Learning objectivesLearning objectivesPulmonary structure and mechanics.Pulmonary structure and mechanics.

Gas transport and exchange.Gas transport and exchange.

Regulation of respiration.Regulation of respiration.

Why We Breathe?

We need to breathe because our cells require oxygen for cellular respiration and must remove carbon dioxide from the cell as a by-product of the cellular respiration (metabolism).

What is the respiratory system?What is the respiratory system?

Your respiratory system is made up Your respiratory system is made up of the organs in your body that help of the organs in your body that help you to breathe. Remember, that you to breathe. Remember, that Respiration = Breathing.Respiration = Breathing.

RespirationRespiration means taking up of oxygen (O2), its utilization in the tissues and removal of carbon dioxide (CO2). In the process, O2 is drawn in as a part of inspired air and then taken up by blood from the lungs. O2 is then transported by blood to the tissues where it is used up and CO2 is produced. This CO2 is again taken up by blood and delivered to the lungs wherefrom the CO2 is expelled through the expired air.

OO22 & CO & CO22 exchange between body tissues & environment exchange between body tissues & environment

Atmospheric Atmospheric air contains air contains approx. 21% approx. 21% OO22; 79% N; 79% N22 and 0.04% and 0.04% COCO22..

Types of RespirationTypes of RespirationThe general term respiration refers to two The general term respiration refers to two integrated processes: integrated processes: external respiration and external respiration and internal respiration.internal respiration.

External respirationExternal respiration It is the process of bringing air from the external It is the process of bringing air from the external environment and transporting it to the cell while environment and transporting it to the cell while COCO22 is carried from the cell to the external is carried from the cell to the external environment. environment. The process of external respiration involves three The process of external respiration involves three major events: major events: pulmonary ventilation, pulmonary pulmonary ventilation, pulmonary diffusion and transport of gases.diffusion and transport of gases.

Internal respiration (cellular respiration)Internal respiration (cellular respiration)It consists of a series of complex metabolic It consists of a series of complex metabolic reactions that utilizes Oreactions that utilizes O22 and releases CO and releases CO22 and and energy. energy.

Overview of Overview of External & External &

Internal Internal RespirationRespiration

Functional anatomy of the respiratory systemFunctional anatomy of the respiratory systemThe respiratory system consists of the The respiratory system consists of the upper upper respiratory tractrespiratory tract includes the mouth, nose, includes the mouth, nose, pharynx and larynx; pharynx and larynx; The The lower respiratory tractlower respiratory tract starts at the starts at the trachea, and includes bronchi and lungs. trachea, and includes bronchi and lungs. The two The two lungslungs are enclosed within the are enclosed within the thoracic thoracic cagecage which is formed by the ribs, sternum, which is formed by the ribs, sternum, vertebral column and the dome-shaped vertebral column and the dome-shaped diaphragm.diaphragm. The diaphragm is separating the thorax from the The diaphragm is separating the thorax from the abdomen. abdomen. The left lung has The left lung has two lobestwo lobes and the right has and the right has three.three. Each lung lobe is made up of several Each lung lobe is made up of several bronchopulmonary segments.bronchopulmonary segments.

PleuraPleura

The lungs are covered by a thin membrane The lungs are covered by a thin membrane (visceral pleura)(visceral pleura) and inside surface of the and inside surface of the thoracic cage is lined by another thin thoracic cage is lined by another thin membrane, membrane, parietal pleuraparietal pleura.. The tiny space between the two pleura is called The tiny space between the two pleura is called pleural cavitypleural cavity which is filled with the which is filled with the ultrafiltrate of plasma called ultrafiltrate of plasma called pleural fluidpleural fluid (about 10ml) helps in lubrication of the pleura.(about 10ml) helps in lubrication of the pleura.

Tracheobronchial TreeTracheobronchial Tree

The airway tree consists of a series of highly branched The airway tree consists of a series of highly branched hollow tubes that decrease in diameter and become hollow tubes that decrease in diameter and become more numerous at each branching (refers by their more numerous at each branching (refers by their generation number).generation number).Trachea (zero generation),Trachea (zero generation), the main airway in turn the main airway in turn branches into two branches into two bronchi (first generation),bronchi (first generation), one of one of which enters each lung.which enters each lung.There is a total of approximatelyThere is a total of approximately 23 generations23 generations of of airways. airways.

Tracheobronchial Tree (23 generations of airways)

As generation number increases (airways become As generation number increases (airways become smaller), the smaller), the amount ofamount of cilia,cilia, the number of the number of mucus-mucus-secreting cellssecreting cells, the presence of , the presence of submucosal glandssubmucosal glands and the and the amount of cartilageamount of cartilage in the airway walls all in the airway walls all gradually gradually decrease.decrease. Airways maintain some cartilage to Airways maintain some cartilage to about 10about 10thth generation, up to which point they are referred to as generation, up to which point they are referred to as bronchi.bronchi. At about the At about the 1111thth and succeeding generations, and succeeding generations, the now the now cartilage-free airways are called cartilage-free airways are called bronchioles.bronchioles.The The cartilagecartilage is important for preventing airway is important for preventing airway collapse. The collapse. The mucusmucus is important for trapping small is important for trapping small foreign particles. The foreign particles. The ciliacilia sweep the carpet of mucus sweep the carpet of mucus and kept moist by secretions. and kept moist by secretions. Bronchial treeBronchial tree:: Trachea→ bronchi→ smaller Trachea→ bronchi→ smaller bronchi→ terminal bronchiolesbronchi→ terminal bronchioles..

Wall of Tracheobronchial Wall of Tracheobronchial TreeTree

Respiratory air passagesRespiratory air passages

Functionally, the respiratory air passages are Functionally, the respiratory air passages are divided into two zones: divided into two zones: – Conductive zoneConductive zone and and – Respiratory zoneRespiratory zone

Conducting zoneConducting zoneThe first 16 subdivisions The first 16 subdivisions (from trachea to (from trachea to terminal bronchioles)terminal bronchioles) form form conducting zoneconducting zone of of airway. airway. The terminal bronchioles redivide to form The terminal bronchioles redivide to form respiratory bronchiolesrespiratory bronchioles and then to and then to alveolar alveolar ducts and sacs which end as ducts and sacs which end as alveoli.alveoli.

The conducting zone of the respiratory system, in The conducting zone of the respiratory system, in summary consists of the following parts:summary consists of the following parts:Mouth→ nose→ pharynx→ larynx→ trachea→ Mouth→ nose→ pharynx→ larynx→ trachea→ bronchi→ all successive branches of bronchioles bronchi→ all successive branches of bronchioles including terminal bronchioles.including terminal bronchioles.

No gas exchange occurs in these regions. The No gas exchange occurs in these regions. The amount of air present in these regions is called amount of air present in these regions is called ‘’anatomical dead space’’‘’anatomical dead space’’.. The quantity of air present in these regions is about The quantity of air present in these regions is about 150 ml. 150 ml. The remaining subdivisions form the The remaining subdivisions form the transitionaltransitional and and respiratory zonerespiratory zone where gas exchange occurs. where gas exchange occurs.

Functions of conducting zoneFunctions of conducting zone1.1. Warming and cooling of inspired airWarming and cooling of inspired air2.2. Moistening or humidification of the inspired airMoistening or humidification of the inspired air3.3. Filtration and cleaningFiltration and cleaning4.4. Secretion of IgA in the bronchial secretions, an Secretion of IgA in the bronchial secretions, an

additional protection against respiratory infectionsadditional protection against respiratory infections5.5. Tonsils and adenoids, immunologically active Tonsils and adenoids, immunologically active

lymphoid tissue in the pharynxlymphoid tissue in the pharynx6.6. Distribute air to the gas exchange surface of the lung.Distribute air to the gas exchange surface of the lung.

Respiratory zoneRespiratory zoneThe respiratory zone includes the The respiratory zone includes the respiratory respiratory bronchiolebronchiole which opens into a number of which opens into a number of alveolar ductsalveolar ducts and each alveolar duct opens and each alveolar duct opens into number of into number of alveoli.alveoli. Alveoli are tiny air sacs, Alveoli are tiny air sacs, having a having a diameter of 0.25 mm.diameter of 0.25 mm. There are about There are about 300 million300 million alveoli in the two lungs. alveoli in the two lungs.

AcinusAcinusThe acinus is the The acinus is the functional or terminal respiratory unitfunctional or terminal respiratory unit of the lung and includes all structures from of the lung and includes all structures from respiratory respiratory bronchiole to the alveolusbronchiole to the alveolus (alveolar ducts, alveolar (alveolar ducts, alveolar sacs and alveoli). sacs and alveoli). An acinus averages An acinus averages 0.75 mm diameter.0.75 mm diameter. Each person has about Each person has about 20,000 acini.20,000 acini.

AcinusAcinus

The alveolar surfaceThe alveolar surfaceThe alveolar lining consists of two distinct types of The alveolar lining consists of two distinct types of epithelial cells, epithelial cells, type-I and type-II alveolar type-I and type-II alveolar pneumocytespneumocytes.. The elongated The elongated type I cells cover 90% to 95%type I cells cover 90% to 95% of the of the alveolar surface, and it is the primary site for alveolar surface, and it is the primary site for gas gas exchangeexchange.. The The cuboidal type-IIcuboidal type-II cells are secreting cells are secreting surfactant,surfactant, responsible for preventing the collapse of lungs. responsible for preventing the collapse of lungs. After an injury,After an injury, type-I cells degenerate, whereas type- type-I cells degenerate, whereas type-II cells proliferate and line the alveolar space II cells proliferate and line the alveolar space (repairing cell).(repairing cell). Third typesThird types of cells, the of cells, the pulmonary alveolar pulmonary alveolar macrophage,macrophage, are found which ingest the inhaled are found which ingest the inhaled bacteria and small particles.bacteria and small particles.

Muscular wall of respiratory passageways and its Muscular wall of respiratory passageways and its control:control: The rings of cartilage in the walls of the trachea and The rings of cartilage in the walls of the trachea and bronchi prevent them from collapse.bronchi prevent them from collapse.The The smooth muscle fiberssmooth muscle fibers in their walls can alter in their walls can alter (change) the size of their lumen and (change) the size of their lumen and vary airway vary airway resistance. resistance. The terminal bronchiolesThe terminal bronchioles have abundant of smooth have abundant of smooth muscle and muscle and no cartilageno cartilage but the but the respiratory respiratory bronchiolesbronchioles are occupied by are occupied by pulmonary epitheliumpulmonary epithelium and and underlying fibrous tissue plus few smooth muscleunderlying fibrous tissue plus few smooth muscle fiber.fiber.

These respiratory smooth muscles are richly These respiratory smooth muscles are richly innervated by cholinergic parasympathetic nerve innervated by cholinergic parasympathetic nerve fibers.fibers.Their stimulation causes mild to moderate Their stimulation causes mild to moderate bronchial bronchial constriction. constriction. Histamine and slow reactive substance of anaphylaxisHistamine and slow reactive substance of anaphylaxis are potent broncho-constrictor. During allergic are potent broncho-constrictor. During allergic reactions, these are released by reactions, these are released by mast cellsmast cells in the lung in the lung tissues.tissues. Direct control of the bronchioles by sympathetic nerve Direct control of the bronchioles by sympathetic nerve fiber is relatively weak but fiber is relatively weak but bronchial smooth fibers bronchial smooth fibers contain βcontain β22 adrenergic receptors. adrenergic receptors.Therefore, they respond to Therefore, they respond to circulating epinephrine and circulating epinephrine and norepinephrinenorepinephrine (from adrenal medulla) and inhaled or (from adrenal medulla) and inhaled or injected sympathomimetic drugs injected sympathomimetic drugs (salbutamol, (salbutamol, isoproterenol etc,) resulting in bronchodilation. isoproterenol etc,) resulting in bronchodilation.

learning objectiveslearning objectives

Pulmonary circulation& pressurePulmonary circulation& pressure

Ventilation Ventilation

Circulation through lungsCirculation through lungs

The lungs receive blood from two sources: The lungs receive blood from two sources: 1.1. The bronchial circulation and The bronchial circulation and 2.2. The pulmonary circulation.The pulmonary circulation.

Bronchial circulationBronchial circulationIt accounts for only a small part of the cardiac It accounts for only a small part of the cardiac output output (~2%).(~2%). The The walls of the large airwayswalls of the large airways are supplied by bronchial circulation are supplied by bronchial circulation (oxygenated blood) (oxygenated blood) through bronchial arteriesthrough bronchial arteries from the aorta.from the aorta.

Pulmonary circulationPulmonary circulationThe output of the The output of the right ventricleright ventricle passes through the passes through the pulmonary artery, branched and supplies the pulmonary artery, branched and supplies the individual alveoli of the lung. individual alveoli of the lung. The The capillaries lie in the walls of the alveoli.capillaries lie in the walls of the alveoli. This This network is so dense that the blood forms almost a network is so dense that the blood forms almost a continuous sheet in the alveolar wall. continuous sheet in the alveolar wall. There may be about There may be about 1000 pulmonary capillaries per 1000 pulmonary capillaries per alveolus.alveolus.The entire pulmonary vasculature is a distensible low-The entire pulmonary vasculature is a distensible low-pressure system (normal pulmonary capillary pressure pressure system (normal pulmonary capillary pressure is 7 mm Hg). is 7 mm Hg).

Capillary fluid exchange in the lung and Capillary fluid exchange in the lung and pulmonary interstitial fluid dynamicspulmonary interstitial fluid dynamics

The differences in fluid dynamicsThe differences in fluid dynamics between lung between lung capillary membranes and peripheral tissues: capillary membranes and peripheral tissues:

1.1. The The pulmonary capillary pressurepulmonary capillary pressure is low about is low about 7 mm 7 mm HgHg (peripheral tissue pressure (peripheral tissue pressure 17 mm Hg17 mm Hg).).

2.2. The The interstitial fluid pressureinterstitial fluid pressure in the lung is in the lung is slightly slightly negativenegative than peripheral tissue. than peripheral tissue.

3.3. Pulmonary capillaries are Pulmonary capillaries are leaky to protein molecules,leaky to protein molecules, so so oncotic pressure is 14 mmHgoncotic pressure is 14 mmHg (28 mmHg in (28 mmHg in peripheral tissues).peripheral tissues).

4.4. Alveolar walls are extremely thinAlveolar walls are extremely thin and the alveolar and the alveolar epithelium covering the alveolar surfaces is so weak epithelium covering the alveolar surfaces is so weak that that it can be ruptured by any positive pressure in the it can be ruptured by any positive pressure in the interstitial spacesinterstitial spaces greater than alveolar air pressure greater than alveolar air pressure (greater than 0 mm Hg).(greater than 0 mm Hg).

Interrelations between interstitial fluid pressure Interrelations between interstitial fluid pressure and other pressures in the lungand other pressures in the lung

Forces tending to cause movement of fluid outward from the Forces tending to cause movement of fluid outward from the capillaries and into the pulmonary interstitium:capillaries and into the pulmonary interstitium:

mmHgmmHgCapillary pressureCapillary pressure 77Interstitial fluid colloid osmotic pressure (oncotic pressure) Interstitial fluid colloid osmotic pressure (oncotic pressure) 1414Negative interstitial fluid pressure (ISF)Negative interstitial fluid pressure (ISF) 88

Total outward forceTotal outward force 2929

Forces tending to cause absorption of fluid to the capillaries:Forces tending to cause absorption of fluid to the capillaries:Plasma Colloid osmotic pressurePlasma Colloid osmotic pressure 2828

Total inward forceTotal inward force 2828

Therefore, the mean filtration pressure is (29-28) = +1 mm Therefore, the mean filtration pressure is (29-28) = +1 mm Hg.Hg.

Negative pulmonary interstitial pressure and the mechanism Negative pulmonary interstitial pressure and the mechanism for keeping alveoli dryfor keeping alveoli dry

This filtration pressure causes a This filtration pressure causes a slight continual flowslight continual flow of of fluid from the fluid from the pulmonary capillaries into the interstitial pulmonary capillaries into the interstitial space.space.Small amount Small amount evaporatesevaporates in the alveoli. in the alveoli.Rest of the fluid is Rest of the fluid is pumped backpumped back to the circulation to the circulation through the through the pulmonary lymphatic system.pulmonary lymphatic system.

Negative interstitial fluid pressure and the Negative interstitial fluid pressure and the mechanism for keeping alveoli drymechanism for keeping alveoli dry

There are small pores between alveolar epithelial cells There are small pores between alveolar epithelial cells ((pores of Kohnpores of Kohn)) through which water, electrolytes through which water, electrolytes and even protein molecules can pass.and even protein molecules can pass.However, However, alveoli do not fill with fluidalveoli do not fill with fluid (kept dry) (kept dry) because the because the negative ISFnegative ISF helps the absorption of fluid. helps the absorption of fluid.Whenever, Whenever, fluid appears in the alveoli,fluid appears in the alveoli, it will be simply it will be simply sucked mechanicallysucked mechanically into the lung interstitium through into the lung interstitium through the small pores. The the small pores. The excess fluidexcess fluid in lung ISF is carried in lung ISF is carried away through away through pulmonary lymphatics.pulmonary lymphatics.Thus, under normal condition, the alveoli are kept in a Thus, under normal condition, the alveoli are kept in a ‘‘dry state’dry state’ except for a small amount of fluid that except for a small amount of fluid that seeps from the alveoliseeps from the alveoli to keep them moist. to keep them moist.

Pulmonary edemaPulmonary edema

An organ which is very much sensitive to proper fluid An organ which is very much sensitive to proper fluid balance is the lung. balance is the lung. Slight increases in the Slight increases in the hydrostatic pressurehydrostatic pressure of the of the pulmonary capillaries can lead to pulmonary edema.pulmonary capillaries can lead to pulmonary edema.This condition decreases the This condition decreases the pulmonary compliancepulmonary compliance (making lung expansion more difficult).(making lung expansion more difficult).It may severely It may severely compromises gas exchangecompromises gas exchange across across the pulmonary capillary bed. the pulmonary capillary bed. Acute pulmonary edema is a Acute pulmonary edema is a life-threatening condition.life-threatening condition.

Causes of pulmonary edemaCauses of pulmonary edema(a) Left heart failure(a) Left heart failure

Pulmonary edema is often associated with left heart Pulmonary edema is often associated with left heart failure. failure. Contractile properties of the left ventricle are Contractile properties of the left ventricle are inadequate to eject all of the blood that enters from the inadequate to eject all of the blood that enters from the lungs. lungs. This causes a sharp rise in left end- diastolic volume This causes a sharp rise in left end- diastolic volume and pressure and a resultant increase in pulmonary and pressure and a resultant increase in pulmonary venous and capillary pressures causing pulmonary venous and capillary pressures causing pulmonary edema.edema.

(b) (b) Damage to the pulmonary blood capillary Damage to the pulmonary blood capillary membranesmembranes Damage to the pulmonary blood capillary membranes Damage to the pulmonary blood capillary membranes caused by infection such as pneumonia.caused by infection such as pneumonia.Breathing noxious substances (chlorine gas, sulfur Breathing noxious substances (chlorine gas, sulfur dioxide gas) cause rapid leakage of plasma proteins dioxide gas) cause rapid leakage of plasma proteins and fluid out of the capillaries into both the lung and fluid out of the capillaries into both the lung interstitial spaces and the alveoli.interstitial spaces and the alveoli.

(c) (c) Rapid infusion of intravenous fluids or blood Rapid infusion of intravenous fluids or blood transfusiontransfusionHypervolemia due to rapid infusion of intravenous Hypervolemia due to rapid infusion of intravenous fluids or blood transfusion may cause pulmonary fluids or blood transfusion may cause pulmonary edema.edema.

Functions of the Respiratory SystemFunctions of the Respiratory SystemPrimary FunctionPrimary Function

Exchange of oxygen and carbon dioxideExchange of oxygen and carbon dioxide

Secondary FunctionsSecondary FunctionsVoice productionVoice productionRegulation of plasma pH (acid-base balance)Regulation of plasma pH (acid-base balance)Temperature regulationTemperature regulationSense of smellSense of smellInfection prevention (lysozyme, IgA, PAM)Infection prevention (lysozyme, IgA, PAM)Metabolic function (Metabolic function (synthesis ofsynthesis of surfactant, conversion of surfactant, conversion of angiotensin I to II, formation of bradykinin, histamine, serotonin, angiotensin I to II, formation of bradykinin, histamine, serotonin, heparin, prostaglandins).heparin, prostaglandins).

Events of RespirationEvents of Respiration

The goals of respiration are to The goals of respiration are to provide Oprovide O22 to the to the tissues and to remove COtissues and to remove CO22. .

To achieve these goals, respiration can be divided To achieve these goals, respiration can be divided into into four major functional events:four major functional events:

1.1. Pulmonary ventilation:Pulmonary ventilation: the inflow and outflow of air the inflow and outflow of air between the atmosphere and the lung alveoli.between the atmosphere and the lung alveoli.

2.2. Diffusion of ODiffusion of O22 and CO and CO22 between the alveoli and the between the alveoli and the blood.blood.

3.3. Transport of OTransport of O22 and CO and CO22 in the blood to and from the in the blood to and from the cells.cells.

4.4. Regulation of respiration.Regulation of respiration.

Pulmonary ventilationPulmonary ventilationMovement of air from the conducting zone to the Movement of air from the conducting zone to the terminal bronchioles occurs as a result of the terminal bronchioles occurs as a result of the pressure pressure differences between the two ends of the airways.differences between the two ends of the airways.Airflow through the bronchioles is directly proportional Airflow through the bronchioles is directly proportional to the pressure differenceto the pressure difference and and inversely proportional to inversely proportional to the frictional resistance to flow (airway resistance).the frictional resistance to flow (airway resistance). The pressure differences in the pulmonary system are The pressure differences in the pulmonary system are induced by:induced by:– Lung volumesLung volumes– Compliance and elasticityCompliance and elasticity– Surface tensionSurface tension

The Muscles of Respiration

Primary MusclesThe DiaphragmExternal and Internal Intercostal Muscles

Accessory MusclesSternocleidomastoidScaleneMuscles of shoulder girdleAbdominal Muscles

Muscles of InspirationPrimary Muscles

The DiaphragmExternal Intercostal Muscles

Accessory MusclesSternocleidomastoidScalene

Muscles of the shoulder girdle – anterior seratti

– elevators of scapulae – pectorals

Muscles of ExpirationPrimary Muscles

The DiaphragmInternal Intercostal Muscles

Accessory MusclesAbdominal Muscles – transversus thoracis – transversus abdominis – external obliques– internal oblique – rectus abdominis

Mechanics of pulmonary ventilationMechanics of pulmonary ventilationThe lungs can be The lungs can be expanded and contracted in two expanded and contracted in two ways:ways:

1.1. By downward and upward movement of the By downward and upward movement of the diaphragm to lengthen or shorten the chest cavity.diaphragm to lengthen or shorten the chest cavity.

2.2. By elevation and depression of the ribs to increase or By elevation and depression of the ribs to increase or decrease the antero-posterior diameter of the chest decrease the antero-posterior diameter of the chest cavity.cavity.Normal quiet breathing is accomplished almost Normal quiet breathing is accomplished almost entirely by the first method that is by movement of the entirely by the first method that is by movement of the diaphragm. diaphragm.

Following events involved in a normal inspirationFollowing events involved in a normal inspirationRespiratoryRespiratory centerscenters in the in the medullamedulla oblongataoblongata become active.become active.Signals are sent down the Signals are sent down the phrenicphrenic nervenerve to the to the diaphragmdiaphragm and down the and down the intercostal nervesintercostal nerves to the to the externalexternal intercostalintercostal musclesmuscles..Diaphragm and external intercostals Diaphragm and external intercostals contract.contract.Volume of the thoracic cavity increases.Volume of the thoracic cavity increases.Lung volume increases.Lung volume increases.Alveolar pressure decreases.Alveolar pressure decreases.Air flows down the pressure gradient from the Air flows down the pressure gradient from the atmosphere into the alveoli.atmosphere into the alveoli.Inspiration continues until alveolar pressure = Inspiration continues until alveolar pressure = atmospheric pressure.atmospheric pressure.

Forceful inspirationForceful inspirationDuring forced inspiration accessory muscles During forced inspiration accessory muscles

are involved so as to further increase thoracic are involved so as to further increase thoracic volume. Such muscles include:volume. Such muscles include:

– scalenesscalenes– sternocleidomastoidssternocleidomastoids

– shoulder girdle musclesshoulder girdle muscles

Contraction and expansion of the thoracic cageContraction and expansion of the thoracic cage

InspirationInspiration

Following events involved in a normal Following events involved in a normal expirationexpiration

Phrenic and intercostal nerves Phrenic and intercostal nerves cease firing.cease firing.Diaphragm and external intercostals Diaphragm and external intercostals relax.relax.The thoracic volume The thoracic volume decreases.decreases.Lung volume Lung volume decreases.decreases.Alveolar pressure Alveolar pressure increases.increases.Air flows down the pressure gradient from Air flows down the pressure gradient from the the alveoli into the atmosphere.alveoli into the atmosphere.Expiration continues until the alveolar Expiration continues until the alveolar pressure = atmospheric pressure.pressure = atmospheric pressure.

Forceful expirationForceful expiration

Forced expiration differs in that muscles Forced expiration differs in that muscles contract in order to further reduce the size of contract in order to further reduce the size of thoracic cavity. thoracic cavity. Such muscles include:Such muscles include:

– transversus thoracis – transversus abdominis – external obliques– internal oblique – rectus abdominis

ExpirationExpiration

Alveolar pressure, pleural pressure and Alveolar pressure, pleural pressure and transpulmonary pressuretranspulmonary pressure

Changes in lung volume, alveolar pressure, pleural Changes in lung volume, alveolar pressure, pleural pressure and transpulmonary pressurepressure and transpulmonary pressure

Pressure changes throughout the respiratory cyclePressure changes throughout the respiratory cycle

Changes in lung volume, alveolar pressure, pleural Changes in lung volume, alveolar pressure, pleural pressure and transpulmonary pressurepressure and transpulmonary pressure

Valsalva Manoeuvre:Valsalva Manoeuvre:Valsalva manoeuvre refers to a forced expiration Valsalva manoeuvre refers to a forced expiration against a closed glottis. against a closed glottis. This causes marked decrease in the thoracic volume This causes marked decrease in the thoracic volume causing deflation of lungs. Under such circumstances causing deflation of lungs. Under such circumstances the intrapleural pressure can become positive by 60-the intrapleural pressure can become positive by 60-70 mmHg. 70 mmHg. The common everyday activities in which Valsalva The common everyday activities in which Valsalva manoeuvre effect is seen in manoeuvre effect is seen in straining during straining during defecation, initial phase of coughing, during defecation, initial phase of coughing, during parturition.parturition.

Muller’s Manoeuve:Muller’s Manoeuve:Muller’s manoeuvre refers to forced Muller’s manoeuvre refers to forced inspiration against closed glottis. It is just inspiration against closed glottis. It is just reverse of the Valsalva manoeuvre, i.e., it reverse of the Valsalva manoeuvre, i.e., it reduces the intrapleural pressure up to -80 reduces the intrapleural pressure up to -80 mmHg.mmHg.

Factors Affecting Pulmonary VentilationFactors Affecting Pulmonary Ventilation

Elastic recoil of the lungElastic recoil of the lungSurfaceSurface tensiontensionComplianceComplianceAirway resistanceAirway resistance

Elastic recoil of the lungElastic recoil of the lungElastic behaviour of the lungs depends upon its Elastic behaviour of the lungs depends upon its collagen and elastic fiber.collagen and elastic fiber.Elastic behaviour of the lungs depends upon its Elastic behaviour of the lungs depends upon its geometric arrangements geometric arrangements (nylon shock (nylon shock arrangement).arrangement).It also depends on the It also depends on the surface tensionsurface tension at the at the air-liquid interface.air-liquid interface.Surface tensionSurface tension forces a generated even forces a generated even interfaces interfaces between two immiscible liquids.between two immiscible liquids.They are generated by the They are generated by the cohesive forcescohesive forces between the molecules of the liquid.between the molecules of the liquid.

What is surface tension?

x x

Therefore,Therefore,1.1. Larger alveoli have low collapsing pressure & Larger alveoli have low collapsing pressure & 2.2. Smaller alveoli have high collapsing pressure.Smaller alveoli have high collapsing pressure.

Surface tension tends to produce collapse of Surface tension tends to produce collapse of the alveoli.the alveoli.But, two factors are responsible for not But, two factors are responsible for not collapsing of alveoli:collapsing of alveoli:1. Pulmonary surfactant1. Pulmonary surfactant2. Structural interdependence of alveoli make 2. Structural interdependence of alveoli make

the alveoli more stablethe alveoli more stable

SurfactantSurfactantThis This high surface tensionhigh surface tension can lead to alveolar can lead to alveolar collapse.collapse.

Collapsed alveoli require large amounts of Collapsed alveoli require large amounts of energy to inflate during inspiration.energy to inflate during inspiration.Luckily, the Luckily, the type II alveolar cellstype II alveolar cells produce the produce the chemical surfactant.chemical surfactant. Surfactant decreasesSurfactant decreases the cohesiveness of the the cohesiveness of the water molecules lining the alveoli and thus, water molecules lining the alveoli and thus, reduces reduces alveolar surface tension.alveolar surface tension.

x x

Importance of Surfactant

1. Reduces surface tension, therefore increases compliance

2. Prevention of alveolar collapse3. Stability of alveoli4. Expansion of lungs at birth5. Helps keep alveoli dry; helps prevent

pulmonary edema

InfantInfant RespiratoryRespiratory DistressDistress SyndromeSyndrome

Surfactant production is inadequate until Surfactant production is inadequate until the last 2 months of fetal development. the last 2 months of fetal development. Thus, premature babies may suffer from Thus, premature babies may suffer from infantinfant respiratoryrespiratory distressdistress syndromesyndrome,, where the lack of surfactant leads to where the lack of surfactant leads to alveolar collapse and tremendous difficulty alveolar collapse and tremendous difficulty breathing.breathing.

Structural Interdependence of AlveoliStructural Interdependence of Alveoli

All alveoli are surrounded by other alveoli & All alveoli are surrounded by other alveoli & therefore supported by each other.therefore supported by each other.In a structure having connecting links like this, In a structure having connecting links like this, any tendency for any one unit to expand or any tendency for any one unit to expand or contract is opposed by others. contract is opposed by others.

ComplianceCompliance

Compliance is the measure of distensibility of lungs.Compliance is the measure of distensibility of lungs.The ease with which the lungs can expand facilitates The ease with which the lungs can expand facilitates efficient ventilation.efficient ventilation.

Compliance of normal human lung is 200 Compliance of normal human lung is 200 ml/cm.Hml/cm.H22O.O.

Replacement of the elastic lung tissue with Replacement of the elastic lung tissue with non non elastic scar tissueelastic scar tissue as well as as well as reduced surfactant reduced surfactant productionproduction will will decreasedecrease lung compliance. lung compliance.Inflation of lungs (inspiration) follows a different Inflation of lungs (inspiration) follows a different curve than deflation of the lung (expiration); this curve than deflation of the lung (expiration); this difference is called difference is called hysteresis.hysteresis.

Measurement of complianceMeasurement of compliance

Comparison of the compliance diagrams of Comparison of the compliance diagrams of saline-filled and air-filled lungssaline-filled and air-filled lungs

Factors influencing lung complianceFactors influencing lung compliance

Factors which decrease lung complianceFactors which decrease lung compliance1. Disease that destroy lung tissue1. Disease that destroy lung tissue2. Decreased distensibility of fibrotic tissue 2. Decreased distensibility of fibrotic tissue 3. Raised pulmonary venous pressure3. Raised pulmonary venous pressure4. Chest deformities & paralysis of respiratory muscle4. Chest deformities & paralysis of respiratory muscle

Factors which increase lung complianceFactors which increase lung compliance1. Greater size of lungs1. Greater size of lungs2. Increased age (because of alteration in elastic 2. Increased age (because of alteration in elastic tissue fibers of lungs)tissue fibers of lungs)3. Emphysema3. Emphysema

Clinical significanceClinical significanceLow compliance:Low compliance: Indicating stiff lung, means more Indicating stiff lung, means more work is required to bring in a normal volume of air. work is required to bring in a normal volume of air. Very high compliance:Very high compliance: Lungs of patients with Lungs of patients with emphysemaemphysema have a high compliance and are have a high compliance and are extremely easy to inflate. extremely easy to inflate. Lungs with abnormally high compliance Lungs with abnormally high compliance have poor have poor elastic recoil.elastic recoil. Thus, a lung affected by emphysema is Thus, a lung affected by emphysema is easily easily distended but does not recoil back during expiration.distended but does not recoil back during expiration. Consequently, a lot of effort is required to get air out of Consequently, a lot of effort is required to get air out of the lungs and the lungs and looks “baggy”. looks “baggy”. Thus, smoking-induced emphysema can lead to a Thus, smoking-induced emphysema can lead to a “baggy-lungs” that retain air.“baggy-lungs” that retain air.

Airway resistanceAirway resistanceIt is the resistance the air encounters while passing It is the resistance the air encounters while passing through the airways. through the airways. It is explained by the following equation (Poiseuille's It is explained by the following equation (Poiseuille's law): law):

Where, R = Resistance, η = Viscosity, l = Length of Where, R = Resistance, η = Viscosity, l = Length of the tube, r = Radius of the tube.the tube, r = Radius of the tube.Therefore, resistance will increase when there is: Therefore, resistance will increase when there is: (i) Decreased radii of the air passages,(i) Decreased radii of the air passages,(ii) Increased length of the passage and(ii) Increased length of the passage and(iii) Increased viscosity of the air.(iii) Increased viscosity of the air.The reverse conditions will decrease the resistance. The reverse conditions will decrease the resistance.

As such, the As such, the viscosity of airviscosity of air and the and the length of length of the passagethe passage do not change. do not change. So, the So, the resistance is mainly dependent on the resistance is mainly dependent on the radiusradius of the airways. of the airways. The major site of airway resistance is the The major site of airway resistance is the medium-sized bronchi.medium-sized bronchi. The smallest airways would seem to offer the The smallest airways would seem to offer the highest resistance, but they do not because of highest resistance, but they do not because of their their parallel arrangement.parallel arrangement.

Factors determining airway resistanceFactors determining airway resistanceLung volume:Lung volume: Less resistance when lung volume is Less resistance when lung volume is bigger; more resistance when lung volume is bigger; more resistance when lung volume is smaller.smaller.

Contraction of smooth muscle:Contraction of smooth muscle: Contraction of Contraction of smooth muscle increases airway resistance. This by smooth muscle increases airway resistance. This by irritants and by vagal stimulation. irritants and by vagal stimulation. Sympathetic Sympathetic stimulation and adrenaline stimulation and adrenaline relax bronchial relax bronchial musculature via beta-adrenergic receptors.musculature via beta-adrenergic receptors.

Viscosity or density of the inspired air:Viscosity or density of the inspired air: It depends It depends on the density of the air. So, in on the density of the air. So, in compressed air compressed air (deep-sea diving), the resistance is more(deep-sea diving), the resistance is more and and resistance is resistance is low in high altitude.low in high altitude.

Dynamic compression of airwaysDynamic compression of airwaysExpiration is normally a passive process. Expiration is normally a passive process. Forced expiration increases the intrapleural and thus Forced expiration increases the intrapleural and thus alveolar pressure, increasing the pressure gradient to alveolar pressure, increasing the pressure gradient to the mouth and therefore theoretically leading to the mouth and therefore theoretically leading to increased flow. increased flow. Forced expiration from fully inflated lungs is Forced expiration from fully inflated lungs is effort effort dependent.dependent. Towards the end of the breath increasing force does Towards the end of the breath increasing force does not increase flow, i.e. it is not increase flow, i.e. it is effort independent.effort independent. This occurs as a result of the pressure gradient This occurs as a result of the pressure gradient between the alveoli and the mouth. between the alveoli and the mouth.

Midway between them, generally in the bronchi, the Midway between them, generally in the bronchi, the pressure in the airway falls below the intrapleural pressure in the airway falls below the intrapleural pressure causing the airway collapse. pressure causing the airway collapse. Thus the Thus the dynamic compressiondynamic compression occurs. occurs. As there is now no flow, the pressure rises again until As there is now no flow, the pressure rises again until it is greater than the intrapleural pressure, and the it is greater than the intrapleural pressure, and the airway reopens.airway reopens. This sequence happens repeatedly, producing the This sequence happens repeatedly, producing the brassy sound heard during forced expiration. brassy sound heard during forced expiration. This does not occur in normal expiration because the This does not occur in normal expiration because the intrapleural pressure remains negative throughout. intrapleural pressure remains negative throughout. In diseases in which the airways are already narrowed In diseases in which the airways are already narrowed (e.g. asthma), this leads to expiratory (e.g. asthma), this leads to expiratory wheezingwheezing and and air trapping.air trapping.

Work of breathingWork of breathingCompliance work:Compliance work: Work which is required to expand Work which is required to expand the lungs against its elastic forces.the lungs against its elastic forces.Tissue resistance work:Tissue resistance work: Required to overcome the Required to overcome the viscosity of the lung and chest wall structure. viscosity of the lung and chest wall structure. Airway resistance work:Airway resistance work: Required to overcome the Required to overcome the resistance to the airflow.resistance to the airflow.

During normal breathing, only 3 – 5% of the total During normal breathing, only 3 – 5% of the total energy is required for pulmonary ventilation. energy is required for pulmonary ventilation.

Factors which increase work of breathing:Factors which increase work of breathing:1. Structural changes in lung and thorax.1. Structural changes in lung and thorax.2. Loss of surfactant.2. Loss of surfactant.3. Increased airway resistance.3. Increased airway resistance.

Three different types of work done during inspirationThree different types of work done during inspiration

SpirometerSpirometer

SpirogramSpirogram

Lung VolumesLung Volumes

Tidal volume (VT) = 500 ml.Tidal volume (VT) = 500 ml.Inspiratory Reserve Volume (IRV) = 3000 ml.Inspiratory Reserve Volume (IRV) = 3000 ml.Expiratory Reserve Volume (ERV) = 1100 ml.Expiratory Reserve Volume (ERV) = 1100 ml.Residual Volume (RS) = 1200 ml.Residual Volume (RS) = 1200 ml.

Lung CapacitiesLung CapacitiesInspiratory Capacity (IC) = 3500 ml.Inspiratory Capacity (IC) = 3500 ml.Functional Residual Capacity (FRC) = 2300 ml.Functional Residual Capacity (FRC) = 2300 ml.Vital Capacity (VC) = 4600 ml.Vital Capacity (VC) = 4600 ml.Total Lung Capacity (TLC) = 5800 ml.Total Lung Capacity (TLC) = 5800 ml.All lung volume & capacities are 20-25% less in All lung volume & capacities are 20-25% less in female than male; greater in large & athletic person.female than male; greater in large & athletic person.

Significance of Vital CapacitySignificance of Vital Capacity

Average vital capacity in young adult male of is about Average vital capacity in young adult male of is about 4.6 L4.6 L and in female and in female 3.2 L.3.2 L.

The major factors that affect VC are:The major factors that affect VC are:1. Position of the person during measurement1. Position of the person during measurement

(standing(standing>sitting>lying)>sitting>lying)2. Strength of respiratory muscle2. Strength of respiratory muscle3. Distensibility 3. Distensibility of the lungs and chest wall of the lungs and chest wall (compliance)(compliance)4. Pulmonary congestion4. Pulmonary congestion

Significance of Residual VolumeSignificance of Residual VolumeIt provides air in the alveoli to aerate the blood It provides air in the alveoli to aerate the blood even between breaths.even between breaths.It prevents marked fluctuation in the It prevents marked fluctuation in the composition of alveolar air.composition of alveolar air.It prevents the complete collapse of lung.It prevents the complete collapse of lung.

FRC and RV can not be measured with a FRC and RV can not be measured with a simple spirometer.simple spirometer. Therefore, an indirect Therefore, an indirect method such as helium dilution method is method such as helium dilution method is used to measure FRC. used to measure FRC. RVRV = FRC-ERV and = FRC-ERV and TLCTLC = FRC+IC = FRC+IC

Measurement of FRCMeasurement of FRC

Helium-Dilution Technique:Helium poorly soluble in water and thus diffuses very poorly across the alveolar wall. Subjects breath a gas that cannot escape from the lungs.After several minutes of breathing, the helium concentrations in the spirometer and lung become the same. From the law of conservation of matter, we know that the total amount of helium before and after is the same.

FUNCTIONAL RESIDUAL CAPACITYFUNCTIONAL RESIDUAL CAPACITY

• Helium dilution• Spirometer of known volume and helium concentration connected to the patient• Closed circuit • Law of conservation of mass

At beginning After several minutes

RVRV = FRC - ERV and = FRC - ERV and TLCTLC = FRC + IC = FRC + IC

Anatomical dead spaceAnatomical dead spaceTV is distributed between the TV is distributed between the conducting zone and conducting zone and alveoli. alveoli. Since the gas exchange occurs only in the alveoli and Since the gas exchange occurs only in the alveoli and not in the conducting zone, not in the conducting zone, part of the tidal volume part of the tidal volume becomes wasted air. becomes wasted air. This volume of air is known as This volume of air is known as dead space volume.dead space volume. The normal dead space volume in a young adult man The normal dead space volume in a young adult man is about is about 150 ml150 ml but but increases slightly with age.increases slightly with age.

Tidal volume = 500 mlTidal volume = 500 mlDead space volume = 150 mlDead space volume = 150 ml

Fresh air entering alveoli = 350mlFresh air entering alveoli = 350ml

Physiological dead spacePhysiological dead spaceIf areas of the lung do not function well they add to If areas of the lung do not function well they add to dead space. dead space. Physiological dead space is equal to Physiological dead space is equal to Anatomical dead Anatomical dead space space plus Alveolar dead space.plus Alveolar dead space. Physiological VPhysiological VDD = Anatomical V = Anatomical VD D + Alveolar V+ Alveolar VDD..Alveolar dead spaceAlveolar dead space is the volume of air that enters is the volume of air that enters unperfused alveoliunperfused alveoli per minute. No gas exchange in per minute. No gas exchange in these alveoli.these alveoli.For example:For example:●● Alveoli not perfused by blood (pulmonary embolism)Alveoli not perfused by blood (pulmonary embolism)●● Collapsed alveoli (atelectasis)Collapsed alveoli (atelectasis)●● Damaged alveoli (smoking related emphysema)Damaged alveoli (smoking related emphysema)

Pulmonary ventilation or Minute ventilationPulmonary ventilation or Minute ventilation= Tidal volume (V= Tidal volume (VTT) x Respiratory Rate (R.R.) ) x Respiratory Rate (R.R.)

= 0.5 L x 12 breaths/min = 0.5 L x 12 breaths/min = 6 L/min.= 6 L/min.

Alveolar ventilationAlveolar ventilation= (V= (VTT – V – VDD) x R.R. ) x R.R.

= (500-150) x 12= (500-150) x 12= 350 x 12= 350 x 12= 4.2 L/min.= 4.2 L/min.

Ventilation – Perfusion RatioVentilation – Perfusion RatioNormal Normal alveolar ventilation (V) is 4.0 L/minalveolar ventilation (V) is 4.0 L/min and the and the normal blood flow through the alveolar capillaries or normal blood flow through the alveolar capillaries or perfusion (Q) is about 5.0 L/min.perfusion (Q) is about 5.0 L/min.

Thus the normal Thus the normal ventilation-perfusion ratio is equal to ventilation-perfusion ratio is equal to 0.80.8 (V/Q = 4/5 = 0.8).(V/Q = 4/5 = 0.8).

In upright position,In upright position, blood flow is decreased much more blood flow is decreased much more than the ventilation. Therefore, at the top of the lung than the ventilation. Therefore, at the top of the lung V/Q ratio is about 3.3.V/Q ratio is about 3.3.

At the bottom of the lung,At the bottom of the lung, V/Q ratio is V/Q ratio is less (0.6).less (0.6).

Ventilation-Perfusion Relationship in the LungVentilation-Perfusion Relationship in the Lung

Ventilation- Perfusion MismatchingVentilation- Perfusion Mismatching

Basic Properties of GasesBasic Properties of Gases

Air is made up of 79% nitrogen, 21% oxygen, smaller Air is made up of 79% nitrogen, 21% oxygen, smaller amounts of carbon dioxide (0.04%) and water vapor, amounts of carbon dioxide (0.04%) and water vapor, and minute amounts of other gases.and minute amounts of other gases.The pressure exerted by atmospheric air is a sum of The pressure exerted by atmospheric air is a sum of the pressures exerted by each individual gas in the the pressures exerted by each individual gas in the air. air. Thus each gas in a mixture of gases exerts a certain Thus each gas in a mixture of gases exerts a certain amount of pressure. This is known as the amount of pressure. This is known as the partialpartial pressurepressure for that gas.for that gas.Individual gases tend to Individual gases tend to move from one place to move from one place to anotheranother based on their partial pressure gradient. based on their partial pressure gradient.

Partial Pressures of Respiratory GasesPartial Pressures of Respiratory Gases

Gas Atmospheric Alveolar Expired Arterial Gas Atmospheric Alveolar Expired Arterial Air Air Air Air Air Air BloodBlood

OO22 159 159 104 120 104 120 95 95

COCO22 0.3 40 27 0.3 40 27 40 40

HH22O 3.7 47 O 3.7 47 47 47 47 47

NN22 597 597 569 569 566 566 573573

Difference between the composition of Difference between the composition of alveolar air and the atmospheric airalveolar air and the atmospheric air

OO22 is constantly is constantly removedremoved from alveolar air from alveolar air

COCO22 is constantly is constantly addedadded to alveolar air to alveolar air

Only a small amount of Only a small amount of freshfresh atmosphericatmospheric airair (350 (350 ml) is added to the alveolar air (2200 ml; FRC)ml) is added to the alveolar air (2200 ml; FRC)Atmospheric air is Atmospheric air is humidifiedhumidified by the upper by the upper respiratory passages before it enters alveoli.respiratory passages before it enters alveoli.

Respiratory MembraneRespiratory Membrane• Gas exchange between alveolar air and pulmonary Gas exchange between alveolar air and pulmonary

blood occurs through the blood occurs through the blood-gas barrier calledblood-gas barrier called respiratory membrane.respiratory membrane.

• Total area of respiratory membrane about Total area of respiratory membrane about 70 square 70 square meters.meters.

• The thickness of this membrane does not exceed The thickness of this membrane does not exceed 0.6 0.6 m.m.

• It is composed of 6 layers:It is composed of 6 layers:1)1) A thin layer of fluid (surfactant and water)A thin layer of fluid (surfactant and water)2)2) Alveolar wall (simple squamous epithelium)Alveolar wall (simple squamous epithelium)3)3) Basement membrane of alveolar wallBasement membrane of alveolar wall4)4) Interstitial space (between 3 and 5 layers) Interstitial space (between 3 and 5 layers) 5)5) Basement membrane of capillary wallBasement membrane of capillary wall6)6) Capillary wall (capillary endothelium)Capillary wall (capillary endothelium)

Respiratory Membrane

DIFFUSION ACROSS THE RESPIRATORY MEMBRANEDIFFUSION ACROSS THE RESPIRATORY MEMBRANE

The amount of gas transferred is proportional to:The amount of gas transferred is proportional to:Surface area (A)Surface area (A)Diffusion constant (D)Diffusion constant (D)Difference in partial pressure (P1 –P2), andDifference in partial pressure (P1 –P2), andThickness of respiratory membrane (T)Thickness of respiratory membrane (T)

The constant (D) is proportional to gas solubility, but The constant (D) is proportional to gas solubility, but inversely proportional to the square root of its molecular inversely proportional to the square root of its molecular weight (MW).weight (MW).

V gas V gas AD (P1 –P2)AD (P1 –P2) D D SS T T MW MWSolubility of COSolubility of CO22 in normal saline at 37 in normal saline at 3700C is approximately 24 C is approximately 24 times greater than that of Otimes greater than that of O22..The diffusion rate of COThe diffusion rate of CO22 through a tissue sheet is about 20 through a tissue sheet is about 20 times that of Otimes that of O22

Factors affecting net gas diffusion Factors affecting net gas diffusion through respiratory membranethrough respiratory membrane

O2

CO2

P1

P2

Thickness

Area

O2

CO2

P1

P2

Thickness

Area

Gas ExchangeGas Exchange

● ● The partial pressure of OThe partial pressure of O22 in the alveoli is 104 mmHg. The partial pressure of in the alveoli is 104 mmHg. The partial pressure of OO22 in blood entering pulmonary capillaries is 40 mmHg. in blood entering pulmonary capillaries is 40 mmHg.

●● The partial pressure of COThe partial pressure of CO22 in the alveoli is 40 mmHg. The partial pressure in the alveoli is 40 mmHg. The partial pressure of COof CO22 in blood entering the pulmonary capillaries is 45 mmHg. in blood entering the pulmonary capillaries is 45 mmHg.

●● At the systemic tissues the situation is somewhat reversed. Arterial blood At the systemic tissues the situation is somewhat reversed. Arterial blood POPO22 is 95 mmHg while tissue PO is 95 mmHg while tissue PO22 is less than 40 mmHg. is less than 40 mmHg.

●● Arterial blood PCOArterial blood PCO22 is 40 mmHg while tissue PCO is 40 mmHg while tissue PCO22 is greater than 45 mmHg. is greater than 45 mmHg.

●● Notice that the partial pressure gradients for CONotice that the partial pressure gradients for CO22 are much smaller are much smaller than the partial pressure gradients for Othan the partial pressure gradients for O22. . COCO22 does not require such a big gradient because it is much more does not require such a big gradient because it is much more soluble in water; thus it enters the plasma much more readily than soluble in water; thus it enters the plasma much more readily than does Odoes O22..

Oxygen exchange through alveolocapillary Oxygen exchange through alveolocapillary membranemembrane

Diffusion of oxygen from tissue capillary to Diffusion of oxygen from tissue capillary to the cellsthe cells

Diffusion of carbon dioxide from pulmonary Diffusion of carbon dioxide from pulmonary blood into the alveolusblood into the alveolus

Uptake of carbon dioxide by the blood in Uptake of carbon dioxide by the blood in the tissue capillariesthe tissue capillaries

Concept of Physiological ShuntConcept of Physiological Shunt

Shunt means Shunt means alternative pathway. alternative pathway. Blood, if Blood, if bypassesbypasses the the pulmonary capillaries and is not oxygenated, called pulmonary capillaries and is not oxygenated, called shunted shunted blood.blood. Therefore, a physiological shunt is the Therefore, a physiological shunt is the mixing of deoxygenated mixing of deoxygenated blood with oxygenated blood.blood with oxygenated blood.Normally, about Normally, about 2% of cardiac output passing through bronchial 2% of cardiac output passing through bronchial vessels,vessels, rather than alveolar capillaries, is remain rather than alveolar capillaries, is remain unoxygenated (shunted blood from right to left side).unoxygenated (shunted blood from right to left side).Perfusion of collapsed alveoli Perfusion of collapsed alveoli (atelectasis) (atelectasis) will result in no gas will result in no gas exchange and that blood will mix with pulmonary capillary exchange and that blood will mix with pulmonary capillary blood. blood. Thebessian circulation conveys blood from myocardium Thebessian circulation conveys blood from myocardium and and empties directly into the heart chambers without passing empties directly into the heart chambers without passing through the lung.through the lung.

Transport of Oxygen by BloodTransport of Oxygen by Blood

OO22 is carried by blood in 2 ways: is carried by blood in 2 ways:1.1. 3% of the O3% of the O22 is simply dissolved in plasma. is simply dissolved in plasma.

2.2. 97% is bound to 97% is bound to hemoglobinhemoglobin within RBC. within RBC.

– Each Hb molecule can combine with up to 4 oxygen Each Hb molecule can combine with up to 4 oxygen molecules. molecules. [Hb[Hb44+4O+4O22 Hb Hb44 (O (O22))44].].

– Hemoglobin with bound OHemoglobin with bound O22 is is oxyhemoglobinoxyhemoglobin..

– Hemoglobin without bound OHemoglobin without bound O22 is is deoxyhemoglobin.deoxyhemoglobin.– Loading and unloading of OLoading and unloading of O22 is given by a single is given by a single

reversible equation: reversible equation: HHb + OHHb + O22 ↔ HbO ↔ HbO22 + H + H++..

Contd…Contd…

– When Hb has 4 OWhen Hb has 4 O22 molecules bound to it, it is molecules bound to it, it is saturatedsaturated..

– When Hb has less than 4 OWhen Hb has less than 4 O22 molecules bound molecules bound to it, it is to it, it is unsaturatedunsaturated..

– Note that in the Note that in the lungs (where Polungs (where Po22 is 104 is 104 mmHg), Hb is fully saturated.mmHg), Hb is fully saturated.

– In the In the tissues (where Potissues (where Po22 is 40 mmHg), Hb is is 40 mmHg), Hb is 75% saturated.75% saturated.

– That means, on average, each That means, on average, each Hb molecule Hb molecule has 3 molecules of Ohas 3 molecules of O22 bound to it. bound to it.

Transport of Oxygen by BloodTransport of Oxygen by Blood

OO22 content of blood & transport from blood to content of blood & transport from blood to tissuetissue

Arterial blood at PoArterial blood at Po22 = 95 mmHg, Hb is 97% saturated = 95 mmHg, Hb is 97% saturated & contains about & contains about 19.4 ml O19.4 ml O22/100 ml./100 ml.

Venous blood at PoVenous blood at Po22 = 40 mmHg, Hb is 75% saturated = 40 mmHg, Hb is 75% saturated & contains about & contains about 14.4 ml O14.4 ml O22/100 ml./100 ml.

Thus, Thus, 19.4 - 14.4 = 5 ml of O19.4 - 14.4 = 5 ml of O22/100 ml blood/100 ml blood is released is released from Hb and transported to the tissue.from Hb and transported to the tissue.Therefore, with normal cardiac output of 5 L/min, Therefore, with normal cardiac output of 5 L/min, 250 ml of O250 ml of O22 is delivered to the tissues per minute is delivered to the tissues per minute (5x5000/100).(5x5000/100).

Oxygen-hemoglobin dissociation curveOxygen-hemoglobin dissociation curve

The curve is The curve is S – shaped or sigmoid shaped.S – shaped or sigmoid shaped. At alveolar At alveolar PoPo22 of 104 mm Hg, of 104 mm Hg, Hb is 100% saturated Hb is 100% saturated At arterial blood PoAt arterial blood Po22 of of 95 mm Hg, 95 mm Hg, Hb is 97% saturated. Hb is 97% saturated. When alveolar PoWhen alveolar Po22 is decreased to as low as is decreased to as low as 60 mm Hg, 60 mm Hg, Hb is still 90% saturated.Hb is still 90% saturated.This property of Hb ensures fairly high uptake of OThis property of Hb ensures fairly high uptake of O22 by by blood even when alveolar Poblood even when alveolar Po22 is moderately decreased. is moderately decreased.The middle & lower parts of the OThe middle & lower parts of the O22- Hb dissociation - Hb dissociation curve are curve are concerned with Oconcerned with O22 delivery to the tissue. delivery to the tissue.At PoAt Po22 of of 40 mm Hg, Hb is 75% saturated40 mm Hg, Hb is 75% saturated with O with O22..At this point, OAt this point, O22- Hb dissociation curve is very steep. - Hb dissociation curve is very steep. This means, in a small decrease in PoThis means, in a small decrease in Po22 can result can result substantial further dissociation of Osubstantial further dissociation of O2 2 for tissue use.for tissue use.At At PoPo22 of 20 mm Hg, Hb is 20% of 20 mm Hg, Hb is 20% saturated with O saturated with O22. The . The total total OO22 content is only 4.4 ml/100 ml blood. content is only 4.4 ml/100 ml blood.

Concept of PConcept of P5050 and its significance and its significance

PP5050 refers to the partial pressure of O refers to the partial pressure of O22 that produces a that produces a 50% saturation of the Hb with O50% saturation of the Hb with O22..

Normal PNormal P5050 for arterial blood is for arterial blood is 25-27 mm Hg.25-27 mm Hg.

Decreased PDecreased P5050 indicates increased affinity of Hb for O indicates increased affinity of Hb for O22.. Thus, decreased PThus, decreased P5050 is equivalent to shift of Hb-O is equivalent to shift of Hb-O22 curve curve to left. to left. Fetal Hb and myoglobinFetal Hb and myoglobin has lower P has lower P5050 value than value than adult Hb.adult Hb.Increased PIncreased P5050 indicates decreased affinity of Hb for O indicates decreased affinity of Hb for O22.. Thus, increased PThus, increased P5050 is equivalent to shift of Hb-O is equivalent to shift of Hb-O22 curve curve to right. Increase in to right. Increase in PCOPCO22, H, H++ concentration, concentration, temperature, and 2,3-DPGtemperature, and 2,3-DPG causes increased P causes increased P5050..

Concept of PConcept of P5050

Factors affecting oxygen-hemoglobin Factors affecting oxygen-hemoglobin dissociation curvedissociation curve

– Increased temperatureIncreased temperature in skeletal muscles due to in skeletal muscles due to more heat production,more heat production,

– Increased PCOIncreased PCO22 due to accumulation of CO due to accumulation of CO22 resulting from rapid metabolism,resulting from rapid metabolism,

– Decreased PODecreased PO22 due to rapid consumption, due to rapid consumption,

– Increased HIncreased H++ due to more production of CO due to more production of CO22 and and– Decreased pHDecreased pH due to accumulation of lactic acid due to accumulation of lactic acid

produced in muscular exercise.produced in muscular exercise.– Increased 2,3-DPGIncreased 2,3-DPG due to anaerobic metabolism. due to anaerobic metabolism.

Effect of pHEffect of pH

Effect of PCOEffect of PCO22

Effect of temperatureEffect of temperature

Effect of 2,3-diphosphoglycerateEffect of 2,3-diphosphoglycerate

The RBC are rich in 2,3-DPG which is formed from 3-The RBC are rich in 2,3-DPG which is formed from 3-phosphoglyceraldehyde produce during glycolysis.phosphoglyceraldehyde produce during glycolysis.The 2,3-DPG is a highly charged anion that binds to The 2,3-DPG is a highly charged anion that binds to ββ–chain of deoxygenated adult haemoglobin.–chain of deoxygenated adult haemoglobin.

HbOHbO22 + 2,3-DPG Hb. 2,3-DPG + O + 2,3-DPG Hb. 2,3-DPG + O22

Thus, an increase in the concentration of 2,3-DPG Thus, an increase in the concentration of 2,3-DPG decreases the affinity of Hb for Odecreases the affinity of Hb for O22 and shifts the and shifts the normal Onormal O22-Hb dissociation curve to the right.-Hb dissociation curve to the right.

Causes of increased level of 2,3-DPG are Causes of increased level of 2,3-DPG are anaemia, anaemia, exposure to chronic hypoxia at high altitude and exposure to chronic hypoxia at high altitude and certain pulmonary diseases.certain pulmonary diseases.

Effect of 2,3-DPGEffect of 2,3-DPG

Bohr EffectBohr Effect

A rise in PCOA rise in PCO22 or a decrease in pH or a decrease in pH decreases the decreases the binding affinity of Hb for Obinding affinity of Hb for O22 and hence shifts the O and hence shifts the O22-Hb -Hb dissociation curve to the right.dissociation curve to the right.The The significance of Bohr effectsignificance of Bohr effect lies in the fact that it lies in the fact that it increases oxygenation of the blood in the lungs and increases oxygenation of the blood in the lungs and also increases the release of Oalso increases the release of O22 from the blood in the from the blood in the tissues.tissues.

Other Factors Affecting Oxygen TransportOther Factors Affecting Oxygen TransportExercise:Exercise: Production of larger amount of COProduction of larger amount of CO22, heat , heat and acids that will shift the curve to the right side.and acids that will shift the curve to the right side.

Carbon Monoxide (CO):Carbon Monoxide (CO): Toxic CO has 200-250 times Toxic CO has 200-250 times more binding affinity than Omore binding affinity than O22. They shift the curve . They shift the curve towards left.towards left.

Fetal hemoglobin:Fetal hemoglobin: HbF shift the curve to the left. HbF HbF shift the curve to the left. HbF has higher affinity for Ohas higher affinity for O22 than HbA promotes transport than HbA promotes transport of Oof O22 across the placenta even at lower PO across the placenta even at lower PO22..

Myoglobin:Myoglobin: Mb, a heme protein that occurs in muscle Mb, a heme protein that occurs in muscle cells, consists of a single polypeptide chain attached cells, consists of a single polypeptide chain attached to a heme group. Therefore it can bind to a single to a heme group. Therefore it can bind to a single molecule of Omolecule of O22. The curve is towards the left.. The curve is towards the left.

Carbon monoxide poisoningCarbon monoxide poisoning

How would this affect OHow would this affect O22 transport? transport?

Carbon monoxide binds to hemoglobin Carbon monoxide binds to hemoglobin (carboxyhemoglobin) in the same binding site (carboxyhemoglobin) in the same binding site as oxygen, but binds far more tightly (binding as oxygen, but binds far more tightly (binding affinity 200-250 times greater than Oaffinity 200-250 times greater than O22).).

It shifts the Hb-OIt shifts the Hb-O22 curve to the left. Thus CO curve to the left. Thus CO prevent the loading of Oprevent the loading of O22 into the blood in the into the blood in the lungs and also interfere with unloading of Olungs and also interfere with unloading of O22 at the tissues. This is second deleterious at the tissues. This is second deleterious effect.effect.

Carbon monoxide Carbon monoxide -hemoglobin -hemoglobin dissociation curvedissociation curve

Comparison of oxygen & carbon monoxide Comparison of oxygen & carbon monoxide --hemoglobin dissociation curvehemoglobin dissociation curve

Comparison of the OComparison of the O22-Hb dissociation curves -Hb dissociation curves for HbA & HbFfor HbA & HbF

Dissociation curves for HbA and MbDissociation curves for HbA and Mb

Transport of COTransport of CO22 by Blood by Blood

Transported primarily in 3 ways:Transported primarily in 3 ways:Dissolved in plasma (7%)Dissolved in plasma (7%)Bound to hemoglobin (23%)Bound to hemoglobin (23%)– In the plasma,In the plasma, CO CO22 combines with amino group of plasma proteins to combines with amino group of plasma proteins to

form form carbamino proteins.carbamino proteins.– In the RBC,In the RBC, COCO22 combines with amino group of hemoglobin. combines with amino group of hemoglobin.– Hb + COHb + CO22 ↔ HbCO ↔ HbCO22. HbCO. HbCO22 is known as is known as carbaminohemoglobincarbaminohemoglobin..

As bicarbonate ion in plasma (70%)As bicarbonate ion in plasma (70%)– When COWhen CO22 diffuses out of the tissue fluid, it enters the plasma and then diffuses out of the tissue fluid, it enters the plasma and then

the RBC. Within the RBC, COthe RBC. Within the RBC, CO22 combines with water to form combines with water to form carboniccarbonic acidacid,, which dissociates into a which dissociates into a bicarbonatebicarbonate ionion and a and a hydrogenhydrogen ionion..

– The equation that describes what happens at the RBC in the tissues is:The equation that describes what happens at the RBC in the tissues is:COCO22 + H+ H22O ↔ HO ↔ H22COCO33 ↔ HCO ↔ HCO33

-- + H + H++..– This reaction is catalyzed by the enzyme This reaction is catalyzed by the enzyme carboniccarbonic anhydraseanhydrase..

Transport of COTransport of CO22 by Blood by Blood

Chloride shiftChloride shift

As carbonic acid (As carbonic acid (HH22COCO33) is formed, it readily ) is formed, it readily dissociates to Hdissociates to H++ and HCO and HCO33

-- ions. ions.

HCOHCO33-- ions diffuse out of RBC in exchange for ions diffuse out of RBC in exchange for

chloride (Clchloride (Cl--) diffusion into the cell to maintain ) diffusion into the cell to maintain electrical neutrality. electrical neutrality. The ClThe Cl- - movement is known as the movement is known as the chloride shift.chloride shift.

The Carbon Dioxide Dissociation CurveThe Carbon Dioxide Dissociation Curve

The Carbon Dioxide Transport in the BloodThe Carbon Dioxide Transport in the Blood

Venous blood at Venous blood at PCOPCO22 = 45 mmHg = 45 mmHg contains about contains about 52 ml CO52 ml CO22/100 ml/100 ml of blood. of blood.

Arterial blood at Arterial blood at PCOPCO22 = 40 mmHg = 40 mmHg contains about contains about 48 ml CO48 ml CO22/100 ml/100 ml of blood. of blood.

Thus, Thus, 52-48 = 4 ml CO52-48 = 4 ml CO22/100 ml of blood/100 ml of blood is is transported from tissues to the blood to the lungs.transported from tissues to the blood to the lungs.

Haldane EffectHaldane Effect

Binding of OBinding of O22 with hemoglobin tends to with hemoglobin tends to displace COdisplace CO2 2 from the blood. This effect from the blood. This effect called the called the Haldane effect.Haldane effect.In the lungs, it causes increased release In the lungs, it causes increased release of COof CO22 because of O because of O22 uptake by the uptake by the hemoglobin.hemoglobin.

Respiratory QuotientRespiratory Quotient

Normal transport of Normal transport of OO22 from the lungs to the from the lungs to the tissue is tissue is 5 ml/100 ml5 ml/100 ml of blood, whereas of blood, whereas transport of transport of COCO22 from the tissues to the lungs is from the tissues to the lungs is 4 ml/100 ml4 ml/100 ml of blood. of blood.The ratio of COThe ratio of CO22 output to O output to O22 uptake is called uptake is called the the respiratory exchange ratio or respiratory respiratory exchange ratio or respiratory quotient (R).quotient (R). For a person on a normal diet the average For a person on a normal diet the average value for value for R is considered to be 0.8.R is considered to be 0.8.

Respiratory acidosisRespiratory acidosisWhen plasma COWhen plasma CO22 level increases (more than 45 mm level increases (more than 45 mm Hg), this in turn, increases the plasma HHg), this in turn, increases the plasma H++ that leads to that leads to a decrease in plasma pH. a decrease in plasma pH. If plasma pH drops below normal levels, we call it If plasma pH drops below normal levels, we call it respiratory acidosis.respiratory acidosis.

Causes: Causes: Respiratory depression/muscle paralysis, pulmonary Respiratory depression/muscle paralysis, pulmonary edema, pneumonia, asthma, anything causing edema, pneumonia, asthma, anything causing decrease in ability to ventilate.decrease in ability to ventilate.

Signs/Symptoms:Signs/Symptoms:Breathlessness, restlessness, lethargy, disorientation, Breathlessness, restlessness, lethargy, disorientation, muscle twitching, tremors, convulsions and coma. muscle twitching, tremors, convulsions and coma.

Respiratory alkalosisRespiratory alkalosisWhen plasma COWhen plasma CO22 drops (below 35 mm Hg), this in drops (below 35 mm Hg), this in turn, decreases the plasma Hturn, decreases the plasma H++ that leads to an that leads to an increase in plasma pH. increase in plasma pH. If plasma pH rises above normal levels, we call it If plasma pH rises above normal levels, we call it respiratory alkalosis.respiratory alkalosis.

Causes:Causes:Voluntary hyperventilation, hypoxemia, congestive Voluntary hyperventilation, hypoxemia, congestive heart failure, hysteria, cirrhosis, improper use of heart failure, hysteria, cirrhosis, improper use of mechanical ventilation. mechanical ventilation.

Signs/Symptoms:Signs/Symptoms:Dizziness, confusion, tingling of extremities, Dizziness, confusion, tingling of extremities, convulsions, coma, cerebral vasoconstriction.convulsions, coma, cerebral vasoconstriction.

Control of RespirationControl of Respiration

Respiration is regulated by a complex integration of Respiration is regulated by a complex integration of neural control mechanismsneural control mechanisms which are modified by which are modified by chemoreceptors, lung receptors and inputs from chemoreceptors, lung receptors and inputs from higher centers.higher centers.Neural control mechanisms:Neural control mechanisms:● ● A system for automatic control of respirationA system for automatic control of respiration as an as an involuntary function. The involuntary control system of involuntary function. The involuntary control system of respiration is located in the respiration is located in the medullary and pontine medullary and pontine centers of the brainstem.centers of the brainstem.●● Involuntary control which allows human to breathe Involuntary control which allows human to breathe without conscious efforts under all circumstances without conscious efforts under all circumstances including sleep and is thus essential for life.including sleep and is thus essential for life.

I. Neural controlI. Neural control

The nervous system controls respiration by:The nervous system controls respiration by:1.1. Respiratory center located in the brainstemRespiratory center located in the brainstem2.2. Higher centersHigher centers3.3. Respiratory reflexesRespiratory reflexes

Respiratory centerRespiratory centerThe respiratory center is located bilaterally in the The respiratory center is located bilaterally in the medulla oblongata and pons. medulla oblongata and pons. It is divided into 4 major collections of neurons:It is divided into 4 major collections of neurons:

1.1. Dorsal respiratory group:Dorsal respiratory group: Located in the dorsal Located in the dorsal portion of the portion of the medullamedulla

2.2. Ventral respiratory group:Ventral respiratory group: Located in the ventral part Located in the ventral part of the of the medullamedulla

3.3. Pneumotaxic center:Pneumotaxic center: Located dorsally in the superior Located dorsally in the superior portion of the portion of the pons. pons.

4.4. Apneustic center:Apneustic center: Located in the lower part of the Located in the lower part of the pons.pons.

Medullary Respiratory CentersMedullary Respiratory Centers

2 sets of neurons in the medulla oblongata are 2 sets of neurons in the medulla oblongata are the primary control centers.the primary control centers.

1.1. Dorsal respiratory group (DRG)Dorsal respiratory group (DRG)2.2. Ventral respiratory group (VRG)Ventral respiratory group (VRG) Dorsal respiratory group (DRG)Dorsal respiratory group (DRG)

●● DRG are located bilaterally in the DRG are located bilaterally in the nucleus of the tractus nucleus of the tractus solitarius (NTS).solitarius (NTS). NTS is the primary projection of visceral NTS is the primary projection of visceral afferent fibers of the afferent fibers of the IXth (glossopharyngeal) and Xth IXth (glossopharyngeal) and Xth (vagus) cranial nerves.(vagus) cranial nerves.

Stimulation of the DRG always causes inspiration, never Stimulation of the DRG always causes inspiration, never expiration. expiration.

Inputs to the DRG come from the Inputs to the DRG come from the vagus and vagus and glossopharyngeal nerves. glossopharyngeal nerves. The vagus nerve relays information from The vagus nerve relays information from peripheral peripheral chemoreceptors and mechanoreceptors in the lung.chemoreceptors and mechanoreceptors in the lung.The glossopharyngeal nerve relays information from The glossopharyngeal nerve relays information from peripheral chemoreceptors.peripheral chemoreceptors. Outputs from the DRG travel via the Outputs from the DRG travel via the phrenic nervephrenic nerve to to the diaphragm.the diaphragm.

Organization of the respiratory centerOrganization of the respiratory center

Genesis of rhythm of inspiratory signalGenesis of rhythm of inspiratory signalThe The inspiratory neurons initiateinspiratory neurons initiate the inspiratory signals the inspiratory signals to the to the diaphragm and other inspiratory muscles,diaphragm and other inspiratory muscles, which which contract. contract. The increase in inspiratory signals last for The increase in inspiratory signals last for about 2 about 2 secondsseconds and then and then stops for about 3 secondsstops for about 3 seconds in normal in normal respiration. The entire cycle repeats again. respiration. The entire cycle repeats again. The The expiratory neurons remain inactive during normal expiratory neurons remain inactive during normal quiet respiration,quiet respiration, because inspiration is achieved by because inspiration is achieved by contraction of inspiratory muscles, while expiration contraction of inspiratory muscles, while expiration results from passive recoil of elastic structures of the results from passive recoil of elastic structures of the lungs and the chest cage. lungs and the chest cage. When the When the respiratory drive for increased ventilationrespiratory drive for increased ventilation is is great, the great, the expiratory center becomes activeexpiratory center becomes active and and impulses go to the expiratory muscles, which impulses go to the expiratory muscles, which contribute their powerful contractile forces to the contribute their powerful contractile forces to the respiratory process.respiratory process.

VentralVentral respiratory group (VRG)respiratory group (VRG)

– The VRG are located bilaterally and the nucleus The VRG are located bilaterally and the nucleus are: the are: the nucleus ambiguus and the nucleus nucleus ambiguus and the nucleus retroambiguus. retroambiguus.

– Involved in forced inspiration and forced Involved in forced inspiration and forced expiration.expiration.

– They consist of both inspiratory and expiratory They consist of both inspiratory and expiratory neurons.neurons.

– The neurons of the VRG remain almost totally The neurons of the VRG remain almost totally inactiveinactive during normal quiet respiration. during normal quiet respiration.

– Their major function is to drive either Their major function is to drive either spinal spinal neurons innervating mainly the intercostal and neurons innervating mainly the intercostal and abdominal muscles, or accessory muscles of abdominal muscles, or accessory muscles of respiration innervated by the vagus nerve.respiration innervated by the vagus nerve.

Secondary control centers: Pons.Secondary control centers: Pons.

Pneumotaxic center:Pneumotaxic center: Located dorsally in the nucleus Located dorsally in the nucleus parabrachialis of the upper pons.parabrachialis of the upper pons.It transmits signals to the inspiratory area. It transmits signals to the inspiratory area. The primary effect of this center is to control the The primary effect of this center is to control the "switch-off" point of the inspiratory ramp, thus "switch-off" point of the inspiratory ramp, thus controlling the duration of the filling phase of the lung controlling the duration of the filling phase of the lung cycle. cycle. A pneumotaxic centerA pneumotaxic center limits the duration of inspiration limits the duration of inspiration and increases the respiratory rate. and increases the respiratory rate. A strong pneumotaxic signal can increase the rate of A strong pneumotaxic signal can increase the rate of breathing to 30 to 40 breaths per minute.breathing to 30 to 40 breaths per minute.A weak pneumotaxic signal may reduce the rate to A weak pneumotaxic signal may reduce the rate to only 3 to 5 breaths per minute. only 3 to 5 breaths per minute.

Apneustic centerApneustic centerApneustic centerApneustic center is located in the lower portion of the is located in the lower portion of the pons. pons. This center transmits signals to the inspiratory area in This center transmits signals to the inspiratory area in an attempt to prevent turn off of the inspiratory signals. an attempt to prevent turn off of the inspiratory signals. This increases the tidal volume and duration of This increases the tidal volume and duration of inspiration.inspiration.Thus it also helps to adjust respiratory rate and depth Thus it also helps to adjust respiratory rate and depth of respiration.of respiration.It gets It gets feedback from the vagal afferents and also from feedback from the vagal afferents and also from other respiratory centers. other respiratory centers. As long as the pneumotaxic center is active, it As long as the pneumotaxic center is active, it overrides the apneustic center.overrides the apneustic center.

Higher centersHigher centersCerebral cortex, hypothalamus, and other parts of the limbic Cerebral cortex, hypothalamus, and other parts of the limbic system can also influence respiration. The higher centers may system can also influence respiration. The higher centers may control respiration in two possible ways:control respiration in two possible ways:(1) This control may bypass the respiratory centers completely, (1) This control may bypass the respiratory centers completely, using pyramidal fibers that innervate the same lower motor using pyramidal fibers that innervate the same lower motor neurons controlled by the DRG and VRG, andneurons controlled by the DRG and VRG, and(2) Higher centers may have an inhibitory or stimulatory effect (2) Higher centers may have an inhibitory or stimulatory effect on the respiratory centers.on the respiratory centers.Breathing can be under voluntary control through cerebral Breathing can be under voluntary control through cerebral cortex;cortex; therefore, a person can voluntarily therefore, a person can voluntarily hyperventilatehyperventilate or or hypoventilate hypoventilate (breath-holding). (breath-holding). The voluntary control system facilitates acts likeThe voluntary control system facilitates acts like talking, talking, singing, swimming, etc.singing, swimming, etc.Limbic systemLimbic system can alter the pattern of breathing in can alter the pattern of breathing in emotional emotional states such as rage and fear. states such as rage and fear. HypothalamusHypothalamus can modulate respiratory pattern can modulate respiratory pattern during pain.during pain.

Respiratory reflexesRespiratory reflexesThe respiratory rhythm is altered reflexly not The respiratory rhythm is altered reflexly not only in response to only in response to metabolic signalsmetabolic signals but also in but also in response to response to proprioceptive and irritant stimuli.proprioceptive and irritant stimuli.These receptors are protective and operate on These receptors are protective and operate on exposure to toxic vapors, chemical irritants, exposure to toxic vapors, chemical irritants, excessive lung inflation, or mechanical excessive lung inflation, or mechanical stimulation of the respiratory tract.stimulation of the respiratory tract. Some of the better known respiratory reflexes Some of the better known respiratory reflexes are described here.are described here.

(a) Hering-Breuer reflexes(a) Hering-Breuer reflexesThere are two reflexes involved: There are two reflexes involved: inflation reflex and deflation inflation reflex and deflation reflex. reflex. This reflex does not play a role in normal quite This reflex does not play a role in normal quite respiration.respiration.Hering-Breuer inflation reflexHering-Breuer inflation reflexLocated in the smooth muscles of the airways throughout the Located in the smooth muscles of the airways throughout the lungs.lungs.These are stretch receptors that transmit signals through the These are stretch receptors that transmit signals through the vagi into the DRG neuronsvagi into the DRG neurons when the lungs become when the lungs become overstretched. overstretched. These signals affect inspiration in much the same way as These signals affect inspiration in much the same way as signals from the signals from the pneumotaxic center, i.e., they limit the duration pneumotaxic center, i.e., they limit the duration of respiration. of respiration. Therefore, when the lungs become Therefore, when the lungs become overly inflatedoverly inflated, , the stretch the stretch receptors activatereceptors activate an appropriate feedback response that an appropriate feedback response that “switches off” the respiratory ramp“switches off” the respiratory ramp and thus limits further and thus limits further inspiration. inspiration. This is called This is called Hering-Breuer inflation reflex.Hering-Breuer inflation reflex. This reflex also This reflex also increases the rate of inspiration because of the reduced period increases the rate of inspiration because of the reduced period of inspiration. of inspiration.

Hering-Breuer deflation reflexHering-Breuer deflation reflexThis reflex inhibits the expiratory center and This reflex inhibits the expiratory center and stimulates the inspiratory center when the lungs stimulates the inspiratory center when the lungs are collapsing. are collapsing. The receptors, which are distinct from those of The receptors, which are distinct from those of inflation reflex, are inflation reflex, are located in the alveolar wall located in the alveolar wall near the alveolar capillary network. near the alveolar capillary network. The smaller the volume of the lungs, the The smaller the volume of the lungs, the greater the degree of inhibition, until expiration greater the degree of inhibition, until expiration stops and inspiration begins.stops and inspiration begins. This reflex normally functions only during forced This reflex normally functions only during forced expiration, when both the inspiratory and expiration, when both the inspiratory and expiratory centers are active.expiratory centers are active.

(b) Irritation reflexes (sneezing & coughing)(b) Irritation reflexes (sneezing & coughing)Irritant receptors are Irritant receptors are located between the airway located between the airway epithelial cells in the trachea, major airways, and also epithelial cells in the trachea, major airways, and also intrapulmonary airways. intrapulmonary airways. The highest concentration of irritant receptors is in the The highest concentration of irritant receptors is in the larynx and at the point where the trachea divides into larynx and at the point where the trachea divides into bronchi, called carina. bronchi, called carina. Irritant receptors are naturally Irritant receptors are naturally stimulated by cold air, stimulated by cold air, mucus, dust, and any other particulate stimulimucus, dust, and any other particulate stimuli that that might reach the airways. might reach the airways. Information from the irritant receptors is conveyed to Information from the irritant receptors is conveyed to the CNS by vagal afferent fibers. the CNS by vagal afferent fibers. It is possible that irritant receptors It is possible that irritant receptors play a role in the play a role in the bronchoconstriction of asthma attacksbronchoconstriction of asthma attacks as a result of as a result of their response to the their response to the released histamine.released histamine.

(c) J-Receptors(c) J-ReceptorsThe term The term ‘’juxta-capillary,’’ or J,‘’juxta-capillary,’’ or J, is used is used because these receptors are believed to be in because these receptors are believed to be in the the alveolar walls close to the capillaries. alveolar walls close to the capillaries. J-receptors are stimulated when the pulmonary J-receptors are stimulated when the pulmonary capillaries become engorged with blood, capillaries become engorged with blood, interstitial fluid volume increases or when interstitial fluid volume increases or when pulmonary edema occurs as in congestive pulmonary edema occurs as in congestive heart failure. heart failure. They may play a role in the They may play a role in the rapid, shallow rapid, shallow breathing and dyspneabreathing and dyspnea (sensation of difficulty (sensation of difficulty in breathing) associated with left heart failure in breathing) associated with left heart failure and interstitial lung disease.and interstitial lung disease.

(d) Joint and muscle receptors(d) Joint and muscle receptors

Impulses from Impulses from moving limbsmoving limbs are believed are believed to be part of the stimulus to ventilation to be part of the stimulus to ventilation during exercise,during exercise, especially in the early especially in the early stages.stages.

Other Reflexes Affecting RespirationOther Reflexes Affecting Respiration

Chemical controlChemical control The chemoreceptors are located in a The chemoreceptors are located in a chemosensitive chemosensitive area near the ventral surface of the medullaarea near the ventral surface of the medulla near the near the root of IXroot of IXthth and X and Xthth cranial nerves. cranial nerves. This area is highly sensitive to changes in either blood This area is highly sensitive to changes in either blood COCO2 or H or H++..

This, in turn, excites the This, in turn, excites the other portionsother portions of the of the respiratory center. respiratory center. Especially, it increases the activity of the inspiratory Especially, it increases the activity of the inspiratory center, which causes an center, which causes an increaseincrease in the in the respiratory respiratory rate.rate.

COCO2 stimulates the chemosensitive area stimulates the chemosensitive area

Respiratory control by Respiratory control by Central ChemoreceptorsCentral Chemoreceptors

COCO22 in the plasma in the plasma COCO22 in the CSF in the CSF HH+ + in the CSFin the CSF CSF pHCSF pHDetected by the Detected by the medullary (central) medullary (central) chemoreceptors.chemoreceptors.Respiratory rate and Respiratory rate and

depth are adjusted.depth are adjusted.85% of the respiratory 85% of the respiratory

drive is mediated through drive is mediated through central chemoreceptors.central chemoreceptors.

Central (medullary) Chemoreceptors (Mechanisms: H+ & CO2 sensors)

Respiratory control by peripheral Respiratory control by peripheral chemoreceptorschemoreceptors

The The peripheral chemoreceptorsperipheral chemoreceptors which regulate which regulate respiration are located in the respiration are located in the carotid body and aortic carotid body and aortic body. body. These These transmit nervous signalstransmit nervous signals to the to the respiratory respiratory center in the braincenter in the brain to help regulate respiration. to help regulate respiration. Both the Both the carotid and aortic bodies monitorcarotid and aortic bodies monitor the levels of the levels of POPO22, PCO, PCO22, and H, and H++ concentration in the arterial blood. concentration in the arterial blood.

Approximately, Approximately, 15% of the effect of respiratory drive15% of the effect of respiratory drive is is mediated through mediated through peripheral chemoreceptors.peripheral chemoreceptors.

● ● Decreases in arterial PODecreases in arterial PO22

The most potent natural stimulus for peripheral The most potent natural stimulus for peripheral chemoreceptors is chemoreceptors is low arterial POlow arterial PO22.. When PO When PO22 is is less less than 60 mmHg,than 60 mmHg, ventilation is exquisitely sensitive to PO ventilation is exquisitely sensitive to PO22. .

● ● Increases in arterial PCOIncreases in arterial PCO22

The response of the peripheral chemoreceptors to The response of the peripheral chemoreceptors to PCOPCO22 is less importantis less important than the response of the central than the response of the central chemoreceptors to PCOchemoreceptors to PCO22. .

● ● Increases in arterial HIncreases in arterial H++

Increase in Increase in arterial Harterial H++ stimulate the peripheral stimulate the peripheral chemoreceptors directly,chemoreceptors directly, independent of changes in independent of changes in PCOPCO22. . In In metabolic acidosis,metabolic acidosis, breathing rate breathing rate increasesincreases (hyperventilation) because of increased arterial H(hyperventilation) because of increased arterial H++ and and decreased pH. decreased pH.

Respiratory control by peripheral Respiratory control by peripheral chemoreceptors (carotid & aortic bodies)chemoreceptors (carotid & aortic bodies)

Peripheral Chemoreceptors

Summary of Chemo-receptor Reflexes

A Summary of Chemoreceptor Reflexes

Over all Over all Regulation of Regulation of RespirationRespiration

Dorsal and ventral group of neurons

Alteration in breathing patternAlteration in breathing patternPeriodic breathingPeriodic breathingAn An abnormality of breathingabnormality of breathing called periodic called periodic breathing occurs in a number of disease breathing occurs in a number of disease conditions. conditions. The person The person breathes deeplybreathes deeply for a short interval for a short interval of time and then breathes of time and then breathes slightly or not at allslightly or not at all for an additional interval. for an additional interval. Thus the cycle repeats itself over and over Thus the cycle repeats itself over and over again.again.

Cheyne - Stokes breathingCheyne - Stokes breathingThe most common type of periodic breathing is The most common type of periodic breathing is Cheyne-Stokes breathing.Cheyne-Stokes breathing.Characterized by slowly Characterized by slowly waxing and waning waxing and waning respiration.respiration. It followed by It followed by apnea apnea (lasting (lasting 10 to 3010 to 30 seconds) seconds) occurring over and over again every occurring over and over again every 45 seconds to 3 45 seconds to 3 minutes.minutes.Occurrence in diseaseOccurrence in disease(a) (a) Congestive heart failure and uremiaCongestive heart failure and uremia:: Cheyne- Cheyne-Stokes breathing is commonly found in congestive Stokes breathing is commonly found in congestive heart failure and uremia.heart failure and uremia.(b) (b) Brain diseaseBrain disease:: It also occurs in patients with brain It also occurs in patients with brain disease.disease.

Occurrence in healthy individualsOccurrence in healthy individuals SleepSleep High altitudeHigh altitude InfancyInfancy

CausesCauses Cheyne-Stokes breathing is due to Cheyne-Stokes breathing is due to sluggishness of sluggishness of

chemical regulationchemical regulation of respiration. of respiration. Respiratory centers are depressed which do not Respiratory centers are depressed which do not

behave properly.behave properly. If stimulated there is If stimulated there is over reaction.over reaction. The result is alternate The result is alternate apnea and hyperventilation. apnea and hyperventilation.

Cheyne - stokes breathingCheyne - stokes breathing

Biot’s Respiration:Biot’s Respiration:Characterize by episodes of Characterize by episodes of rapid uniformly rapid uniformly deepdeep inspirations, followed by long periods (10- inspirations, followed by long periods (10-30 seconds) of 30 seconds) of apnea.apnea. Commonly seen in patients suffering from Commonly seen in patients suffering from meningitis, increased intracranial pressure, meningitis, increased intracranial pressure, severe brain damage etc. severe brain damage etc.

Kussmaul breathingKussmaul breathingThe other name of this condition is The other name of this condition is acidotic breathing.acidotic breathing.It occurs in case of It occurs in case of metabolic acidosismetabolic acidosis as in as in diabetic diabetic keto -acidosis, renal failure, etc. keto -acidosis, renal failure, etc. The respiration is characterized by The respiration is characterized by rapid and deep rapid and deep breathing.breathing. This is due to This is due to stimulation by increased Hstimulation by increased H++..The main action of HThe main action of H++ of blood is via of blood is via peripheral peripheral chemoreceptors. chemoreceptors. But HBut H++ can also cross the can also cross the blood brain barrier slowlyblood brain barrier slowly when the when the concentration is high and persistent.concentration is high and persistent. In that case, the central chemoreceptors are In that case, the central chemoreceptors are stimulated. stimulated. Its aim is to Its aim is to wash out COwash out CO22..

Kussmaul breathingKussmaul breathing

Common abnormal ventilatory patternsCommon abnormal ventilatory patternsHyperventilationHyperventilation

When both the rate and depth of respiration are When both the rate and depth of respiration are increased the condition is called hyperventilation. increased the condition is called hyperventilation. A combination of both causes the A combination of both causes the decreased PAcodecreased PAco22 and Pacoand Paco22..

HypoventilationHypoventilationWhen the alveolar ventilation is less than normal When the alveolar ventilation is less than normal caused by a decreased ventilatory rate and an caused by a decreased ventilatory rate and an increased depth of breathing.increased depth of breathing.A combination of both causes A combination of both causes increased PAcoincreased PAco22 and and PacoPaco2.2.

HypercapniaHypercapniaWhen COWhen CO22 content in the body increases the condition content in the body increases the condition is called hypercapnia. is called hypercapnia. It is mostly due to ventilatory failure or due to high COIt is mostly due to ventilatory failure or due to high CO22 in inspired air.in inspired air.

AsphyxiaAsphyxiaIt is a condition characterized by decreased oxygen It is a condition characterized by decreased oxygen and increased carbon dioxide in the body. and increased carbon dioxide in the body. Asphyxia = hypoxia + hypercapnia.Asphyxia = hypoxia + hypercapnia.

OrthopneaOrthopneaThe condition in which an individual is able to breath The condition in which an individual is able to breath comfortably only in upright position. comfortably only in upright position. In the left ventricular failure the lungs are congested, In the left ventricular failure the lungs are congested, and therefore the patient may feel dyspneic. and therefore the patient may feel dyspneic. The patient feels much better on standing up or sitting. The patient feels much better on standing up or sitting.

HyperpneaHyperpneaHyperpnea is the general term for an increase in the Hyperpnea is the general term for an increase in the rate or depth of breathing. rate or depth of breathing. Hyperpnea is normal immediately after exercise. Hyperpnea is normal immediately after exercise. It is also associated with respiratory disease, infection, It is also associated with respiratory disease, infection, cardiac disease, etc. cardiac disease, etc.

TachypneaTachypneaIt is rapid and shallow breathing.It is rapid and shallow breathing.

ApneaApneaApnea means Apnea means absence of spontaneous breathing.absence of spontaneous breathing.Apnea may last for more than Apnea may last for more than 10 seconds. 10 seconds. Apnea occur in one third of normal individuals but frequent Apnea occur in one third of normal individuals but frequent among older men. among older men. Occasional apneas occur during normal sleep.Occasional apneas occur during normal sleep.Persons with Persons with sleep apnea the frequency and duration are sleep apnea the frequency and duration are greatly increased.greatly increased.

1.1. Obstructive sleep apnea:Obstructive sleep apnea: caused by blockage of upper airway. caused by blockage of upper airway.2.2. Central sleep apnea:Central sleep apnea: occur when the neural drive to respiratory occur when the neural drive to respiratory

muscles is abolished.muscles is abolished.

Other forms of apneaOther forms of apnea1.1. Deglutition (deglutition apnea)Deglutition (deglutition apnea)2.2. Breath holding (voluntary apnea)Breath holding (voluntary apnea)

Some important respiratory insufficienciesSome important respiratory insufficienciesHypoxiaHypoxia

Hypoxia is a condition in which there is lack of OHypoxia is a condition in which there is lack of O22 or or decreased Odecreased O2 2 supply at tissue level.supply at tissue level.

TypesTypesDepending on the cause, hypoxia is generally Depending on the cause, hypoxia is generally divided into four categories- divided into four categories-

1.1. Hypoxic hypoxiaHypoxic hypoxia2. Anemic hypoxia3. Stagnant hypoxic4. Histotoxic hypoxia

(1) Hypoxic hypoxia(1) Hypoxic hypoxiaIt refers to the hypoxia that results from a It refers to the hypoxia that results from a low arterial low arterial POPO22. .

There are a number of causes of hypoxic hypoxia, but There are a number of causes of hypoxic hypoxia, but each result in lowering of the Oeach result in lowering of the O22 content of the content of the systemic arterial blood. systemic arterial blood. The disorders which can lower the arterial POThe disorders which can lower the arterial PO22 are: are:

(a) Low alveolar PO(a) Low alveolar PO22

ExamplesExamplesThis is quite common following This is quite common following ascent to high altitudeascent to high altitude as the barometric pressure and as the barometric pressure and POPO22 falls falls with with increasing altitude.increasing altitude.

(b) Reduced ventilation (Hypoventilation)(b) Reduced ventilation (Hypoventilation)ExamplesExamples

– Respiratory depression due to drug overdose (barbiturate Respiratory depression due to drug overdose (barbiturate poisoning)poisoning)

– Severe weakness of the muscles that support respiration Severe weakness of the muscles that support respiration e.g. poliomyelitis, myasthenia gravis.e.g. poliomyelitis, myasthenia gravis.

– Airway obstructionAirway obstruction(c) Reduced diffusing capacity(c) Reduced diffusing capacityExamplesExamples

– Fibrosis of the lung parenchymaFibrosis of the lung parenchyma– Pulmonary edemaPulmonary edema

(d) Low ventilation-perfusion ratio(d) Low ventilation-perfusion ratio(e) Arteriovenous shunt (physiologic shunt)(e) Arteriovenous shunt (physiologic shunt)

(2) Anemic hypoxia(2) Anemic hypoxiaThis is due to a decrease in OThis is due to a decrease in O22 carrying capacity of carrying capacity of blood. blood. It is caused by a decrease in the amount of It is caused by a decrease in the amount of hemoglobin available for binding of Ohemoglobin available for binding of O22 so that the O so that the O22 content of the arterial blood is abnormally low. content of the arterial blood is abnormally low.

Examples:Examples:Reduced erythropoiesisReduced erythropoiesisBlood lossBlood lossSynthesis of abnormal hemoglobinSynthesis of abnormal hemoglobinCarbon monoxide poisoningCarbon monoxide poisoning

(3) Stagnant hypoxia(3) Stagnant hypoxiaIf the blood flow through a tissue is If the blood flow through a tissue is sluggish.sluggish. Blood Blood would stay in the capillaries for a would stay in the capillaries for a longer timelonger time than than the normal. the normal. The stay of blood in the capillaries may be so long The stay of blood in the capillaries may be so long that even after extracting a very large fraction of Othat even after extracting a very large fraction of O22 carried by the blood, all the requirements of the carried by the blood, all the requirements of the tissue cannot be met. The result will be hypoxia. tissue cannot be met. The result will be hypoxia.

Examples:Examples:Reduced cardiac output: Reduced cardiac output: cardiac failure, cardiac failure, hemorrhage, circulatory shockhemorrhage, circulatory shockEmbolism: Embolism: slow or no circulationslow or no circulationLocal vasoconstriction: Local vasoconstriction: exposure of the extremities exposure of the extremities to the coldto the cold

(4) Histotoxic hypoxia(4) Histotoxic hypoxiaIf the tissues are If the tissues are unable to use oxygenunable to use oxygen brought to brought to them by blood, even that results in hypoxia. them by blood, even that results in hypoxia. Histotoxic hypoxia refers to poisoning of the Histotoxic hypoxia refers to poisoning of the oxidative oxidative enzymes of the cells. enzymes of the cells. In this situation the supply of OIn this situation the supply of O22 to the tissues is to the tissues is normal but they are unable to make full use of it. normal but they are unable to make full use of it. As a result the As a result the venous POvenous PO22 is abnormally high. is abnormally high.

Examples:Examples:– Cyanide poisoningCyanide poisoning

Effectiveness of OEffectiveness of O2 therapy in different therapy in different types of Hypoxiatypes of Hypoxia

Hypoxic hypoxiaHypoxic hypoxia: Oxygen therapy is useful in all the : Oxygen therapy is useful in all the forms of hypoxia excepting shunts. forms of hypoxia excepting shunts. In atmospheric hypoxia, In atmospheric hypoxia, OO2 therapy therapy can completely can completely correct the decreased Ocorrect the decreased O2 level in arterial blood and level in arterial blood and provide 100% effective therapy. provide 100% effective therapy. Even in the case of Even in the case of hypoventilation orhypoventilation or low Olow O2 diffusion in lungdiffusion in lung, breathing pure , breathing pure OO2 can increase can increase transport of transport of more Omore O2 into the alveoli. into the alveoli.

In shunts, admixture is after oxygenation in the lungs. In shunts, admixture is after oxygenation in the lungs. Hence oxygen therapy does not help. Hence oxygen therapy does not help.

Anemic hypoxia:Anemic hypoxia: O O2 therapy has only slight value therapy has only slight value because the amount of Obecause the amount of O2 transported by Hb can transported by Hb can hardly be increased. However, a small amount of hardly be increased. However, a small amount of extra extra OO2 can be transported in the can be transported in the dissolved state (7-30%).dissolved state (7-30%).

Stagnant Hypoxia:Stagnant Hypoxia: OO2 therapy is of very little value, therapy is of very little value, because the problem is because the problem is slow blood flow and not slow blood flow and not insufficient Oinsufficient O2 . .

Histotoxic Hypoxia:Histotoxic Hypoxia: In this type of hypoxia, the tissue In this type of hypoxia, the tissue metabolic enzyme system is simply incapable of using metabolic enzyme system is simply incapable of using the oxygen that is delivered. Therefore, the oxygen that is delivered. Therefore, oxygen oxygen therapy has no measurable benefit.therapy has no measurable benefit.

Hyperbaric oxygenHyperbaric oxygenHyperbaric oxygen (high pressure oxygen) is specially Hyperbaric oxygen (high pressure oxygen) is specially valuable in valuable in carbon monoxide poisoningcarbon monoxide poisoning.. It is also useful in the treatment of It is also useful in the treatment of gas gangrenegas gangrene.. Since most of the hemoglobin is not available for Since most of the hemoglobin is not available for carrying oxygen, carrying oxygen, dissolved oxygendissolved oxygen assumes special assumes special importance for supplying oxygen to tissues. importance for supplying oxygen to tissues. The The solubilitysolubility of oxygen in blood is of oxygen in blood is 0.003ml/100ml/mmHg0.003ml/100ml/mmHg. . Therefore if an arterial Therefore if an arterial POPO22 of of 2000mmHg2000mmHg can be can be achieved by administering 100% oxygen at a pressure achieved by administering 100% oxygen at a pressure of of 3 atmosphere3 atmosphere, the blood will have , the blood will have 6ml/100ml6ml/100ml dissolved oxygen, which is adequate to meet the dissolved oxygen, which is adequate to meet the metabolic requirements at rest. metabolic requirements at rest. Hyperbaric oxygen administered through a mask.Hyperbaric oxygen administered through a mask.

DyspneaDyspneaDyspnea is a subjective sensation of difficulty in Dyspnea is a subjective sensation of difficulty in breathing. breathing. The terms The terms dyspneadyspnea, , breathlessnessbreathlessness, and , and shortness shortness of breathof breath are often used interchangeably. are often used interchangeably. It is often associated with It is often associated with respiratory diseases, respiratory diseases, but it but it can occur in can occur in healthy individuals also. healthy individuals also. A common synonym is A common synonym is air hungerair hunger..

Dyspnea in diseaseDyspnea in diseaseDyspnea is observed in Dyspnea is observed in different cardiopulmonary different cardiopulmonary disease states:disease states:(a) (a) Primary lung diseasesPrimary lung diseases:: Such as Such as pneumonia, pneumonia, asthma, asthma, andand emphysema. emphysema.(b) (b) Heart diseaseHeart disease:: Pulmonary edema.Pulmonary edema.(c) (c) Neuromuscular disordersNeuromuscular disorders:: Myasthenia gravisMyasthenia gravis and and muscular dystrophy of the respiratory musclesmuscular dystrophy of the respiratory muscles..

Dyspnea in healthy individualsDyspnea in healthy individuals(a) (a) ExerciseExercise:: In healthy individuals dyspnea occurs In healthy individuals dyspnea occurs during exercise, particularly in untrained individuals. during exercise, particularly in untrained individuals. (b) (b) High altitudeHigh altitude:: It is also common in subjects who It is also common in subjects who have rapidly climbed to a high altitude.have rapidly climbed to a high altitude.(c) (c) Emotional or neurogenic dyspneaEmotional or neurogenic dyspnea:: In neurogenic In neurogenic dyspnea or emotional dyspnea, the person's dyspnea or emotional dyspnea, the person's respiratory functions may be normal and still dyspnea respiratory functions may be normal and still dyspnea may be experienced because of an may be experienced because of an abnormal state of abnormal state of mind.mind. This feeling is greatly enhanced in people who This feeling is greatly enhanced in people who have a have a psychological fear of not being able to receivepsychological fear of not being able to receive a sufficient quantity of air, such as in a sufficient quantity of air, such as in very small or very small or crowded rooms.crowded rooms.

CausesCausesA person becomes very dyspneic especially from A person becomes very dyspneic especially from excess build up of COexcess build up of CO22 in the body fluids. in the body fluids.

Dyspneic Index Dyspneic Index ==

Where, MVV = Maximum voluntary ventilation.Where, MVV = Maximum voluntary ventilation. PV = Pulmonary ventilation PV = Pulmonary ventilation

CyanosisCyanosisIt is a clinical condition characterized by It is a clinical condition characterized by bluish discoloration of bluish discoloration of the skin and mucus membrane. the skin and mucus membrane. Cyanosis is due to excessive amounts of Cyanosis is due to excessive amounts of deoxygenated deoxygenated hemoglobin (HHb) in blood. hemoglobin (HHb) in blood. The amount of HHb in blood must be The amount of HHb in blood must be more than 5G/100ml. more than 5G/100ml.

Causes of CyanosisCauses of Cyanosis1.1. Asphyxia:Asphyxia: Defective aeration of the lungs resulting in Defective aeration of the lungs resulting in impaired gas exchange, hypoxia and hypercapnia.impaired gas exchange, hypoxia and hypercapnia.2.2. Hypoxia:Hypoxia: Cyanosis is observed in Cyanosis is observed in hypoxic hypoxia and hypoxic hypoxia and stagnant hypoxia only.stagnant hypoxia only. Cyanosis Cyanosis does not occur in anemic hypoxiadoes not occur in anemic hypoxia when the total Hb is when the total Hb is low. Cyanosis also low. Cyanosis also does not occur in histotoxic hypoxia.does not occur in histotoxic hypoxia.3.3. Cold:Cold: Cyanosis may occur when the blood flow through the Cyanosis may occur when the blood flow through the skin is reduced due to skin vasoconstriction by cold.skin is reduced due to skin vasoconstriction by cold.

Types of cyanosisTypes of cyanosisPeripheral CyanosisPeripheral CyanosisCentral CyanosisCentral Cyanosis

Peripheral cyanosisPeripheral cyanosisResults from Results from slow blood flowslow blood flow due to due to severe severe vasoconstrictionvasoconstriction which produces which produces stagnant circulation.stagnant circulation. This can occur in peripheral circulatory failure resulting This can occur in peripheral circulatory failure resulting in in cold blue extremities.cold blue extremities. More OMore O22 is taken is taken by the tissues and by the tissues and more HHb is more HHb is foundfound. The peripheral cyanosis appears in the . The peripheral cyanosis appears in the fingers fingers and toes.and toes.

Central cyanosisCentral cyanosisCentral cyanosis is mainly due to Central cyanosis is mainly due to shunting of blood shunting of blood from right to the left side bypassing the lungsfrom right to the left side bypassing the lungs as as occurs in occurs in congenital heart disease. congenital heart disease. It also occurs in It also occurs in different lung diseasesdifferent lung diseases where where pulmonary pulmonary gas exchange is affected.gas exchange is affected. Due to Due to generalized causes, the central cyanosis appears in generalized causes, the central cyanosis appears in all parts of the body. all parts of the body. E.g. skin, mucous membrane, E.g. skin, mucous membrane, tongue and nails of the hands. tongue and nails of the hands.

Chronic obstructive pulmonary diseases (COPD)Chronic obstructive pulmonary diseases (COPD)

The term chronic obstructive pulmonary disease The term chronic obstructive pulmonary disease (COPD) denotes (COPD) denotes a group of respiratory disordersa group of respiratory disorders characterized by characterized by small airway obstructionsmall airway obstruction and and reduction in expiratory flow rate. reduction in expiratory flow rate. The most prevalent of these disorders are The most prevalent of these disorders are emphysemaemphysema, , chronic bronchitis, asthma, etcchronic bronchitis, asthma, etc. . Since the most Since the most common cause of COPD is smoking,common cause of COPD is smoking, the disease is largely preventable. the disease is largely preventable. In COPD, the In COPD, the time time required for required for FVC is increased,FVC is increased, the the FEV1.0 is decreased, and FEV1.0/FVC is decreased.FEV1.0 is decreased, and FEV1.0/FVC is decreased.These are used in the These are used in the diagnosis of COPD.diagnosis of COPD.

EmphysemaEmphysemaEmphysema is characterized by a Emphysema is characterized by a loss of lung loss of lung elasticity and abnormal dilationelasticity and abnormal dilation of the air spaces distal of the air spaces distal to the terminal bronchioles.to the terminal bronchioles.There is There is destruction of the alveolar wallsdestruction of the alveolar walls and and hyperinflation of the lungs.hyperinflation of the lungs.Breath soundsBreath sounds are decreased. are decreased.

Types Types There are two principal types of emphysema- There are two principal types of emphysema- centrilobular and panlobular. centrilobular and panlobular. (a) Centrilobular emphysema(a) Centrilobular emphysemaCentrilobular emphysema affects the central or Centrilobular emphysema affects the central or proximal parts of the acinus, notably the respiratory proximal parts of the acinus, notably the respiratory bronchioles.bronchioles.(b) Panlobular emphysema(b) Panlobular emphysemaIt involves the entire acinus from the respiratory It involves the entire acinus from the respiratory bronchioles to the alveolar sacs.bronchioles to the alveolar sacs.

CENTRILOBULAR EMPHYSEMACENTRILOBULAR EMPHYSEMA

PANLOBULAR EMPHYSEMAPANLOBULAR EMPHYSEMA

CausesCausesThere are several known or suspected causes of There are several known or suspected causes of emphysema. emphysema. However, the most common causes are: However, the most common causes are: (1) cigarette smoking and inhalation of pollutants and (1) cigarette smoking and inhalation of pollutants and (2) deficiency of α1-antitrypsin(2) deficiency of α1-antitrypsin

(1) Cigarette smoking and inhalation of pollutants(1) Cigarette smoking and inhalation of pollutantsInhalation of tobacco smoke is related to human Inhalation of tobacco smoke is related to human emphysema. emphysema. Among the many particulate and gaseous fractions to Among the many particulate and gaseous fractions to be found in cigarette smoke are be found in cigarette smoke are carbon dioxidecarbon dioxide, , nitrogenous oxidesnitrogenous oxides, , sulphur dioxidesulphur dioxide, , hydrocarbonshydrocarbons, , radioactive elementsradioactive elements, , phorbol phorbol estersesters and, of particular interest relative to and, of particular interest relative to emphysema, emphysema, cadmiumcadmium. .

(2) Deficiency of α(2) Deficiency of α11-antitrypsin-antitrypsin

αα11-antitrypsin is a -antitrypsin is a proteinase inhibitor.proteinase inhibitor.

It It blocks the action of the proteolytic enzymesblocks the action of the proteolytic enzymes that are that are destructive to elastin and other tissue components in destructive to elastin and other tissue components in the alveolar wall. the alveolar wall. The deficiency is an The deficiency is an inherited autosomal recessive inherited autosomal recessive disorder. disorder.

Chronic bronchitisChronic bronchitisIn chronic bronchitis, airway obstruction is caused by In chronic bronchitis, airway obstruction is caused by inflammation of both major and small airways. inflammation of both major and small airways. It is more common in men than in women, but It is more common in men than in women, but changing changing smoking habitssmoking habits may soon change this may soon change this disproportion. disproportion. It usually first appear in the It usually first appear in the fourth to fifth decadesfourth to fifth decades of of the life.the life.

CausesCauses(1) Smoking and pollutants(1) Smoking and pollutants(2) Infections:(2) Infections: Viral and bacterial infections are the Viral and bacterial infections are the common cause of the problem.common cause of the problem.

AsthmaAsthma

Asthma is characterized by Asthma is characterized by spastic contraction of the spastic contraction of the bronchiolar smooth muscles,bronchiolar smooth muscles, which causes extremely which causes extremely difficult breathing. difficult breathing. It is a disease characterized by intermittent attacks of It is a disease characterized by intermittent attacks of dyspnea and wheezingdyspnea and wheezing caused by caused by narrowing of the narrowing of the bronchial airways. bronchial airways. The The FRC and the RV of the lung become greatly FRC and the RV of the lung become greatly increasedincreased during the asthmatic attack because of the during the asthmatic attack because of the difficulty in expiring air from the lungs. difficulty in expiring air from the lungs. Asthma occurs in 3 to 5% of the population at some Asthma occurs in 3 to 5% of the population at some time in life.time in life.

Types and etiologyTypes and etiologyThe usual cause of asthma is hypersensitivity of the The usual cause of asthma is hypersensitivity of the bronchioles to foreign substances in the air. bronchioles to foreign substances in the air. (1) Allergic hypersensitivity(1) Allergic hypersensitivity:: In younger patients, In younger patients, under the age of 30 years, the asthma in about 70% is under the age of 30 years, the asthma in about 70% is caused by allergic hypersensitivity, especially caused by allergic hypersensitivity, especially sensitivity to some allergens. sensitivity to some allergens. (2) Nonallergic hypersensitivity(2) Nonallergic hypersensitivity:: In older persons, In older persons, the cause is almost always hypersensitivity to the cause is almost always hypersensitivity to nonallergic types of irritants in the air, such as smog. nonallergic types of irritants in the air, such as smog.

Lung Function TestsLung Function TestsLung function tests are used to evaluate the Lung function tests are used to evaluate the state of the respiratory system. state of the respiratory system. Lung function tests are useful to identify Lung function tests are useful to identify patients with patients with early airway disease. early airway disease. By identifying disease at an early stage, By identifying disease at an early stage, its its progression can be slowed.progression can be slowed.

THE SPIROMETERTHE SPIROMETER

• Old version– spirometer bell– kymograph pen

• New version– portable

1. Vital capacity (VC)1. Vital capacity (VC)Maximum volume of air that can be expired after Maximum volume of air that can be expired after maximum inspiration. It is measured by spirometer. maximum inspiration. It is measured by spirometer. Normal value:Normal value: 4.6 L in men 4.6 L in men (20% less in women).(20% less in women).

Major factors that affect vital capacityMajor factors that affect vital capacity– Posture (Standing>sitting>lying)Posture (Standing>sitting>lying)– Strength of respiratory muscleStrength of respiratory muscle– Distensibility of lungs and chest wall (compliance)Distensibility of lungs and chest wall (compliance)– Pulmonary congestionPulmonary congestion

2. Forced vital capacity (FVC)2. Forced vital capacity (FVC)Forced maximal expiration after maximal Forced maximal expiration after maximal inspiration. inspiration. It is measured by vitalograph. It is measured by vitalograph. Normal value equal to VC. Normal value equal to VC. FVC and VC are measures of ventilatory FVC and VC are measures of ventilatory capacity. capacity. Both values are reduced in:Both values are reduced in: – thoracic cage disease, thoracic cage disease, – paralysis of respiratory muscle, paralysis of respiratory muscle, – abnormalities of pleural cavity, abnormalities of pleural cavity, – pathology in lung itself.pathology in lung itself.

3. Forced expiratory volume in first second (FEV3. Forced expiratory volume in first second (FEV11))Volume of air expired by maximal effort in the first Volume of air expired by maximal effort in the first second after a maximal inspiration. second after a maximal inspiration.

Normal FEVNormal FEV11%% = 75 - 80% of FVC. = 75 - 80% of FVC. FEVFEV11% is affected by airway resistance during forced % is affected by airway resistance during forced expiration. It is reduced in:expiration. It is reduced in:i) Bronchoconstriction (asthma)i) Bronchoconstriction (asthma)ii) Inhalation of irritant (cigarette smoking)ii) Inhalation of irritant (cigarette smoking)iii) Structural changes in the airwayiii) Structural changes in the airwayiv) Obstruction within airwayiv) Obstruction within airwayFEVFEV11% is reduced in obstructive lung diseases but % is reduced in obstructive lung diseases but remains normal or increased in restrictive lung remains normal or increased in restrictive lung diseases.diseases.

FEVFEV11 & FVC & FVC• Forced expiratory volume in 1 second

– 4.0 L

• Forced vital capacity– 5.0 L

• FEV1/FVC = 80%

4. Middle forced expiratory flow (FEF4. Middle forced expiratory flow (FEF25-75 %25-75 %))FEFFEF25-75%25-75% is the middle half volume of air in liters is the middle half volume of air in liters divided by the time in seconds. divided by the time in seconds. FEFFEF25-75%25-75% and FEV and FEV11% is generally close in patients % is generally close in patients with obstructive lung disease.with obstructive lung disease.Normal value:Normal value: 300 L / min. 300 L / min.

5. Peak expiratory flow rate (PEFR)5. Peak expiratory flow rate (PEFR)Is the volume air expired in the first tenth of a second Is the volume air expired in the first tenth of a second (1/10(1/10thth of a second) of a forced expiration after a of a second) of a forced expiration after a forced inspiration. forced inspiration. It is measured by Wright’s peak flow meter. It is measured by Wright’s peak flow meter. Normal value:Normal value: 400-600 L / min. 400-600 L / min.

6. Maximum Voluntary ventilation (MVV) or Maximum 6. Maximum Voluntary ventilation (MVV) or Maximum breathing capacity (MBC)breathing capacity (MBC)It is the maximum rate of pulmonary ventilation that a It is the maximum rate of pulmonary ventilation that a person can sustain for 15 seconds. person can sustain for 15 seconds. Normal value:Normal value: 100 – 160 L / min in male; 100 – 160 L / min in male;

60 – 100 L / min in female.60 – 100 L / min in female.

7. Residual volume (RV)7. Residual volume (RV)Volume of air left in the lungs after maximum Volume of air left in the lungs after maximum expiration. expiration. Normal values:Normal values:

20% of total lung capacity (TLC) at age of 20 20% of total lung capacity (TLC) at age of 20 yrs. yrs.

40% of TLC at age 60 yrs.40% of TLC at age 60 yrs.RV is increased in asthma, emphysema.RV is increased in asthma, emphysema.

8. Compliance8. ComplianceIs the change in lung volume per unit change in Is the change in lung volume per unit change in pressure (pressure (Δ V/Δ P)Δ V/Δ P). . Normal value: 0.2 L/cm HNormal value: 0.2 L/cm H22O. Compliance is reduced O. Compliance is reduced in in pulmonary congestion and interstitial pulmonary pulmonary congestion and interstitial pulmonary fibrosis.fibrosis. It is increased in It is increased in emphysema.emphysema.

9. Airway resistance9. Airway resistanceIs the pressure difference between the alveoli and Is the pressure difference between the alveoli and the mouth divided by the flow rate. Normal value: 1-3 the mouth divided by the flow rate. Normal value: 1-3 cm Hcm H22O. It is moderately O. It is moderately increased in bronchitis and increased in bronchitis and asthma.asthma.

10. Blood gases analysed10. Blood gases analysed– Arterial POArterial PO22

– Arterial PCOArterial PCO22

– Arterial blood pHArterial blood pH