The Respiratory SystemByDr. Imtiaz Rabbani

OutlineFunctional anatomy of respiratory systemMechanism of Pulmonary ventilationPulmonary volume and capacitiesPhysical principals of gas exchangeRespiratory membrane and Diffusion of different gases through itNeural and hormonal control of respiration*

Recommended BooksPrinciples of Human Physiology by Lauralee SheerwoodMedical Physiology by Guyton and Hall*

Learning ObjectivesExternal and cellular respirationConcept of breathingExchange of gasesClinical correlations*

Non Respiratory functions of respiratory systemHeat eliminationMoistening of airVenous return (5 mmHg less)Acid base regulationConditioning of bloodspeech*

*Respiration IncludesPulmonary ventilationAir moves in and out of lungsContinuous replacement of gases in alveoli (air sacs)External respirationGas exchange between blood and air at alveoliO2 (oxygen) in air diffuses into bloodCO2 (carbon dioxide) in blood diffuses into airTransport of respiratory gasesBetween the lungs and the cells of the bodyPerformed by the cardiovascular systemBlood is the transporting fluidInternal respirationGas exchange in capillaries between blood and tissue cellsO2 in blood diffuses into tissuesCO2 waste in tissues diffuses into blood

*Cellular RespirationOxygen (O2) is used by the cellsO2 needed in conversion of glucose to cellular energy (ATP)All body cells Carbon dioxide (CO2) is produced as a waste productThe bodys cells die if either the respiratory or cardiovascular system fails

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*The Respiratory OrgansConducting zoneRespiratory passages that carry air to the site of gas exchangeFilters, humidifies and warms airRespiratory zoneSite of gas exchangeComposed ofRespiratory bronchiolesAlveolar ductsAlveolar sacsConducting zone labeled

*LungsEach is cone-shaped with anterior, lateral and posterior surfaces contacting ribsSuperior tip is apex, just deep to clavicleConcave inferior surface resting on diaphragm is the baseapexapexbasebase

*Hilus or (hilum)Indentation on mediastinal (medial) surfacePlace where blood vessels, bronchi, lymph vessel, and nerves enter and exit the lungRoot of the lungAbove structures attaching lung to mediastinumMain ones: pulmonary artery and veins and main bronchus Medial view R lungMedial view of L lung

*Right lung: 3 lobesUpper lobeMiddle lobeLower lobeLeft lung: 2 lobesUpper lobeLower lobeOblique fissureOblique fissureHorizontal fissureAbbreviations in medicine:e.g. RLL pneumoniaEach lobe is served by a lobar (secondary) bronchus

*Each lobe is made up of bronchopulmonary segments separated by dense connective tissueEach segment receives air from an individual segmental (tertiary) bronchusApproximately 10 bronchopulmonary segments in each lungLimit spread of infectionCan be removed more easily because only small vessels span segmentsSmallest subdivision seen with the naked eye is the lobuleHexagonal on surface, size of pencil eraserServed by large bronchiole and its branchesBlack carbon is visible on connective tissue separating individual lobules in smokers and city dwellers

*Pulmonary arteries bring oxygen-poor blood to the lungs for oxygenationThey branch along with the bronchial treeThe smallest feed into the pulmonary capillary network around the alveoliPulmonary veins carry oxygenated blood from the alveoli of the lungs to the heart

*Stroma framework of connective tissue holding the air tubes and spaces Many elastic fibersLungs light, spongy and elasticElasticity reduces the effort of breathingBlood supplyLungs get their own blood supply from bronchial arteries and veinsInnervation: pulmonary plexus on lung root contains sympathetic, parasympathetic and visceral sensory fibers to each lungFrom there, they lie on bronchial tubes and blood vessels within the lungs

*Bronchopulmonary means both bronchial tubes and lung alveoli togetherBronchopulmonary segment chunk receiving air from a segmental (tertiary) bronchus*: tertiary means its the third order in size; also, the trachea has divided three times nowAnatomical dead spaceThe conducting zone which doesnt participate in gas exchangePrimary bronchus:(Left main)Secondary:(left lower lobar bronchus)(supplyingleft lowerlobe)Does this clarify a little?*Understand the concepts; you dont need to know the names of the tertiary bronchi

*NoseProvides airwayMoistens and warms airFilters airResonating chamber for speechOlfactory receptors

External noseConducting zone will be covered first

*Nasal cavityAir passes through nares (nostrils)Nasal septum divides nasal cavity in midline (to right & left halves)Perpendicular plate of ethmoid bone, vomer and septal cartilageConnects with pharynx posteriorly through choanae (posterior nasal apertures*)Floor is formed by palate (roof of the mouth)Anterior hard palate and posterior soft palate

*palate

*Linings of nasal cavityVestibule* (just above nostrils)Lined with skin containing sebaceous and sweat glands and nose hairsFilters large particulars (insects, lint, etc.)The remainder of nasal cavity: 2 types of mucous membraneSmall patch of olfactory mucosa near roof (cribriform plate)Respiratory mucosa: lines most of the cavity

*Olfactory mucosa

*Respiratory MucosaPseudostratified ciliated columnar epitheliumScattered goblet cellsUnderlying connective tissue lamina propriaMucous cells secrete mucousSerous cells secrete watery fluid with digestive enzymes, e.g. lysozymeTogether all these produce a quart/dayDead junk is swallowed

*Nasal Conchae

Inferior to each is a meatus*Increases turbulence of air3 scroll-like structuresReclaims moisture on the way out*** (its own bone)Of ethmoid

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*Paranasal sinusesFrontal, sphenoid, ethmoid and maxillary bonesOpen into nasal cavityLined by same mucosa as nasal cavity and perform same functionsAlso lighten the skullCan get infected: sinusitis

*The Pharynx (throat)

3 parts: naso-, oro- and laryngopharynxHouses tonsils (they respond to inhaled antigens)Uvula closes off nasopharynx during swallowing so food doesnt go into noseEpiglottis posterior to the tongue: keeps food out of airwayOropharynx and laryngopharynx serve as common passageway for food and airLined with stratified squamous epithelium for protection**

*The Larynx (voicebox)Extends from the level of the 4th to the 6th cervical vertebraeAttaches to hyoid bone superiorlyInferiorly is continuous with trachea (windpipe)Three functions:Produces vocalizations (speech)Provides an open airway (breathing)Switching mechanism to route air and food into proper channelsClosed during swallowingOpen during breathing

*Framework of the larynx9 cartilages connected by membranes and ligamentsThyroid cartilage with laryngeal prominence (Adams apple) anteriorlyCricoid cartilage inferior to thyroid cartilage: the only complete ring of cartilage: signet shaped and wide posteriorly

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Behind thyroid cartilage and above cricoid: 3 pairs of small cartilagesArytenoid: anchor the vocal cordsCorniculateCuneiform9th cartilage: epiglottis

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*Epliglottis* (the 9th cartilage)Elastic cartilage covered by mucosaOn a stalk attached to thyroid cartilageAttaches to back of tongueDuring swallowing, larynx is pulled superiorlyEpiglottis tips inferiorly to cover and seal laryngeal inletKeeps food out of lower respiratory tract**Posterior views

*Cough reflex: keeps all but air out of airwaysLow position of larynx is required for speech (although makes choking easier)Paired vocal ligaments: elastic fibers, the core of the true vocal cords

*Pair of mucosal vocal folds (true vocal cords) over the ligaments: white because avascular

*Glottis is the space between the vocal cordsLaryngeal muscles control length and size of opening by moving arytenoid cartilagesSound is produced by the vibration of vocal cords as air is exhaled

*Innervation of larynx (makes surgery at neck risky)Recurrent laryngeal nerves of Vagus These branch off the Vagus and make a big downward loop under vessels, then up to larynx in neckLeft loops under aortic archRight loops under right subclavian arteryDamage to one: hoarsenessDamage to both: can only whisper

*Trachea (the windpipe)Descends: larynx through neck into mediastinumDivides in thorax into two main (primary) bronchi16-20 C-shaped ringsof hyaline cartilage joined by fibroelastic connective tissueFlexible for bendingbut stays open despitepressure changesduring breathing

*Posterior open parts of tracheal cartilage abut esophagusTrachealis muscle can decrease diameter of tracheaEsophagus can expand when food swallowedFood can be forcibly expelledWall of trachea has layers common to many tubular organs filters, warms and moistens incoming airMucous membrane (pseudostratified epithelium with cilia and lamina propria with sheet of elastin)Submucosa ( with seromucous glands)Adventitia - connective tissue which contains the tracheal cartilages)

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*Carina*Ridge on internal aspect of last tracheal cartilagePoint where trachea branches (when alive and standing is at T7)Mucosa highly sensitive to irritants: cough reflex

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*Bronchial tree bifurcationRight main bronchus (more susceptible to aspiration)Left main bronchusEach main or primary bronchus runs into hilus of lung posterior to pulmonary vessels

1. Oblique fissure 2. Vertebral part 3. Hilum of lung 4. Cardiac impression 5. Diaphragmatic surface(Wikipedia)

*Main=primary bronchi divide into secondary=lobar bronchi, each suppliesone lobe3 on the right2 on the leftLobar bronchi branch into tertiary = segmental bronchiContinues dividing: about 23 timesTubes smaller than 1 mm called bronchiolesSmallest, terminal bronchioles, are less the 0.5 mm diameterTissue changes as becomes smallerCartilage plates, not rings, then disappearsPseudostratified columnar to simple columnar to simple cuboidal without mucus or ciliaSmooth muscle important: sympathetic relaxation (bronchodilation), parasympathetic constriction (bronchoconstriction)

*Respiratory ZoneEnd-point of respiratory treeStructures that contain air-exchange chambers are called alveoliRespiratory bronchioles lead into alveolar ducts: walls consist of alveoliDucts lead into terminal clusters called alveolar sacs are microscopic chambers There are 3 million alveoli!

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Lungs are normally stretchedIntrapleural Fluid CohesivenessTransmural Pressure Gradient*

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*Pneumothorax (collapsed lung) Think about the processes involved and then try and imagine the various scenariosTrauma causing the thoracic wall to be pierced so air gets into the pleuraVisceral pleura breaks, letting alveolar air into pleural space

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*Pneumothorax

*VentilationBreathing = pulmonary ventilationPulmonary means related to the lungsTwo phasesInspiration (inhalation) air inExpiration (exhalation) air outMechanical forces cause the movement of airGases always flow from higher pressure to lowerFor air to enter the thorax, the pressure of the air in it has to be lower than atmospheric pressureMaking the volume of the thorax larger means the air inside it is under less pressure(the air has more space for as many gas particles, therefore it is under less pressure)The diaphragm and intercostal muscles accomplish this

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VENTILATIIONA balloon can be filled by 2 mechanisms

a) Positive-pressure filling

b) Negative-pressure filling

*Muscles of InspirationDuring inspiration, the dome shaped diaphragm flattens as it contractsThis increases the height of the thoracic cavity

The external intercostal muscles contract to raise the ribsThis increases the circumference of the thoracic cavityTogether:

*Inspiration continuedIntercostals keep the thorax stiff so sides dont collapse in with change of diaphragmDuring deep or forced inspiration, additional muscles are recruited:ScalenesSternocleidomastoidPectoralis minorQuadratus lumborum on 12th ribErector spinae(some of these accessory muscles of ventilation are visible to an observer; it usually tells you that there is respiratory distress working hard to breathe)

*Expiration Quiet expiration in healthy people is chiefly passiveInspiratory muscles relaxRib cage drops under force of gravityRelaxing diaphragm moves superiorly (up)Elastic fibers in lung recoilVolumes of thorax and lungs decrease simultaneously, increasing the pressureAir is forced out

MECHANISM OF VENTILATION

*Expiration continuedForced expiration is activeContraction of abdominal wall musclesOblique and transversus predominantlyIncreases intra-abdominal pressure forcing the diaphragm superiorlyDepressing the rib cage, decreases thoracic volumeSome help from internal intercostals and latissimus dorsi

(try this on yourself to feel the different muscles acting)

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Breathing Cycle

RESPIRATORY PRESSURES Change in the size of thoracic cavity brings changes in the pressures of respiratory apparatus

Alveolar/intrapulmonary pressureIntrathoracic/ intrapleural pressure Visceral (adjacent to lungs) Parietal layer (lining thoracic cavity) Space between 2 layers is called pleural cavity

A) Alveolar/intrapulmonary pressureWhen glottis is open, it is not different from pressure in the airways (atmospheric pressure) 1cm of water at peak of inspiration and is +1 cm at peak of expiration during quite breathing Health person can develop 60-100 mm Hg (- or + pressure)

B) Intra-pleural PressurePressure is negative (sub-atmospheric) during inspiration and expiration

Fluctuates -5 to -8 cm of water depending on phase of respiration

Change in lung volume for each unit change in transpulmonary pressure. = stretchiness of lungs

Transpulmonary pressure is the difference in pressure between alveolar pressure and pleural pressure.

Compliance of Lungs

2 different curves

Inspiratory compliance curveExpiratory compliance curve

Shows the capacity of lungs to adapt to small changes of transpulmonary pressure.

Compliance is seen at low volumes (because of difficulty with initial lung inflation) and at high volumes (because of the limit of chest wall expansion)

Difference in both curves is called HysteresisFor a given pressure, compliance is high during expiration than inspiration limbCompliance of Lungs

Compliance of lungs occurs due to elastic forces.Elastic forces of the lung tissue itself

Elastic forces of the fluid that lines the inside walls of alveoli and other lung air passages

Elastin + Collagen fibres

Is provided by the substance called surfactant that is present inside walls of alveoli.

MoreCompliantSaline InflationLessCompliantAir Inflation

Experiment:

By adding saline solution there is no interface between air and alveolar fluid. (B forces were removed) surface tension is not present, only elastic forces of tissue (A)Transpleural pressures required to expand normal lung = 3x pressure to expand saline filled lung.

Conclusion of this experiment:

Tissue elastic forces (A) = represent 1/3 of total lung elasticityFluid air surface tension elastic forces in alveoli (B) = 2/3 of total lung elasticity.

Surface active agent in water = reduces surface tension of water on the alveolar walls

Pure water (surface pressure)72 dynes/cmNormal fluid lining alveoli without surfactant (surface pressure)50 dynes/cmNormal fluid lining alveoli with surfactant5-30 dynes/cm

SURFACTANTSLungs have capacity to collapseAlveolar cells type II secret surface tension reducing substances called surfactantsComplex mixture Phospholipids (Dipalmitoyl lecithin) Ca++ Proteins (2 of proteins are called SP-A and SP-D) Proteins belong to a group of protein (Collectins) Collectins stimulate the phagocytosis and release of cytokins by the immune cells. Therefore, surfactants facilitates the phagocytosis of inhaled foreign materials (alveolar M)

FUNCTIONSImproves dispensability of lungs & less muscular force is needed to inflate lungs Protects the emptying of small alveoli into large alveoli La Place Law

P = 2T/r

Surface TensionLaw of Laplace:

P = 2T/r

Pressure in alveoli is directly proportional to surface tension; and inversely proportional to radius of alveoli.Pressure in smaller alveolus would be greater than in larger alveolus, if surface tension were the same in both.Insert fig. 16.11

Surfactant & alveolar collapse****

If some alveoli were smaller and other large = smaller alveoli would tend to collapse and cause expansion of larger alveoliThat doesnt happen because:Normally larger alveoli do not exist adjacent to small alveoli = because they share the same septal walls.All alveoli are surrounded by fibrous tissue septa that act as additional splints.Surfactant reduces surface tension = as alveolus becomes smaller surfactant molecules are squeezed together increasing their concentration = reduces surface tension even more.

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Clinical CorrelationNeonatal respiratory distress syndromeIn man, surfactant synthesis begins as early as 24 wkAlmost present by 35 wkIn sheep, late gestation periodCollapse of alveoli (Atelectasis)

Lung volume and capacitiesTidal volume (500ml)Inspiratory reserve volume (3000ml)Inspiratory capacity (TV + IRV = 3500ml)Expiratory reserve volume (1000ml)Residual volume (1200ml)Vital capacity (4500ml)Lung capacity (5700ml)*

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*CXR(chest x-ray)

*Chest x raysNormal femaleLateral (male)

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*Gas ExchangeAir filled alveoli account for most of the lung volumeVery great area for gas exchange (1500 sq ft)Alveolar wallSingle layer of squamous epithelial cells (type 1 cells) surrounded by basal lamina0.5um (15 X thinner than tissue paper)External wall covered by cobweb of capillariesRespiratory membrane: fusion of the basal laminas ofAlveolar wallCapillary wall

Alveolar sacRespiratorybronchioleAlveolarductAlveoli(air on one side; blood on the other)

*This air-blood barrier (the respiratory membrane) is where gas exchange occursOxygen diffuses from air in alveolus (singular of alveoli) to blood in capillaryCarbon dioxide diffuses from the blood in the capillary into the air inthe alveolus

*Microscopic detail of alveoliAlveoli surrounded by fine elastic fibersAlveoli interconnect via alveolar poresAlveolar macrophages free floating dust cellsNote type I and type II cells and joint membrane

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*you might want to think twice about smoking.

Transport of respiratory gases

Transport of Respiratory gases in BloodTransport of Oxygen a) Dissolved form (3%) 0.003mL/dL/mm Hgb) Combination form Hb (97%)

Role of HaemoglobinOxygen combines reversibly with Haeme portion of Hb At Alveolar Level 1g Hb combines with 1.34 mL of O2 when fully saturated If Hb is 15 g/dl of blood, 1.34 x 15 = 20.1 mL O2 (20 Vol. %)

At Tissue Level Hb is still 75% saturated or 14.4 mL of O2 is bounded with Hb

Utilization Coefficient 20.1-14.4 = 5 mL of oxygen (25%) In exercise, it may go upto 70-85%

Transport of OxygenOxygen transported at various Hb concentrations

Oxygen transported at various tension

Hb(g/100mL)PO2(mm Hg)Oxygen transported (mL/100 mL of blood)SaturationBy HbDissolvedTotal15100510010010010010010020.113.46.70.30.30.320.413.77.0

Hb(g/100mL)PO2(mm Hg)Oxygen transported (mL/100 mL of blood)SaturationBy HbDissolvedTotal1515151510070402010093753520.118.715.17.00.300.210.120.0620.4018.9115.227.06

O2-Hb Dissociation CurveSigmoid shapeGenerally, affinity of Hb is high at higher PO2 (alveoli) and is low at decreased PO2 (tissue) a) Steep portion 15-40 mm Hg b) Flat portion above 60 mm Hg (3700m2/12000ft)

HB-O2 Dissociation Curve at Rest

HB-O2 Dissociation Curve During Exercise

Factors Affecting O2-Hb Dissociation CurvepHTemperatureCO2 concentration2,3,diphosphoglycerate (by-product of glycolytic pathway. It binds with oxyHb, not with Hb. DPG+ HbO Hb-DPG+ O2

Factors Affecting O2-Hb Dissociation Curve

BOHRS EFFECTHigher concentration of CO2 (H+) shifts HbO2 curve to right-side direction, enhancing un-loading of O2 from Hb At Tissue Level Higher production of CO2 cause shifting curve in right-ward & upward direction At Alveolar Level Removal of CO2 decrease its concentration causing moving of curve back to normal (left-ward) enhancing up-loading of O2

Carbon monoxide poisoningCO is 250 times more soluble than O2

A) Dissolved FormSolubility of CO2 = 0.06 mL/dl blood/mm H PCO2 = 40 mm Hg 40 x 0.06 = 2.4 mL/dl PCO2 = 45 mm Hg 45 x 0.06 = 2.7 mL/dl Difference = 2.7-2.4 = 0.3 mL/dl

B) Bicarbonate Form

C) Carbamino compound CO2 reacts with amine radicals of Hb to form CarbaminoHb (CO2 Hb) Small amount of CO2 also reacts with plasma proteins

Carbon dioxide dissociation curve

Control of Respiration

Control of RespirationComponents of BreathingChemoreceptors for O2 & CO2Mechanoreceptors in lungs & jointsCentral control centres (brain stem)Respiratory muscles

*Neural Control of VentilationReticular formation in medullaResponsible for basic rate and rhythmCan be modified by higher centersLimbic system and hypothalamus, e.g. gasp with certain emotionsCerebral cortex conscious controlChemoreceptors Central in the medullaPeripheral: see next slideAortic bodies on the aortic archCarotid bodies at the fork of the carotid artery: monitor O2 and CO2 tension in the blood and help regulate respiratory rate and depth

The carotid sinus (dilated area near fork) helps regulate blood pressure and can affect the rate (stimulation during carotid massage can slow an abnormally fast heart rate)

*Peripheral chemoreceptors regulating respirationAortic bodies*On aortaSend sensory info to medulla through X (vagus n) Carotid bodies+At fork of common carotid arterySend info mainly through IX (glossopharyngeal n)*+

*There are many diseases of the respiratory system, including asthma, cystic fibrosis, COPD (chronic obstructive pulmonary disease with chronic bronchitis and/or emphysema) and epiglottitis

example:normalemphysema

Medullary Respiratory CenterRespiratory center is composed of several groups of neurons located in Medulla Oblongata and Pons of Brain Stem 3 major collections of neurons 1. A dorsal respiratory group 2. A ventral respiratory group 3. Pneumatic center

1. DORSAL RESPIRATORY GROUP

LocationInspratory centerMost of neurons are located within nucleus of the tractus solitarius Extends most of the length of dorsal portion of medulla

Functions Controls the basic rhythm of inspiration (quiescence and then burst of action potentials and then again quiescence)

DRG get afferent (sensory) fibers via Vagal and Glossopharyngeal nerves, those tranmit sensory signals from Peripheral chemoreceptorsBaroreceptorsVarious receptors in the lungs

The efferent signals are transmitted to Diaphragm (mainly) by phrenic nerve Other inspiratory muscles

Effect of Pneumotaxic CenterLocated dorsally in the Nucleu parabrachialis of upper Pons and transmits signals to the Inspiratory Area

FunctionsLimits the inspiration and consequently may increase the rate of breathing by shortening the respiratory cycle. Strong Inhibition Inspiration may decrease up to 0.5 s (30-40 breaths/min) Weak Inhibition Inspiration may increase up to 5 s or more or (3-5 breaths/min)

2. VENTRAL RESPIRATORY GROUPLocated in each side of medulla, 5 mm anterior and lateral to DRG and is found in a) Nucleus ambiguus b) Nucleus retroambiguus

FunctionsThese neurons are normally inactive during quiet respiration Do not take part in basic rhythmical breathingWorks only in forced respiration and contribute with DRG neuronsVRG will produce eupnea (12-15 beats/min)

Factors Affecting Respiration

CHEMICAL CONROL OF RESPIRATIONRole of CO2/H+

affect a special area in the medulla called Chemosensitive area

Located 0.2 mm beneath the ventral part of medulla

Sensory neurons are especially excited by H+ ions, but these ions can not cross the blood brain barrier (BBB) easily

CO2 has less effect on RC compared to H+, but can easily cross BBB

Indirectly affects RC

Role of Oxygen

No direct effect on RC as O2 is sufficient with PO2 ranging from 60 to 1000 mm Hg and substantial amount of Oxygen is bounded with Hb No direct effect of oxygen on the alveolar ventilation

PERIPHERAL CHEMORECEPTORS SYSTEM FOR CONTROLLING OXYGEN LEVELResponds to change in the concentration of oxygen with lesser response with CO2/H+ 1. Carotid Bodies 2. Aortic Bodies 3. Larger arteries of thoracic & abdominal regions

Carotid Located bilaterally in the bifurcation of common carotid arteries Afferent fibers pass through Herings nerve to glossopharyngeal nerve and then to DRG

Aortic Along the arch of aorta Afferent fiber pass through Vagi and then to DRG

Each of body receive blood supply through a very small artery from the adjacent arterial trunk

Mechanism of stimulation of chemoreceptors by oxygenDecreased concentration of arterial oxygen increases the rate of nerve impulses from peripheral Chemoreceptors

More sensitive to changes in arterial PO2 in range of 30-60 mm Hg (a range in which Hb saturation with O2 decreases rapidly

Stimulation of peripheral chemoreceptors 1. Oxygen 2. CO2 Peripheral effect of CO2/H+ is less potent on RC as compared to central effect of stimuli on RC, but peripheral effect is more rapid (5 times more)

Inflation Hysteresis

Transport of Carbon dioxideA) Dissolved Form (7%)B) As Bicarbonate (70%)C) Carbamino compounds (20%)

*general CXR site:http://www.radiologyinfo.org/en/info.cfm?pg=chestrad&bhcp=1CXR atlas:http://www.meddean.luc.edu/lumen/MedEd/medicine/pulmonar/cxr/atlas/cxratlas_f.htm (penumothorax)

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