Regulation of Respiration 2024-2025 Lecture Notes (PDF)

Block 1.3 lectures 2024-2025 lecture Highlighter key Writer Reviewer...

Block 1.3 lectures 2024-2025 lecture Highlighter key Writer Reviewer Doctor explanation Abbreviation Key information Book >> >> Fatimah Adnan Al-Zahraa Marai Al-khamis Student explaintion 221-222-223 notes References Deleted Al-Shakhs  12/31/2024 Regulation of Respiration Dr.TarekBENAMEUR Department of Biomedical Sciences College of Medicine King Faisal University Learning Objectives What is the anatomical location of the chemoreceptors sensitive to changes in arterial PO2, PCO2 & pH that participate in the control of ventilation? Which chemoreceptor population is the most important for sensing short-term (acute) & long-term (chronic) alterations in blood gases? What changes occur in alveolar ventilation immediately upon ascent to high altitude? After remaining at high altitude for two weeks? & immediately upon return to sea level? What is the relevance of the feed forward control of ventilation during exercise? What effects does exercise have on arterial and mixed venous PCO2, PO2 & pH ? Describe the interaction between hypoxia and hypercapnia in the control of alveolar ventilation. What are the main four causes of hypoxemia? 1  12/31/2024 Brainstorming… when you hear the regulation of Respiration respiration what come for your mind ? Expiration Alveolar ventilation Inspiration Hypoxemia Hypoxia Hypoventilation Hyperventilation Hypercapnia Acclimatization General Definitions due to low hemoglobin concentration Hypercapnia elevation in the partial pressure of CO2(PaCO2) above 45 mm Hg 2  12/31/2024 Ventilation Mechanical process that moves air in & outofthe lungs. Don’t forget the information that mentioned in the VENTILATION LUCTURE and other previous lectures which include ( elastic recoil, capacity of the lung expan , lung expansion & contraction , The increasing & decreasing the volume) [O2]of air Is higher in the lungs thin in the blood ,O2 diffuses from air to the blood. CO2moves from the blood to the air by diffusing down its concentration gradient. Gas exchange occurs entirely by diffusion. partial pressure of the air (atmospheric air) more than in the lungs 🫁 and that’s why the oxygen has the ability to get inside the lungs and this is varied also between the alveoli & systematic circulation partial pressure of oxygen in the alveoli GREATER than the partial pressure of oxygen in the blood Gas always diffuse with great partial pressures. without Great partial pressure the gases cannot move Hyper-and Hypoventilation You may find other definitions but , what’s important for us are these definitions here. Hyperventilation: Greater ventilation than needed to maintain PaCO2at the normal level ⇒PaCO2< 40 mmHg Hypoventilation: Less ventilation than needed to maintain PaCO2at its normal level ⇒PaCO2>40 mmHg 3  12/31/2024 Components of Respiratory Regulation we already need different factors for we have the effecors which execute the signals Voluntary, emotions etc. respiratory regulation transmitted by control centers of this respiration. these factors are Higher brain centers We have the central controller which localised in the 1-stimulus pons , medulla oblongata and other parts of the brain 2-sensors which are responsible of regulating the respiration 3-effector 4-control centers Central controller Pons, medulla, other parts input of brain output Stimulus Sensors Effectors - E.g increase the level of Central & peripheral Respiratory muscles CO2 in the systemic chemoreceptors, circulation, low oxygen Stretch receptors, etc. level , low PaO2 Sensors send input to the central controller, which outputs signals to the effectors to adjust breathing as needed. Once reaching homeostasis, this will be observed as stable respiratory rates, providing feedback that allows the sensors to stop sending messages to the central controller. This reduction in signaling helps prevent overcorrection and maintains a balanced state in the respiratory system. sensors Same principle of the air conditioner Respiratory Center Respiratory Regulation Factors 1. Stimulus: - Triggers changes in breathing. - Examples: Increased CO2 levels, decreased O2 levels, changes in blood pH. thermistor ( Temperature scale) works as a sensor 2. Sensors thermostat & compressor work as control centre 1. Central Chemoreceptors: Detect and pH changes in cerebrospinal fluid. -Example: Increased (hypercapnia) triggers faster, deeper breathing. For example : 2. Peripheral Chemoreceptors: Detect pH changes in blood. the compressor will start working once the temperature - Example: Decreased (hypoxemia) stimulates increased breathing. increase into 35 C , after reaching the 35 C the negative 3. Mechanoreceptors: Respond to lung stretch and airway irritation. feedback mechanism will send the message to the control - Example: Limit overinflation during deep breaths (Hering-Breuer reflex). centere to stop now because of reaching the target. This is Dorsaland maintain homeostasis. Function: Ensure balanced gas exchange Ventral varying from physiology of human beings because human Pneumotaxic Respiratory respiratory has different types of sensors which include ( central center (PRG) Group (DRG) 3. Effector: group (VRG) receptors , peripheral receptors , chemoreceptors and other - Components that respond to the stimulus. receptors we will discuss them in more details - Examples: - Respiratory Muscles (diaphragm, intercostal muscles) adjust breathing rate and depth. 4. Control Centers: - Brain regions coordinating responses to stimuli. - Examples: - Medulla Oblongata: Controls the rhythm of breathing. - Pons: Regulates transitions between inhalation and exhalation. These factors work together to maintain homeostasis in the body's respiratory function. 4  12/31/2024 Components of Respiratory Regulation Brain higher centers, which are involved in golden voluntary actions, promote praise and are also responsible for various control mechanisms what does this matter to us ? The respiratory center - What is the respiratory center ? The respiratory center: is a group of brain regions, primarily located in the medulla oblongata and pons that control the rhythm and rate of breathing. It integrates information from chemoreceptors that monitor levels of oxygen (O2), carbon dioxide (CO2), and blood pH, adjusting breathing patterns to maintain homeostasis. The medulla generates the basic rhythm, while the pons regulates transitions between inhalation and exhalation.. Respiratory Center Composed of several groups of neuronsin the medulla oblongata & ponsof the brain stem. Divided into three major collections of neurons : Respiratory center Dorsal Ventral *PRG: pontine respiratory group Pneumotaxic Respiratory respiratory center (PRG) Group (DRG) group (VRG) Inspiration is active process which means it needs energy , it is leading to Controls rate & the contraction of the muscles Mainly causes Mainly depth of (diaphragm, intercostal inspiration expiration breathing muscles) expiration is a passive process 4  12/31/2024 Respiratory Center Dorsal Respiratory Most of DRGneurons are located within the NTS Group (DRG) Nucleus tractus NTS : sensory termination of vagus (CNX) & solitarius (NTS) glossopharyngeal nerves (CNIX) (CNX) : cranial nerve X (10) (CNX) : cranial nerve IX (9) VRGhas multiple functional areas: Ventral respiratory e.g. Pre-Bötzingercomplex: rhythm generating group (VRG) neurons Here we can see that how all these rhythms are sync with each other and how they the picture shows you the direct effects of transmitted through the cranial these different groups of neurons. nerves to the different effectors we can see the pneumotaxic center has an inhibitory effect on the Apneustic center VRG responsible for contraction of the which has a stimulatory effect internal intercostal muscles while DRG responsible for contraction of the Apneustic center : affect (DRG &VRG) by external intercostal muscles. In addition, stimulatory effects (stimulatory pathway ) DRG responsible for contraction of the However , the VRG is not directly affected diaphragm because it connects to the by this center but when the Apneustic phrenic nerve all of there happen during center stimulates the DRG ,the DRG will inhalation stimulates the VRG Regulation of Respiration-Respiratory Center VRG only active during This showing the intense ventilation- patterns of these mainly expiratory MNs (motor neurons) pathways how these Voluntary control Pneumotaxic center can override the groups of neurons induce (limits duration of inspiration) respiratory centers inspiratory muscles for - Inspiration & expiration the DRG and directly to inspiration the expiratory muscles depending on the either Pneumotaxic center (PRG)”, acts as an“off” it is quite breathing or switch controlling the In/expiratory MNs forceful breathing point at which in spinal cord inspiration is The capacity of breathing can terminated and affect which effects are controls the depth & responsible for increase or rate of breathing. decrease the ventilation. 5  12/31/2024 Regulation of Respiration-Respiratory Center the lungs expand and return to the original size due to the elastic tissue fibers , there fibers has a low capacity to expand (stretch) (b) During forceful breathing remember this when you read elastic tissue fibers Receptors They also called sensors why they called chemo-receptors?  Answer : because they are detecting Chemoreceptors chemicals -Central chemoreceptors Baroreceptors : the receptors detect the -Peripheral chemoreceptors changes is the blood pressure  Other receptors Baro ——> refers to the pressure -stretch receptors: Hering-Breuer this receptor is important , it prevents Doctor said : all of them are important but reflex -joint and muscle receptors - the inflation of the lungs to protect we will not go in details , we nociceptors -irritant receptors - them in the case of inflation. will just discuss the types of temperature receptors chemoreceptors. 6  12/31/2024 Chemoreceptors Peripheral chemoreceptors -found in major blood vessels aortic bodies -signals medulla by vagusnerve (CNX) carotid bodies -signals medulla by glossopharyngeal nerve (CN IX) Central chemoreceptors - in medulla Peripheral Chemoreceptors (PCR) High amount of the Stimulated by: CO2 Arterial hypoxia Hypercapnia High concentration Acidity (H+) of hydrogen ions Strongly vascularized ➙ superfast!! Extremely high blood flow ⇒sensing of acute alterations characteristics of the prepheral chemoreceptors 1/ superfast (because it is strongly vascularized) 2/sensing of a cute alteration in O2 & CO2 & PH level ( because it is extremely high blood flow) ⇒Response to high CO 2by Central chemoreceptor is greaterthan peripheral chemoreceptor 7  12/31/2024 Central Chemoreceptors (CCR) keep this slide in your mind It is very important to know the central Located under the ventral side of the medulla chemoreceptors are not located inside the medulla Stimulated by : -Arterial Hypercapnia : -CCR : highly sensitive to CO₂, which crosses BBB & reacts with H2Oto form H2CO3 which dissociates into H⁺ ⇒↑ H⁺directly stimulates CCR -Plasma acidity: -Plasma H⁺ have minimal direct effect (little H+ crosses BBB). -Changes in plasma acidity, play a limited role in stimulating CCR -Little Sensitivity to O₂: -CCR are not sensitive to PaO₂. *CA= carbonic anhydrase Hypoxemia is detected by peripheral CR in the carotid & aortic bodies. 1/ Once PCO2 increase , the CO2 has a capacity to cross the CCR monitor CO2in CSF. cerebral capillaries. CCR : central chemoreceptors 2/ once it crosses the cerebral capillaries( the cerebrospinal CFS : cerebrospinal fluid fluid which is one of the components that is responsible for protecting the body) the CO2 will react with water (H2O) to produce the carbonic what is the CA ( carbonic anhydrase ) & why it is acid (H2CO3) important? and that is similar to what are we discussing in (GAS Answer : TRANSPORT 1 LUCTURE) Carbonic anhydrase (CA) is an enzyme that catalyzes 3/ once the carbonic acid is form , it will dissociate in term the reversible conversion of carbon dioxide (CO₂) and into H+ (hydrogen ions ) & HCO3 - (bicarbonate ions ) water (H₂O) into carbonic acid (H₂CO₃), which can in the presence of carbonic anhydrase( CA) further dissociate into bicarbonate (HCO₃⁻) and hydrogen ions (H⁺). 4/it is important because it will remove the (CO2) out of 5/ the central chemoreceptors will detect the increase level of the blood which is toxic &harmful (why toxic ?) H+&CO2 because it will react With water (H2O) to make H2CO3 6/ once the central chemoreceptors detect there changes , they will carbonic acid which dissociates into HCO3- &H+, once send signals to the respiratory control centers ( because the needed the H+ increase the PH will be decreased and leading for immediate action. to the acidity of the plasma or blood , this acidity will 7/ the response will be ( increase ventilation ) respiratory rate will affect many different organs. be increased and the parts which are responsible for ventilation are 🫁 lungs , precisely in the muscles include (diaphragm & intercostal muscles) 8  12/31/2024 Describe the interaction between Hypoxia and Hypercapnia in the control of alveolar ventilation. Main control by CO2 1/ one arterial PCO2 Increase 2/increase PCO2 lead to decrease PH level in CSF due to increase the concentration of H+ 3/ these changes will be sensed by chemoreceptors in the medulla oblongata (central 70% & prepheral 30%) Negative both chemoreceptors are important but feedback more important chemoreceptors (central ) - 4/ the chemoreceptors will send the signals to the Medullaray respiratory centers 5/ Medullary respiratory centers will send a signals to the respiratory muscles. 6/ respiratory muscle will respond by increasing ventilation and removing the CO2 via the exhalation process. 7/ after all these the Arterial PCO2 and PH will return to normal. ⇑ PO2 Normal IncreaseDiffusion of gases Hypoxia across theResp.Membrane Peripheral chemoreceptor Increasein Rate&Depth stimulated of Respiration Afferent nerves carry signal Increased activity of reps. to brainstem centers Muscles Respiratory center Stimulated Efferent impulses cometary Phrenic and intercostal 9  12/31/2024 Chemoreceptor Response to Changes in Plasma CO2 1.Central Chemoreceptors: Stimulated by: Increased levels of carbon dioxide (PCO₂) and hydrogen ions (H⁺) in the cerebrospinal fluid (CSF). 2.Peripheral Chemoreceptors: Stimulated by: Decreased levels of oxygen (PO₂) in the arterial blood, specifically when PO₂ drops below 60 mm Hg. ⇑ Inspired PO2 Return of alveolar & arterialPO2toward normal ⇑ Alveolar PO2 ⇑ Ventilation ⇑ Arterial PO2 Peripheral Chemoreceptors Repiratory Muscles ⇑ Firing ⇑ Contractions 10  12/31/2024 Reflex control of Ventilation we have mentioned most of things in previous slides , the additional stimulus here is emotions and voluntary control what are the particular conditions you can see the hyperventilation? crying , excersice, fear ,fight or flight Chemical Signal in CNS The levels of what chemicals are going to control respiration? CO2 H+ ions andO2. IntheCNS,CO2 andH+ are particularly important. O2 has angreater effect in the PNS.  In the chemosensitiveareas of the respiratory center, increased H+is themain stimulus. *PNS: peripheral nervous system 11  12/31/2024 Why then, does activation of central chemoreceptor occur mainly after a rise in peripheral CO2, but not so much with peripheral H+? Theblood-brain barrier is not very permeable toH+;however,CO2 easily diffuses across the BBB(asusual). IncreasedCO 2can cause increasesinH. + So, once CO2 diffuses into the chemosensitive regions of theCNS, H+is formed and stimulates the dorsal group(DRG). Influence of Chemical Factors on Respiration 12  12/31/2024 Effect of PCO2& plasma pH on Ventilation pH Note that an acute change in Pco2 has a greater effect on alveolar ventilation than a chronic change  The marked ⇑ ventilation caused by ⇑ Pco2 in the normal range 35 -75 mm Hg, which demonstrates the tremendous effect that CO2 changes have in controlling respiration. Effect of arterial PO2 on Ventilation Arterial PO2> 100 mm Hg ⇒No effect on ventilation Arterial PO2=60 mm Hg ⇒ventilation (2x) Through the respiratory control centers At very low arterial PO2—> ventilation (5x) ⇒low arterial PO2 drives ventilation strongly For example , arterial PO2 = 20 , the ventilation here is Hypoxic threshold 5 times more than normal Normal 13  12/31/2024 Respiration During Exercise It depends in the type of excercise and the capacity of During exercise: O2consumption&CO2formationcan ventilation ⇑20-fold. What happens to the partial pressures of O2 and CO2in the blood? - Arterial PO2, PCO2, and pH remain almost exactly normal. - This can occur if the ventilation⇑ in proportiontothe ⇑ in O2 consumption & CO2 production. Doctor mention this slide from ( GAS TRANSPORT 1) lucture and asked about the curve will shift to which site during excercise ? the answer is right Alveolar Ventilation & ArterialPCO2During Exercise At the onset of exercise: important ⇑ Alveolar ventilation —> arterial PCO2 , why ? ⇑ prevent something before it happens like when I avoid walking next to a hole to not fall in it. Because : brain provides an anticipatory stimulation of respiration at onset of exercise increasing ventilation before it is necessary. After30 sec, CO2 is releasedinto blood from active muscles and matches the ⇑ventilation ⇒The arterial PCO2returns to normal 14  12/31/2024 Respiration During Exercise What causes increased ventilation during exercise ? Chemical : no change -Collateral impulses into the brain stem to excite the respiratory center -Excitation of proprioceptors in joints and muscles-excitation of respiratory center (passive movement and severed nerves) Hypoxic muscles, variations in PO2, PCO2 Effect of High Altitude on alveolar PO2 Sea level. 1. At Sea Level (0 ft): - High barometric pressure results in high partial pressure of oxygen (P₀₂) in both air and alveoli. when altitude increase the - Arterial oxygen saturation is nearly 100%. barometric pressure, PO2 , breathing air will decrease. 2. As Altitude Increases: ‫كل ما زاد االرتفاع عن مستوى سطح البحر‬ - Barometric pressure and P₀₂ decrease. ‫ قل الضغط‬. - Partial pressure of oxygen in the alveoli drops, leading to lower arterial oxygen saturation. without this response of respiratory centers from our body , we will die. 3. Breathing Pure Oxygen: - At high altitudes, breathing pure oxygen maintains arterial oxygen saturation at or near 100%, despite lower atmospheric pressure. 15  12/31/2024 Ventilation at high altitudes Barometric(atmospheric)pressure is-lower; - When PaO2 is < 60 mm Hg, ventilation is ⇑ What happenstoPaCO 2? - it is lowered as a result of hyperventilation What happens to PH of arterial blood? - pH increases slightly from 7.4 to 7.45 Arterial blood gases:Hypoxemia(lowPaO 2); hypocapnia (PaCO2 < 35 mm Hg); -respiratory alkalosis (pH > 7.45 because of hypocapnia) Ventilation at high altitude Acute reaction: Ventilation ⇑, because P iO2⇓(and therefore PaO2 ) ⇓ Therefore PCO2⇓ Arterial pH⇑(peripheral chemoreceptors) Ventilation ⇓ CSF pH ⇑(central chemoreceptors) Acclimatization ? Ventilation ⇑⇑, because : -HCO-3excretion by kidneys ⇑, so pH ⇓ -lower threshold PaCO2stimulus, because central chemoreceptors become less sensitive * PIO2Partial Pressure of Inspired Oxygen 16  12/31/2024 Acclimatization to Low PO2 (High altitude) The principle means of acclimatisation in high altitude: Increased pulmonary ventilation. Increased RBCs synthesis (EPO) due to chronic hypoxia.Increased diffusing capacity of the lungs. Increased vascularity of the tissues. Increased ability of the cells to utilize O2despite the low PO2 through increased number of mitochondria and oxidative enzymes activity. Main causes of Hypoxemia 17  12/31/2024 Summary Summary Respiratory control resides in networks of neurons in the medulla & pons, influenced by : central & peripheral sensory receptors & higher brain centers DRG contains mostly inspiratory neurons that control somatic motor neurons to the diaphragm. VRG with its pacemakers and neurons for inspiration & active expiration. Peripheral chemoreceptors in the carotid & aortic bodies monitor PO2, PCO2, & pH.PO2