Transcript Pulmonary Physiology

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
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
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
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)
Ventilation-expiration
• Muscles of expiration when contract pull rib
cage down ⇓ thoracic cage volume (forced
expiration
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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
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
Compliance of the lung
• ΔV/ΔP
• 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
Pleural relationships-lung & chestwall
forces
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
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
Patterns of Breathing
• Eupnea
– normal breathing (12-17 B/min, 500-600 ml/B)
• Hyperpnea
– ⇑ pulmonary ventilation matching ⇑ metabolic
demand
• Hyperventilation (⇓ CO2)
– ⇑ pulmonary ventilation > metabolic demand
• Hypoventilation (⇑ CO2)
– ⇓ pulmonary ventilation < metabolic demand
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
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”
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
Pleural Fluid
• Thin layer of mucoid fluid
– provides lubrication
– transudate (interstitial fluid + protein)
– total amount is only a few ml’s
• Excess is removed by lymphatics
– mediastinum
– superior surface of diaphragm
– lateral surfaces of parietal pleural
– helps create negative pleural pressure
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
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
Stabilization of Alveolar size
• Role of surfactant
– Law of Laplace P=2T/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
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
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
Static Lung Capacities
• Functional residual capacity (RV+ERV)
– vol. of air left in the lungs after a normal expir.,
balance point of lung recoil & chest wall forces
• Inspiratory capacity (TV+IRV)
– max. vol. one can inspire during an insp effort
• Vital capacity (IRV+TV+ERV)
– max. vol. one can exchange in a resp. cycle
• Total lung capacity (IRV+TV+ERV+RV)
– the air in the lungs at full inflation
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= ([He]i/[He]f-1)Vi
• [He]i=initial concentration of helium in jar
• [He]f=final concentration of helium in jar
• Vi=initial volume of air in bell jar
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
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
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
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
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)
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”
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 2α
– Some responses may be secondary to mechanical distortion
produced by bronchoconstriction
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
Control of Airway Smooth Muscle
(cont.)
• Local factors
– histamine binds to H1 receptors-constriction
– histamine binds to H2 receptors-dilation
– slow reactive substance of anaphylaxsisconstriction-allergic response to pollen
– Prostaglandins E series- dilation
– Prostaglandins F series- constriction
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
Effect of pH on ventilation
• Normal level of HCO3- = 24 mEq/L
– Metabolic acidosis (HCO3- < 24) will + ventilation
– Metabolic alkalosis (HCO3- >24) will – ventilation
– Kidney regulates HCO3-
• Normal level of CO2 = 40 mmHg
– Respiratory acidosis (CO2 > 40) will + ventilation
– Respiratory alkalosis (CO2 < 40) will – ventilation
– Lung regulates CO2
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
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
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
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”
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.
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
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)
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
Effect of hydrostatic P on regional
pulmonary blood flow
• From apex to base capillary P ⇑ (gravity)
– Zone 1- no flow
• alveolar P > capillary P
• normally does not exist
– Zone 2- intermittent flow (toward the apex)
• during systole; capillary P > alveolar P
• during diastole; alveolar P > capillary P
– Zone 3- continuous flow (toward the base)
• capillary P > alveolar P
– During exercise entire lung ⇒ zone 3
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
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Filtration forces = 15 mmHg.
Reabsorption forces = 14 mmHg.
Net forces favoring filtration = 1 mmHg.
Excess fluid removed by lymphatics
Basic Gas Laws
• Boyle’s Law
– At a constant T the V of a given quantity of gas is 1/∝ to
the P it exerts
• Avogadro’s 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:
– PV=nRT
PV = nRT
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P=gas pressure
V=volume a gas occupies
n= number of moles of a gas
R= gas constant
T= absolute temperature in Kelvin(C - 273)
Additional Gas Laws
• Graham’s Law
– the rate of diffusion of a gas is 1/∝ to the square
root of its molecular weight
• Henry’s Law
– the quantity of gas that can dissolve in a fluid is =
to the partial P of the gas X the solubility
coefficient
• Dalton’s Law of Partial Pressures
– the P exerted by a mixture of gases is = Σ of the
individual (partial) P exerted by each gas
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.
Atmospheric Air vs. Alveolar Air
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H2O vapor 3.7 mmHg
Oxygen 159 mmHg
Nitrogen 597 mmHg
CO2 .3 mmHg
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H2O vapor 47 mmHg
Oxygen 104 mmHg
Nitrogen 569 mmHg
CO2 40 mmHg
Diffusion across the respiratory
membrane
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Temperature ∝
Solubility ∝
Cross-sectional area ∝
sq root of molecular weight 1/ ∝
concentration gradient ∝
distance 1/ ∝
Which of the above are properties of the gas?
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
Alveolar gas concentrations
• [O2] in the alveoli averages 104 mmHg
• [CO2] in the alveoli averages 40 mmHg
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
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
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)
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
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
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
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 spacearea in the lungs where oxygenation is not taking
place
• includes non functional alveoli
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%
Oxygen
Carbon Dioxide
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
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
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)
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%)
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
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
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
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
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
Neural Control of Ventilation
• Herring-Breuer Inflation reflex
– stretch receptors located in wall of airways
– + when stretched at tidal volumes > 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
Chemical Control of Ventilation
• Chemosensitive area of respiratory center
– Hydrogen ions-primary stimulus but can’t 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.
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
Pathophysiologic consequences of
hyperventilation
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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)
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
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
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
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
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
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)
Effect of altitude on barometric P
• As one ascends the barometric P (bP) ⇓
• PO2 = (.21) (barometric P)
– the fractional [O2] in air doesn’t Δ with altitude
• As bP ⇓ so does PO2 (alt ⇒ bP ⇒ PO2)
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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”
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.
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
Chronic Mountain Sickness
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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
Acclimatization
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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
Natural Acclimatization
• Humans living at altitudes > 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%)
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
Relationship of pressure to sea depth
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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)
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•
•
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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
Effect of High Partial Pressures
• High PN2
– Causes narcosis in about an hour of being submerged
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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
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 (> 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
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 > 80 mmHg.
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Depression of respiratory centers
Respiratory acidosis
Lethargy
Narcosis
anesthesia
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
Decompression (cont.)
• Blood does not flow rapidly enough & N2
doesn’t diffuse rapidly enough to cause
instantaneous equilibration
• N2 dissolved in H2O equilibrates in < 1 hour
• N2 dissolved in fat equilibrates in several
hours
• Potential problem if person is submerged at
a deep level for several hours
Volume of N2 dissolved in body
Feet below
liters
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O
33
100
200
300
1
2
4
7
10
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%)
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
– 50 minutes at 20 foot depth
– 84 minutes at 10 foot depth
• Scuba diving link
(total decompression
time = 3 hours)
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
Defenses of the Respiratory
System
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
Defense Mechanisms
• Protect tracheobronchial tree & alveoli from
injury
• Prevent accumulation of secretions
• Repair
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
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 (>10 microns)
• Moisten air – 650 ml H2O/day
– Nasal turbinates
• Highly vascularized, act as radiators to warm air
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
– can’t generate sufficient velocity
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
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
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
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
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