Renin–angiotensin System
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Renin–angiotensin System
The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance. When renal blood flow is reduced, juxtaglomerular cells in the kidneys convert the precursor prorenin (already present in the blood) into renin and secrete it directly into the circulation. Plasma renin then carries out the conversion of angiotensinogen, released by the liver, to a decapeptide called angiotensin I. Angiotensin I is subsequently converted to angiotensin II (an octapeptide) by the angiotensin-converting enzyme (ACE) found on the surface of vascular endothelial cells, predominantly those of the lungs. Angiotensin II has a short life of about 1 to 2 minutes. Then, it is rapidly degraded into a heptapeptide called angiotensin III by angiotensinases which are present in red blood cells and vascular beds in many tissues. Angiotensin III increases blood pres ...
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Angiotensin III
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys. An oligopeptide, angiotensin is a hormone and a dipsogen. It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver. Angiotensin was isolated in the late 1930s (first named 'angiotonin' or 'hypertensin') and subsequently characterized and synthesized by groups at the Cleveland Clinic and Ciba laboratories. Precursor and types Angiotensinogen Angiotensinogen is an α-2-globulin synthesized in the liver and is a precursor for angiotensin, but has also been indicated as having many other roles not related to angiotensin peptides. It is a member of the serpin family of proteins, leading to another name: Serpin A8, although it is not known to ...
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Hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high blood pressure, however, is a major risk factor for stroke, coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, vision loss, chronic kidney disease, and dementia. Hypertension is a major cause of premature death worldwide. High blood pressure is classified as primary (essential) hypertension or secondary hypertension. About 90–95% of cases are primary, defined as high blood pressure due to nonspecific lifestyle and genetic factors. Lifestyle factors that increase the risk include excess salt in the diet, excess body weight, smoking, and alcohol use. The remaining 5–10% of cases are categorized as secondary high blood pressure, defined as high blood pressure due to an identifiable cause, such ...
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Renin Inhibitors
Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I, which in turn reduces the formation of angiotensin II that facilitates blood pressure. Renin inhibitor is often preceded by ''direct'', called ''direct'' renin inhibitor in order to distinguish its mechanism from other renin–angiotensin–aldosterone system-interfering drugs such as angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and aldosterone receptor antagonists. These drugs inhibit the first and rate-limiting step of the renin–angiotensin–aldosterone system (RAAS), namely the conversion of angiotensinogen to angiotensin I. This leads to a totality in absence of angiotensin II based on the rationale that renin only acts to inhibit this step unlike Angiotensin Converting Enzyme which is also involved in other biochemical reactions. Since the 1970s, scientists have been trying to deve ...
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Angiotensin II Receptor Blocker
Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system. Their main uses are in the treatment of hypertension (high blood pressure), diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. They ''selectively'' block the activation of the AT1 receptor, preventing the binding of angiotensin II compared to ACE inhibitors. ARBs and the similar-attributed ACE inhibitors are both indicated as the first-line antihypertensives in patients developing hypertension along with left-sided heart failure. However, ARBs appear to produce less adverse effects compared to ACE inhibitors. Medical uses Angiotensin ...
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ACE Inhibitors
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart. ACE inhibitors inhibit the activity of angiotensin-converting enzyme, an important component of the renin–angiotensin system which converts angiotensin I to angiotensin II, and hydrolyses bradykinin. Therefore, ACE inhibitors decrease the formation of angiotensin II, a vasoconstrictor, and increase the level of bradykinin, a peptide vasodilator. This combination is synergistic in lowering blood pressure. As a result of inhibiting the ACE enzyme in the bradykinin system, the ACE inhibitor drugs allow for increased levels of bradykinin which would normally be degraded. Bradykinin produces prostaglandin. This mechanism can explain the two most common side e ...
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Extracellular Fluid
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower percentage than lean men. Extracellular fluid makes up about one-third of body fluid, the remaining two-thirds is intracellular fluid within cells. The main component of the extracellular fluid is the interstitial fluid that surrounds cells. Extracellular fluid is the internal environment of all multicellular animals, and in those animals with a blood circulatory system, a proportion of this fluid is blood plasma. Plasma and interstitial fluid are the two components that make up at least 97% of the ECF. Lymph makes up a small percentage of the interstitial fluid. The remaining small portion of the ECF includes the transcellular fluid (about 2.5%). The ECF can also be seen as having two components – plasma and lymph as a delivery s ...
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Potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmospheric oxygen to form flaky white potassium peroxide in only seconds of exposure. It was first isolated from potash, the ashes of plants, from which its name derives. In the periodic table, potassium is one of the alkali metals, all of which have a single valence electron in the outer electron shell, that is easily removed to create an ion with a positive charge – a cation, that combines with anions to form salts. Potassium in nature occurs only in ionic salts. Elemental potassium reacts vigorously with water, generating sufficient heat to ignite hydrogen emitted in the reaction, and burning with a lilac- colored flame. It is found dissolved in sea water (which is 0.04% potassium by weight), and occurs in many minerals such as orthocl ...
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Sodium In Biology
Sodium ions (Na) are necessary in small amounts for some types of plants, but sodium as a nutrient is more generally needed in larger amounts by animals, due to their use of it for generation of nerve impulses and for maintenance of electrolyte balance and fluid balance. In animals, sodium ions are necessary for the aforementioned functions and for heart activity and certain metabolic functions. The health effects of salt reflect what happens when the body has too much or too little sodium. Characteristic concentrations of sodium in model organisms are: 10 mM in ''E. coli'', 30mM in budding yeast, 10mM in mammalian cell and 100mM in blood plasma. Sodium distribution in species Humans The minimum physiological requirement for sodium is between 115 and 500 milligrams per day depending on sweating due to physical activity, and whether the person is adapted to the climate. Sodium chloride is the principal source of sodium in the diet, and is used as seasoning and preserva ...
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Distal Convoluted Tubule
The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lumen side), cells of the DCT have a thiazide-sensitive Na-Cl cotransporter and are permeable to Ca, via the TRPV5 channel. On the basolateral surface (peritubular capillary side) there is an ATP-dependent Na/K antiporter pump, a secondary active Na/Ca transporter, and an ATP dependent Ca transporter. The basolateral ATP dependent Na/K pump produces the gradient for Na to be absorbed from the apical surface via the Na/Cl symporter, and for Ca to be reclaimed into the blood by the Na/Ca basolateral antiporter. * It regulates pH by absorbing bicarbonate and secreting protons (H+) into the filtrate, or by absorbing protons and secreting bicarbonate into the filtrate. * Sodium and potassium levels are controlled by secreting K+ and absorbing Na+. ...
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Adrenal Cortex
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is also a secondary site of androgen synthesis. – "Adrenal Gland" Layers The adrenal cortex comprises three main zones, or layers that are regulated by distinct hormones as noted below. This ''anatomic zonation'' can be appreciated at the microscopic level, where each zone can be recognized and distinguished from one another based on structural and anatomic characteristics. ;Zona glomerulosa :The outermost layer, the zona glomerulosa is the main site for the production of aldosterone, a mineralocorticoid. The synthesis and secretion of aldosterone are mainly regulated by the renin–angiotensin–aldosterone system. The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2). Aldosterone is largel ...
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Aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a central role in the homeostatic regulation of blood pressure, plasma sodium (Na+), and potassium (K+) levels. It does so primarily by acting on the mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron. It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the kidney, thereby indirectly influencing water retention or loss, blood pressure, and blood volume.Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14 When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and kidney disease. Aldosterone has exactly the opposite function of the atrial natriu ...
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