alveoli - Diffusion: of O2 and CO2 between alveoli and blood - Perfusion: of the lungs with blood - Transport: of O2 and CO2 in blood - Regulation: of respiration

Structure of the respiratory tract

- Upper airways: nose, nasopharynx & larynx (laryngeal inlet) - Lower airways: trachea, bronchi & bronchioles. The bronchioles are divided into 23 segments between trachea and the alveoli. - Alveoli: • 300 mill • Total surface area is 70m2 • Lined with pneumocytes • Contains type I (flat cells) and type II (surfactant) cells • Also contains lymphocytes, plasma cells, alveolar macrophages (dust cells), mast cells

Non-respiratory functions

- Voice production - Protective reflexes: apnoea, laryngospasm, prevents entering of foreign substance - Defensive reflexes: cough, sneeze, if a foreign substance has already entered and must be expelled - Thermoregulation - Increased abdominal pressure: defecation, micturition, child birth

The factors affecting gas diffusion are:

- the thickness of the membrane which may increase in the increase of interstitial fluid during edema - surface are, which may decrease in severe states such as removal of lung - diffusion coefficient, which is influenced by solubility coefficient. The solubility coefficient is the degree of how much molecule is attracted to water - cross sectional area - molecular weight - temperature - pressure gradient

Artificial ventilation

1)

pulmonary ventilation consists of?

1) Alveolar ventilation 2) Dead space

Functionally, the respiratory system can be divided into two zones:

1) Conductiong zone: - provide a route for incoming and outgoing air - remove debris and pathogens from the incoming air - warm and humidify incoming air - sensing odors - metabolize some airborne carcinogens 2) Respiratory zone: - responsible for gas exchange

Work of breathing can be minimised by optimising the determinants:

1) Elastic work: - PEEP - Keep lung volume at FRC and maximise number of ventilated alveoli. - Positioning - Optimise lung volume. - Surfactant: Minimising surface tension. - Optimise respiratory rate: Elastic work of breathing typically decreases with increased respiratory rate. 2) Resistive work: - Decrease respiratory rate: Respiratory rate is directly proportional to resistive work. - Increase laminar flow: - Laminar flow is more efficient than turbulent flow. Laminar flow can be increased by: Reducing gas density Heliox. - Increase Radius: - Increase lung volume - Bronchodilators

Respiration involves two processes

1) External respiration: includes the uptake of O2 and excretion of CO2 by the lungs 2) Internal respiration: the O2 and CO2 exchange between cells and capillaries

Respiratory responses to diving reflex

1) Inhibition of ventilation 2) Laryngoconstriction - stop breathing

Protective reflexes of lung

1) Kratschmer's apnoeic reflex 2) Diving reflex

Regulation of pulmonary surfactant

1) LOCAL: - The primary physiological stimulus is thought to be direct mechanical stretching of the type II cells that results from breathing. One deep breath appears to be sufficient to induce surfactant secretion. Mechanical stretching of type II cells triggers an increase in cytoplasmic Ca2 levels, which is required for the cell response - SP-A has negative effects => more SP-A present in the alveoli, less SF is synthesized and secreted 2) NEURAL: - Both sympathatic/parasympathetic has positive effects 3) HUMORAL: - Corticosteroids, T3, T4, TRH, estrogens, prostaglandins has positive effect - Negative effect: Hyperglycemia, hyperinsulinemia, androgens => inhibitioin of corticosteroids action, general stimulatory effect for growth

Types of exogenous surfactants

1) Natural: Bovine (storfe) Porcine (svin) 2) Artificial: synthetic

Receptors of lower airways and lung receptors

1) Pulmonary stretch receptors - mechanoreceptors of the airway in smooth muscles. They are stimulated when there is an increase in volume and pressure in airways and lungs during large inspirations. The result in Hering Breuer reflex 2) Irritant receptors - C-fiber receptors of the airways which are stimulated when there has been inhaled irritants or mechanical deformation of the airway mucosa. The result is coughing, hyperapnea, bronchoconstriction, laryngoconstriction, hypersecretion of mucus 3) Pulmonary C-fiber receptors or juxtacapillary receptors of the lungs - stimulated: - mechanical: an increase in interstitial lung pressure such as edema, embolism, «wet lungs» which cause a decrease in oxygenation and thus lead to an increase in ventilation/respiration. - chemical: smoke, capsaicin, histamine, serotonin, prostaglandin The results is pulmonary chemoreflex and J-reflex which increase in breathing rate, and is also thought to be involved in the sensation of dyspnea, the subjective sensation of difficulty breathing. The reflex response that is produced is apnea followed by rapid breathing, bradycardia, and hypotension. Because these receptors have been found in the walls of bronchi, the larynx, and the nose, they appear to be part of a widespread population of nociceptors found in most tissue. For this reason, they are now usually referred to as pulmonary C-fiber receptors.

Parameters of mechanisms of breathing

1) Resistance 2) Compliance 3) Work

Other factors involved in influencing the respiratory activity in addition to concentrations of CO2 are:

1) Systemic arterial concentrations of hydrogen ions. Increasing carbon dioxide levels can lead to increased H+ levels, as mentioned above, as well as other metabolic activities, such as lactic acid accumulation after strenuous exercise. Peripheral chemoreceptors of the aortic arch and carotid arteries sense arterial levels of hydrogen ions. When peripheral chemoreceptors sense decreasing, or more acidic, pH levels, they stimulate an increase in ventilation to remove carbon dioxide from the blood at a quicker rate. Removal of carbon dioxide from the blood helps to reduce hydrogen ions, thus increasing systemic pH. 2) Blood levels of oxygen. The peripheral chemoreceptors are responsible for sensing large changes in blood oxygen levels. If blood oxygen levels become quite low—about 60 mm Hg or less—then peripheral chemoreceptors stimulate an increase in respiratory activity. The chemoreceptors are only able to sense dissolved oxygen molecules, not the oxygen that is bound to hemoglobin. As you recall, the majority of oxygen is bound by hemoglobin; when dissolved levels of oxygen drop, hemoglobin releases oxygen. Therefore, a large drop in oxygen levels is required to stimulate the chemoreceptors of the aortic arch and carotid arteries. 3) The hypothalamus and other regions associated with the limbic system are involved in regulating respiration in response to emotions, pain, and temperature. For example, an increase in body temperature causes an increase in respiratory rate. Feeling excited or the fight-or-flight response will also result in an increase in respiratory rate.

Factors other than partial pressure also affect the oxygen-hemoglobin saturation/dissociation curve

1) Temperature: a higher temperature promotes hemoglobin and oxygen to dissociate faster, whereas a lower temperature inhibits dissociation. However, the human body tightly regulates temperature, so this factor may not affect gas exchange throughout the body. The exception to this is in highly active tissues, which may release a larger amount of energy than is given off as heat. As a result, oxygen readily dissociates from hemoglobin, which is a mechanism that helps to provide active tissues with more oxygen. 2) Hormones: Certain hormones, such as androgens, epinephrine, thyroid hormones, and growth hormone, can affect the oxygen-hemoglobin saturation/disassociation curve by stimulating the production of a compound called 2,3-bisphosphoglycerate (BPG) by erythrocytes. BPG is a byproduct of glycolysis. Because erythrocytes do not contain mitochondria, glycolysis is the sole method by which these cells produce ATP. BPG promotes the disassociation of oxygen from hemoglobin. Therefore, the greater the concentration of BPG, the more readily oxygen dissociates from hemoglobin, despite its partial pressure. 3) The pH of the blood is another factor that influences the oxygen-hemoglobin saturation/dissociation curve. The Bohr effect is a phenomenon that arises from the relationship between pH and oxygen's affinity for hemoglobin: A lower, more acidic pH promotes oxygen dissociation from hemoglobin. In contrast, a higher, or more basic, pH inhibits oxygen dissociation from hemoglobin. The greater the amount of carbon dioxide in the blood, the more molecules that must be converted, which in turn generates hydrogen ions and thus lowers blood pH. Furthermore, blood pH may become more acidic when certain byproducts of cell metabolism, such as lactic acid, carbonic acid, and carbon dioxide, are released into the bloodstream.

Defensive reflexes of lung

1) sneezing 2) Coughing

Adverse effects of oxygen therapy

1. Irritation of airways: - Mucosa with inhalation of dry (non humidified) and cold O2 2. Changes in the lungs - A decrease of surfactant production - Inhibition of pulmonary macrophages activity - Inhibition of mucociliary transport - Lung oedema 3. Vasoconstriction - Cerebral (increased O2) - Retina - ischaemia - formation of fibrotic scares - visual defects - Blindness - retrolental fibroplasia 4. Effect on the brain and other organs - Decreased brain GABA content, ATP

Maximum voluntary ventilation value

120-180 L/min

Pulmonary blood flow velocity

40 cm/s

Pulmonary blood flow

5.5 L/min

Transport of carbon dioxide in form of bicarbonate

A large fraction—about 70 percent—of the carbon dioxide molecules that diffuse into the blood is transported to the lungs as bicarbonate. Most bicarbonate is produced in erythrocytes after carbon dioxide diffuses into the capillaries, and subsequently into red blood cells. Carbonic anhydrase (CA) causes carbon dioxide and water to form carbonic acid (H2CO3), which dissociates into two ions: bicarbonate (HCO3-) and hydrogen (H+). The following formula depicts this reaction: CO2 + H2O CA ↔ H2CO3↔H+ + HCO3− Bicarbonate tends to build up in the erythrocytes, so that there is a greater concentration of bicarbonate in the erythrocytes than in the surrounding blood plasma. As a result, some of the bicarbonate will leave the erythrocytes and move down its concentration gradient into the plasma in exchange for chloride (Cl-) ions. This phenomenon is referred to as the chloride shift and occurs because by exchanging one negative ion for another negative ion, neither the electrical charge of the erythrocytes nor that of the blood is altered. At the pulmonary capillaries, the chemical reaction that produced bicarbonate (shown above) is reversed, and carbon dioxide and water are the products. Much of the bicarbonate in the plasma re-enters the erythrocytes in exchange for chloride ions. Hydrogen ions and bicarbonate ions join to form carbonic acid, which is converted into carbon dioxide and water by carbonic anhydrase. Carbon dioxide diffuses out of the erythrocytes and into the plasma, where it can further diffuse across the respiratory membrane into the alveoli to be exhaled during pulmonary ventilation.

Transport of carbon dioxide with hemoglobin

About 20 percent of carbon dioxide is bound by hemoglobin and is transported to the lungs. Carbon dioxide does not bind to iron as oxygen does; instead, carbon dioxide binds amino acid moieties on the globin portions of hemoglobin to form carbaminohemoglobin, which forms when hemoglobin and carbon dioxide bind. When hemoglobin is not transporting oxygen, it tends to have a bluish-purple tone to it, creating the darker maroon color typical of deoxygenated blood. Similar to the transport of oxygen by heme, the binding and dissociation of carbon dioxide to and from hemoglobin is dependent on the partial pressure of carbon dioxide. Because carbon dioxide is released from the lungs, blood that leaves the lungs and reaches body tissues has a lower partial pressure of carbon dioxide than is found in the tissues. As a result, carbon dioxide leaves the tissues because of its higher partial pressure, enters the blood, and then moves into red blood cells, binding to hemoglobin. In contrast, in the pulmonary capillaries, the partial pressure of carbon dioxide is high compared to within the alveoli. As a result, carbon dioxide dissociates readily from hemoglobin and diffuses across the respiratory membrane into the air. In addition to the partial pressure of carbon dioxide, the oxygen saturation of hemoglobin and the partial pressure of oxygen in the blood also influence the affinity of hemoglobin for carbon dioxide. The Haldane effect is a phenomenon that arises from the relationship between the partial pressure of oxygen and the affinity of hemoglobin for carbon dioxide. Hemoglobin that is saturated with oxygen does not readily bind carbon dioxide. However, when oxygen is not bound to heme and the partial pressure of oxygen is low, hemoglobin readily binds to carbon dioxide.

Dissolved carbon dioxide

Although carbon dioxide is not considered to be highly soluble in blood, a small fraction—about 7 to 10 percent—of the carbon dioxide that diffuses into the blood from the tissues dissolves in plasma. The dissolved carbon dioxide then travels in the bloodstream and when the blood reaches the pulmonary capillaries, the dissolved carbon dioxide diffuses across the respiratory membrane into the alveoli, where it is then exhaled during pulmonary ventilation.

expiratory reserve volume

Amount of air that can be forcefully exhaled after a normal tidal volume exhalation. 1000 mL

inspiratory reserve volume

Amount of air that can be forcefully inhaled after a normal tidal volume inhalation. 2000-2500 mL

Tidal volume

Amount of air that moves in and out of the lungs during a normal breath. 500 mL

Change in ventilation during hypoxia (high altitude effects)

An increase in altitude results in a decrease in atmospheric pressure. Although the proportion of oxygen relative to gases in the atmosphere remains at 21 percent, its partial pressure decreases. As a result, it is more difficult for a body to achieve the same level of oxygen saturation at high altitude than at low altitude, due to lower atmospheric pressure. In fact, hemoglobin saturation is lower at high altitudes compared to hemoglobin saturation at sea level. For example, hemoglobin saturation is about 67 percent at 19,000 feet above sea level, whereas it reaches about 98 percent at sea level. A lower partial pressure of oxygen means that there is a smaller difference in partial pressures between the alveoli and the blood, so less oxygen crosses the respiratory membrane. As a result, fewer oxygen molecules are bound by hemoglobin. Despite this, the tissues of the body still receive a sufficient amount of oxygen during rest at high altitudes. This is due to two major mechanisms. First, the number of oxygen molecules that enter the tissue from the blood is nearly equal between sea level and high altitudes. At sea level, hemoglobin saturation is higher, but only a quarter of the oxygen molecules are actually released into the tissue. At high altitudes, a greater proportion of molecules of oxygen are released into the tissues. Secondly, at high altitudes, a greater amount of BPG is produced by erythrocytes, which enhances the dissociation of oxygen from hemoglobin. Physical exertion, such as skiing or hiking, can lead to altitude sickness due to the low amount of oxygen reserves in the blood at high altitudes. At sea level, there is a large amount of oxygen reserve in venous blood (even though venous blood is thought of as "deoxygenated") from which the muscles can draw during physical exertion. Because the oxygen saturation is much lower at higher altitudes, this venous reserve is small, resulting in pathological symptoms of low blood oxygen levels. You may have heard that it is important to drink more water when traveling at higher altitudes than you are accustomed to. This is because your body will increase micturition (urination) at high altitudes to counteract the effects of lower oxygen levels. By removing fluids, blood plasma levels drop but not the total number of erythrocytes. In this way, the overall concentration of erythrocytes in the blood increases, which helps tissues obtain the oxygen they need.

How much surfactant in whole adult lung?

Approx. 1 g (mL)

Automatic control of breathing

Bulbospinal pathway in ventrolateral tract

How does residual volume makes breathing easier?

By preventing the alveoli from collapsing

Carbon dioxide transport in blood

Carbon dioxide is transported by three major mechanisms. The first mechanism of carbon dioxide transport is by blood plasma, as some carbon dioxide molecules dissolve in the blood. The second mechanism is transport in the form of bicarbonate (HCO3-), which also dissolves in plasma. The third mechanism of carbon dioxide transport is similar to the transport of oxygen by erythrocytes

Apnoea

Cessation of breathing

Thermal balance responses to diving reflex

Cold shock response is the initial reaction to immersion in cold water. It generally starts with a gasp reflex in response to sudden and rapid chilling of the skin, and if the head is immersed there is a risk of inhaling water and drowning. This is followed by a reflexive hyperventilation, with a risk of panic and fainting if not controlled. Cold induced vasoconstriction causes the heart to work harder and the additional work can overload a weak heart, with a possible consequence of cardiac arrest. Cold incapacitation is the next stage, and generally occurs within 5 to 15 minutes in cold water. Blood flow to the extremities is reduced by vasoconstriction as the body attempts to reduce heat loss from the vital organs of the core. This accelerates the cooling of the periphery, and reduces the functionality of the muscles and nerves. The duration of exposure to produce hypothermia varies with health, body mass and water temperature. It generally takes in the order of 30 minutes for an unprotected person in water to become hypothermic

Voluntary control of breathing

Corticospinal pathway in dorsolateral spinal medulla

Gas exchange in the lungs

Diffusion of gases over alveolar/capillary membrane. Diffusion occurs due to the concentration gradient of a particular gas. The concentration of oxygen in the alveoli is higher than in the capillaries, and the concentration of carbon dioxide in the capillaries is higher than in the alveoli. The composition of air in the atmosphere and in the alveoli differs. In both cases, the relative concentration of gases is nitrogen > oxygen > water vapor > carbon dioxide. The amount of water vapor present in alveolar air is greater than that in atmospheric air (Table 3). Recall that the respiratory system works to humidify incoming air, thereby causing the air present in the alveoli to have a greater amount of water vapor than atmospheric air. In addition, alveolar air contains a greater amount of carbon dioxide and less oxygen than atmospheric air. This is no surprise, as gas exchange removes oxygen from and adds carbon dioxide to alveolar air. Both deep and forced breathing cause the alveolar air composition to be changed more rapidly than during quiet breathing. As a result, the partial pressures of oxygen and carbon dioxide change, affecting the diffusion process that moves these materials across the membrane. This will cause oxygen to enter and carbon dioxide to leave the blood more quickly. Two important aspects of gas exchange in the lung are ventilation and perfusion. Ventilation is the movement of air into and out of the lungs, and perfusion is the flow of blood in the pulmonary capillaries. For gas exchange to be efficient, the volumes involved in ventilation and perfusion should be compatible. However, factors such as regional gravity effects on blood, blocked alveolar ducts, or disease can cause ventilation and perfusion to be imbalanced.

Change in ventilation during exercise (kompendiumet)

During exercise, the lungs are inhaling more oxygen and thud more oxygen is reaching the blood. The PO2 of blood flowing into the pulmonary capillaries fall from 40à25mmHg or less so that the alveolar-capillary PO2 gradient is increased and more oxygen can enter the blood. The blood flow per minute is now increased from 5.5L/min to as much as 20 - 35L/min, which means that the total amount of oxygen entering the blood is therefore increasing from 250mL/min at rest to as much as 4000mL/min! The increase of O2 uptake is proportional to the maximum work load and above this maximum, the O2 consumption falls of an the blood lactate levels start to rise from working muscles. At the same time, the amount of carbon dioxide removed from the body is also increased. The excretion increases from 200mL/min to 8000mL/min. Ventilation increases abruptly at the start of exercise, followed by a short pause before further gradual increase. For moderate exercise this increase is mostly due to increased depth of breathing accompanied by an increase in respiratory rate when the exercise becomes more strenuous. After exercise the ventilation abruptly decreases followed of a break before further decline to pre-workout values. The abrupt increase at the start of exercise is presumed to be psychic as well as stimuli from the proprioceptors of the muscles, joints and tendons. The further increase in thought to be humoral even though the values of PO2, PCO2 and pH remain pretty constant throughout a moderate workout. Increased ventilation is proportional to the increased O2 consumption but the mechanism behind this is still under investigation. Temperature is increasing and may play a role, increased [K+] may also play a role as this may stimulate the peripheral chemoreceptors. During strenuous exercise the production of lactic acid leads to increased levels of CO2 , which further increases ventilation. With the hyperventilation, the increased ventilation will cancel out the CO2 production and the alveolar PCO2 will fall as well as arterial. This decline in arterial PCO2 provides respiratory compensation for the metabolic acidosis produced by the lactic acid. The respiratory rate after exercise does not reach basal levels until the O2 debt is paid and this may take up to 90 minutes. The increased arterial H+ due to lactic acidaemia is the stimulus for ventilation after exercise. During this repayment of the oxygen, the O2 levels of the muscle myoglobin slightly increase. ATP and phoshorylcreatine are resynthesised and lactic acid is removed. 80% of lactic acid is converted to glycogen and 20% is metabolised to H2O and CO2. During exercise, the alveolar ventilation can increase as much as 20x. This is due to the brain sending impulses to the exercising muscles as well as the respiratory centres. This is because the ventilation is increasing immediately after onset of exercise so that chemical signals are too slow to be used as pathway in this type of process. PCO2 will be negative the first period of exercise because there is an increased ventilation (more PO2). After 30 - 40s the muscles will start releasing CO2 and it will be positive again.

Upon initiation of the diving reflex, physiological changes occur on the heart:

During sustained breath-holding while submerged, blood oxygen levels decline while carbon dioxide and acidity levels rise, stimuli that collectively act upon chemoreceptors located in the bilateral carotid bodies. As sensory organs, the carotid bodies convey the chemical status of the circulating blood to brain centers regulating neural outputs to the heart and circulation. Preliminary evidence in ducks and humans indicates that the carotid bodies are essential for these integrated cardiovascular responses of the diving response, establishing a "chemoreflex" characterized by parasympathetic (slowing) effects on the heart and sympathetic (vasoconstrictor) effects on the vascular system. The human heart rate slows down 10-25%. Slowing the heart rate reduces the cardiac oxygen consumption, and compensates for the hypertension due to vasoconstriction. However, breath-hold time is reduced when the whole body is exposed to cold water as the metabolic rate increases to compensate for accelerated heat loss even when the heart rate is significantly slowed

In the clinics an increased compliance means

Emphysema (harder to breath out)

Oxygen transport in blood

Even though oxygen is transported via the blood, you may recall that oxygen is not very soluble in liquids. A small amount of oxygen does dissolve in the blood and is transported in the bloodstream, but it is only about 1.5% of the total amount. The majority of oxygen molecules are carried from the lungs to the body's tissues by a specialized transport system, which relies on the erythrocyte—the red blood cell. Erythrocytes contain a metalloprotein, hemoglobin, which serves to bind oxygen molecules to the erythrocyte (Figure 1). Heme is the portion of hemoglobin that contains iron, and it is heme that binds oxygen. One hemoglobin molecule contains iron-containing Heme molecules, and because of this, each hemoglobin molecule is capable of carrying up to four molecules of oxygen. As oxygen diffuses across the respiratory membrane from the alveolus to the capillary, it also diffuses into the red blood cell and is bound by hemoglobin. The following reversible chemical reaction describes the production of the final product, oxyhemoglobin (Hb-O2), which is formed when oxygen binds to hemoglobin. Oxyhemoglobin is a bright red-colored molecule that contributes to the bright red color of oxygenated blood. Partial pressure is an important aspect of the binding of oxygen to and disassociation from heme. An oxygen-hemoglobin dissociation curve is a graph that describes the relationship of partial pressure to the binding of oxygen to heme and its subsequent dissociation from heme (Figure 2). Remember that gases travel from an area of higher partial pressure to an area of lower partial pressure. In addition, the affinity of an oxygen molecule for heme increases as more oxygen molecules are bound. Therefore, in the oxygen-hemoglobin saturation curve, as the partial pressure of oxygen increases, a proportionately greater number of oxygen molecules are bound by heme. Not surprisingly, the oxygen-hemoglobin saturation/dissociation curve also shows that the lower the partial pressure of oxygen, the fewer oxygen molecules are bound to heme. As a result, the partial pressure of oxygen plays a major role in determining the degree of binding of oxygen to heme at the site of the respiratory membrane, as well as the degree of dissociation of oxygen from heme at the site of body tissues

The effect of gravity on the pulmonary circulation

Gravity has a relatively marked effect on the pulmonary circu- lation. In the upright position, the upper portions of the lungs are well above the level of the heart, and the bases are at or be- low it. Consequently, in the upper part of the lungs, the blood flow is less, the alveoli are larger, and ventilation is less than at the base. The pressure in the capillaries at the top of the lungs is close to the atmospheric pressure in the al- veoli. Pulmonary arterial pressure is normally just sufficient to maintain perfusion, but if it is reduced or if alveolar pressure is increased, some of the capillaries collapse. Under these cir- cumstances, no gas exchange takes place in the affected alveoli and they become part of the physiologic dead space. In the middle portions of the lungs, the pulmonary arterial and capillary pressure exceeds alveolar pressure, but the pres- sure in the pulmonary venules may be lower than alveolar pressure during normal expiration, so they are collapsed. Under these circumstances, blood flow is determined by the pulmonary artery-alveolar pressure difference rather than the pulmonary artery-pulmonary vein difference. Beyond the constriction, blood "falls" into the pulmonary veins, which are compliant and take whatever amount of blood the constriction lets flow into them. This has been called the waterfall effect. Obviously, the compression of vessels produced by alveolar pressure decreases and pulmonary blood flow increases as the arterial pressure increases toward the base of the lung. In the lower portions of the lungs, alveolar pressure is lower than the pressure in all parts of the pulmonary circulation and blood flow is determined by the arterial-venous pressure

Henry's law in relation to gas exchange

Henry's law describes the behavior of gases when they come into contact with a liquid, such as blood. Henry's law states that the concentration of gas in a liquid is directly proportional to the solubility and partial pressure of that gas. The greater the partial pressure of the gas, the greater the number of gas molecules that will dissolve in the liquid. The concentration of the gas in a liquid is also dependent on the solubility of the gas in the liquid. For example, although nitrogen is present in the atmosphere, very little nitrogen dissolves into the blood, because the solubility of nitrogen in blood is very low. The exception to this occurs in scuba divers; the composition of the compressed air that divers breathe causes nitrogen to have a higher partial pressure than normal, causing it to dissolve in the blood in greater amounts than normal. Too much nitrogen in the bloodstream results in a serious condition that can be fatal if not corrected. Gas molecules establish an equilibrium between those molecules dissolved in liquid and those in air.

Hyperbaric chamber treatment

Hyperbaric chamber treatment is based on the behavior of gases. As you recall, gases move from a region of higher partial pressure to a region of lower partial pressure. In a hyperbaric chamber, the atmospheric pressure is increased, causing a greater amount of oxygen than normal to diffuse into the bloodstream of the patient. Hyperbaric chamber therapy is used to treat a variety of medical problems, such as wound and graft healing, anaerobic bacterial infections, and carbon monoxide poisoning. Exposure to and poisoning by carbon monoxide is difficult to reverse, because hemoglobin's affinity for carbon monoxide is much stronger than its affinity for oxygen, causing carbon monoxide to replace oxygen in the blood. Hyperbaric chamber therapy can treat carbon monoxide poisoning, because the increased atmospheric pressure causes more oxygen to diffuse into the bloodstream. At this increased pressure and increased concentration of oxygen, carbon monoxide is displaced from hemoglobin. Another example is the treatment of anaerobic bacterial infections, which are created by bacteria that cannot or prefer not to live in the presence of oxygen. An increase in blood and tissue levels of oxygen helps to kill the anaerobic bacteria that are responsible for the infection, as oxygen is toxic to anaerobic bacteria. For wounds and grafts, the chamber stimulates the healing process by increasing energy production needed for repair. Increasing oxygen transport allows cells to ramp up cellular respiration and thus ATP production, the energy needed to build new structures.

Change in ventilation during exercise (forklart fra nettside)

Hyperpnea is an increased depth and rate of ventilation to meet an increase in oxygen demand as might be seen in exercise or disease, particularly diseases that target the respiratory or digestive tracts. This does not significantly alter blood oxygen or carbon dioxide levels, but merely increases the depth and rate of ventilation to meet the demand of the cells. In contrast, hyperventilation is an increased ventilation rate that is independent of the cellular oxygen needs and leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH. Interestingly, exercise does not cause hyperpnea as one might think. Muscles that perform work during exercise do increase their demand for oxygen, stimulating an increase in ventilation. However, hyperpnea during exercise appears to occur before a drop in oxygen levels within the muscles can occur. Therefore, hyperpnea must be driven by other mechanisms, either instead of or in addition to a drop in oxygen levels. The exact mechanisms behind exercise hyperpnea are not well understood, and some hypotheses are somewhat controversial. However, in addition to low oxygen, high carbon dioxide, and low pH levels, there appears to be a complex interplay of factors related to the nervous system and the respiratory centers of the brain. First, a conscious decision to partake in exercise, or another form of physical exertion, results in a psychological stimulus that may trigger the respiratory centers of the brain to increase ventilation. In addition, the respiratory centers of the brain may be stimulated through the activation of motor neurons that innervate muscle groups that are involved in the physical activity. Finally, physical exertion stimulates proprioceptors, which are receptors located within the muscles, joints, and tendons, which sense movement and stretching; proprioceptors thus create a stimulus that may also trigger the respiratory centers of the brain. These neural factors are consistent with the sudden increase in ventilation that is observed immediately as exercise begins. Because the respiratory centers are stimulated by psychological, motor neuron, and proprioceptor inputs throughout exercise, the fact that there is also a sudden decrease in ventilation immediately after the exercise ends when these neural stimuli cease, further supports the idea that they are involved in triggering the changes of ventilation.

Describe the mechanism of inspiration

In general, two muscle groups are used during normal inspiration: the diaphragm and the external intercostal muscles. Additional muscles can be used if a bigger breath is required. When the diaphragm contracts, it moves inferiorly toward the abdominal cavity, creating a larger thoracic cavity and more space for the lungs. Contraction of the external intercostal muscles moves the ribs upward and outward, causing the rib cage to expand, which increases the volume of the thoracic cavity. Due to the adhesive force of the pleural fluid, the expansion of the thoracic cavity forces the lungs to stretch and expand as well. This increase in volume leads to a decrease in intra-alveolar pressure, creating a pressure lower than atmospheric pressure. As a result, a pressure gradient is created that drives air into the lungs.

Dalton's law in relation to gas exchange

In order to understand the mechanisms of gas exchange in the lung, it is important to understand the underlying principles of gases and their behavior. In addition to Boyle's law, several other gas laws help to describe the behavior of gases. Gas molecules exert force on the surfaces with which they are in contact; this force is called pressure. In natural systems, gases are normally present as a mixture of different types of molecules. For example, the atmosphere consists of oxygen, nitrogen, carbon dioxide, and other gaseous molecules, and this gaseous mixture exerts a certain pressure referred to as atmospheric pressure. Partial pressure (Px) is the pressure of a single type of gas in a mixture of gases. For example, in the atmosphere, oxygen exerts a partial pressure, and nitrogen exerts another partial pressure, independent of the partial pressure of oxygen (Figure 1). Total pressure is the sum of all the partial pressures of a gaseous mixture. Dalton's law describes the behavior of nonreactive gases in a gaseous mixture and states that a specific gas type in a mixture exerts its own pressure; thus, the total pressure exerted by a mixture of gases is the sum of the partial pressures of the gases in the mixture. Partial pressure is extremely important in predicting the movement of gases. Recall that gases tend to equalize their pressure in two regions that are connected. A gas will move from an area where its partial pressure is higher to an area where its partial pressure is lower. In addition, the greater the partial pressure difference between the two areas, the more rapid is the movement of gases.

Airway resistance

Increase in pressure that occurs as the diameter of the airways decreases from mouth/nose to alveoli. It depends on: 1) length and diamter of airway 2) velocity of flow 3) type of flow The value of airway resistance represents the alveolar pressure needed for maintaining a flow in the airways of 1 L/sec. Pressure/flow, where pressure is the alveolar pressure in kPa and the flow is the airflow in L/sec. Normal value is 0.5 kPa/L/s.

Tachypnoea

Increased respiratory rate (rapid breathing)

Artificial ventilation

It can be used as a short-term measure, for example during an operation or critical illness (often in the setting of an intensive-care unit). It may be used at home or in a nursing or rehabilitation institution if patients have chronic illnesses that require long-term ventilatory assistance. Due to the anatomy of the human pharynx, larynx, and esophagus and the circumstances for which ventilation is needed, additional measures are often required to secure the airway during positive-pressure ventilation in order to allow unimpeded passage of air into the trachea and avoid air passing into the esophagus and stomach. The common method is by insertion of a tube into the trachea: intubation, which provides a clear route for the air. This can be either an endotracheal tube, inserted through the natural openings of mouth or nose, or a tracheostomy inserted through an artificial opening in the neck. In other circumstances simple airway maneuvres, an oropharyngeal airway or laryngeal mask airway may be employed. If the patient is able to protect his/her own airway and non-invasive ventilation or negative-pressure ventilation is used then an airway adjunct may not be needed.

What is Hering Breuer reflex?

It is to prevent over-inflation of the lung. Pulmonary stretch receptors present in the smooth muscle of the airways respond to excessive stretching of the lung during large inspirations. Once activated, they send action potentials through large myelinated fibers of the vagus nerve to the inspiratory area in the medulla and apneustic center of the pons. In response, the inspiratory area is inhibited directly and the apneustic center is inhibited from activating the inspiratory area. This inhibits inspiration, allowing expiration to occur. The lung afferents also send inhibitory projections to the cardiac vagal motor neurones (CVM) in the nucleus ambiguus (NA) and dorsal motor vagal nucleus (DMVN). The CVMs, which send motor fibers to the heart via the vagus nerve, are responsible for tonic inhibitory control of heart rate. Thus, an increase in pulmonary stretch receptor activity leads to inhibition of the CVMs and an elevation of heart rate (tachycardia). This is a normal occurrence in healthy individuals and is known as sinus arrhythmia.

Compliance parameter

Lung compliance refers to the ability of lung tissue to stretch under pressure, which is determined in part by the surface tension of the alveoli and the ability of the connective tissue to stretch. Lung compliance plays a role in determining how much the lungs can change in volume, which in turn helps to determine pressure and air movement. The more the lungs can stretch, the greater the potential volume of the lungs. The greater the volume of the lungs, the lower the air pressure within the lungs. Thoracic wall compliance is the ability of the thoracic wall to stretch while under pressure. This can also affect the effort expended in the process of breathing. In order for inspiration to occur, the thoracic cavity must expand. The expansion of the thoracic cavity directly influences the capacity of the lungs to expand. If the tissues of the thoracic wall are not very compliant, it will be difficult to expand the thorax to increase the size of the lungs.

respiratory distress syndrome treatment

Medical advances have resulted in an improved ability to treat RDS and support the infant until proper lung development can occur. At the time of delivery, treatment may include resuscitation and intubation if the infant does not breathe on his or her own. These infants would need to be placed on a ventilator to mechanically assist with the breathing process. If spontaneous breathing occurs, application of nasal continuous positive airway pressure (CPAP) may be required. In addition, pulmonary surfactant is typically administered

Non-reflexive mechanisms

Mucous-ciliary transport (MCT). Moves particles by cilia that moves the mucous layer

The effect of SP-A on pulmonary surfactant

Negative biofeedback - the more SP-A is present in alveoli, the less of SF is synthesized and secreted

Eupnea

Normal quiet breathing and does not require the cognitive thought of the individual

Normobaric oxygenation

Normobaric A lifesaving modality in clinical medicine Indications: hypoxemia, hypoxia (mainly hypoxic hypoxia) Applications: incubators, intranasal catheter, O2 mask When 100% O2 (FiO2 = 1.0) is inhaled - the Hb is fully saturated and 5x increased O2 dissolved inplasma (from 3 to 14 - 15mL/L)

What happens if the automatic control of breathing pathway is damaged (bulbospinal pathway)?

Ondine's curse - Failure from birth of central nervous system control over breathing while asleep. There are usually no breathing problems while awake. The involuntary (autonomic) control of respiration is impaired, but the voluntary control of ventilation which operates during waking hours is generally intact.

Diaphragm is innervated by?

Phrenic n. (C3-C5)

Upon initiation of the diving reflex, physiological changes occur on the circulatory system:

Plasma fluid losses due to immersion diuresis occur within a short period of immersion. Head-out immersion causes a blood shift from the limbs and into the thorax. The fluid shift is largely from the extravascular tissues and the increased atrial volume results in a compensatory diuresis (increased urination).Plasma volume, stroke volume, and cardiac output remain higher than normal during immersion. The increased respiratory and cardiac workload causes increased blood flow to the cardiac and respiratory muscles. Stroke volume is not greatly affected by immersion or variation in ambient pressure, but bradycardia reduces the overall cardiac output, particularly due to the diving reflex in breath-hold diving. Blood shift is a term used when blood flow to the extremities is redistributed to the head and torso during a breathhold dive. Peripheral vasoconstriction occurs during submersion by resistance vessels limiting blood flow to muscles, skin, and viscera, regions which are "hypoxia-tolerant", thereby preserving oxygenated blood for the heart, lungs, and brain. The increased resistance to peripheral blood flow raises the blood pressure, which is compensated by bradycardia, conditions which are accentuated by cold water.

Positive pressure machines

Positive-pressure ventilators work by increasing the patient's airway pressure through an endotracheal or tracheostomy tube. The positive pressure allows air to flow into the airway until the ventilator breath is terminated. Then, the airway pressure drops to zero, and the elastic recoil of the chest wall and lungs push the tidal volume — the breath-out through passive exhalation.

Respiratory muscles assists in inspiration

Principal: 1) Diaphragm: main muscle. When contracting, expands the thoracic cavity thus decreasing PO2 below O2 atm. allowing oxygen to flow in. When relaxing, air is expelled due to an increase in the thoracic pressure 2) External intercostals: ventrocaudally in direction, will assist in inspiration by elevating the ribcage Accessory: 1) SCM: elevates sternum 2) Scalenes group: elevate upper ribs

Regulation of pulmonary blood flow

Pulmonary blood flow is affected by both active and passive factors. There is an extensive autonomic innervation of the pulmonary vessels, and stimulation of the cervical sympathetic ganglia reduces pulmonary blood flow by as much as 30%. The vessels also respond to circulating humoral agents. Many of the dilator responses are endothelium-dependent and presum- ably operate via release of nitric oxide (NO). Passive factors such as cardiac output and gravitational forces also have significant effects on pulmonary blood flow. Local adjustments of perfusion to ventilation are determined by local effects of O2 (or the lack of O2). With exercise, cardiac output increases and pulmonary arterial pressure rises pro- portionately with little or no vasodilation. More red cells move through the lungs without any reduction in the O2 satu- ration of the hemoglobin in them, and consequently, the total amount of O2 delivered to the systemic circulation is increased. Capillaries dilate, and previously underperfused capillaries are "recruited" to carry blood. The net effect is a marked increase in pulmonary blood flow with few, if any, alterations in autonomic outflow to the pulmonary vessels. When a bronchus or a bronchiole is obstructed, hypoxia develops in the underventilated alveoli beyond the obstruc- tion. The O2 deficiency apparently acts directly on vascular smooth muscle in the area to produce constriction, shunting blood away from the hypoxic area. Accumulation of CO2 leads to a drop in pH in the area, and a decline in pH also pro- duces vasoconstriction in the lungs, as opposed to the vasodi- lation it produces in other tissues. Conversely, reduction of the blood flow to a portion of the lung lowers the alveolar PCO2 in that area, and this leads to constriction of the bronchi supplying it, shifting ventilation away from the poorly per- fused area. Systemic hypoxia also causes the pulmonary arte- rioles to constrict, with a resultant increase in pulmonary arterial pressure.

Respiratory muscles assists in expiration

Quit breathing: Expiration results from passive, elastic recoil of the lungs, dib cage and diaphragm Active breathing: 1) Internal intercostal: dorsocaudally in direction, will help exhalation by narrowing the ribcage 2) Abdominals: pull ribs down, compress abdominal contents thus pushing diaphragm up

Resistance parameter

Resistance is a force that slows motion, in this case, the flow of gases. The size of the airway is the primary factor affecting resistance. A small tubular diameter forces air through a smaller space, causing more collisions of air molecules with the walls of the airways. Airway resistance is responsible for 80% of total lung resistance

Dyspnea

Shortness of breath

Kratschmer's apnoeic reflex

Stimulated by chemical irritation of nasal mucosa. The effects are: 1) Inhibition of ventilation 2) Laryngoconstriction - stop breathing 3) Peripheral vasoconstriction - redistribution of the blood 4) Bradycardia

What is Arnold's reflex?

Stimulation of the auricular branch of the vagus nerve supplying the ear may also elicit a cough.

What happens if the voluntary control of breathing pathway is damaged (corticospinal pathway)?

Syndrome of the automatic breathing

Respiratory centers in medulla oblongata

The DRG is involved in maintaining a constant breathing rhythm by stimulating the diaphragm and intercostal muscles to contract, resulting in inspiration. When activity in the DRG ceases, it no longer stimulates the diaphragm and intercostals to contract, allowing them to relax, resulting in expiration. The VRG is involved in forced breathing, as the neurons in the VRG stimulate the accessory muscles involved in forced breathing to contract, resulting in forced inspiration. The VRG also stimulates the accessory muscles involved in forced expiration to contract.

Alveolar ventilation

The amount of air that reaches the alveoli If the frequency of breathing is 12/min and the tidal volume is 500mL the pulmonary ventilation is 6L. But if the dead space is 150mL, it will be 500mL - 150 mL = 350mL x 12 = 4200mL =A 4,2L for the alveolar ventilation.

residual volume

The amount of air that remains in the lungs after a person exhales as forcefully as he or she can. 1000-2000 mL

Respiratory centers in pons

The apneustic center is a double cluster of neuronal cell bodies that stimulate neurons in the DRG, controlling the depth of inspiration, particularly for deep breathing. The pneumotaxic center is a network of neurons that inhibits the activity of neurons in the DRG, allowing relaxation after inspiration, and thus controlling the overall rate.

What is the major factor that stimulates the medulla oblongata and pons to produce respiration?

The concentration of carbon dioxide in the blood. As you recall, carbon dioxide is a waste product of cellular respiration and can be toxic. Concentrations of chemicals are sensed by chemoreceptors. A central chemoreceptor is one of the specialized receptors that are located in the brain and brainstem, whereas a peripheral chemoreceptor is one of the specialized receptors located in the carotid arteries and aortic arch. Concentration changes in certain substances, such as carbon dioxide or hydrogen ions, stimulate these receptors, which in turn signal the respiration centers of the brain. In the case of carbon dioxide, as the concentration of CO2 in the blood increases, it readily diffuses across the blood-brain barrier, where it collects in the extracellular fluid. increased carbon dioxide levels lead to increased levels of hydrogen ions, decreasing pH. The increase in hydrogen ions in the brain triggers the central chemoreceptors to stimulate the respiratory centers to initiate contraction of the diaphragm and intercostal muscles. As a result, the rate and depth of respiration increase, allowing more carbon dioxide to be expelled, which brings more air into and out of the lungs promoting a reduction in the blood levels of carbon dioxide, and therefore hydrogen ions, in the blood. In contrast, low levels of carbon dioxide in the blood cause low levels of hydrogen ions in the brain, leading to a decrease in the rate and depth of pulmonary ventilation, producing shallow, slow breathing.

Cough reflex

The cough receptors or rapidly adapting irritant receptors are located mainly on the posterior wall of the trachea, pharynx, and at the carina of trachea, the point where the trachea branches into the main bronchi. The receptors are less abundant in the distal airways, and absent beyond the respiratory bronchioles. When triggered, impulses travel via the internal laryngeal nerve, a branch of the superior laryngeal nerve which stems from the vagus nerve (CN X), to the medulla of the brain. This is the afferent neural pathway. Unlike other areas responsible for involuntary actions like swallowing, there is no definitive area that has been identified as the cough center in the brain. The efferent neural pathway then follows, with relevant signals transmitted back from the cerebral cortex and medulla via the vagus and superior laryngeal nerves to the glottis, external intercostals, diaphragm, and other major inspiratory and expiratory muscles. The mechanism of a cough is as follows: 1) Diaphragm (innervated by phrenic nerve) and external intercostal muscles (innervated by segmental intercostal nerves) contract, creating a negative pressure around the lung. 2) Air rushes into the lungs in order to equalise the pressure. 3) The glottis closes (muscles innervated by recurrent laryngeal nerve) and the vocal cords contract to shut the larynx. 4) The abdominal muscles contract to accentuate the action of the relaxing diaphragm; simultaneously, the other expiratory muscles contract. These actions increase the pressure of air within the lungs. 5) The vocal cords relax and the glottis opens, releasing air at over 100 mph. 6) The bronchi and non-cartilaginous portions of the trachea collapse to form slits through which the air is forced, which clears out any irritants attached to the respiratory lining.

What drives the pulmonary ventilation?

The difference in pressures drives pulmonary ventilation because air flows down a pressure gradient, that is, air flows from an area of higher pressure to an area of lower pressure. Air flows into the lungs largely due to a difference in pressure; atmospheric pressure is greater than intra-alveolar pressure, and intra-alveolar pressure is greater than intrapleural pressure. Air flows out of the lungs during expiration based on the same principle; pressure within the lungs becomes greater than the atmospheric pressure.

Why does the fetal's hemoglobin have a higher affinity for oxygen than maternal hemoglobin and why is this important?

The fetus has its own circulation with its own erythrocytes; however, it is dependent on the mother for oxygen. Blood is supplied to the fetus by way of the umbilical cord, which is connected to the placenta and separated from maternal blood by the chorion. The mechanism of gas exchange at the chorion is similar to gas exchange at the respiratory membrane. However, the partial pressure of oxygen is lower in the maternal blood in the placenta, at about 35 to 50 mm Hg, than it is in maternal arterial blood. The difference in partial pressures between maternal and fetal blood is not large, as the partial pressure of oxygen in fetal blood at the placenta is about 20 mm Hg. Therefore, there is not as much diffusion of oxygen into the fetal blood supply. The fetus' hemoglobin overcomes this problem by having a greater affinity for oxygen than maternal hemoglobin (Figure 3). Both fetal and adult hemoglobin have four subunits, but two of the subunits of fetal hemoglobin have a different structure that causes fetal hemoglobin to have a greater affinity for oxygen than does adult hemoglobin.

Why is surfactant important at birth?

The fetus makes respiratory movements in utero, but the lungs remain collapsed until birth. After birth, the infant makes several strong inspira- tory movements and the lungs expand. Surfactant keeps them from collapsing again. Surfactant deficiency is an im- portant cause of infant respiratory distress syndrome (IRDS, also known as hyaline membrane disease), the seri- ous pulmonary disease that develops in infants born before their surfactant system is functional. Surface tension in the lungs of these infants is high, and the alveoli are collapsed in many areas (atelectasis). An additional factor in IRDS is retention of fluid in the lungs. During fetal life, Cl- is se- creted with fluid by the pulmonary epithelial cells. At birth, there is a shift to Na+ absorption by these cells via the epi- thelial Na+ channels (ENaCs), and fluid is absorbed with the Na+. Prolonged immaturity of the ENaCs contributes to the pulmonary abnormalities in IRDS.

Sneezing reflex

The function of sneezing is to expel mucus containing irritants from the nasal cavity and clease the nasal cavity. It can be stimulated by: - irritants of the nasal mucosa - light - cold air - sudden change (fall) in temperature - full stomach - infection During a sneeze, the soft palate and palatine uvula depress while the back of the tongue elevates to partially close the passage to the mouth so that air ejected from the lungs may be expelled through the nose. Because the closing of the mouth is partial, a considerable amount of this air is usually also expelled from the mouth. The force and extent of the expulsion of the air through the nose varies. Sneezing typically occurs when foreign particles or sufficient external stimulants pass through the nasal hairs to reach the nasal mucosa. This triggers the release of histamines, which irritate the nerve cells in the nose, resulting in signals being sent to the brain to initiate the sneeze through the trigeminal nerve network. The brain then relates this initial signal, activates the pharyngeal and tracheal muscles and creates a large opening of the nasal and oral cavities, resulting in a powerful release of air and bioparticles.

Composition of surfactant

The hydrophilic proteins are SP-A and SP-D, which have a regulatory function in metabolism of surfactant. The hydrophobic proteins are SP-B and SP-C, which promote rapid phospholipid insertion into air/liquid interphase.

Negative pressure machines

The iron lung, also known as the Drinker and Shaw tank, was developed in 1929 and was one of the first negative-pressure machines used for long-term ventilation. It was refined and used in the 20th century largely as a result of the polio epidemic that struck the world in the 1940s. The machine is, in effect, a large elongated tank, which encases the patient up to the neck. The neck is sealed with a rubber gasket so that the patient's face (and airway) are exposed to the room air.[citation needed] While the exchange of oxygen and carbon dioxide between the bloodstream and the pulmonary airspace works by diffusion and requires no external work, air must be moved into and out of the lungs to make it available to the gas exchange process. In spontaneous breathing, a negative pressure is created in the pleural cavity by the muscles of respiration, and the resulting gradient between the atmospheric pressure and the pressure inside the thorax generates a flow of air. In the iron lung by means of a pump, the air is withdrawn mechanically to produce a vacuum inside the tank, thus creating negative pressure. This negative pressure leads to expansion of the chest, which causes a decrease in intrapulmonary pressure, and increases flow of ambient air into the lungs. As the vacuum is released, the pressure inside the tank equalizes to that of the ambient pressure, and the elastic coil of the chest and lungs leads to passive exhalation. However, when the vacuum is created, the abdomen also expands along with the lung, cutting off venous flow back to the heart, leading to pooling of venous blood in the lower extremities. There are large portholes for nurse or home assistant access. The patients can talk and eat normally, and can see the world through a well-placed series of mirrors. Some could remain in these iron lungs for years at a time quite successfully.

The mechanisms behind the oxygen-hemoglobin saturation/dissociation curve

The mechanisms behind the oxygen-hemoglobin saturation/dissociation curve also serve as automatic control mechanisms that regulate how much oxygen is delivered to different tissues throughout the body. This is important because some tissues have a higher metabolic rate than others. Highly active tissues, such as muscle, rapidly use oxygen to produce ATP, lowering the partial pressure of oxygen in the tissue to about 20 mm Hg. The partial pressure of oxygen inside capillaries is about 100 mm Hg, so the difference between the two becomes quite high, about 80 mm Hg. As a result, a greater number of oxygen molecules dissociate from hemoglobin and enter the tissues. The reverse is true of tissues, such as adipose (body fat), which have lower metabolic rates. Because less oxygen is used by these cells, the partial pressure of oxygen within such tissues remains relatively high, resulting in fewer oxygen molecules dissociating from hemoglobin and entering the tissue interstitial fluid. Although venous blood is said to be deoxygenated, some oxygen is still bound to hemoglobin in its red blood cells. This provides an oxygen reserve that can be used when tissues suddenly demand more oxygen.

Describe the mechanism of expiration

The process of normal expiration is passive, meaning that energy is not required to push air out of the lungs. Instead, the elasticity of the lung tissue causes the lung to recoil, as the diaphragm and intercostal muscles relax following inspiration. In turn, the thoracic cavity and lungs decrease in volume, causing an increase in interpulmonary pressure. The interpulmonary pressure rises above atmospheric pressure, creating a pressure gradient that causes air to leave the lungs.

Innervation of the respiratory tract

The smooth muscles are innervated by ANS: - Parasympathetic: muscarinic receptors - ACh on M3 - bronchoconstriction - Sympathetic: β2-receptors - adrenalin - bronchodilation - Non-cholinergic, non-adrenergic innervation: VIP (vasoactive intestinal peptide)

Biosynthesis of surfactant

The surfactant is synthesized by pneumocytes II in ER where they are transformed into lamellar bodies and secreted from the cells through exocytosis. Tubes of lipid called tubular myelin form from the extruded bodies, and the tubular myelin in turn forms the phospholipid film. Following secretion, the phospholipids of surfactant line up in the alveoli with their hydrophobic fatty acid tails facing the alveolar lumen. Surface tension is inversely proportional to their concentration per unit area. The surfactant molecules move further apart as the alveoli enlarge during inspiration, and surface tension increases, whereas it decreases when they move closer together during expiration. Some of the protein- lipid complexes in surfactant are taken up by endocytosis in type II alveolar cells and recycled. Formation of the phospholipid film is greatly facilitated by the proteins in surfactant. This material contains four unique proteins: surfactant protein (SP)-A, SP-B, SP-C, and SP-D. SP- A is a large glycoprotein and has a collagen-like domain within its structure. It has multiple functions, including regulation of the feedback uptake of surfactant by the type II alveolar epithelial cells that secrete it. SP-B and SP-C are smaller pro- teins, which facilitate formation of the monomolecular film of phospholipid. However, SP-A and SP-D are members of the col- lectin family of proteins that are involved in innate immunity in the conducting airway as well as in the alveoli. Substrates are taken from blood of pulmonary circulation and reuptake by pneumocytes II, where the substrates are reutilized. It can either be phagocytosed or degraded by alveolar macrophages or it can be eliminated through lymphatic or vascular system and mucociliary transport

CPAP (continuous positive airway pressure)

Treatment of sleep apnea commonly includes the use of a device called a continuous positive airway pressure (CPAP) machine during sleep. The CPAP machine has a mask that covers the nose, or the nose and mouth, and forces air into the airway at regular intervals. This pressurized air can help to gently force the airway to remain open, allowing more normal ventilation to occur. Other treatments include lifestyle changes to decrease weight, eliminate alcohol and other sleep apnea-promoting drugs, and changes in sleep position. In addition to these treatments, patients with central sleep apnea may need supplemental oxygen during sle

Breath delivery in artificial ventilation

Trigger: The trigger is what causes a breath to be delivered by a mechanical ventilator. Breaths may be triggered by a patient taking their own breath, a ventilator operator pressing a manual breath button, or by the ventilator based on the set breath rate and mode of ventilation. Cycle: The cycle is what causes the breath to transition from the inspiratory phase to the exhalation phase. Breaths may be cycled by a mechanical ventilator when a set time has been reached, or when a preset flow or percentage of the maximum flow delivered during a breath is reached depending on the breath type and the settings. Breaths can also be cycled when an alarm condition such as a high pressure limit has been reached, which is a primary strategy in pressure regulated volume control. Limit: Limit is how the breath is controlled. Breaths may be limited to a set maximum circuit pressure or a set maximum flow.

Ortopnea

Using auxiliary muscles

Diving reflex

When the face is submerged and water fills the nostrils, sensory receptors sensitive to wetness within the nasal cavity and other areas of the face supplied by the fifth (V) cranial nerve (the trigeminal nerve) relay the information to the brain. The tenth (X) cranial nerve, (the vagus nerve) - part of the autonomic nervous system - then produces bradycardia and other neural pathways elicit peripheral vasoconstriction, restricting blood from limbs and all organs to preserve blood and oxygen for the heart and the brain (and lungs), concentrating flow in a heart-brain circuit and allowing the animal to conserve oxygen. In humans, the diving reflex is not induced when limbs are introduced to cold water. Mild bradycardia is caused by subjects holding their breath without submerging the face in water. When breathing with the face submerged, the diving response increases proportionally to decreasing water temperature. However, the greatest bradycardia effect is induced when the subject is holding breath with the face wetted. Apnea with nostril and facial cooling are triggers of this reflex.

Work parameter

Work of breathing is the energy used by the muscles for respiration. It is defined as pressure X volume. This gives the work for a single respiratory cycle. Energy expenditure over time is better described as «power of breathing». It is divided into: - Elastic work: 65% - stored as elastic potential energy. Energy required to overcome elastic forces: lung elastic recoil and surface tension of alveoli - Resistive work: 35% - lost as heat. This is due to the energy required to overcome frictional forces: - between tissues: increased with increased intestitial lung tissue - between gas molecules: - increased at high flow rates - increased with turbulent flow - high respiratory rates - upper airway obstruction - increased airway density - hyperbaric - diving - increased with decreased airway radius - low lung volume - broncoconstriction The resistive expiratory work is typically done by elastic work of breathing, it is a purely passive process, using stored elastic potential energy for inspiration. If part of this area falls outside the area of elastic work of breathing, it demonstrates additional active work of expiration, which may occur in obstructive lung disease or when minute ventilation is high

Alveolar dead space

air in alveoli that are unable to function due to disease or abnormal blood flow

hyperpnea

deep breathing - forced breathing is a mode of breathing that can occur during exercise or actions that require the active manipulation of breathing, such as singing. During forced breathing, inspiration and expiration both occur due to muscle contractions. In addition to the contraction of the diaphragm and intercostal muscles, other accessory muscles must also contract. During forced inspiration, muscles of the neck, including the scalenes, contract and lift the thoracic wall, increasing lung volume. During forced expiration, accessory muscles of the abdomen, including the obliques, contract, forcing abdominal organs upward against the diaphragm. This helps to push the diaphragm further into the thorax, pushing more air out. In addition, accessory muscles (primarily the internal intercostals) help to compress the rib cage, which also reduces the volume of the thoracic cavity.

Function of pulmonary circulation

enated blood from the heart (right ventricle) to the lungs for oxygenation, and then returning the oxygenated blood to the heart (left ventricle) before it continues into the greater, or systemic, circulation.

functional residual capacity

expiratory reserve volume + residual volume = volume of air left in the lungs after a normal expiration

In the clinic a decreased compliance means

fibrosis, oedema (harder to breath in)

Forced expiratory volume in 1 sec

how much air expelled during first second of forced vital capacity manoeuvre. If decreased compared to normal values, it can indicate asthma or other bronchoconstrictory diseases with increased airway resistance

vital capacity

inspiratory reserve volume + expiratory reserve volume + tidal volume = largest amount of air to be expired after a maximum inspiration. Give information about compliance of the thorax and lungs, strength of the respiratory muscles. Between 4-5 L

forced vital capacity

maximum amount of air that can be removed from the lungs during forced expiration as quickly as possible

Dead space

passageways that transport air but are not available for gaseous exchange (e.g., trachea, bronchi). It is divided into the anatomical dead space and the alveolar dead space. In healthy individuals, these two spaces are identical

bradypnea

slow rate of breathing

Total dead space

sum of anatomical and alveolar dead space, and represents all of the air in the respiratory system that is not being used in the gas exchange process

inspiratory capacity

tidal volume + inspiratory reserve volume = Amount a person can inspire beginning the normal expiratory level and distending the lungs to a maximum extent

total lung capacity

vital capacity + residual volume = maximum volume of air that the lungs can hold after a forceful inhalation. It is about 6 L in men and 4.2 L in women

Anatomical dead space

volume of the conducting respiratory passages (150 ml), from nose to the terminal bronchioles.