biology and environmental pathophysiology of hypoxia and environmental... · biology and...

Biology and environmental pathophysiology of hypoxia

Capita Selecta Dive Medicine

Malta 29-09-2016

Mattijn Buwalda Anaesthesiologist-intensivist & DMP

[email protected]

Runtime: 50 min

Slides: 44 Slides available at www.mattijnb.nl

• ischemia = insufficient blood flow

• hypoxemia = low pO2 in art blood

• asphyxia = no air entry lungs

• anoxia = extreme end of hypoxia

• hypoxia = low pO2 in tissues

– oxygen affinity hypoxia – stagnant hypoxia – hypoxic hypoxia – anemic hypoxia – environmental hypoxia

Semantics

Low inspiratory PO2:

physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

Atmospheric pressure

10.000 kg air = 100.000 N 100.000 n/m2 = 100.000 Pa 1000 hPa = 1000 mbar = 1 bar

1 Pascal = 1 N/ m2


• 1 N/M2 = 1 Pascal (Pa)

• 100 Pa = 1 hecto Pascal (hPa)

• 1 hPa = 1 millibar (mbar)

• 1000 mbar = 1 bar

• 1 bar ≈ 1 atm

1 atmosphere (atm)

(sea level/15oC)

= 1013,25 hPa

= 1013,25 mbar

= 1,01325 bar

= 760 mmHG

= 760 torr

= 14,696 psi 4

Atmospheric pressure physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

average pressure at sea level

Atmospheric pressure

Constituent Chemical symbol Mole percent

Nitrogen N2 78.084

Oxygen O2 20.947

Argon Ar 0.934

Carbon dioxide CO2 0.0350

Neon Ne 0.001818

Helium He 0.000524

Methane CH4 0.00017

Krypton Kr 0.000114

Hydrogen H2 0.000053

Nitrous oxide N2O 0.000031

Xenon Xe 0.0000087


Humidification

PPO2 dry air sea level: 0.21 x 760 = 160 mmHg (21.3 kPa) PPO2 tracheal air: 0.21 x (760 – 47) = 150 mmHg (20 kPa)


Alveolar air equation

modifiers: • oxygen consumption • alveolar ventilation

Healthy person at sea level PAO2 = 110 mmHg (14.6 kPa)


Venous admixture

Physiological: • bronchial veins • thebesian vessels

Pathological: alveolar collapse or infiltration


Shunt fraction

Normal value: 2-3%


A-a difference

A healthy young adult breathing air at sea level Blood gas: normal, PaCO2 = 40 mmHg, PaO2 = 100 mmHg

PAO2 = (0.21 x (760 - 47)) – (40/0.8) = 110 mmHg (14.6 kPa) A-a difference: 110 – 100 = 10 mmHg (1.3 kPa)

A patient on the ventilator with a bilateral pneumonia

FiO2 = 0.5 Blood gas: 7.34/ 55/ 80/28/+3 (in mmHg) 7.34/ 7.3/10.6/28/+3 (in kPa) PAO2 = (0.5 x (760 - 47)) – (55/0.8) = 287 mmHg (38 kPa) A-a difference: 207 mmHg (27.6 kPa)

A young healthy climber nearly on top of the Mount Everest (without supplemental oxygen) FiO2 = 0.21 8400 m, barometric pressure 272 mmHg (36.3 kPa) Averaged 4 men blood gas: 7.53/13.3/24.6/ 10.8/ -6.9 (SaO2 = 54%) PAO2 = (0.21 x (272 – 47)) – (13.3/0.8) = 30.6 mmHg (4.1 kPa) A-a difference: 30.6-24.6 = 6 mmHg (0.8 kPa)

Crocott MPW, et al. Arterial blood gases and oxygen content in climbers on mount Everest. NEJM 2009;360:140-149


Anaerobics physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

Pasteur point: 1.5 – 3 mmHg 0.2 – 0.4 kPa anaerobic glycolysis • less efficient • tissue acidosis

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Oxygen sensing physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

• peripheral O2 sensors

– carotid & aortic bodies

• cerebral O2 sensors

– hypothalamic, pons, medulla

– pre Bötzinger complex > gasping/ sighing

• pulmonal O2 sensors

– pulmonal vasculature

– hypoxic pulmonary vasoconstrictor response

• HIF

Hypoxic ventilatory response physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

• Effect: hyperventilation!

• 10% of respiratory drive

• relevant < ppO2 70 mmHg (9.3 kpa)

• blunted > ppO2 170 mmHg (22.6 kpa)

• enhanced by hypercapnia

• diminished: – in the very fit

– residence at altitude

– cyanotic heart disease

– narcotic abuse

Hypoxic pulmonary vasoconstriction physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

• vasoconstriction of pulmonary arterial vessels of alveoli with low PO2

• decrease shunting and improve oxygenation

• very effective in pneumonia, aspiration or atelectasis

• local and general effect

• side effect: pulmonary hypertension

Cardiovascular response to hypoxemia physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

• Increased sympathetic tone • SPO2 > 80%

– Increased heart rate and stroke volume – Normal blood pressure

• SPO2 60 – 80% – local vasodilation predominates – hypotension – tachycardia

• SPO2 < 60% – myocardial ischemia – arrhythmia, VF

Symptoms physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

Symptoms Signs

dyspnea tachypnea

restlessness tachycardia

palpitations dysrhythmias

confusion cyanosis

agitation hypertension

headache hypotension

tremor lethargy

asterixis coma

diaphoresis

[i] Pierson DJ. pathophysiology and clinical effects of chronic hypoxia. Resp Crit care 2000;45:39-53

the problem: • symptom threshold variability • hypoxia usually not recognized • 60% feel elated and hyperactive! • not well studied in diving

Aviation physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

5000 ft: impaired night vision 10.000 ft: drowsiness, poor judgement, impaired coordination and efficiency

15.000 ft: impaired flight control, handwriting, coordination, vision, cognitive functions especially decreased memory and judgement 20.000 ft: circulatory failure, convulsions, death

Time of useful consciousness: 10 seconds at 40.000 ft (13 km)

Na/K-ATPase physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

Mammalian ATP use: • 30% Protein synthesis • 28% Na/K -ATPase • 8% Ca-ATPase

Rolfe, D. F. S. and Brown, G. C. (1997). Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol. Rev. 77, 731–758.

Hypoxic and anoxic trics.... physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

oxyregulators • high obligatory energy

consumption • the warm blooded: mammals,

birds • Pasteur effect

– minutes in brain tissue – hours in muscle

• oxygen storage • dive response • hibernation • hypothermia • Ischemic preconditioning

oxyconformers

• anoxia induced hypometabolism

• cold blooded

• reduced energy turnover

• channel arrest

• protein synthesis arrested

• large glycogene stores

• lactate buffering

• alternative fermentation

The painted turtle (Chrysemys picta) physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

• facultative anaerobe • 3 months submerged in anoxic water • suspended animation • protein synthesis halted • channel arrest • lactate buffering by the shell • high antioxidant defences

Bickler PE, Buck LT. Hypoxia tolerance in reptiles, amphibians, and fishes: life with variable oxygen availability. Annu Rev Physiol. 2007;69:145-70.

weight 10.000 kg blood volume 20% Ht 52 myoglobin 56 gr/kg

68 ml O2/kg lungs 4% blood 38% muscle 58%

Kooyman GL, Ponganis PJ. The physiological basis of diving to depth: Birds and mammals. Annu Rev Physiol 1998;60:19-32

Sperm whale physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

Dive response • centralisation of circulation • heart, brain and lungs • peripheral anaerobic metabolism

Loss of consciousness (LOC) physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

hypoxia and unconsciousness

in unacclimatized individuals

PaO2 SaO2

mental function starts to

deteriorate

< 44 mmHg

(5.9 kPa)

< 80%

unconsciousness increasingly

likely

< 32 mmHg

(4.3 kPa)

< 60%

everybody unconscious < 23 mmHg

(3.1 kPa)

< 40%

Gibson GE, et al. Brain dysfunction in mild to moderate hypoxia. The American Journal of medicine. 1981;70:1247-1254

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Open circuit

Deep mix O2: 10% He: 50% N2: 40%

110 msw 12 bar ppO2 = 1.2 bar

surface 1 bar ppO2 = 0.1 bar

alveolair air equation: (0.1 x (760 – 47)) – (30/0.8) = 33 mmHg (4.5 kPa)


Theoretical time to LOC physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving

loop volume: 5L • 2 counterlungs • hoses • scrubber

lung volume: 2.5L (FRC)

rebreather • not switched on • O2 valve closed • air in loop 7.5 L

21% O2

1.6 L O2

O2 consumption diving: 20 ml/kg/min (6 MET) = 1.4 L/ min (70 kg) on the surface, choppy sea, heavy stages, stress)

Time to LOC < 1 min!

wet contacts Auto activation after 10 sec

Mitchell SJ, Bove AA. Medical screening of recreational divers for cardiovascular disease: consensus discussion at the DAN fatality workshop. Undersea Hyperb Med 2011;38:289-96

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Apnoea diving

24 mmHg (3.3 kPa) 36 mmHg (4.9 kPa)

Muth CM et al. Blood Gases during diving in elite apnea divers. nt J Sports Med 2003; 24: 104–107


Thank you for listening!

Slides available at www.mattijnb.nl

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