Respiratory System. By Dr. Carmen Rexach Physiology Mt San Antonio College

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1 Respiratory System By Dr. Carmen Rexach Physiology Mt San Antonio College

2 External vs. internal respiration External respiration ventilation gas exchange Internal respiration cellular respiration

3 Structure Conducting zone Nasal cavity to respiratory bronchioles Respiratory zone Respiratory bronchi Alveoli

4 Thoracic cavity Diaphragm Pleura Potential space

5 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

6 Relationship between intrapulmonary and intrapleural pressure

7 Pneumothorax Air in interpleural space is below atm When wall is breached, air rushes in GSW, stabbing, trauma Result: collapsed lung

8 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

9 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

10 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

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13 Physical properties of the lungs Three properties Compliance Elasticity= tendency to recoil Surface tension Two forces resist distension Surface tension and recoil surfactant

14 Pulmonary ventilation Normal inspiration = active Normal expiration = passive Forced inspiration Scalenes, pectoralis major, sternocleidomastoid Forced expiration Internal intercostals,abdominals

15 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)

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17 Differences by gender

18 Pulmonary disorders Dyspnea Asthma Emphysema COPD =chronic bronchitis + emphysema Pulmonary fibrosis

19 bronchi Normal lung asthma alveoli Chronic bronchitis Emphysema

20 Partial pressure of gases Dalton s law P N2 + P O2 + P CO2 + P H2O = P ATM = 760mmHg air = 21% O + 78% N mm Hg mm Hg mm Hg

21 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 O 2 = 105 mm Hg in alveoli

22 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 P O2, # of RBC s, hemoglobin content Remember: Oxygen is primarily bound to Hb in RBC s keeping the amount of O 2 in the plasma low

23 How oxygen is carried in the blood Normal resting oxygen consumption = 250ml/min P O2 = 100mm Hg in PV = 20ml O 2 /100 ml blood 0.3ml O 2 dissolved in plasma 19.7ml O 2 in RBC s

24 Partial pressure of CO 2 and O 2 in circulation

25 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 P O2 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

26 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

27 Disorders caused by high partial pressures of gases Oxygen toxicity P O2 > 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 N 2 bubbles in blood channels blocked, joint & muscle pain = the bends

28 Hyperbaric oxygen therapy 100% oxygen at >1atm (US = atm abs) Duration:60-90 min. Result: Arterial P O2 = 1200mmHg Benefits: Enhanced fibroblast replication Activation of osteoclasts Stimulation of capillary growth Upregulation vascular endothelial growth factor Upregulation of platelet derived growth factor CID: 2006 (43):

29 Hyperbaric treatment for diabetic foot ulcers 40 days after hyperbaric treatment & skin graft Before hyperbaric treatment

30 Brain stem respiratory centers Medulla oblongata rythmicity center Pons 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 apneusticcenter -- constant I neuron stimulation pneumotaxic center -- inhibitory = cyclic inhibition Chemoreceptors -- respond to changes in P CO2, ph, P O2 central peripheral = aortic and carotid bodies

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32 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

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34 Control of ventilation: blood CO 2 Chemoreceptors control rate & depth of breathing by measuring P CO2, P O2, ph Hypoventilation = hypercapnia Hyperventilation = hypocapnia reflex control of ventilation goal: to maintain relatively constant P CO2 = 40 mm Hg chemoreceptors in ventral medulla increased arterial P CO2 = inc [H + ] blood CSF = CO 2 crosses blood blain barrier to stimulate receptors Periphery = rise in [H + ] decreases blood ph = stimulus In the brain, CO 2 levels directly stimulate receptors in the periphery, H + levels provide the stimulus

35 Peripheral chemoreceptors

36 Effects of blood P O2 on ventilation Indirect influence by changing chemoreceptor sensitivity to CO 2 low P O2 = increased sensitivity high P O2 = decreased sensitivity effect of breathing pure oxygen dilutes effect of CO 2 Chronic CO 2 exposure diminished response (emphysema)

37 Hemoglobin

38 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 + O 2 = oxyhemoglobin Hb - O 2 = deoxyhemoglobin oxygen saturation = statistical average of all oxygen bound relative to total amount that can be bound

39 What binds to hemoglobin? oxyhemoglobin = Hb + O 2 deoxyhemoglobin = Hb - O 2 carbaminohemoglobin = Hb + CO 2 carboxyhemoglobin = Hb + CO methemoglobin = Fe 3+ instead of Fe 2+ cannot bind oxygen normally represents 1-2% of Hb Sulfhemoglobin = Hb + Sulfur

40 Unusual conditions Sulfhemoglobinemia Increased amounts of sulfur, usually drug induced Blood is green due to binding of sulfur to Hb Methemoglobinemia Increased amount of Fe 3+ 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

41 Hemoglobin concentration oxygen carrying capacity of the blood = maximum amount that can be bound by Hb <normal =anemia >normal = polycythemia (common at high altitudes) RBC/Hbproduction erythropoietin androgens

42 Properties of Hb:O 2 binding Hb binds reversibly with O 2 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

43 Loading and unloading reactions Loading reaction Unloading reaction Determined by: P O2 of the environment Affinity of Hb for oxygen

44 Oxyhemoglobin dissociation curve Relationship between P O2 and oxygen saturation of Hb Oxygen reserve 80% saturation even at P O2 of 40 mm Hg Effects of high P O2 Can be modified by physiological and pathological factors ph temperature 2,3-DPG

45 Oxyhemoglobin dissociation curve

46 Effect of ph, temperature, &2,3 DPG on Oxygen transport incr [H + ], P CO2, 2,3-DPG, temperature = decr affinity of Hb for oxygen = incr unloading entire curve shifts to the right of the standard curve decr [H + ], P CO2, 2,3-DPG, temperature = incr affinity of Hb for oxygen = incr loading entire curve shifts to the left of the standard curve

47 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)

48 Shifts in oxyhemoglobin dissociation curve

49 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

50 Muscle myoglobin Special functions middleman oxygen storage function Slow twitch fibers & cardiac muscle cells rhabdomyolysis

51 How is CO 2 carried in blood? 1/10 = dissolved 1/5 = carbaminohemoglobin 7/10 = bicarbonate CO 2 + H 2 0 H 2 CO 3 H + + HCO 3 - Carbonic anhydrase in RBC s

52 Chloride shift: tissue level Equation shifts to the right H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - Steps: CO 2 diffuses out of the tissue cells into the blood CO 2 moved into the red blood cells Combines with H 2 O in the presence of carbonic anhydrase to produce carbonic acid Carbonic acid dissociates producing H + + HCO 3 - H + buffered by hemoglobin, facilitating the offloading of O 2 net positive charge in RBC results in chloride shift Chloride moves into the RBC in exchange for HCO 3 - Bohr effect increased oxygen unloading continued H 2 CO 3 production enhanced transport of CO 2

53 Chloride Shift: Tissue Level

54 Chloride shift: Pulmonary capillaries Hb oxygenated decrease in affinity for H + Reverse chloride shift as Cl - moves out and HCO 3- moves in HCO 3- + H + H 2 CO 3 Carbonic acid dissociates to CO 2 & H 2 O CO 2 expired out Remember: H + is buffered by Hb in RBC HCO 3- goes into the plasma and buffers incoming H +

55 Reverse Chloride Shift

56 Ventilation and acid-base balance Acidosis and alkalosis Regulated by respiratory system Respiratory acidosis Respiratory alkalosis Regulated by the kidneys Metabolic acidosis Metabolic alkalosis

57 Ventilation during exercise Neurogenic sensory nerve activity = stimulates respiratory muscles cerebral cortex = brain stem alteration of ventilation humoral cyclic variations in values of P CO2 & 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

58 Higher altitudes Conditions differ rapid fatigue: decreased P O2, oxygen content of blood decreased (P O2 =69-74mmHg, oxyhemoglobin saturation = 92-93%) Changes in ventilation hypoxic ventilatory response: decr arterial P O2 = hyperventilation = respiratory alkalosis mediated by incr in ph, stabilizes after a few days cannot increase P O2 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

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