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Extended Response Case Study Question: Taking into account the role of the myelin sheath and the nodes of Ranvier, explain how APs are propagated along an axon, in a healthy subject, and how this is changed in MS.     Answer: Nervous System The axons of neurons often are myelinated i.e. they are wrapped around by a sheath of myelin. Myelin is a protein-lipid complex, which is formed by Schwan Cells of in the Central Nervous System when they wrap their membrane around the axon, eventually locked together by a membrane protein, P0. Nodes of Ranvier are the portions of the axon that are not being enveloped by the myelin i.e. these about 1µm periodic gaps of separated by 1mm are unmyelinated. Myelin acts as insulation to nerve impulse conduction. Nerve impulses are sent between neurons which is the only mode of communication for the nervous system. Electronic potentials that can produce propagated disturbances are called action potentials or nerve impulses. The nerve impulses are produced due to change in ionic conduction across the cell membrane of the neurons. The potential of nerve cells are found to be negative inside relative to outside; it is about -70mV. When the neuron is stimulated a series of potential changes occur across its membrane and the stimulus thus propagates through the axon to another adjacent neuron. Depolarization increases the membrane potential to +35mV and again reverses and falls rapidly causing to reach the resting depolarized state. In unmyelinated nerve fibres local circuits of ion current are produced in the active regions of the neuron which is stimulated; the local circuit thus produced can depolarize the adjacent part of the membrane which continues in s sequential fashion (Arancibia-Carcamo & Attwell, 2014). Conversely, in myelinated neurons ion exchange is allowed only at the Nodes of Ranvier and rest of the axon is insulated by myelin itself. This increases the speed of transmission of impulse through the axon. When an impulse reaches a Node of Ranvier it cannot flow through the high-resistance myelin sheath instead depolarizes the membrane at the next Node of Ranvier about 1mm away from it. Thus myelin increases the length constant i.e. the distance an ion travels before leaking out of the membrane by increasing the membrane resistance and thus resulting in insulation of the neuron. Further myelin decreases the capacitance of the membrane by separating the opposite charges across the two sides of the membrane by a considerable distance.  Thus in myelinated neurons impulse flows in a jumping fashion from one Node to the next which is termed as Saltatory Conduction. Multiple Sclerosis is an idiopathic, autoimmune, inflammatory disorder of the Central Nervous System that causes patchy destruction of the myelin sheath of the neurons. The destruction of the myelin sheath results in delayed or blocked conduction of impulses through the affected neurons leading to several neurodegenerative symptoms. Further the damage of myelin causes patches of scar tissues at various regions of the Brain and Spinal Cord and hence the name Multiple Sclerosis (Scleroses meaning scar tissue) (Dendrou, Fugger & Friese, 2015). The impairment of nerve impulse conduction can affect physiological functions such as movement, speech or sight. Diagnosis at early stages of the disease prognosis is very difficult which causes delay in commencement of treatment.   Endocrine System Metabolism is one of the most significant physiological processes necessary for the sustenance if life. Each and every cell of the human body undergoes various levels of metabolism to perform the fundamental bodily functions. Thyroid gland plays a key role in this context by regulating the level of metabolism in the cells required for the optimal functioning of the same. The hormones secreted by the thyroid gland are Thyroxine (T4) and triiodothyronine (T4), which primarily regulates the oxygen consumption of cells, lipid and carbohydrate metabolism, thermogenesis, growth and nervous system development. Thus they play a pivotal role in growth and maturity and deregulation of the hormone levels can lead to severe disorders. Hence, the hormone secretion is intensely regulated to maintain normal body functioning. Thyroid stimulating hormone or Thyrotropin secreted from the anterior pituitary regulates the secretion of the thyroid gland. It is a tropic hormone and secretion of Thyrotropin in turn is regulated by Thyrotropin releasing hormone secreted from the paraventricular nucleus of the hypothalamus. Circulating thyroid hormones have feedback effects at hypothalamic and pituitary levels thus completing the Hypothalamus pituitary thyroid axis to maintain optimum levels of both the thyroid hormones in circulating blood (Ortiga?Carvalho, Chiamolera, Pazos?Moura & Wondisford, 2016). Increased secretion and hence occurrence of thyroid hormones in the circulating blood results in decreased secretion of Thyrotropin and Thyrotropin releasing hormone and the opposite occurs when thyroid hormones levels are low in circulating blood. Thyroid hormones levels are maintained at a very narrow range by the three glands, failure of any of them causes excess or too less production of thyroid hormones resulting in hyperthyroidism or hypothyroidism respectively. However, the state of normal functioning of the thyroid gland is known as euthyroidism. Hypothyroidism, generally called Myxedema in adults can be caused by a number of diseases of the thyroid gland or can be secondary effects of pituitary gland or hypothalamus dysfunction. In case of pituitary hypothyroidism and hypothalamic hypothyroidism the patient responds to a dose of Thyroid stimulating hormone or Thyroxin; but in can of thyroid gland dysfunction no response to Thyroxin is obtained (Pearce et al., 2013). Symptoms of hypothyroidism may include markedly decreased basal metabolic rate, coarse and sparse hair, dry and yellow skin and low tolerance of cold. Hyperthyroidism is more common in women than in men and is often caused by self-antibodies that stimulate the receptor for thyroid hormones. This results in non-functioning of thyroid hormone in spite of being present in the circulating blood. Both the thyroid hormone secretion are substantially increased and due to over activity of the thyroid gland, it gets enlarged leading to a condition called Goitre (Biondi et al., 2015). However, as thyroid hormone levels remain adequate in the circulating blood Thyroid stimulating hormone is maintained at a low level due to feedback inhibition of the same. Some of the significant symptoms of hyperthyroidism are weight loss, low tolerance of heat, increased blood pressure, and a markedly increase in the basal metabolic rate of the body.   References Ortiga?Carvalho, T. M., Chiamolera, M. I., Pazos?Moura, C. C., & Wondisford, F. E. (2016). Hypothalamus?Pituitary?Thyroid Axis. Comprehensive Physiology. Pearce, S. H., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J. L. (2013). 2013 ETA guideline: management of subclinical hypothyroidism. European thyroid journal, 2(4), 215-228. Biondi, B., Bartalena, L., Cooper, D. S., Hegedüs, L., Laurberg, P., & Kahaly, G. J. (2015). The 2015 European Thyroid Association guidelines on diagnosis and treatment of endogenous subclinical hyperthyroidism. European thyroid journal, 4(3), 149-163. Arancibia-Carcamo, I. L., & Attwell, D. (2014). The node of Ranvier in CNS pathology. Acta neuropathologica, 128(2), 161-175. Dendrou, C. A., Fugger, L., & Friese, M. A. (2015). Immunopathology of multiple sclerosis. Nature reviews. Immunology, 15(9), 545.

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