Pulmonary Physiology

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Pulmonary Physiology

• Respiratory neurons in brain stem
• sets basic drive of ventilation
• descending neural traffic to spinal cord
• activation of muscles of respiration
• Ventilation of alveoli coupled with perfusion of
  pulmonary capillaries
• Exchange of oxygen and carbon dioxide

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Respiratory Centers

• Located in brain stem
• Dorsal Ventral Medullary group
• Pneumotaxic Apneustic centers
• Affect rate and depth of ventilation
• Influenced by
• higher brain centers
• peripheral mechanoreceptors
• peripheral central chemoreceptors

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Muscles of Ventilation

• Inspiratory muscles-
• increase thoracic cage volume
• Diaphragm, External Intercostals, SCM,
• Ant Post. Sup. Serratus, Scaleni, Levator
  Costarum
• Expiratory muscles-
• decrease thoracic cage volume
• Abdominals, Internal Intercostals, Post Inf.
  Serratus, Transverse Thoracis, Pyramidal

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Ventilation-Inspiration

• Muscles of Inspiration-when contract ?
  thoracic cage volume (uses 3 of TBE)
• diaphragm
• drops floor of thoracic cage
• external intercostals
• sternocleidomastoid
• anterior serratus
• scaleni
• serratus posterior superior
• levator costarum
• (all of the above except diaphragm lift rib cage)

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Ventilation-expiration

• Muscles of expiration when contract pull rib cage
  down ? thoracic cage volume (forced expiration
• rectus abdominus
• external and internal obliques
• transverse abdominis
• internal intercostals
• serratus posterior inferior
• transversus thoracis
• pyramidal
• Under resting conditions expiration is passive
  and is associated with recoil of the lungs

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Movement of air in/out of lungs

• Considerations
• Pleural pressure
• negative pressure between parietal and visceral
  pleura that keeps lung inflated against chest
  wall
• varies between -5 and -7.5 cmH2O (inspiration to
  expiration
• Alveolar pressure
• subatmospheric during inspiration
• supra-atmospheric during expiration
• Transpulmonary pressure
• difference between alveolar P pleural P
• measure of the recoil tendency of the lung
• peaks at the end of inspiration

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Compliance of the lung

• ?V/?P
• At the onset of inspiration the pleural pressure
  changes at faster rate than lung
  volume-hysteresis
• Air filled lung vs. saline filled lung
• Easier to inflate a saline filled lung than an
  air filled lung because surface tension forces
  have been eliminated in the saline filled lung

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Pleural relationships-lung chestwall forces
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Effect of Thoracic Cage on Lung

• Reduces compliance by about 1/2 around functional
  residual capacity (at the end of a normal
  expiration)
• Compliance greatly reduced at high or low lung
  volumes

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Work of Breathing

• Compliance work (elastic work)
• Accounts for most of the work normally
• Tissue resistance work
• viscosity of chest wall and lung
• Airway resistance work
• Energy required for ventilation
• 3-5 of total body energy

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Patterns of Breathing

• Eupnea
• normal breathing (12-17 B/min, 500-600 ml/B)
• Hyperpnea
• ? pulmonary ventilation matching ? metabolic
  demand
• Hyperventilation (? CO2)
• ? pulmonary ventilation gt metabolic demand
• Hypoventilation (? CO2)
• ? pulmonary ventilation lt metabolic demand

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Patterns of breathing (cont.)

• Tachypnea
• ? frequency of respiratory rate
• Apnea
• Absense of breathing. e.g. Sleep apnea
• Dyspnea
• Difficult or labored breathing
• Orthopnea
• Dyspnea when recumbent, relieved when upright.
  e.g. congestive heart failure, asthma, lung
  failure

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Pleural Pressure

• Lungs have a natural tendency to collapse
• surface tension forces 2/3
• elastic fibers 1/3
• What keeps lungs against the chest wall?
• Held against the chest wall by negative pleural
  pressure suction

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Collapse of the lungs

• If the pleural space communicates with the
  atmosphere, i.e. pleural P atmospheric P the
  lung will collapse
• Causes
• Puncture of the parietal pleura
• Sucking chest wound
• Erosion of visceral pleura
• Also if a major airway is blocked the air trapped
  distal to the block will be absorbed by the blood
  and that segment of the lung will collapse

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Pleural Fluid

• Thin layer of mucoid fluid
• provides lubrication
• transudate (interstitial fluid protein)
• total amount is only a few mls
• Excess is removed by lymphatics
• mediastinum
• superior surface of diaphragm
• lateral surfaces of parietal pleural
• helps create negative pleural pressure

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Pleural Effusion

• Collection of large amounts of free fluid in
  pleural space
• Edema of pleural cavity
• Possible causes
• blockage of lymphatic drainage
• cardiac failure-increased capillary filtration P
• reduced plasma colloid osmotic pressure
• infection/inflammation of pleural surfaces which
  breaks down capillary membranes

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Surfactant

• Reduces surface tension forces by forming a
  monomolecular layer between aqueous fluid lining
  alveoli and air, preventing a water-air interface
• Produced by type II alveolar epithelial cells
• complex mix-phospholipids, proteins, ions
• dipalmitoyl lecithin, surfactant apoproteins,
  Ca ions

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Stabilization of Alveolar size

• Role of surfactant
• Law of Laplace P2T/r
• Without surfactant smaller alveolar have
  increased collapse p would tend to empty into
  larger alveoli
• Big would get bigger and small would get smaller
• Surfactant automatically offsets this physical
  tendency
• As the alveolar size ? surfactant is concentrated
  which ? surface tension forces, off-setting the ?
  in radius
• Interdependence
• Size of one alveoli determined in part by
  surrounding alveoli

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Air filled vs. Saline filled lung

• Experimentally it is much easier to expand a
  saline filled lung compared to an air filled lung
• In a saline filled lung, surface tension forces
  are eliminated
• Surface tension forces are normally responsible
  for 2/3 of the collapse tendency of the lung

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Static Lung Volumes

• Tidal Volume (500ml)
• amount of air moved in or out each breath
• Inspiratory Reserve Volume (3000ml)
• maximum vol. one can inspire above normal
  inspiration
• Expiratory Reserve Volume (1100ml)
• maximum vol. one can expire below normal
  expiration
• Residual Volume (1200 ml)
• volume of air left in the lungs after maximum
  expiratory effort

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Static Lung Capacities

• Functional residual capacity (RVERV)
• vol. of air left in the lungs after a normal
  expir., balance point of lung recoil chest wall
  forces
• Inspiratory capacity (TVIRV)
• max. vol. one can inspire during an insp effort
• Vital capacity (IRVTVERV)
• max. vol. one can exchange in a resp. cycle
• Total lung capacity (IRVTVERVRV)
• the air in the lungs at full inflation

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Determination of RV, FRC, TLC

• Of the static lung volumes capacities, the RV,
  FRC, TLC cannot be determined with basic
  spirometry.
• Helium dilution method for RV, FRC, TLC
• FRC (Hei/Hef-1)Vi
• Heiinitial concentration of helium in jar
• Heffinal concentration of helium in jar
• Viinitial volume of air in bell jar

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Determination of RV, FRC, TLC

• After FRC is determined with the previous
  formula, determination of RV TLC is as follows
• RV FRC- ERV
• TLC RV VC
• ERV VC values are determined from basic
  spirometry
• VC, IRV, IC ? with restrictive lung conditions

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Pulmonary Flow Rates

• Compromised with obstructive conditions
• decreased air flow
• minute respiratory volume
• RR X TV
• Forced Expiratory Volumes (timed)
• FEV/VC
• Peak expiratory Flow
• Maximum Ventilatory Volume

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Airways in lung

• 20 generations of branching
• Trachea (2 cm2)
• Bronchi
• first 11 generations of branching
• Bronchioles (lack cartilage)
• Next 5 generations of branching
• Respiratory bronchioles
• Last 4 generations of branching
• Alveolar ducts give rise to alveolar sacs which
  give rise to alveoli
• 300 million with surface area 50-100 M2

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Dead Space

• Area where gas exchange cannot occur
• Includes most of airway volume
• Anatomical dead space (150 ml)
• Airways
• Physiological dead space
• anatomical non functional alveoli
• Calculated using a pure O2 inspiration and
  measuring nitrogen in expired air (fig 37-7)
• area X Ve

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Alveolar Volume

• Alveolar volume (2150 ml) FRC (2300 ml)- dead
  space (150 ml)
• At the end of a normal expiration most of the FRC
  is at the level of the alveoli
• Slow turnover of alveolar air (6-7 breaths)
• Rate of alveolar ventilation
• Va RR (Vt-Vd)

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Autonomic control of airways

• Efferent Neural control
• SNS-beta receptors causing dilatation
• direct effect weak due to sparse innervation
• indirect effect predominates via circulating
  epinephrine
• Parasympathetic-muscarinic receptors causing
  constriction
• NANC nerves (non-adrenergic, non-cholinergic)
• Inhibitory release VIP and NO ? bronchodilitation
• Stimulatory ? bronchoconstriction, mucous
  secretion, vascular hyperpermeability, cough,
  vasodilation neurogenic inflammation

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Autonomic control of airways

• Afferent nerves
• Slow adapting receptors
• Associated with smooth muscle of proximal airways
• Stretch receptors
• Involved in reflex control of breathing and
  cough reflex
• Rapidly adapting receptors
• Sensitive to mechanical , protons, low Cl-
  solutions, histamine, cigarette smoke, ozone,
  serotonin, PGF 2?
• Some responses may be secondary to mechanical
  distortion produced by bronchoconstriction

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Autonomic control of airways

• C-fibers (high density)
• Contain neuropeptides
• Substance P, neurokinin A, calcitonin
  gene-related peptide
• Selectively by capsaicin
• Also activated by bradykinin, protons,
  hyperosmole solutions and cigarette smoke

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Control of Airway Smooth Muscle (cont.)

• Local factors
• histamine binds to H1 receptors-constriction
• histamine binds to H2 receptors-dilation
• slow reactive substance of anaphylaxsis-constricti
  on-allergic response to pollen
• Prostaglandins E series- dilation
• Prostaglandins F series- constriction

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Control of Airway Smooth Muscle (cont)

• Environmental pollution
• smoke, dust, sulfur dioxide, some acidic elements
  in smog
• elicit constriction of airways
• mediated by
• parasympathetic reflex
• local constrictor responses

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Effect of pH on ventilation

• Normal level of HCO3- 24 mEq/L
• Metabolic acidosis (HCO3- lt 24) will
  ventilation
• Metabolic alkalosis (HCO3- gt24) will
  ventilation
• Kidney regulates HCO3-
• Normal level of CO2 40 mmHg
• Respiratory acidosis (CO2 gt 40) will
  ventilation
• Respiratory alkalosis (CO2 lt 40) will
  ventilation
• Lung regulates CO2

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Pulmonary circulation

• Pulmonary artery wall 1/3 as thick as aorta
• RV 1/3 as thick as LV
• All pulmonary arteries have larger lumen
• more compliant
• operate under a lower pressure
• can accommodate 2/3 of SV from RV
• Pulmonary veins shorter but similar compliance
  compared to systemic veins

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Total Pulmonic Blood Volume

• 450 ml (9 of total blood volume)
• reservoir function 1/2 to 2X TPBV
• shifts in volume can occur from pulmonic to
  systemic or visa versa
• e.g. mitral stenosis can ? pulmonary volume 100
• shifts have a greater effect on pulmonary
  circulation

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Systemic Bronchial Arteries

• Branches off the thoracic aorta which supplies
  oxygenated blood to the supporting tissue and
  airways of the lung. (1-2 CO)
• Venous drainage is into azygous (1/2) or
  pulmonary veins (1/2) (short circuit)
• drainage into pulmonary veins causes LV output to
  be slightly higher (1) than RV output also
  dumps some deoxygenated blood into oxygenated
  pulmonary venous blood

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Pulmonary lymphatics

• Extensive extends from all the supportive
  tissue of lungs courses to the hilum mainly
  into the right lymphatic duct
• remove plasma filtrate, particulate matter
  absorbed from alveoli, and escaped protein from
  the vascular system
• helps to maintain negative interstitial pressure
  which pulls alveolar epithelium against capillary
  endothelium. respiratory membrane

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Pulmonary Pressures

• Pulmonary artery pressure 25/8
• mean 15 mmHg
• Mean pulmonary capillary P 7 mmHg.
• Major pulmonary veins and left atrium
• mean pressure 2 mmHg.

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Control of pulmonary blood flow

• Since pulmonary blood flow CO, any factors that
  affect CO (e.g. peripheral demand) affect
  pulmonary blood flow in a like way.
• However within the lung blood flow is distributed
  to well ventilated areas
• low alveolar O2 causes release of a local
  vasoconstrictor which automatically redistributes
  blood to better ventilated areas

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ANS influence on pulmonary vascular smooth muscle

• SNS will cause a mild vasoconstriction
• ?3 Hz to 30 Hz ? pulmonary arterial BP about 30
• Mediated by alpha receptors
• With alpha blockage response abolished and at 30
  Hz. vasodilatation observed as beta receptors are
  unmasked
• Parasympathetic will cause a mild
  vasodilatation
• (major constrictor effect on pulmonary vascular
  smooth muscle is low alveolar O2)

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Oxygenation of blood in Pulmonary capillary

• Under resting conditions blood is fully
  oxygenated by the time it has passed the first
  1/3 of pulmonary capillary
• even if velocity ? 3X full oxygenation occurs
• Normal transit time is about .8 sec
• Under high CO transit time is ?.3 sec which
  still allows for full oxygenation
• Limiting factor in exercise is SV

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Effect of hydrostatic P on regional pulmonary
blood flow

• From apex to base capillary P ? (gravity)
• Zone 1- no flow
• alveolar P gt capillary P
• normally does not exist
• Zone 2- intermittent flow (toward the apex)
• during systole capillary P gt alveolar P
• during diastole alveolar P gt capillary P
• Zone 3- continuous flow (toward the base)
• capillary P gt alveolar P
• During exercise entire lung ? zone 3

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Pulmonary Capillary dynamics

• Starling forces (ultrafiltration)
• Capillary hydrostatic P 7 mmHg.
• Interstitial hydrostatic P -8 mmHg.
• Plasma colloid osmotic P 28 mmHg.
• Interstitial colloid osmotic P 14 mm
• Filtration forces 15 mmHg.
• Reabsorption forces 14 mmHg.
• Net forces favoring filtration 1 mmHg.
• Excess fluid removed by lymphatics

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Basic Gas Laws

• Boyles Law
• At a constant T the V of a given quantity of gas
  is 1/? to the P it exerts
• Avogadros Law
• V of gas at the same T P contain the same
  of molecules
• Charles Law
• At a constant P the V of a gas is ? to its
  absolute T
• The sum of the above gas laws
• PVnRT

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PV nRT

• Pgas pressure
• Vvolume a gas occupies
• n number of moles of a gas
• R gas constant
• T absolute temperature in Kelvin(C - 273)

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Additional Gas Laws

• Grahams Law
• the rate of diffusion of a gas is 1/? to the
  square root of its molecular weight
• Henrys Law
• the quantity of gas that can dissolve in a fluid
  is to the partial P of the gas X the solubility
  coefficient
• Daltons Law of Partial Pressures
• the P exerted by a mixture of gases is ? of the
  individual (partial) P exerted by each gas

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Vapor P of H2O

• The pressure that is exerted by the H2O molecules
  to escape from the liquid to air
• Due to molecular motion
• Proportional to temperature
• At body temperature (37oC) the vapor P of H2O is
  47 mmHg.

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Atmospheric Air vs. Alveolar Air

• H2O vapor 3.7 mmHg
• Oxygen 159 mmHg
• Nitrogen 597 mmHg
• CO2 .3 mmHg

• H2O vapor 47 mmHg
• Oxygen 104 mmHg
• Nitrogen 569 mmHg
• CO2 40 mmHg

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Diffusion across the respiratory membrane

• Temperature ?
• Solubility ?
• Cross-sectional area ?
• sq root of molecular weight 1/ ?
• concentration gradient ?
• distance 1/ ?
• Which of the above are properties of the gas?

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Relative Diffusion Coefficients

• These coefficients represent how readily a
  particular gas will diffuse across the
  respiratory membrane is ? to its solubility and
  1/? to sq. rt of MW.
• O2 1.0
• CO2 20.3
• CO 0.81
• N2 0.53
• He 0.95

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Alveolar gas concentrations

• O2 in the alveoli averages 104 mmHg
• CO2 in the alveoli averages 40 mmHg

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The respiratory unit

• Consists of about 300 million alveoli
• Respiratory membrane
• 2 cell layers
• alveolar epithelium
• capillary endothelium
• averages about .5-.6 microns in thickness
• total surface area 50-100 sq. meters
• 60-140 ml of pulmonary capillary blood

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Diffusing capacity of Respiratory Membrane

• Oxygen under resting conditions
• 21 ml/min/mmHg
• mean pressure gradient of 11 mmHg.
• 230 ml/min (21 X 11)
• increases during exercise
• Carbon dioxide diffuses at least 20X more readily
  than oxygen

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Expired Air

• As one expires a normal tidal volume of 500 ml
  the concentrations of oxygen and carbon dioxide
  change
• O2 falls from about 159 to 104 mmHg
• CO2 rises from O to 40 mmHg
• 1st 100 ml of expired air is from dead space
• last 250 ml of expired air is alveolar air
• Middle 150 ml of expired air is a mix of above
• (dead space alveolar air)

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Alveolar air turnover

• Each normal breath (tidal volume) turns over
  only a small percentage of the total alveolar air
  volume.
• 350/2150 mls
• Approximately 6-7 breaths for complete turnover
  of alveolar air.
• Slow turnover prevents large changes in gas
  concentration in alveoli from breath to breath

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Ventilation-Perfusion ratios

• Normally alveolar ventilation is matched to
  pulmonary capillary perfusion at a rate of 4L/min
  of air to 5L/min of blood
• 4/5 .8 is the normal V/P ratio
• If the ratio decreases, it is usually due to a
  problem with decreased ventilation
• If the ratio increases, it is usually due to a
  problem with decreased perfusion of lungs

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Ventilation-Perfusion ratios

• A decreased V/P ratio as ventilation goes to zero
• Not enough ventilation for the amount of
  pulmonary blood flow (perfusion)
• Alveolar PO2 will decrease toward 40 mmHg
• Alveolar PCO2 will increase toward 45 mmHg
• Results in an increase in physiologic shunt
  blood- blood that is not oxygenated as it passes
  the lung

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Ventilation-Perfusion ratios

• An increased V/P ratio due to a decreased
  perfusion of the lungs from the RV
• Not enough pulmonary blood flow (perfusion) for
  the amount of ventilation
• Alveolar PO2 will increase toward 149 mmHg
• Alveolar PCO2 will decrease toward O mmHg
• Results in an increase of physiologic dead space-
  area in the lungs where oxygenation is not taking
  place
• includes non functional alveoli

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VO2 Maximum

• The maximum oxygen that can be absorbed from the
  lung delivered to the tissue/min
• Best measure of cardiovascular fitness
• COmax X A-V O2 max
• Limited by CO, not pulmonary ventilation
• During exercise training, VO2 max improves as
  SVmax ? as HRmax stays constant
• Ranges
• 1.5 L/min Cardiac patient
• 3.0 L/min Sedentary person
• 6.0 L/min endurance athlete

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Transport of O2 CO2

• Oxygen- 5 ml/dl carried from lungs-tissue
• Dissolved-3
• Bound to hemoglobin-97
• increases carrying capacity 30-100 fold
• Carbon Dioxide- 4 ml/dl from tissue-lungs
• Dissolved-7
• Bound to hemoglobin (and other proteins)-23
• Bicarbinate ion-70

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Oxygen
63
Carbon Dioxide
64
Blood pH

• Arterial blood (Oxygenated)
• 7.41
• Venous blood (Deoxygenated)
• 7.37 (slightly more acidic but buffered by blood
  buffers)
• In exercise venous blood can drop to 6.9

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Respiratory exchange ratio

• Ratio of CO2 output to O2 uptake
• R 4/5.8
• What happens to Oxygen in the cells
• converted to carbon dioxide (80)
• converted to water (20)
• As fatty acid utilization for E increases the
  percentage of metabolic water generated from O2
  increases to a maximum of 30.
• If only CHO are used for energy no metabolic
  water is generated from O2, all O2 is converted
  to CO2

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Oxy-Hemoglobin Dissociation

• As Po2 ?, hemoglobin releases more oxygen
• Po2 95 mmHg ? 97 saturation (arterial)
• Po2 40 mmHg ? 70 saturation (venous)
• Sigmoid shaped curve with steep portion below a
  Po2 of 40 mmHg
• slight ? in Po2 ? large release in O2 from Hgb
• Shift to the right (promote dissociation)
• increase temperature
• increase CO2 (Bohr effect) decrease pH
• increase 2,3 diphosphoglycerate (2,3 DPG)

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Carbon Dioxide

• carried in form of bicarbinate ion (70)
• CO2 H2O ? H2CO3 ? H HCO3-
• carbonic anhydrase in RBC catalyses reaction of
  water and carbon dioxide
• carbonic acid dissociates into H HCO3 -
• Chloride shift
• As HCO3- leaves RBC it is replaced by Cl -
• Bound to hemoglobin (23)
• reacts with amine radicals of hemoglobin other
  plasma proteins
• Dissolved CO2 (7)

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Carbon Monoxide

• Competes with oxygen for binding sites on
  Hemoglobin
• affinity for hemoglobin (Hgb) 250 X that of O2
• Small partial pressures (Pco .4 mmHg) will
  saturate 97 of Hgb can decrease oxygen
  carrying capacity of Hgb by 50
• .1 CO (Pco .6 mmHg) can be lethal
• CO poisoning treated with 95 O2 5 CO2
• To rapidly displace CO
• CO2 ventilation

69
Physiologic role of CO

• Produced by the body in small quantities
• Functions
• Signaling molecule in nervous system
• Vasodilator
• Important role in immune, respiratory, GI,
  kidney, and liver systems
• Review paper

70
Neural control of ventilation

• Goals of regulation of ventilation is to keep
  arterial levels of O2 CO2 constant
• The nervous system adjusts the level of
  ventilation (RR TV) to match perfusion of the
  lungs (pulmonary blood flow)
• By matching ventilation with pulmonary blood flow
  (CO) we also match ventilation with overall
  metabolic demand

71
Neural control of ventilation

• Dorsal respiratory group
• located primarily in the nucleus tractus
  solitarius in medulla
• termination of CN IX X
• receives input from
• peripheral chemoreceptors
• baroreceptors
• receptors in the lungs
• rhythmically self excitatory
• ramp signal
• excites muscles of inpiration
• Sets the basic drive of ventilation

72
Neural control of ventilation

• Pneumotaxic center
• dorsally in N. parabrachialis of upper pons
• inhibits the duration of inspiration by turning
  off DRG ramp signal after start of inspiration
• Ventral respiratory group of neurons
• located bilaterally in ventral aspect of medulla
• can both inspiratory expiratory respiratory
  muscles during increased ventilatory drive
• Apneustic center (lower pons)
• functions to prevent inhibition of DRG under some
  circumstances

73
Neural Control of Ventilation

• Herring-Breuer Inflation reflex
• stretch receptors located in wall of airways
• when stretched at tidal volumes gt 1500 ml
• inhibits the DRG
• Irritant receptors-among airway epithethium
• ? sneezing coughing possibly airway
  constriction
• J receptors - in alveoli next to pulmonary caps
• when pulmonary caps are engorged or pulmonary
  edema
• create a feeling of dyspnea

74
Chemical Control of Ventilation

• Chemosensitive area of respiratory center
• Hydrogen ions-primary stimulus but cant cross
  membranes (blood brain barrier-BBB)
• carbon dioxide-can cross BBB
• inside cell converted to H
• rises of CO2 in CSF- effect on ventilation
  faster due to lack of buffers compared to plasma
• unresponsive to falls in oxygen-hypoxia depresses
  neuronal activity
• 70-80 of CO2 induced increase in vent.

75
Chemical Control of Ventilation

• Peripheral Chemoreceptors
• aortic and carotid bodies
• 20-30 of CO2 induced increase in vent.
• Responsive to hypoxia
• response to hypoxia is blunted if CO2 falls as
  the oxygen levels fall
• responsive to slight rises in CO2 (2-3 mmHg) but
  not similar falls in O2
• sensitivity altered by CNS
• SNS decreasing flow-increased sensitivity to
  hypoxia

76
Pathophysiologic consequences of hyperventilation

• SV CO decreased
• Coronary blood flow decreased
• Repolarization of heart impaired
• Oxyhemoglobin affinity increased
• Cerebral blood flow decreased
• Skeletal muscle spasm tetany
• Serum potassium decreased
• (common thread in most of above is hypocapnic
  alkalosis)

77
Other effect on ventilation

• Effect of brain edema
• depression or inactivation of respiratory centers
• use of intravenous hypertonic solution (e.g.
  mannitol) to treat
• Effect of Anesthesia/Narcotics
• most prevalent cause of respiratory depression
• sodium pentobarbital
• morphine

78
Stimulation of ventilation during exercise

• Increased corticospinal traffic which will
  collaterally stimulate respiratory centers in the
  brain stem
• reflex neural signals from active muscle spindles
  and joint proprioceptors
• fluctuations in O2 and CO2 levels in active
  muscle stimulating local chemoreceptors

79
O2 debt

• The extra O2 that is consumed post exercise to
  replenish O2 stores remove lactic acid
• The body contains about 2 L of stored O2 that can
  be used for aerobic metabolism
• .5 L in lungs
• .25 L in body fluids
• 1 L combined with hemoglobin
• .3 L in muscle myoglobin
• In heavy exercise stored O2 is used within 2
  mins.
• O2 debt can reach 11.5 L

80
O2 debt (cont.)

• After exercise this O2 debt is replenished
• After exercise, ventilation and O2 uptake remains
  high until O2 debt is repaid
• Alactacid oxygen debt (3.5 L)
• First couple of minutes post exercise
• Reconditioning of the phosphagen system (1.5 L)
• Replenishing oxygen stores (2 L)
• Lactic acid oxygen debt (8.0 L)
• Over 40 minutes post exercise
• Removal of lactic acid
• Lactic acid causes extreme fatigue

81
Respiratory adjustments at birth

• Most important adjustment is to breath
• normally occurs within seconds
• stimulated by
• cooling of skin
• slightly asphyxiated state (elevated CO2)
• 40-60 cm H20 of negative pleural P necessary to
  open alveoli on first breath
• 1 mmHg 1.36 cm H20

82
Circulatory changes at birth

• Placenta disconnects
• TPR increases
• Pulmonic resistance decreases (elimination of
  hypoxia)
• Closure of foramen ovale (atria)
• Closure of ductus arteriosis (great vessels)
• Closure of ductus venosus (bypass liver)

83
Effect of altitude on barometric P

• As one ascends the barometric P (bP) ?
• PO2 (.21) (barometric P)
• the fractional O2 in air doesnt ? with
  altitude
• As bP ? so does PO2 (alt ? bP ? PO2)
• 0 ft. ? 760 mmHg.? 159 mmHg.
• 10,000 ft. ? 523 mmHg.? 110 mmHg.
• 20,000 ft. ? 349 mmHg.? 73 mmHg.
• 30,000 ft. ? 226 mmHg.? 47 mmHg.
• 40,000 ft. ? 141 mmHg ? 29 mmHg.
• At 63,000 ft. the bP is 47 mmHg. blood boils

84
Acute effects of ascending to great heights

• Unacclimatized person suffers deterioration of
  nervous system function
• effects due primarily to hypoxia
• sleepiness, false sense of well being, impaired
  judgement , clumsiness, blunted pain perception,
  ? visual acuity, tremors, twitching, seizures
• Acute mountain sickness (onset hours - 2 d)
• cerebral edema ?hypoxia local vasodilatation
• pulmonary edema ? hypoxia local vasoconst.

85
Exposure to low PO2

• Hypoxic stimulation of arterial chemoreceptors
  (1.65 X) immediately
• decreased CO2 limits ?
• After several days ventilation ? 5X as inhibition
  fades
• ? HCO3? ? ? pH ? chemosensitive area of
  brainstem

86
Chronic Mountain Sickness

• Red cell mass (Hct) ?
• ? pulmonary arterial BP
• enlarged right ventricle
• ? total peripheral resistance
• congestive heart failure
• death if person is not removed to lower altitude

87
Acclimatization

• Great ? in pulmonary ventilation
• ? RBC (Hct)
• ? diffusing capacity of the lungs
• ? tissue vascularity (? capillary density)
• ? ability of tissues to use O2
• slight ? cell mitochondria (animals)
• slight ? cellular oxidative systems (animals)
• Increased synthesis of 2,3-DPG
• Shifts oxy-hemoglobin dissoc. curve to right
• Advantages-tissue Disadvantages-lung

88
Natural Acclimatization

• Humans living at altitudes gt 13,000 ft in the
  Andes Himalayas
• Acclimatization begins in infancy
• chest to body ratio ?
• high ratio of ventilatory capacity to body mass
• increased size of right ventricle
• shift in oxy-hemoglobin dissociation curve
• PO2 of 40 have greater O2 in blood than
  lowlanders at 95
• Work capacity greater than even well acclimatized
  lowlanders at high altitudes (17,000 ft) (87 vs.
  68)

89
Hyperbaric conditions

• As people descend beneath the sea, the pressure
  increases tremendously which can have a profound
  impact on the respiratory system.
• To keep the lungs from collapsing air must be
  supplied at high pressures which exposes
  pulmonary capillary blood to extremely high
  alveolar gas pressures ? hyperbarism
• These high pressures can be lethal

90
Relationship of pressure to sea depth

• Depth
• Sea level
• 33 feet (10.1 m)
• 66 feet (20.1 m)
• 100 feet (30.5 m)
• 133 feet (40.5 m)
• 166 feet (50.6 m)
• 233 feet (71.1 m)
• 300 feet (91.4 m)
• 400 feet (121.9 m)
• 500 feet (152.4 m)

• Atmospheres/vol of gas
• 1 1 liter of gas
• 2 ½ liter of gas
• 3
• 4 ¼ liter of gas
• 5
• 6
• 8 1/8 liter of gas
• 10
• 13
• 16

91
Effect of High Partial Pressures

• High PN2
• Causes narcosis in about an hour of being
  submerged
• 120 feet- joviality, carefree
• 150-200- drowsyness
• 200-250- weakness
• Beyond 250- unable to function
• Similar to alcohol intoxication
• raptures of the deep
• Mechanism similar to gas anesthetics
• Dissolves in neuronal membranes altering ionic
  conductance

92
Effect of High Partial Pressures

• High PO2
• Oxygen toxicity
• Seizures followed by coma within 30-60 minutes
• Likely lethal to divers
• Above a critical alveolar PO2 (gt 2 atmospheres
  PO2)
• Free radical damage can occur
• Damage to cell membranes, cellular enzymes,
• Nervous tissue highly suscpectable resulting in
  brain dysfunction
• Oxygen toxicity is preventable if one never
  exceeds the established maximum depth of a given
  breathing gas.
• For deep dives - generally past 180 feet (55 m),
  divers use "hypoxic blends" containing a lower
  of O2 than atmospheric air

93
Effect of High Partial Pressures

• High PCO2
• Usually not a problem as depth does not increase
  the alveolar PCO2
• Can increase in certain types of diving gear
• problems can occur when alveolar PCO2 gt 80 mmHg.
• Depression of respiratory centers
• Respiratory acidosis
• Lethargy
• Narcosis
• anesthesia

94
Decompression

• When a person breaths air under high pressure for
  an extended period of time the amount of N2 in
  the body fluids increases as higher N2 levels
  equilibrate with levels in tissues.
• N2 is not metabolized by the body
• It remains dissolved in the tissues until N2
  pressure in the lungs decreases as the person
  ascends back to sea level.
• Several hours are required for gas pressures of
  N2 in all body tissues to equilibrate with
  alveolar PN2

95
Decompression (cont.)

• Blood does not flow rapidly enough N2 doesnt
  diffuse rapidly enough to cause instantaneous
  equilibration
• N2 dissolved in H2O equilibrates in lt 1 hour
• N2 dissolved in fat equilibrates in several hours
• Potential problem if person is submerged at a
  deep level for several hours

96
Volume of N2 dissolved in body

• Feet below

• liters

• O
• 33
• 100
• 200
• 300

• 1
• 2
• 4
• 7
• 10

97
Decompression sickness Bends

• Nitrogen bubbles out of fluids after sudden
  decompression
• Bubbles block many blood vessels
• First smaller blood vessels, then as bubbles
  coalesce larger vessels are blocked
• S/S
• Pain in joints, muscles of arms/legs (85-90)
• Nervous system symptoms (5-10)
• Dizziness, paralysis, unconsciousness
• Pulmonary capillaries blockes the chokes (2)

98
Preventing Decompression sickness

• Decompression tables (U.S. Navy) link
• A diver who has been breathing air and has been
  on the sea bottom at a depth of 190 feet for 60
  minutes is decompressed as follows
• 10 minutes at 50 foot depth
• 17 minutes at 40 foot depth
• 19 minutes at 30 foot depth (total
  decompression
• 50 minutes at 20 foot depth time 3 hours)
• 84 minutes at 10 foot depth
• Scuba diving link

99
The lung as an organ of metabolism

• As an organ of body metabolism the lung ranks
  second behind the liver
• One advantage the lung has over the liver is the
  fact that all blood passes through the lungs with
  every complete cycle
• Some examples
• Angiotensin I converted to Angiotensin II
• Prostaglandins inactivated in one pass through
  pulmonary circulation

100
Defenses of the Respiratory System
101
Defenses of Respiratory System

• Respiratory membrane represents a major source of
  contact with the environment with a separation of
  .5 microns between the air the blood over a
  surface area of 50-100 sq. meters
• The average adult inhales about 10000 L air/day
• Inert dust
• Particulate matter
• Plant animal
• Gases
• Fossil fuel combustion
• Infectious agents
• Viruses bacteria

102
Defense Mechanisms

• Protect tracheobronchial tree alveoli from
  injury
• Prevent accumulation of secretions
• Repair

103
Depression of Defense Mechanisms

• Chronic alcohol is associated with an increase
  incidence of bacterial infections
• Cigarette smoke and air pollutants is associated
  with an increase incidence of chronic bronchitis
  and emphysema
• Occupational irritants is associated with and
  increased incidence of hyperactive airways or
  interstitial pulmonary fibrosis

104
Upper respiratory tract

• Nasal passages protect airways and alveolar
  structures from inhaled foreign materials
• Long hairs (vibrassae) in nose (nares) filters
  out larger particles
• Mucous coating the nasal mucous membranes traps
  particles (gt10 microns)
• Moisten air 650 ml H2O/day
• Nasal turbinates
• Highly vascularized, act as radiators to warm air

105
Cough

• From trachea to alveoli sensitive to irritants
• Afferents utilize primarily CN X
• Process
• 2.5 L of air rapidly inspired
• Epiglottis closes and vocal chords close tightly
• muscles of expiration contract forcefully which
  causes pressure in lungs to rise to 100 mm Hg
• Epiglottis and vocal chords open widely which
  results in explosive outpouring of air to clear
  larger airways
• at speeds of 75 100 MPH
• Cough is ineffective at clearing smaller airways
  due to large total X-sectional area
• cant generate sufficient velocity

106
Sneeze

• Sneeze reflex
• Associated with nasal passages
• Irritation sends signal over CN V to the medulla
• Response similar to cough, but in addition uvula
  is depressed so large amounts of air pass rapidly
  through the nose to clear nasal passages
• With sneeze and cough velocity of air escaping
  from the mouth nose has been clocked at speeds
  of 75-100 MPH

107
Mucociliary elevator

• Clears smaller airways
• Mucous produced by globlet cells in epithelium
  and small submucosal glands
• Ciliated epithelium which lines the respiratory
  tract all the way down to the terminal
  bronchioles moves the mucous to the pharynx
• Beat 1000 X/minute
• Mucous flows at about speed of 1 cm/min
• Swallowed or coughed out
• Organisms in mucous are destroyed by acid
  environment in stomach if swallowed

108
Immune reaction in the lung

• Alveolar macrophages
• Capable of phagocytosing intraluminal particles
• Principal phagocytic cells in the distal air
  spaces
• Complement system
• Small proteins found in the blood synthesized in
  the liver
• Complements the ability of antibodies and
  phagocytic cells to clear pathogens from an
  organism
• Part of the innate immune system along with
  macrophages

109
Immune rxn in the lung

• Antibodies associated with the mucosa
• IgG- lower respiratory tract
• IgA- dominate in upper respiratory tract
• IgE- predominantly a mucosal antibody

110
Immune reaction in the lung (cont)

• Macrophages
• present pieces of organisms to other effector
  cells through a series of interactions involving
  cytokines which promote a more vigorous/widespread
  immune response
• Humoral immune system
• Antibodies
• Accessory processes
• Th2 activation, Cytokine production, germinal
  center formation, isotype switching, affinity
  maturation, memory cell generation
• Various lipoproteins and glycoproteins