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Autoregulation is a process within many biological systems, resulting from an internal adaptive mechanism that works to adjust (or mitigate) that system's response to stimuli. While most systems of the body show some degree of autoregulation, it is most clearly observed in the kidney, the heart, and the brain. [1] Perfusion of these organs is essential for life, and through autoregulation the body can divert blood (and thus, oxygen) where it is most needed.
More so than most other organs, the brain is very sensitive to increased or decreased blood flow, and several mechanisms (metabolic, myogenic, and neurogenic) are involved in maintaining an appropriate cerebral blood pressure. Brain blood flow autoregulation is abolished in several disease states such as traumatic brain injury, [2] stroke, [3] brain tumors, or persistent abnormally high CO2 levels. [4] [5]
Homeometric autoregulation, in the context of the circulatory system, is the heart's ability to increase contractility and restore stroke volume when afterload increases. [6] Homeometric autoregulation occurs independently of cardiomyocyte fiber length, via the Bowditch and/or Anrep effects. [7]
This is in contrast to heterometric regulation, governed by the Frank-Starling law, which results from a more favorable positioning of actin and myosin filaments in cardiomyocytes as a result of changing fiber lengths. [8]
Since the heart is a very aerobic organ, needing oxygen for the efficient production of ATP & Creatine Phosphate from fatty acids (and to a smaller extent, glucose & very little lactate), the coronary circulation is auto regulated so that the heart receives the right flow of blood & hence sufficient supply of oxygen. If a sufficient flow of oxygen is met and the resistance in the coronary circulation rises (perhaps due to vasoconstriction), then the coronary perfusion pressure (CPP) increases proportionally, to maintain the same flow. In this way, the same flow through the coronary circulation is maintained over a range of pressures. This part of coronary circulatory regulation is known as auto regulation and it occurs over a plateau, reflecting the constant blood flow at varying CPP & resistance. The slope of a CBF (coronary blood flow) vs. CPP graph gives 1/Resistance. Autoregulation maintains a normal blood flow within the pressure range of 70–110 mm Hg. Blood flow is independent of bp. However autoregulation of blood flow in the heart is not so well developed like that in brain.
Regulation of renal blood flow is important to maintaining a stable glomerular filtration rate (GFR) despite changes in systemic blood pressure (within about 80-180 mmHg). In a mechanism called tubuloglomerular feedback, the kidney changes its own blood flow in response to changes in sodium concentration. The sodium chloride levels in the urinary filtrate are sensed by the macula densa cells at the end of the ascending limb. When sodium levels are moderately increased, the macula densa releases ATP [9] and reduces prostaglandin E2 release [10] to the juxtaglomerular cells nearby. The juxtaglomerular cells in the afferent arteriole constrict, and juxtaglomerular cells in both the afferent and efferent arteriole decrease their renin secretion. These actions function to lower GFR. Further increase in sodium concentration leads to the release of nitric oxide, a vasodilating substance, to prevent excessive vasoconstriction. [10] In the opposite case, juxtaglomerular cells are stimulated to release more renin, which stimulates the renin–angiotensin system, producing angiotensin I which is converted by Angio-Tensin Converting Enzyme (ACE) to angiotensin II. Angiotensin II then causes preferential constriction of the efferent arteriole of the glomerulus and increases the GFR.
This is so-called "steady-state system". An example is a system in which a protein P that is a product of gene G "positively regulates its own production by binding to a regulatory element of the gene coding for it," [11] and the protein gets used or lost at a rate that increases as its concentration increases. This feedback loop creates two possible states "on" and "off". If an outside factor makes the concentration of P increase to some threshold level, the production of protein P is "on", i.e. P will maintain its own concentration at a certain level, until some other stimulus will lower it down below the threshold level, when concentration of P will be insufficient to make gene G express at the rate that would overcome the loss or use of the protein P. This state ("on" or "off") gets inherited after cell division, since the concentration of protein a usually remains the same after mitosis. However, the state can be easily disrupted by outside factors. [11]
Similarly, this phenomenon is not only restricted to genes but may also apply to other genetic units, including mRNA transcripts. Regulatory segments of mRNA called a Riboswitch can autoregulate its transcription by sequestering cis-regulatory elements (particularly the Shine-Dalgarno sequence) located on the same transcript as the Riboswitch. The Riboswitch stem-loop has a region complementary to the Shine-Dalgarno but is sequestered by complementary base pairing in the loop. With sufficient ligand, the ligand may bind to the stem-loop and disrupt intermolecular bonding, resulting in the complementary Shine-Dalgarno stem-loop segment binding to the complementary Riboswitch segment, preventing Ribosome from binding, inhibiting translation. [12]
In biology, homeostasis is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance, being kept within certain pre-set limits. Other variables include the pH of extracellular fluid, the concentrations of sodium, potassium and calcium ions, as well as that of the blood sugar level, and these need to be regulated despite changes in the environment, diet, or level of activity. Each of these variables is controlled by one or more regulators or homeostatic mechanisms, which together maintain life.
Azotemia is a medical condition characterized by abnormally high levels of nitrogen-containing compounds in the blood. It is largely related to insufficient or dysfunctional filtering of blood by the kidneys. It can lead to uremia and acute kidney injury if not controlled.
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: they convey blood between the arterioles and venules. These microvessels are the site of exchange of many substances with the interstitial fluid surrounding them. Substances which cross capillaries include water, oxygen, carbon dioxide, urea, glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in the microcirculation.
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure called Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 1 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the foot processes of the podocytes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged ; first with the interstitial fluid outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—urine—exits: it is composed of water, metabolic waste, and toxins.
Renin, also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the renin–angiotensin–aldosterone axis—that increases the volume of extracellular fluid and causes arterial vasoconstriction. Thus, it increases the body's mean arterial blood pressure.
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.
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.
The juxtaglomerular apparatus is a structure in the kidney that regulates the function of each nephron, the functional units of the kidney. The juxtaglomerular apparatus is named because it is next to (juxta-) the glomerulus.
Thirst is the craving for potable fluids, resulting in the basic instinct of animals to drink. It is an essential mechanism involved in fluid balance. It arises from a lack of fluids or an increase in the concentration of certain osmolites, such as sodium. If the water volume of the body falls below a certain threshold or the osmolite concentration becomes too high, structures in the brain detect changes in blood constituents and signal thirst.
The glomerulus is a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally supported by the mesangium, composed of intraglomerular mesangial cells. The blood is filtered across the capillary walls of this tuft through the glomerular filtration barrier, which yields its filtrate of water and soluble substances to a cup-like sac known as Bowman's capsule. The filtrate then enters the renal tubule of the nephron.
In the kidney, the macula densa is an area of closely packed specialized cells lining the wall of the distal tubule, at the point where the thick ascending limb of the Loop of Henle meets the distal convoluted tubule. The macula densa is the thickening where the distal tubule touches the glomerulus.
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.
An osmoreceptor is a sensory receptor primarily found in the hypothalamus of most homeothermic organisms that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including two of the circumventricular organs – the vascular organ of the lamina terminalis, and the subfornical organ. They contribute to osmoregulation, controlling fluid balance in the body. Osmoreceptors are also found in the kidneys where they also modulate osmolality.
Juxtaglomerular cells, also known as granular cells are cells in the kidney that synthesize, store, and secrete the enzyme renin. They are specialized smooth muscle cells mainly in the walls of the afferent arterioles that deliver blood to the glomerulus. In synthesizing renin, they play a critical role in the renin–angiotensin system and thus in autoregulation of the kidney.
Renovascular hypertension is a condition in which high blood pressure is caused by the kidneys' hormonal response to narrowing of the arteries supplying the kidneys. When functioning properly this hormonal axis regulates blood pressure. Due to low local blood flow, the kidneys mistakenly increase blood pressure of the entire circulatory system. It is a form of secondary hypertension - a form of hypertension whose cause is identifiable.
The afferent arterioles are a group of blood vessels that supply the nephrons in many excretory systems. They play an important role in the regulation of blood pressure as a part of the tubuloglomerular feedback mechanism.
In the physiology of the kidney, tubuloglomerular feedback (TGF) is a feedback system inside the kidneys. Within each nephron, information from the renal tubules is signaled to the glomerulus. Tubuloglomerular feedback is one of several mechanisms the kidney uses to regulate glomerular filtration rate (GFR). It involves the concept of purinergic signaling, in which an increased distal tubular sodium chloride concentration causes a basolateral release of adenosine from the macula densa cells. This initiates a cascade of events that ultimately brings GFR to an appropriate level.
The myogenic mechanism is how arteries and arterioles react to an increase or decrease of blood pressure to keep the blood flow constant within the blood vessel. Myogenic response refers to a contraction initiated by the myocyte itself instead of an outside occurrence or stimulus such as nerve innervation. Most often observed in smaller resistance arteries, this 'basal' myogenic tone may be useful in the regulation of organ blood flow and peripheral resistance, as it positions a vessel in a preconstricted state that allows other factors to induce additional constriction or dilation to increase or decrease blood flow.
Extraglomerular mesangial cells are light-staining pericytes in the kidney found outside the glomerulus, near the vascular pole. They resemble smooth muscle cells and play a role in renal autoregulation of blood flow to the kidney and regulation of systemic blood pressure through the renin–angiotensin system. Extraglomerular mesangial cells are part of the juxtaglomerular apparatus, along with the macula densa cells of the distal convoluted tubule and the juxtaglomerular cells of the afferent arteriole.
Contraction alkalosis refers to the increase in blood pH that occurs as a result of fluid losses. The change in pH is especially pronounced with acidic fluid losses caused by problems like vomiting.