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© 2007 McGraw-Hill Higher Education. All rights reserved.
Topics
• Oxygen cascade from air-to-tissue
• Effects of reduced barometric pressure
• Alveolar ventilation equation• Hyperventilation• Acid-base changes• Control of ventilation
© 2007 McGraw-Hill Higher Education. All rights reserved.
Case Study #2: Bill• Mountain climber• Hyperventilates on exposure to
hypoxia– What causes this? Is it good?
Bad?• Alveolar gas equation
• Relationship between PACO2 and PAO2
• pH effects• Oxygen transport
• Blood-myocyte O2 exchange
© 2007 McGraw-Hill Higher Education. All rights reserved.
Case Study #2: Bill• Barometric pressure and altitude
– Dalton’s law of partial pressures
• PiO2 varies with PB
– PiO2 = PB * 20.93
– SL: (760-47) * .2093 = 149 mmHg
– Mt Everest: (250-47) * .2093 = 42.5 mmHg
– 19,200 m: (47-47) * .2093 = 0
© 2007 McGraw-Hill Higher Education. All rights reserved.
Oxygen cascade: air to tissue• Po2 falls as it enters the
body and ultimately reaches the tissues– Inspired air: 149 mmHg– Alveolar air: 100– Arterial blood: ~100– Capillary blood: 20-40
mmHg– Tissue: 5-20– Mitochondria: <1
© 2007 McGraw-Hill Higher Education. All rights reserved.
Hyperventilation: secret weapon
• Tidal volume is a composite of dead space and alveolar gas– However, all Co2 comes from the
alveolar gas• Vco2 = VA * Fco2
• Pco2 = Fco2 * K• Pco2 = [Vco2/VA]*K
– Alveolar ventilation eq.• PAO2 = PiO2 – [PACO2/R]
– Normal: 149 – [40/0.8] =100 mmHg
– Hypoxia: 100 – [40/0.8] = 50– Hypoxia + hyperventilation:
100 – [20/0.8] = 75
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Reasons why arterial gas approaches but does not equal alveolar– Diffusion limitation
(esp. at altitude)– Shunt
– VA/Q mismatching
Alveolar and arterial gas
© 2007 McGraw-Hill Higher Education. All rights reserved.
Acid-base status• Has respiratory and metabolic components
– In other words, the lung can affect acid-base– Henderson-Hasselbalch eq.
• H2CO3 ↔ H+ + HCO3-
• Dissociation constant of H2CO3; because H2CO3 and Co2 are proportional
KA = [H+] * [HCO3-]/[Co2]
Log KA = log [H+] + log [HCO3-]/[Co2]
-Log [H+] = - Log KA + log [HCO3-]/[Co2]
pH = pKA + log [HCO3-]/[Co2]
© 2007 McGraw-Hill Higher Education. All rights reserved.
Acid-base statusBecause CO2 obeys Henry’s law: At a constant temperature, the amount of a given gas dissolved in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid
pH = pKA + log [HCO3-]/{0.03 * Pco2}
pH = 6.1 + log (24/{0.03 * 40})pH = 6.1 + log (20)
pH = 6.1 + 1.3pH =7.4
HCO3- typically determined by
the kidneyPCO2 by the lung
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Davenport diagram
– HCO3- can be raised or lowered
• Renal excretion or retention–Renal compensation
– Pco2 can be raised or lowered
• Hyper or hypo ventilation–Respiratory compensation
– Respiratory acidosis, Respiratory alkalosis, metabolic acidosis, metabolic alkalosis
Acid-base status
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Caused by hyperventilation• Altitude, anxiety
– Decrease in Pco2
– Elevates pH– Buffer line moves from A to C
• Over time kidney compensates by excreting HCO3
-
– Buffer line moves from C to F– “compensated respiratory
alkalosis”– Usu. Not complete– Degree to which it compensates can be
derived by the distance betw. Buffer lines A-C and G-F or the base deficit
Respiratory alkalosis
© 2007 McGraw-Hill Higher Education. All rights reserved.
Respiratory acidosis• Caused by hypoventilation• Drug overdose, chronic COPD
– Increase in Pco2
– Reduces pH– Buffer line moves from A to B
• Over time kidney compensates by conserving HCO3
-
– Buffer line moves from B to D– “compensated respiratory acidosis”– Usu. Not complete– Degree to which it compensates can be
derived by the distance betw. Buffer lines A-B and D-E or the base excess
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Hco3- falls
– Accumulation of lactic acid or diabetes
– Move along line A-G
• Respiratory compensation– Hyperventilation– Move from G to F– Base deficit will occur
Metabolic acidosis
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Increase in HCO3-
– Vomiting• Move along line A to E
• Respiratory compenstaion– Hypoventilation– Move along line E to D– Base excess
Metabolic alkalosis
© 2007 McGraw-Hill Higher Education. All rights reserved.
Control of Ventilation
• Basics– Ventilatory system can
defend against • Changes in PiO2
• Acid-base disturbances
– Precisely controlled• Central controller• Sensors • Effectors
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Central Controller– Brainstem– Three main groups
• Medullary respiratory center– Just below 4th ventricle– Dorsal (inspiration) and
ventral (expiration) respiratory groups
– Dorsal group responsible for the rhythmicity of the system
– Inspiration can be “cut off” by pneumotaxic center: may help increase rate of breathing
Control of Ventilation
© 2007 McGraw-Hill Higher Education. All rights reserved.
Control of Ventilation• Expiratory center
– Becomes active during exercise
– Apneustic center• Inspiration• Prolongs insp
– Increases depth of breathing
– Coordinates switch betw insp and exp
– Pneumotaxic center• Switches “off” inspiration• fine-tune respiratory
rhythm
© 2007 McGraw-Hill Higher Education. All rights reserved.
Control of Ventilation
• Cortex– Breathing is under
voluntary control– Can alter basic
breathing pattern within limits
– Can also help initiate changes in ventilation when exercise commences, “central command”
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Effectors– Muscles of respiration we discussed last week
• Sensors– Central chemoreceptors
• Respond to changes in the chemical composition of the blood or fluid surrounding it
• Near the ventral surface of the medulla• Surrounded by ECF (extracellular fluid) and
CSF– Respond to Co2 and assoc pH changes– Low buffering capacity of CSF
» Responds readily to Co2
» Co2 + H2O →H2CO3→H+ + HCO3-
Control of Ventilation
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Peripheral chemoreceptors– Carotid bodies– Aortic bodies
• Respond to – ↑Pco2
– ↑H+ – ↓Po2
– Carotid body almost wholly resp. for inc. ventilation in response to hypoxia
– Respiratory compensation to metabolic acidosis
Control of Ventilation
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Lung receptors– Pulm stretch receptors
• Mechanoreceptors• Impulses travel along vagus nerve• Inhibit inspiration
– Irritant receptors• In the airways• Respond to noxious gases• Bronchoconstriction and hyperventilation
– Juxtracapillary or J receptors• Innervated by Vagus• Respond to engorgement of the capillaries• Pulmonary edema, pulm embolism, pneumonia and baraotrauma• Rapid, shallow breathing; may play a role in the dyspnea assoc with these
diseases– Bronchial C fibers
• In bronchial mucosa– Rapid, shallow breathing, bronchoconstriction, cough, increased
vascular permeability and mucus secretion– Sensitive to chemical stimuli (ozone, cigarette smoke, capsaicin)
Control of Ventilation
© 2007 McGraw-Hill Higher Education. All rights reserved.
Integrated responses• Response to Carbon Dioxide
– Normally, the most important determinant in the control of ventilation
– Very sensitive• Paco2 does not change by much,
even with exercise (maybe 3 mmHg)• Normal rise in vent for an increase in
Pco2 is 2-3 L/min/mmHg• For lower PAO2, higher vent for any
Pco2 and steeper slope– Ventilatory sensitivity to CO2 varies
• Lower in trained athletes and divers• Barbiturates severely depress
respiratory centers
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Response to O2
– Doesn’t begin until subject is quite hypoxic
– Increased PACO2 increases the sensitivity to hypoxia
– Mostly a factor at altitude
Integrated responses
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Response to pH– Mostly caused by peripheral
chemoreceptors– Acidemia causes increased
ventilation– Alkalemia causes reduced
ventilation– As the ventilatory changes cause
corresponding changes in PaCO2 we call these ventilatory changes hyperventilation or hypoventilation
Integrated responses
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Response to Exercise– Ventilation increases
up to 25 fold
– PaCO2 does not rise (in humans), and usu. Falls
– PaO2 may stay the same, rise or fall
– pH falls
Integrated responses
© 2007 McGraw-Hill Higher Education. All rights reserved.
Acclimatization and High-altitude diseases
• Hyperventilation– Hypoxemia stimulates peripheral chemoreceptors; blows off
Co2, raises PAO2
– PB 250 mmHg do calculation– Renal compensation reduces HCO3
-
• Polycythemia– Increased Hct and [Hb]– Increases O2 carrying capacity: draw eq.– EPO form kidney
• Other features– Rightward shift in O2-Hb dissociation curve (Leftward at
extreme altitude)• Improves off-loading of O2 at the tissues• Caused by ↑2,3 DPG at altitude• Increased capillary-to-fiber volume ratio
– Muscle mass drops at altitude
© 2007 McGraw-Hill Higher Education. All rights reserved.
• Acute mountain sickness– Headache, dizziness, palpitations, insomnia, loss of appetite
and nausea• Hypoxemia and resp. alkalosis
• Chronic mountain sickness– Cyanosis, fatigue, severe hypoxemia, marked polycythemia
• High altitude pulmonary edema– Severe dyspnea, orthopnea, cough, cyanosis, crackles and
pink, frothy sputum– Life threatening– Associated with elevated Ppa (hypoxic pulm
vasoconstriction)• High altitude cerebral edema
– Confusion, ataxia, irrationality, hallucinations, loss of consciousness and death
– Fluid leakage into brain
Acclimatization and High-altitude diseases