:: wikimiki.org ::

Glucocorticoid

Glucocorticoid

Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger similar effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by the specific receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Cortisol (or hydrocortisone) is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions. Glucocorticoid receptors are found in the cells of almost all vertebrate tissues.

Effects

The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. In the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. These effects include:
- Stimulation of gluconeogenesis, particularly in the liver: This pathway results in the synthesis of glucose from non-hexose substrates such as amino acids and lipids and is particularly important in carnivores and certain herbivores. Enhancing the expression of enzymes involved in gluconeogenesis is probably the best known metabolic function of glucocorticoids.
- Mobilization of amino acids from extrahepatic tissues: These serve as substrates for gluconeogenesis.
- Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve glucose.
- Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis. Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. This is particularly evident when they administered at pharmacologic doses, but also is important in normal immune responses. As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and as adjunction therapy for conditions such as autoimmune diseases. Glucocorticoids have multiple effects on fetal development. An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function. Mice with homozygous disruptions in the corticotropin-releasing hormone gene (see below) die at birth due to pulmonary immaturity. Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems. Some examples include inhibition of bone formation, suppression of calcium absorption and delayed wound healing. These observations suggest a multitude of less dramatic physiologic roles for glucocorticoids.

Mode of action

Glucocorticoids bind to the cytosolic glucocorticoid receptor. This type of receptors gets activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. This process is called transactivation and mediates most of the main metabolic and cardiovascular side effects of glucocorticoids. The opposite mechanism is called transrepression. The activated hormone receptor interacts with specific transcription factors and prevents the transcription of targeted genes. Glucocorticoids are able to prevent the transcription of any of immune genes, including the IL-2 gene. The ordinary glucocorticoids do not distinguish among transactivation and transrepression and influence both the "wanted" immune and "unwanted" genes regulating the metabolic and cardiovascular functions. Currently, intensive research is aimed at discovering selectively acting glucocorticoids that will be able to repress only the immune system.

Pharmacologic properties

A variety of synthetic glucocorticoids, some far more potent than cortisol, have been created for therapeutic use. They differ in the pharmacokinetics (absorption factor, half-life, volume of distribution, clearance) and in pharmacodynamics (for example the capacity of mineralocorticoid activity: retention of sodium (Na+) and water; see also: renal physiology). Because they absorb well through the intestines, they are primarily administered per os (by mouth), but also by other ways like topically on skin. More than 90 per cent of them bind different plasma proteins, however with a different binding specificity. Endogenous glucocorticoids and some synthetic corticoids have high affinity to the protein transcortin (also called CBG, corticosteroid binding protein), while all of them bind albumin. In the liver, they quickly metabolise by conjugatiion with a sulfate or glucuronic acid and are secreted in the urine. Glucocorticoid potency, duration of effect, and overlapping mineralocorticoid potency varies (Table). Cortisol (hydrocortisone) is the standard of comparison for glucocorticoid potency. Hydrocortisone is the name used for pharmaceutical preparations of cortisol. Data refer to oral dosing, except when mentioned. Note that oral potency may be less than parenteral potency because significant amounts (up to 50% in some cases) may not be absorbed from the intestine. Note that fludrocortisone, DOCA, and aldosterone are not considered glucocorticoids and are included in this table to provide perspective on mineralocorticoid potency.

Physiologic replacement of glucocorticoid

Any glucocorticoid can be given in a dose that provides approximately the same glucocorticoid effects as normal cortisol production; this is referred to as physiologic, replacement, or maintenance dosing. This is approximately 6-12 mg/m²/day (m² refers to body surface area (BSA) and is a measure of body size; an average man is 1.7 m²).

Medical uses and effects of high dose glucocorticoids

In much higher doses (termed pharmacologic doses), glucocorticoids are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and the graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. Some drugs used are cortisol (hydrocortisone), prednisone and dexamethasone.

Immunosuppressive mechanism

Glucocorticoids suppress the cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-γ, the most important of which is the IL-2. Smaller cytokine production reduces the T cell proliferation. Glucocorticoids also suppress the humoral immunity, causing B cells to express smaller amounts of IL-2 and of IL-2 receptors. This diminishes both B cell clone expansion and antibody synthesis. The diminished amounts of IL-2 also causes less T lymphocyte cells to be activated. Since glucocorticoid is a steroid, it regulates transcription factors, another factor it down regulates is the expression of Fc receptors on Macrophages, so there is a decreased phagocytosis of opsonised cells.

Antiinflammatory effects

Glucocorticoids influence all types of inflammatory events, no matter what their cause. They induce the lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes.

Side effects

Glucocorticoid drugs currently being used act nonselectively, so in the long run they may impair many healthy anabolic processes. To prevent this, much research has been focused recently on the elaboration of selectively acting glucocorticoid drugs. These are the side effects that could be prevented:
- muscle breakdown (proteolysis), weakness; reduced muscle mass and repair
- reduced bone density (osteoporosis, higher fracture risk, slower fracture repair)
- increased skin fragility, easy bruising
- increased visceral and truncal fat deposition (central obesity), appetite stimulation
- increased gluconeogenesis, insulin resistance, impaired glucose tolerance, "steroid diabetes" (see diabetes mellitus)
- expansion of malar fat pads and dilation of small blood vessels in skin
- anovulation, irregularity of menstrual periods
- growth failure, pubertal delay
- increased plasma amino acids, increased urea formation; negative nitrogen balance
- increased hepatic glycogen synthesis
- excitatory effect on central nervous system In high doses, hydrocortisone (cortisol) and those glucocorticoids with appreciable mineralocorticoid potency can exert a mineralocorticoid effect as well, although in physiologic doses this is prevented by rapid degradation of cortisol by 11β-hydroxysteroid dehydrogenase isoenzyme 2 (11β-HSD2) in mineralocorticoid target tissues. Mineralocorticoid effects can include salt and water retention, extracellular fluid volume expansion, hypertension, potassium depletion, and metabolic alkalosis. The combination of clinical problems produced by prolonged, excess glucocorticoids, whether synthetic or endogenous, is termed Cushing's syndrome.

Adrenal suppression and withdrawal

In addition to the effects listed above, use of high dose steroids for more than a week begins to produce suppression of the patient's adrenal glands because the exogenous glucocorticoids suppress hypothalamic corticotropin releasing hormone (CRH) and pituitary adrenocorticotropic hormone (ACTH). With prolonged suppression the adrenal glands atrophy (physically shrink) and can take months to recover full function after discontinuation of the exogenous glucocorticoid. During this recovery time, the patient is vulnerable to adrenal insufficiency during times of stress, such as illness. While there is wide individual variation in suppressive dose and time for adrenal recovery, clinical guidelines have been devised to estimate potential adrenal suppression and recovery, to reduce risk to the patient. The following is one example, but many variations exist or may be appropriate in individual circumstances.
- If a patient has been receiving daily high doses for 5 days or less, they can be abruptly stopped (or reduced to physiologic replacement if patient is adrenal deficient). Full adrenal recovery can be assumed to occur by a week afterward.
- If high doses were used for 6-10 days, reduce to replacement dose immediately and taper over 4 more days. Adrenal recovery can be assumed to occur within 2-4 weeks of completion of steroids.
- If high doses were used for 11-30 days, cut immediately to twice replacement, and then by 25% every 4 days. Stop entirely when dose is less than half of replacement. Full adrenal recovery should occur within 1-3 months of completion of withdrawal.
- If high doses were used more than 30 days, cut dose immediately to twice replacement, and reduce by 25% each week until replacement is reached.
- Then change to oral hydrocortisone or cortisone as a single morning dose, and gradually decrease by 2.5 mg each week. When a.m. dose is less than replacement, the return of normal basal adrenal function may be documented by checking 0800 cortisol levels prior to the morning dose; stop drugs when 0800 cortisol is 10 μg/dl. It is difficult to predict the time to full adrenal recovery after prolonged suppressive exogenous steroids; some people may take nearly a year.
- Flare-up of the underlying condition for which steroids are given may require a more gradual taper than outlined above.

Steroid hormone

Steroid hormones are steroids which act as hormones. They can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens. Vitamin D derivatives are a sixth closely related hormone system with homologous receptors, though technically sterols rather than steroids.

Overview

The natural steroid hormones are generally synthesized from cholesterol in the gonads and adrenal glands. Steroid hormones are generally carried in the blood bound to specific carrier proteins such as sex hormone binding globulin or corticosteroid binding globulin. Further conversions and catabolism occurs in the liver, other "peripheral" tissues, and in the target tissues. Because steroids and sterols are lipid soluble, they can diffuse fairly freely from the blood through the cell membrane and into the cytoplasm of target cells. In the cytoplasm the steroid may or may not undergo an enzyme-mediated alteration such as reduction, hydroxylation, or aromatization. In the cytoplasm, the steroid binds to the specific receptor, a large metalloprotein. Upon steroid binding, many kinds of steroid receptor dimerizes, two receptor subunits join together to form one funcional DNA-binding unit that can enter the cell nucleus. In some of the hormone systems known, the receptor is associated with a heat shock protein which is released on the binding of the ligand, the hormone. Once in the nucleus, the steroid-receptor ligand complex binds to specific DNA sequences and induces transcription of its target genes.

Synthesis

gene

Principal natural human steroid hormones

- Glucocorticoids
- cortisol
- Mineralocorticoids
- aldosterone
- Sex steroids
- Androgens
- testosterone
- dehydroepiandrosterone (DHEA)
- dehydroepiandrosterone sulfate (DHEAS)
- androstenedione
- dihydrotestosterone (DHT)
- Estrogens
- estradiol
- estrone
- estriol
- Progestagens
- progesterone The principal sterol hormone:
- Vitamin D derivatives
- calcitriol

Synthetic steroids and sterols

A variety of synthetic steroids and sterols have also been contrived. Most are steroids but some non-steroidal molecules can interact with the steroid receptors because of a similarity of shape. Some synthetic steroids are weaker, some much stronger, than the natural steroids whose receptors they activate. Some examples of synthetic steroid hormones:
- Glucocorticoids: prednisone, dexamethasone, triamcinolone
- Mineralocorticoid: fludrocortisone
- Vitamin D: dihydrotachysterol
- Androgens: oxandrolone, decadurabolin (also known as anabolic steroids)
- Estrogens: diethylstilbestrol (DES)
- Progestins: norethindrone, medroxyprogesterone acetate Steroidogenic enzymes: [http://hi/science.co.il/hi/pub/1992-JSBMB-43-779.asp Review on structure, function, and role in regulation of steroid hormone biosynthesis] Category:Steroid hormones

Cortisol

Cortisol is a corticosteroid hormone that is involved in the response to stress; it increases blood pressure and blood sugar levels and suppresses the immune system. Synthetic cortisol, also known as hydrocortisone, is used as a drug mainly to fight allergies and inflammation.

Synthesis

Image:Reaction-Progesterone-Cortisol.png Cortisol is synthesized from progesterone, the precursor of all steroid hormones. The conversion involves hydroxylation of C-11, C-17 and C-21. The synthesis takes place in the zona fasciculata of the cortex of the adrenal glands. While the adrenal cortex also produces aldosterone (in the zona glomerulosa) and some sex hormones (in the zona reticulosa), cortisol is its main secretion. (The name cortisol comes from cortex.) The synthesis of cortisol in the adrenal gland is stimulated by the anterior lobe of the pituitary gland with adrenocorticotropic hormone (ACTH); production of ACTH is in turn stimulated by corticotropin releasing hormone (CRH), released by the hypothalamus.

Physiology

The amount of cortisol present in the serum undergoes diurnal variation, with the highest levels present in the early morning, and lower levels in the evening, several hours after the onset of sleep. Information about the light/dark cycle is transmitted from the retina to the paired suprachiasmatic nuclei in the hypothalamus. Changed patterns of the serum cortisol levels have been observed in connection with abnormal ACTH levels, clinical depression, psychological stress, and such physiological stressors as hypoglycemia, illness, fever, trauma, surgery, fear, pain, physical exertion or extremes of temperature. There is also significant individual variation, although a given person tends to have consistent rhythms. Cortisol also inhibits the secretion of corticotropin releasing hormone (CRH), resulting in feedback inhibition of ACTH secretion. Some researchers believe that this normal feedback system may break down when animals are exposed to chronic stress. In normal release, cortisol has widespread actions which help restore homeostasis after stress. It acts as a physiological antagonist to insulin by promoting breakdown of carbohydrates, lipids, and proteins and so mobilizing energy reserves. This leads to increased blood glucose concentrations and increased glycogen formation in the liver (Freeman, 2002). It also increases blood pressure. In addition, immune and inflammatory cells have their responses to stress attenuated by cortisol, and the hormone thus lowers the activity of the immune system. Bone formation is also lowered by cortisol. These normal endogenous functions are the basis for the physiological consequences of chronic stress - prolonged cortisol secretion causes muscle wastage, hyperglycemia, and suppresses immune / inflammatory responses. The same consequences arise from long-term use of glucocorticoid drugs. Also, long-term exposure to cortisol results in damage to cells in the hippocampus. This damage results in impaired learning. However, short-term exposure of cortisol helps to create memories; this is the proposed mechanism for storage of flash bulb memories. Most serum cortisol, all but about 4 percent, is bound to proteins including corticosteroid binding globulin (CBG), and albumin. Only free cortisol is available to most receptors.

Pharmacology

As an oral or injectable drug, cortisol is also known as hydrocortisone. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients who need steroid treatment but cannot take oral medication, and peri-operatively in patients on long-term steroid treatment to prevent an Addisonian crisis. It is given by topical application for its anti-inflammatory effect in allergic rashes, eczema and certain other inflammatory conditions. It may also be injected into inflamed joints resulting from diseases such as gout. Compared to prednisolone, hydrocortisone is about 1/4th the strength. Dexamethasone is about 40 times stronger than hydrocortisone. For side effects, see corticosteroid and prednisolone.

Diseases

Excessive levels of cortisol in the blood result in Cushing's syndrome. If on the other hand the adrenal glands do not produce sufficient amounts of cortisol, Addison's disease is the consequence.

References

Online

- [http://www.duchs.com/information/Hydrocortisone Hydrocortisone] Fact Sheet

Printed

- Freeman, Scott (2002). Biological Science. Prentice Hall; 2nd Pkg edition (December 30, 2004). ISBN 0132187469.
- A. C. Guyton, J. E. Hall. Textbook of Medical Physiology. W.B. Saunders Company; 10th edition (August 15, 2000). ISBN 072168677X. Category:Glucocorticoids Category:Immunosuppressive agents

Mineralocorticoid

Mineralocorticoids is a class of steroids characterised by their similarity to aldosterone and their influence on salt and water metabolism. The only endogenous mineralocorticoid is aldosterone, although a number of hormones (mainly progesterone) have mineralocorticoid function. An example of synthetic mineralocorticoids is fludrocortisone (Florinef®). An important mineralocorticoid inhibitor is spironolactone. Aldosterone acts on the kidneys to provide active reabsorption of sodium, passive reabsorption of water, and the active secretion of potassium in the distal convoluted tubule. This in turn results in an increase of blood pressure and blood volume.

Corticosteroid

In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.
- Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.
- Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney. kidney] Some common natural hormones are corticosterone (C₂₁H₃₀O₄), cortisone (C₂₁H₂₈O₅, 17-hydroxy-11-dehydrocorticosterone) and aldosterone.

Uses

Synthetic drugs with corticosteroid-like effect are used in a variety of conditions, ranging from brain tumors to skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef®) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is available for replacement therapy, e.g. in adrenal insufficiency and congenital adrenal hyperplasia. Synthetic glucocorticoids are used in the treatment of joint pain or inflammation (arthritis), dermatitis, allergic reactions, asthma, hepatitis, lupus erythematosus, inflammatory bowel disease (ulcerative colitis and Crohn's disease), sarcoidosis and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency. Topical formulations for treatment of skin or inflammatory bowel disease are available. Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side effects are hypertension (abnormally high blood pressure), hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood) without causing peripheral edema, and metabolic alkalosis.

History

Tadeus Reichstein together with Edward Calvin Kendall and Philip Showalter Hench were awarded the Nobel Prize for Physiology and Medicine in 1950 for their work on hormones of the adrenal cortex which culminated in the isolation of cortisone. Corticosteroids have been used as a drug treatment for some time. Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a complicated 36-step process that started with desoxycholic acid, which was extracted from ox bile. The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker, at Syntex, discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams. His conversion of diosgenin into progesterone by a four-step process now known as Marker Degradation was an important step in mass production of all steroidal hormones, including cortisone and the birth control pill. In 1952, D.H. Peterson and H.C. Murray of Upjohn Co. developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone. The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $0.46 per gram by 1980. The research of Percy Julian also aided progress in the field. The exact nature of cortisone's anti-inflammatory nature remained a mystery for years after however, until the leukocyte adhesion cascade was fully understood in the early 1980s.

Cardiovascular

:This is an article about circulation in animals. For transport in plants, see Vascular tissue. For the band, see Circulatory System. The circulatory system or cardiovascular system is the organ system which circulates blood around the body of most animals.

Types of circulatory systems

Open circulatory system

The circulatory system of arthropods and most mollusks is open, meaning that there are no capillaries and veins: one or more hearts pump the blood (more properly called hemolymph in this case) through the arteries to spaces called sinuses which surround the organs, allowing the tissues to exchange materials with the hemolymph. The hemolymph is drawn back into the heart as the heart relaxes.

Closed circulatory system

The circulatory systems of all vertebrates, as well as of annelids (for example, earthworms) and cephalopods (squids and octopuses) are closed, meaning that the blood never leaves the system of blood vessels consisting of arteries, capillaries and veins. The systems of fish, amphibians, reptiles, birds and mammals show various stages of evolution. In fish, the system has only one circuit, with the blood being pumped through the capillaries of the gills and on to the capillaries of the body tissues. This is known as single circulation. The heart of fish is therefore only a single pump (consisting of two chambers). In amphibians and reptiles, a double circulation is used, but the heart is not always completely separated into two pumps. Amphibians have a three-chambered heart. Birds and mammals show complete separation of the heart into two pumps, for a total of four heart chambers; it is thought that the four-chambered heart of birds evolved independently of that of mammals.

No circulatory system

An example of an animal with no circulatory system is the flatworm (class Turbellaria). They have a mouth leading into a digestive system. The digestive system is very branched, and because the worm is so flat, digested materials can be diffused to all the cells of the flat worm. Oxygen can diffuse from water into the cells of the flatworm. Thus every cell is able to obtain nutrients, water and oxygen without the need of a transport system.

Measurement techniques

- Electrocardiogram
- Sphygmomanometer
- Pulse meter

Health and disease

- See heart disease

History of discovery

The valves of the heart were discovered by a physician of the Hippocratean school around the 4th century BC. However their function was not properly understood then. Because blood pools in the veins after death, arteries look empty. Ancient anatomists assumed they were filled with air and that they were for transport of air. Herophilus distinguished veins from arteries but thought that the pulse was a property of arteries themselves. Erasistratus observed that arteries that were cut during life bleed. He ascribed the fact to the phenomenon that air escaping from an artery is replaced with blood that entered by very small vessels between veins and arteries. Thus he apparently postulated capillaries but with reversed flow of blood. Galen in the 2nd century AD knew that blood vessels carry blood and identified venous (dark red) and arterial (brighter and thinner) blood, each with distinct and separate functions. Growth and energy were derived from venous blood created in the liver from chyle, while arterial blood gave vitality by containing pneuma (air) and originated in the heart. Blood flowed from both creating organs to all parts of the body where it was consumed and there was no return of blood to the heart or liver. The heart did not pump blood around, the heart's motion sucked blood in during diastole and the blood moved by the pulsation of the arteries themselves. Galen believed that the arterial blood was created by venous blood passing from the left ventricle to the right by passing through 'pores' in the interventricular septum, air passed from the lungs via the pulmonary artery to the left side of the heart. As the arterial blood was created 'sooty' vapors were created and passed to the lungs also via the pulmonary artery to be exhaled. Ibn Nafis in 1242 was the first person to accurately describe the process of blood circulation in the human body. Contemporary drawings of this process have survived. In 1552 Servetus described the same and Realdo Colombo proved the concept. All these results were not widely accepted however. Finally William Harvey, a pupil of Hieronymus Fabricius (who had earlier described the valves of the veins without recognizing their function), performed a sequence of experiments and announced in 1628 the discovery of the human circulatory system as his own and published an influential book about it. This work with its essentially correct exposition slowly convinced the medical world. Harvey was not able to identify the capillary system connecting arteries and veins; these were later described by Marcello Malpighi.

External links

- [http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookcircSYS.html The Circulatory System], a comprehensive overview
- [http://www.ncvc.go.jp/english/res/Car_Dyn_A.html Studies on Hemodynamics and Coronary Circulation]
- [http://www.invisionguide.com/heart The InVision Guide to a Healthy Heart] An interactive website

References

- Iskandar, Albert Z. [http://www.islamset.com/isc/nafis/iskandar.html "Comprehensive Book on the Art of Medicine by Ibn al-Nafis"]. Retrieved May 2 2005. Category:Cardiovascular system simple:Circulatory system

Metabolism

Metabolism (from μεταβολισμος ("metabolismos"), the Greek word for "change", or "overthrow" ([http://www.etymonline.com Etymonline])), is the biochemical modification of chemical compounds in living organisms and cells. This includes the biosynthesis of complex organic molecules (anabolism) and their breakdown (catabolism). Metabolism usually consists of sequences of enzymatic steps, also called metabolic pathways. The total metabolism are all biochemical processes of an organism. The cell metabolism includes all chemical processes in a cell. Without metabolism we would not be able to survive.

Metabolic pathways

Important metabolic pathways are:

General pathways

- Carbohydrate metabolism
- Fatty acid metabolism
- Citric acid cycle (Krebs cycle, tricarboxylic acid cycle)

Catabolism

Catabolic pathways that breakdown complex molecules into simple compounds:
- Cellular respiration, metabolic pathways that create energy (ATP and NADPH) from fuel molecules. These pathways are also involved in the digestion of food.
- Carbohydrate catabolism
- Glycogenolysis, the conversion of glycogen into glucose.
- Glycolysis, the conversion of glucose into pyruvate and ATP, does not require oxygen.
- Embden-Meyerhof pathway, the common glycolysis pathway.
- Entner-Doudoroff Pathway, an alternative glycolysis pathway in few bacteria.
- Pentose phosphate pathway (hexose monophosphate shunt), generation of NADPH from glucose.
- Protein catabolism, the hydrolysis of proteins into amino acids.
- Aerobic respiration
- Electron transfer chain
- Oxidative phosphorylation
- Anaerobic respiration,
- Cori cycle
- Lactic acid fermentation
- Fermentation
- Ethanol fermentation

Anabolism

Anabolic pathways that create building blocks and compounds from simple precursors:
- Glycogenesis
- Gluconeogenesis
- Porphyrin synthesis pathway
- HMG-CoA reductase pathway, leading to cholesterol and isoprenoids.
- Secondary metabolism, metabolic pathways that are not essential for growth, development or reproduction, but that usually have ecological function.
- Photosynthesis
- Light-dependent reaction (light reaction)
- Light-independent reaction (dark reaction)
- Calvin cycle
- Carbon fixation

Drug metabolism

Drug metabolism pathways, the modification or degradation of drugs and other xenobiotic compounds through specialized enzyme systems:
- Cytochrome P450 oxidase system
- Flavin-containing monooxygenase system
- Alcohol metabolism

Nitrogen metabolism

Nitrogen metabolism includes the pathways for turnover and excretion of nitrogen in organisms as well as the biological processes of the biogeochemical nitrogen cycle:
- Urea cycle, important for excretion of nitrogen as urea.
- Biological nitrogen fixation
- Nitrogen assimilation
- Nitrification
- Denitrification

Other

- Human iron metabolism

History

The first controlled experiments in human metabolism were published by Santorio Santorio in 1614 in his book Ars de statica medecina that made him famous throughout Europe. He describes his long series of experiments in which he weighed himself in a chair suspended from a steelyard balance (see image), before and after eating, sleeping, working, sex, fasting, depriving from drinking, and excreting. He found that by far the greatest part of the food he took in was lost from the body through perspiratio insensibilis (insensible perspiration).

External links

- [http://www2.ufp.pt/~pedros/bq/integration.htm Interactive Flow Chart of the Major Metabolic Pathways]
- [http://www.biochemweb.org/metabolism.shtml Metabolism, Cellular Respiration and Photosynthesis - The Virtual Library of Biochemistry and Cell Biology]
- [http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/MB1index.html The Biochemistry of Metabolism at Rensselaer Polytechnic Institute]
- [http://www.expasy.org/cgi-bin/show_thumbnails.pl Flow Chart of Metabolic Pathways at ExPASy]
- [http://www.istrianet.org/istria/illustri/santorio/ Santorio Santorio's experiments]
- [http://www.genome.ad.jp/kegg/ KEGG: Kyoto Encyclopedia of Genes and Genomes]
- th:การเผาผลาญ ja:代謝 simple:Metabolism

Immunology

Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with, among other things, the physiological functioning of the immune system in states of both health and disease; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, allograft rejection); the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo. Immunology has various applications in several disciplines of science, and as such is further divided.

Histological examination of the immune system

Before even the concept of immunity was developed numerous early physicians characterised organs that would later prove to be part of the immune system. The key organs of the immune system are thymus, spleen, bone marrow, lymph vessels, lymph nodes and secondary lymphatic tissues such as tonsils and adenoids) and skin. The major organs, the thymus and spleen, are examined histologically only post-mortem during autopsy. However some lymph nodes, and secondary lymphatic tissues can be surgically excised for examination while patients are still alive. Many components of the immune system are actually cellular in nature and not associated with any specific organ, but embedded or circulating in various tissues located about the body.

Classical immunology

Classical immunology ties in with the fields of epidemiology and medicine. It studies the relationship between the body systems, pathogens and immunity. The earliest written mention of immunity can be traced back to the plague of Athens in 430 BC. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without coming down with the illness a second time. Many other ancient societies have references to this phenomenon, but it was not until the 19th and 20th centuries before the concept developed into scientific theory. The study of molecular and cellular components that comprise the immune system, including their function and interaction, is the central science of immunology. The immune system has been divided into innate immune system, and acquired or adaptive immune system, the latter of which is further divided into humoral and cellular components. The humoral (antibody) response is defined as the interaction between antibodies and antigens. Without an understanding of the properties of these two biological entities, much of immunology would be non-existent. However, equally important is the cellular response which can not only kill infected cells in its own right, but is also crucial in controlling the antibody response. Put simply, both systems are highly interdependent. In the 21st century though, immunology has broadened its horizons with much research being performed in the more specialized niches of immunology. This includes the immunological function of cells, organs and systems not normally associated with the immune system, as well as the function of the immune system outside classical models of immunity.

Clinical immunology

Clinical immunology is the study of diseases caused by the immune system and diseases of the immune system from a medical perspective. Many diseases caused by the immune system fall into two broad categories: immunodeficiency, in which parts of the immune system fail to provide an adequate response (examples include chronic granulomatous disease), and autoimmunity, in which the immune system attacks its own antigens (examples include systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's disease and myasthenia gravis). Other immune system disorders include different hypersensitivities, in which the system responds inappropriately to harmless compounds (asthma and allergies) or responds too intensively. The most well-known disease that affects the immune system itself is AIDS, caused by the HIV virus. AIDS is an immunodeficiency characterized by the lack of CD4+ ("helper") T cells and macrophages, which are destroyed by the HIV virus. Clinical immunologists also study ways to prevent transplant rejection, in which the immune system attempts to destroy allografts or xenografts.

Immunotherapy

See main article Immunotherapy The use of immune system components to treat a disease or disorder is known as immunotherapy. Immunotherapy is most commonly used in the context of the treatment of cancers together with chemotherapy (drugs) and radiotherapy (radiation). However, immunotherapy is also often used in the immunosuppressed (such as HIV patients) and people suffering from other immune deficiencies or autoimmune diseases.

Diagnostic immunology

The specificity of the bond between antibody and antigen has made it an excellent tool in the detection of substances in a variety of diagnostic techniques. Antibodies specific for a desired antigen can be conjugated with a radiolabel, fluorescent label, or color-forming enzyme and are used as a "probe" to detect it. Well known applications of this include immunoblotting, ELISA and immunohistochemical staining of microscope slides. The speed, accuracy and simplicity of such tests has led to the development of rapid techniques for the diagnosis of disease, microbes and even illegal drugs in vivo (of course tests conducted in a closed environment have a higher degree of accuracy). Such testing is also used to distinguish compatible blood types.

Evolutionary immunology

Study of the immune system in extant and extinct species is capable of giving us a key understanding of the evolution of species and the immune system. A development of complexity of the immune system can be seen from simple phagocytotic protection of single celled organisms, to circulating antimicrobial peptides in insects to lymphoid organs in vertebrates. Of course, like much of evolution, this is often seen from the anthropocentric aspect, but it must be recognised, that every organism's immune system is absolutely capable of protecting it from most forms of harm. Insects and other arthropods, while not possessing true adaptive immunity, show highly evolved systems of innate immunity, and are additionally protected from external injury (and exposure to pathogens) by their chitinous shells.

References

- Goldsby RA, Kindt TK, Osborne BA and Kuby J (2003) Immunology, 5th Edition, W.H. Freeman and Company, New York, New York, ISBN 0-7167-4947-5 ko:면역학 ja:免疫学 simple:Immunology th:ภูมิคุ้มกันวิทยา

Glucocorticoid receptor

The glucocorticoid receptor (GR) is a ligand-activated intracytoplasmatic transcription factor that interacts with high affinity to cortisol and other glucocorticoids. The GR is controlled by gene NR3Cl on chromosome 5 ( 5q31). Like the other steroid receptors the structure of the GR consists of a variable domain, the DNA-binding domain with zinc fingers, a hinge region, and the hormone-binding domain with a final carboxy terminal. Cortisol diffuses through the cell wall into the cytoplasm and binds to the glucocorticoid receptor (GR) forming a GR-hormone complex. Initially the GR includes the heat shock protein 90 (hsp90), the heat shock protein 70 (hsp70) and the protein FKBP52. Dissociation of the GR complex releases the heat shock chaperones and yields the free cortisol-receptor subunits that link up as homodimers. These are translocated via nucleopores into the nucleus and bind with zinc fingers to the specific DNA responsive elements activating gene transcription. The biologic response depends on the cell type. Relaxin is an agonist, and RU486 and cyproterone are antagonists of the GR. Also, progesterone and DHEA have antagonist effects on the GR. The GR is abnormal in familial glucocorticoid resistance (PMID 11932321).

External links

- [http://www.hprd.org/protein/00679 Human Protein Reference Database]
- Category:Intracellular receptors

Vertebrate

Conodonta
Hyperoartia
:Petromyzontidae (lampreys)
Pteraspidomorphi (early jawless fish)
Thelodonti
Anaspida
Cephalaspidomorphi (early jawless fish)
:Galeaspida
:Pituriaspida
:Osteostraci
Gnathostomata (jawed vertebrates)
:Placodermi
:Chondrichthyes (cartilaginous fish)
:Acanthodii
:Osteichthyes (bony fish)
::Actinopterygii (ray-finned fish)
::Sarcopterygii (lobe-finned fish)
:::Actinistia (coelacanths)
:::Dipnoi (lungfish)
:::Tetrapoda ::::Amphibia
::::Amniota
:::::Sauropsida/(Reptiles)
::::::Aves (Birds)
:::::Synapsida
::::::Mammalia Vertebrata is a subphylum of chordates, specifically, those with backbones or spinal columns. Vertebrates started to evolve about 530 million years ago during the Cambrian explosion, which is part of the Cambrian period (first known vertebrate is Myllokunmingia). The bones of the spinal column (or vertebral column) are called vertebrae. Vertebrata is the largest subphylum of chordates, and contains most animals with which people are generally familiar (except insects). Fish (including lampreys, but traditionally not hagfish, though this is now disputed), amphibians, reptiles, birds, and mammals (including humans) are vertebrates. Additional characteristics of the subphylum are a muscular system that mostly consists of paired masses, as well as a central nervous system which is partly located inside the backbone. The internal skeleton which defines vertebrates consists of cartilage or bone, or in some cases both. The skeleton provides support to the organism during the period of growth. For this reason vertebrates can achieve larger sizes than invertebrates, and on average vertebrates are in fact larger. The skeleton of most vertebrates, that is excluding the most primitive ones, consists of a skull, the vertebral column and two pairs of limbs. In some forms of vertebrates, one or both of these pairs of limbs may be absent, such as in snakes or whales. These limbs have been lost in the course of evolution. The skull is thought to have facilitated the development of intelligence as it protects vital organs such as the brain, the eyes and the ears. The protection of these organs is also thought to have positively influenced the development of high responsiveness to the environment often found in vertebrates. Both the vertebral column and the limbs support the body of the vertebrate overall. This support facilitates movement. Movement is normally achieved with muscles that are attached directly to the bones or cartilages. The contour of the body of a vertebrate is formed by the muscles. A skin covers the inner parts of a vertebrate's body. The skin sometimes acts as a structure for protective features, such as horny scales or fur. Feathers are also attached to the skin. The trunk of a vertebrate is hollow and houses the internal organs. The heart and the respiratory organs are protected in the trunk. The heart is located behind the gills, or where there are lungs, in between the lungs. The central nervous system of a vertebrate consists of the brain and the spinal cord. Both of these are characterized by being hollow. In lower vertebrates the brain mostly controls the functioning of the sense organs. In higher vertebrates the size of the brain relative to the size of the body is larger. This larger brain enables more intensive exchange of information between the different parts of the brain. The nerves from the spinal cord, which lies behind the brain, extend to the skin, the inner organs and the muscles. Some nerves are directly connected to the brain, linking the brain with the ears and lungs. Vertebrates have been traced back to the ostracoderms of the Silurian Period (444 million to 409 million years ago) and the conodonts, a group of eel-like vertebrates characterized by multiple pairs of bony toothplates. All vertebrates have: the ability to form bones; paired, specialised sensory organs and a brain.

External links

- [http://tolweb.org/tree?group=Amniota&contgroup=Terrestrial_vertebrates Tree of Life]
- [http://reference.allrefer.com/encyclopedia/categories/vertz.html Vertebrate Zoology] Category:Chordates ko:척추동물 ms:Vertebrata ja:脊椎動物 simple:Vertebrate th:สัตว์มีกระดูกสันหลัง

Hormone

A hormone (from Greek horman - "to set in motion") is a chemical messenger from one cell (or group of cells) to another. All multicellular organisms produce hormones (including plants - see article phytohormone). The best known animal (and human) hormones are those produced by endocrine glands of vertebrate animals, but hormones are produced by nearly every organ system and tissue type in a human or animal body. Hormone molecules are secreted (released) directly into the bloodstream (however, some hormones, called ectohormones are secreted to the outside environment). They move by circulation or diffusion to their target cells, which may be nearby cells (paracrine action) in the same tissue or cells of a distant organ of the body. The function of hormones is to serve as a signal to the target cells; the action of hormones is determined by the pattern of secretion and the signal transduction of the receiving tissue. Hormone actions vary widely, but can include stimulation or inhibition of growth, induction or suppression of apoptosis (programmed cell death), activation or inhibition of the immune system, regulating metabolism and preparation for a new activity (e.g. fighting, fleeing, mating) or phase of life (e.g. puberty, caring for offspring, menopause). In many cases, one hormone may regulate the production and release of other hormones. Many of the responses to hormone signals can be described as serving to regulate metabolic activity of an organ or tissue. Hormones also control the reproductive cycle of virtually all multicellular organisms.

History

The concept of internal secretion developed in the 19th century; Claude Bernard described it in 1855, but did not specifically address the possibility of secretions of one organ acting as messengers to others. Still, various endocrine conditions were recognised and even treated adequately (e.g. hypothyroidism with extract of thyroid glands). The major breakthrough was the identification of secretin, the hormone secreted by the duodenum that stimulates pancreatic secretions, by Ernest Starling and William Bayliss in 1902. Previously, the process had been considered (e.g. by Ivan Pavlov) to be regulated by the nervous system. Starling and Bayliss demonstrated that injecting duodenal extract into dogs rapidly increased pancreatic secretions, raising the possibility of a chemical messenger. Starling is also credited with introducing the term "hormone", having coined it in a 1905 lecture. Later reports indicate it was suggested to him by the Cambridge physiologist William B. Hardy (Henderson 2005). The remainder of the 20th century saw all the major hormones discovered, as well as the cloning of the relevant genes and the identification of the many interlocking feedback mechanisms that characterise the endocrine system.

Physiology of hormones

Every cell is capable of producing a vast number of regulatory molecules. The classical endocrine glands and their hormone products are specialized to serve regulation on the overall organism level, but can in many instances be used in other ways or only on the tissue level. The rate of production of a given hormone is most commonly regulated by a homeostatic control system, generally by negative feedback. Homeostatic regulation of hormones depends, apart from production, on the metabolism and excretion of hormones. Hormone secretion can be stimulated and inhibited by:
- Other hormones (stimulating or releasing-hormones)
- Plasma concentrations of ions or nutrients, as well as binding globulins
- Neurons and mental activity
- Environmental changes, e.g. of light or temperature One special group of hormones are trophic hormones that act as stimulants of hormone production of other endocrine glands. For example: thyroid-stimulating hormone (TSH) causes growth and increased activity of another endocrine gland - the thyroid - hence increasing output of thyroid hormones. A recently identified and studied class of hormones is that of the "Hunger Hormones" - ghrelin, orexin and PYY 3-36 - and their antagonists - e.g. leptin.

Types of hormones

Vertebrate hormones fall into four chemical classes: #Amine-derived hormones are derivatives of the amino acids tyrosine and tryptophan. Examples are catecholamines and thyroxine. #Peptide hormones consist of chains of amino acids. Examples of small peptide hormones are TRH and vasopressin. Peptides composed of scores or hundreds of amino acids are referred to as proteins. Examples of protein hormones include insulin and growth hormone. #Steroid hormones are derived from cholesterol. The adrenal cortex and the gonads are primary sources. Examples of steroid hormones are testosterone and cortisol. Sterol hormones such as calcitriol are a homologous system. #Lipid and phospholipid hormones are derived from lipids such as linoleic acid and phospholipids such as arachidonic acid. The main class is the eicosanoids, which includes the widely studied prostaglandins.

Pharmacology

A large number of hormones are used as medication. The most commonly prescribed hormones are estrogens and progestagens (in the contraceptive pill and as HRT), thyroxine (as levothyroxine, for hypothyroidism) and steroids (for autoimmune diseases and several respiratory disorders). Insulin is used by many diabetics. Local preparations for use in otolaryngology often contain pharmacologic equivalents of adrenalin, while steroid and vitamin D creams are used extensively in dermatological practice. A "pharmacologic dose" of a hormone is a medical usage referring to an amount of a hormone far greater than naturally occurs in a healthy body. The effects of pharmacologic doses of hormones may be different from responses to naturally occurring amounts and may be therapeutically useful. An example is the ability of pharmacologic doses of glucocorticoid to suppress inflammation.

Important human hormones

Spelling is not uniform for many hormones. Current North American and international usage is estrogen, gonadotropin, while British usage retains the Greek diphthong in oestrogen and the unvoiced aspirant h in gonadotrophin.

Amine hormones

Amine-derived hormones:
- adrenaline (or epinephrine)
- dopamine
- melatonin (N-acetyl-5-methoxytryptamine)
- noradrenaline (or norepinephrine)
- serotonin (5-HT)
- thyroxine (T4)
- triiodothyronine (T3)

Peptide hormones

Peptide hormones:
- antimullerian hormone (AMH, also mullerian inhibiting factor or hormone)
- adiponectin (also Acrp30)
- adrenocorticotropic hormone (ACTH, also corticotropin)
- angiotensinogen and angiotensin
- antidiuretic hormone (ADH, also vasopressin, arginine vasopressin, AVP)
- atrial-natriuretic peptide (ANP, also atriopeptin)
- calcitonin
- cholecystokinin (CCK)
- corticotropin-releasing hormone (CRH)
- erythropoietin (EPO)
- follicle stimulating hormone (FSH)
- gastrin
- glucagon
- gonadotropin-releasing hormone (GnRH)
- growth hormone-releasing hormone (GHRH)
- human chorionic gonadotropin (hCG)
- growth hormone (GH or hGH)
- insulin
- insulin-like growth factor (IGF, also somatomedin)
- leptin
- luteinizing hormone (LH)
- melanocyte stimulating hormone (MSH or α-MSH)
- neuropeptide Y
- oxytocin
- parathyroid hormone (PTH)
- prolactin (PRL)
- renin
- secretin
- somatostatin
- thrombopoietin
- thyroid-stimulating hormone (TSH)
- thyrotropin-releasing hormone (TRH)

Steroid and sterol hormones

Steroid hormones:
- Glucocorticoids
- cortisol
- Mineralocorticoids
- aldosterone
- Sex steroids
- Androgens
- testosterone
- dehydroepiandrosterone (DHEA)
- dehydroepiandrosterone sulfate (DHEAS)
- androstenedione
- dihydrotestosterone (DHT)
- Estrogens
- estradiol
- Progestagens
- progesterone
- Progestins Sterol hormones:
- Vitamin D derivatives
- calcitriol

Lipid hormones

Lipid and phospholipid hormones (eicosanoids):
- prostaglandins
- leukotrienes
- prostacyclin
- thromboxane

Reference

- Henderson J. Ernest Starling and 'Hormones': an historical commentary. J Endocrinol 2005;184:5-10. PMID 15642778. Category:Endocrinology Category:Signal transduction ko:호르몬 ja:ホルモン simple:Hormone th:ฮอร์โมน

Cortisol

Synthesis

Physiology

Pharmacology

Diseases

Excessive levels of cortisol in the blood result in Cushing's syndrome. If on the other hand the adrenal glands do not produce sufficient amounts of cortisol, Addison's disease is the consequence.

References

Online

- [http://www.duchs.com/information/Hydrocortisone Hydrocortisone] Fact Sheet

Printed

Liver

The liver is an organ in vertebrates, including humans. It plays a major role in metabolism and has a number of functions in the body including drug detoxification, glycogen storage, and plasma protein synthesis. It also produces bile, which is important for digestion. Medical terms related to the liver often start in hepato- or hepatic from the Greek word for liver, hepar.

Anatomy

Greek Greek The adult human liver normally weighs between 1.0 - 2.5 kilograms, and is a soft, pinkish-brown "boomerang shaped" organ. It is the largest internal organ (the largest organ being the skin) and sits immediately under the diaphragm on the right side of the upper abdomen. The liver lies on the right of the stomach and makes a kind of bed for the gallbladder (which stores bile). The liver is supplied by two major blood vessels: the hepatic artery and the portal vein. The hepatic artery normally comes off the celiac trunk. The portal vein brings venous blood from the spleen, pancreas, and small intestines, so that the liver can process the nutrients and byproducts of food digestion. The hepatic veins drain directly into the inferior vena cava. The bile produced in the liver is collected in bile canaliculi, which merge to form bile ducts. These eventually drain into the right and left hepatic ducts, which in turn merge to form the common hepatic duct. The cystic duct (from the gallbladder) joins with the common hepatic duct to form the common bile duct. Bile can either drain directly into the duodenum via the common bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the duodenum together at the ampulla of Vater. The branchings of the bile ducts resemble those of a tree, and indeed the term "biliary tree" is commonly used in this setting. The liver is one of the only internal human organs capable of natural regeneration of lost tissue; as little as 25% of remaining liver can regenerate into a whole liver again. This is predominantly due to the hepatocytes acting as unipotential stem cells. There is also some evidence of bipotential stem cells, called oval cells, which can differentiate into either hepatocytes or cholangiocytes (cells that line the bile ducts).

Surface anatomy

Apart from a patch where it connects to the diaphragm, the liver is covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction against other organs. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments. These "ligaments" are in no way related to the true anatomic ligaments in joints, and have essentially no functional importance, but they are easily recognizable surface landmarks. Traditional gross anatomy divided the liver into four lobes based on surface features. The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe. If the liver is flipped over, to look at it from behind (the visceral surface), there are two additional lobes between the right and left. These are the caudate lobe (the more superior), and below this the quadrate lobe. From behind, the lobes are divided up by the ligamentum venosum and ligamentum teres (anything left of these is the left lobe), the transverse fissure (or porta hepatis) divides the caudate from the quadrate lobe, and the right sagittal fossa, which the inferior vena cava runs over, separates these two lobes from the right lobe.

Functional anatomy

For purposes such as advanced liver surgery, it is crucial to understand the organization of liver based on blood supply and biliary drainage. The central area where the common bile duct, portal vein, and hepatic artery enter the liver is the hilum or "porta hepatis". The duct, vein, and artery divide into left and right branches, and the portions of the liver supplied by these branches constitute the functional left and right lobes. The functional lobes are separated by a plane joining the gallbladder fossa to the inferior vena cava. In the widely used Couinaud or "French" system, the functional lobes are further divided into a total of eight segments based on secondary and tertiary branching of the blood supply. The segments corresponding to the surface anatomical lobes are as follows:

Physiology

The various functions of the liver are carried out by the liver cells or hepatocytes.
- The liver produces and excretes bile required for food digestion. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
- The liver performs several roles in carbohydrate metabolism:
- Gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol)
- Glycogenolysis (the formation of glucose from glycogen)
- Glycogenesis (the formation of glycogen from glucose)
- The breakdown of insulin and other hormones
- The liver also performs several roles in lipid metabolism:
- Cholesterol synthesis
- The production of triglycerides (fats).
- The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, and XI, as well as protein C, protein S and antithrombin.
- The liver breaks down hemoglobin (bile pigments are its metabolites), toxic substances and most medicinal products. This sometimes results in toxication, when the metabolite is more toxic than its precursor.
- The liver converts ammonia to urea.
- The liver stores a multitude of substances, including glucose in the form of glycogen, vitamin B12, iron, and copper.
- In the first trimester fetus, the liver is the main site of red blood cell production. By the 42nd week of gestation, the bone marrow has almost completely taken over that task. Producing an artificial organ or device capable of emulating all functions of the liver is outside the reach of science in the foreseeable future. Some functions can be emulated by liver dialysis, an experimental treatment for liver failure.

Diseases of the liver

Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.
- Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
- Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals
- Hemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage
- Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract)
- Wilson's disease, a hereditary disease which causes the body to retain copper
- Primary sclerosing cholangitis, an inflammatory disease of the bile duct, autoimmune in nature.
- Primary biliary cirrhosis, autoimmune disease of small bile ducts
- Budd-Chiari syndrome, obstruction of the hepatic vein. A number of liver function tests are available to test the proper function of the liver. These are enzymes that are most abundant in liver tissue, metabolites or products.

Liver transplantation

Liver transplantation is an option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism, autoimmune hepatitis, and many others. Less commonly, liver transplantation is done for fulminant hepatic failure, in which liver failure occurs over days to weeks. Liver allografts for transplant usually come from non-living donors who have died from fatal brain injury. Living donor liver transplantation is a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20% of an adult's liver (Couinaud segments 2 and 3) is

Glucocorticoid

Effects

Mode of action

Pharmacologic properties

Physiologic replacement of glucocorticoid

Medical uses and effects of high dose glucocorticoids

Immunosuppressive mechanism

Antiinflammatory effects

Side effects

Adrenal suppression and withdrawal

See also

Steroid hormone

Overview

Synthesis

Principal natural human steroid hormones

Synthetic steroids and sterols

Cortisol

Synthesis

Physiology

Pharmacology

Diseases

See also

References

Online

Printed

Mineralocorticoid

Corticosteroid

Uses

History

See also

Cardiovascular

Types of circulatory systems

Open circulatory system

Closed circulatory system

No circulatory system

Measurement techniques

Health and disease

History of discovery

See also

External links

References

Metabolism

Metabolic pathways

General pathways

Catabolism

Anabolism

Drug metabolism

Nitrogen metabolism

Other

History

See also

External links

Immunology

Histological examination of the immune system

Classical immunology

Clinical immunology

Immunotherapy

Diagnostic immunology

Evolutionary immunology

See also

References

Glucocorticoid receptor

External links

Vertebrate

External links

Hormone

History

Physiology of hormones

Types of hormones

Pharmacology

Important human hormones

Amine hormones

Peptide hormones

Steroid and sterol hormones

Lipid hormones

See also

Reference

Cortisol

Synthesis

Physiology