Multiple Sclerosis

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Multiple sclerosis (MS) is an immunemediated inflammatory disease that attacks myelinated axons in the central nervous system (CNS) Destroy the myelin and the axon in variable degrees. During an MS attack, inflammation occurs in areas of the white matter of the central nervous system in random patches called plaques.

the spinal cord. high-speed transmission of electrochemical messages between the brain. when it is damaged. This process is followed by destruction of myelin. 4/10/12   . the fatty covering that insulates nerve cell fibers in the brain and spinal cord Myelin facilitates the smooth. neurological transmission of messages may be slowed or blocked completely. and the rest of the body. leading to diminished or lost function.

bacteria.  4/10/12 .ETIOLOGY  The cause of MS is unknown. It has been hypothesized that MS results when an environmental agent or event (eg. but it is likely that multiple factors are the reason for MS. virus. lack of sun exposure) acts in concert with a genetic predisposition to immune dysfunction. chemicals.

leading to uncontrolled immune cell proliferation and autoimmunity. 4/10/12 .Genetic and molecular factors  It may be that an individual with a polymorphism within the promoter region of a gene that is involved in immune reactivity generates an exaggerated response (eg. elevated gene expression of a proinflammatory gene) to a given antigen. HLADRB1 is the only chromosomal locus that has been consistently associated with MS susceptibility.

Vitamin D levels  Low levels of vitamin D have been proposed as one environmental factor contributing to the development of MS. by decreasing production of proinflammatory cytokines and increasing production of anti-inflammatory cytokines. also. high circulating levels of vitamin D appear to be associated with a reduced risk of MS. Vitamin D has a role in regulating immune response.[12  4/10/12 .

The incidence of the disease is lower in the equatorial regions of the world than in the southernmost and northernmost regions.Environmental factors  Geography is clearly an important factor in the etiology of MS.  4/10/12 .

Viruses  Another hypothesis is that a virus may infect the immune system. activating self-reactive T cells (myelin reactive) that would otherwise remain quiescent A virus that infects cells of the immune and nervous systems can possibly be reactivated periodically and thus lead to acute exacerbations in MS  4/10/12 .

4/10/12    .Symptoms  Symptoms of MS may be mild or severe depending on the area of the nervous system affected The initial symptom of MS is often blurred or double vision. red-green color distortion. muscle weakness in their extremities and difficulty with coordination and balance at some time during the course of the disease. or even blindness in one eye is due to the Inflammatory problems of the optic nerve may be diagnosed as retrobulbaror optic neuritis.

or "pins and needles" sensations. prickling.the involuntary increased tone of muscles leading to stiffness and spasms . memory. attention. cognitive impairments such as difficulties with common. Spasticity . and poor judgment. Cognitive symptoms occur when lesions develop in brain areas responsible for information processing. transitory abnormal sensory feelings such as numbness. as is fatigue.  MS can produce partial or complete paralysis. exhibit paresthesias. 4/10/12    .

sexual dysfunction may become a problem. 4/10/12 . As the disease progresses. Bowel and bladder control may also be lost.

helps to maintain    4/10/12 . approximately 70% of the ATP is consumed to fuel sodium pumps. Roughly 25% of all cytoplasmic ATP is hydrolyzed by sodium pumps in resting humans. In nerve cells.Na⁺-K⁺ ATPase  The Na+-K+-ATPase is a highly-conserved integral membrane protein that is present in all cells of higher organisms. The Na+/K+-ATPase resting potential .

 4/10/12 . The ionic transport conducted by sodium pumps creates both an electrical and chemical gradient across the plasma membrane. Abnormalities in the number or function of Na+-K+-ATPases are thought to be involved in several pathologic states.

The sodium-potassium pump moves 3 sodium ions out by hydrolysing ATP and allows 2 potassium ions in through active transport. cells must keep a low concentration of sodium ions and high levels of potassium ions within the cell ( intracellular).Function Resting potential  In order to maintain the cell membrane potential.  4/10/12 .

Transport  Export of sodium from the cell provides the driving force for several secondary active transporters membrane transport proteins. 4/10/12 . amino acids. and other nutrients into the cell by use of the sodium gradient. which import glucose.

which. can cause the cell to swell up and lyse.Controlling cell volume  Inside the cell. 4/10/12    . The Na+-K+ pump is a mechanism to prevent this. Most. unless checked. being negatively charged. there are many proteins and other organic compounds that cannot escape from the cell. All these substances tend to cause the osmosis of water into the cell. collect around them a large number of positive ions .

and varies in size from –20 to – 200 mV (milivolt) in different cells and species (in humans it is –70mV). The membrane potential is always negative inside the cell. called the resting membrane potential. 4/10/12   .The Action Potential  The combination of the Na+K+ATPase pump and the leak channels cause a stable imbalance of Na+ and K+ ions across the membrane This imbalance of ions causes a potential difference (or voltage) between the inside of the neurone and its surroundings.

The normal membrane potential inside the axon of nerve cells is –70mV. where the nerve and muscle cells resting membrane potential changes. This involves an explosion of electrical activity. and since this potential can change in nerve cells it is called the resting potential The threshold potential is the membrane potential to which a membrane must be depolarized to initiate an action potential. An action potential occurs when a neurone sends information down an axon. a stimulus is applied a brief reversal of     4/10/12 When .

 The voltage-gated ion channels can detect this change. A stimulus can cause the membrane potential to change a little.  The causes sodium ions to rush in.5ms. and when the potential reaches – 30mV the sodium channels open for 0. . making the inside of the cell more positive.Depolarisation.  This phase is referred to as a depolarisation since the normal voltage polarity (negative 4/10/12 inside) is reversed (becomes positive inside).

4/10/12 .

it is called repolarisation. there is a slight ‘overshoot’ in the movement of potassium ions (called hyperpolarisation). 4/10/12    . At a certain point. causing potassium ions to rush out. Since this restores the original polarity. As the polarity becomes restored. making the inside more negative again. the depolarisation of the membrane causes the sodium channels to close. The resting membrane potential is restored by the Na+K+ATPase pump. Repolarisation.5ms. As a result the potassium channels open for 0.

    .Carbohydrate and amino acid metabolism in brain. Neurons oxidize glucose by glycolysis and the TCA cycle and provides almost all the ATP to these cells. It uses 20% of total oxygen consumed by the body 4/10/12 at rest. TCA cycle is fully operated and it uses oxygen at fairly constant rate.  The neuron of mammalian brain normally use glucose as fuel. Brain is constantly depend on incoming glucose in the blood in the well-fed state.

The nuerons of the brain cannot directly use free fatty acids or lipids from the blood as fuels. 4/10/12     . By four hours after a meal. They uses a β-hydroxybutyrate ( a ketone body). insulin secretion will slow and glucagon secretion is increased. the blood glucose will decrease more. the blood glucose level is diminished slightly. and the tissue receive glucose released from liver glycogen.  Glycolysis is 20% operated. In the first two hour after a meal. formed from fatty acids in the liver.

valine and threonine. isoleucine. arginine and histidine. There are certain amino acid that enters the TCA cycle as α-ketogluterate or as succinylCoA and produce the energy for brain. glutamine. glutamate. the liver degrades certains protein to amino acid.From PROTEIN:  To provide glucose for the brain. Five amino acid that’s are converted to αketogluterate are proline. Four amino acids are converted to succinulCoA are methionine. 4/10/12    .