1.
Drug
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A drug is any substance that, when inhaled, injected, smoked, consumed, absorbed via a patch on the skin, or dissolved under the tongue, causes a physiological change in the body. In pharmacology, a drug, also called a medication or medicine, is a chemical substance used to treat, cure, prevent. Traditionally drugs were obtained through extraction from plants, but more recently also by organic synthesis. Pharmaceutical drugs may be used for a duration, or on a regular basis for chronic disorders. Another major classification system is the Biopharmaceutics Classification System and this classifies drugs according to their solubility and permeability or absorption properties. Psychoactive drugs are chemical substances that affect the function of the nervous system, altering perception. They include alcohol, a depressant, and the nicotine and caffeine. These three are the most widely consumed psychoactive drugs worldwide and are also considered recreational drugs since they are used for rather than medicinal purposes. Other recreational drugs include hallucinogens, opiates and amphetamines and some of these are used in spiritual or religious settings. Some drugs can cause addiction and all drugs can have side effects, excessive use of stimulants can promote stimulant psychosis. Many recreational drugs are illicit and international such as the Single Convention on Narcotic Drugs exist for the purpose of their prohibition. The transitive verb to drug arose later and invokes the psychoactive rather than properties of a substance. A medication or medicine is a drug taken to cure or ameliorate any symptoms of an illness or medical condition, the use may also be as preventive medicine that has future benefits but does not treat any existing or pre-existing diseases or symptoms. In the United Kingdom, behind-the-counter medicines are called pharmacy medicines which can only be sold in registered pharmacies and these medications are designated by the letter P on the label. The range of medicines available without a prescription varies from country to country, medications are typically produced by pharmaceutical companies and are often patented to give the developer exclusive rights to produce them. Those that are not patented are called generic drugs since they can be produced by other companies without restrictions or licenses from the patent holder, pharmaceutical drugs are usually categorised into drug classes. A group of drugs will share a chemical structure, or have the same mechanism of action. Another major classification system is the Biopharmaceutics Classification System and this groups drugs according to their solubility and permeability or absorption properties
2.
Interstitial fluid
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Interstitial fluid or tissue fluid is a solution that bathes and surrounds the tissue cells of multicellular animals. It is the component of the extracellular fluid, which also includes plasma. The interstitial fluid is found in the interstices - the spaces between cells, on average, a person has about 10 litres of interstitial fluid, providing the cells of the body with nutrients and a means of waste removal. Plasma and interstitial fluid are very similar and this similarity exists because water, ions, and small solutes are continuously exchanged between plasma and interstitial fluids across the walls of capillaries. Plasma, the component in blood, communicates freely with interstitial fluid through pores. Hydrostatic pressure is generated by the force of the heart. It pushes water out of the capillaries, the water potential is created due to the inability of certain blood proteins to pass through the walls of capillaries. The build-up of these proteins within the capillaries induces osmosis, the water passes from a high concentration outside of the vessels to a low concentration inside of the vessels, in an attempt to reach an equilibrium. The osmotic pressure drives water back into the vessels, because the blood in the capillaries is constantly flowing, equilibrium is never reached. The balance between the two forces differs at different points on the capillaries, at the arterial end of a vessel, the hydrostatic pressure is greater than the osmotic pressure, so the net movement favors water and other solutes being passed into the tissue fluid. At the venous end, the pressure is greater, so the net movement favors substances being passed back into the capillary. This difference is created by the direction of the flow of blood, to prevent a build-up of tissue fluid surrounding the cells in the tissue, complementing the venous system is the lymphatic system, which plays a part in the transport of tissue fluid. Tissue fluid can pass into the lymph vessels, and eventually ends up rejoining the blood. Sometimes the removal of fluid does not function correctly. This can cause swelling, often around the feet and ankles, the position of swelling is due to the effects of gravity. Interstitial fluid consists of a solvent containing sugars, salts, fatty acids, amino acids, coenzymes, hormones, neurotransmitters, white blood cells. This water solvent accounts for 26% of the water in the human body, the composition of tissue fluid depends upon the exchanges between the cells in the biological tissue and the blood. This means that tissue fluid has a different composition in different tissues, not all of the contents of the blood pass into the tissue, which means that tissue fluid and blood are not the same
3.
Capillary
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Capillaries are the smallest of a bodys blood vessels that make up the microcirculation. Their endothelial linings are only one layer thick. Lymph capillaries connect with larger vessels to drain lymph collected in the microcirculation. The term angiogenesis denotes the formation of new capillaries from pre-existing blood vessels, blood flows from the heart through arteries, which branch and narrow into arterioles, and then branch further into capillaries where nutrients and wastes are exchanged. The capillaries then join and widen to become venules, which in turn widen and converge to become veins, capillaries do not function on their own, but instead in a capillary bed, an interweaving network of capillaries supplying organs and tissues. The more metabolically active a cell or environment is, the capillaries are required to supply nutrients. Metarterioles are found primarily in the mesenteric microcirculation and were thought to be present in most or all capillary beds. The physiological mechanisms underlying precapillary resistance is no longer considered to be a result of precapillary sphincters outside of the mesentery organ, lymphatic capillaries are slightly larger in diameter than blood capillaries, and have closed ends. This structure permits interstitial fluid to flow into them but not out, lymph capillaries have a greater internal oncotic pressure than blood capillaries, due to the greater concentration of plasma proteins in the lymph. However lipid-soluble molecules can diffuse through the endothelial cell membranes along concentration gradients. Tight junctions can be divided into two subtypes, Those with numerous transport vesicles, which are found primarily in skeletal muscles, fingers, gonads. Those with few vesicles, which are found in the central nervous system. These capillaries are a constituent of the blood–brain barrier, fenestrated capillaries have pores in the endothelial cells that are spanned by a diaphragm of radially oriented fibrils and allow small molecules and limited amounts of protein to diffuse. In the renal glomerulus there are cells with no diaphragms, called foot processes or pedicels. Both of these types of vessels have continuous basal laminae and are primarily located in the endocrine glands, intestines, pancreas. Sinusoidal capillaries are a type of open-pore capillary, that have larger openings in the endothelium. These types of blood vessels allow red and white cells and various serum proteins to pass. These capillaries lack pinocytotic vesicles, and therefore utilize gaps present in cell junctions to permit transfer between cells, and hence across the membrane
4.
Cardiac output
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Cardiac output, is a term used in cardiac physiology that describes the volume of blood being pumped by the heart, in particular by a left or right ventricle, per unit time. CO values can be represented using many physical units, such as dm3/min and L/min, because cardiac output is related to the quantity of blood delivered to various parts of the body, it is an important indicator of how efficiently the heart can meet the demands of the body. For instance, infections are correlated with high CO and heart failure with low CO, along with stroke volume, cardiac output is a global blood flow parameter of interest in hæmodynamics – the study of the flow of blood under external forces. The factors affecting stroke volume and heart rate also affect cardiac output, the figure to the right illustrates this dependency and lists some of these factors. A detailed hierarchical illustration is provided in a subsequent figure, there are many methods of measuring CO, both invasively and non-invasively, each with its own advantages and drawbacks. No standard or reference measurement against which all of these methods can be compared exists, the function of the heart is to drive blood through the circulatory system in a cycle that delivers oxygen, nutrients and chemicals to the bodys cells and removes cellular waste. This is detailed in equation below, there are a number of clinical methods to measure cardiac output, ranging from direct intracardiac catheterisation to non-invasive measurement of the arterial pulse. Each method has advantages and drawbacks, relative comparison is limited by the absence of a widely accepted gold standard measurement. Cardiac output can also be affected significantly by the phase of respiration – intra-thoracic pressure changes influence diastolic filling and this is especially important during mechanical ventilation, in which cardiac output can vary by up to 50% across a single respiratory cycle. Cardiac output should therefore be measured at evenly spaced points over a cycle or averaged over several cycles. Invasive methods are accepted, but there is increasing evidence that these methods are neither accurate nor effective in guiding therapy. Consequently, the focus on development of methods is growing. This method uses ultrasound and the Doppler effect to measure cardiac output, the blood velocity through the heart causes a Doppler shift in the frequency of the returning ultrasound waves. Echocardiography is a method of quantifying cardiac output using ultrasound. Two-dimensional ultrasound and Doppler measurements are used together to calculate cardiac output, the result is then multiplied by the heart rate to obtain cardiac output. Although used in medicine, it has a wide test-retest variability. It is said to require training and skill, but the exact steps needed to achieve clinically adequate precision have never been disclosed. 2D measurement of the valve diameter is one source of noise, others are beat-to-beat variation in stroke volume
5.
Heart rate
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Heart rate is the speed of the heartbeat measured by the number of contractions of the heart per minute. The heart rate can vary according to the physical needs, including the need to absorb oxygen. It is usually equal or close to the pulse measured at any peripheral point, activities that can provoke change include physical exercise, sleep, anxiety, stress, illness, and ingestion of drugs. Many texts cite the normal resting adult heart rate range from 60–100 bpm. Tachycardia is a fast heart rate, defined as above 100 bpm at rest, bradycardia is a slow heart rate, defined as below 60 bpm at rest. Several studies, as well as expert consensus indicates that the normal resting heart rate is probably closer to a range between 50–90 bpm. During sleep a slow heartbeat with rates around 40–50 bpm is common and is considered normal, when the heart is not beating in a regular pattern, this is referred to as an arrhythmia. Abnormalities of heart rate sometimes indicate disease, while heart rhythm is regulated entirely by the sinoatrial node under normal conditions, heart rate is regulated by sympathetic and parasympathetic input to the sinoatrial node. Therefore, stimulation of the accelerans nerve increases heart rate, while stimulation of the nerve decreases it. Due to individuals having a constant blood volume, one of the ways to deliver more oxygen to an organ is to increase heart rate to permit blood to pass by the organ more often. Normal resting heart rates range from 60–100 bpm, bradycardia is defined as a resting heart rate below 60 bpm. However, heart rates from 50 to 60 bpm are common among healthy people, tachycardia is defined as a resting heart rate above 100 bpm, though persistent rest rates between 80–100 bpm, mainly if they are present during sleep, may be signs of hyperthyroidism or anemia. Central nervous system such as substituted amphetamines increase heart rate. Central nervous system depressants or sedatives decrease the heart rate, there are many ways in which the heart rate speeds up or slows down. Most involve stimulant-like endorphins and hormones being released in the brain, many of which are those that are forced/enticed out by the ingestion and this section discusses target heart rates for healthy persons and are inappropriately high for most persons with coronary artery disease. The heart rate is generated by the sinoatrial node. It is also influenced by central factors through sympathetic and parasympathetic nerves, nervous influence over the heartrate is centralized within the two paired cardiovascular centres of the medulla oblongata. During rest, both centers provide slight stimulation to the heart, contributing to autonomic tone and this is a similar concept to tone in skeletal muscles
6.
Tissue (biology)
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In biology, tissue is a cellular organizational level intermediate between cells and a complete organ. A tissue is an ensemble of similar cells from the origin that together carry out a specific function. Organs are then formed by the grouping together of multiple tissues. The study of tissue is known as histology or, in connection with disease, the classical tools for studying tissues are the paraffin block in which tissue is embedded and then sectioned, the histological stain, and the optical microscope. In the last couple of decades, developments in microscopy, immunofluorescence. With these tools, the appearances of tissues can be examined in health and disease. Animal tissues are grouped into four types, connective, muscle, nervous. Collections of tissues joined in structural units to serve a common function compose organs, while all animals can generally be considered to contain the four tissue types, the manifestation of these tissues can differ depending on the type of organism. For example, the origin of the cells comprising a particular type may differ developmentally for different classifications of animals. By contrast, a true epithelial tissue is present only in a layer of cells held together via occluding junctions called tight junctions. This tissue covers all surfaces that come in contact with the external environment such as the skin, the airways. It serves functions of protection, secretion, and absorption, and is separated from other tissues below by a basal lamina and they are made up of cells separated by non-living material, which is called an extracellular matrix. This matrix can be liquid or rigid, for example, blood contains plasma as its matrix and bones matrix is rigid. Connective tissue gives shape to organs and holds them in place, blood, bone, tendon, ligament, adipose and areolar tissues are examples of connective tissues. One method of classifying tissues is to divide them into three types, fibrous connective tissue, skeletal connective tissue, and fluid connective tissue. Muscle cells form the active contractile tissue of the known as muscle tissue or muscular tissue. Muscle tissue functions to force and cause motion, either locomotion or movement within internal organs. Cells comprising the nervous system and peripheral nervous system are classified as nervous tissue
7.
Organ (anatomy)
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In biology, an organ or viscus is a collection of tissues joined in a structural unit to serve a common function. In anatomy, a viscus is an organ, and viscera is the plural form. Organs are composed of main tissue, parenchyma, and sporadic tissues, the main tissue is that which is unique for the specific organ, such as the myocardium, the main tissue of the heart, while sporadic tissues include the nerves, blood vessels, and connective tissues. The main tissues that make up an organ tend to have common embryologic origins, functionally related organs often cooperate to form whole organ systems. Organs exist in all biological organisms, in particular they are not restricted to animals. In single-cell organisms like bacteria, the analogue of an organ is called organelle. A hollow organ is an organ that forms a hollow tube or pouch, such as the stomach or intestine, or that includes a cavity. Two or more organs working together in the execution of a specific body function form an organ system, the functions of organ systems often share significant overlap. For instance, the nervous and endocrine system both operate via an organ, the hypothalamus. For this reason, the two systems are combined and studied as the neuroendocrine system, the same is true for the musculoskeletal system because of the relationship between the muscular and skeletal systems. Mammals such as humans have a variety of organ systems and these specific systems are also widely studied in human anatomy. Cardiovascular system, pumping and channeling blood to and from the body and lungs with heart, digestive system, digestion and processing food with salivary glands, esophagus, stomach, liver, gallbladder, pancreas, intestines, colon, rectum and anus. Excretory system, kidneys, ureters, bladder and urethra involved in balance, electrolyte balance. Integumentary system, skin, hair and nails, nervous system, collecting, transferring and processing information with brain, spinal cord and nerves. Reproductive system, the sex organs, such as ovaries, fallopian tubes, uterus, vulva, vagina, testes, vas deferens, seminal vesicles, prostate, respiratory system, the organs used for breathing, the pharynx, larynx, trachea, bronchi, lungs and diaphragm. Skeletal system, structural support and protection with bones, cartilage, ligaments, the organ level of organisation in animals can be first detected in flatworms and the more advanced phyla. The less-advanced taxa do not show consolidation of their tissues into organs, the study of plant organs is referred to as plant morphology, rather than anatomy, as in animal systems. Organs of plants can be divided into vegetative and reproductive, vegetative plant organs are roots, stems, and leaves
8.
Metabolism
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Metabolism is the set of life-sustaining chemical transformations within the cells of living organisms. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, usually, breaking down releases energy and building up consumes energy. The chemical reactions of metabolism are organized into metabolic pathways, in one chemical is transformed through a series of steps into another chemical. Enzymes act as catalysts that allow the reactions to proceed more rapidly, enzymes also allow the regulation of metabolic pathways in response to changes in the cells environment or to signals from other cells. The metabolic system of a particular organism determines which substances it will find nutritious, for example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals. The speed of metabolism, the rate, influences how much food an organism will require. A striking feature of metabolism is the similarity of the metabolic pathways. These striking similarities in metabolic pathways are likely due to their appearance in evolutionary history. Most of the structures that make up animals, plants and microbes are made from three classes of molecule, amino acids, carbohydrates and lipids. These biochemicals can be joined together to make such as DNA and proteins. Proteins are made of amino acids arranged in a linear chain joined together by peptide bonds, many proteins are enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as those that form the cytoskeleton, Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle. Lipids are the most diverse group of biochemicals and their main structural uses are as part of biological membranes both internal and external, such as the cell membrane, or as a source of energy. Lipids are usually defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as benzene or chloroform, the fats are a large group of compounds that contain fatty acids and glycerol, a glycerol molecule attached to three fatty acid esters is called a triacylglyceride. Several variations on this structure exist, including alternate backbones such as sphingosine in the sphingolipids. Steroids such as cholesterol are another class of lipids. Carbohydrates are aldehydes or ketones, with hydroxyl groups attached. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy, the basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose
9.
Paracrine signalling
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Paracrine signaling is a form of cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior of those cells. Signaling molecules known as paracrine factors diffuse over a short distance, as opposed to endocrine factors, juxtacrine interactions. Cells that produce paracrine factors secrete them into the extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome, however, the exact distance that paracrine factors can travel is not certain. Although paracrine signaling elicits a diverse array of responses in the cells, most paracrine factors utilize a relatively streamlined set of receptors. In fact, different organs in the body -even between different species - are known to utilize a sets of paracrine factors in differential development. The highly conserved receptors and pathways can be organized into four major families based on structures, Fibroblast growth factor family, Hedgehog family, Wnt family. Binding of a factor to its respective receptor initiates signal transduction cascades. Additionally, the cell must also have the ability to be mechanistically induced. Although the FGF family of paracrine factors has a range of functions. To fulfill many diverse functions, FGFs can be spliced or even have different initiation codons to create hundred of different FGF isoforms. One of the most important functions of the FGF receptors is in limb development and this signaling involves nine different alternatively spliced isoforms of the receptor. Fgf8 and Fgf10 are two of the players in limb development. In the forelimb initiation and limb growth in mice, axial cues from the intermediate mesoderm produces Tbx5, Fgf10 then signals to the ectoderm to begin production of Fgf8, which also stimulates the production of Fgf10. Deletion of Fgf10 results in limbless mice, additionally, paracrine signaling of Fgf is essential in the developing eye of chicks. The fgf8 mRNA becomes localized in what differentiates into the retina of the optic cup. These cells are in contact with the ectoderm cells, which will eventually become the lens. Phenotype and survival of mice after knockout of some FGFR genes, Paracrine signaling through fibroblast growth factors and this signaling pathway has been highly studied, using Drosophila eyes and human cancers
10.
Calcium channel blocker
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Calcium channel blockers, calcium channel antagonists or calcium antagonists are several medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as drugs, i. e. as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also used to alter heart rate, to prevent cerebral vasospasm. CCBs have been shown to be more effective than beta blockers at lowering cardiovascular mortality. Potential major risks however were found to be associated with short-acting CCBs. Dihydropyridine calcium channel blockers are derived from the molecule dihydropyridine and often used to reduce systemic vascular resistance, dihydropyridine calcium channel blockers can worsen proteinuria in patients with nephropathy. This CCB class is identified by the suffix -dipine. Therefore, as vasodilation is minimal with the phenylalkylamines, the mechanism of action is causing negative inotropy. Phenylalkylamines are thought to access calcium channels from the intracellular side, diltiazem While most of the agents listed above are relatively selective, there are additional agents that are considered nonselective. These include mibefradil, bepridil, flunarizine, fluspirilene, and fendiline, gabapentinoids, such as gabapentin and pregabalin, are selective blockers of α2δ subunit-containing voltage-gated calcium channels. They are used primarily to treat epilepsy and neuropathic pain and it must be delivered via the intrathecal route via an intrathecal infusion pump. One study showed the nature of binding to L-type calcium channels is according to first-order kinetics with a Hill coefficient around 1. Vasopressin levels are reduced after the ingestion of alcohol, the lower levels of vasopressin from the consumption of alcohol have been linked to ethanol acting as an antagonist to voltage-gated calcium channels. Studies conducted by Treistman et al. in the aplysia confirm inhibition of VGCC by ethanol, voltage clamp recordings have been done on the aplysia neuron. VGCCs were isolated and calcium current was recorded using patch clamp technique having ethanol as a treatment, recordings were replicated at varying concentrations at a voltage clamp of +30 mV. Results showed calcium current decreased as concentration of ethanol increased, similar results have shown to be true in single-channel recordings from isolated nerve terminal of rats that ethanol does in fact block VGCCs. Studies done by Katsura et al. in 2006 on mouse cerebral cortical neurons, neurons were exposed to sustained ethanol concentrations of 50 mM for 3 days in vitro
11.
Hyperpolarization (biology)
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Hyperpolarization is a change in a cells membrane potential that makes it more negative. It is the opposite of a depolarization and it inhibits action potentials by increasing the stimulus required to move the membrane potential to the action potential threshold. Hyperpolarization is often caused by efflux of K+ through K+ channels, on the other hand, influx of cations, e. g. Na+ through Na+ channels or Ca2+ through Ca2+ channels, inhibits hyperpolarization. If a cell has Na+ or Ca2+ currents at rest, then inhibition of those currents will result in a hyperpolarization. This voltage-gated ion channel response is how the state is achieved. In neurons, the cell enters a state of hyperpolarization immediately following the generation of an action potential, while hyperpolarized, the neuron is in a refractory period that lasts roughly 2 milliseconds, during which the neuron is unable to generate subsequent action potentials. Voltage gated ion channels respond to changes in the membrane potential and these channels work by selecting an ion based on electrostatic attraction or repulsion allowing the ion to bind to the channel. This releases water molecules attached to the ion, and the ion passes through the pore, at this voltage the sodium channels begin to inactivate and voltage gated potassium channels begin to open. This combination of closed sodium channels and open potassium channels leads the neuron to become hyperpolarized, the neuron continues to repolarize until the cell reaches approximately –75 mV, which is the reversal potential of potassium ions. At this point the voltage gated potassium channels close and the permeability of the membrane to sodium and potassium allows the neuron to return to its resting potential of –70 mV. HCN channels are activated by hyperpolarization, hyperpolarization is a change in membrane potential, neuroscientists measure it using a technique known as patch clamping. Using this method they are able to record ion currents passing through individual channels and this is done using a glass micropipette, also called a patch pipette, with a 1 micrometer diameter. There is a patch that contains a few ion channels. The membrane currents giving rise to hyperpolarization are either an increase in current or a decrease in inward current. During the afterhyperpolarization period after a potential, the membrane potential is more negative than when the cell is at the resting potential. In the figure to the right, this occurs at approximately 3 to 4 milliseconds on the time scale. The afterhyperpolarization is the time when the potential is hyperpolarized relative to the resting potential. During the rising phase of a potential, the membrane potential changes from negative to positive
