Transcript Musculoskeletal Function #1

Biology 350:
Biology & Space Exploration
Col Ronald D. Reed, PhD
Professor & Head of Biology
U.S. Air Force Academy
1999
Learning Objectives
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
Objectives (cont’d)
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 patches
when effects were
studied
Skeletal Muscle Functions
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Exert force to change joint angle
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Concentric - muscle shortening
Eccentric - muscle lengthening
Exert force to maintain joint angle isometric (static tension)
Produce body heat
Review of Anatomy
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Whole Muscle
Muscle fiber (cell)
Myofibril
Sarcomere
Myofilaments
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Myosin
Actin
Cross-bridging & “ratcheting”
Binding Site
(need Ca2+)
Z membrane
(end of sarcomere)
Cross-bridge
Thin Filament
(actin)
Thick Filament (myosin)
Muscle contraction
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Coupled reaction:
Chem. energy  physical motion
ATP hydrolysis  force
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 [Ca2+] in cell allows reaction
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Slow- & fast-twitch muscle
specializations
Slow- & Fast-Twitch Muscles
Twitch Rate
Glycogen Content
Glycolytic Capacity
Fatigue Resistance
Respiration Type
Capillary Supply
Slow
Low
Low
High
Aerobic
High
Fast
High
High
Low
Anaerobic
Low
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.
Power (un x ft/s)
Atrophied Fiber
Control Fiber
Force (% of Peak Force)
Studies of Rat Hindlimb Muscle,
Nerves, Biomechanics, etc.
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Focus on antigravity (postural) muscles
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Why hindlimb? In mg rats use forelimbs to
move in cages; hindlimbs float except
for grasping. Also, have Earth model.
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Results:
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Significant atrophy,  protein & mass
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Shift in major muscle fiber type (ST  FT)
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 capacity to break down certain nutrients &
some shift from fat to glycogen use in ST
Studies of Rat Hindlimb Muscle,
Nerves, Biomechanics, etc.
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More Results:
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Muscle atrophy in mg not returned
to normal in 14 days back on Earth
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 susceptibility to damage
on return to Earth
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Interstitial edema & lesions in
sarcomeres developed postflight -damage
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May impair movements linked to antigravity
muscle function and/or postural control
Some Human Results in
Spaceflight
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On one 27-day mission:
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10%  leg muscle volume
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20%  strength
Negative nitrogen balance (muscle & body)
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Highest day #1 ( food intake)
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 lean body mass, especially calves, &  strength
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Negative phosphate balance
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Some  fatiguability (plus, see on landing)
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Some evidence reach new steady state with time
Motion & Coordination
Issues
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Rearrange biomechanical nature of moving
Changes relation of body mass & effort
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Elimination of static work &  dynamic work
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 activity of postural-tonic musculature
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Few eccentric muscle contractions
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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 mg
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Removal of mechanical loads & less
work for many muscle groups
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Deconditioning of postural muscles
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Elimination of foot support
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Restructuring of normal motor patterns
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Fluid shifts, microcirculatory changes,
or altered tissue nutrition?
Bones !
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Dynamic, living tissue
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Mechanical support
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Calcium hemostasis
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Strength due to matrix
of calcium, phosphorous,
and collagen
Cells in Bone
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Osteoblasts bone-forming
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Osteoctyes embedded
osteoblasts
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Osteoclasts Breakdown bone
& release Ca2+
Formation or Resorption?
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Depends on stress (“?” Effect) &
hormones
In space, overall:
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Bone demineralization
 strength & density
Metabolic changes & Ca2+ mobilization
Elevated Ca2+ excretion (I.e., negative
calcium balance)
Net Calcium
Absorption
Intestine
&
Kidney
Osteo______?
Blood
Calcium
Bone
Osteo______?
Factor
-blasts
-clasts
Physical
Direct
Stress
Activates
Inhibits
Calcitonin
PTH
Net Calcium
Absorption
N/A
Blood
Calcium
No
Effect
?
?
Inhibits
Activates
Net Calcium
Absorption
Intestine
&
Kidney
Osteo______?
Blood
Calcium
Bone
Osteo______?
Factor
-blasts
-clasts
Physical
Direct
Stress
Activates
Inhibits
Calcitonin
PTH (PH)
Net Calcium
Absorption
N/A
Blood
Calcium
No
Effect
?
?
Inhibits Decreases
Activates Increases
Down
Up
Mechanism of mg
Demineralization
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Not well known
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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.)
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Used young rats in rapid growth stage
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Housing affects the response
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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
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Long bones  formation on the periosteal
surface, but not endosteal surface
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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.)
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In mg 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
Notes from video: Adaptations
to Microgravity
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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
Cross-bridge
Binding Site
Z membrane
Thin Filament (actin)
Thick Filament (myosin)
Muscular System Specifics
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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 & 3methylhistidine
Physiological mechanisms that may
explain muscle related adaptations
associated with microgravity
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Loss of static & dynamic loads
along longitudinal axis of body
Cephalic fluid shifts
Adaptations associated with the
skeletal system during microgravity
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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 density
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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 loss
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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 deconditioning
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Principal stimuli to skeleton are
altered
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Biomechanical stress
Fluid pressure
Bone redistribution from feet to
head during space flight
Cell mechanism unknown
Spaceflight
(- biomechanical stress/fluid shifts)
Skeleton
Focal/Regional
Calcium/Endocrine
+ serum Calcium levels
Resorption > formation
- Parathyroid hormone
Diet
+ Serum Phosphorous
Adrenal Activity
- 1,25 dihydroxyvitamin D
Calcitonin
- Intestinal calcium
absorption
- Bone Mass
+ Urinary Calcium
- Calcium balance
Excretion
Spinal Changes
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Increased height
68% experience back pain
Possible Factors
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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 deconditioning
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Current countermeasures
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Treadmill
Rowing
Bicycle
Current measures time consuming
(how much?) & ineffective (why?)
Recovery on Earth also incomplete
Potential countermeasures for
musculoskeletal deconditioning
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Exercise:
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Resistive
Aerobic
Human centrifuge
Exercise against LBNP (possibly
with counter-pressure suit)
Pharmacologic agents -- e.g.??
Benefits of research to Earth
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Disease - osteoporosis,
muscular dystrophy
Fracture healing
Rehabilitation