Physiology
Physiology is the scientific study of the functions and mechanisms which work within a living system. As a sub-discipline of biology, the focus of physiology is on how organisms, organ systems, organs and biomolecules carry out the chemical and physical functions that exist in a living system. Central to an understanding of physiological functioning is the investigation of the fundamental biophysical and biochemical phenomena, the coordinated homeostatic control mechanisms, the continuous communication between cells; the physiologic state is the condition occurring from normal body function, while the pathological state is centered on the abnormalities that occur in animal diseases, including humans. According to the type of investigated organisms, the field can be divided into, animal physiology, plant physiology, cellular physiology and microbial physiology; the Nobel Prize in Physiology or Medicine is awarded to those who make significant achievements in this discipline by the Royal Swedish Academy of Sciences.
Human physiology seeks to understand the mechanisms that work to keep the human body alive and functioning, through scientific enquiry into the nature of mechanical and biochemical functions of humans, their organs, the cells of which they are composed. The principal level of focus of physiology is at the level of systems within systems; the endocrine and nervous systems play major roles in the reception and transmission of signals that integrate function in animals. Homeostasis is a major aspect with regard to such interactions within plants as well as animals; the biological basis of the study of physiology, integration refers to the overlap of many functions of the systems of the human body, as well as its accompanied form. It is achieved through communication that occurs in a variety of both electrical and chemical. Changes in physiology can impact the mental functions of individuals. Examples of this would be toxic levels of substances. Change in behavior as a result of these substances is used to assess the health of individuals.
Much of the foundation of knowledge in human physiology was provided by animal experimentation. Due to the frequent connection between form and function and anatomy are intrinsically linked and are studied in tandem as part of a medical curriculum. Plant physiology is a subdiscipline of botany concerned with the functioning of plants. Related fields include plant morphology, plant ecology, cell biology, genetics and molecular biology. Fundamental processes of plant physiology include photosynthesis, plant nutrition, nastic movements, photomorphogenesis, circadian rhythms, seed germination and stomata function and transpiration. Absorption of water by roots, production of food in the leaves, growth of shoots towards light are examples of plant physiology. Although there are differences between animal and microbial cells, the basic physiological functions of cells can be divided into the processes of cell division, cell signaling, cell growth, cell metabolism. Microorganisms can be found everywhere on Earth.
Types of microorganisms include archaea, eukaryotes, protists and micro-plants. Microbes are important in human culture and health in many ways, serving to ferment foods, treat sewage, produce fuel and other bioactive compounds, they are essential tools in biology as model organisms and have been put to use in biological warfare and bioterrorism. They are a vital component of fertile soils. In the human body microorganisms make up the human microbiota including the essential gut flora, they are the pathogens responsible for many infectious diseases and as such are the target of hygiene measures. Most microorganisms can reproduce and bacteria are able to exchange genes through conjugation and transduction between divergent species; the study of human physiology as a medical field originates in classical Greece, at the time of Hippocrates. Outside of Western tradition, early forms of physiology or anatomy can be reconstructed as having been present at around the same time in China and elsewhere.
Hippocrates incorporated his belief system called the theory of humours, which consisted of four basic substance: earth, water and fire. Each substance is known for having a corresponding humour: black bile, phlegm and yellow bile, respectively. Hippocrates noted some emotional connections to the four humours, which Claudius Galenus would expand on; the critical thinking of Aristotle and his emphasis on the relationship between structure and function marked the beginning of physiology in Ancient Greece. Like Hippocrates, Aristotle took to the humoral theory of disease, which consisted of four primary qualities in life: hot, cold and dry. Claudius Galenus, known as Galen of Pergamum, was the first to use experiments to probe the functions of the body. Unlike Hippocrates, Galen argued that humoral imbalances can be located in specific organs, including the entire body, his modification of this theory better equipped doctors to make more precise diagnoses. Galen played off of Hippocrates idea that emotions were tied to the humours, added the notion of temperaments: sanguine corresponds with blood.
Galen saw the human body consisting of three connected systems: the brain and nerves, which are responsible for thoughts and sensations.
Insulin
Insulin is a peptide hormone produced by beta cells of the pancreatic islets. It regulates the metabolism of carbohydrates and protein by promoting the absorption of carbohydrates glucose from the blood into liver and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is inhibited by high concentrations of insulin in the blood. Circulating insulin affects the synthesis of proteins in a wide variety of tissues, it is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism of reserve body fat. Beta cells are sensitive to glucose concentrations known as blood sugar levels; when the glucose level is high, the beta cells secrete insulin into the blood. Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, decreased secretion when glucose concentrations are high.
Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis. If beta cells are destroyed by an autoimmune reaction, insulin can no longer be synthesized or be secreted into the blood; this results in type 1 diabetes mellitus, characterized by abnormally high blood glucose concentrations, generalized body wasting. In type 2 diabetes mellitus the destruction of beta cells is less pronounced than in type 1 diabetes, is not due to an autoimmune process. Instead there is an accumulation of amyloid in the pancreatic islets, which disrupts their anatomy and physiology; the pathogenesis of type 2 diabetes is not well understood but patients exhibit a reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, peripheral tissue insulin resistance.
Type 2 diabetes is characterized by high rates of glucagon secretion into the blood which are unaffected by, unresponsive to the concentration of glucose in the blood. Insulin is still secreted into the blood in response to the blood glucose; as a result, the insulin levels when the blood sugar level is normal, are much higher than they are in healthy persons. The human insulin protein is composed of 51 amino acids, has a molecular mass of 5808 Da, it is a dimer of a B-chain, which are linked together by disulfide bonds. Insulin's structure varies between species of animals. Insulin from animal sources differs somewhat in effectiveness from human insulin because of these variations. Porcine insulin is close to the human version, was used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies; the crystal structure of insulin in the solid state was determined by Dorothy Hodgkin. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.
Insulin may have originated more than a billion years ago. The molecular origins of insulin go at least as far back. Apart from animals, insulin-like proteins are known to exist in the Fungi and Protista kingdoms. Insulin is produced by beta cells of the pancreatic islets in most vertebrates and by the Brockmann body in some teleost fish. Cone snails Conus geographus and Conus tulipa, venomous sea snails that hunt small fish, use modified forms of insulin in their venom cocktails; the insulin toxin, closer in structure to fishes' than to snails' native insulin, slows down the prey fishes by lowering their blood glucose levels. The preproinsulin precursor of insulin is encoded by the INS gene. A variety of mutant alleles with changes in the coding region have been identified. A read-through gene, INS-IGF2, overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. In the pancreatic β cells, glucose is the primary physiological stimulus for the regulation of insulin synthesis.
Insulin is regulated through the transcription factors PDX1, NeuroD1, MafA. PDX1 is in the nuclear periphery upon low blood glucose levels interacting with corepressors HDAC1 and 2, downregulating the insulin secretion. An increase in blood glucose levels causes phosphorylation of PDX1 and it translocates centrally and binds the A3 element within the insulin promoter. Upon translocation it interacts with coactivators HAT p300 and acetyltransferase set 7/9. PDX1 affects the histone modifications through deacetylation as well as methylation, it is said to suppress glucagon. NeuroD1 known as β2, regulates insulin exocytosis in pancreatic β cells by directly inducing the expression of genes involved in exocytosis, it is localized in the cytosol, but in response to high glucose it becomes glycosylated by OGT and/or phosphorylated by ERK, which causes translocation to the nucleus. In the nucleus β2 heterodimerizes with E47, binds to the E1 element of the insulin promoter and recruits co-activator p300 which acetylates β2.
It is able to interact with other transcription factors as well in activation of the insulin gene. MafA is degraded by proteasomes upon low blood glucose levels
Arteriole
An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries. Arterioles are the primary site of vascular resistance; the greatest change in blood pressure and velocity of blood flow occurs at the transition of arterioles to capillaries. In a healthy vascular system the endothelium lines all blood-contacting surfaces, including arteries, veins, venules and heart chambers; this healthy condition is promoted by the ample production of nitric oxide by the endothelium, which requires a biochemical reaction regulated by a complex balance of polyphenols, various nitric oxide synthase enzymes and L-arginine. In addition there is direct electrical and chemical communication via gap junctions between the endothelial cells and the vascular smooth muscle. Blood pressure in the arteries supplying the body is a result of the work needed to pump the cardiac output through the vascular resistance termed total peripheral resistance by physicians and researchers.
An increase in the media to lumenal diameter ratio has been observed in hypertensive arterioles as the vascular wall thickens and/or lumenal diameter decreases. The up and down fluctuation of the arterial blood pressure is due to the pulsatile nature of the cardiac output and determined by the interaction of the stroke volume versus the volume and elasticity of the major arteries; the decreased velocity of flow in the capillaries increases the blood pressure, due to Bernoulli's principle. This induces gas and nutrients to move from the blood to the cells, due to the lower osmotic pressure outside the capillary; the opposite process occurs when the blood leaves the capillaries and enters the venules, where the blood pressure drops due to an increase in flow rate. Arterioles receive autonomic nervous system innervation and respond to various circulating hormones in order to regulate their diameter. Retinal vessels lack a functional sympathetic innervation. Further local responses to stretch, carbon dioxide, pH, oxygen influence arteriolar tone.
Norepinephrine and epinephrine are vasoconstrictive acting on alpha 1-adrenergic receptors. However, the arterioles of skeletal muscle, cardiac muscle, pulmonary circulation vasodilate in response to these hormones when they act on beta-adrenergic receptors. Stretch and high oxygen tension increase tone, carbon dioxide and low pH promote vasodilation. Pulmonary arterioles are a noteworthy exception. Brain arterioles are sensitive to pH with reduced pH promoting vasodilation. A number of hormones influence arteriole tone such as angiotensin II, bradykinin, atrial natruretic peptide, prostacyclin. Arteriole diameters decrease with exposure to air pollution. Any pathology which constricts blood flow, such as stenosis, will increase total peripheral resistance and lead to hypertension. Arteriolosclerosis is the term used for the hardening of arteriole walls; this can be due to decreased elastic production from fibrinogen, associated with ageing, or hypertension or pathological conditions such as atherosclerosis.
The muscular contraction of arterioles is targeted by drugs that lower blood pressure, for example the dihydropyridines, which block the calcium conductance in the muscular layer of the arterioles, causing relaxation. This decreases the resistance to flow into peripheral vascular beds, lowering overall systemic pressure. A "metarteriole" is an arteriole. Surface chemistry of microvasculature Venule
Krogh's principle
Krogh's principle states that "for such a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied." This concept is central to those disciplines of biology that rely on the comparative method, such as neuroethology, comparative physiology, more functional genomics. Krogh's principle is named after the Danish physiologist August Krogh, winner of the Nobel Prize in Physiology for his contributions to understanding the anatomy and physiology of the capillary system, who described it in The American Journal of Physiology in 1929. However, the principle was first elucidated nearly 60 years prior to this, in the same words as Krogh, in 1865 by Claude Bernard, the French instigator of experimental medicine, on page 27 of his "Introduction à l'étude de la médecine expérimentale": Dans l'investigation scientifique, les moindres procédés sont de la plus haute importance. Le choix heureux d'un animal, d'un instrument construit d'une certaine façon, l'emploi d'un réactif au lieu d'un autre, suffisent souvent pour résoudre les questions générales les plus élevées.
Claude Bernard: Introduction à l'étude de la médecine expérimentale, J. B. Baillière et Fils, Libraires de L'Académie Impériale de Médecine, 1865. Pp. 400 Krogh wrote the following in his 1929 treatise on the current'status' of physiology:... I want to emphasize that the route by which we can strive toward the ideal is by a study of the vital functions in all their aspects throughout the myriads of organisms. We may find out, nay, we will find out before long the essential mechanisms of mammalian kidney function, but the general problem of excretion can be solved only when excretory organs are studied wherever we find them and in all their essential modifications; such studies will be sure, moreover, to expand and deepen our insight into problems of the human kidney and will prove of value from the narrowest utilitarian point of view. For such a large number of problems there will be some animal of choice or a few such animals on which it can be most conveniently studied. Many years ago when my teacher, Christian Bohr, was interested in the respiratory mechanism of the lung and devised the method of studying the exchange through each lung separately, he found that a certain kind of tortoise possessed a trachea dividing into the main bronchi high up in the neck, we used to say as a laboratory joke that this animal had been created expressly for the purposes of respiration physiology.
I have no doubt that there is quite a number of animals which are "created" for special physiological purposes, but I am afraid that most of them are unknown to the men for whom they were "created," and we must apply to the zoologists to find them and lay our hands on them." August Krogh The Progress of Physiology, The American Journal of Physiology, 1929. 90 pp. 243-251 "Krogh's principle" was not utilized as a formal term until 1975 when the biochemist Hans Adolf Krebs, first referred to it. More at the International Society for Neuroethology meeting in Nyborg, Denmark in 2004, Krogh's principle was cited as a central principle by the group at their 7th Congress. Krogh's principle has been receiving attention in the area of functional genomics, where there has been increasing pressure and desire to expand genomics research to a more wide variety of organisms beyond the traditional scope of the field. A central concept to Krogh's principle is evolutionary adaptation. Evolutionary theory maintains that organisms are suited to particular niches, some of which are specialized for solving particular biological problems.
These adaptations are exploited by biologists in several ways: Methodology:: The need to manipulate biological systems in the laboratory has driven the use of an organismal specialization. One example of Krogh's principle presents itself in the used Polymerase Chain Reaction, a method which relies on the rapid exposure of DNA to high heat for amplification of particular sequences of interest. DNA polymerase enzyme from many organisms would denature at high temperatures, however, to solve this problem and colleagues turned to Thermus aquaticus, a strain of bacteria native to hydrothermal vents. Thermus aquaticus has a polymerase, heat stable at temperatures necessary for PCR. Biochemically modified Taq polymerase, as it is called, is now used in PCR applications. Overcoming technical limitations:: Two Nobel Prize–winning bodies of study were facilitated by using ideas central to Krogh's principle to overcome technical limitations in nervous system physiology; the ionic basis of the action potential was elucidated in the squid giant axon in 1958 by Hodgkin and Huxley, developers of the original voltage clamp device and co-recipients of the 1963 Nobel Prize in Physiology or Medicine.
The voltage clamp is now a central piece of technology in modern neurophysiology, but was only possible to develop using the wide diameter of the squid giant axon. Another marine mollusc, the opisthobranch Aplysia possesses small number of large nerve cells that are identified and mapped from individual to individual. Aplysia was selected for these reasons for the study of the cellular and molecular basis of learning and memory which led to Eric Kandel's receipt of the Nobel Prize in 2000. Understanding more complex/subtle systems: Beyond overcoming technical limitations, Krogh's principle has important implications in the light of convergent evolution and homology. Either because of evolutionary history, or particular constraints on a given niche, there
Novo Nordisk
Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, with production facilities in eight countries, affiliates or offices in 75 countries. Novo Nordisk is controlled by majority shareholder Novo Holdings A/S which holds 25% of its shares and a supermajority of its voting shares. Novo Nordisk markets pharmaceutical products and services. Key products include diabetes care devices. Novo Nordisk is involved with hemostasis management, growth hormone therapy and hormone replacement therapy; the company makes several drugs under various brand names, including Levemir, NovoLog, Novolin R, NovoSeven, NovoEight and Victoza. Novo Nordisk employs more than 40,000 people globally, markets its products in 180 countries; the corporation was created in 1989 through a merger of two Danish companies which date back to the 1920s. The Novo Nordisk logo is one of the sacred animals of ancient Egypt. Novo Nordisk is a full member of the European Federation of Pharmaceutical Industries and Associations.
The company was ranked 25th among 100 Best Companies to Work For in 2010 and 72nd in 2014 by Fortune. In January 2012, Novo Nordisk was named as the most sustainable company in the world by the business magazine Corporate Knights while spin-off company Novozymes was named fourth. In 1989, Novo Industri A/S and Nordisk Gentofte A/S merged to become Novo Nordisk A/S, the world's largest producer of insulin with headquarters in Bagsværd, Copenhagen. In 1994, Novo Nordisk's existing information technology units was spun out as NNIT A/S; the company was converted into a wholly owned aktieselskab in 2004 In March 2015, NNIT was floated on the NASDAQ OMX Nordic. In 2000, Novo's enzymes business, Novozymes A/S, was spun-out. In 2013, Novo acquired Xellia for $700 million. In 2015, the company announced it would collaborate with Ablynx, using its nanobody technology to develop at least one new drug candidate. In January 2018, Reuters reported that Novo had offered to acquire Ablynx for $3.1 billion - having made an unreported offer in mid December for the company.
However the Ablynx board rejected this offer the same day, saying that the price undervalued the business. Novo lost out to Sanofi who bid $4.8 billion. In the same year the company announced it would acquire Ziylo for around $800 million. Novo Nordisk is involved in publicly funded collaborative research projects with other industrial and academic partners. One example in the area of non-clinical safety assessment is the InnoMed PredTox; the company is expanding its activities in joint research projects within the framework of the Innovative Medicines Initiative of European Federation of Pharmaceutical Industries and Associations and the European Commission. Novo Nordisk founded the World Diabetes foundation to save the lives of those affected by diabetes in developing countries and supported a UN resolution to fight diabetes, making diabetes the only other disease alongside HIV / AIDS to have a commitment to combat at a UN level. Diabetes treatments account for 85% of Novo Nordisk’s business.
Novo Nordisk works with doctors and patients, to develop products for self-managing diabetes conditions. The DAWN 2001 study was a global survey of the psychosocial aspects of living with diabetes, it involved over 5,000 people with diabetes and 4,000 care providers. This study was designed to identify barriers to optimal quality of life. A follow-up study completed in 2012 involved more than 15,000 people living with, or caring for, those with diabetes. In response to UK findings, a National Action Plan was developed, with a multidisciplinary steering committee, to support the delivery of individualized person-centered care in the UK; the NAP seeks to provide a holistic approach to diabetes treatment for their families. The i3-diabetes programme is a collaboration between the King's Health Partners, one of only six Academic Health Sciences Centres in England, Novo Nordisk; the programme is a five-year collaboration designed to deliver personalised care that will lead to improved outcomes for people living with diabetes, more efficient and effective ways of caring for people with diabetes.
Novo Nordisk have sponsored the International Diabetes Federation's Unite for Diabetes campaign. In March 2014, Novo Nordisk announced a partnership program entitled ‘Cities Changing Diabetes,’ which entails combating urban diabetes. Partnership includes University College London and supported by Steno Diabetes Center, as well as a range of local partners including healthcare professionals, city authorities, urban planners, businesses and community leaders. A November 2014 newspaper article suggested that a recent medical research breakthrough at Harvard University could put Novo Nordisk out of business. Dr Alan Moses, the chief medical officer of Novo Nordisk, commented that the biology of diabetes is complex but that Novo Nordisk's mission is to alleviate and cure diabetes. If this new medical advance "...meant the dissolution of Novo Nordisk, that'd be fine." Novo Nordisk was researching pulmonary delivery systems for diabetic medications, in the early stages of research into autoimmune and chronic inflammatory diseases, using technologies such as translational immunology and monoclonal antibodies In September 2014 the company announced a decision to discontinue all research in inflammatory disorders, including the discontinuation of R&D in anti-IL-20 for the treatment of rheumatoid arthritis.
In September 2018 it was reported that the company would lay
Muscle
Muscle is a soft tissue found in most animals. Muscle cells contain protein filaments of actin and myosin that slide past one another, producing a contraction that changes both the length and the shape of the cell. Muscles function to produce motion, they are responsible for maintaining and changing posture, locomotion, as well as movement of internal organs, such as the contraction of the heart and the movement of food through the digestive system via peristalsis. Muscle tissues are derived from the mesodermal layer of embryonic germ cells in a process known as myogenesis. There are three types of muscle, skeletal or striated and smooth. Muscle action can be classified as being either involuntary. Cardiac and smooth muscles contract without conscious thought and are termed involuntary, whereas the skeletal muscles contract upon command. Skeletal muscles in turn can be divided into slow twitch fibers. Muscles are predominantly powered by the oxidation of fats and carbohydrates, but anaerobic chemical reactions are used by fast twitch fibers.
These chemical reactions produce adenosine triphosphate molecules that are used to power the movement of the myosin heads. The term muscle is derived from the Latin musculus meaning "little mouse" because of the shape of certain muscles or because contracting muscles look like mice moving under the skin; the anatomy of muscles includes gross anatomy, which comprises all the muscles of an organism, microanatomy, which comprises the structures of a single muscle. Muscle tissue is a soft tissue, is one of the four fundamental types of tissue present in animals. There are three types of muscle tissue recognized in vertebrates: Skeletal muscle or "voluntary muscle" is anchored by tendons to bone and is used to effect skeletal movement such as locomotion and in maintaining posture. Though this postural control is maintained as an unconscious reflex, the muscles responsible react to conscious control like non-postural muscles. An average adult male is made up of 42% of skeletal muscle and an average adult female is made up of 36%.
Smooth muscle or "involuntary muscle" is found within the walls of organs and structures such as the esophagus, intestines, uterus, bladder, blood vessels, the arrector pili in the skin. Unlike skeletal muscle, smooth muscle is not under conscious control. Cardiac muscle, is an "involuntary muscle" but is more akin in structure to skeletal muscle, is found only in the heart. Cardiac and skeletal muscles are "striated" in that they contain sarcomeres that are packed into regular arrangements of bundles. While the sarcomeres in skeletal muscles are arranged in regular, parallel bundles, cardiac muscle sarcomeres connect at branching, irregular angles. Striated muscle contracts and relaxes in short, intense bursts, whereas smooth muscle sustains longer or near-permanent contractions. Skeletal muscle is further divided into two broad types: slow twitch and fast twitch: Type I, slow twitch, or "red" muscle, is dense with capillaries and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color.
It can sustain aerobic activity using fats or carbohydrates as fuel. Slow twitch fibers contract for long periods of time but with little force. Type II, fast twitch muscle, has three major subtypes that vary in both contractile speed and force generated. Fast twitch fibers contract and powerfully but fatigue rapidly, sustaining only short, anaerobic bursts of activity before muscle contraction becomes painful, they have greater potential for increase in mass. Type IIb is anaerobic, glycolytic, "white" muscle, least dense in mitochondria and myoglobin. In small animals this is the major fast muscle type; the density of mammalian skeletal muscle tissue is about 1.06 kg/liter. This can be contrasted with the density of adipose tissue, 0.9196 kg/liter. This makes muscle tissue 15% denser than fat tissue. Skeletal muscles are sheathed by a tough layer of connective tissue called the epimysium; the epimysium anchors muscle tissue to tendons at each end, where the epimysium becomes thicker and collagenous.
It protects muscles from friction against other muscles and bones. Within the epimysium are multiple bundles called fascicles, each of which contains 10 to 100 or more muscle fibers collectively sheathed by a perimysium. Besides surrounding each fascicle, the perimysium is a pathway for nerves and the flow of blood within the muscle; the threadlike muscle fibers are the individual muscle cells, each cell is encased within its own endomysium of collagen fibers. Thus, the overall muscle consists of fibers that are bundled into fascicles, which are themselves grouped together to form muscles. At each level of bundling, a collagenous membrane surrounds the bundle, these membranes support muscle function both by resisting passive stretching of the tissue and by distributing forces applied to the muscle. Scattered throughout the muscles are muscle spindles that provide sensory feedback information to the central nervous system.. This same bundles-within-bundles structure is replicated within the muscle cells.
Within the cells of the muscle are myofibrils, which themselves are bu
