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Environmental Variables vs. Physiological Control

Environmental Variables vs. Physiological Control. Environmental variables Pressure (760 mm-Hg) Hyperbaric vs. Hypobaric Temperature (22°C) Hypothermic vs. Hyperthermic Gas composition (78% N 2 , 21% O 2 ) Hypoxic vs. hyperoxia Nitrogen saturation Gravity (1 x G = 9.8 m/s 2 )

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Environmental Variables vs. Physiological Control

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  1. Environmental Variables vs. Physiological Control • Environmental variables • 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

  2. 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

  3. 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)

  4. 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

  5. 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

  6. 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

  7. 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

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

  9. Space Flight and Physiological Effects

  10. 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

  11. Vestibular Apparatus

  12. 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

  13. 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

  14. 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

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

  16. Skeletal Response to Exercise 30 Moderately Active Sedentary Bone density (%) 0 Normal Range Lazy zone Spinal injury, immobolization, bed rest, space flight. -40 • Changes only occur with significant habitual changes in activities over several months

  17. 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%)

  18. Femur Mineral Mass 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

  19. Elastic Strength

  20. 5.50 SF 5.00 4.50 /day) SF D Placebo 4.00 2 SF OPG 3.50 3.00 SF D En.BFR (0.001xmm 2.50 2.00 1.50 1.00 Flight AEM GC Viv GC Formation of Cortical Bone: Bone Formation Rate

  21. 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 sectionsBefore Flight After Flight From Space Research News, Winter, 2001 Dan Riley, The Medical College of Wisconsin and Riley et al., 2002

  22. 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 From Fitts, Riley and Widrick, (2000), J Appl Pysiol, 89:823-839.

  23. SF AEM Control • 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

  24. Summary of Muscle Feedback Circulating IGF-1 Insulin + IGF-1 Transduction * Mechanical * Electrical External Loads / Demands Muscle Strength (PCSA) Myostatin -  Protein Synthesis  MuscleHypertrophy  - ProteinDegradation - + MuscleHyperplasia - Satellite CellActivation 

  25. 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 Astronaut Fitness - Muscle • Reduce health risks to acceptable limits • Maximize crew time availability for mission

  26. Sun Sun g g 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 Manned Mission to Mars - anAmbitious Objective Arrive Earth 12/11/20 Arrive Earth 11/28/32 Depart Mars 1/25/32 Arrive Mars 11/7/18 Depart Earth 2/6/31 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

  27. 16 14 12 Soleus Wet Mass (mg) 10 8 6 4 2 7.9 10.9 0 TS P US P Hindlimb Suspension Effects Muscle Mass Isolated Muscle Strength Whole Animal Leg Strength

  28. Myostatin Blockade Total Body Mass

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

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

  31. Motor Control • Effects of space flight include • Short 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

  32. 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

  33. X X X EDV SV CO CC HR BP TPR

  34. X X X EDV SV + CO CC HR BP + TPR

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

  36. 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

  37. 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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