http://www.rci.rutgers.edu/~uzwiak/AnatPhys/Respira tory_System.html Respiration I. Background A. Function 1. Supply body with oxygen and dispose of carbon dioxide B. Processes 1.

Pulmonary ventilation a. Moving air in and out of lungs 2. External respiration a. Gas exchange between blood and chambers of lungs 3. Transport of respiratory gases a. Gases must be transported between lungs and tissue cells of the body i. Accomplished by cardiovascular system 4. Internal respiration a. Gas exchanges between blood and tissue cells II. Anatomy of the Respiratory System

A. Organs 1. Nose 2. Nasal cavity 3. Pharynx 4. Larynx 5. Trachea 6. Bronchi 7. Lungs a. Alveoli B. Respiratory zone 1. Site of gas exchange a. Respiratory bronchioles b. Alveolar ducts c. Alveoli d. Microscopic structures C. Conducting zone 1. Conduits that provide air to reach respiratory zone a. Warm, filter and humidify air III. Organs of the Respiratory System A. Nose and paranasal sinuses

1. Functions a. Airway for respiration b. Moistens and warms air c. Filters air i. Removes foreign matter d. Resonating chamber for speech e. Houses olfactory receptors 2. External nose a. Root and bridge b. Dorsum nasi c. Apex d. Philtrum e. External nares (nostrils) f. Alae 3. Nasal cavity a. Divided by nasal septum b. Air enters through external nares c. Continuous with nasal portion of pharynx 4. Vestibule a. Cavity superior to nostrils b. Glands i. Sebaceous and sweat c. Hair follicles i. Filter course particles 5. Remaining nasal cavity is lined with mucous membranes a. Olfactory mucous (see Sensory Lecture) b. Respiratory mucous 6. Respiratory mucous a. Pseudostratified ciliated columnar epithelium b. Mucous and serous glands i. Mucous cells secrete mucous ii. Serous cells secrete enzyme laden watery fluid c. Mucous contains lysozyme i. Antibacterial enzyme d. Ciliated cells create current that moves mucous toward pharynx i. Swallowed and digested 7. Paranasal sinuses a. Located in frontal, sphenoid, ethmoid, and maxillary bones b. Connected to nasal cavity by small openings c. Produce mucous that drains into nasal cavity d. Warm and moisten air B. Pharynx 1. Connects mouth and nasal cavity to the larynx and esophagus 2. Common pathway for food and air 3. Three regions a. Nasopharynx b. Oropharynx c. Laryngopharynx 4. Nasopharynx a. Serves as only an air passage b. During swallowing uvula closes off nasopharynx to prevent from entering the nasal cavity c. Opening of the auditory tube (eustachian tube) d. Lymphatic tissue i. Pharyngeal tonsils (adenoids) 5. Oropharynx a. Continuous with the oral cavity i. Fauces b. More stratified squamous epithelium i. Protects against friction damage of food c. Lymphatic tissue i. Palatine tonsil d. Passage for air and food 6. Laryngopharynx a. Passage for air and food b. Lined with stratified squamous epithelium c. Posterior to epiglottis d. Extend to larynx i. Respiratory and digestive tracts diverge e. Larngopharynx is continuous with esophagus

i. Air passage is blocked during swallowing C. Larynx

1. Functions a. Provide an open airway b. Direct air and food into proper channels c. Voice production 2. Anatomy a. Arrangement of nine cartilages i. Thyroid2 fused; laryngeal prominence ii. Cricoid cartilage ii. Arytenoid cuneiform3 pairs iii. Corniculate cartilages3 pairs iv. Epiglottis 3. Epiglottis a. Extends from tongue to anterior edge of thyroid cartilage b. During swallowing, epiglottis is pulled superiorly i. Covers laryngeal inlet 4. Glottis

a. Layers of the tracheal wall i. Mucosa ii. Submucosa iii. Adventia b. Mucosa i. Ciliated pseudostratified columnar epithelium ii. Cilia propels particulate materials toward pharynx c. Submucosa i. Connective tissue layer ii. Seromucous glands that help produce mucous d. Connective tissue reinforced with hyaline cartilage i. Cartilage prevents the trachea from collapsing E. Bronchial tree

a. Laryngeal opening b. Involved in speech production c. Vestibular folds can cover to act as a sphincter D. Trachea 1. Descends from larynx into the mediastinum 2. Divides into two primary bronchi 3. Structure

1. Trachea divides to form right and left primary bronchi 2. Primary bronchi enter lungs 3. Inside lung, primary bronchi subdivide into secondary bronchi a. Three on right b. Two on left c. Each secondary bronchi supplies one lung lobe 4. Secondary bronchi branch into tertiary bronchi 5. Tertiary bronchi repeatedly divide, becoming progressively smaller a. 23 orders of branching passageways 6. Terms a. Bronchiole i. Air passage less than 1 mm b. Terminal bronchiole i. Smallest bronchiole ii. Less than 0.5 mm c. Respiratory tree i. Collective term for the conducting network within the lungs 7. Tissue composition of primary bronchi parallels that of the trachea 8. Composition changes as conducting tubes become smaller

a. Cartilage rings are replaced by irregular plates of cartilage i. Absent in bronchioles b. Epithelium changes (large tube toward small) i. Pseudostratified columnar ii. Columnar iii. Cuboidal iv. No cilia or mucous producing cells at and below level of bronchioles c. Amount of smooth muscle increases i. Relative amount increases as tubes become smaller ii. In combination with the absence of support structure, allows constriction F. Respiratory zone a. Walls of alveoli b. Capillary walls i. Pulmonary capillaries cover external surface of alveoli c. Basal lamina d. Gas crosses readily by simple diffuse i. Oxygen from alveolus to capillary ii. Carbon dioxide from capillary to alveolus e. Types of cells i. Type I ii. Type II f. Type I comprise the alveolar wall i. Simple squamous epithelium g. Type II i. Secrete surfactant h. Surfactant reduces surface tension (see below) G. Lungs and pleural coverings 1. Lungs a. Paired organs b. Occupies the entire thoracic cavity except the mediastinum, great vessels, esophagus, and a limited number of other organs (e.g., thymus) c. Each lung is suspended in its own pleural cavity 2. Parts of the lungs

1. Components a. Respiratory bronchioles b. Alveolar ducts i. Smooth muscle ii. Elastic and collagen fibers iii. Alveoli iv. Terminate into clusters of alveoli alveolar sacs c. Alveolar sacs i. Groups of alveoli d. Alveoli

a. Root i. Provide surface area for gas exchange e. Features of alveoli i. Surrounded by elastic fibers ii. Adjacent alveoli are connected via alveolar poresequalizes air pressure within lung iii. Alveolar macrophages eliminate pathogens (microorganisms) 2. Respiratory membranealveolar-capillary membrane i. Bronchial and vascular attachments to mediastinum b. Apex i. Superior tips ii. Deep to clavicle c. Base i. Concave surface lying on top of diaphragm d. Hilus i. Indentation through which blood vessels enter and leave ii. Bronchi also enter through hilus 3. Differences between right and left lungs a. Right is larger i. More of the heart is on the left side of midline b. Right has three lobes i. Horizontal and oblique fissures c. Left has two lobes

i. Oblique fissure only 4. Organization of lung lobes a. Bronchopulmonary segments i. Subdivision of lung lobe ii. 10 segments per lobe iii. Segments are divided by connective tissue septa iv. Each segment is serviced by its own artery and vein and receives from an unique bronchus b. Lobule i. Subdivision of lung (smaller than segment) ii. Served by a large bronchiole and its branches 5. Blood supply a. Two circulations i. Pulmonary and bronchial b. Pulmonary delivers oxygen poor blood from heart and returns oxygen rich blood to heart (see pulmonary circulation in Circulatory System Lecture) c. Bronchial arteries provide systemic blood to lung tissue 6. Pleura a. Double-layered serosa covering of lungs b. Layers i. Parietal pleura ii. Visceral (pulmonary) pleura c. Parietal covers exterior surface i. Lines thoracic wall and superior diaphragm d. Visceral covers external surface of lung e. Space between layers is fluid filled i. Permits membranes to slide during respiration ii. Surface tension prevents separation from wall of thorax (like a drop of water between two plates of glass) IV. Mechanics of Breathing

1. Described relative to atmospheric pressure 2. Atmospheric pressure a. Pressure exerted by gases around the body b. By convention, respiratory pressure is described relative to atmospheric pressure i. Negative pressure indicates pressure is lower relative to atmospheric pressure ii. Positive pressure indicates pressure is greater relative to atmospheric pressure 3. Intrapulmonary pressure (Palv) a. Pressure within alveoli b. Changes with phases of breathing c. Ultimately is equalized with atmospheric pressure 4. Intrapleural pressure (Pip) a. Always negative relative to both intrapulmonary and atmospheric pressures b. Fluctuates with phases of breathing c. Amount of pleural fluid must be at a minimum i. Lose surface tension d. Forces pulling lungs away from thorax wall (pleural membrane) i. Elasticity of lungs favor smallest dimension ii. Surface tension of alveolar fluid e. Forces pulling lungs toward thorax wall i. Elasticity of chest wall f. Forces (d and e above) result in negative Intrapleural pressure 5. Transpulmonary pressure a. Difference between intrapulmonary and intrapleural pressures b. Keeps lungs from collapsing (i.e., atelectasis) C. Pulmonary ventilation 1. Volume changes lead to pressure changes a. V1P1 = V2P2 2. Inspiration (inhalation)active process a. Depends on decreasing pressure in lungs i. Achieved by increasing lung volume ii. Inspiratory muscles change lung volume b. Inspiratory muscles i. Diaphragm ii. External intercostal muscles 3. Quiet inhalation a. Diaphragm constricts i. Moves inferiorly and flattens ii. Increases superior-inferior dimension of lungs (i.e., volume increases) b. External intercostals lift the rib cage and pull the sternum forward i. Thoracic diameter increases laterally ii. Thoracic diameter increases anteroposteriorly c. Intrapulmonary volume increases and pressure decreases i. Air rushes into lungs along pressure gradient d. Intrapleural pressure declines relative to atmospheric pressure

A. Background 1. Phases of pulmonary ventilation a. Inspiration b. Expiration B. Respiratory pressures

e. As inhalation ends, intrapulmonary and atmospheric pressures are equal 4. Deep (forced) inhalation a. Accessory muscles further increase thoracic volume i. Scalenes and sternocleidomastoid muscles of neck ii. Pectoralis muscles of chest iii. Erector spinae of back (reduce curvature of spine) 5. Expirationpassive process a. Inspiratory muscles relax i. Rib cage descends ii. Lungs recoil b. Intrapulmonary volume decreases c. Alveoli compress i. Pressure within alveoli rises above atmospheric pressure ii. Air moves along pressure gradient out of lungs 6. Forced expiration a. Abdominal wall muscles contract i. Increase abdominal cavity pressure ii. Force abdominal organs superiorly against diaphragm iii. Depress rib cage b. Other muscles may also depress rib cage and decrease thoracic volume i. Internal intercostal muscles ii. Latissimus dorsi D. Factors affecting pulmonary ventilation 1. Airway resistance a. Friction i. Nonelastic source of resistance b. Flow is inversely related to resistance (like blood flow) c. Resistance is determined by diameters of conducting tubes d. Resistance does not contribute significantly to ventilation i. No flow in areas where friction is greatest ii. Large tubes where flow is greatest e. Pathological constrictionasthma 2. Alveolar surface tension a. Surface tension i. At liquid-gas boundaries, molecules of the liquid are more strongly attracted to each other than to the gaseous molecules ii. Surface area does not readily increase iii. Liquid molecules are drawn tightly together to reduce contact with dissimilar gas molecules b. Without modification, surface tension created by the aqueous film covering alveolar surfaces would cause the alveoli to collapse between breaths c. Surfactant reduces the cohesiveness of water molecules i. Reduces surface tension of alveolar fluid ii. Less energy is needed to expand lungs 3. Lung compliance a. Measure of lung distensibility (expandability) b. Greater compliance allows greater ease to expand c. Factors i. Elasticity of lung tissue and thoracic cage ii. Surface tension of alveoli d. Elasticity is high and surface tension is low, favors compliance e. Factors diminishing compliance i. Reduced lung resilience ii. Blocked respiratory passages iii. Reduced production of surfactant iv. Decreased thoracic cage flexibility E. Respiratory volumes

1. Types of respiratory volumes a. Tidal b. Inspiratory reserve c. Expiratory reserve d. Residual volumes 2. Tidal volume (TV) a. Volume of air moving into lungs during quiet breathing i. 500 ml is normal 3. Inspiratory reserve volume (IRV) a. Amount of air that can be forcibly inspired beyond tidal volume i. 2100 3200 ml 4. Expiratory reserve volume (ERV) a. Amount of air that can be exhaled after a tidal volume i. 1000 1200 ml 5. Residual volume (RV) a. Amount of air remaining after maximum voluntary expiration i. 1200 ml b. Amount of air to keep alveoli inflated F. Respiratory capacities 1. Types a. Inspiratory capacity b. Functional residual capacity c. Vital capacity d. Total lung capacity 2. Inspiratory capacity a. Amount of air that can be inspired after a tidal expiration i. Sum of tidal and inspiratory reserve volumes 3. Functional residual capacity (FRC) a. Sum of residual and expiratory reserve volume 4. Vital capacity (VC) a. Total amount of exchangeable air i. Sum of total, inspiratory reserve and expiratory reserve volumes ii. 80% of total lung capacity iii. 4800 ml (young males) 5. Total lung capacity (TLC) a. Sum of all lung volumes i. Sum of total, inspiratory reserve, expiratory reserve, and residual volumes ii. 6000 ml (males) G. Anatomical dead space 1. Air in conducting zone that never contributes to gas exchange in alveoli a. Approximately 150 ml (equivalent to body weight in pounds) b. Represents part of tidal volume i. 500 150 = 350 ml H. Pulmonary function tests 1. Total (minute) ventilation a. Total amount of air that flows into or out of the respiratory tract in 1 minute 2. Forced vital capacity (FVC) a. Maximum amount of gas forcibly expired following a deep breath 3. Forced expiratory volume (FEV) a. FVC as a function of time 4. Alveolar ventilation rate (AVR) a. Gases in and out of the alveoli (ml/min)

b. AVR = frequency (breaths/min) x (TV anatomical dead space) V. Gas Exchanges in the Body A. Physical properties of gases and their behavior in liquids 1. Daltons law of partial pressure a. Total pressure exerted by a mixture of gases is equal to the sum of the individual pressures exerted by each gas i. Sum of partial pressures equals total pressure of gas mixture ii. Direction of movement is dependent on the partial pressure in the two phases b. Partial pressure is proportionate to percentage in the total mixture 2. Henrys law a. Each gas in a mixture will dissolve into (and from) a liquid in proportion to its partial pressure i. Reflected in final proportion and speed that a gas dissolves b. Different gases have different solubilities i. Some gases (e.g., carbon dioxide) go into solution readily B. Alveolar gas composition 1. More CO2 and H2O, less O2 than atmosphere a. Difference reflects i. Gas exchange at lungs (CO2 out and O2 in) ii. Humidification of air by conducting passages iii. Mixing of atmospheric air and alveolar gases with each breathe C. External respirationoxygen enters and carbon dioxide leaves the blood 1. Occurs across the respiratory membrane 2. Factors affecting the movement of oxygen and carbon dioxide a. Partial pressure gradients and gas solubility b. Structure of respiratory membrane c. Functional aspects 3. Partial pressure gradients and gas solubility

5. Surface area a. In healthy lungs, surface area is immense i. 140 m2 b. Disease may drastically reduce this area (e.g., emphysema) 6. Ventilation-perfusion coupling a. For gas exchange to be efficient, perfusion of pulmonary capillaries must match alveolar conditions i. If alveolar ventilation is inadequate, terminal arterioles constrict to redirect blood flow to more highly ventilated areas ii. If alveoli are maximally ventilated, pulmonary arterioles dilate to increase blood flow into the more highly ventilated area b. Bronchiole diameter parallels CO2 levels i. Bronchioles dilate in areas with high PCO2 ii. Bronchioles constrict in areas with low PCO2 c. Poor alveolar ventilation results in low PO2and high PCO2 i. Bronchioles dilate ii. Terminal arterioles constrict d. Increased alveolar ventilation results in high PO2 and low PCO2 i. Bronchioles constrict ii. Terminal arterioles dilate D. Internal respiration 1. Reverse of external respiration processes a. Oxygen diffuses readily from blood into tissue i. PO2 in blood is 104 mm HG ii. PO2 in tissue is 40 mm HG b. Carbon dioxide readily diffuses from tissues into blood i. PCO2 in blood is 40 mm HG ii. PCO2 in tissue is 45 mm HG VI. Blood Transport of Respiratory Gases A. Oxygen is carried two ways 1. Bound to hemoglobin a. Primary mechanism of oxygen transport i. 98.5% of oxygen transport 2. Dissolved in plasma a. Only 1.5% of oxygen is carried in the dissolved form i. Oxygen does not go into solution readily B. Association and dissociation of oxygen and hemoglobin 1. Structure of hemoglobin (see Hematopoiesis Lecture) 2. Terms a. Oxyhemoglobin (HbO2)oxygen bound to hemoglobin b. Deoxyhemoglobin (HHb)hemoglobin that has released its oxygen c. Partially saturatedless than four hemoglobin hemes bound to oxygen d. Fully saturatedall four hemoglobin hemes bound to oxygen 3. Affinity increases as oxygen is serially added (loaded) to four hemoglobin polypeptide chains a. After initial oxygen molecule is bound, molecular conformation changes i. Infinity for oxygen is enhanced b. Addition of next two oxygen molecules further enhances the addition of the fourth oxygen to hemoglobin 4. Affinity decreases as oxygen is released by hemoglobin (unloaded) C. Factors affecting the rate at which hemoglobin reversibly binds or releases oxygen

a. Oxygen has a steep partial pressure gradient i. PO2 of venous blood is 40 mm Hg ii. PO2 in alveoli is 104 mm Hg iii. O2 diffuses rapidly into blood iv. PO2 of pulmonary capillary reaches equilibrium at 104 mm Hg within 0.25 s b. Carbon dioxide has a less steep partial pressure gradient i. PCO2 of venous blood is 45 mm Hg ii. PCO2 in alveoli is 40 mm Hg iii. CO2 diffuses rapidly out of blood iv. PCO2 of pulmonary capillary reaches equilibrium at 40 mm Hg 4. Structure of respiratory membrane a. Thickness affects rate of diffusion b. In a healthy individual, gas exchange is very efficient c. In pathological conditions, exchange may be slowed by thickening of the respiratory membrane (e.g., pneumonia)

ii. Abnormal or reduced amount of hemoglobin b. Ischemic hypoxiaimpaired or blocked blood flow i. Congestive heart failurebody-wide ischemia ii. Embolism or thrombosislocal interruption in blood flow c. Histotoxic hypoxiaadequate delivery but tissues are unable to use oxygen i. Metabolic poisons d. Hypoxemic hypoxiareduced arterial PO2 i. CO poisoning is an example ii. CO is more readily bound by heme than oxygen VII. Carbon Dioxide Transport 1. Factorsaffect shape and affinity of hemoglobin to oxygen a. PO2 b. Temperature c. Blood pH d. PCO2 e. [BPG] 2. Oxygen-hemoglobin dissociation curve a. Percent O2 saturation of hemoglobin vs. Tissue PO2 b. S-shaped i. Steep slope between 10 and 50 mm Hg PO2 ii. Plateaus between 70 and 100 mm Hg c. Arterial blood is 98% saturated d. Blood loses 25% of its oxygen in capillary beds i. Venous blood is now 75% saturated e. High PO2 are not necessary for hemoglobin to be saturated i. Hemoglobin is 90% saturated at PO2 of 70 ii. Permits adequate delivery of oxygen even when PO2 is lower (e.g., high altitudes) f. Unloading occurs on the steep part of the curve (i.e., below 40 mm Hg) i. Very little O2 is unloaded during a single systemic cycle ii. Hemoglobin is still 75% saturated after leaving capillary bed g. Large amount s of oxygen remain in reserve at any given point in the venous reserve 3. Temperature, pH, PCO2, and biphosphoglycerate levels increase with metabolic activity a. Active metabolism increases body temperature i. Oxygen binding to hemoglobin is directly related to temperature ii. Shifts dissociation curve to the right (i.e., oxygen more readily dissociated at higher temperature) b. Active metabolism increases amount of CO2 released and hence blood pH i. Oxygen binding to hemoglobin is directly related to PCO2 and pH ii. Shifts dissociation curve to the right c. Anaerobic metabolism produces biphosphoglycerate as an intermediate i. Shifts dissociation curve to the right 4. Bohr effect a. Declining pH weakens oxygen-hemoglobin bond i. Oxygen unloading is accelerated D. Nitrous oxide (NO) 1. Vasodilator 2. Nitrous oxide is destroyed by the hemoglobin heme group a. Hemoglobin acts as a vasoconstrictor i. Offsets effect of NO E. Pathologies associated with oxygen transport 1. Hypoxiainadequate oxygen delivery to body tissues a. Anemic hypoxia i. Reduced RBC number

A. Forms that CO2 is transported in blood 1. Dissolved in plasma a. Minimum amount i. 7 10% b. CO2 in solution is readily taken up by RBCs 2. Bound to hemoglobin in RBCs a. Carbaminohemoglobin i. 20 30% of CO2 is transported this way b. Does not compete with oxygen transport i. Not bound to heme ii. Binds to globin 3. As bicarbonate ion in plasma a. Most CO2 is converted to bicarbonate ion (HCO3-) i. 60 70% ii. Slow reaction b. CO2 can diffuse into RBC where it is enzymatically converted to carbonic acid (H2CO3) i. Carbonic anhydrase ii. Rapid iii. Unstable c. Carbonic acid rapidly dissociates to form bicarbonate ion (HCO3-) and H+ d. H+ triggers the Bohr effect i. Facilitating oxygen release e. Bicarbonate ion rapidly diffuses out of the RBCs into the plasma and carried to lungs i. Loss of negatively charges bicarbonate ion is offset by Cl- influxchloride shift f. Process is reversed in the lungs i. Bicarbonate ions re-enter the RBCs and converted back to ii. CO2 is released from lung into blood iii. CO2 diffuses from blood into alveoli 4. Haldane effectwhen PO2 and hemoglobin saturation is low, greater amounts of CO2 can be carried a. Uptake of CO2 by RBCs causes more oxygen to dissociate (Bohr effect) b. Oxygen dissociation permits more CO2 to combine with hemoglobin c. More bicarbonate ions can form VIII. Control of Respiration

A. Reticular formation of medulla and pons controls breathing B. Medulla respiratory centers 1. Two areas a. Dorsal respiratory group (DRG) b. Ventral respiratory group (VRG) 2. DRG a. Pacesetting respiratory center i. Neural activity in DRG activates intercostal muscles and diaphragm ii. Phrenic and intercostal nerves iii. Thoracic cage expands (see above) iv. DRG becomes dormant v. Expiration occurs passively vi. Cycle repeated 12 15 times per minute b. Eupneanormal rate and rhythm of respiration i. Inspiratory phase: 2 s ii. Expiratory phase: 3 s 3. VRG a. Involved in both inspiration and expiration b. Regulate activity of respiratory muscles c. Forced expiration C. Pons respiratory center 1. Pneumotaxic center a. Inhibition of medulla D. Factors affecting rate and depth of breathing

b. Peripheral chemoreceptors i. Walls of great vessels 2. PCO2 has the greatest effect a. CO2 is closely controlled i. 40 3 mm Hg b. Mostly the result of a brain based mechanism c. CO2 leaves blood and enters CSF where it is converted to carbonic acid and hydrogen ions i. No protein buffers in CSF ii. pH dropshypercapnia iii. Brainbased chemoreceptors respond to increased [H+] iv. Depth (and rate) increase hyperventilation v. Flushed CO2 out of blood and CSF pH returns to normal 3. Influence of PO2 a. Oxygen sensors located in aortic arch and common carotids i. Aortic bodies ii. Carotid bodies b. Changes in oxygen levels act indirectly by enhancing the sensitivity of brain-based CO2 receptors c. Only at extremely low levels of oxygen do peripheral receptors regulate ventilation 4. Changes in pH a. Indirect effect through peripheral chemoreceptors i. Falling pH increases ventilation

1. Depth is determined by how many respiratory muscle motor neurons are activated the respiratory center 2. Rate is determined by how quickly the inspiratory center is turned on and off 3. Stretch and irritant receptors generally inhibit the respiratory centers in the medulla a. Vagus nerve i. Promotes expiration 4. Higher brain areas a. Hypothalamuspart of limbic system i. Activates sympathetic NS ii. Modulates depth and rate of breathing b. Cortical controls i. Limited voluntary control of respiratory muscles ii. Ultimately when CO2 levels become too high, medullar respiratory center reactivate breathing 5. Chemical factors 1. Blood chemical are detected by chemoreceptors a. Central chemoreceptors i. Medulla