Musculoskeletal Physiology and Spaceflight
Musculoskeletal Physiology and Spaceflight
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Skeletal structures
Bone chemistry
Muscle physiology
Muscle chemistry
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How the musculo-skeletal system works in Earth gravity to ensure
upright posture, movements and storage of nutrients (calcium)
Physiology of bone and muscle
Effects of space flight on bone and muscle
Implications of such changes for long term missions and potential
countermeasures
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Humans have about 700 muscles in their bodies
There are 3 types of muscles:
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The function of the muscle is to contract; they work by shortening
Contractions of skeletal muscles are coordinated by the brain
from Lujan and White, Human Physiology in Space NASA/NIH/USRA/UTSW
http://www.nsbri.org/HumanPhysSpace/
•Skeletal muscle is the largest tissue in the body,
accounting for 40-45% of total body weight
•Skeletal muscle may form direct and indirect
attachments
Direct attachments: directly connect muscle to
bone or cartilage
Indirect attachments: connect muscle to bone
indirectly by using either a tendon (a small band)
or an aponeurosis (fibrous sheet)
•Skeletal muscles work in pairs: one muscle
contracts to pull a bone forward, the other to
pull it back
•The anti-gravity muscles, also known as
postural muscles, owe their importance and
strength to the presence of gravity
Cohen B. Memmler’s: The human body in health and disease. 11th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2009.
Kibble J, Halsey C. The big picture: Medical physiology. New York (NY): McGraw Hill; 2009.
Marieb E, Hoehn K. Anatomy & physiology. 4th ed. San Francisco (CA): Benjamin Cummings; 2011.
Silverthorn D. Human Physiology: An integrated approach. 4th ed. San Francisco (CA): Pearson Benjamin-Cummings; 2009.
Lujan and White, Human Physiology in Space NASA/NIH/USRA/UTSW
http://www.nsbri.org/HumanPhysSpace/
Muscle Contraction
• Muscles are composed of fibers
• Each fiber is made up of myofibrils,
consisting of many filaments (myosin
and actin), the engines of the muscle
• Together the actin and myosin
provide all the muscle’s movement
and force as they slide together
(contraction) and apart (during relaxation)
• In healthy muscles, there is a continual
process of muscle protein production and
breakdown
• When protein breakdown occurs more
rapidly than protein production,
there is a loss of muscle mass
Muscle Strength
• Contraction refers to the
active process of generating
a force in a muscle
• The force exerted by a contracting
muscle on an object is the
muscle tension
• The force exerted on a muscle by
the weight of an object is the load
• When a muscle shortens and
lifts a load, the muscle contraction
is isotonic (constant tension)
• When shortening is prevented by a load that is greater than muscle tension,
the muscle contraction is isometric (constant length)
Mechanisms of muscle
contraction part I
A)An action potential travels down the axon of the
alpha motor neuron connected to a skeletal
muscle cell at its motor end-plate
B)Once the action potential reaches the axon
terminal it causes calcium ion channels to open
(resulting in calcium ion influx)
C)The influx of calcium ions into the axon terminal
triggers the release of acetylcholine (ACh) from
the axon
D)ACh then binds to receptors on the skeletal
muscle cell membrane causing sodium ion
channels to open (leading to an influx of sodium
ions into the skeletal muscle cell)
E)The influx of positively charged ions into the
skeletal muscle cell will ultimately trigger the cell
membrane of that cell to have an action potential
Cohen B. Memmler’s: The human body in health and disease. 11th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2009.
Kibble J, Halsey C. The big picture: Medical physiology. New York (NY): McGraw Hill; 2009.
Marieb E, Hoehn K. Anatomy & physiology. 4th ed. San Francisco (CA): Benjamin Cummings; 2011.
Silverthorn D. Human Physiology: An integrated approach. 4th ed. San Francisco (CA): Pearson Benjamin-Cummings; 2009.
Mechanisms of muscle
contraction part II
F)The action potential generated at
the cell membrane will propagate
along the cell membrane and down
the t-tubule where it will induce
the smooth endoplasmic reticulum
(SER) to release calcium ions (this is
a vital step for muscle contraction)
G)Calcium ions will then stick to
troponin-C. This will induce
troponin (composed of T, I, and C
subunits) to pull tropomyosin out
of the way, which will expose the
“active site” on actin where the
myosin head can immediately
strike
Cohen B. Memmler’s: The human body in health and disease. 11th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2009.
Kibble J, Halsey C. The big picture: Medical physiology. New York (NY): McGraw Hill; 2009.
Marieb E, Hoehn K. Anatomy & physiology. 4th ed. San Francisco (CA): Benjamin Cummings; 2011.
Silverthorn D. Human Physiology: An integrated approach. 4th ed. San Francisco (CA): Pearson Benjamin-Cummings; 2009.
Mechanisms of muscle
contraction part III
H)Once the myosin head contacts
actin it will eject Adenosine
diphosphate (ADP) and inorganic
phosphate (Pi) during the “Power
stroke” (aka “working stroke”). This
is the step where the sarcomere
(the contractile unit of a skeletal
muscle cell) is contracting.
Here is a four-step simplified model of this process.
I)Following this ATP will bind to the
myosin head to make it release
actin so that it may re-grab it again
(a ratcheting-type action), thus
continuing the cycle over and over
resulting in sarcomere shortening.
A skeletal muscle is composed of
many sarcomeres arranged end to
end. As they all contract you
visually see the muscle shorten.
Cohen B. Memmler’s: The human body in health and disease. 11th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2009.
Kibble J, Halsey C. The big picture: Medical physiology. New York (NY): McGraw Hill; 2009.
Marieb E, Hoehn K. Anatomy & physiology. 4th ed. San Francisco (CA): Benjamin Cummings; 2011.
Silverthorn D. Human Physiology: An integrated approach. 4th ed. San Francisco (CA): Pearson Benjamin-Cummings; 2009.
Major structures of a sarcomere
Steps involved in a neuron stimulating a muscle cell
Six step version of the sliding filament theory model
Mechanisms of muscle relaxation
A)Acetylcholinesterase (AChE) is
an enzyme located in the synapse
and motor endplate between a
neuron and a skeletal muscle cell.
This enzyme quickly breaks down
ACh so that it stops activating a
muscle cell. This is important to
help with you rapidly turning “off”
a muscle once it has contracted
that way your body can choose to
contract that muscle or a different
muscle quickly to engage in
complex motions. AChE breaks
down acetylcholine into acetate
and choline. Choline will be
recycled into the axon that
secreted it. Acetate may be
brought into any cell and used in
various metabolic processes.
Cohen B. Memmler’s: The human body in health and disease. 11th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2009.
Kibble J, Halsey C. The big picture: Medical physiology. New York (NY): McGraw Hill; 2009.
Marieb E, Hoehn K. Anatomy & physiology. 4th ed. San Francisco (CA): Benjamin Cummings; 2011.
Silverthorn D. Human Physiology: An integrated approach. 4th ed. San Francisco (CA): Pearson Benjamin-Cummings; 2009.
Muscle soreness
Delayed Onset Muscle Soreness (DOMS) is due
primarily to heavy eccentric activity and is thought
to be the result of microtears in the muscle.
Symptoms can be Z-disc streaming and major
disruption of thick and thin filaments. After
muscle injury there is commonly a release of
Creatine Kinase, myoglobin (Mb), and troponin I.
All of these substances can be measured in blood
samples.
Creatine kinase- is an enzyme that helps replenish
ATP.
Myoglobin- temporarily it will pick up oxygen
molecules from hemoglobin in our blood so that
skeletal muscle cells can engage in oxidative
metabolic pathways (e.g., Kreb’s cycle and
Electron Transport Chain) to make ATP.
Troponin I- it is one of three components of
troponin that is involved in exposing the active
site on actin so the myosin head can strike it.
Cohen B. Memmler’s: The human body in health and disease. 11th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2009.
Kibble J, Halsey C. The big picture: Medical physiology. New York (NY): McGraw Hill; 2009.
Marieb E, Hoehn K. Anatomy & physiology. 4th ed. San Francisco (CA): Benjamin Cummings; 2011.
Silverthorn D. Human Physiology: An integrated approach. 4th ed. San Francisco (CA): Pearson Benjamin-Cummings; 2009.
Energy for Muscle Contraction
• Basic source is Adenosine Tri-Phosphate or ATP
ATP is the universal currency of biological energy
~ represent high energy phosphate bonds.
Each one releases 7,500 calories when broken
Energy for Muscle Contraction
• Basic source as Adenosine Tri-Phosphate or ATP
• The amount of ATP present in the muscle cells is only
sufficient to sustain maximal muscle power for 5-6 seconds
• New ATP must be formed continuously:
- creatine phosphate: can sustain 10-15 more sec of muscle activity
- anaerobic step of glucose breakdown: for another 30-40 sec “bursts” of energy
- aerobic system: provides unlimited time muscle activity (as long as nutrients last)
Functioning of Muscle Fiber
from Lujan and White, Human Physiology in Space NASA/NIH/USRA/UTSW
Muscle Metabolism
Energy Transfer Kinetics
from Johnson, Biomechanics and Exercise Physiology - John Wiley and Sons, 1991
Changes in Muscle Fibers to Bed Rest
from Nicogossian et. al., Space Biology and Medicine - AIAA, 1996
Muscle Activity
• The filament’s force is all or nothing. When called upon it always applies
the same amount of force at the same speed
• There are 2 kinds of muscle fibers:
- Type 1 , or “slow twitch”, are slow-moving but high endurance fibers
Use oxygen
Marathon runners typically develop those in the soleus muscle in the calf
for prolonged lower leg muscle activity
- Type II, or “fast twitch”, are high speed, high output fibers.
Sprinters and weight-lifters tytpically develop those in the gastocnemius
muscle in the calf and in the biceps muscle for quick, powerful “bursts” of
movement.
They fatigue rapidly (use glycogen rather than oxygen)
• The average person has about 50% - 50% of Type I and Type II fibers
throughout the body
Muscular Exercise
• Strength and endurance can be increased by exercise (training)
• Capacity of a muscle for activity can be altered:
• - by transformation of one type of fiber to another
e.g. muscle required to perform endurance-type activity will develop
more Type I fibers and number of blood capillaries will increase
- by the growth in size (hypertrophy) of the muscles fibers:
e.g. weightlifting will induce hypertrophy in Type II fibers, with an
increase in synthesis of actin and myosin filaments.
• Endurance exercise also produces changes in the respiratory and
circulatory systems, which improves the delivery of oxygen and
nutrients to muscle fibers
Muscle Atrophy
Denervation atrophy : if the nerve fibers to
a muscle are severed, the denervated
muscle fibers become progressively
smaller. Their content of actin and myosin
decreases, and connective tissue (e.g.,
adipose tissue) proliferates around them.
•Disuse atrophy: a muscle can also
atrophy with its nerve supply intact if it is
not used for a long period of time.
Cohen B. Memmler’s: The human body in health and disease. 11th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2009.
Kibble J, Halsey C. The big picture: Medical physiology. New York (NY): McGraw Hill; 2009.
Marieb E, Hoehn K. Anatomy & physiology. 4th ed. San Francisco (CA): Benjamin Cummings; 2011.
Silverthorn D. Human Physiology: An integrated approach. 4th ed. San Francisco (CA): Pearson Benjamin-Cummings; 2009.
Effects of Space Flight on Muscle
• Decrease in body mass
Effects of Space Flight on Muscle
• Decrease in body mass
• Decrease in leg volume
Effects of Space Flight on Muscle
• Decrease in body mass
• Decrease in leg volume
• Atrophy of the antigravity muscles (thigh, calf)
- seen on muscle scans/biopsies
- decrease in leg muscle strength
- extensor muscles more affected than flexor muscles
• Data in flown rats showed an increase in number of Type II “fast twitch” muscle
fibers (those which are useful for quick body movements but more prone to
fatigue)
ground control
flight
Muscle Atrophy Countermeasures
• 2 daily 1 to 1.5 hour sessions of exercise:
- treadmill with axial loading
- cycle ergometer
- resistive exercise device
- traction on “bundee cords”
• 4-day cycle
- Day 1, low load but high intensity
- Day 2, moderate load at moderate intensity
- Day 3, high load at low intensity
- Day 4, ad lib
“Penguin Suit”
The inside of the suit contains a system of elastic,
straps and buckles that can be used to adjust the
fit and tension of the suit
Muscle Atrophy - Challenges
•Exercise alone has not prevented muscle atrophy during space flight
•The increase in fast-twitch fibers could result in a higher susceptibility to
contraction damage
Sprain: injury to ligaments
Strain: injury to muscle tissue
•Muscle atrophy caused by weightlessness participates in postural instability and
locomotion difficulties after space flight
•Astronauts data are complicated by prior physical fitness and inflight
countermeasures or workloads, including EVA
•Muscle development was disrupted when gravity-loading exercise was
removed from immature rats flown on the Neurolab Spacelab mission
•The muscle weakness, fatigue, faulty coordination, and muscle soreness that
astronauts experience after space flight mimics the changes seen in bed rest
patients and the elderly
Cohen B. Memmler’s: The human body in health and disease. 11th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2009.
Kibble J, Halsey C. The big picture: Medical physiology. New York (NY): McGraw Hill; 2009.
Marieb E, Hoehn K. Anatomy & physiology. 4th ed. San Francisco (CA): Benjamin Cummings; 2011.
Silverthorn D. Human Physiology: An integrated approach. 4th ed. San Francisco (CA): Pearson Benjamin-Cummings; 2009.
Skeletal Structure
The ‘anti-gravity’
bones are
responsible for bearing
the weight of the body in a
gravitational environment
from Lujan and White, Human Physiology in Space NASA/NIH/USRA/UTSW
http://www.nsbri.org/HumanPhysSpace/
Function of Bone
Weight Bearing Bone
Categories of Articulated Joints
from Lujan and White, Human Physiology in Space NASA/NIH/USRA/UTSW
Major Parts of a Long Bone
• two extremitie, cylindrical midshaft and
hollow center (which contains the
bone marrow)
• bone can be layered around a blood vessel
(lamellar bone)
from Lujan and White, Human Physiology in Space NASA/NIH/USRA/UTSW
Bone Remodeling
Bone Growth
Calcium Balance
Osteoporosis on Earth
Bone Loss During Space Flight
Progression of understanding:
Bone Loss During Space Flight
Postflight changes in bone density compared to preflight
Calcium Loss During Space Flight
Compiled data from Gemini 7, Skylab 2-4, and Shuttle missions
(each data point represents the mean + SD of n=2 to 14 subjects
Bone Loss During a Mars Mission
During a mission to Mars, a 45 year old astronaut could see bone
Deterioration reach the weakened state of sever osteoporosis
Bone Construction and Maintenance
• All bones start out cartilagenous
• Ossification - conversion of cartilage to bone
• Osteoblasts - deposit minerals and salts
• Osteoclasts - break down unused/damaged areas
• Rates of bone growth and harvesting driven by stress on bone
Basic Multicellular Unit in Bone Growth
from Churchill, Fundamentals of Space Life Sciences - Krieger Publishing, 1997
Calcium Regulation System
from Lujan and White, Human Physiology in Space NASA/NIH/USRA/UTSW
Skylab Early Urinary Calcium Output
from Churchill, Fundamentals of Space Life Sciences - Krieger Publishing, 1997
Skylab Long-Duration Urine and Fecal Ca
Bone Density - 5-6 Months on Mir
from Nicogossian et. al., Space Biology and Medicine - AIAA, 1996
Efficacy of Countermeasures on Ca Loss
from Nicogossian et. al., Space Biology and Medicine - AIAA, 1996
Definition of Stress and Strain
Stress versus Strain
Bone Loss Countermeasures
Bone Density Measurements
Bone Loss Challenges
Muscle and Bone Summary
Long-Term Adaptation to Microgravity
from Nicogossian, Huntoon, and Pool, Space Physiology and Medicine - Lea and Fabiger,
1994
Overall Body Response to Space Flight
from Lujan and White, Human Physiology in Space NASA/NIH/USRA/UTSW
Other References
• R. L. DeHart, ed., Fundamentals of Aerospace Medicine, Second Edition
Williams and Wilkins, 1996
• A. E. Nicogossian, C. L. Huntoon, and S. L. Pool, Space Physiology
and Medicine, Third Edition Lea and Febiger, 1994
• A. E. Nicogossian, S. R. Mohler, O. G. Gazenko, and A. I. Grigoriev,
eds., Space Biology and Medicine (Volume III, Book 1: Humans in
Spaceflight) American Institute of Aeronautics and Astronautics, 1996
• J. T. Joiner, ed., NOAA Diving Manual: Diving for Science and
Technology, Fourth Edition Best Publishing, 2001