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Home , Central chemoreceptors, Perfusion, Respiration (physiology)

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TOPIC Standard Pathophysiology Competency Applies fundamental knowledge of the pathophysiology of and to patient assessment and management. 7 Regulation of Ventilation, Ventilation/ Perfusion Ratio, and of Gases

INTRODUCTION he pathophysiology included in this topic is among the most formative and challenging changes to the new T education standards. Previously, EMTs had to know only about the air moving in and out of the body—and, quite frankly, in very simple terms and concepts. It was the belief, in The body’s regulation of normal ventilation through creating the standards that include this information, that EMTs chemistry values and the receptors that control them: would understand the internal processes of perfusion and gas – Central . transport that would make assessment and care performed – Peripheral chemoreceptors. more intuitive and effective. – Hypoxic and hypercarbic drive. How normal ventilation is affected by REGULATION OF VENTILATION receptors and respiratory control centers in the Although can be altered voluntarily, it is primarily brainstem. controlled involuntarily by the autonomic nervous system. A The ventilation/perfusion ratio and how it pertains to large part of the regulation is related to maintaining normal gas oxygenation of the bloodstream: exchange and normal blood gas levels. Receptors within the – Illustration of how changes to the ventilation/ perfusion ratio affect other bodily processes. body constantly measure the amount of (O2 ), (CO2 ), and hydrogen ions (pH) and signal the brain to The role blood, red blood cells, and play in adjust the rate and depth of respiration ( Figure 7-1 ). Centers cellular oxygenation and the removal of carbon dioxide responsible for ventilatory control are the chemoreceptors, lung from the cells. receptors, and specialized centers in the brainstem. Alveolar and cellular in the blood. Chemoreceptors Chemoreceptors are specialized receptors that monitor the number of hydrogen ions (pH) and the carbon dioxide and oxy- there is an association between CO 2 and the level of acid in the gen levels in the arterial blood. There are two different types of body as follows: chemoreceptors: central and peripheral. An increase in the amount of CO2 in the blood will increase the amount of acid in the blood. The central chemoreceptors A decrease in the amount of CO in the blood will decrease are located near the in the medulla. These 2 the amount of acid in the blood. receptors are most sensitive to changes in the amount of car- bon dioxide in arterial blood and the pH of The central chemoreceptors are highly sensitive to the amount (CSF). The pH of CSF is directly related to the amount of carbon of hydrogen in the CSF. After the CO2 and H2 O molecules com- + dioxide in the arterial blood. Carbon dioxide readily crosses the bine to form H 2 CO3 , the hydrogen ions (H ) disassociate from blood–brain barrier and moves into the CSF. In the CSF, the CO2 the H 2 CO3 , enter the CSF, and stimulate the central chemore- + combines with water (H2 O) to form carbonic acid (H2 CO3 ). Thus ceptors. Small changes in the H level in the CSF will stimulate MM07_LIMM3516_01_SE_C07.indd07_LIMM3516_01_SE_C07.indd PPageage 3388 11/28/11/28/11 4:384:38 PMPM user-s146user-s146 //Users/user-s146/Desktop/Merry_X-Mas/NewUsers/user-s146/Desktop/Merry_X-Mas/New

Voluntary and higher centers

Pneumotaxic center

Central A

Apneustic center

Ventral respiratory Vagus nerve group B A) C D Dorsal respiratory B) Aortic bodies group E C) Stretch receptors D) Irritant receptors E) J-receptors

Intercostal nerve

Phrenic nerve (to diaphragm)

Figure 7-1 Respiration is controlled by the autonomic nervous system. Receptors within the body measure oxygen, carbon dioxide, and hydrogen ions and send signals to the brain to adjust the rate and depth of respiration.

a change in respirations. Because CO2 is PERIPHERAL CHEMORECEPTORS The increase in the rate and depth of needed to produce H 2 CO 3 , the changes peripheral chemoreceptors are located in ventilation aimed at increasing the in the breathing rate and depth are the aortic arch and carotid bodies arterial oxygen content. geared toward increasing or decreasing in the neck. These chemoreceptors are Stimulation of both the central and the CO level in the arterial blood. The also sensitive to CO and pH; however, 2 2 peripheral chemoreceptors have a response of ventilation can be summa- the arterial oxygen level is the strongest greater influence on changing the rate rized as follows: stimulus. Thus, a change in the arterial oxy- and depth of ventilation than either alone. gen level is what stimulates the brain to An increase in arterial CO will 2 increase or decrease ventilation. It takes a increase the number of hydrogen ions Hypoxic Drive significant decrease in the arterial oxygen in the CSF, stimulating an increase in content to trigger the peripheral chemore- A person’s ventilation is normally control- the rate and depth of respiration to ceptors to stimulate the respiratory center led by the strong stimulus provided by blow off more CO . 2 to increase rate and depth of respiration. the amount of CO2 in the arterial blood. A decrease in arterial CO2 will The activity of the peripheral chemorecep- This is referred to as a hypercapnic drive decrease the number of hydrogen tors can be summarized as follows: or hypercarbic drive . However, some ions in the CSF, causing a decrease patients with chronic obstructive pulmo- in the rate and depth of respiration to A significant decrease in the arte- nary disease (COPD), such as emphysema blow off less CO2 . rial oxygen content will result in an or chronic bronchitis, have a tendency

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to retain carbon dioxide in their arterial 2 seconds, followed by 3 seconds with no bases of the , air In a typical blood from poor gas exchange. Because stimulation, resulting in respiratory muscle travels upward to the the CO2 level is chronically elevated, the relaxation. apexes (tops) of the respiratory central chemoreceptors become desen- The ventral respiratory group (VRG) lungs and increases cycle, the DRG sitized to fluctuations that typically would has both inspiratory and expiratory neu- the residual volume. stimulate a change in the rate or depth rons. However, the VRG is basically inac- Interestingly, the alve- stimulates the of ventilation. Because of the desensitiza- tive during normal quiet breathing. The oli in the apexes of the respiratory tion of the central chemoreceptors, the VRG becomes active when accessory lungs have a greater muscles to peripheral chemoreceptors become the muscles are needed to assist in inspira- residual volume of primary stimulus to control ventilation. tion or expiration. The VRGI , in which air, are larger, and contract for Thus, , rather than CO 2 , becomes the I subscript indicates inspiratory VRG have a higher surface 2 seconds, the stimulus for the person to breathe; neurons, stimulates the pectoralis minor, tension, but they are this is referred to as a hypoxic drive . scalene, and sternocleidomastoid mus- fewer in number com- followed by cles to inspiration. The VRGE , in pared with other areas 3 seconds Lung Receptors which the E subscript indicates expira- of the lungs. These with no stim- Three different types of receptors are tory VRG neurons, stimulates the internal larger alveoli in the found within the lungs: irritant receptors, intercostal and abdominal muscles to apexes have a higher ulation. stretch receptors, and J-receptors. The force . , which irritant receptors are found in the airways The apneustic center does not con- makes them less compliant and harder to and are sensitive to irritating gases, aero- trol the rhythm of respiration; however, inflate during ventilation. Thus, the tidal sols, and particles. Irritant receptors will it provides stimulation to the DRG and volume is shifted to the lower lobes, where cause a cough, , and VRGI to intensify the effort. The the lung is more compliant and there is an increase in the rate of ventilation. apneustic center may prolong inspiration, less surface tension. The stretch receptors are located within increasing the ventilatory volume. Because gravity pulls the blood the smooth muscle of the airways. These The pneumotaxic center sends inhibi- downward, less is required to are responsible for measuring the size and tory impulses to the apneustic center to perfuse the lower lobes of the lungs, as volume of the lungs. To prevent overin- cease inhalation before the lungs become compared with the apexes, which are flation when stimulated by high tidal vol- overinflated. It can promote passive exha- above the level of the . As a result, umes, these receptors decrease the rate lation both by shutting off the DRG and the bases of the lungs receive a greater and volume of ventilation when stretched. VRGI and by activating the VRGE . amount of blood and are much better J-receptors are located in the capillar- perfused than the apexes. This is a desir- ies surrounding the alveoli and are sen- VENTILATION/ able condition, as the greatest amount sitive to increases in pressure within the of ventilation also exists in the base of . When activated, these receptors PERFUSION RATIO the lungs. stimulate rapid, shallow respiration. The ventilation/perfusion (V/Q) ratio The V/Q ratio is never at an ideal state describes the dynamic relationship in any zones of the lungs. In the apexes, between the amount of ventilation in the amount of available ventilation in the SPECIALIZED the alveoli and the amount of perfusion alveoli exceeds the amount of perfusion RESPIRATORY through the alveolar . This rela- through the pulmonary capillaries; that CENTERS IN tionship determines the quality of gas is, more oxygen is available in the alveoli exchange across the alveolar–capillary than the supply of blood is able to pick THE BRAIN membrane, which in turn determines the up and transport. This is considered to The brainstem contains four respiratory amount of oxygen entering the blood and be wasted ventilation. In the bases, the control centers: the dorsal respiratory CO2 offloading from the blood. This rela- amount of perfusion exceeds the amount group, the ventral respiratory group, the tionship can be used to explain the etiol- of ventilation; this means more blood is apneustic center, and the pneumotoxic ogy of . moving through the pulmonary capillar- center. These centers stimulate the respi- In the ideal lung, each alveolus would ies than there is alveolar oxygen avail- able for it to pick up. ratory muscles to either contract or relax, receive an adequate amount of ventila- The bases depending on the impulse. tion and a matching amount of blood flow This is considered to The dorsal respiratory group (DRG) is through the surrounding capillary, result- be wasted perfusion. of the lungs responsible for setting the basic rhythm ing in a V/Q ratio of 1—that is, ventilation Overall, under nor- receive of respiration. It consists of inspiratory and perfusion are equal. This ideal condi- mal conditions, per- neurons that send nerve impulses to the tion never exists, though, because of the fusion exceeds the a greater external intercostal muscles and dia- effects of gravity on blood flow, the struc- amount of available amount of phragm, stimulating them to contract, ture of the lungs, and shunting of blood. ventilation. blood and are which results in inspiration. The DRG is When a person is in a standing posi- active in every respiratory cycle, whether tion, gravity pulls the lungs downward Pressure much better breathing is quiet or forced. In a typi- toward the diaphragm, compressing the Imbalances perfused than cal respiratory cycle, the DRG stimulates lower lobes. As the lower lobes are com- The perfusion of blood the respiratory muscles to contract for pressed and blood is pulled down to the through the pulmonary the apexes.

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the bronchioles to improve airflow. This treatment would not only increase the ABamount of air in the alveoli, Bronchiole but it would also increase Respiratory the of oxygen in the alveolar air, making bronchiole Smooth muscle more oxygen available for Elastin fi bers the blood moving through the pulmonary capillaries. This would reduce or elimi- Capillaries nate the hypoxemia and cellular hypoxia.

Alveoli Perfusion Disturbances

Alveoli A perfusion disturbance may (air sacs) also lead to severe cellular hypoxia. Consider a patient Figure 7-2 Perfusion of the pulmonary capillaries is affected by pressure within the alveoli and you encounter who has cut pressure within the capillaries. his radial artery on a saw and suffered severe blood loss. The patient has no chest or lung injury capillaries is affected by the amount of air to hypoxia. If a condition or injury causes and has an increased rate and depth of and pressure inside the alveoli and the less oxygenated air to be available in the ventilation. His and pressure of the blood flowing through the alveoli for the amount of blood flowing alveolar ventilation are increased; how- capillary bed ( Figure 7-2 ). If the pressure through the pulmonary capillaries, the ever, his cells are becoming hypoxic. in an alveolus exceeds the hydrostatic pres- end result will be less oxygen saturating Although he is moving more oxygenated sure of blood in the capillary bed, blood the blood and less oxygen delivered to air into the alveoli, his blood loss has sig- flow through the capillary stops. This is the cells, creating hypoxemia and cellu- nificantly reduced the amount of blood most likely to occur in the apexes of the lar hypoxia. flow through the pulmonary capillaries. lungs, where the pressure inside the alve- For example, if a patient is having an This represents a perfusion disturbance oli is highest and the blood flow is lowest. asthma attack and the bronchioles are because there is not enough blood to However, it may also occur in the patient inflamed and constricted, the restricted pick up the oxygen available in the alveoli. who is losing blood from an injury and has airways reduce airflow and provide This would create a state of wasted venti- a decreasing . less oxygenated air to the alveoli for lation, hypoxemia, and cellular hypoxia. A decrease in the systemic blood pres- gas exchange. The blood pressure is By placing the patient on oxygen, sure will also cause the pressure in the not affected; therefore, the amount of you might reduce some of the cellular pulmonary capillaries to decrease. If the blood passing through the pulmonary hypoxia; however, it will not be elimi- patient does not have a chest or lung capillaries remains normal. A ventilation nated until the perfusion disturbance is injury, the lungs will continue to receive disturbance has been created by mak- fixed. The bleeding must be stopped, adequate volumes of air, creating ade- ing less oxygen available to the blood and this patient needs to receive fluid quate pressure in the alveoli. However, passing through the capillaries. In this and blood to increase the flow and the reduction in blood pressure may allow condition, there is wasted perfusion, pressure in the pulmonary capillaries so the alveolar pressure to exceed the pul- as the blood is available but there is enough hemoglobin is available for oxy- monary capillary pressure and impede an inadequate amount of oxygen to be gen in the alveoli to attach to and be blood flow. This will result in poor alveolar picked up. This disturbance in ventila- transported to the cells. perfusion, hypoxemia (reduced oxygen tion leads to hypoxemia and cellular Hypoxia generally results from a ven- in the blood), and cellular hypoxia. tilation or perfusion disturbance. Myriad hypoxia (oxygen defi- In the situation just described, in conditions can cause one of these dis- ciency in the cells). which an asthma attack has caused a turbances to occur. The management Hypoxia gen- ventilatory disturbance, the ventilation of hypoxia resulting from a ventilatory erally results side of the ventilation/perfusion ratio disturbance should focus on improving Ventilatory from a venti- must be improved by relieving the bron- ventilation and oxygenation. Managing Disturbances chiole airway restriction and increasing a disturbance in perfusion must focus lation or A disturbance on the the amount of oxygenated air entering on increasing blood flow through the perfusion ventilation side of the alveoli. An EMT would achieve this pulmonary capillaries, the availability of the ventilation/per- by placing the patient on oxygen and hemoglobin, and delivery of oxygen to disturbance. fusion ratio can lead administering a medication to dilate the cells.

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TRANSPORT OF to 3 percent, is dissolved in plasma. The dissolved in plasma, 23 percent is attached majority of oxygen, approximately 97 per- to hemoglobin, and 70 percent is in the OXYGEN AND CARBON cent to 98.5 percent, is attached to hemo- form of bicarbonate. DIOXIDE IN THE BLOOD globin molecules. As CO 2 leaves the cells, it crosses over Oxygen must be continuously delivered Hemoglobin is a protein molecule that into the capillaries, where a small amount by the blood to the cells for normal cellu- has four iron sites to which oxygen can dissolves into the plasma. A larger lar to occur. Carbon dioxide, bind. Thus, one hemoglobin molecule amount of CO2 attaches to hemoglobin. a byproduct of aerobic metabolism, must could carry up to four oxygen molecules. The largest amount of CO2 diffuses into be carried back to the lungs to be elimi- If one oxygen molecule is attached to the the red blood cells and combines with nated during exhalation. A disturbance in hemoglobin molecule, it is considered to water to form H2 CO3 , which then dissoci- the transport system may lead to both cel- have 25 percent saturation. Attachment of ates into hydrogen and bicarbonate. The lular hypoxia (a lack of oxygen available two oxygen molecules would be consid- bicarbonate exits the cell and is trans- to the cells) and hypercarbia (a buildup ered 50 percent saturation, three molecules ported in the blood plasma. When the of carbon dioxide in the blood). Both 75 percent saturation, and four molecules blood reaches the , hypoxia and hypercarbia pose problems 100 percent saturation. The attachment the bicarbonate diffuses back into the for normal cellular function and stability. of one oxygen molecule to a hemoglobin red blood cell, where it combines with Both oxygen and carbon dioxide are iron-binding site will increase the affinity for hydrogen and splits back into water and transported by the blood but in differ- the other sites to also bind with oxygen. carbon dioxide. Regardless of the trans- ent ways ( Figure 7-3 ). It is important to Once an oxygen molecule binds port mechanism, the carbon dioxide dif- remember that oxygen and carbon diox- with hemoglobin, the hemoglobin mol- fuses into the alveoli, which are low in ide move from areas of higher concentra- ecule is referred to as oxyhemoglobin . CO 2 concentration, and is eliminated tion to areas of lower concentration. This A hemoglobin molecule that has no oxy- during exhalation. helps to explain the movement of gas gen attached is referred to as deoxy- molecules between alveoli and capillaries hemoglobin . Without hemoglobin, the Alveolar/Capillary and between capillaries and cells. negligible amount of oxygen that can Gas Exchange A pulmonary is another be transported by plasma would not be After inhalation, the alveoli are filled with example of a common perfusion distur- enough to sustain normal cellular func- oxygen-rich air that contains very little bance in which blood flow to a portion of tion or . A loss of hemoglobin, which carbon dioxide. Conversely, the venous the lung is physically blocked. commonly occurs as a result of bleeding, can easily lead to severe cellular hypoxia, blood that flows through the capillar- ies surrounding the alveoli contains low Oxygen Transport even though an adequate amount of oxy- gen is available in the alveoli. levels of oxygen and higher amounts of Approximately 1000 mL of oxygen is deliv- carbon dioxide. ered to the cells every minute. Oxygen is Because gas molecules naturally move transported by the blood in two ways: dis- Carbon Dioxide Transport from an area of high concentration to an solved in plasma and attached to hemo- Carbon dioxide is transported in the blood area of low concentration, the high oxy- globin. A small amount, only 1.5 percent in three ways: Approximately 7 percent is gen content in the alveoli moves across

O2 Transport 97% attached to hemoglobin 3% dissolved in plasma

Red blood cells with hemoglobin Gas exchange LUNGS BLOOD Gas exchange TISSUES at lungs at tissues Plasma

CO2 Transport 70% bicarbonate 23% attached to hemoglobin 7% dissolved in plasma

Figure 7-3 Oxygen is transported in the blood in two ways: attached to hemoglobin and dissolved in plasma. Carbon dioxide is transported in the blood in three ways: as bicarbonate, attached to hemoglobin, and dissolved in plasma.

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Pulmonary capillary External respiration

CO2 Alveolus Pulmonary circuit

O2

Internal respiration

O2 Body Systemic circuit cells CO2

Interstitial fl uid Systemic capillary

Figure 7-4 Overview of ventilation and perfusion.

the membranes and into the capillaries, from which it is ejected into the aorta and the cell and crosses over into the capil- where the oxygen content is very low to the throughout the body. This lary, where it dissolves in the plasma, ( Figure 7-4 ) There, as described ear- blood that is circulating throughout the attaches to hemoglobin, or enters the lier, a small amount of oxygen dissolves in body will be used in the cell/capillary gas red blood cell to be converted to bicar- the plasma and a larger amount attaches exchange described next. bonate ( Figure 7-4). to the hemoglobin. Simultaneously, CO 2 As the blood leaves the capillary, it moves in the opposite direction, from the enters a small venule, from which it is high levels contained in the capillaries Cell/Capillary Gas Exchange eventually dumped into a larger vein. into the alveoli, where the CO 2 content The blood that was ejected from the The blood in the venules and veins is low. It happens this way: The bicarbo- left into the arteries contains contains low concentrations of oxygen nate ions in the blood convert to water high concentrations of oxygen and low and high concentrations of CO 2 . This and CO2 ; additional CO2 diffuses out of concentrations of CO2 . This blood trav- CO2-carrying blood is transported the plasma and offloads from the hemo- els through an artery and then enters a to the right atrium of the heart, from globin; and all this CO 2 crosses from the smaller that leads to a capillary which it enters the right ventricle and capillaries into the alveoli. bed that is surrounded by cells. Dur- is pumped to the lungs. There, the After these exchanges—from alveoli to ing cell metabolism, the cells have used blood enters the pulmonary capillaries capillaries and from capillaries to alveoli— oxygen and produced carbon dioxide to give off CO2 and pick up oxygen in the alveoli contain low levels of oxygen as a byproduct. Thus, whereas the cap- the alveolar/capillary gas exchange, as and high levels of CO 2 , whereas the blood illary beds contain blood that is high in described earlier. in the capillaries contains high levels of oxygen and low in CO2 , the cells con- For the cells to receive an adequate oxygen and low levels of CO 2 . Basically, tain low levels of oxygen and high levels amount of oxygen and eliminate CO 2, the gases have switched concentrations. of CO2 . both the alveolar/capillary gas exchange The CO2-rich air in the alveoli is exhaled As the blood enters the capillary, and cell/capillary gas exchange must from the lungs. The oxygen-rich blood oxygen breaks free of the hemoglobin be functioning properly. A disturbance in the capillaries is transported from the and diffuses out of the plasma, crosses in either will result in either inadequate pulmonary circulation to the left atrium the capillary membrane, and enters amounts of oxygen being delivered to and then to the left ventricle of the heart, the cell. Simultaneously, CO 2 leaves the cells or the accumulation of CO 2 .

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REVIEW ITEMS Circle the correct answer.

1. An increase in the level of carbon dioxide in the arterial blood c. VRG E will result in ______. d. pneumotaxic center a. a decrease in the respiratory 4. Hypoxia associated with an acute asthma attack would likely b. a decrease in the number of hydrogen ions result from ______. c. an increase in the a. a ventilation disturbance d. an increase in bicarbonate b. an upper airway occlusion 2. Increasing the oxygen content in the arterial blood in a patient c. a perfusion disturbance breathing on a hypoxic drive will possibly lead to ______. d. chemoreceptor dysfunction a. stimulation of the central chemoreceptors 5. The primary method of transport of carbon dioxide in the b. a decrease in the rate and depth of respiration blood is ______. c. an increase in the amount of carbonic acid a. dissolved in plasma d. collection of hydrogen ions in the CSF b. attached to hemoglobin 3. A patient presents with use of the sternocleidomastoid muscle c. as carbonic acid and retractions during respiration. You would suspect that d. in the form of bicarbonate which of the following respiratory centers is providing respiratory muscle stimulation? a. DRG

b. VRG I

APPLIED PATHOPHYSIOLOGY Write your answers in the spaces provided. 1. Explain how the central chemoreceptors regulate the rate and 4. Explain a normal respiratory cycle based on activity of the DRG. depth of respiration.

5. Explain the respiratory cycle in forced breathing based on activ- 2. Explain how the peripheral chemoreceptors regulate the rate and ity of the VRG. depth of respiration.

3. Describe how admonition of a high concentration of oxygen in 6. Explain hypoxia based on the ventilation/perfusion ratio. a patient with a hypoxic drive may lead to respiratory depression and failure.

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7. Explain how a ventilation disturbance would lead to hypoxia. 10. Explain three ways carbon dioxide is transported in the blood.

8. Explain how a perfusion disturbance would lead to hypoxia. 11. Explain gas exchange at the alveolar/capillary level.

9. Explain two ways oxygen is transported in the blood. 12. Explain gas exchange at the /capillary level.

CLINICAL DECISION MAKING Write your answers in the spaces provided. You arrive on the scene and find a 28-year-old female patient who was 4. Would the hypoxia be related to a ventilation or perfusion distur- shot in the chest. The patient complains that he is struggling to breathe. bance? His airway is open, and his respirations are rapid. His is pale, cool, and clammy, and he is exhibiting circumoral cyanosis. His SpO2 read- ing is 76 percent on room air. 1. Following scene safety, what is your first immediate action after approaching this patient?

5. Based on stimulation of the chemoreceptors, what is causing an increase in the respiratory rate?

2. What are the life threats to this patient?

3. What do you suspect is causing the cyanosis and poor SpO2 reading?

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