Respiratory Physiology PDF

Respiratory Physiology PARA 1002 1 Overview Specific processes: – Ventilation (mechanical process) – Gas exchange at the lung and body tissues (external and internal respiration) – Gas Transport in the blood (Circulatory)...

Respiratory Physiology PARA 1002 1 Overview Specific processes: – Ventilation (mechanical process) – Gas exchange at the lung and body tissues (external and internal respiration) – Gas Transport in the blood (Circulatory) – Regulation of respiratory function (autonomic and somatic) PARA 1002 2 1  Physics of Ventilation Recall a few basic facts: Air is considered a fluid and therefore behaves as other fluids with respect to physical principles Gasses move from one region to another in response to pressure differences (gradient) – Gas moves down its pressure gradient (high to low) Normal atmospheric pressure is 760 mmHg Ventilation occurs in response to intraalveolar pressure differing from atmospheric – Alveolar pressure < 760 mm Hg = inspiration – Alveolar pressure > 760 mm Hg = expiration Remember the Gas Laws??? >>> PARA 1002 3 Ventilation Mechanics (inspiration) Contraction of diaphragm and external intercostals enlarges thoracic cavity (“quiet inspiration”)  intraalveolar pressure (below atmospheric) Parietal pleura “pulls” visceral pleura, expanding lung Air enters lungs to equalize pressure (back to atmospheric) Elastic recoil of lungs and thorax resist expansion *additional muscles involved in forced inspiration (sternocleidomastoid, pectorals, serratus anterior) PARA 1002 4 2  Ventilation Mechanics PARA 1002 5 Ventilation Mechanics (expiration) Relaxation of inspiratory muscles decreasing volume of thoracic cavity (“quiet expiration”)  intraalveolar pressure *Note that there is always a negative pressure between the pleural membranes (resists tendency to collapse) Positive pressure gradient forces air out of lungs additional muscles involved in forced expiration (abdominals and internal intercostals) PARA 1002 6 3  Ventilation Mechanics PARA 1002 7 Accessory Muscles Identify some Accessory Muscles of Ventilation? How are accessory muscles related to assessment / clinical evaluation of ventilatory status? PARA 1002 8 4  Lung Volumes PARA 1002 9 Lung Volumes Tidal volume (TV) Pulmonary volumes are Volume of air exhaled after normal inspiration (~500 mL) measured with a spirometer Inspiratory reserve volume (IRV) Volume of air that can be forcibly inspired following normal inspir (~3300 mL) Expiratory reserve volume (ERV) Volume of air that forcibly expired following normal expiration (~1200 mL) Residual volume (RV) Volume of air remaining in resp. tract following max expiration (~1200 mL) PARA 1002 10 5  Pulmonary Capacities Total Lung Capacity (TLC) Vital Capacity (VC) Total volume held by lung Largest volume of air that can be moved in and out of TV+IRV+ERV+RV (~5700- lung TV+IRV+ERV (~4500- 6200 mL) 5000 mL) Inspiratory Capacity (IC) Max volume of inspiration following normal expiration TV+IRV (~3500-3800 mL) T L C Functional Residual Capacity (FRC) Volume of air remaining following normal expiration ERV+RV (~2200-2400 mL) PARA 1002 11 Dead Space **Only the air that enters the “Respiratory Zone” takes part in gas exchange with blood (Alveolar ventilation) Anatomical Dead Space The air occupying the conducting pathways that is not available for gas exchange (Why?) Physiological Dead Space The anatomical dead space along with any “Alveolar Dead Space” Increased physiological dead space results from alveoli that are not perfused properly Consider what is happening in this case How much of our ventilation is useable? PARA 1002 12 6  Partial Pressures *Partial pressure = tension Recall that concentration and partial pressure of a gas in a mixture are related (Dalton’s Law) Partial pressures of gasses in air and liquid (blood plasma) determine the direction of flow (gradients) Atmospheric PO2 = 21% X 760 = 159.6 mm Hg Alveolar PO2 = 100 mm Hg / Arterial PO2 = 100 mm Hg Venous PO2 = 37 mm Hg PARA 1002 13 Pulmonary Gas Exchange Recall that gasses move in both directions across the respiratory membrane CO2 and O2 move down respective pressure gradients between alveolar air and pulmonary blood Rate of diffusion of O2 into the blood depends upon: 1. PO2 gradient between alveolar air and blood 2. Functional SA of respiratory membrane 3. Respiratory minute volume 4. Alveolar ventilation What could affect / change the above factors ? PARA 1002 14 7  Pulmonary Gas Exchange Oxygen Diffusion Alveolar PO2 will change in relation to changes in atmospheric pressure (high altitude = low PO2) Functional surface area of the respiratory membrane will decrease as a result of certain pulmonary pathologies such as emphysema Minute volume may be reduced by certain pharmaceuticals (opiates) as well as deep sleep PARA 1002 15 Why do alveolar PO and PCO remain relatively constant? PARA 1002 2 2 16 8  Structure Determines Function As mentioned previously, structure of the gas exchange mechanism is ideally suited to its function – Extremely thin diffusion distance from alveoli to capillaries (.3 -.4 μm) – Large capillary and alveolar surface areas – Large blood volume within pulmonary capillaries – Narrow pulmonary capillaries (significance?) PARA 1002 17 Gas Transport Small amounts of gas will dissolve in a given liquid Blood plasma is not able to hold sufficient O2 or CO2 in solution to transport it effectively In the blood, O2 and CO2 bind to other components, effectively removing them from solution How does this allow for diffusion of large quantities of gas? PARA 1002 18 9  Hemoglobin (Hb) Transport of both O2 and CO2 Protein molecule in RBC’s (respiratory pigment) 4 subunits (2 α and 2 β) and vital heme group (iron) Each Hb molecule can potentially bind four O2 molecules to form oxyhemoglobin (HbO2) Each Hb molecule can potentially bind CO2 as well to form carbaminohemoglobin (HbCO2) What about carbon monoxide? PARA 1002 19 Oxygen Transport Oxygen is carried in blood as: 1. Very small amount of dissolved O2 in the plasma (.3mL / 100mL) 2. Majority is carried as HbO2 Oxygen carrying capacity depends [Hb] – ~ 1.34 mL O2 / 1 g Hb – 15 g Hb / 100 mL blood What is anemia? PARA 1002 20 10  Oxygen Transport Since hemoglobin is located inside the red blood cell, O2 must diffuse from the plasma into RBC’s Association of Hb and O2 is influence by blood PO2 Increased PO2 = increased rate of association Decreased PO2 = increased rate of dissociation Average O2 saturation = 97-98% PARA 1002 21 Oxyhemoglobin Curve *(dissociation curve) Recall that the relationship between PO2 and dissolved O2 content is a linear one… Chemical nature of HbO2 association/dissociation result in a nonlinear relationship Conformational changes in Hb What is occurring at the various portions of the curve (note relative slopes) PARA 1002 22 11  Oxyhemoglobin Curve The “sigmoid” shape of the curve is due to changes in O2 affinity of Hb at different PO2 ‘s How do small changes in PO2 affect O2 content? Steep slope represents rapid loading / unloading of oxygen PARA 1002 23 Carbon Dioxide Transport Carbon dioxide is carried in blood as: 1. ~10% of total CO2 is carried dissolved in the plasma 2. 20–25% of total CO2 transported as carbaminohemoglobin, bound to amine groups of Hb molecules Association of CO2 and Hb is accelerated by increased PCO2 PARA 1002 24 12  Carbon Dioxide Transport 3. The majority of CO2 is carried in the blood in the form of the bicarbonate ion (HCO3-) In water, some molecules associate with H2O to form H2CO3 (carbonic acid) Catalyzed by carbonic anhydrase A portion of the H2CO3 molecules dissociate to form the bicarbonate ion (very soluble in water) and protons (H+) As the HCO3- diffuses out of the RBC, it is exchanged for a Cl- ion (chloride shift) Reversible reaction What controls the direction of this reaction? How is CO2 carrying capacity affected? PARA 1002 25 CO2 and pH Production of carbaminohemoglobin or bicarbonate ions also results in the generation of protons (H+) What result does addition of H+ to a solution (blood plasma) do?  pH (increased acidity) is a characteristic of blood carrying larger amounts of CO2 Very important to mechanisms of respiratory regulation PARA 1002 26 13  Systemic Gas Exchange As tissues metabolize O2 , intracellular / interstitial PO2 decrease in response Dissolved arterial O2 diffuses into these tissues down its gradient (offloading) O2 dissociates from HbO2 to “replace” O2 as it leaves the blood PO2 , oxygen saturation and total oxygen content are lower in the venous blood What about CO2? Similarly, PCO2 increases in the tissues as a result of metabolism and diffuses into the capillaries This initiates formation of carbaminohemoglobin and bicarbonate *Recall, these processes reverse at the lungs… PARA 1002 27 PARA 1002 28 14  Rest –vs- Exercise PARA 1002 29 Regulation of Breathing Control of blood gas homeostasis is maintained primarily by alterations in ventilation Integrators regulating nervous control of inspiration and expiration are located in the brainstem (ANS) Inspiratory and expiratory control centres in the medulla maintain regular “quiet rhythm” Additional respiratory control centres are located in the pons (“pattern generators” and “controllers”) PARA 1002 30 15  Chemical Control Chemoreceptors detect changes in blood chemistry Central chemoreceptors are found in the medulla Peripheral chemoreceptors found in carotid bodies of both common carotid arteries and aortic bodies of aortic arch Both types are highly perfused When exposed to appropriate chemical stimuli (hypoxia, hypercapnia, pH), associated nerve endings are stimulated (catecholamine release) Sensory impulses sent to respiratory control centres at increasing frequencies PARA 1002 31 Chemoreceptors PARA 1002 32 16  Carbon Dioxide Normal range for arterial PCO2 is 38-40 mm Hg Central chemoreceptors in the medulla** and peripheral chemoreceptors in the carotid bodies and aorta are stimulated by increases in PCO2 The result is increased rate and volume of ventilation Decreased PCO2 has an opposite effect and may induce apnea when PCO2 drops below 35 mm Hg Feedback? ** Note that this is an “indirect” effect with respect to Central Chemoreceptors PARA 1002 33 Central Chemoreceptors Located in medulla PCO2=primary regulator of ventilation Bathed in CSF (not blood) Indirectly stimulated by CO2… Explain Blood-brain barrier very permeable to CO2 but only slightly to H+ or HCO3- CO2 diffuses into CSF Accumulation of H+ stimulates medullary inspiratory neurons   ventilation PARA 1002 34 17  Hypercapnic Drive Recall what happens to CO2 in solution… CO2 + H2O → H2CO3 → H+ + HCO3- Central chemoreceptors respond “indirectly” to CO2 levels since they are sensitive to [H+] CO2 crosses BBB into the CSF quite easily, but bicarbonate does not (also no buffers in CSF like in blood) pH changes very quickly ** With chronically elevated PCO2 (COPD), there is time for blood buffers to diffuse into CSF pH does not stimulate receptors (reduced sensitivity) *Also seen with CNS depressants PARA 1002 35 Central Chemoreceptors and O2 PO2 has no direct effect on central chemoreceptors Recall: SaO2 may still be 90% at PO2 as low as 60 mmHg Changes in ventilation have a relatively minor effect on PaO2 under normal conditions Consider the O2Hb dissociation curve Oxygen is insignificant as a controller of normal ventilation … CO2 is the major controller PARA 1002 36 18  Peripheral Chemoreceptors Recall location and high perfusion rates Respond to  PaO2,  PCO2,  arterial pH with increased firing rate Carotid bodies and aortic bodies respond to stimuli in a similar manner, but carotid bodies provide a greater magnitude of response PARA 1002 37 Peripheral Receptors - Blood pH Recall that increased CO2 in the plasma is accompanied by a decrease in pH Chemoreceptors in the aortic and carotid bodies respond to moderate decreases in pH in a similar manner as to increased PCO2 What is it about the “location” of the central –vs- peripheral chemoreceptors that cause them to respond differently to CO2 and H+? PARA 1002 38 19 Peripheral Receptors - Blood pH Acid – Base Balance: Since peripheral receptors are also sensitive to pH changes, any source of metabolic acidosis or metabolic alkalosis will also initiate compensatory responses Respiratory responses related to acid/base disturbances Associated with acid/base regulation by kidney PARA 1002 39 Hypoxic Drive Note that these chemoreceptors are sensitive to the amount of O2 dissolved in the plasma Therefore… Conditions that affect total O2 but not the amount of “dissolved” O2 will not stimulate receptors Carbon monoxide poisoning, Anemia Stimulation generally occurs when: Arterial PO2 is extremely low Total O2 delivery is extremely depressed Cellular uptake of O2 is chemically inhibited (cyanide) PARA 1002 40 20  Hypoxic Drive Normal PO2 is 80 – 100 mmHg (no stimulation) At normal PCO2 hypoxic drive is relatively insensitive When PaO2 drops from 60-30 mmHg there is a dramatic increase in firing rate ( ventilation) PARA 1002 41 Hypoxic Drive The sensitivity of the hypoxic drive increases in response to increasing arterial PCO2 (>40mmHg) This shift in sensitivity is particularly significant in the case of certain COPD’s (explain!) PARA 1002 42 21  Hypoxic Drive Can you “knock out” hypoxic drive? Does oxygen administration induce hypercapnia in COPD patients through suppression of Hypoxic Drive? PARA 1002 43 Extreme Hypoxia It is important to note that if neurons of the respiratory centres are exposed to extreme hypoxic conditions, their function may be impaired As a result, signals from the centres may not be sent and ventilation may be reduced or fail completely Clinically significant since respiratory centres may not respond to normal stimulation such as increased PCO2 PARA 1002 44 22  PARA 1002 45 Vascular Resistance and Flow Chemical Factors: – Decreased alveolar oxygen tension has a direct influence on blood vessels supplying those alveoli – Reduced PO2 in a specific alveolar region results in vasoconstriction of “Upstream” arterioles supplying the associated alveolar capillary bed (How does this compare to systemic vasculature?) – Blood flow is shunted to alveoli with higher PO2 – This hypoxic pulmonary vasoconstriction (HPV) ensures efficient ventilation/perfusion matching – Low arterial blood pH augments HPV * Note that hyperoxia has little or no effect on pulmonary vasculature of “normal” lungs… PARA 1002 46 23  Blood Pressure Aortic and carotid baroreceptors respond to changes in arterial pressure (internal and external) Sudden rise in arterial pressure results in reflexive slowing of ventilatory rate Sudden decrease in arterial pressure results in reflexive increase of rate and depth of ventilation PARA 1002 47 Hering –Breuer Reflex Expansion of the lungs to normal maximum tidal volume stimulates stretch receptors This results in inhibition of the inspiratory centre Relaxation of the lungs inhibits the stretch receptor response PARA 1002 48 24  Other Factors Recall that “voluntary” impulses from the cerebral cortex can modify and override normal breathing rhythms (to a point…) Reflexive acute apnea results from stimuli such as: – Sudden painful stimulation (opposite effect if stimulation is maintained) – Sudden cold exposure to the skin – Irritation of the larynx or pharynx (choking reflex) PARA 1002 49 What is dead space? What do you know about V/Q matching? PARA 1002 50 25