Ch4 Respiratory Systems Summer 2023 PDF

Physiology (0603302) Ch.4 Respiratory System, gas exchange, and Control of Respiration Summer semester-2023/2024 Dr. Mohammad A. Abedal-Majed Scho...

Physiology (0603302) Ch.4 Respiratory System, gas exchange, and Control of Respiration Summer semester-2023/2024 Dr. Mohammad A. Abedal-Majed School of Agriculture The University of Jordan 1 Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 1  An Overview over the Respiration Respiration is the process by which the body takes in and utilizes oxygen (O2) and gets rid of carbon dioxide (CO2). A- External respiration: exchange of O2 and CO2 between the external environment and the cells of the body B- Internal respiration: Gas exchange between the blood and tissues(metabolic process in the mitochondria) Ventilation: gas exchange between the atmosphere and air sacs (alveoli) in the lungs Gas exchange of O2 and CO2 between air in the alveoli and the blood Transport of O2 and CO2 between the lungs and the tissues Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 2  Respiratory System Functions **Primary functions 1.Gas exchange: Oxygen enters blood and carbon dioxide ***Other functions 1.Regulation of blood pH: Altered by changing blood carbon dioxide levels ↑ CO2 → ↓ pH -CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+ 2.Voice production: Movement of air past vocal folds makes sound and speech 3.Protection: Against microorganisms by preventing entry and removing them In the nasal cavity, (Filters the foreign bodies) hairs and mucus trap small particles, viruses, bacteria, dust, and dirt to prevent entry. If particulates make it beyond the nose or enter via the mouth, the bronchi and bronchioles contain several protective devices Dr. Mohammad A. Abedal-Majed 6-4-2023 3 Inhale the future, exhale the past.  Respiratory System Divisions A- Conducting airways gas enters at nasopharynx -no gas exchange (anatomic dead space) &/or oropharynx ↓ Upper Airway= before trachea: larynx Function: 1- Filters, warms, and ↓ humidifies incoming air. trachea 2- Protects delicate lower tract. ↓ carina & L & R main-stem bronchi Nose: is primary route for air entering respiratory system. ↓ Pharynx: common passageway for bronchioles respiratory and digestive systems) Larynx: (voice box) Lower Airway Function: Conducts air to and from gas exchange surfaces. –trachea + bronchi + bronchioles Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 4  Respiratory System Divisions B- Respiratory airways -all lower airways (gas exchange) Bronchioles ↓ alveolar ducts ↓ alveolar sacs -non-respiratory & respiratory bronchioles -large surface area for gas exchange -capillaries = 70-80 m2, alveoli = 50-100 m2 -(High density of capillaries around alveolus) ~ 1000 capillaries for each alveolus -RBCs pass through the alveolar capillary network in ˂ 1 sec Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 5  Respiratory System Divisions *Airways -cartilaginous airways = trachea & bronchi -non-cartilaginous airways = bronchioles & alveolar ducts Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 6  Muscles of inspiration *inspiration = inhalation of air into the lungs -contraction of the diaphragm drives inspiration -major muscle of respiration -contraction → ↑ the size of the thoracic cavity & pushes against the abdominal contents -moves ~ 1 cm during quiet breathing & up to 10 cm during active breathing -other inspiratory muscles help expand the rib cage -e.g. external intercostals Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 7  Muscles of expiration *Expiration = exhalation of air out of the lungs -exhalation is passive during quiet breathing -the diaphragm relaxes during exhalation -exhalation requires assistance during active breathing (e.g. exercise, hyperventilation) -internal intercostals -abdominal wall muscles (abdominal breathing) Breathing rate: At rest: 10-20 breaths / minute During exercise: 40 - 45 at maximum exercise in adults Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 8  Static Lung Mechanics *Lung pressures PB = pressure surrounding chest wall (barometric pressure) PPL=pressure surrounding the lung within the pleural space= Pleural Pressure (Space between Lungs and chest wall) PA = pressure within alveoli PL = Transpulmonary pressure = PA – PPL -difference between alveolar & pleural pressures (determined the lung size) -The bigger the difference, the bigger the lung PW = transmural pressure = PPL – PB -difference between pleural & barometric pressures Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 9  Principles of Breathing Follows Boyle’s Law: Pressure (P) x Volume (V) = Constant Conducting Airways Lungs Gas Exchange ***Pleural Cavity Very small space Maintained at negative pressure Transmits pressure changes Chest Wall Allows lung and ribs to slide (muscle, ribs) Diaphragm (muscle) Pleural Cavity Imaginary Space between Inhale the future, exhale the past. Lungs and chest wall 10 Dr. Mohammad A. Abedal-Majed 6-4-2023  Principles of Breathing -lungs require positive PL (transpulmonary pressure) to inflate PL = PA – PPL (alveoli pressure-plural pressure) 1 - ↑ PA (positive pressure ventilators) -excessively high PA (> 20 cm H2O) (14mmHg) can rupture alveoli -exceed elastic limits of elastin/collagen in the lung 2 - ↓ PPL (activate inspiratory muscles) -contraction of diaphragm → ↑ volume of thoracic cavity → ↓ PPL (Boyle’s law: ∆V * ∆P = constant) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 11  Principles of Breathing -prior to inspiration -PPL is slightly negative (-5 cm H2O) (-3.7mmHg) -PA is equal to PB (0 cm H2O) -tidal inspiration (contraction of diaphragm) -PPL slightly ↓ (becomes more negative; ~ -6 to -8 cm H2O during quiet breathing) -PA ↓ (-2 cm H2O) -expiration (relaxation of diaphragm & elastic recoil) -PPL ↑ (becomes less negative) -PA ↑ (+2 cm H2O) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 12  Static Lung Mechanics (Compliance and Elastic recoil) *Compliance -measure of the elastic properties of the lung - measured by the change in volume resulting from a 1 cm H2O change in pressure -i.e. slope of the pressure volume curve (∆V/∆P) -compliance is the inverse of elastic recoil -high compliance = easily distended -low compliance = difficult to distend -the lung distends easily at low lung volumes (steep slope) - high lung volumes require larger ↑ in pressure as alveoli/airways become maximally distended (flatter slope) -↑ compliance – curve will shift up/left -↓ compliance – curve will shift down/right *elastic recoil = tendency to resist stretching -how easily lungs snap back & push air out Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 13  Static Lung Mechanics (Compliance and Elastic recoil) *Compliance -↓ compliance → ↑ the workload of breathing -↓ compliance (pressure volume curve shifts downward) characterizes restrictive pulmonary disease -lungs: fibrosis, pulmonary edema/hemorrhage, -chest wall: obesity (extra adipose tissue) & muscular diseases -↑ compliance (pressure volume curve shifts upward) can result from obstructive pulmonary disease -lungs: emphysema -↓ elastic recoil → ↑ compliance Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 14  Static Lung Mechanics (Surface Tension) -elastic properties of the lung (e.g. elastin, collagen) are responsible for some but not all of the elastic recoil -surface tension is the other primary contributor to elastic recoil Inhale the future, exhale the past. 15 Dr. Mohammad A. Abedal-Majed 6-4-2023  Static Lung Mechanics (Surface Tension) Law of Laplace: describes the relationship between pressure within a sphere & the tension in the wall – Pressure in alveoli –directly proportional to surface tension inversely proportional to radius of alveoli **alveoli of different sizes that are connected with equal surface tension -larger volume = smaller pressure -smaller volume = larger pressure -air moves from areas of higher pressure to lower pressure → air will move from smaller alveolus to larger alveolus → smaller alveolus will collapse → large distending force required for reopening -this is not what physiologically occurs -2 physiologic phenomena prevent this: -surfactant -Alveolar interdependence 16 Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023  Effect of Surface Tension on Alveoli size Surfactants to reduce the surface tension at liquid-gas or liquid-solid interfaces Air Flow Expand Collapse Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 17  Static Lung Mechanics (Surfactant) *Surfactant -anti-stick properties similar to a detergent -Mixture of phospholipids, lipids, fatty acids, & proteins -components primarily secreted by type II pneumocytes --- Main role is to lower alveolar surface tension - Reduces attractive forces of hydrogen bonding - Surface tension in alveoli is reduced Prevents alveolar collapse (at end of expiration). -without surfactant -surface tension remains constant -pressure required to keep an alveolus inflated ↓ as lung volume ↑ -If the alveoli were lined with water alone, surface tension would be so great that the lungs would collapse (due to great cohesive forces between water molecules) -with surfactant: -↓ surface tension in smaller alveoli & ↑ surface tension in larger alveoli -pressure required to keep an alveolus inflated ↑ as lung volume ↑ Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 18  Static Lung Mechanics (Surfactant) Surfactant prevents alveolar collapse Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 19  Static Lung Mechanics (Surfactant) Physiology Importance of Surfactant 1.Reduce the work of breathing and increases compliance 2.Stabilize alveoli ( Prevent collapse and sticking of alveoli) 3.Maintain the dryness of the alveoli ( Prevent the edema of the alveoli) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 20  Clinical Applications *Premature births -surfactant production/secretion begins in late gestation -its appearance correlates with the rise in fetal plasma cortisol levels -Human born prematurely have difficulty inflating their lungs -inadequate surfactant in alveoli Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 21  Pulmonary Volume and Capacity Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 22  Pulmonary Volume and Capacity Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 23  Pulmonary Volume and Capacity Tidal Volume (VT) = volume of air breathed into & out of the lung during quiet (normal) breathing (400 – 500 ml) Inspiratory Reserve Volume (IRV) = Amount of air inspired forcefully after inspiration of normal tidal volume (1500 – 2000 ml) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 24  Pulmonary Volume and Capacity Expiratory Reserve Volume (ERV) Amount of air forcefully expired after expiration of normal tidal volume (900 – 1200 ml) Residual Volume (RV) =Volume of air remaining in respiratory passages and lungs after the most forceful expiration (1500 ml in male and 1000 ml in female) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 25  Pulmonary Volume and Capacity -lung capacities = the sum of 2 or more lung volumes (Forced) Vital Capacity (VC) (FVC) = total volume of air that can be exhaled from max. inhalation to max. exhalation = (VT + IRV + ERV) (Sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume) Total Lung Capacity (TLC) = total volume of air that can be contained in the lung = (VC + RV) (Sum of inspiratory and expiratory reserve volumes plus the tidal volume and residual volume) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 26  Pulmonary Volume and Capacity Inspiratory Capacity (IC) = total volume of air that can be inhaled = VT + IRV (Tidal volume plus inspiratory reserve volume) Functional Residual Capacity (FRC) = volume of air in the lungs after a normal exhalation = (RV + ERV) (Expiratory reserve volume plus the residual volume) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 27  Summary of Lung Volumes and Capacities Description Avg. Value Tidal volume (TV) Volume of air entering or leaving lungs during a single breath 500 ml Inspiratory reserve volume Extra volume of air that can be maximally inspired over and 3000 ml (IRV) above the typical resting tidal volume Inspiratory capacity (IC) Maximum volume of air that can be inspired at the end of a 3500 ml normal quiet expiration (IC =IRV + IV) Expiratory reserve volume Extra volume of air that can be actively expired by maximal 1000 ml (ERV) contraction beyond the normal volume of air after a resting tidal volume Residual volume (RV) Minimum volume of air remaining in the lungs even after a 1200 ml maximal expiration Functional residual Volume of air in lungs at end of normal passive expiration 2200 ml capacity (FRC) (FRC = ERV + RV) Vital capacity (VC) Maximum volume of air that can be moved out during a single 4500 ml breath following a maximal inspiration (VC = IRV + TV + ERV) Total lung capacity (TLC) Maximum volume of air that the lungs can hold 5700 ml (TLC = VC + RV) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 28  Summary of Lung Volumes and Capacities 4 Volumes 4 Capacities : Sum of 2 or more lung volumes IRV IC VC TV TLC ERV FRC RV RV Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 29  Clinical application RV/TLC : Normally less than 0.25 The ratio Increase by the obstructive pulmonary disease (RV) The ratio Increase during the restrictive lung disease (TLC) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 30  Clinical application Restrictive pulmonary disease Restrictive pulmonary disease (reduced compliance) These are diseases that reduce the effective surface area available for gas exchange Normal Lung Volume Lung Volume in Restrictive Disease eg fibrosis / pulmonary oedema -primarily associated with ↓ lung volumes (e.g. pulmonary fibrosis) -↑ RV/TLC ratio due to a relative ↓ in TLC Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 31  Clinical application Restrictive pulmonary disease Can be measured by a spirometer Spirogram is a graph that records inspiration and expiration Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 32  Clinical application Obstructive pulmonary disease These are diseases that reduce the diameter of the airways and increase airway resistance - remember Resistance increases with 1/radius 4 Normal Airway Calibre Airway Calibre in Obstructive Disease e.g asthma / bronchitis emphysema -↓ elastic recoil → ↑ compliance which mean increase RV Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 33  Clinical application Obstructive & Restrictive Pulmonary function test A) Forced Vital Capacity – FVC (Pulmonary function test) B) Forced Expiratory Volume - FEV C) Minute ventilation Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 34  Clinical application Obstructive & Restrictive Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 35  Dynamic Lung Mechanics A: 2 airways/alveoli with equal resistance & compliance -alveoli fill with air identically B: 1 airway has twice the normal resistance -alveolus associated with ↑ resistance will have ↓ air flow (volume/time) -will fill to the same volume as normal alveolus if given enough time -time limited – insufficient time to fill at rapid respiratory rates C: 1 alveoli has ½ of the normal compliance -alveolus with ↓ compliance will fill in approximately the same amount of time -volume limited – only fills with ½ of the normal volume of air Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 36  Respiratory Gases Exchange *Respiratory gases -must consider the partial pressure of gases in the inspired air, respiratory airways, & blood -gas mixture (e.g. air in alveoli) is in contact with a liquid (e.g. blood) -movement of gases is determined by the partial pressures & the solubility in a liquid -gases will move down their partial pressure gradient (alveoli ↔ blood) -movement of a gas is also determined by its solubility in blood -the solubility of O2 & CO2 are different in blood -only free, unbound gas molecules contribute to partial pressure -O2 bound to hemoglobin does not contribute to the partial pressure of O2 in blood Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 37  PO2 and PCO2 in Blood -exchange of gases between the alveoli & capillaries is via diffusion -PaO2 in blood entering tissue capillaries is ~ 85-100 mm Hg -PaCO2 in blood entering tissue capillaries is ~ 40 mm Hg -partial pressure gradient for O2 averages 45-60 mm Hg -tissue PO2 determined by delivery rate & consumption rate (averages 40 mm Hg) -tissue PCO2 determined by removal rate & production rate (averages 46 mm Hg) -partial pressure gradient for CO2 averages 6 mm Hg deoxygenated blood oxygenated blood Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 38  Oxygen Transport -O2 is poorly soluble in H2O & plasma -only a small amount dissolves in plasma -[O2] in plasma ↑ linearly with ↑ PAO2 -if PAO2 = 100 mm Hg, 0.3 ml O2 dissolves into 100 ml of blood -if PAO2 = 600 mm Hg (inspiring pure O2), 1.8 ml O2 dissolves into 100 ml of blood -with only dissolved O2, extremely high cardiac output would be necessary to deliver adequate O2 to tissues Method Percentage Dissolved in Plasma 1.5 % Combined with Hemoglobin 98.5 % Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 39  Oxygen Transport -hemoglobin -consists of 4 units, each composed of a globin & a heme - each iron molecule can reversibly bind with a single O2 molecule -Reversible binding allows for continuous O2 uptake (lungs) & release (tissues)  High PO2 (alveolar capillaries): Hb loads up O2  Low PO2 (systemic capillaries): Hb unloads O2 blood PO2 is not a measure of the total O2 content of the blood but only of the dissolved portion of O2. Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 40  Affinity of hemoglobin for O2 * PH & PCO2 and affinity of hemoglobin for O2 -↑ tissue metabolism → ↑ CO2 & H+ production → ↓ pH -change in pH alters hemoglobin structure (primary effect) -binding of CO2 also alters hemoglobin structure (minor effect) -↓ pH → shifts oxyhemoglobin curve to the right (↑ P50, ↓ Hb affinity for O2) -promotes the dissociation (i.e. release) of O2 from hemoglobin (desirable with ↑ tissue metabolism) -↑ pH → shifts oxyhemoglobin curve to the left (↓ P50, ↑ Hb affinity for O2) -inhibits dissociation of O2 from hemoglobin Increase in CO2 in the blood decreases the affinity of Hb for O2, so Hb unloads more O2 at the tissue level Increased blood acidity increases Hb release of O2 Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 41  Affinity of hemoglobin for O2 *Blood temperature and affinity of hemoglobin for O2 -↑ tissue metabolism → ↑ heat production → ↑ blood temperature -↑ temperature → shifts oxyhemoglobin curve to the right (↑ P50, ↓ Hb affinity for O2) -promotes the dissociation (i.e. release) of O2 from hemoglobin (desirable with ↑ tissue metabolism) -↓ temperature → shifts oxyhemoglobin curve to the left (↓ P50, ↑ Hb affinity for O2) -inhibits dissociation of O2 from hemoglobin Increase in temperature results in more unloading of O2 at a given PO2 Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 42  Shifting the O2 Curve Inhale the future, exhale the past. 43 Dr. Mohammad A. Abedal-Majed 6-4-2023  Fetal Hemoglobin Advantage Increased O2 release to the fetal tissues under the hypoxic condition. Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 44  Clinical Applications *Carbon monoxide poisoning -carbon monoxide (CO) & O2 bind the same sites on hemoglobin -hemoglobin’s affinity for CO is 200-fold of that for O2 -hemoglobin will preferentially bind CO → ↓ O2 content in the blood (PaO2 is normal) -binding of CO to hemoglobin shifts the oxyhemoglobin curve to the left -inhibits the dissociation of O2 from hemoglobin -prolonged inspiration of CO can fully saturate hemoglobin with CO -inspiration of air with < 1% of CO can lead to death Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 45  Carbon Dioxide Transport -majority of CO2 in the blood diffuses into RBCs &/or undergoes chemical reactions ~ 5% of CO2 is transported as CO2 in plasma -CO2 can be converted into carbamino compounds -formed by coupling CO2 to –NH (amine) groups of proteins -e.g. carbaminohemoglobin Dissolved in Plasma 7 - 10 % Chemically Bound to Hemoglobin in RBC’s 20 - 30 % Carbonic acid As Bicarbonate Ion in Plasma 60 -70 % Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 46  Carbon Dioxide Transport -primary reaction is hydration of CO2 in plasma & RBCs to form carbonic acid (H2CO3) -carbonic anhydrase is present in RBCs & accelerates CO2 hydration by several hundredfold -carbonic acid dissociates into bicarbonate (HCO3-) & H+ -bicarbonate transported out of RBCs (down concentration gradient) -exchanged for Cl- to maintain electro neutrality Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 47  Control of Respiration *Regulation of bronchial/bronchiolar smooth muscle contraction → bronchoconstriction relaxation → bronchodilation Respiratory center in the brain diaphragm intercostal muscles abdominal muscles Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 48  Summary for control of Respiration Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 49  Regulation of respiration Two types of receptors: 1. Mechanoreceptors. It's Slowly adapting stretch receptors in bronchial airways, which mean it prevent overstretching of the lung and prevent rupture, terminate the inspiration its significant only in the situation of increase inspiration or diseases. 2. Chemoreceptors. Respond to changes in CO2 and O2 levels by sense it by Chemoreceptors ( Central in the brain) & Peripheral ( in blood vessels) Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 50  Regulation of respiration Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 51  Summary for regulation of respiration Inhale the future, exhale the past. Dr. Mohammad A. Abedal-Majed 6-4-2023 52