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Physiology inextreme conditions
http://physiology.lf2.cuni.cz/
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Which extremes?
Just about any environmental variablecan reach extreme values
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Stages of response to
extreme exposition Acute reaction
Adaptation
Exhaustion
Evolutionary" adjustments
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Acute (emergency")
reaction
Maximal use of reserves,
non-specific stress response
e.g. fall into icy water
Usually cannot be sustainedpermanently
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Exhaustion
Too long/strong exposure
e.g. Titanic sinking victims
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Adaptation (resistance)
Selective strengthening of the mostadvantageous specific means of defense
e.g. winter swimming in Vltava river
Has limits
e.g even winter Vltava swimmers wouldnt havesurvived Titanic sinking
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Evolutionary" adjustments
Species/population for many generations
e.g. Inuit
more resistantto cold
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Low partial pressure of O2
High altitude Lung & heart diseases
Air travel
Decompression Cabin pressure normally ~1800-2500 m
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Extreme altitude> 5 800 m
High altitude> 3 000 m
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Altitude hypoxia
Atmosphere: 21 % O2 up to ~ 110 km
Air is compressible
Therefore less molecules in the same
volume at lower pressure - thus also lessO2 molecules
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Additional factors in high
mountains Cold (~1oC every 150 m) humidity
Sun radiation (esp. UV) smaller portion filtered by air
reflection from snow
Bacteria & alergens concentrations
withaltitude(sterile air on Jungfrajouch 3450 m)
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Acute response to altitude
Above 3 700 m: muscle fatigue
dizziness
mental capacity
(judgement, memory, fine movements) Contributes to mortality at extreme altitudes
Slowly reversible(cognitive abnormalitties 1 year after Everest)
nausea
euforia
headache
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Acute response to altitude
> 5 500 m: cramps, seizures
> 7 000 m: comma
(when SaO2 ~ 40-50 %)
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Adaptation
PO2
0
50
100
150
inspire
d
alve
olar
arterial
capilla
ryve
nous
Air/blood
0 m
4540 m
6700 m
slope of O2cascade
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0
100
200
300
400
500
-2 0 2 4 6 8 10 12 14 16 18 20 22
1. lung ventilation
chemosensors
CO2 exhalation -> pH -> breathing center
bicarbonate in CSF( pH)
(kidneys)
days at altitude
ventilation
(% of normal)
(Hb dissociation curveshifts left)
Periodic breathing at night (Cheyne-Stokes respiration)
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Hyperventilation
Usually only > 3000 m
Reduces inspired - alveolar PO2 difference
Probably not necessary weak in some top mountaineers
(Peter Habeler - first on Everest w/o O2 - 1978with Messner)
altitude natives < lowland people
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Carotid body hyperplasia
0
10
20
30
40
0 m 4330 m
Weigth of carotid bodies (mg)
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2. erythropoiesis
0
20
40
60
0 m 4540 m
Hematocrit (%)
0
5
10
15
20
0 m 4540 m
Hb (g/100 ml)
Initially dehydration ( drinking, ventilation) -> plasma volume -> relative [Hb]
Soon RBC formation
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Hypoxia stimulates
erythropoietinPlasma erythropoietin
80
100
120
140
160
180
200
-1 0 1 2 3 4 7 8 9
Days at altitude
6 000 m
4 500 m
3 500 m
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3. gas diffusion to blood Normal ~ 21 ml O2/mmHg/min,
3x Lung distension by hyperventilation
-> alveolar surface
Relative lung growth Pulmonary hypertension -> dead space (zones)
Diffusion can limit oxygenation during exercise
at extreme altitudes: A-a PO2
faster RBC transit through lung capillaries
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4.
tissue capillarity VEGF (HIF-1)
diffusion distance
Small SBP (~10 mmHg)
More pronounced in altitude natives
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5. O2extraction &utilization in tissues
Crucial
Unclear:-
(
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Additional effects of
hypoxia Weigh loss (anorexia, dehydration)
Fertility , menstrual disorders, smaller
newborns (HFPV?) Often patent ductus arteriosus
(normally closed by normoxia)
Pulmonary hypertension Right ventricle hypertrophy
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Hypoxia slows PAP afterbirthPulmonary artery pressure (PAP)
(mmHg)
0
20
40
60
80
0 7 15 23 31
Age (years)
4540 m
0 m
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Hypoxia slows right ventricle
weigh
after birthRV weigh
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 1 2 3 4 5
Age (years)
~4000 m
0 m
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Adjustments of populations 4570 m highest permanent settlement in Tibet
5330 m highest permanent settlement (Andes)
5790 m highest permanent workplace (Andes,miners sleep at only 5330 m)
Adaptation from birth better than (even a longone) later
large chest, small body
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Disorders of adaptation
Acute mountain sickness
High altitude pulmonary edema (HAPE)
High altitude brain edema
Chronic mountain sickness
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Acute mountain sickness
Acclimatization slower than ascent
Frequent, esp. after quick ascent 15-25 % of travelers to 2000-3000 m
up to 67% of travelers to 4300 m
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Acute mountain sickness:
causes Not quite clear
Probably light edema of brain (& lung& legs)
Excessive hypoxic vasodilation?
Also oliguria (unclear cause)- Na+ & water retention
M h i f t
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Mechanisms of acutemountain sickness
cerebral blood flow
ACUTE MOUNTAIN SICKNESS
Inadequate buffering by CSF
Brain swelling
cerebral blood volume blood-brain barrier permeability
Hypoxemia
HYPOXIA
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Acute mountain sickness:
signs & symptoms
Usually starts within 6 hr, but can
start after 12-24 hr
Culminates on day 2-3
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Acute mountain sickness:
signs & symptoms (at least 3) Headache most frequent (~70% of travelers above 2500 m)
can be very strong
Insomnia >30% of cases
Excessive fatigue
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Acute mountain sickness:
signs & symptoms Dyspnea, esp. on exertion ~20% SaO2 usually ~normal
Loss of apetite
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Acute mountain sickness:
signs & symptoms Disorientation Loss of concentration
Oliguria
Caugh
Chest pain
Tachycardia
Palpitations
Swollen legs
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Acute mountain sickness:
treatment Usually spontaneous recession in 3-4 days
O2 not much help
Diuretics Rest
Pause ascent until symptoms leave!!!
(otherwise risk of HAPE, HACE, +) If no improvement, descend
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Acute mountain sickness:
prevention Slow ascent Sufficient drinking, not
alcohol
In some casescarboanhydrase inhibitoracetazolamide bicarbonate excretion pH (metabolic acidosis) breathing
0
10
2030
40
50
6070
Placebo Acetazolamide 250 mg
2x/d
AMS score 24 hr at 3630 m (% at 0 hr)
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HAPE
Non-cardiogenic pulmonary edema Very different from other types First 2-4 days of ascent (usually quick) above
~2500 m,most often 2nd night
Incidence 15% Without treatment fatal within hours
(exceptionally even with it; most frequent causeof death at altitude),otherwise complete cure w/o consequences
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HAPE: mechanisms
~uneven HPV localizedhyperperfusion pressure
hypoxic pulmonaryvenoconstriction?
Hypoxic
permeability of lungcapillaries
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HAPE diagnosis
Extreme fatigue, weakness, cough, dyspnea atrest, chest congestion Loud breathing, central cyanosis (lips, nails),
arterial desaturation, tachycardia, tachypnea
Fever, pink sputum
Symptoms similar to MI, pneumonia, embolism(relat. frequent due to dehydration &polycythemia) - suspect if no improvement withdescent
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Management of HAPE
Treatment: Immediate DESCENT !!!
(down where last time no problems)
O2 (field hyperbaric chamber) Nifedipin (inhibits HPV, but systemic hypotension!)
Experimental: gingko, -agonists
Prevention: Slow ascent
2 nights at 2500-3000 m before further ascent Above 3000 m dont sleep >300-400 m higher than previous
night
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High altitude brain edema Rare, sometimes together with HAPE After continuing ascent with acute mountain
sickness
Symptoms similar to hypothermia (errors indiagnosis easy) strong headache irrationality, confusion, lethargy
delusions cerebelar ataxia (chaotic movements as if drunk) retinal bleeding
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High altitude brain edema
Treatment: Immediate DESCENT!!!
O2
Dexamethasone
Prognosis: Without treatment
fatal within hours With therapy usually
cure w/o consequences
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Main rules to high altitude
With acute mountain sickness haltascent!
With worsening, descent!
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Chronic mountain sickness polycythemia
pulmonary hypertension
right ventricle hypertrophy
Congestive right ventricle failure
Prevalence ~ 5-18 % above 3,200 m
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Causes of chronic mountain
sickness Unclear
Perhaps excessive "adaptation
(weak mechanisms limiting adaptation- NO, PGI2,...?)
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Extreme altitudes Above ~5800 m: complete adaptation
impossible
rapid worsening of weakness, mental state,
anorexia, exhaustion, dyspnea, headache Above ~7900 m struggle for life; delusions,
poor judgment
Sudden exposure (decompression):at 10 km unconsciousness within 30 sec
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High pressure: diving
Also building tunels
(high pressure against water seeping)
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High pressure chambers
Max 0.3 MPa, 120 min
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Hyperbaric oxygenotherapy
CO & cyanide intoxications
Air embolism
Anaerobic infections Traumatic ischemia (crush syndrome) after heavy injury to extremity & its
circulation, often with infection Ischemic disease of the leg
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How long underwater?
Dolphin: 2 hr Whale, seal: 18 min
Beaver, duck: 15 min
Rat, rabbit, cat, dog: 2-4 min
Man: ~1 min Synchronized swimming: PaO
230-35 mmHg
Korean pearl divers: 2 min(20 m, 20x/hr)
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Under surface
Pressure by 1 atm per each 10 m
To prevent lung collapse, the inhaled
mixture must come under
pressure
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pressure -> gas density At 4 atm: 2x work of respiratory muscle
to move air through airways
Plus the need to move air in added deadspace
Together with breath-holding causes CO2
retention -> unconsciousness He has density than N2
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High PO2
e.g. PO2 at 40 m:21% O2, 5 atm ~ 100% O2, 1 atm
O2 radical productionovercomes cellular defenses
Worsened by exercise
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High PO2 60% O
2at 1 atm:
OK even for a long time (adults)
PO2 760 mmHg (100% O2 at 1 atm) pharyngitis, tracheitis after ~8 hr then atelectasis, lung edema, mental
activity
100% O2 at >1.7 atm (~30 min):
irritation, nausea, dizziness, muscle cramps& seizures, vision problems, disorientation,unconsciousness
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Nitrogen narcosis
Air breathing at 4-5 atm
Similar to alcohol: euphoria, confusion,
sleepiness, motoric coordination & strength
By dissolving in cell membranes ofneurons, nitrogen reduces theirexcitability (similar to volatileanesthetics)
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Decompression sickness Bubble formation during surfacing in blood
& tissues from supersaturated gas
solution created during exposure to pressure
Pain in muscles, joints, paralysis, collapse,unconsciousness; dyspnea, lung edema,embolism
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Decompression sickness
Only after a longer exposure it takes time for nitrogen to saturate body
fluids (poor solubility) esp. little vascularized fat (easiest for N2
to dissolve in)
Worsened by activity
He dissolves less than N2
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Decompression sickness Therapy:
Recompression & slow decompression in hyperbaricchamber
Can be accelerated by hyperbaric O2 no more N2 is supplied
gradient N2 between bubbles & their surroundings
difuse O2 into obstructed areas
Prevention slow surfacing
days/weeks in hyperbaric tanks
D i ft 1 h t
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Decompression after 1 hr at60 m
-60
-50
-40
-30
-20
-10
0
-80 -50 -20 10 40 70 100 130 160 190
Doba(min
)
Depth (m)
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He instead of N2 density
work of breathing CO2 retention voice pitch communication
solubility narcotic effect
decompression sickness
heat conductivity risk of hypothermia
High pressure nervous
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High pressure nervoussyndrome (HPNS)
Below 130 m
Hyperexcitation of nerves by pressure
hand tremor nausea, dizziness
Worse with faster descent
Reduced by blunting effects of N2(-> Trimix)
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Depth of divewith variousgas mixtures
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BarotraumaDue to gas pressure change where it cannotequilibrate with surroundings:
nasal cavities
rotten teeth middle ear (obliteration of Eustachs tube)
bowel gases
alveoli (if no exhalation during ascent)
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Submarines
Emergency escape
Inner environment(e.g. CO in cigarette
smoke)
QuickTi me and a Video decompressor are neede d to see thi s picture.
E f b
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Emergency escape from subs From 100 m possible
without devices
During ascent gas in lungsexpands
Constant exhalationnecessary
That also removes CO2 need for inhalation
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QuickTime and a Video decompressor ar e needed to see this pic ture.
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Gravitational acceleration
Car accidents, falls,rockets (3-8 G), airplanes
G = multiple of normal gravitationalacceleration
+ in the direction head -> feet,
- opposite direction
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Positive longitudinal G
Sitting man:
4 G ~ 40-50 sec
15-20 G ~ 1 sec(less if standing)
P iti l it di l G
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Positive longitudinal G2 G:
heavy, difficult to move extremities3-4 G:
upright posture is a problem keep the eyes open is difficult breathing is difficult
4-6 G: blackout in several sec
20 G: vertebral fracture
Black out"
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Black-out
+5G: pressure in leg veins 450 mmHg distension of veins of legs and abdomen
blood shifts downwards
drastic venous return
blood pressure to ~20 mmHg(transient, quick partial by baroreceptors)
blood flow to brain & retina
seeing gray -> loss of vision
Positive longitudinal G
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Positive longitudinal G
Partially helped by anti-G suit pushes water or motorized cushions at legs &
abdomen does not prevent downward shift of heart &
diaphragm
(thus limit ~10 G)Training:
abdominal compression by bending forward andcontraction of abdominal muscles
thoracic pressure
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Positive transversal G
Rocket launch almost 10 G
Best G tolerance lying (10-17 Gup to 3 min)
Most difficult:
breathing hypoventilation
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Negative G
Less tolerated than + G High pressures in brain vessels
despite cerebrospinal fluid centrifuged in
the same direction but not in retina -> red-out
Facial swelling, risk of brain bleeding
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Red-out"
Excessive blood flow to retina
Seeing red
Loss of vision quickly follows
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Weightlessness
(microgravity) Position sensing
Water shifts
Bones & musclesDenis Tito on orbit
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Challenges in space
Acceleration on launch & re-entry
Microgravity
Radiation but e.g. in Appolo flights less than in
rtg diagnostics
worse in longer flights
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Position sensing
Middle ear semicircular canals
otholites Mechanoreceptors in muscles &
tendons
Tactile receptors in skin (e.g. feet) Visual cues
Position sensing in
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Position sensing in
microgravity Dissociation of gravitationally-dependent
and visual cues
Defects of spatial orientation Shaking the rocket instead push-ups Sudden flip upside down on entry to
microgravity Finally: down is where the feet are
Syndrome of adaptation to space
S d f d t ti t
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Syndrome of adaptation to
space Sea sickness from dissociationbetween visual, tactile & gravitational cues
Loss of appetite, sweating, upset stomach,
dizziness, headache, attention deficits,nausea, vomiting
Starts in 1 hr - 2 dlasts up to 4 d, ends spontaneously
~50% of astronauts Can be simulated by virtual reality
W t hift
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Water shifts
H2O moves (head, chest)
Each leg looses ~1 l of fluid - 10% of itsvolume - during the 1st day
Aided by chest volume ( weight of
its wall) Prevention: H2O intake
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Water shifts in microgravity
Face swelling, nasal congestion, runnynose for the whole flight
chest blood volume stroke volume & cardiac output CO eventually (inactive muscles do not
need much)
H O in upper parts of body
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H2O in upper parts of body pressure in afferent arterioles glomerular filtration (by 20%)
aldosterone
plasma volume (by 10-20%)tissue dehydration Normalizes soon after return
However, at first orthostatic intolerance( stroke volume when standing due to bloodvolume & its shift downwards)
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Heart
blood volume
energy expense of movement & posture
demands on heart size & effectiveness of the heart
Normalization within a few weeks afterreturn
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Bones & muscles
Astronauts grow taller(no pressure on spine)
~1-1.5 % of bone mass (& Ca2+)lost/month for the whole flight
Not stopped by vigorous exercise, onlyslowed down
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Bone mass loss
Stops ~1 month after return
Completely reversible ???
Osteolysis: plasma Ca2+
-> kidney stone risk
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Muscles in microgravity
Atrophy Slow (body weight support) change to
fast myosin proteosynthesis
Less vessels &neuromuscular junctionsin muscles
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Heat
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Heat
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Dry heat
Typically deserts (1/5 of land),elsewhere
Man probably evolved in arid areas Sunny seaside beach 4x more
radiation (reflected) than on a
meadow
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Thermoregulation control
Hypothalamic centers front - response to heat
rear - response to cold
Blood temperature sensors in hypothalamus &large vessels
Sympaticus:
periferal arterioles (NA) sweat glands (ACh)
Heat loss
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Heat loss
Conduction insufficiently effective from deeper layers
Radiation
Evaporation skin humidity, sweat glands
skin vasodilation( cardiac output, visceral vasoconstriction-> GI discomfort)
works even whenbody temperature > surrounding temperature
Cooling:
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Cooling:mainly sweat evaporation
0
0.5
1
1.5
2
2.5
l/hod
sit
shade
sit sun walk
shade
walk
sun
walk
sun 11
kg
walk
sun 18
kg
35 C
45 C
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Additional mechanisms
Heat loss by evaporation fromrespiration - not much important in
humans(only minimal respiration)
heat production by reducing activity
- second line of defense
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Heat cramps
From low blood NaCl(mechanism unknown, but NaClreplenishment is the only effective therapy)
NaCl can be diluted by increased waterdrinking
Abdominal can resemble sudden abdominalevents, in legs similar to exhaustion cramps
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Adaptation to heat
Within 1-3 weeks
NaCl loss via sweat & urine( aldosterone)
maximal sweating capacity (2x)
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Hyperthermia
Briefly 43oC (hypothalamus) - OK(adults)
Longer >40oC damage to hypothalamiccenter thermoregulatory failure
Overheating
metabolism overheating
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Hyperthermia
Nerves most vulnerable
Apathy, irritation, nausea/vomiting,
headache, seizures, delirium,unconsciousness, +
Often worsened by circulatory failure
Help: cooling preferably by ice (more gentle cooling can be
negated by skin vasoconstriction)
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Wet heat
Relatively little natives in rain forests (30 % ofland), perhaps forced there by more successfulcompetition
Small variation of air temperature around skintemperature, humidity 70-100%, no wind, butlittle direct sun radiation
Adaptation much more difficult than to dry heat(ineffective sweating)
ld
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Cold muscle tone ( heat production)
Shiver - essential
simultaneous twitches of antagonistic muscles heat production 2-3x
with adaptation, more shiver of muscles inside thebody - more effective warming of body core
Non-shivering thermogenesis(brown fat, muscle?)
H h
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Hunting phenomenon
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