Chapter 2 Normal Physiology: Hypoxia

© 2007 McGraw-Hill Higher Education. All rights reserved.

Chapter 2Normal Physiology:

Hypoxia


Topics

• Oxygen cascade from air-to-tissue

• Effects of reduced barometric pressure

• Alveolar ventilation equation• Hyperventilation• Acid-base changes• Control of ventilation


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


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


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


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


• Reasons why arterial gas approaches but does not equal alveolar– Diffusion limitation

(esp. at altitude)– Shunt

– VA/Q mismatching

Alveolar and arterial gas


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]


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


• 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


• 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


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


• 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


• Increase in HCO3-

– Vomiting• Move along line A to E

• Respiratory compenstaion– Hypoventilation– Move along line E to D– Base excess

Metabolic alkalosis


Control of Ventilation

• Basics– Ventilatory system can

defend against • Changes in PiO2

• Acid-base disturbances

– Precisely controlled• Central controller• Sensors • Effectors


• 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• 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



• 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”


• 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-



• 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



• 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)



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


• 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


• 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



• 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



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


• 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

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Chapter 2 Normal Physiology: Hypoxia

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