Respiratory Physiology Lecture - Biomed Groups PDF

Respiratory Physiology Adrian H Kendrick Senior Lecturer in Respiratory/Sleep Consultant Clinical Scientist Outline Integrated System – Pathway of Oxygen Anatomy & Histology of the Respiratory System Physiology Measurements in clinical practice...

Respiratory Physiology Adrian H Kendrick Senior Lecturer in Respiratory/Sleep Consultant Clinical Scientist Outline Integrated System – Pathway of Oxygen Anatomy & Histology of the Respiratory System Physiology Measurements in clinical practice Linking disease, measurements and clinical history Respiratory Physiology - The Pathway of Oxygen Cardiovascular & Respiratory Interactions Rest & Sleep Exercise Cheng L, Khoo MC. Modeling the autonomic and metabolic effects of obstructive sleep apnea: a simulation study. Front Physiol. 2012 Jan 4;2:111. doi: 10.3389/fphys.2011.00111. PMID: 22291654; PMCID: PMC3250672. Model of the Mammalian Respiratory System Convective Conductance Ventilation Cardiac Output Metabolic/ Molecular Model of the Mammalian Respiratory System Diffusive Conductance Air to Blood Blood to Cells Global Interactions Cardiovascular and ventilatory systems must be coupled Efficient coupling reduces to a minimum the stress to the component mechanisms supporting energy transformations Cellular respiratory requirements can only be met by interaction of the physiological mechanisms that link gas exchange between muscle cells and the atmosphere Outline Integrated System – Pathway of Oxygen Anatomy & Histology of the Respiratory System Physiology Measurements in clinical practice Linking disease, measurements and clinical history The Upper Airway Rib Cage What’s Inside the Chest? The Airways Major Airway Histology Trachea Respiratory Bronchiole Alveolus Pulmonary Capillary Alveolar Capillary Membrane Airway Surface Mucous layer Goblet cell Cilia Alveoli Circulation Pulmonary Circulation Alveolar Surface Area 143 m2 Capillary Surface Area 126 m2 Capillary volume (rest) 70 mL Capillary volume (max) 213 mL Systemic Circulation Cellular Respiration - Mitochondria Energy production Mature red blood cell = 0 Liver cell > 2000/cell Summary The respiratory systems starts at the mouth and ends at the mitochondria – the Pathway of Oxygen Understanding the anatomy and histology of the human respiratory system is essential in understanding how gas exchange occurs, and in disease states how gas exchange is affected. Outline Integrated System – Pathway of Oxygen Anatomy & Histology of the Respiratory System Physiology Measurements in clinical practice Linking disease, measurements and clinical history Mechanics of Ventilation Static Lung Volumes Simple Model Chest Wall Conducting Airway Pleural Space Lung Alveoli Compliance 8 Lung Volume (litres) CW L RS 6 4 FRC 2 0 -4 -3 -2 -1 0 1 2 3 4 Transorgan Pressure (kPa) The Respiratory Cycle -0.3 -0.5 -0.5 (b) (a) -0.8 -0.5 Inhale -0.7 0 0.5 0 0 -0.1 -0.1 -0.8 -0.3 -0.3 (c) (d) -0.9 -0.6 1 0 Exhale -0.9 0.7 0 0 Respiratory Muscles Respiratory Muscles No inherent rhythm Generate tension due to rhythmic pattern of neuron-induced action potentials activating them Muscles attempt to overcome the resistance to airflow within the airways When at rest, the thorax assumes the FRC position Muscles of Inspiration and Expiration Diaphragm Diaphragm accounts for 70% of minute ventilation Diaphragm contraction results in movement of the central tendon, causing a pressure increase below the diaphragm and to become more subatmospheric above the diaphragm in the chest Dome shaped musculofibrous septum separating the thoracic and abdominal cavities Shape due to the elastic recoil of the lungs tending P to pull it into the chest cavity Surface area of 250 cm2 P Innervation by phrenic nerve Diaphragm Tension generation by the muscular fibres draws the central tendon downwards Increases thoracic volume and lowers intrathoracic pressure Decreases abdominal volume thereby increasing intra-abdominal pressure Breath in occurs Expiration is simply the reverse Diaphragm Not just for ventilation When both abdominal muscles and diaphragm tense at the same time, this aids the rectal contents to be discharged, more so when constipation is present Facilitates coughing, sneezing, singing, and playing wind instruments Diaphragm & Sleep Only muscle of breathing working when in dreaming (REM) sleep Ventilation may become erratic In some normals and patients with chest Normal wall problems, may result in clear O2 desaturation REM Summary The respiratory muscles are essential to respiration and vary in the degree of activity depending on whether resting breathing or heavy exercise occurs The major respiratory muscle is the diaphragm , accounting for most of each tidal breath Any damage that occurs to the muscles or their nerve supply will have an adverse effect on respiration 10 Airflow Flow Characteristics L a m in a r F lo w 50 40 ) -1 30 F lo w (l.s 20 10 T u r b u le n t F lo w 0 0 1 2 3 4 5 D r iv in g P r e s s u r e (k P a ) Airways Resistance 100 100 C o n d u c tin g Z o n e R e s p ir a t o r y Z o n e C u m u la t iv e R e s is t a n c e ( % t o t a l) ) -4 80 80 R e s is t a n c e ( S I U n it s x 1 0 60 60 40 40 20 20 0 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 A ir w a y G e n e r a t io n Factors Affecting Airways Resistance Airway Length 0.3 30 A ir w a y C o n d u c t a n c e ( S I U n it s ) A ir w a y R e s is t a n c e ( S I U n it s ) Radius of the airways Lung Volume 0.2 20 Elastic Recoil 0.1 10 Bronchomotor Tone RV TLC 0.0 0 0 2 4 6 8 L u n g V o lu m e ( l ) Flow-Volume-Time Relationships 6 6 4 4 Volume (l) 2 2 0 0 0 200 400 600 0 2 4 6 Flow Rate (l.min-1) Time (s) Flow Limitation 600 Effort Independent Region 500 Flow rate (l.min-1) 400 300 200 100 0 0 1 2 3 4 5 6 Volume (l)  Gas Exchange Alveolar Gas Exchange Successful Gas Exchange The lungs must be ventilated The lungs must be perfused The ventilation & perfusion must be matched Transport of Oxygen Inspired Oxygen Inspired Barometric Concentration Oxygen Pressure Alveolar Alveolar Oxygen Ventilation Oxygen Uptake V/Q Ratios Arterial Venous Oxygen Admixture Cellular Haemoglobin Blood Flow Oxygen Concentration Diffusion of Oxygen Max Ex Rest Normal Abnormal Transport of Carbon Dioxide (CO2) Tidal Volume Alveolar Dead Space Breathing Frequency Ventilation Inspired CO2 Barometric PACO2 Concentration Pressure CO2 Output V/Q Ratios PaCO2 Shunts Diffusion of Carbon Dioxide Max Ex Rest Thickened blood-gas barrier Normal Gas Transport in Blood Haemoglobin – Its Task Haemoglobin achieves it task by: Having a large capacity for O2 as compared to that of the plasma Carrying several O2 molecules for every haemoglobin molecule Releasing O2 upon demand Loading and unloading O2 quickly over the range of PO2 found in tissues Haemoglobin – Its Task Haemoglobin achieves it task by: Altering its binding affinity for O2 when demands for O2 alter Apart from being involved in the transport of CO2 and hydrogen ions (H+) one of its other major functions is the buffering of acidity Transport of Oxygen Oxygen is stored in the body in four forms - As a gas in the lungs Dissolved in tissue fluids As oxyhaemoglobin in blood As oxymyoglobin in muscle Oxygen and Haemoglobin O2 + Hb HbO2 4O2 + Hb4 Hb4O8 Transport of Oxygen Bound O2 = [Hb] x binding affinity x SaO2 = 15.0 x 1.39 x 0.97 = 20.22 ml/100 ml Total O2 = Dissolved O2 + Bound O2 = 0.30 + 20.22 = 20.52 ml/100 ml Oxyhaemoglobin Dissociation Curve Systemic Pulmonary 100 SO 2 (% ) 80 60 40 20 0 0 3 6 9 12 15 PO 2 (k P a ) Oxyhaemoglobin Dissociation Curve 100 Curve shift to Right - 80 In c r e a s e s in - Hb has a lower affinity for O2 S a t u r a t io n ( % ) 60 At the muscles, PCO2 is higher T e m p e ra tu re + [H ] = pH P50 than in the alveoli and pH is lower 40 PCO2 Similar issues seen when 2 ,3 - B P G exercising as increased need to 20 effectively deliver O2 to the 0 respiring cells 0 4 8 12 16 P a r t ia l P r e s s u r e o f O 2 ( k P a ) Oxyhaemoglobin Dissociation Curve 100 Curve shift to Left - 80 Hb has a higher affinity for O2 D e c r e a s e s in - S a t u r a t io n ( % ) 60 T e m p e ra tu re + P50 At the alveoli, PCO2 is lower than [H ] = pH 40 PCO2 in the muscle and the pH is higher 2 ,3 - B P G Higher affinity results in more O2 20 being taken up. 0 0 4 8 12 16 P a r t ia l P r e s s u r e o f O 2 ( k P a ) Transport of Oxygen - anaemia -1 [ H b ] = 1 5. 0 g.d l 200 Bound O2 = [Hb] x binding affinity x SaO2 O x y g e n C o n c e n tr a tio n (m l.l ) -1 -1 = 15.0 x 1.39 x 0.97 150 [ H b ] = 1 1. 3 g.d l = 20.22 ml/100 ml [ H b ] = 7. 5 0 g.d l -1 100 Bound O2 = [Hb] x binding affinity x SaO2 = 7.50 x 1.39 x 0.97 50 = 10.11 ml/100 ml 0 0 4 8 12 16 P a r t ia l P r e s s u r e o f O 2 ( k P a ) Transport of Carbon Dioxide (CO2) Physical Solution: CO2 is moderately soluble in water, so the concentration of CO2 in blood is related to the PCO2 and the solubility coefficient (α). For a PCO2 of 5.3kPa, the dissolved CO2 is about 1.22 mmol.L-1. Carbonic Acid: In solution, CO2 combines with H2O to form carbonic acid. The reaction, in the red blood cell where the enzyme carbonic anhydrase is present, is very rapid. The H2CO3 spontaneously dissociates into H+ and bicarbonate ions (HCO3-). Carbonic Acid (CA) In solution, CO2 slowly combines with H2O to form carbonic acid CO2 + H2O H2CO2 H+ + HCO3- The reaction, in the red blood cell where the enzyme carbonic anhydrase is present, is very rapid. H2CO3 rapidly dissociates to H+ and bicarbonate ions (HCO3-). CA CO2 + H2O H2CO2 H+ + HCO3- Transport of Carbon Dioxide Bicarbonate Ion: To prevent accumulation of HCO3-, the HCO3- diffuses out into the extracellular fluid, whilst Cl- diffuses into the red blood cell thereby maintaining electrical neutrality. The H+ combines with haemoglobin and to a lesser extent with various plasma proteins. About 19.3 mmol.l-1 (90%) of CO2 is carried this way. Carbamino-Haemoglobin Carriage: The amino groups (R-) in the R-NH2 on the haemoglobin molecule combine with CO2 to form carbamic acid (R- NHCOOH), which dissociates to form carbamino compounds (R-NHCOO-) at normal body pH. Only small quantities of CO2 are carried in this way. Transport of CO2 & O2 Ventilation-Perfusion Relationships Three-Zone Model V/Q Ratios in the Upright Lung 0.7 0.8 1.0 1.6 3.0 200 Q>V V=Q V>Q relative to middle lung region (%) 3.0 160 Blood Flow & Ventilation 120 1.0 80 40 0 0.7 Base Middle Apex Lung Region A Simple Model Area x Constant Vgas ∝ x (P1 – P2) thickness Airway P1 Pulmonary Capillary P2 V/Q Scans – Normal & Severe COPD Ventilation Perfusion Ventilation Perfusion L R L R L R L R Normal Normal L R L R L R L R COPD COPD  Acid-Base Balance Acidosis Alkalosis Respiratory acid component Metabolic alkaline component Acid-Base PCO2 HCO3- Balance Acidosis Basic Concepts We have several body systems that maintain the acidity of body fluids within defined, tight, narrow ranges. This is important as enzyme catalysed reaction rates are strongly affected by even quite small changes in acidity. Apart from the influence of acidity of enzyme reactions, acidity can also have significant effects on the excitability of the nervous system. Basic Concepts A significant number of chemical reactions in the body produce or absorb protons. One major source of protons is the H+ formed indirectly from the reaction of CO2 with H2O to give H+ and HCO3-. The excess CO2 and H+ generated by the metabolism are removed by the lungs and the kidneys. The lungs are a fast response system, the kidneys are more sedate. To aid in the maintenance of the level of [H+], in the short term, various buffer systems prevent the [H+] varying wildly pH The normal way of expressing the acidity or alkalinity is the pH pH = - log10[H+] So, if the [H+] = 3.30 x 10-8 mol.L-1 pH = - log10[3.30 x 10-8] = - (-7.481) = 7.481 7.8 Resp Muscle 7.6 Spasm 7.4 Normal pH 7.2 Poor Prognosis 7.0 Death 6.8 0 5×10 -8 1×10 -7 1.5×10 -7 Hydrogen Ion Concentration Normal Values Units Mean Range pH 7.4 7.36 – 7.44 [H+] mmol.L-1 39.8 35.8 – 43.8 PaCO2 kPa 5.47 4.97 – 6.00 PaO2 @40 yrs kPa 12.6 10.5 – 14.7 [HCO3-] mmol.L-1 24.8 22.6 – 27.0 SaO2 % - 93.0 – 97.5 The Body Buffer Systems Acid may be added to the system as either CO2 or metabolic acid. The addition of significant amounts of H+ to the body system would result in a significant change in the pH without the body buffer systems. The buffer systems can be divided into three components – Bicarbonate/carbonic acid Protein Phosphates The Body Buffer Systems Bicarbonate, Carbonic Acid and Carbon Dioxide The principal feature of this system is its volatility. The relationship between HCO3- and H2CO3 is important, as the level of H2CO3 is a function of the PCO2. The relationship between PCO2 and H2CO3 in body fluids is - H2CO3 = 0.226PCO2 Changes in PCO2 induced by alterations in alveolar ventilation will be reflected by changes in both intracellular and extracellular fluids. In this buffer system, the kidney not only reabsorbs HCO3-, but may also generate it. This buffer system is adaptable, since acid concentration can be adjusted rapidly, and base is readily generated. Clinical Acid-Base Disturbances Primary Primary Compensatory Mechanism of Disturbance Event Event Compensatory Event Acid titration of tissue buffers. Respiratory ↑ PaCO2 ↑ [HCO3-] ↑ in acid excretion and reabsorption of Acidosis HCO3- by kidney Alkaline titration of tissue buffers. Respiratory ↓ PaCO2 ↓ [HCO3-] ↓ reabsorption of HCO3- by kidney and Alkalosis acid excretion. Metabolic ↓ [HCO3-] ↓ PaCO2 Alveolar hyperventilation Acidosis Metabolic ↑ [HCO3-] ↑ PaCO2 Alveolar hypoventilation Alkalosis Acid-Base Diagram 100 5 10 15 20 25 90 H y d r o g e n Io n C o n c e n t r a t io n ( m m o l. l ) -1 80 pH 30 70 is s do 7.2 ci M A 60 et ry o 40 ab r at ol ic pi 50 7.3 A es ci R do te 50 si cu s A 40 7.4 60 s 7.5 o si M 30 al et lk ab 7.6 A ol y or ic 20 ir at A lk e sp al os R is 10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 A r t e r ia l P C O 2 ( k P a ) Innervation of Respiratory Muscles and Airways Control of Respiration Breathing is spontaneously initiated within the central nervous system (CNS). A cycle of inspiration and expiration is automatically generated by neurones in the brainstem. This cycle can be modified, altered or temporarily suppressed by several mechanisms. The system controlling breathing regulates a complex series of usually complimentary, but occasionally competitive or even incompatible activities. Control of Respiration Perform The system must perform three key functions Maintain, through involuntary controls, a regular rhythmic Maintain breathing pattern Adjust the tidal volume (VT) and breathing frequency (fb) such Adjust that alveolar ventilation is sufficient to meet the demands for gas exchange at cellular level Adjust the breathing pattern to be consistent with other activities Adjust using the same muscles, such as speech Control of Respiration Under most circumstances, breathing is controlled so finely that the PaO2 and PaCO2 are kept within normal limits. To achieve this, the system has three control pathways – 1. The PCO2 is the main pathway, controlling the rate and depth of breathing on a breath-by- breath basis. 2. Under certain circumstances, such as acclimatization to altitude, the PO2 pathway (the second pathway) can override the PCO2 pathway. 3. A third pathway is required to allow all other actions such as talking, swallowing and coughing to break through the normal pattern of breathing and try to match breathing to the expected voluntary or behavioural activity. In essence, we have two controllers - the metabolic controller serving the basic body needs and a behavioural controller that can temporarily override the metabolic controller. Brainstem Global Innervation Airways Innervated by the vagus nerve – Parasympathetic Innervated by the Sympathetic nerve chain Muscles Innervated by the intercostal (motor) nerves Phrenic nerve innervates the diaphragm Central and Peripheral Chemoreceptors Overall Control Control of Breathing Pattern Breathing is the product of chemical and neurological influences on a network of neurons, motor nerves and muscles Breathing is dependent on the mechanical properties of the chest, the lungs and the airways Mechanical Work of Breathing The two major components of the work of breathing - the elastic and resistive work, are known to be influenced differently by the breathing pattern There is probably an optimal setting of VT and fb at which the total work of breathing is minimal Gas Exchange and Breathing The dead space ventilation is affected by changes in the VT.fb relationship Additionally, the distribution of inspired air in the lungs as well as VO2 and VCO2 are affected by the flow pattern Fundamental Stimulus Tidal volume is controlled so that PaCO2 is maintained within narrow bands and varies little over time ( 98% indicates a non-physiological problem Checks whether patients are hypoxic at rest and can be used on exercise Pulse Oximeter Technology Estimation of arterial oxygen saturation is achieved by - Pulse Oximeter Technology Absorption spectra Pulse Oximeter Technology Detection of pulsatile blood flow Pulse Oximeter Technical Issues - Practical Substance interference – COHb, skin dye Blood Flow Nail Varnish Technical Limitations – Skin Pigmentation Technical Limitations – Skin Pigmentation Clinical Limitations Oxyhaemoglobin dissociation curve Pulse dependence Skin perfusion hypothermia, hypotension, vasoconstriction Carbon dioxide, Carbon monoxide, Anaemia Non differentiation of apnoea/disorders Interpretation Pulse Oximetry Non-invasive Useful screening tool Serial measurement Therapeutic management Skilled interpretation Limitations – technical & clinical Summary Respiration is essential for the transportation of O2 and the removal of CO2 from the whole-body system Understanding the anatomy and physiology of the normal system allows an understanding of the clinical measurements undertaken to assess the effects of disease Any part of the pathway of oxygen can be affected by disease – lungs, heart, circulation, brain, muscles and mitochondria