Respiration PDF - Sante Medical College

Sante Medical College Respiratory system [email protected] 11/4/2024 1  Objectives To discuses about – Respiratory system components and functions – Respiratory structures innervations...

Sante Medical College Respiratory system [email protected] 11/4/2024 1  Objectives To discuses about – Respiratory system components and functions – Respiratory structures innervations – Mechanism of respiration – Lung function test (volumes, capacities..) – Minute ventilation and dead spaces – Gas transport and oxyhemoglobin dissociation curve – Partial pressure of gas, ventilation perfusion ration – Related disorders 11/4/2024 2  Functions of Respiratory system Structures involved for gas exchange and has functions – Respiratory functions: gas exchange – Non respiratory functions Sensation (olfaction), vocalization,T0 regulation, body fluid regulation, adjustment, secreting ACE from ECs of pulmonary capillary Anticoagulation: heparin and fibrolytic agents secretions Acid base balance – CO2+H2O H2CO3 H+ + HCO- Metabolism CO2 and ventilation increase to remove CO2 11/4/2024 3  Functions of the respiratory system … Defense – Nose: hairs – Alveoli macrophages, lymphocytes: engulf dust and other foreign bodies – Reflexes Chemical productions: lung tissue – Prostaglandins, Ach, Bradykinin, serotonin Enhances venous return 11/4/2024 4  Components of the respiratory system Airways (upper and lower) – Highly supplied with blood vessels, thick mucus Chest , glottis (opening) and epiglottis: tissue closing the glottis Lungs, cerebrum, brainstem, sensory and motor nerve Respiratory muscles Surfactant and pleural sac Pleural fluid Pathway of air: nasal cavities (or oral cavity)  pharynx  larynx trachea  primary bronchi (right & left) secondary bronchi tertiary bronchi  bronchioles alveolar ducts  alveoli 11/4/2024 5  Components of the respiratory system… Upper respiratory tract – Nose, nasal cavity, paranasal sinuses, pharynx, and larynx Lower respiratory tract – Trachea, 1O 2O & 3O bronchi, – Terminal & respiratory bronchioles, – Alveolar ducts and alveoli of the lungs 11/4/2024 6  Components of the respiratory system… Lungs – Fundamental organ for respiration – Has lobes Right lung: three lobes (right upper, right middle and right lower) Left lung: two lobes (left upper and the left lower) – Foreign bodies lodged to the right lung Bronchi are wider Strgihted (trachea–bronchus angle =20-25O, while in left is 40- 50O) – Cells: Alveoli (300 million) 11/4/2024 7  Components of respiratory system… Trachea – Surrounded by C – shaped cartilages Protects the tracheal wall and prevent it from collapse Keep the trachea open to allow easy passage of air – No cartilage at the back side of trachea For peristalsis and deglutination Bronchioles – The walls lack cartilaginous supports, – Dominated by smooth muscle tissue – The ANS regulates the activity of smooth muscle layer Alters the diameter of the bronchioles 11/4/2024 8  Respiratory zones Conducting unit Thick membrane Air conduct Humidification Defending Respiratory unit  Respiratory bronchiole  Alveolar duct  Alveolar sac 11/4/2024 Figure 2 : Respiratory airways 9  Phases of respiration External Respiration – Gas exchange between atmosphere and lungs Called pulmonary ventilation – Gas exchange b/n lung and blood (breathing), normal rate 10-18 breaths/min (adult) but higher in infant Called alveolar ventilation – Hyperpnea: high depth and tachypnea Gas Transport Internal Respiration – Gas exchange b/n blood and tissue 11/4/2024 10  The four integrated processes Fig 3: Processes of Respiration 11/4/2024 11  Refluxes Coughing reflex – Removes irritants from respiratory passages and is the function of medulla oblongata – Initiated by irritants in the pharynx, larynx, or trachea Sneezing reflexes – Removes irritants from respiratory passages – Initiated by irritants in the nasal mucosa – Both reflexes uses inhalation and is followed by exhalation beginning with the glottis closed to build up pressure. Then the glottiss suddenly, and the exhalation is explosive 11/4/2024 12  Refluxes… Hiccup reflux – caused by spasms of the diaphragm. – The result is a quick inhalation and is stopped when the glottis snaps shut, causing the “hic” sound. – Stimulated by irritation of the phrenic nerves or nerves of the stomach. – Excessive alcohol is an irritant that can cause it and Some causes are simply unknown. Hering-beruer reflex – Reflex results in the inhibition of further lung inflation 11/4/2024 13  Respiratory Innervation 11/4/2024 14  Respiratory innervation Phrenic nerve – Mixed: somatic and autonomic (sympathetic: sensory section) fibers are found – Sensory and motor – From C 3,45 of spinal segment Innervates diaphragm Intercostals nerve: innervates intercostal muscles SNS and PNS: Innervates airways 11/4/2024 15  Respiratory Innervation con’t Autonomic (tracheobronchiol) – Sympathetic nerve Via 2 adrenergic: bronchodilator Via α1 constrict bronchial blood vessels and bronchiole secretion 2 also found at the cholinergic terminals – Autoreceptors and inhibits the release of Ach that constrict bronchioles Its tone increased during inspiration – Parasympathetic (vagal cholinergic): Bronchioconstrictor and increases bronchiole secretion PNS activity is maximum in the morning, but sympathetic activity high late in the afternoon (pulmonary ANS supply is circadian) 11/4/2024 16  Respiratory Receptors and Sensory Innervation 11/4/2024 17  Respiratory Receptors Receptors in the Lungs – Chemoreceptors In the respiratory zones nearer to capillary : juxtacapillary receptors (J- receptors) Stimulated by chemicals (irritants, tobacco, histamine, prostaglandins, capsaicin, bradykinin and serotonin in the blood) – Stretch receptors Stimulated by lung inflation, edema, lung congestion, marked inflation, emboli – Hering- breurer reflex: Inhibitory reflex 11/4/2024 18  Sensory innervation Olfactory sensory nerve: take signals from olfactory chemo- receptors in the nose Maxillary trigeminal sensory nerve: take signals from irritant receptors (tobacco, histamine and prostaglands) Vagal sensory nerve: take signals from the lower respiratory passages 11/4/2024 19  Respiratory circulation 1. Pulmonary circulation: – Right ventricle  pulmonary artery  lung  Pulmonary vein  left auricle – For blood to be oxygenated 2. Bronchial circulation – 1-2% of CO – Aorta bronchial artery supplies O2 to surrounding tissues of the lung Venous admixture and shunted blood 1/3 deoxygenated blood getting into the right atrium The remaining into pulmonary vein 11/4/2024 20  Bronchial circulation… The process is called physiologic shunt or venous admixture The blood that is shunted is shunted blood Lt ventricular CO is 1to 2% greater than Rt ventricular CO Bronchial blood not move into gas exchange area 11/4/2024 21  Features of Components in the Pulmonary Circulation Thin wall, 1/3 of in in the systemic circulation More elastic, less SMCs Capillaries are larger Less resistance, and pressure (25/10) Includes pulmonary arteries, pulmonary capillaries and pulmonary veins 11/4/2024 22  Lung cells Alveoli/pneumocytes: Principle structure in the lung – 300 million in a lung with 0.2-0.3mm diameter – Type I Principal cells, thin and flat – Type II Less in number and thicker, produces surfactant Lymphocytes and Pulmonary alveolar macrophage Mast cells (histamine) 11/4/2024 23  Alveoli and other cells Figure 3 : Alveoli and other cells in the lung 11/4/2024 24  Alveoli con’t Alveoli are supplied with capillary Gas is exchanged b/n blood and the alveoli – Alveolo-capillary membrane/respiratory membrane (0.5m thickness) – Total surface area of the respiratory membrane 70m2 11/4/2024 25  Pleural and respiratory membranes Pneumothorax (air in the intrapleural space) Pleural cavity Pneumothorax- when air accumulates in the pleural cavity Hydrothorax- when water accumulates in the pleural cavity Heamothorax – when Haemothorax blood accumulates Respiratory membrane Figure 4 : Respiratory membrane 11/4/2024 26  Respiratory membrane Water film on interior of alveolus Nucleus Alveolar epithelium: alveolar Air filed lumen membrane Interstitial Respiratory membrane fluid Capillary endothelium: capillary membrane Plasma Red cell Basement membrane (fused) Capillary network forms in the respiratory unit Two membranes: alveolar membrane and capillary membrane The membrane separates air in the alveoli and blood in the capillaries Figure 4.1 : Respiratory membrane 11/4/2024 27  Components of respiratory membrane Surfactant layer Fluid layer in the alveolar Alveolar epithelium Interstial space Basement membrane Capillary endothelium And the thickness: 0.1micron 11/4/2024 28  Respiratory membrane and fick’s law of diffusion XD D= diffusion constant: Solubility (high for C02 than O2) The DR of C02 is higher than O2 and p for C02 is 7 and for O2 is 60mmHg 11/4/2024 29  The diffusion capacity of the lung Volume of air crossing the respiratory membrane per minute per pressure gradient – For O2 =25 ml/min/mmHg – For CO2= 500ml/min/mmHg Thickening of the membrane affect O2 diffusion than the CO2 O2 Loaded into blood= 250ml/min/mmHg and CO2 unloaded = from the blood 200ml/min/mmHg 11/4/2024 30  Mechanism of Breathing  Thoracic gradients are required  Pressures gradient  Atmospheric, intrapleural, intrapulmonary and transpulmonary pressure  Volume gradient  Respiratory muscles are involved  Inspiratory muscles Normal and Accessory  Expiratory muscles Forceful  Nerves involved 11/4/2024 31  Respiratory pressures 1. Atmospheric pressure 2. Intraalveolar/pulmonary pressure 3. Intrapleural pressure 4. Transpulmonary pressures Transpulmonary pressure= alveolar pressure – pleural pressure. Distends the lung Intrapleurla pressure =  -4 at the end of normal expi  -8 at the end of normal inspiration -40 at the end of deepest inspiration  -70 at the end of deepest inspiration and glottis closed Diaphragm +100cm H2O at the end of forced expiration and glottis closed Intraalveolar pressure Why this pressure = negative  At rest = 760 mmHg The fluid is constantly taken by lymphatic vessels  Inspiration = -4/756 mmHg  Measured by directly using needle inserted and  Expiration = +4/764 mmHg indirectly using esophageal balloon connected  Important for with manometer Air in and out  Used to gas exchanges Prevents lung collapsing = being –ve Vein dilated : VR, this is called respiratory pump for VR 11/4/2024 Figure 5: Respiratory Pressures 32  Other Functions of Negative Intrapleural Pressure Helps lung inflation and prevent collapse Reduces work of breathing Helps to venous return and lymphatic drainage Increases lung compliance 11/4/2024 33  Respiratory muscles External oblique, rectus abdominal, Fig 6: Respiratory muscles internal oblique and transverse 11/4/2024 34  Phases of breathing and chest volume In the respiratory pause:  Muscles relaxed  The chess is in the position of expiratory end No air in and out Inspiration This position called midlethoracic position expiration Respiratory pause Chest volume 0 2 4 5 Times (sec) Fig 7: Chest volume Changes During Breathing 11/4/2024 35  Inspiration: normal and forceful Primary inspiratory muscles : involved in the normal inspiration – Diaphragm Innervated by phrenic nerve (C3-5)) Contracted and the volume of thoracic cavity increased Dome shaped is lost – External intercostals muscle Innervated by intercostals nerve (T1-12) Contracted and ribs rise up Volume of thoracic cavity increased Sternocleidomastoid, scalene, and pectoralis minor – Forceful inspiration 11/4/2024 36  Factors affecting pulmonary blood flow CO: factors affecting it, affects the flow – VR, cardiac contractility, rate of contraction, peripheral resistance Rate: increase rate, diastolic time decreased, decrease CO and then flow – Peripheral resistance: load against the heart pumps blood Inversely proportional to CO Maximum at splanchnic region 11/4/2024 37  Factors affecting pulmonary blood flow Pulmonary vascular resistance and increased by: – Inspiration: as the lungs expanded, intrathoracic pressure increased, vessels compressed and flow decreased – SNS Chemicals: CO2 and O2 in the lung : hypoxia constricts pulmonary artery Positions 11/4/2024 38  Expiration Normal expiration is passive – The elastic property of the lung and the chest – Surface tension Forceful expiration is active – Muscles are involved – Internal intercostals and abdominal (pelvic floor) muscles Contracted 11/4/2024 39  Phenomena during breathing Figure 8: Phenomena during breathing 11/4/2024 40  Surface tension and alveolar stability Surface tension (T) is inward force created by water molecules in the inner wall of alveoli Creates pressure (p) pulling the alveoli into the center P is proportional to the surface tension: P =2T/r Alveoli with smaller in size is the larger the pressure Laplace law: Pressure collapsing the alveolus is directly proportional to T and inversely proportional to the radius (r) of the alveoli 11/4/2024 41  Lung surfactants Chemicals reduce surface tension of smaller alveoli From type two alveolar cells, Type II pneumocytes – They also expresse immunomodulatory proteins that are necessary for host defense The mixture of dipalmitoylphosphatidylcholine (DPPC), other lipids and proteins, ions More effective in smaller alveoli – More effective during expiration 11/4/2024 42  Functions of lung surfactants Increase compliance, reduce recoiling and work of breathing Equalizes pressure in the smaller and larger alveoli Prevents pulmonary edema – Fluid collapses and reduces alveolar cells interestial pressure reduced (-ve) fluid from pulmonary capillary gets into pulmonary interstitium (suction force) edema 11/4/2024 43  Surfactant and pulmonary edema When the lung size reduced, intrathoracic pressure reduced and fluid inter into the pulmonary interstitium from blood vessel that causes edema Intrathoracic cavity Surfactant deficiency and smaller the alveoli cause pulmonary edema Fig 9: Surfactant and pulmonary edema 11/4/2024 44  Factors affecting lung surfactant secretion Alveolar cells maturity Hormones – Thyroid hormone and glucocorticoid stimulate the cells – Inhibited by insulin, smocking, prolonged inhalation of pure O2 (during surgery) 11/4/2024 45 Manifestations of Respiratory distress syndrome Respiratory abnormality related with surfactant insufficiency In the premature birth and destruction of the type II alveolar cells and results in:- – ↓C and ↑ST and ↑work of breathing – Pulmonary edema, ↓the size of the alveolar cells – Atelectasis (recoiling) : increase the tendency of recoiling of alveoli – More negative intrathoracic pressure required for lung inflation 11/4/2024 46  Compliance of the lung Stretchability of the lung /change in volume for change in pressure (C= V/p, and is increased when intra-alveolar pressure is increased or intrapleural pressure decreased Example : lungs and thorax = 130 ml/1cm of H20 and for the lungs alone = 220 ml/1cm of H20 intra-alveolar pressure incensement or 100 ml/1cm of H20 and 200 ml/1cm of H20 intrapleural pressure decrement Affected by – Distensibility of the lung and the chest – Surface tension and surfactants, collapsibility of the lung – Lung fibrous and alveolar size – IPP and work of breathing – Deformation: Kyphosis and scoliosis – Fibrotic pleurisy – Respiratory muscle paralysis and pleural effusion 11/4/2024 47  Graphic representation of lung compliance Normal C Volume Decreased C Thickening of lung tissue , Lung fibrosis Transpulnonary pressure (Pal- Pip ) Fig 10: Lung Compliance 11/4/2024 48  Effects of smocking on compliance Air heat damages epithelial cells in the air passage Cigarette components – Inhibit production of antibodies, surfactants, – Irritate mucosal lining and increase thick mucus secretion – Alveolar macrophages overloaded – Increase carbonmonoxide and reduce Hb oxygen affinity – Oxygen transported is affected 11/4/2024 49  Work of breathing Energy expend by respiratory muscles – Elastic resistance/compliance work (65%) Energy expend to expand the lungs To inflate the lung and overcoming lung and chest elastic recoil – Resistive work Viscosity/ tissue resistance work (7%): to overcoming the viscosity of the lung and chest wall structures, – Airway resistance work (28%). To overcome airway resistance Affected by bronchial dilation and constriction, mucus secretion, histamine levels 11/4/2024 50  Work of breathing increased by: Lung fibrosis and restrictive lung diseases Exercise and bronchial asthma Respiratory distress syndrome Less surfactants and less compliance More surface tension Pulmonary effusion Amniotic fluid infiltration in the lung tissue 11/4/2024 51  Work of breathing and airway diameter Cholinergic and adrenergic receptor levels and affecting drugs CO2, O2 level in the lungs Histamine – Opposite with sympathetic nerve Sympathetic and parasympathetic stimulation 11/4/2024 52  Minute ventilation Amount of air getting into the air passages per given time (minute) – Pulmonary minute ventilation = RT X TV = 12 breaths/minx 500ml/breath = 6L/min – Alveolar minute ventilation : amount of air utilized for gas exchange per minute in normal subject = RTX(TV-dead air volume) = 12 breaths/min x (500-150) = 4.2 L/min 11/4/2024 53  Types of dead space 1. Anatomical dead space : conducting zones that contain dead air  The effective volume in normal subject is TV-DV = 500-150 = 350 ml/breath 2. Alveolar dead space: site where dead air in the alveoli  When no blood is supplied to some area of alveoli (pulmonary artery thrombosis)  No in the normal subject 3. Physiological dead space – Anatomical dead space + alveolar dead space – Due to certain disorders 11/4/2024 54  Composition of air in the anatomical dead space At the end of expiration – Before inspiration started 500ml/breath More CO2 More CO2 At the end of inspiration – Before expiration 500ml/breath = 150 expired and 350 fresh No CO2 Fig 12: Respiratory and expiratory air compositions 11/4/2024 55  Dead space ventilation (VD) Air ventilates the dead space but not reach into gas exchange areas – Wasted ventilation – VD= DV x RR = 1.8L/min – Thus alveolar ventilation = 4.2L/min 11/4/2024 56  Structural deviations/deformities affecting Anatomical dead air volume Lordosis: exaggerated lumbar spinal cord curvature Kyphosis: exaggerated thoracic spinal cord curvature: round back at thoracic region Scoliosis: lateral deviation of the spinal cord or s shaped spinal cord Fig 13: Spinal cord anatomical variation 11/4/2024 57  Pulmonary Volumes and Capacities Parameters used to asses the respiratory system performs Using spirometer – Tidal Volume (TV) = 500ml – Inspiratory reserve volume (IRV) = 3000ml – Expiratory reserve volume (ERV) = 1100ml – Residual volume (RV) = 1200ml Amount of air that can not be expelled at the end of forceful expiration Increased in COPD – Asthma 11/4/2024 58  Residual volume measurement Helium Dilution method – Respirometer filled with known amount of helium – Make the subject to breath normally – Breath from respiremeter – Helium diluted in the lung and equals to helium remains in the respirometer – Concentration of helium in the respirometer determined – Functional residual capacity (FRC)= V (C1-C2)/C2 – Then FRC= ERV+RV, RV=FRC-ERV FRC: Volume of air remain in the lung after normal expiration = RV+ERV 11/4/2024 59  Residual volume measurement … Nitrogen washout method – Subject makes to inspire pure O2 and out to the Douglass bag, repeat for 6 to 7 minutes – Then N2 in the lung replaced by oxygen and comes out to the bag – Then measure Volume of air in the bag Concentration N2 in the bag – FRC= C1xV/C2, where C1: N2 conc in the bag, C2: N2 conc in the air, 78%, V:volume of air collected in the bag – E.g volume of air collected: 4OL, N2 in the collected air: 5% and N2 in the air:78% – FRC=ERV+RV, RV=FRC-ERV 11/4/2024 60  Capacities Capacities are the sum of different volumes – Total lung capacity, TLC Total amount of air the lungs hold during forceful inspiration and is about 6L TLC= RV+IRV +ERV+TV Different from vital capacity – Maximum air expelled following forceful inspiration – TLC- RV 11/4/2024 61  Pulmonary Capacities Vital capacity (VC)… – Volume of air expelled via deepest expiration following deepest inspiration (IRV) – VC= IRV+TV+ERV or TLC-RV – Affected by body size = 2.6L/m2, Otherwise is about 4.5 L 11/4/2024 62  Other Factors affecting VC Strength of respiratory muscle: the more the force of contraction is the more the VC Range of diaphragm mobility – Posture: sting and standing increase VC than lying (gravitational effect) – Abdominal content: pregnancy, hepatho-splenomegaly, ascitis limits diaphragm movement – Chest deformities: reduce diaphragm movement Sex, occupation (high in musicians) Athletes 11/4/2024 63  Other factors affecting VC… Residual volume: conditions increasing RV reduce VC – Bronchial asthma and emphysema Reduction of total lung capacity – Pneumothorax: when air in the pleural sac – Chest deformities ( chest cavity): kyphoscoliosis (restrict breathing) and lung inflation restricted – Pulmonary congestion: high pulmonary pressure: left heart problem Lung compliance reduction 11/4/2024 64  Timed vital capacity Called forced expiratory volume (FEV) – Percentage of air breathed out per given time using force after deep inspiration and is about 4.8L – FEV1: air breath out in the 1st one second Normally= 83% but reduced in asthmatic patients The more the airway resistance is the less FEV1 – FEV2: air breath out in the 1st two second =94% – FEV3: air breath out in the 1st three second =97% – After third second = 100% and reduced by obstructive Pulmonary obstructive (FEV=1.5L) Pulmonary restrictive (FEV=2.8L) lung diseases. 11/4/2024 65  FEV1 and FVC Forced vital capacity (FVC =80%): Total volume of air that can be exhaled forcefully from TLC , following forcefully inspiration and is 4.8 liters, some air remains The majority of FVC can be exhaled in diastolic peruse Blood flow is during systolic phase Called intermittent flow – Lower portion Alveolar pressure < the systolic and diastolic pressure Blood flow during both phases Called continuous blood flow 11/4/2024 78  Ventilation/perfusion ratio Extent of air in the lung and blood flow to the lung If TV, dead air volume and Q= 5000 are given then determine VA/Q and affected by – Extent of Ventilation : hyper or hypoventilation – Blood flow to the lung – Obstructive diseases …decrease the ratio 11/4/2024 79  Alveolar Ventilation (V) More –ve IPP Before inspiration Flow of air into the lung Not uniform along the lung units Apex Affected by gravity and intrapleural pressure (IPP) Base Gravity Less – ve IPP before inspiration V and is due to the hydrostatic pressure of the intrapleural fluid. Thus, alveoli less distended Base Apex 0 -2 -10 -13 11/4/2024 IPP(cm H20) 80 Fig 18: Ventilation and IPP  Ventilation … Small volume change at the apex during inspiration Least ventilation – But compared to the blood flow , more air is available But the base – More compliant during inspiration – More ventilated  Ventilation not uniform, regional differences 11/4/2024 81  Perfusion Blood flow into the lung Pulmonary circulation Affected by gravity Not uniform Affected by gravity and cardiac cycle Apex V/Q Ratio can therefore be defined as: the Effect of gravity on ratio of the amount of air reaching the alveoli the lung areas Base perfusion. In to the amount of blood reaching the alveoli upright position the apex get little blood V/Q relationship, in terms of gravity Apex : less ventilation and less perfusion Fig 19: Ventilation and Lung blood flow Base : more ventilation and more perfusion Note :  even the apex is less ventilated, it is too high for a very low blood flow = over ventilation Even the base is more ventilated, the blood flow is too more = under ventilated 11/4/2024 82  Factors affecting blood flow into the lung Gravity – It also affects ventilation, not only blood flow Sympathetic nerve Level of oxygen in the lung Pulmonary hypertension, afterload Pulmonary artery thrombosis and embolism Left heart diseases Right-left shunts – No blood flows into the gas exchange area 11/4/2024 83  Sections of lung and blood flow variations Alveolar pressure is greater than pulmonary capillary pressure in the upper section of lung – Absence of blood flow Pulmonary capillary pressure is greater than alveolar pressure during systole in the middle section of the lung – Intermittent blood flow: flow during systole Pulmonary capillary pressure is greater than alveolar pressure in systolic and diastolic phases of a cardiac cycle in the bottom section of the long – Continuous blood flow 11/4/2024 84  Zone of perfusion (Q) Zone 1: no perfusion, alveolar dead space, not in normal Zone 2: flow during systole The zones are not static Zone 2: flow during entire cardiac cycle Ventilation (V) perfusion(Q) ratio And flow to lung (Q)= 5L , thus V/Q = 0.8 to 1.2 Average= 1 And high at the top of the lung Fig 20: Lung Sections and Blood flow 11/4/2024 85 Perfusion getting less into the apex of the lung > Pa >> PAV/Q 1, 3 (high V &less Q) V/Q = 1, normally V/Q < 1, 0.6 Fig 21: Sections of the lung and V/Q ratio 11/4/2024 86  Shunt vs Dead space An area with perfusion but no ventilation (and thus a V/Q of zero) is termed shunt. An area with ventilation but no perfusion (and thus a V/Q undefined though approaching infinity) is termed “dead space“ – Space where gas is there but no flow of blood for gas exchange Thus, dead space causes (infinite V/Q) and shunt (zero V/Q). – In the shunt: no air ventilated into the blood 11/4/2024 87  Factors affecting V/Q Dead space Hypoperffusion Hyperventilation Increase the ration Less airway resistance High lung compliance air Alveolus CO2=40mmHg Blood 11/4/2024 Fig 22: Blood flow and V/Q 88  Partial pressure of gas Force exerted by single gas from the mixture Affected by – Fractional concentration of gas 0.21 for O2 and 0.03 for CO2 – Partial pressure of water – Total atmospheric pressure Different in different areas 11/4/2024 89  Partial Pressure of gases at different loci 11/4/2024 90 Fig:23: Partial pressure of gas at different s  Partial pressure of oxygen (P O2) 1. In ambient(dry) air PO2 = % X TAP = 160mmHg 2. Inspired air – The inspired air should be humidified and the temperature should be regulated – The humidification reduce the PO2 – PH20 for humidification = 47mmHg – PIO2 = % (760-47) mmHg= 153mmHg 11/4/2024 91  Factors affecting the PACO2 Two – Ventilation and metabolism – The more the ventilation is the les the CO2 in the alveolus – Metabolism increases the pressure PACO2 = metabolic (ml/min)/alveolar ventilation (ml/min) Alveolus CO2=40mmHg Tissue and metabolism Fig:24: Factors affecting PACO2 11/4/2024 92  Gas transport 11/4/2024 93  Oxygen transport Dissolved , in 1L= 3ml x 5= 15ml/min Combined, in 1L = 197ml x 5 = 985ml/min But the dissolved O2 important for PO2 Activating the chemoreceptors Alveolus CO2=40mmHg Fig:25: O2 Transportation 11/4/2024 94  Hemoglobin (Hb) Adult Hb (HbA)= 2α2β (4 protein subunits) Fetal Hb (Hb F)= 22, high affinity to oxygen Reduced form of Hb (ferrous iron, Fe2+) Methemoglobin: oxidized from of Hb (Fe2+ to Fe3+ ) – Oxygen not bind – Oxidation by cyanide and nitrites 11/4/2024 95  Hemoglobin molecule Hb= fully saturated when it carries 4 O2 Fig:26: Hg Structure and compositions 11/4/2024 96  O2 Carrying capacity of the blood: dissolved and complex with Hg Volume of O2 combined with Hb in 100 mL blood – In 100 mL blood, Hb=15g and one Hb carries 1.34 mL of O2 by volume in male – Then O2 Carrying capacity of this blood = 1.34 x15 = 20mL O2 /dL of blood (binding capacity of blood) Determine amount of O2 by volume in in 5L of blood in female The total oxygen content of blood = Hb-O2 + dissolved O2 11/4/2024 97  CO2 Transport Dissolved: 8% Carbonic acid :1% – Parts of dissolved CO2 reacts with H2O in the plasma, but is insignificant as the CA in plasma is absent, but is in the RBCs Bicarbonates (68%) – CO2 enters to RBCs: CO2+ H2O ….H2CO3 (fast as there is more CA in the RBCs), dissociated to H+ and H2CO3-. – Diffused out from cells with Cl- enters into the cell, and is called chloride shift Carbamino: 23% – Product when CO2 combined to the free amino group of an amino acid or a protein, such as hemoglobin – Some portion of CO2 can combine with Hg 11/4/2024 98  CO2 Transport … Reverse chloride shift – This is in the pulmonary capillary – H2CO3- is required to be released from the cells into plasma, while Cl- enters to the cell, called reverse chloride shift – In this pulmonary capillary O2 is diffused into the RBCs the Hg, and H+ is displaced 11/4/2024 99  CO2 Transport … Carbamino … – CO2 is combined on the terminal amine group of Hb = Carboamine hemoglobin – Even though the partial pressure of CO2 is b/n 40 and 47, % of carbondixied dissolved (5%) is greater than oxygen (1.5%). 11/4/2024 100  O2 and CO2 Transport : Summary Tissue Bohr effect Dissolved (1.5%) 90% Haldan effect 5% 5% Systemic capillary 11/4/2024 Fig:27: Gas Transport 101  CO2 dissociation curve  The Conc of CO2 in the blood is % of CO2 in the blood depending on the PCO2 52%  CO2 content in the blood is 48% when 48% PCO2= 40 mmHg  The curve is affected by  O2 content in the blood: when O2 is increased, Hg affinity to O2 is 40 mmHg 48 mmHg decreed. And this is in the pulmonary PCO2 (mmHg) capillary and more O2 in the blood Fig 28: CO2 dissociation curve shift the cove to the right Haldane's effect: in the pulmonary cappilary  The displacement effect of CO2 by O2 from Hg  This is when O2 is high and is in the pulmonary capillary 11/4/2024 102  Haldane's effect Causes – Combination of 02 with Hg – Acidity of Hg Advantage – For CO2 to be released into alveoli 11/4/2024 103  Oxyhemoglobin dissociation curve 11/4/2024 104  Oxyhemoglobin dissociation curve Amount of O2 unloaded in the tissue capillary 97 Myoglobin The curve is (hyperpola) sigmoidal: as the Hb 75 affinity to O2 is high Hb saturation (%) Oxygenated blood at small O2 level Normal leaving the lungs blood %Hb saturation = 50 oxyhemoglobin /HB in the sample 25 Blood returning from the tissue 0 Artery PO2 25 40 75 100 =100 vein PO2(mmHg) Myoglobin in muscle and found in the blood after muscle injury PO2 =40 11/4/2024 105 Fig 29: Oxyhemoglobin dissociation curve  Factors affecting Oxyhemoglobin dissociation Left shift curve Fetal HB & Stored blood conditions that reduces CO Normal Hb affinity to O2 shift the curve to the right Right shift Hb saturation (%)  2,3 DPG, TO  CO2 (bohr effect) , ↑H+ Indicates the reduction of and  O2, pH, Hb affinity to O2, Exercise, higher unloading/dissociation, altitude , in the tissue RBSc, Anemia Carboxyhemoglobin: Hb+ CO. Hb affinity to CO is 200x higher than O2 Carboaminehemoglobin : Hb+CO2 , not on the same site where is O2 bind Oxyhemoglobin : Hb+ O2 Fig 30: Factors affecting Oxyhemoglobin dissociation curve when blood stored, 2,3 DPG lost 11/4/2024 106  P50 in Oxyhemoglobin dissociation curve 97 myoglobin 75 Hb saturation (%) Oxygenated blood Normal leaving the lungs blood 50 25 Blood returning from the tissue 0 50 75 P50 2526 100 Right and left shift PO2(mmHg) Fig 31: P50 and affecting factors 11/4/2024 107  Bohr effect of CO2 The effects of CO2 on O2 affinity of HG In the systemic capillary, there is more CO2 from the blood This reduces Hg affinity to O2 More O2 released to tissue and the oxyhemoglobin dissociation curve shifted to right Increases bohr effect:- – High Temperature, pH, PCO2 and 2,3 diphosphoglycerate (2,3 DPG) – Generally, all factors affecting the oxyhemoglobin dissociation curve affect the bohr effect of CO2 – Temperature increases CO2 formation and decreases Hg affinity to O2 11/4/2024 108  Breathing rhythm and respiratory control center 11/4/2024 109  Breathing Controls Breathing centers – In the brainstem – Inspiratory center, I neurons Found in the medulla oblongata Inspiratory neurons, DRG cells + Electrical stimulation causes contraction of inspiratory muscles Inhibited by pneumotaxic neurons – Expiratory center, E neurons This stimulation is to I VRG, expiratory cells neurons, otherwise is Inactive during normal expiration inhibitory to E neurons Fig 32: Breathing control centers 11/4/2024 110  Respiratory neurons The DRG … – a part of Nucleus of Tractus solitarius (NTS) of medulla oblongata – I neurons connected with the frenic nerve in the s cord ipsilaterally. – NTS receives messages from respiratory related receptors (mechano and chemo) The VRG … – In the ventrolateral of medulla oblongata containing I(upper part) and E neurons (the lower part in the retroambigulis) – I neurons to inspiratory muscles other than diaphragm – Located in the nucleus ambiguus and retroambigulis 11/4/2024 111  Respiratory neurons… Botzinger complex (BC) : excites I neurons – Contains I neurons above the nucleus ambiguus – Receives message from the NTS and stimulate DRG I neurons and inhibit VRG E neurons – Has inherent rhythmic action: medullary respiratory pacemaker Apneustic center (AC) : in the lower part of pons – Has inherent tonic activity stimulate DRG I neurons – Creating breathing rhythm – The rhythmic intermittent inhibitory discharges from vagus nerve and pneumotaxic center affects AC activities – Increases depth of inspiration 11/4/2024 112  Respiratory neurons… Pneumotaxic center (PC) : pontine respiratory group – In the upper part of pons and contains these nuclei Nucleus parabrachialis medilais (E - neurons) Nucleus parabrachialis lateralis (I- neurons) Kolliker –fuse nucleus (I- neurons) – Inhibits inspiratory neurons and stimulate expiratory neurons and initiates expiration – Decreases duration of inspiration – That means increases respiratory rate 11/4/2024 113  Respiratory neurons… Thus breathing rhythm is contributed by – The rhythmic activity of the apneustic center – The rhythmic intermittent inhibitory inputs from vagal nerve – The rhythmic activity of the botzinger complex Sending rhythmic discharge stimulating I neurons and inhibiting E neurons – The rhythmic activity of the DRG of neurons 11/4/2024 114  Brainstem transection and breathing Depend on where the brainstem is cut – Apneustic breathing: if the cut is at the middle of the pons – Prolonged inspiratory spasm: like breathing hold – Expiration weak (pneumotaxic inhibitory input removed) 11/4/2024 115  Reciprocal activity of the inspiratory and expiratory muscles When inspiraotry muscle are contracted, the expiratory relaxed and vice versa Mechanism – Brainstem mechanism When I neurons stimulated irradiates the inhibitory discharges to E neurons – Spinal mechanism The descending fibers activate the motor fibers have collateral inhibitory inputs to the fibers innervating antagonize muscles 11/4/2024 116  Central control of ventilation Pneuomtaxic center(stop inspiration) The brainstem = autonomic Pons center Apneustic center (stimulates I n) Medulla oblongata I and E (quite Rhythm Periodical discharging- on at rest) and off pattern neurons Ipsilateral connection C3 I and E neurons to Spinal motor Spinal cord neurons inspiratory and neurons expiratory muscles (frenic nerve) respectively C5 Fig 33: Spinal cord Neurons and Breathing control centers 11/4/2024 117  Reciprocal activation of respiratory muscles I neurons When I neurons are E neurons stimulates irradiates that inhibits E neurons Descending tract collateral branch Spinal cord motor neurons Diaphragm Fig 34: Breathing control centers communication 11/4/2024 118  Voluntary control system of breathing By motor area of the cerebral cortex Pyramidal tracts getting into the cervical and thoracic segment of spinal cord (by passing the brainstem centers) – Terminates on the lower motor neuron of frenic and intercostal nerve – Imitates breath holding Aftersometimes, the voluntary mechanism of breathing overrides by autonomic mechanism – Involuntary breathing initiated 11/4/2024 119  Voluntary control of breathing voluntary breathing control The pyramidal tract directly affect the spinal cord motor Cerebral cortex Descending tract for neurons getting into respiratory muscles Brainstem neurons Autonomic (brainstem) mechanism may be override They Converge to the same nerve in the Cord the voluntary mechanism C3 Spinal motor neurons (frenic nerve) C5 Fig 35:Brain area for voluntary breathing control 11/4/2024 120  Ondines curse Paralyzing of the autonomic breathing control system – Infection: poliomyelitis of medulla oblongata or when its compressed – Subject can alive when staying awake and remembering to breath – Causes hypoventilation – One form of central sleep apnea which develops as a result of diminished ventilatory response to PCO2 11/4/2024 121  Breathing modifiers /regulatories chemical and non chemicals Determine breathing rhythm generator center Hering -breuer Breathing reflex Fig 36: Breathing Modifiers 11/4/2024 122  Factors stimulate ventilation during exercise Arterial PO2,PCO2,H+ Motor cortex Temperature Respiratory center Skeletal muscle Baroreceptors High plasma NE Conditioned and K+ response concentration Breathing stimulated by ↓Ph and O2 , acidosis and ↑ CO2 reduced by alkalosis Fig 36.1: Breathing Modifiers 11/4/2024 123  Breathing Modifiers … Information from baroreceptors – Increase in BP detected – Herring nerve, branch of glossopharyngeal nerve activated – Information projected to the respiratory center and causes BP reduction Breathing inhibition Otherwise information to respiratory center from – Chemoreceptor Facilitate breathing – Proprioceptors Facilitating – Thermo receptors Facilitating – Nociceptors Facilitating 11/4/2024 124  Respiratory chemoreceptors Monitor PO2, PCO2 and pH of the blood Adjust the respiratory center accordingly Peripheral – Carotid bodies in the carotid sinus Most important in human body as they are the highest blood supply in the body At the bifurcation of the common carotid arteries Innervating by hering nerve (branch of glosopharyngeal nerve) More sensitive to hypoxia than to acidosis Activated by free or dissolved O2 11/4/2024 125  Peripheral chemoreceptors con’t Aortic bodies – On the wall of aortic arch supplied with less blood – Innervated by vagus afferents – Their sensitivity to hypoxia, hypercapenia and acidosis is less than the carotid bodies – The ventilation response caused by these bodies is weak – Causes cardiovascular reflexes 11/4/2024 126  Central chemoreceptr In the medulla oblongata Stimulated by H+ from CO2 in the CSF H+ is from CO2: cross the BBB No central O2 sensing receptors 11/4/2024 127  Chemical inputs affect ventilation Arterial P02 non H2CO3 arterial PCO2  Brain ECF(CSF) PCO2 Arterial [H+] Brain ECF [H+] Peripheral chemoreceptor Firing Firing of modularly Central chemoreceptor inspiratory neurons Firing Firing of neurons into diaphragm and inspiratory intercostals These muscle contract and increase ventilation Fig 37: Chemical inputs affecting ventilation 11/4/2024 128  R/N between the systemic arterial blood and central chemoreceptor BBB Arterial blood Medulla CO2 CO2/H+ H+ Pass the BBB slowly Thus, the central chemoreceptors are very sensitive to the CSF H+ change than the systemic H+ changes as the H+ cross the BBB slowly Fig 38: BBB and Breathing Center 11/4/2024 129  A rise in PaCO2 lowers CSF pH which is sensed by medullary central chemoreceptors CO2 blood brain ISF CO2 + H2O H2CO3 H+ + HCO3 Carbonic anhydrase Diaphragm and external intercostal Drop in CSF pH muscle activated more Medullary chromo receptor  Respiratory Adaptation Respiratory adaptation to exercise ↑ O2 consumption and ↑ CO2 production leading to ↑ depth and rate of ventilation (hyperventilation) ↑ Venous CO2 and ↓venous O2 ↑ HR,SV, CO, pulmonary blood flow, arterial lactic acid, V/P ratio Arterial Ph, as lactic acid is increased Right oxygen dissociation curve sift 11/4/2024 131  Respiratory Adaptation… Respiratory adaptation to higher altitude – ↓ PaO2 ↑ ventilation rate (stimulated by hypoxemia ↓PaCO2 and ↑ arterial pH (Respiratory alkalosis) – ↑Hg, EPO and Hcr, 2, 3 DPG concentration↓Hg affinity to O2 O2 dissociation curve right shift – ↑Pulmonary vascular resistance chronic hypoxia pulmonary vasoconstriction pulmonary hypertension right ventricular hypertrophy – ↑ Renal HCO3- excretion (to compensate for respiratory alkalosis) – ↑Mitochondrial numbers in the cell 11/4/2024 132  Respiratory Problems 11/4/2024 133  Respiratory abnormalities Apnea: Breathing arrest, temporarily Tachypnea: rapid rate and high force Bradypnea: reduced rate Polypnea: rapid rate but shallow breathing Hyperventilation: too high rate and depth Hypoventilation: too low rate and depth Dyspnea: difficulty in breathing 11/4/2024 134  Respiratory problems Apnea: unlike to dyspnea (difficult to breath) apnea is periodic arresting of breathing – Central apnea: when the problem is breathing center – Obstructive sleep apnea: obstruction when sleep on the back When pharyngeal muscles get relax during sleep Common in obese, throat and tongue and other muscle relaxed excessively Soft tissues around airways obstruct the tract – Voluntary apnea – Apnea after hyperventilation – Deglutition apnea Berthing stop during swallowing … esophageal phase Bolus in the esophagus activate nerve endings and respiratory neurons are inactivated – Vagal apnea Vagal nerve stimulation inhibits inspiratory neurons 11/4/2024 135  Respiratory problems … Adrenalin apnea – NA…increases BP… Vasomotor center activity inhibited Inspiratory neurons inhibited 11/4/2024 136  Emphysema Destruction of alveolar wall by enzymes produced by white blood cells in the lung in response to d/f conditions (smocking) – Neutrophil trypsin like protease, (elastase and proteinases), but their production is inhibited by α1-antitrypsin – act against elastin Overstretching of alveoli causes damaging of airways distal to terminal bronchiole – Respiratory bronchiole, alveolar sacs, alveolar ducts, and alveoli Airspaces are abnormally dilated and wall is broken down by proteinases Expiration is mainly affected than inspiration 11/4/2024 137  Emphysema … The broken-down of alveoli decreases the gas exchange area Atrophy and collapse of airways: airway resistance elevated Generally, – Mucus hyper secretion – Large size of airspaces – Reduces the SA for diffusion – Destruction is not uniform along the lung brings ventilation perfusion inequality along the areas of lungs and high work of breathing 11/4/2024 138  Fig 39: Emphysema and factors involved 11/4/2024 139  Emphysema Neutrophil elastase: enzyme produced by white blood cells in the lung that kill bacteria. This enzyme also destruct the lung tissue if the Fig 39.1: Emphysema and factors involved lung tissue is not protected by alpha I antitrypsin 11/4/2024 140  Acidosis and alkalosis Respiratory Alkalosis – Increase in the blood Ph – Causes hypoventilation Respiratory acidosis – Caused by respiratory failure In this case, respiration is important in acid-base balance – Regulating the blood levels of carbonic acid 11/4/2024 141  Regulation of Acid-Base Balance The acid-base balance aims at keeping the (H+) in the body fluids constant. H+ affects the PH of the blood PH= -Log H+ = 7.4 at [H+]= 0.00004 mEq/L Acidosis: PH< 7.4 Alkalosis: PH> 7.4 Abebaye A (BSC, MSc, PHD, AAU- Dept of 11/4/2024 142 medical physiology)  Acid-base balance Chemicals buffers – Hemoglobin, bicarbonate aion,monohydrogen phosphate Physiological buffers – Renal system – Respiratory system Regulates Ph via its affect on arterial partial pressure of carbon dioxide level 11/4/2024 143  Action of respiration in blood Ph regulation  pH…acidosis…activates chemoreceptors….hyperve ntilation….PCO2…Ph  Ph …alkalosis …chemoreceptor stimulated…hypoventilatio n … PCO2…pH Fig 40: Roles of respiratory system in acid-base balance 11/4/2024 144  Pulmonary hypertension Consequence of left ventricular problem Results in – Right ventricular failure – Jugular vein distention – Hepathomegaly 11/4/2024 145  Pleural effusion Excessive fluid in the pleural membrane surrounding the lungs Caused by – Left ventricular failure and pulmonary edema – Membrane inflammation Induced reflex from : J receptor reflex – BY J receptors Normally inactive, but stimulated when the pressure in the interstitial space surrounding the lung elevated Brings tachypnea 11/4/2024 146  Hypoxia 11/4/2024 147  Types of hypoxia Hypoxic Hypoxia – Reduced O2 in tissue and cells, anoxia is absence of oxygen – Caused by Lungs and heart problems Insufficient surfactant Suffocation Higher altitude elevation Airways obstruction Anemia 11/4/2024 148  Causes … Alveolar hypoventilation, low barometric pressure (high altitude), large airway obstruction, Pneumonia, disorders of the respiratory muscles and neuromuscular junction, diseases of the pleural and chest wall Respond to O2 therapy V/Q mismatch (may compensated by the body) – E.g if V is getting less ----constriction and Q gets less This ratio affected by different factors 11/4/2024 149  Shunt to dead space comparison Air not exchanged b/se of reduced flow 11/4/2024 150 Fig 41: Blood flow and ventilation  Causes of hypoxic hypoxia con’t 11/4/2024 Fig 42: Hypoxic hypoxia 151  Hypoxic hypoxia Reduction of oxygen in the tissue and attributed to – Less oxygen tension in air Elevation, closed space, breath in gas with low oxygen – Diseases causing decreasing pulmonary ventilation Hydrothorax, hemothorax, pneumothorax, lack of surfactant, obstruction – Cardiac diseases 11/4/2024 152  Stagnant hypoxia When oxygen not transported in the circulation – Low pulmonary vein out flow (pulmonary embolism), congestive heart failure, MI – Less CO (affected by cardiac preload, contractility and after- load), cardiac arrest, cardiogenic shock – Hypotension – Embolus (localize blockage) – Hemorrhage – Vasospasm – Thrombosis 11/4/2024 153  Histotoxic hypoxia Unable the tissue extracts available oxygen from blood Disruption of cellular enzymes used to O2 (cytochrome oxidase system) by sulfide or cyanide poisoning Paralysis of cytochrome oxidase in the mitochondria Narcotics and alcohol also contribute for this hypoxia This is without hypoxemia 11/4/2024 154  Anemic hypoxia Reduction of RBCs and hemoglobin (