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Environmental Variables vs. Physiological Control

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Presentation on theme: "Environmental Variables vs. Physiological Control"— Presentation transcript:

1 Environmental Variables vs. Physiological Control
Pressure (760 mm-Hg) Hyperbaric vs. Hypobaric Temperature (22°C) Hypothermic vs. Hyperthermic Gas composition (78% N2, 21% O2) Hypoxic vs. hyperoxia Nitrogen saturation Gravity (1 x G = 9.8 m/s2) Hypogravity vs. hypergravity

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3 High Altitude and Hypoxia
Oxygen availability drops with altitude 21% of absolute pressure O2 concentration in alveoli is what counts Water vapor remains constant at 47 mm-Hg CO2 partial pressure drops with increased respiration rates CO2 and H20 partially displace O2

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5 Compensation Mechanisms
System control – keep arterial O2 high Acute compensation for low PO2 Hypoxic stimulation of arterial chemoreceptors increases respiration rate (i.e., breath faster)

6 Compensation Mechanisms
Long-term compensation for low PO2 Chemoreceptor mechanism further increases due to decrease in blood pH (days) Increased hematocrit and blood volume (weeks) RBC production increases via erythropoietin PO2 sensed produced in kidneys acts on hematopoietic stem cells Blood volume under hormonal control of kidneys

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12 Compensation Mechanisms
Long-term compensation for low PO2 Increased diffusion capacity of lungs Increased capillary volume Increased lung volume Increased pulmonary pressure Increased capillarity in tissues Stimulate angiogenesis – growth of new capillaries Feedback control in local tissue beds More effective in young, developing animals/people

13 Compensation Mechanisms
Native adaptation to high altitude All the same compensations of acclimatization plus: Larger chest cavity Larger heart, especially right side Increased cellular efficiency to use O2

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15 Acute High Altitude Sickness
Cerebral edema Hypoxia-induced vasodilatation, high capillary pressure and edema – bad news. Pulmonary edema Vasoconstriction in pulmonary capillaries leads to increased blood pressure in open capillaries leading to edema – bad news. Breathing oxygen, especially under pressure, can reverse symptoms

16 Microgravity Gravity (as any force) can have only two effects
Cause loading (usually with deformation) Cause motion

17 Space Flight and Physiological Effects

18 Neurovestibular Effects
Affects about 50% of astronauts Symptoms begin around 1 hour – recovery occurs around 1-3 days Relates to otolith organs in vestibular apparatus Provoked by movements and/or odd orientations Re-adaptation to 1G can also be challenging

19 Vestibular Apparatus

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22 Theories on Space Motion Sickness
Fluid shift – Cephalic blood movement Sensory conflict – Visual or somatosensory vs. vestibular cues Otolith organ asymmetry – Differences in signal between right and left sides

23 Treatment of Space Motion Sickness
Screening has proven ineffective Training strategies have been studied Drug combinations are commonly used May delay adaptation Astronauts must tough it out

24 Spaceflight Bone Loss Spaceflight (Unloading): 0.5-2% per month
Type I Osteoporosis (Post-Menopause): 20% Tot, 5-7 years, 3-4% per yr. Type II Osteoporosis (Age related): ~1% per year, ongoing

25 Bone Feedback Control System
Hormones / Cytokines Streaming flows and osteocytes deformed Bone mechanical properties Canaliculi network resistance External Loads Strain (Deformation) SGPs or direct strain - Osteoclasts Osteoblasts - + Osteocytes produce Nitrous oxide / Prostaglandins Hormones / Cytokines Osteocytes produce sclerostin

26 Skeletal Response to Exercise
30 Moderately Active Sedentary Bone density (%) Normal Range Lazy zone Spinal injury, immobolization, bed rest, space flight. -40 Changes only occur with significant habitual changes in activities over several months

27 Plasma Calcium Effects
Calcium lost in urine - ~200mg/day Less calcium absorbed – lost in feces Plasma calcium increases in-flight Is normal shortly after landing May be at greater risk for kidney stones PTH is unchanged or decreased in flight but elevates rapidly post-flight (2x) Calcitonin is increased in flight (45%)

28 Femur Mineral Mass Mass (mg) Flight AEM GC Viv GC D D D SF SF Placebo
23.00 D Placebo OPG 22.00 D 21.00 D SF SF Mass (mg) 20.00 19.00 18.00 17.00 16.00 Flight AEM GC Viv GC

29 Elastic Strength

30 Formation of Cortical Bone: Bone Formation Rate
SF SF D 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 Flight AEM GC Viv GC En.BFR (0.001xmm 2 /day) Placebo OPG

31 Muscle Response to Spaceflight
Without resistive exercise for 2-3 months Leg muscle cross-sectional area ↓ ~30% Leg strength ↓ ~50% Shift occurs from slow to fast fiber types Back muscles become weak, soft tissues at risk of injury Astronaut muscle fiber cross sections Before Flight After Flight From Space Research News, Winter, 2001 Dan Riley, The Medical College of Wisconsin and Riley et al., 2002

32 Pattern of atrophy (Type I > Type II) may differ between species
From Fitts, Riley and Widrick, (2000), J Appl Pysiol, 89: Similar levels of muscle atrophy occur in mouse (12 days), rat (14 days) and human (17 days) soleus \ Pattern of atrophy (Type I > Type II) may differ between species

33 AEM Control SF 5-10 fold increase in expression of MHC-IIx and –IIb in soleus but not plantaris or gastroc Similar shift to fast isoforms as seen in other species

34 Summary of Muscle Feedback
Circulating IGF-1 Insulin IGF-1 + External Loads / Demands Muscle Strength (PCSA) Transduction * Mechanical * Electrical Myostatin - Protein Synthesis Muscle Hypertrophy - Protein Degradation + - Muscle Hyperplasia - Satellite Cell Activation

35 Astronaut Fitness - Muscle
Reduce health risks to acceptable limits Maximize crew time availability for mission ISS crew expected to exercise 2.5 hours/day, 7 days per week Too much exercise can be a physical and psychological burden Crews should not have to rely on exercise Crisis or emergency situations Injury or illness

36 Manned Mission to Mars - an Ambitious Objective
MISSION TIMES Outbound 313 days Stay 40 days Return 308 days Total Mission 661 days MISSION TIMES Outbound 180 days Stay 545 days Return 180 days Total Mission 905 days Sun g Sun g Arrive Earth 12/11/20 Arrive Earth 11/28/32 Depart Mars 1/25/32 Depart Earth 2/6/31 Arrive Mars 11/7/18 Arrive Mars 12/16/31 Depart Earth 5/11/18 Depart Mars 6/14/20 Example Short-Stay Mission Example Long-Stay Mission Preserving Astronaut health / fitness is major challenge Credit : John Connolly and Kent Joosten Presentation Title:  Human Mars Mission Architectures and Technologies Meeting: 1/6/2005 meeting of the Robotic and Human Exploration of Mars Roadmap Committee

37 Hindlimb Suspension Effects
Muscle Mass 7.9 10.9 2 4 6 8 10 12 14 16 US P TS P Soleus Wet Mass (mg) Isolated Muscle Strength Whole Animal Leg Strength

38 Myostatin Blockade Total Body Mass

39 Myostatin Blockade Lean Body Mass
US > TS P<0.001 D > P

40 Motor Control Movement shifts from lower to upper body
Weight of limbs is eliminated Neck and hips become flexed

41 Motor Control Effects of space flight include Short term Longer term
Activation of extensor muscles is reduced Longer term Reflexes are affected – Achilles tendon tap Magnitude of movement is reduced Sensitivity to tap is reduced Amplitude of induced electrical response is reduced Post-flight Increased rate of tremors Time to make postural changes increases 2-3 x

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43 Factors governing cardiac function and peripheral flow
Cardiac Contractility (CC) End Diastolic Volume (EDV) Heart Rate (HR) Stroke Volume (SV) Cardiac Output (CO) Total Peripheral Resistance (TPR) Blood Pressure (BP) – Systolic and Diastolic Control of cardiac function – intrinsic and extrinsic

44 EDV X SV X CO CC HR X BP TPR

45 EDV X SV + X CO CC HR X BP + TPR

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47 - - - + SNS PNS + Baroreceptors EDV X SV + + X CO CC + HR X BP + - TPR

48 Short term response to space flight (post-insertion to days)
Post Insertion (minutes to hours) Loss of hydrostatic pressure Cephalic fluid shift Heart volume increases Increased EDV causes decreased HR and cardiac contractility (CC) CVP decreases (unexpected response) Physiological response is comparable to laying down (or standing on one’s head) in 1-G

49 Short term response to space flight (post-insertion to days)
Short Duration Response to Microgravity (hours to days) Fluid shift maintained (facial puffiness, engorged veins, sinus congestion) Increased diuresis Decreased water intake Loss of blood plasma volume and total body water EDV decreases leading to increase in HR over time

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51 On Orbit — Fluid Loss Total loss of fluid from the vascular and tissue spaces is about 1-2 liters (about a 10% volume change compared to preflight) Photo NASA Adapted from Lujan and White (1994)

52 Long term adaptation to space flight (weeks to months)
Continued increase in HR Decrease in baroreceptor reflex function Exaggerated response to LBNP (ΔHR) Cardiac system tends to stabilize Heart volume decreases (atrophy?) Heart rhythm disturbances (?) Disproportionate loss of red blood cell mass (?) Changes in vasculature (peripheral resistance?) Increased venules and decreased arterioles

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54 Anemia of Spaceflight Normal Erythropoietin Level Erythropoietin Level Landing Launch Microgravity Mission Day Adapted from Lujan and White (1994) Erythropoietin is a hormone which stimulates red blood cells production The loss of fluid in the plasma concentrates red blood cells The body responds by decreasing the erythropoietin level Upon landing, when the fluid lost during spaceflight is replaced, the red blood cells are diluted. A 10% decrease in red blood cell count is observed. This causes the phenomena called the “anemia of spaceflight” The body responds to this dilution by increasing the erythropoietin level

55 Post Flight Effects / Recovery
Orthostatic Intolerance (hours) Fluids shift to lower extremities EDV decreases causing increased HR Control of BP may not be adequate Syncope potential Weakened leg muscles results in reduced venous valve blood pumping action

56 Tilt Test After days of bed rest, orthostatic intolerance is evaluated by suddenly tilting the subject from the supine to the upright position Heart rate increases and blood pressure decreases, causing dizziness (pre- syncope) or loss of consciousness (syncope) This orthostatic intolerance also occurs in astronauts when they try to stand immediately after spaceflight Documents MEDES Results after 5-16 day missions Pre-syncopal women Pre-syncopal men Non-pre-syncopal men 100% 20% 80%

57 Syncopy / Pre-syncopy Astronauts
Low total peripheral resistance before and after space flight Strong dependence of standing stroke volume on plasma volume (r=0.91 in pre-syncopal women vs. r=0.17 in non-pre-syncopal men) Deficient norepinephrine release response

58 Post Flight Effects / Recovery
Elevated HR (several days) Similar to disuse / sedentary effects Anemic-like conditions after rehydration (RBC dilution) Duration of the recovery period depends on duration of exposure to reduced-gravity

59 Countermeasures to Cardiovascular Deconditioning
In-flight Exercise Lower Body Negative Pressure Device (LBNP) Russian Chibis (LBNP) and Penguin (elastic load) suits Neck cuff (positive or negative pressure) Thigh cuffs Pre-landing Saline fluid loading G-suits (positive pressure, lower torso) Recumbent seating (ISS crew members) Post-mission Exercise, time


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