Biology 350: Biology & Space Exploration

Biology 350: Biology 350: Biology & Space ExplorationBiology & Space Exploration

Biology 350: Biology 350: Biology & Space ExplorationBiology & Space Exploration

Col Ronald D. Reed, PhDProfessor & Head of Biology

U.S. Air Force Academy 1999

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1. Define key terms/concepts

2. Describe muscle structure & function; explain how normal hypertrophy occurs

3. Describe muscle fiber types and how contraction & relaxation occur (isometric vs. isotonic; concentric vs. eccentric)

4. Explain atrophy with disuse or disease on Earth; compare to selective atrophy of spaceflight (muscle types & groups); discuss possible mechanisms

5. Describe the adaptation to different loading conditions on Earth & in microgravity

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6. Describe bone & connective tissue structures

7. Discuss mechanisms linking physical activity/ stress to the maintenance & reformation of bone

8. Explain bone loss in microgravity, including its long-term impacts; relate to hormonal or other changes

9. Explain the role of intervertebral discs in weightbearing and spinal movements; correlate to mechanisms of spinal lengthening and back pain in space

10. Discuss countermeasures and evaluate their effectiveness vs. musculoskeletal changes in space

Some mission patcheswhen effects were

studied

Skeletal Muscle FunctionsSkeletal Muscle Functions

Exert force to change joint angle Concentric - muscle shortening Eccentric - muscle lengthening

Exert force to maintain joint angle - isometric (static tension)

Produce body heat

Review of AnatomyReview of Anatomy

Whole Muscle Muscle fiber (cell) Myofibril Sarcomere Myofilaments

Myosin Actin Cross-bridging & “ratcheting”

Z membrane(end of sarcomere)

Cross-bridgeBinding Site(need Ca2+)

Thick Filament (myosin)

Thin Filament (actin)

Muscle contractionMuscle contraction

Coupled reaction:

Chem. energy physical motion

ATP hydrolysis force

[Ca2+] in cell allows reaction

Slow- & fast-twitch muscle specializations

Twitch Rate Slow FastGlycogen Content Low HighGlycolytic Capacity Low HighFatigue Resistance High LowRespiration Type Aerobic AnaerobicCapillary Supply High Low

Slow- & Fast-Twitch MusclesSlow- & Fast-Twitch Muscles

Slow-twitch found more in muscles (like postural muscles)that must sustain contractions for long times without fatigue.Depend relatively more on fats for energy.

Atrophied Fiber

Control Fiber

Force (% of Peak Force)

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Studies of Rat Hindlimb Muscle, Nerves, Biomechanics, etc.

Studies of Rat Hindlimb Muscle, Nerves, Biomechanics, etc.

Focus on antigravity (postural) muscles

Why hindlimb? In g rats use forelimbs to move in cages; hindlimbs float except for grasping. Also, have Earth model.

Results:

Significant atrophy, protein & mass

Shift in major muscle fiber type (ST FT)

capacity to break down certain nutrients & some shift from fat to glycogen use in ST

Studies of Rat Hindlimb Muscle, Nerves, Biomechanics, etc.

Studies of Rat Hindlimb Muscle, Nerves, Biomechanics, etc.

More Results: Muscle atrophy in g not returned

to normal in 14 days back on Earth susceptibility to damage

on return to Earth Interstitial edema & lesions in

sarcomeres developed postflight -- damage

May impair movements linked to antigravity muscle function and/or postural control

Some Human Results in Spaceflight

Some Human Results in Spaceflight

On one 27-day mission: 10% leg muscle volume

20% strength

Negative nitrogen balance (muscle & body) Highest day #1 ( food intake)

lean body mass, especially calves, & strength

Negative phosphate balance

Some fatiguability (plus, see on landing)

Some evidence reach new steady state with time

Motion & Coordination Issues

Motion & Coordination Issues

Rearrange biomechanical nature of moving Changes relation of body mass & effort

Elimination of static work & dynamic work activity of postural-tonic musculature Few eccentric muscle contractions

No “gravity assist” when lowering objects No “gravity fighting” posturally

175-day Russian missions show atrophy leads to increase EMG signal per torque

Formation of new coordination patterns and alteration of the motor activity as a whole

Summary of Some Causes for Muscle Changes in gSummary of Some Causes for Muscle Changes in g

Removal of mechanical loads & less work for many muscle groups

Deconditioning of postural muscles Elimination of foot support Restructuring of normal motor patterns Fluid shifts, microcirculatory changes,

or altered tissue nutrition?

Bones !Bones !

Dynamic, living tissue

Mechanical support

Calcium hemostasis

Strength due to matrix of calcium, phosphorous, and collagen

Cells in BoneCells in Bone

Osteoblasts - bone-forming

Osteoctyes - embedded osteoblasts

Osteoclasts - Breakdown bone & release Ca2+

Formation or Resorption?Formation or Resorption?

Depends on stress (“?” Effect) & hormones

In space, overall: Bone demineralization strength & density Metabolic changes & Ca2+ mobilization Elevated Ca2+ excretion (I.e., negative

calcium balance)

Bone

Osteo______?Blood

Calcium

Osteo______?

Net Calcium BloodFactor -blasts -clasts Absorption Calcium

Physical Activates Inhibits N/A No DirectStress Effect

Calcitonin ? InhibitsPTH ? Activates

Intestine&

Kidney

Net CalciumAbsorption

Bone

Osteo______?Blood

Calcium

Osteo______?

Net Calcium BloodFactor -blasts -clasts Absorption Calcium

Physical Activates Inhibits N/A No DirectStress Effect

Calcitonin ? Inhibits Decreases DownPTH (PH) ? Activates Increases Up

Intestine&

Kidney

Net CalciumAbsorption

Mechanism of g DemineralizationMechanism of g Demineralization

Not well known Removal of gravitational load on the

skeleton Changes in blood flow and

metabolism in bones Changes in hormonal and immune

status

Bone, Calcium, & Space Flight (Morey-Holton, et al.)

Bone, Calcium, & Space Flight (Morey-Holton, et al.)

Used young rats in rapid growth stage Housing affects the response

Animals housed individually showed more in-flight changes & slower readaptation to Earth than animals in group cages

Not all regions of bones or all bones affected Long bones formation on the periosteal

surface, but not endosteal surface No changes in the ribs, vertebra ,or maxilla

(jaw), so response is not same everywhere

Pathophysiology of Mineral Loss in Space Flight (Arnaud, et al.)

Pathophysiology of Mineral Loss in Space Flight (Arnaud, et al.)

In g calcium is lost from bones, blood calcium , & calcium is excreted in the urine.

This study examined changes in the balance of calcium entering and leaving the body. Saw: loss of calcium Parathyroid hormone was consistent with

response to the calcium levels

The Musculoskeletal System in Space

NASA video AAV-1543

The Musculoskeletal System in Space

NASA video AAV-1543

Notes from video: Adaptations to MicrogravityNotes from video: Adaptations to Microgravity

Muscle atrophy Reduce muscle tone and strength Increased muscle fatigue Reprogramming muscle synergism Reduced motor control Motor endplate degeneration Increased contraction velocity Bone demineralization and redistribution Connective tissue degeneration Back pain

Z membrane

Cross-bridgeBinding Site

Thick Filament (myosin)

Thin Filament (actin)

Muscular System SpecificsMuscular System Specifics

Does adapt, but have weakness -- possible muscle tears

See muscle atrophy, especially slow-twitch Decreased tone, strength, & size (regional) Decreased protein synthesis Negative nitrogen balance Increased plasma amino acids Increased plasma creatinine & 3-

methylhistidine

Physiological mechanisms that may explain muscle related adaptations associated with microgravity

Loss of static & dynamic loads along longitudinal axis of body

Cephalic fluid shifts

Adaptations associated with the skeletal system during microgravityAdaptations associated with the skeletal system during microgravity

External forces are decreased Bone synthesis is reduced Bone architecture and composition

are modified to accommodate the new lower load conditions

Altered calcium metabolism Reduced bone strength

Bone mineral densityBone mineral density

Normal changes in overall whole body bone density

Increased 4.2% in skull ! Bone loss is functional (structural &

mineral changes; impacts overall quality) Calcium loss at rapid rate at first, then

continues (plateau?) Data suggest bone loss occurs at rates of

0.5 - 2.0% / month

2 Mechanical factors affecting bone loss2 Mechanical factors affecting bone loss

Changes are regional and function specific

Loading bearing Muscle pull - Greatest site of

mineral loss is at muscle insertion sites

Possible physiologic mechanism underlying skeletal deconditioningPossible physiologic mechanism underlying skeletal deconditioning

Principal stimuli to skeleton are altered Biomechanical stress Fluid pressure Bone redistribution from feet to

head during space flight Cell mechanism unknown

Spaceflight(- biomechanical stress/fluid shifts)

+ serum Calcium levels

- Parathyroid hormone

+ Serum Phosphorous

- 1,25 dihydroxyvitamin D

- Intestinal calcium absorption

- Calcium balance

Calcium/Endocrine SkeletonFocal/Regional

Resorption > formation

Diet

Adrenal Activity

Calcitonin

- Bone Mass

+ Urinary CalciumExcretion

Spinal ChangesSpinal Changes

Increased height 68% experience back pain Possible Factors

Spine unloading Intervertebral disc swelling Spinal lengthening Outer disc annulus and facet joint distension Spinal ligament stretching Paraspinal muscle stretching Nerve root dysfunction

Countermeasure for overall musculoskeletal deconditioningCountermeasure for overall musculoskeletal deconditioning

Current countermeasures Treadmill Rowing Bicycle

Current measures time consuming (how much?) & ineffective (why?)

Recovery on Earth also incomplete

Potential countermeasures for musculoskeletal deconditioningPotential countermeasures for musculoskeletal deconditioning

Exercise: Resistive Aerobic

Human centrifuge Exercise against LBNP (possibly

with counter-pressure suit) Pharmacologic agents -- e.g.??

Benefits of research to EarthBenefits of research to Earth

Disease - osteoporosis, muscular dystrophy

Fracture healing Rehabilitation