ANT250 I
Anatomy and Physiology I

The Muscular System

Module Three
Case Assignment
20 May 2013
Professor: Dr. Koronika

Q1. Describe normal anatomy/physiology of muscle contraction.
Anatomy of Skeletal Muscle: A single skeletal muscle, such as the triceps muscle, is attached at its • Origin to a large area of bone; in this case, the humerus. • At its other end, the insertion, it tapers into a glistening white tendon which, in this case, it’s attached to the ulna, one of the bones of the lower arm.
As the triceps contracts, the insertion are pulled toward the origin and the arm is straightened or extended at the elbow. Thus the triceps is an extensor. Because skeletal muscle exerts force only when it contracts, a second muscle a flexor is needed to flex or bend the joint. The biceps muscle is the flexor of the lower arm. Together, the biceps and triceps make up an antagonistic pair of muscles. Similar pairs, working antagonistically across other joints, provide for almost all the movement of the skeleton.

The Muscle Fiber

Skeletal muscle is made up of thousands of cylindrical muscle fibers often running all the way from origin to insertion. The fibers are bound together by connective tissue through which run blood vessels and nerves.

Each muscle fibers contains: • An array of myofibrils that are stacked lengthwise and run the entire length of the fiber; • Mitochondria; • An extensive smooth endoplasmic reticulum (SER) • Many nuclei (thus each skeletal muscle fiber is a syncytium).

The multiple nuclei arise from the fact that each muscle fiber develops from the fusion of many cells (called myoblasts).The number of fibers is probably fixed early in life. This is regulated by myostatin, a cytokine that is synthesized in muscle cells (and circulates as a hormone later in life). Myostatin suppresses skeletal muscle development. (Cytokines secreted by a cell type that inhibit proliferation of that same type of cell are called chalones.) Cattle and mice with inactivating mutations in their myostatin genes develop much larger muscles. Some athletes and other remarkably strong people have been found to carry one mutant myostatin gene. These discoveries have already led to the growth of an illicit market in drugs supposedly able to suppress myostatin.
In adults, increased muscle mass comes about through an increase in the thickness of the individual fibers and increase in the amount of connective tissue. In the mouse, at least, fibers increase in size by attracting more myoblasts to fuse with them. The fibers attract more myoblasts by releasing the cytokine interleukin 4 (IL-4). Anything that lowers the level of myostatin also leads to an increase in fiber size.
Because a muscle fiber is not a single cell, its parts are often given special names such as • sarcolemma for plasma membrane • sarcoplasmic reticulum for endoplasmic reticulum • sarcosomes for mitochondria • sarcoplasm for cytoplasm
Although this tends to obscure the essential similarity in structure and function of these structures and those found in other cells.

The Sliding Filament Theory

For a contraction to occur there must first be a stimulation of the muscle in the form of an impulse (action potential) from a motor neuron (nerve that connects to muscle).

[pic]

Note that one motor neuron does not stimulate the entire muscle but only number of muscle fibres within a muscle. The individual motor neuron plus the muscle fibres it stimulates, is called a motor unit. The motor end plate (also known as the neuromuscular junction) is the junction of the motor neurons axon and themuscle fibres it stimulates.
When an impulse reaches the muscle fibres of a motor unit, it stimulates a reaction in each sarcomere between the actin and myosin filaments. This reaction results in the start of a contraction and the sliding filament theory.
The reaction, created from the arrival of an impulse stimulates the 'heads' on the myosin filament to reach forward, attach to the actin filament and pull actin towards the centre of the sarcomere. This process occurs simultaneously in all sarcomeres, the end process of which is the shortening of all sarcomeres.
Troponin is a complex of three proteins that are integral to muscle contraction. Troponin is attached to the protein tropomyosin within the actin filaments, as seen in the image below. When the muscle is relaxed tropomyosin blocks the attachment sites for the myosin cross bridges (heads), thus preventing contraction.
When the muscle is stimulated to contract by the nerve impulse, calcium channels open in the sarcoplasmic reticulum (which is effectively a storage house for calcium within the muscle) and release calcium into the sarcoplasm (fluid within the muscle cell). Some of this calcium attaches to troponin which causes a change in the muscle cell that moves tropomyosin out of the way so the cross bridges can attach and produce musclecontraction. [pic] In summary the sliding filament theory of muscle contraction can be broken down into four distinct stages, these are;
1.Muscle activation: The motor nerve stimulates an action potential (impulse) to pass down a neuron to the neuromuscular junction. This stimulates the sarcoplasmic reticulum to release calcium into themuscle cell.
2. Muscle contraction: Calcium floods into the muscle cell binding with troponin allowing actin and myosin to bind. The actin and myosin cross bridges bind and contract using ATP as energy (ATP is an energy compound that all cells use to fuel their activity – this is discussed in greater detail in the energy system folder here at ptdirect).
3. Recharging: ATP is re-synthesised (re-manufactured) allowing actin and myosin to maintain their strong binding state
4. Relaxation: Relaxation occurs when stimulation of the nerve stops. Calcium is then pumped back into the sarcoplasmic reticulum breaking the link between actin and myosin. Actin and myosin return to their unbound state causing the muscle to relax. Alternatively relaxation (failure) will also occur when ATP is no longer available.
In order for a skeletal muscle contraction to occur; o There must be a neural stimulus o There must be calcium in the muscle cells o ATP must be available for energy

Q2. Discuss the anatomy/physiology of the pathologic process involved in Myesthenia Gravis. Specifically, focus on how normal anatomy/physiology has been altered to present the disease state.
Myasthenia gravis is a potentially serious but treatable organ specific autoimmune disorder characterised by weakness and fatigability of the voluntary muscles that is caused by autoantibodies against the nicotinic acetylcholine receptor (AChR) on the postsynaptic membrane at the neuromuscular junction.
Anatomy and physiology of the neuromuscular junction in myasthenia gravis:
The major abnormalities of the neuromusculaer junction in myasthenia gravis include (a) reduced number of the AChRs leading to reduced length of the postsynaptic membrane, (b) shortening of the synaptic folds due to destruction of the terminal expansions, and (c) widening of the synaptic clefts caused by the shortening of the junctional folds. These changes are brought about by autoimmune attack on the postsynaptic membrane. It is worth noting that the abnormalities in myasthenia gravis are postsynaptic in location (in contrast to presynaptic abnormality in Lambert-Eaton syndrome). The consequence of these abnormalities is a reduced safety factor. As previously discussed, reduction in safety factor coupled with a normal “synaptic rundown” leads to progressive reduction in amplitude of the EPP. This leads to myasthenic weakness characterised by fatigue on exertion.

References: 1. Lindstrom JM. Acetylcholine receptors and myasthenia. Muscle Nerve2000;23:453–477. [CrossRef][Medline][Web of Science]
2. Vincent A , Beeson D, Lang B. Molecular targets for autoimmune and genetic disorders and neuromuscular transmission. Eur J Biochem2000;267:6717–28. [Medline][Web of Science]
3. Drachman DB, de Silva S, Ramsay D, et al. Humoral pathogenesis of myasthenia gravis. Ann N Y Acad Sci1987;505:90–105. [CrossRef][Medline]
4. Newsome-Davis J , Harcourt G, Sommer N, et al. T-cell reactivity in myasthenia gravis. J Autoimmun1989;2 (suppl) :101–8. [Medline][Web of Science]
5. Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year of experience in over 1200 patients. Mt Sinai J Med1971;38:497–537. [Medline]