Central nervous system extracellular fluid

Both thiamin monophosphate and free thiamin are found in cerebrospinal fluid. Uptake of thiamin monophosphate into cells in the central nervous system involves extracellular hydrolysis to free thiamin, probably catalyzed... 

Entry of drugs into the cerebrospinal fluid (CSF) and extracellular space of the central nervous system (CNS) is relatively restricted. The endothelial cells of the CNS have tight junctions and do not have intercellular pores and pinocytotic vesicles. 

Among the catecholamines, dopamine has long been of interest to both chemists and neuroscientists. It is one of the most important neurotransmitters and is ubiquitous in the mammalian central nervous system[5]. It modulates many aspects of brain circuitry in a major system of the brain including the extra pyramidal and mesolimbic system, as well as the hypothalamic pituitary axis[6]. It also plays a crucial role in the functioning of the central nervous, cardiovascular, renal and hormonal systems[4], A loss of dopamine containing neurons or its transmission is also related to a number of illnesses and conditions including Parkinson s disease, schizophrenia, motivational habit, reward mechanisms and the regulation of motor functions and in the function of the central nervous, hormonal and cardiovascular system[5,18,19]. It is therefore of interest to measure dopamine in the extracellular fluid in animals to order to monitor neurotransmission processes and correlate neurochemistry with behavior[19]. 

Figure 50-12 Key elements in water homeostasis. So/id //nes indicate osmotically stimulated pathways, and dashed lines Indicate volume-stimulated pathways.The dotted lines indicate negative feedback pathways. Abbreviations ANfl atrial natriuretic peptide AVP, arginine vasopressin CNS, central nervous system C/- extracellular fluid OPR, oropharyngeal reflex. (From Reeves W,AndreoliT.The posterior pituitary and water metabolism. /n Wj7son JD, Foster DW, eds. Williams textbook of endocrinology, 8tb ed. Philadelpbia WB Sounders Co, 1992 312.)...

Intracellular nucleotides play an important role in enzyme and ion channel regulation as well as in energy metabolism and nucleic acid synthesis. There is now widespread appreciation that ATP (and other nucleotides) may so be released into the extracellular fluid by exocytosis from nerve terminals or secretory cells. Thus, extracellular ATP can act as a neurotransmitter or modulator in a variety of peripheral tissues and cells, in autonomic ganglia and in the central nervous system [1-3]. The responses to extracellular ATP are mediated via membrane-bound receptors, termed P2-purinoceptors. Evidence has accumulated indicating heterogeneity of P2-purinoceptors, and it has become apparent that ATP acts on at least five P2-purinoceptor subtypes, i.e. P2X> P2Y> P2U> 2T 2Z... 

These polar drugs do not penetrate into most cells, central nervous system (CNS), and the eye. Except for streptomycin, there is negligible binding of aminoglycosides to plasma proteins. The volume of distribution of these drugs approximates the volume of extracellular fluid. 

Fig. 18.4. Glutamate or NMDA receptors in the central nervous system. Binding of agonists (glutamate or NMDA) opens the channel, allowing potassium ions to flow outward to extracellular fluid (ECF) and sodium and calcium ions to flow into the nerve cells. Increased intracellular (IGF) calcium ion concentration triggers a cascade that produces a response and liberates the neuronal messenger nitric oxide (NO). Ketamine may produce anesthesia by blocking these NMDA-controlled channels, which are located at excitatory synapses on pyramidal cells (3). Glycine acts as a positive allosteric modulator at the NMDA receptor.

Blood-brain barrier the barrier that must be crossed when water and solutes are exchanged between blood and extracellular fluid of the central nervous system. Many substances, when injected intravenously, become distributed throughout the various tissues and organs of the body, except for the central nervous system, e. g. acidic dyes, bile acids, tetanus toxin, sodium ferricyanide, trypan blue. 

The permeability properties of cerebral capillaries are quite different from those of capillaries in other organs and tissues. Water-filled channels, which can be demonstrated in the walls of most non-nervous capillaries, are absent from cerebral capillaries. A hydrostatically promoted transcapillary flow of fluid into tissue on the arterial side, with the reverse process on the venous side (i.e. Starling-type transcapillary flow) has never been demonstrated in the brain. The central nervous system does not possess lymphatics. Cerebral capillary endothelial cells have no pino-cytotic activity. Furthermore, the central nervous system and various compartments of cerebrospinal fluid are also excluded from the extracellular fluid of the rest of the body by the tight choroid epithelium and the tight layer of arachnoid. 

In clinical chemistry, the variations of the Na concentration level in the extracellular fluid are interpreted as follows [3] (1) The level of Na" is elevated in dehydration (water deficit), central nervous system trauma or disease, and hyperadrenocorticism with hyperaldosteronism or corticosterone of corticosteroid excess. (2) A decrement of the Na level is observed in adrenal insufficiency, in renal insufficiency (especially with inadequate Na intake), in renal tubular acidosis as a physiological response to trauma and bums (Na shifts into cells), in unusual losses via the gastrointestinal tract as in acute or chronic diarrhea or intestinal obstruction or fistula, and in unusual sweating with inadequate sodium replacement. In some patients with edema associated with cardiac or renal disease, seram Na concentration is low, even though total body sodium content is greater than normal water retention (excess antidiuretic hormone, ADH) and abnormal distribution of sodium between intracellular and extracellular fluid contribute to this paradoxical situation. Hyperglycemia occasionally results in a shift of intracellular water to the extracellular... 

If there is insufficient bicarbonate to compensate for the extra acid, acidosis can occur. Formally, acidosis is a significant decrease in pH of extracellular fluid. This condition can occur due to both respiratory and metabolic abnormalities. Respiratory acidosis occurs when breathing abnormalities result in CO2 retention and an elevation in Pco2 in alveoli and arterial blood (known as hypercapnia). The term Pco2 refers to the partial pressure of CO2 in the pulmonary alveoli during respiration. Retention of CO2 can result from inadequate ventilation during anesthesia, certain conditions that result from central nervous system disease, or from drug use, and it is observed with emphysema. Metabolic acidosis occurs with starvation, uncontrolled diabetes mellitus with ketosis, and with electrolyte and water loss due to diarrhea.il... 

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