GW BGZ 2025 Case 2 - Hiking in the hills

What is muscle tissue and what is its main function?

Muscle tissue is one of the four basic tissue types and is specialized for contraction and force generation. It contains actin and myosin proteins, which interact to produce movement. Muscle functions include body movement, posture, movement of substances through organs, and heat production.

What are the three types of muscle tissue?

Skeletal muscle

• Long multinucleated fibers

• Striated

• Voluntary control

• Produces rapid, forceful contractions

Cardiac muscle

• Branched striated cells

• Intercalated discs

• Involuntary rhythmic contraction

• Found in the heart

Smooth muscle

• Spindle-shaped cells

• Non-striated

• Involuntary contraction

• Found in hollow organs and vesselsWhat are sarcoplasm, sarcolemma, and sarcoplasmic reticulum?

What are sarcoplasm, sarcolemma, and sarcoplasmic reticulum?

• Sarcoplasm: cytoplasm of muscle cells

• Sarcolemma: muscle cell membrane

• Sarcoplasmic reticulum (SR): specialized smooth ER that stores and releases Ca²⁺ for contraction

How does skeletal muscle develop embryologically?

Development sequence:

1. Myoblasts proliferate

2. Myoblasts fuse together

3. Multinucleated structures called myotubes form

4. Contractile proteins accumulate

5. Mature muscle fibers develop

Important features:

• Mature skeletal muscle fibers are multinucleated because they formed by fusion of many myoblasts

• Nuclei migrate to the periphery beneath the sarcolemma

Satellite cells

A population of stem-like cells remains between:

• Sarcolemma

• External lamina

Functions:

• Muscle repair

• Regeneration after injury

• Hypertrophy support

What are the connective tissue layers of skeletal muscle?

Epimysium

• Dense irregular connective tissue

• Surrounds the entire muscle

• Continuous with tendons and fascia

Perimysium

• Surrounds fascicles (bundles of fibers)

• Contains:

  • Blood vessels

  • Nerves

  • Lymphatics

Endomysium

• Delicate connective tissue around each individual muscle fiber

• Contains capillaries and reticular fibers

Functional importance

These layers:

• Support muscle structure

• Carry vessels and nerves

• Transmit force from fibers to tendons and bone

What structures are found inside a skeletal muscle fiber?

Myofibrils

• Long cylindrical contractile structures

• Occupy most of the sarcoplasm

• Composed of repeating sarcomeres

Sarcoplasmic reticulum

• Surrounds myofibrils

• Stores calcium ions

T-tubules

• Invaginations of the sarcolemma

• Conduct action potentials deep into the cell

Triads

A triad consists of:

• One T-tubule

• Two terminal cisternae of the SR

Function:

• Rapid excitation-contraction coupling

What is a sarcomere?

The sarcomere is the:

• Basic functional contractile unit of skeletal muscle

• Repeating unit between two Z discs

Sarcomeres are arranged end-to-end within myofibrils.

During contraction:

• Sarcomeres shorten

• Muscle fibers shorten

• Force is generated

The highly organized arrangement of sarcomeres creates the striated appearance of skeletal muscle.

What are the bands and zones of a sarcomere?

Z disc

• Boundary of a sarcomere

• Anchors thin filaments

I band

• Contains only thin filaments

• Light band

A band

• Contains entire thick filament length

• Includes overlap with thin filaments

• Dark band

H zone

• Central region of A band

• Contains only thick filaments

M line

• Middle of sarcomere

• Anchors thick filaments

During contraction:

• I band shrinks

• H zone shrinks

• A band remains constant

What are thick filaments composed of?

Thick filaments are primarily composed of myosin molecules.

Each myosin molecule contains:

• Two heavy chains

• Tail region

• Two globular heads

Myosin heads:

• Bind actin

• Hydrolyze ATP

• Generate force

The heads form cross-bridges with actin during contraction.

Myosin acts as an ATPase enzyme and converts chemical energy into mechanical movement.

What are thin filaments composed of?

Actin

• Exists as F-actin (filamentous actin)

• Double helical structure

• Contains myosin-binding sites

Tropomyosin

• Long regulatory protein

• Lies along actin filament

• Covers myosin-binding sites during rest

Troponin complex

Function

When calcium binds troponin:

• Tropomyosin shifts away

• Myosin-binding sites exposed

• Contraction becomes possible

What is a cross-bridge?

A cross-bridge is the connection formed when:

• A myosin head binds to actin

Sequence:

1. Calcium binds troponin

2. Tropomyosin moves

3. Binding sites exposed

4. Myosin binds actin

5. Cross-bridge forms

Importance

Cross-bridge cycling:

• Produces force

• Causes sarcomere shortening

• Drives muscle contraction

What are titin and nebulin?

Titin

• Giant elastic protein

• Extends from Z disc to thick filament

Functions:

• Stabilizes sarcomere

• Maintains thick filament alignment

• Contributes to elastic recoil after stretching

Nebulin

• Runs alongside thin filaments

Functions:

• Stabilizes actin

• Maintains thin filament length

• Helps organize sarcomeres

Both proteins are essential accessory structural proteins.

What are the major skeletal muscle fiber types?

Type I (slow oxidative)

• Slow contraction

• Aerobic metabolism

• High fatigue resistance

Type IIA (fast oxidative-glycolytic)

• Fast contraction

• Mixed metabolism

• Intermediate fatigue resistance

Type IIX/IIB (fast glycolytic)

• Very fast contraction

• Anaerobic glycolysis

• Fatigue quickly

Muscles contain mixtures of fiber types depending on function and training.

Females more type 1 and males more type 2

Why do Type II fibers contract faster than Type I fibers?

The contraction speed depends largely on:

• Myosin ATPase activity

Type II fibers

• High ATPase activity

• Faster ATP hydrolysis

• Faster cross-bridge cycling

• Rapid force generation

Type I fibers

• Lower ATPase activity

• Slower cross-bridge cycling

• Slower force production

Functional consequence:

• Type II fibers specialized for explosive movements

• Type I fibers specialized for endurance

How does calcium handling differ between slow and fast fibers?

Fast-twitch fibers

• Rapid Ca²⁺ reuptake into SR

• Short twitch duration

• Quick relaxation

Slow-twitch fibers

• Slower calcium removal

• Longer contraction duration

• Sustained force generation

This difference contributes to:

• Explosive movements in Type II fibers

• Endurance function in Type I fibers

What are the major stages of muscle contraction?

1. Neuromuscular signaling

Motor neuron stimulates muscle fiber.

2. Excitation-contraction coupling

Electrical signal triggers calcium release.

3. Sliding filament mechanism

Actin and myosin interact to generate force.

4. Relaxation

Calcium removed and contraction stops.

What happens at the neuromuscular junction?

Sequence:

1. Action potential reaches axon terminal

2. Voltage-gated Ca²⁺ channels open

3. Calcium enters neuron terminal

4. Acetylcholine released

5. ACh binds nicotinic receptors

6. Na⁺ enters muscle cell

7. End-plate potential forms

8. Muscle action potential generated

Acetylcholine is rapidly degraded by:

• Acetylcholinesterase

What is excitation-contraction coupling?

Excitation-contraction coupling links:

• Electrical excitation
  to

• Muscle contraction

Process:

1. Action potential travels along sarcolemma

2. Signal enters T-tubules

3. DHP receptors detect voltage change

4. Ryanodine receptors open

5. SR releases Ca²⁺

6. Cytosolic calcium rises

7. Contraction begins

Calcium is the critical intracellular signal.

What changes occur in the sarcomere during contraction?

Structural changes:

• Z discs move closer together

• Sarcomere shortens

• I band narrows

• H zone narrows/disappears

• A band unchanged

Important principle:

Filaments do NOT shorten.
They slide past each other.

This is the basis of the sliding filament theory.

What roles does ATP play in muscle contraction?

ATP is essential for multiple processes:

1. Cross-bridge detachment

ATP binding releases myosin from actin.

2. Re-cocking myosin

ATP hydrolysis energizes myosin head.

3. Calcium reuptake

Ca²⁺-ATPase pumps calcium back into SR.

Without ATP:

• Cross-bridges remain attached

• Calcium remains elevated

• Muscle becomes rigid

This causes:

• Rigor mortis after death

How does muscle relaxation occur?

Relaxation process:

1. Neural stimulation stops

2. ACh release ceases

3. Calcium pumped back into SR

4. Cytosolic calcium falls

5. Calcium detaches from troponin

6. Tropomyosin re-covers binding sites

7. Cross-bridge cycling stops

8. Muscle returns to resting length

Relaxation requires ATP because calcium pumps are ATP-dependent.

What is osteogenesis?

Osteogenesis is the process of bone formation during embryonic development, growth, remodeling, and fracture repair. Bone is formed by specialized cells called osteoblasts, which produce bone matrix and mineralize it.

There are two major mechanisms of bone formation:

• Intramembranous ossification

• Endochondral ossification

Both initially produce woven bone, which is later remodeled into stronger lamellar bone.

What are the major bone cell types and their functions?

Osteoblasts

• Bone-forming cells

• Derived from mesenchymal stem cells

• Secrete osteoid

Osteocytes

• Mature bone cells

• Located in lacunae

• Maintain bone matrix

• Sense mechanical stress

Osteoclasts

• Bone-resorbing cells

• Derived from monocyte lineage

• Break down bone using acid and enzymes

What is intramembranous ossification?

Bone formation directly from mesenchyme without cartilage.

Process:

1. Mesenchymal cells condense

2. Osteoblasts differentiate

3. Osteoid secreted

4. Matrix mineralizes

5. Woven bone forms

6. Lamellar bone replaces woven bone

Forms:

• Flat bones of skull

• Mandible

• Clavicle

What is endochondral ossification?

Bone formation by replacing a hyaline cartilage model.

Sequence:

1. Cartilage model forms

2. Bone collar develops

3. Cartilage calcifies

4. Chondrocytes hypertrophy and die

5. Blood vessels invade

6. Osteoblasts deposit bone

7. Primary ossification center forms

8. Secondary ossification centers form later

Responsible for:

• Long bones

• Most bones of body

How do bones grow in length?

Length growth occurs at the:

• Epiphyseal plate (growth plate)

Zones:

1. Reserve cartilage

2. Proliferation zone

3. Hypertrophic zone

4. Calcification zone

5. Ossification zone

Mechanism:

• Chondrocytes divide

• Cartilage enlarges

• Cartilage replaced by bone

After puberty:

• Epiphyseal plates close

• Become epiphyseal lines

• Longitudinal growth stops

How do bones grow in width?

Width growth occurs by:

• Appositional growth

Mechanism:

• Osteoblasts add bone beneath periosteum

• Osteoclasts remove bone internally

Result:

• Increased diameter

• Enlarged marrow cavity

• Stronger bone without excessive weight

How do PTH and calcitonin regulate bone remodeling?

Parathyroid hormone (PTH)

Raises blood calcium by:

• Stimulating osteoclast activity

• Increasing bone resorption

Result:

• Calcium released into blood

Calcitonin

Lowers blood calcium by:

• Inhibiting osteoclasts

• Promoting calcium deposition in bone

PTH and calcitonin help maintain calcium homeostasis.

Why is bone constantly remodeled?

Bone remodeling serves several essential functions:

1. Repair microdamage

Daily stress causes tiny fractures that must be repaired.

2. Adapt to mechanical stress

Bones strengthen where loads increase (Wolff’s law).

3. Calcium homeostasis

Bone acts as a calcium reservoir.

4. Replace old bone

Old bone is continuously renewed.

Remodeling cycle:

1. Osteoclasts resorb bone

2. Osteoblasts lay down new bone

3. Bone mineralizes

Balanced remodeling maintains skeletal strength and metabolic function.

Which types of bone are there?

Compact bone

• Compact bone is dense and strong.

• It forms the outer shell of bones.

• It is organized into osteons.

• Osteons have concentric lamellae around blood vessels.

Cancellous bone

• Cancellous bone is spongy and lightweight.

• It forms trabeculae inside bones.

• It reduces weight but keeps strength.

What is the difference between woven bone and lamellar bone?

Woven bone

• Forms quickly

• Collagen arranged randomly

• Weak and disorganized

• Seen in early development and fracture repair

Lamellar bone

• Organized collagen layers

• Strong and mature

• Replaces woven bone during remodeling

What are the zones of the epiphyseal plate?

1. Reserve zone

• Resting hyaline cartilage

2. Proliferation zone

• Rapid chondrocyte division

• Cells arranged in columns

3. Hypertrophic zone

• Enlarged chondrocytes

4. Calcification zone

• Matrix calcifies

• Chondrocytes die

5. Ossification zone

• Blood vessels invade

• Osteoblasts replace cartilage with bone

Bone growth occurs mainly below the growth plate toward the shaft.

What is Wolff’s law?

Wolff’s law states that bone adapts to the mechanical stresses placed upon it.

Main principle:

• Increased stress → increased bone formation

• Reduced stress → bone loss

Bone structure changes to optimize strength while minimizing unnecessary weight.

Why do eccentric contractions cause more fatigue and soreness?

During eccentric contraction:

• Muscle attempts to shorten

• External force stretches it simultaneously

This creates:

• Greater mechanical stress

• More microdamage to fibers

• Increased delayed-onset muscle soreness (DOMS)

Eccentric contractions are mechanically demanding even though they use less ATP than concentric contractions.

What is the role of calcium in muscle contraction?

Calcium binds to troponin, causing tropomyosin to move away from actin binding sites.

This allows:

• Myosin to bind actin

• Cross-bridge cycling

• Force generation

Without calcium, contraction cannot occur.

What is a motor unit?

A motor unit consists of:

• One motor neuron

• All muscle fibers it innervates

Small motor units:

• Precise control

• Example: eye muscles

Large motor units:

• More force

• Example: hamstrings

What is the force-length relationship?

Muscle force depends on sarcomere length.

• Optimal overlap between actin and myosin → maximal force

• Too stretched or too shortened → lower force

Force depends on how many cross-bridges can form.

Why does overlap between actin and myosin affect force?

Force is produced by cross-bridges.

• More overlap → more cross-bridges → higher force

• Too little overlap → fewer cross-bridges

• Too much overlap → filaments interfere

Optimal overlap produces maximal force.

What is the force-velocity relationship?

The faster a muscle shortens, the less force it can produce.

Reason:

• At high velocity, fewer myosin heads are attached to actin at the same time

Slow shortening allows more cross-bridge attachment and higher force.

Why do eccentric contractions produce high force?

During eccentric contraction:

• Muscle lengthens while active

• Cross-bridges are stretched under tension

This creates:

• High force

• More muscle damage

• More soreness

Example:

• Walking downstairs

What is the force-frequency relationship?

Higher stimulation frequency produces greater muscle force.

Reason:

• Calcium remains elevated

• More cross-bridge formation occurs

Very high frequency can produce tetanic contraction (maximum force).

How does muscle cross-sectional area affect force?

Larger cross-sectional area means:

• More fibers in parallel

• More cross-bridges

Result:

• Greater force production

Thicker muscles are generally stronger.

How does muscle fiber length affect velocity?

Longer fibers contain more sarcomeres in series.

This allows:

• Greater shortening distance

• Faster contraction velocity

Long fibers are specialized for speed and range of motion.

How does muscle architecture affect function?

Pennate muscles

• More fibers packed together

• Greater force production

Parallel muscles

• Longer fibers

• Greater speed and range of motion

Architecture determines muscle function.