Biology and environmental pathophysiology of hypoxia and environmental... · Biology and...
Transcript of 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
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
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
• 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
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Oxygen cascade physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
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)
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Alveolar air equation
modifiers: • oxygen consumption • alveolar ventilation
Healthy person at sea level PAO2 = 110 mmHg (14.6 kPa)
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
V-Q scatter physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Venous admixture
Physiological: • bronchial veins • thebesian vessels
Pathological: alveolar collapse or infiltration
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Shunt fraction
Normal value: 2-3%
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
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
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Diffusion distance physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Krogh cylinder physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
enhance tissue oxygenation: • more capillaries • increase flow • reduce tissue edema • increase arterial PPO2
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
Microvascular autoregulation physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
• hypoxia and metabolites cause local vasodilation
• however, pulmonary vessels vasoconstrict!
• adenosine
Oxygen dissociation curve physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
right shift ODC increased: • temperature • CO2
• H+
• 2,3 DPG
RBC has no mitochondria 2-3 DPG is a by product of anaerobic glycolysis in the RBC tissue hypoxia increases RBC 2-3 DPG
Hypoxia inducible factor (HIF) physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Transcription factor > 60 genes
Hypoxia inducible factor (HIF) physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
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
Most symptoms are caused by compensation!
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
Channel arrest physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Boutilier RG. Mechanisms of cell survival in hypoxia and hypothermia. The Journal of Experimental Biology 2001;204: 3171–3181
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.
Carassius carassius physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
• metabolic suppression to 30% of normal • months at almost anoxic conditions • remains active during anoxia • large glycogen stores • no lactate but alcohol!
the Crusion carp
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
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)
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Semi Closed Rebreather physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Closed Circuit Rebreather physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
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
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
physics | oxygen cascade |biochemistry |compensation |symptoms |evolution | preconditioning | hypoxia in diving
Thank you for listening!
Slides available at www.mattijnb.nl