Sodium Potassium Chloride Symporter Inhibitors
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Sodium Potassium Chloride Symporter Inhibitors
The Na-K-Cl cotransporter (NKCC) is a protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes (''SLC12A2'' and ''SLC12A1'' respectively). Two isoforms of the NKCC1/Slc12a2 gene result from keeping (isoform 1) or skipping (isoform 2) exon 21 in the final gene product. NKCC1 is widely distributed throughout the human body; it has important functions in organs that secrete fluids. It is found specifically in the kidney, where it extracts sodium, potassium, and chloride from the urine so they can be reabsorbed into the blood. Function NKCC proteins are membrane transport proteins that transport sodium (Na), potassium (K), and chloride (Cl) ions across the cell membrane. Because they move each solute in the same direction, they are considered symporters. They maintain electroneutrality by moving two positive ...
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Cotransporter
Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable active transport#Secondary active transport, coupled or cotransport (secondary active transport) and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters. Background Cotransporters are capable of moving solutes either up or down gradients at rates of 1000 to 100000 molecules per second. They may act as channels or transporters, depending on conditions under which they are assayed. The movement occurs by binding to two molecules or ions at a ti ...
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Stoichiometry
Stoichiometry refers to the relationship between the quantities of reactants and products before, during, and following chemical reactions. Stoichiometry is founded on the law of conservation of mass where the total mass of the reactants equals the total mass of the products, leading to the insight that the relations among quantities of reactants and products typically form a ratio of positive integers. This means that if the amounts of the separate reactants are known, then the amount of the product can be calculated. Conversely, if one reactant has a known quantity and the quantity of the products can be empirically determined, then the amount of the other reactants can also be calculated. This is illustrated in the image here, where the balanced equation is: : Here, one molecule of methane reacts with two molecules of oxygen gas to yield one molecule of carbon dioxide and two molecules of water. This particular chemical equation is an example of complete combustion. St ...
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Brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a vertebrate's body. In a human, the cerebral cortex contains approximately 14–16 billion neurons, and the estimated number of neurons in the cerebellum is 55–70 billion. Each neuron is connected by synapses to several thousand other neurons. These neurons typically communicate with one another by means of long fibers called axons, which carry trains of signal pulses called action potentials to distant parts of the brain or body targeting specific recipient cells. Physiologically, brains exert centralized control over a body's other organs. They act on the rest of the body both by generating patterns of muscle activity and by driving the secretion of chemicals called hormones. This centralized control allows rapid and coordinated respon ...
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Deafness
Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written with a lower case ''d''. It later came to be used in a cultural context to refer to those who primarily communicate through sign language regardless of hearing ability, often capitalized as ''Deaf'' and referred to as "big D Deaf" in speech and sign. The two definitions overlap but are not identical, as hearing loss includes cases that are not severe enough to impact spoken language comprehension, while cultural Deafness includes hearing people who use sign language, such as children of deaf adults. Medical context In a medical context, deafness is defined as a degree of hearing difference such that a person is unable to understand speech, even in the presence of amplification. In profound deafness, even the highest intensity sound ...
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Loop Diuretic
Loop diuretics are diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or chronic kidney disease. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function. Mechanism of action Loop diuretics are 90% bonded to proteins and are secreted into the proximal convoluted tubule through organic anion transporter 1 (OAT-1), OAT-2, and ABCC4. Loop diuretics act on the Na+-K+-2Cl− symporter (NKCC2) in the thick ascending limb of the loop of Henle to inhibit sodium, chloride and potassium reabsorption. This is achieved by competing for the Cl− binding site. Loop diuretics also inhibits NKCC2 at macula densa, reducing sodium transported into macula densa cells. This stimulates the release of renin, which through renin ...
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Furosemide
Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by mouth. When taken by mouth, it typically begins working within an hour, while intravenously, it typically begins working within five minutes. Common side effects include feeling lightheaded while standing, ringing in the ears, and sensitivity to light. Potentially serious side effects include electrolyte abnormalities, low blood pressure, and hearing loss. Blood tests are recommended regularly for those on treatment. Furosemide is a type of loop diuretic that works by decreasing the reabsorption of sodium by the kidneys. Common side effects of furosemide injection include hypokalemia (low potassium level), hypotension (low blood pressure), and dizziness. Furosemide was patented in 1959 and approved for medical use in 1964. It is on the Wo ...
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Cochlea
The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory organ of hearing, which is distributed along the partition separating the fluid chambers in the coiled tapered tube of the cochlea. The name cochlea derives . Structure The cochlea (plural is cochleae) is a spiraled, hollow, conical chamber of bone, in which waves propagate from the base (near the middle ear and the oval window) to the apex (the top or center of the spiral). The spiral canal of the cochlea is a section of the bony labyrinth of the inner ear that is approximately 30 mm long and makes 2 turns about the modiolus. The cochlear structures include: * Three ''scalae'' or chambers: ** the vestibular duct or ''scala vestibuli'' (containing perilymph), which lies superior to the cochlear duct and abuts the oval window ** the ty ...
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Endolymph
Endolymph is the fluid contained in the membranous labyrinth of the inner ear. The major cation in endolymph is potassium, with the values of sodium and potassium concentration in the endolymph being 0.91  mM and 154  mM, respectively. It is also called ''Scarpa's fluid'', after Antonio Scarpa. Structure The inner ear has two parts: the bony labyrinth and the membranous labyrinth. The membranous labyrinth is contained within the bony labyrinth, and within the membranous labyrinth is a fluid called endolymph. Between the outer wall of the membranous labyrinth and the wall of the bony labyrinth is the location of perilymph. Composition Perilymph and endolymph have unique ionic compositions suited to their functions in regulating electrochemical impulses of hair cells. The electric potential of endolymph is ~80-90 mV more positive than perilymph due to a higher concentration of K compared to Na. The main component of this unique extracellular fluid is potassium, which is ...
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Osmosis
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of higher solute concentration), in the direction that tends to equalize the solute concentrations on the two sides. It may also be used to describe a physical process in which any solvent moves across a selectively permeable membrane (permeable to the solvent, but not the solute) separating two solutions of different concentrations. Osmosis can be made to do work. Osmotic pressure is defined as the external pressure required to be applied so that there is no net movement of solvent across the membrane. Osmotic pressure is a colligative property, meaning that the osmotic pressure depends on the molar concentration of the solute but not on its identity. Osmosis is a vital process in biological systems, as biological membranes are semiperm ...
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Osmolality
Molality is a measure of the number of moles of solute in a solution corresponding to 1 kg or 1000 g of solvent. This contrasts with the definition of molarity which is based on a specified volume of solution. A commonly used unit for molality in chemistry is mol/ kg. A solution of concentration 1 mol/kg is also sometimes denoted as ''1 molal''. The unit ''mol/kg'' requires that molar mass be expressed in ''kg/mol'', instead of the usual ''g/mol'' or ''kg/kmol''. Definition The molality (''b''), of a solution is defined as the amount of substance (in moles) of solute, ''n''solute, divided by the mass (in kg) of the solvent, ''m''solvent: :b = \frac In the case of solutions with more than one solvent, molality can be defined for the mixed solvent considered as a pure pseudo-solvent. Instead of mole solute per kilogram solvent as in the binary case, units are defined as mole solute per kilogram mixed solvent. Origin The term ''molality'' is formed in analogy to ''mo ...
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Blood Vessel
The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from the tissues. Blood vessels are needed to sustain life, because all of the body's tissues rely on their functionality. There are five types of blood vessels: the arteries, which carry the blood away from the heart; the arterioles; the capillaries, where the exchange of water and chemicals between the blood and the tissues occurs; the venules; and the veins, which carry blood from the capillaries back towards the heart. The word ''vascular'', meaning relating to the blood vessels, is derived from the Latin ''vas'', meaning vessel. Some structures – such as cartilage, the epithelium, and the lens and cornea of the eye – do not contain blood vessels and are labeled ''avascular''. Etymology * artery: late Middle English; from Latin ...
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