RespiratoryRespiratoryRespiratory SystemSystemSystem
By Dr. Carmen Rexach Physiology Mt San Antonio College External vs. internal respiration • External respiration – ventilation – gas exchange • Internal respiration – cellular respiration Structure
• Conducting zone – Nasal cavity to respiratory bronchioles •Respiratory zone –Respiratory bronchi –Alveoli Thoracic cavity
•Diaphragm • Pleura • Potential space Intrapulmonary and intrapleural pressures • Boyle’s law – pressure of a given quantity of gas is inversely proportional to volume • Interpleural space = intrapleural space •Intrapulmonary (intraalveolar) pressure – Pressure in alveoli • Intrapleural pressure – Pressure in pleural cavity • Transpulmonary pressure – Intrapleural pressure – intrapulmonary pressure – Keeps lungs inflated Relationship between intrapulmonary and intrapleural pressure Pneumothorax
• Air in interpleural space is below atm • When wall is breached, air rushes in – GSW, stabbing, trauma • Result: collapsed lung Spontaneous pneumothorax
• Lung collapses due to air or gas collecting in chest without any sign of traumatic injury • Usually occurs when patient is resting •Symptoms – Sudden chest pain with breathlessness, exaccerbated with deep breathing or coughing • Risk factors – Male gender (7x’s more likely than in females) • Smoking (22x’s more likely than nonsmokers) – Smoking females 9x’s more likely than nonsmoking females Inspiration • Pressure of air exceeds intrapulmonary pressure • Steps: – expansion of thoracic cage – pulls on parietal pleura = increase intrapleural cavity volume – pressure decreased by (subatmospheric) – increased transpulmonary difference – alveoli expand = decreased pressure in alveoli – air moves from high to low pressure = moves in Expiration
• Intrapulmonary pressure greater than atmospheric pressure = air moves out • Steps: – diaphragm & inspiratory intercostals relax – chest wall recoils – intrapleural pressure approaches preinspirational value – intrapulmonary pressure exceeds atmospheric pressure –air goes out
Physical properties of the lungs • Three properties – Compliance – Elasticity= tendency to recoil – Surface tension • Two forces resist distension – Surface tension and recoil
•surfactant Pulmonary ventilation
• Normal inspiration = active • Normal expiration = passive • Forced inspiration – Scalenes, pectoralis major, sternocleidomastoid • Forced expiration – Internal intercostals,abdominals Pulmonary function tests • Measured by spirometry • Lung volumes and capacities (approximate volume) –Tidal volume= volume of each breath (500ml) – Vital capacity = largest possible tidal volume; amount of gas that can be forcefully exhaled after maximum inhalation (5000ml) – Inspiratory reserve volume = volume of gas that can be forcefully inhaled after a normal inhalation (3000ml) – Expiratory reserve volume = volume of gas that can be forcefully exhaled after an unforced exhalation (1500ml) – Residual volume = amount of gas remaining in the lungs after a forced expiration (100ml) – Dead space volume = volume of air in the conduction passageways that is not exchanged (150ml)
Differences by gender Pulmonary disorders
• Dyspnea •Asthma • Emphysema • COPD =chronic bronchitis + emphysema •Pulmonary fibrosis bronchi
alveoli Normal lung asthma
Chronic Emphysema bronchitis Partial pressure of gases
• Dalton’s law
•PN2 + PO2 + PCO2+ PH2O = PATM = 760mmHg • air = 21% O + 78% N
0.21 760 159mm Hg
0.78 760 593mm Hg
0.0004 760 0.3mm Hg Other factors influencing pressure • Altitude – Increased = decreased atmospheric pressure – Decreased = increased atmospheric pressure • 1 atm increase for every 33 feet below sea level • Temperature – determinant of water vapor composition of air –in body • water vapor = 47mm Hg
• effects the partial pressure of O2 = 105 mm Hg in alveoli Partial pressure of gases in the blood • Gases diffuse quickly due to: – surface area, large capillary bed, short diffusion distance • Henry’s law = The maximum value of a gas dissolved in a fluid depends on: – the solubility of the gas in fluid – temperature of the fluid – partial pressure of the gases • Oxygen content of the blood depends on
–PO2, # of RBC’s, hemoglobin content – Remember: Oxygen is primarily bound to Hb in RBC’s keeping
the amount of O2 in the plasma low How oxygen is carried in the blood
• Normal resting oxygen consumption = 250ml/min
•PO2 = 100mm Hg in PV = 20ml O2/100 ml blood
–0.3ml O2 dissolved in plasma
– 19.7ml O2 in RBC’s Partial pressure of CO2 and O2 in circulation Vascular resistance in lungs • Vascular resistance – fetal = collapsed lungs, resistance is high –birth = drops • subatmospheric intrapulmonary pressure opens blood vessels • stretching of lungs at inspiration • dilation of pulmonary arterioles due to increased
alveolar PO2 • foramen ovale and ductus arteriosus close – adult = low pressure/low resistance • blood flows to lungs and to systemic circulation at same rate • pulmonary 1/10th of systemic vascular resistance Ventilation/perfusion ratios (V/P)
– Ventilation = respiration rate x tidal volume – Perfusion = pulmonary blood flow = heart rate x right ventricular SV – Nearly matched under normal conditions • apex of lung – overventilated & underperfused –apex =3.4:1 –larger alveoli • base of lung – underventilated & overperfused –base = 0.6:1 Disorders caused by high partial pressures of gases
–PO2 > 2.5 atm – oxidation of enzymes, nervous system damage, coma, death • Nitrogen narcosis – > one hour down – rapture of the deep, drowsiness, “intoxication” • Decompression sickness
– formation of N2 bubbles in blood – channels blocked, joint & muscle pain = the bends Hyperbaric oxygen therapy • 100% oxygen at >1atm (US = 2.0-2.4 atm abs) • Duration:60-90 min.
• Result: Arterial PO2 = 1200mmHg • Benefits: –Enhanced fibroblast replication – Activation of osteoclasts – Stimulation of capillary growth –Upregulationvascular endothelial growth factor – Upregulation of platelet derived growth factor CID: 2006 (43):188-192 Hyperbaric treatment for diabetic foot ulcers
40 days after hyperbaric treatment & skin graft
Before hyperbaric treatment Brain stem respiratory centers • Medulla oblongata – rythmicity center • dorsal group (phrenic nerve) & ventral group (intercostals) • I neurons = inspiration = spinal motor neurons innervate respiratory muscle •E neurons = fire during expiration and inhibit I neurons •Pons –apneusticcenter --constant I neuron stimulation – pneumotaxic center -- inhibitory = cyclic inhibition
•Chemoreceptors--respond to changes in PCO2, pH, PO2 –central – peripheral = aortic and carotid bodies
Irritant and Inflation Reflex
• Pulmonary irritant reflexes – Reflex constriction to prevent particulates from entering lungs – Stimulate cough in trachea & bronchi, sneeze in nasal cavity • Inflation reflex – Stretch receptors respond to lung inflation – Inhibitory signals sent to allow expiration to occur – Hering-Breuer Reflex
Control of ventilation: blood CO2 • Chemoreceptors control rate & depth of breathing by measuring PCO2, PO2, pH – Hypoventilation = hypercapnia – Hyperventilation = hypocapnia • reflex control of ventilation
–goal: to maintain relatively constant PCO2 = 40 mm Hg • chemoreceptors in ventral medulla + – increased arterial PCO2 = inc [H ] blood
–CSF = CO2 crosses blood blain barrier to stimulate receptors – Periphery = rise in [H+] decreases blood pH = stimulus
– In the brain, CO2 levels directly stimulate receptors – in the periphery, H+ levels provide the stimulus Peripheral chemoreceptors Effects of blood PO2 on ventilation
• Indirect influence by changing chemoreceptor sensitivity to CO2
–low PO2 = increased sensitivity
–high PO2 = decreased sensitivity • effect of breathing pure oxygen
– dilutes effect of CO2
• Chronic CO2 exposure – diminished response (emphysema) Hemoglobin Hemoglobin
•2 α & 2 β chains = quaternary structure • 4 hemes = each heme has one Fe and will bind with one oxygen molecule • 280 million Hb per RBC x 4 = >1 billion molecules of oxygen per RBC
•Hb+ O2 = oxyhemoglobin
•Hb-O2 = deoxyhemoglobin • oxygen saturation = statistical average of all oxygen bound relative to total amount that can be bound What binds to hemoglobin?
• oxyhemoglobin = Hb + O2
• deoxyhemoglobin = Hb - O2
• carbaminohemoglobin = Hb + CO2 • carboxyhemoglobin = Hb + CO • methemoglobin = Fe3+ instead of Fe2+ – cannot bind oxygen – normally represents 1-2% of Hb • Sulfhemoglobin = Hb + Sulfur Unusual conditions
•Sulfhemoglobinemia – Increased amounts of sulfur, usually drug induced – Blood is green due to binding of sulfur to Hb • Methemoglobinemia – Increased amount of Fe3+ on Hb – Blood appears chocolate brown in color – Patients look “blue” – NOTE: Venous blood is not blue in normal people!! It just looks blue through skin because veins run deeper than arteries Hemoglobin concentration
• oxygen carrying capacity of the blood = maximum amount that can be bound by Hb •
• Hb binds reversibly with O2 • Molecular oxygen associates and dissociates from Hb very rapidly – Blood is in the exchange capillaries less than one second • The sigmoid shape of the oxyhemoglobin dissociation curve is caused by molecular interactions of the four heme groups Loading and unloading reactions • Loading reaction • Unloading reaction • Determined by:
–PO2 of the environment – Affinity of Hb for oxygen Oxyhemoglobin dissociation curve
• Relationship between PO2 and oxygen saturation of Hb •Oxygen reserve
– 80% saturation even at PO2 of 40 mm Hg
• Effects of high PO2 • Can be modified by physiological and pathological factors –pH – temperature –2,3-DPG Oxyhemoglobin dissociation curve Effect of pH, temperature, &2,3 DPG on Oxygen transport
+ •incr[H], PCO2, 2,3-DPG, temperature = decr affinity of Hb for oxygen = incr unloading – entire curve shifts to the right of the standard curve
+ •decr[H], PCO2, 2,3-DPG, temperature = incr affinity of Hb for oxygen = incr loading – entire curve shifts to the left of the standard curve 2,3-DPG (diphosphoglyceric acid)
• Product of anaerobic respiration in RBC’s • increases with decrease in oxyhemoglobin • result: increased unloading of oxygen at tissues • conditions –anemia – high altitudes – transfer maternal to fetal circulation (Hbf) Shifts in oxyhemoglobin dissociation curve Inherited defects in hemoglobin structure/function
• Sickle cell anemia (HbS) – valine replaces glutamic acid on β chain •thalassemia – Mediterranean ancestry – 2 forms; α & β thalassemia –increased γ chain production, decreased oxygen unloading Muscle myoglobin
• Special functions –middleman – oxygen storage function • Slow twitch fibers & cardiac muscle cells • rhabdomyolysis How is CO2 carried in blood? • 1/10 = dissolved • 1/5 = carbaminohemoglobin • 7/10 = bicarbonate + - –CO2 + H20H2CO3 H + HCO3
• Carbonic anhydrase – in RBC’s Chloride shift: tissue level • Equation shifts to the right + - –H2O + CO2 H2CO3 H + HCO3 •Steps:
–CO2 diffuses out of the tissue cells into the blood
–CO2 moved into the red blood cells
–Combines with H2O in the presence of carbonic anhydrase to produce carbonic acid + - – Carbonic acid dissociates producing H + HCO3 –H+ buffered by hemoglobin, facilitating the offloading of O2 – net positive charge in RBC results in chloride shift - – Chloride moves into the RBC in exchange for HCO3 – Bohr effect •increased oxygen unloading
•continued H2CO3 production • enhanced transport of CO2 Chloride Shift: Tissue Level Chloride shift: Pulmonary capillaries •Hboxygenated •decrease in affinity for H+ • Reverse chloride shift as Cl- moves out and - HCO3 moves in - + •HCO3 + H H2CO3
• Carbonic acid dissociates to CO2 & H2O
•CO2 expired out
• Remember: –H+ is buffered by Hb in RBC - –HCO3 goes into the plasma and buffers incoming H+ Reverse Chloride Shift Ventilation and acid-base balance • Acidosis and alkalosis • Regulated by respiratory system – Respiratory acidosis –Respiratory alkalosis • Regulated by the kidneys – Metabolic acidosis – Metabolic alkalosis Ventilation during exercise • Neurogenic – sensory nerve activity = stimulates respiratory muscles – cerebral cortex = brain stem alteration of ventilation •humoral
– cyclic variations in values of PCO2 & pH stimulates chemoreceptors (small amounts) • anaerobic threshold and endurance training – anaerobic threshold = maximum rate of oxygen consumption attained before blood lactic acid levels rise due to anaerobic respiration – adaptations in athletes =incr mitochondria, aerobic enzymes; incr oxygen utilization by muscles, lower % oxyhemoglobin in venous blood Higher altitudes • Conditions differ
– rapid fatigue: decreased PO2, oxygen content of blood decreased (PO2 =69-74mmHg, oxyhemoglobin saturation = 92- 93%) • Changes in ventilation
– hypoxic ventilatory response: decr arterial PO2 = hyperventilation = respiratory alkalosis • mediated by incr in pH, stabilizes after a few days
– cannot increase PO2 greater than inspired air • Hemoglobin affinity for oxygen decreased – greater unloading due to 2,3-DPG • Hemoglobin and RBC production – tissue hypoxia stimulates increased erythropoietin – increased viscosity due to increase in RBC’s