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List of medical emergencies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


The following is a list of symptoms and conditions that signal or constitute a possible medical emergency and may require immediate first aid, emergency room care, surgery, or care by a physician or nurse. Please note that not all medical emergencies listed below are life-threatening; some conditions require medical attention in order to prevent significant and long-lasting effects on physical or mental health.

Injury and illness

Injury and illness

Infections

Infections

Cardiac and circulatory

Cardiac and circulatory

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]



Cardiology is the branch of medicine pertaining to the heart.

Cardiac pacemaker (Electrical system of the heart)

Basic cardiac physiology

Disorders of the coronary circulation

Sudden cardiac death (The abrupt cessation of blood flow, leading to death)

Treatment of sudden cardiac death

Disorders of the myocardium (muscle of the heart)

Disorders of the pericardium (outer lining of the heart)

Disorders of the heart valves

Disorders of the electrical system of the heart (Cardiac electrophysiology)

Inflammation and infection of the heart

Congenital heart disease

Diseases of blood vessels (Vascular diseases)

Procedures done for coronary artery disease

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Devices used in cardiology

Diagnostic tests and procedures

Electrocardiogram (ECG or EKG)

Cardiac pharmaceutical agents

The followings are medications commonly prescribed in cardiology:

See also

ast:Cardioloxía ca:Cardiologia de:Kardiologie eu:Kardiologia hr:Kardiologija id:Kardiologi it:Cardiologia he:קרדיולוגיה la:Cardiologia nl:Cardiologie no:Kardiologi nds:Kardiologie sq:Kardiologjia sl:Kardiologija sh:Kardiologija sv:Kardiologi uk:Кардіологія


Template:WikiDoc Sources CME Category::Cardiology CME Category::Cardiology

Metabolic

Metabolic

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Structure of the coenzyme adenosine triphosphate, a central intermediate in energy metabolism.

Metabolism is the complete set of chemical reactions that occur in living cells. These processes are the basis of life, allowing cells to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism, which yields energy, an example being is the breakdown of food in cellular respiration. Anabolism, on the other hand, uses this energy to construct components of cells such as proteins and nucleic acids.

The chemical reactions of metabolism are organised into metabolic pathways, in which one chemical is transformed into another by a sequence of enzymes. Enzymes are crucial to metabolism because they allow cells to drive desirable but thermodynamically unfavorable reactions by coupling them to favorable ones. Enzymes also allow the regulation of metabolic pathways in response to changes in the cell’s environment or signals from other cells.

The metabolism of an organism determines which substances it will find nutritious and which it will find poisonous. For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals.[1] The speed of metabolism, the metabolic rate, also influences how much food an organism will require.

A striking feature of metabolism is the similarity of the basic metabolic pathways between even vastly different species. For example, the set of chemical intermediates in the citric acid cycle are found universally, among living cells as diverse as the unicellular bacteria Escherichia coli and huge multicellular organisms like elephants.[2] This shared metabolic structure is most likely the result of the high efficiency of these pathways, and of their early appearance in evolutionary history.[3][4]

Key biochemicals

Further information: [[:Biomolecule, cell (biology) and biochemistry]]
Structure of a triacylglycerol lipid.

Most of the structures that make up animals, plants and microbes are made from three basic classes of molecule: amino acids, carbohydrates and lipids (often called fats). As these molecules are vital for life, metabolism focuses on making these molecules, in the construction of cells and tissues, or breaking them down and using them as a source of energy, in the digestion and use of food. Many important biochemicals can be joined together to make polymers such as DNA and proteins. These macromolecules are essential parts of all living organisms. Some of the most common biological polymers are listed in the table below.

Type of molecule Name of monomer forms Name of polymer forms Examples of polymer forms
Amino acids Amino acids Proteins (also called polypeptides) Fibrous proteins and globular proteins
Carbohydrates Monosaccharides Polysaccharides Starch, glycogen and cellulose
Nucleic acids Nucleotides Polynucleotides DNA and RNA

Amino acids and proteins

Proteins are made of amino acids arranged in a linear chain and joined together by peptide bonds. Many proteins are the enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as the proteins in the cytoskeleton that form a system of scaffolding to maintain cell shape.[5] Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes and the cell cycle.[6]

Lipids

Lipids are the most diverse group of biochemicals. Their main structural uses are as part of biological membranes such as the cell membrane, or as a source of energy.[6] Lipids are usually defined as hydrophobic or amphipathic biological molecules that will dissolve in organic solvents such as benzene or chloroform.[7] The fats are a large group of compounds that contain fatty acids and glycerol; a glycerol molecule attached to three fatty acid esters is a triacylglyceride.[8] Several variations on this basic structure exist, including alternate backbones such as sphingosine in the sphingolipids, and hydrophilic groups such as phosphate in phospholipids. Steroids such as cholesterol are another major class of lipids that are made in cells.[9]

Carbohydrates

Glucose can exist in both a straight-chain and ring form.

Carbohydrates are straight-chain aldehydes or ketones with many hydroxyl groups that can exist as straight chains or rings. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy (starch, glycogen) and structural components (cellulose in plants, chitin in animals).[6] The basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose. Monosaccharides can be linked together to form polysaccharides in almost limitless ways.[10]

Nucleotides

The polymers DNA and RNA are long chains of nucleotides. These molecules are critical for the storage and use of genetic information, through the processes of transcription and protein biosynthesis.[6] This information is protected by DNA repair mechanisms and propagated through DNA replication. A few viruses have an RNA genome, for example HIV, which uses reverse transcription to create a DNA template from its viral RNA genome.[11] RNA in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Individual nucleosides are made by attaching a nucleobase to a ribose sugar. These bases are heterocyclic rings containing nitrogen, classified as purines or pyrimidines. Nucleotides also act as coenzymes in metabolic group transfer reactions.[12]

Coenzymes

Structure of the coenzyme acetyl-CoA.The transferable acetyl group is bonded to the sulphur atom at the extreme left.

Metabolism involves a vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups.[13] This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions.[12] These group-transfer intermediates are called coenzymes. Each class of group-transfer reaction is carried out by a particular coenzyme, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. These coenzymes are therefore continuously being made, consumed and then recycled.[14]

The most central coenzyme is adenosine triphosphate (ATP), the universal energy currency of cells. This nucleotide is used to transfer chemical energy between different chemical reactions. There is only a small amount of ATP in cells, but as it is continuously regenerated, the human body can use about its own weight in ATP per day.[14] ATP acts as a bridge between catabolism and anabolism, with catabolic reactions generating ATP and anabolic reactions consuming it. It also serves as a carrier of phosphate groups in phosphorylation reactions.

A vitamin is an organic compound needed in small quantities that cannot be made in the cells. In human nutrition, most vitamins function as coenzymes after modification; for example, all water-soluble vitamins are phosphorylated or are coupled to nucleotides when they are used in cells.[15] Nicotinamide adenine dinucleotide (NADH), a derivative of vitamin B3 (niacin), is an important coenzyme that acts as a hydrogen acceptor. Hundreds of separate types of dehydrogenases remove electrons from their substrates and reduce NAD+ into NADH. This reduced form of the coenzyme is then a substrate for any of the reductases in the cell that need to reduce their substrates.[16] Nicotinamide adenine dinucleotide exists in two related forms in the cell, NADH and NADPH. The NAD+/NADH form is more important in catabolic reactions, while NADP+/NADPH is used in anabolic reactions.

Structure of hemoglobin. The protein subunits are in red and blue, and the iron-containing heme groups in green. From PDB: 1GZX​.

Minerals and cofactors

Further information: [[:Physiology, bioinorganic chemistry and iron metabolism]]

Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium) while others function at minute concentrations. About 99% of mammals’ mass are the elements carbon, nitrogen, calcium, sodium, chlorine, potassium, hydrogen, oxygen and sulfur.[17] The organic compounds (proteins, lipids and carbohydrates) contain the majority of the carbon and nitrogen and most of the oxygen and hydrogen is present as water.[17]

The abundant inorganic elements act as ionic electrolytes. The most important ions are sodium, potassium, calcium, magnesium, chloride, phosphate, and the organic ion bicarbonate. The maintenance of precise gradients across cell membranes maintains osmotic pressure and pH.[18] Ions are also critical for nerves and muscles, as action potentials in these tissues are produced by the exchange of electrolytes between the extracellular fluid and the cytosol.[19] Electrolytes enter and leave cells through proteins in the cell membrane called ion channels. For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell membrane and T-tubules.[20]

The transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant.[21][22] These metals are used in some proteins as cofactors and are essential for the activity of enzymes such as catalase and oxygen-carrier proteins such as hemoglobin.[23] These cofactors are bound tightly to a specific protein; although enzyme cofactors can be modified during catalysis, cofactors always return to their original state after catalysis has taken place. The metal micronutrients are taken up into organisms by specific transporters and bound to storage proteins such as ferritin or metallothionein when not being used.[24][25]

Catabolism

Further information: [[:Catabolism]]

Catabolism is the set of metabolic processes that release energy. These include breaking down and oxidising food molecules as well as reactions that trap the energy in sunlight. The purpose of these catabolic reactions is to provide the energy and components needed by anabolic reactions. The exact nature of these catabolic reactions differ from organism to organism, with organic molecules being used as a source of energy in organotrophs, while lithotrophs use inorganic substrates and phototrophs capture sunlight as chemical energy. However, all these different forms of metabolism depend on redox reactions that involve the transfer of electrons from reduced donor molecules such as organic molecules, water, ammonia, hydrogen sulfide or ferrous ions to acceptor molecules such as oxygen, nitrate or sulphate.[26] In animals these reactions involve complex organic molecules being broken down to simpler molecules, such as carbon dioxide and water. In photosynthetic organisms such as plants and cyanobacteria, these electron-transfer reactions do not release energy, but are used as a way of storing energy absorbed from sunlight.[6]

The most common set of catabolic reactions in animals can be separated into three main stages. In the first, large organic molecules such as proteins, polysaccharides or lipids are digested into their smaller components outside cells. Next, these smaller molecules are taken up by cells and converted to yet smaller molecules, usually acetyl coenzyme A (CoA), which releases some energy. Finally, the acetyl group on the CoA is oxidised to water and carbon dioxide in the citric acid cycle and electron transport chain, releasing the energy that is stored by reducing the coenzyme nicotinamide adenine dinucleotide (NAD+) into NADH.

Digestion

Further information: [[:Digestion and gastrointestinal tract]]

Macromolecules such as starch, cellulose or proteins cannot be rapidly taken up by cells and need to be broken into their smaller units before they can be used in cell metabolism. Several common classes of enzymes digest these polymers. These digestive enzymes include proteases that digest proteins into amino acids, as well as glycoside hydrolases that digest polysaccharides into monosaccharides.

Microbes simply secrete digestive enzymes into their surroundings,[27][28] while animals only secrete these enzymes from specialized cells in their guts.[29] The amino acids or sugars released by these extracellular enzymes are then pumped into cells by specific active transport proteins.[30][31]

A simplified outline of the catabolism of proteins, carbohydrates and fats.

Energy from organic compounds

Further information: [[:Cellular respiration, fermentation, carbohydrate catabolism, fat catabolism and protein catabolism]]

Carbohydrate catabolism is the breakdown of carbohydrates into smaller units. Carbohydrates are usually taken into cells once they have been digested into monosaccharides.[32] Once inside, the major route of breakdown is glycolysis, where sugars such as glucose and fructose are converted into pyruvate and some ATP is generated.[33] Pyruvate is an intermediate in several metabolic pathways, but the majority is converted to acetyl-CoA and fed into the citric acid cycle. Although some more ATP is generated in the citric acid cycle, the most important product is NADH, which is made from NAD+ as the acetyl-CoA is oxidized. This oxidation releases carbon dioxide as a waste product. In anaerobic conditions, glycolysis produces lactate, through the enzyme lactate dehydrogenase re-oxidizing NADH to NAD+ for re-use in glycolysis. An alternative route for glucose breakdown is the pentose phosphate pathway, which reduces the coenzyme NADPH and produces pentose sugars such as ribose, the sugar component of nucleic acids.

Fats are catabolised by hydrolysis to free fatty acids and glycerol. The glycerol enters glycolysis and the fatty acids are broken down by beta oxidation to release acetyl-CoA, which then is fed into the citric acid cycle. Fatty acids release more energy upon oxidation than carbohydrates because carbohydrates contain more oxygen in their structures.

Amino acids are either used to synthesize proteins and other biomolecules, or oxidized to urea and carbon dioxide as a source of energy.[34] The oxidation pathway starts with the removal of the amino group by a transaminase. The amino group is fed into the urea cycle, leaving a deaminated carbon skeleton in the form of a keto acid. Several of these keto acids are intermediates in the citric acid cycle, for example the deamination of glutamate forms α-ketoglutarate.[35] The glucogenic amino acids can also be converted into glucose, through gluconeogenesis (discussed below).[36]

Oxidative phosphorylation

Structure of ATP synthase, the proton channel and rotating stalk are shown in blue and the synthase subunits in red.
Further information: [[:Oxidative phosphorylation, chemiosmosis and mitochondrion]]

In oxidative phosphorylation, the electrons removed from food molecules in pathways such as the citric acid cycle are transferred to oxygen and the energy released used to make ATP. This is done in eukaryotes by a series of proteins in the membranes of mitochondria called the electron transport chain. In prokaryotes, these proteins are found in the cell’s inner membrane.[37] These proteins use the energy released from passing electrons from reduced molecules like NADH onto oxygen to pump protons across a membrane.[38]

Pumping protons out of the mitochondria creates a proton concentration difference across the membrane and generates a electrochemical gradient.[39] This force drives protons back into the mitochondrion through the base of an enzyme called ATP synthase. The flow of protons makes the stalk subunit rotate, causing the active site of the synthase domain to change shape and phosphorylate adenosine diphosphate – turning it into ATP.[14]

Energy from inorganic compounds

Further information: [[:Microbial metabolism and nitrogen cycle]]

Chemolithotrophy is a type of metabolism found in prokaryotes where energy is obtained from the oxidation of inorganic compounds. These organisms can use hydrogen,[40] reduced sulfur compounds (such as sulfide, hydrogen sulfide and thiosulfate),[41] ferrous iron (FeII)[42] or ammonia[43] as sources of reducing power and they gain energy from the oxidation of these compounds with electron acceptors such as oxygen or nitrite.[44] These microbial processes are important in global biogeochemical cycles such as acetogenesis, nitrification and denitrification and are critical for soil fertility.[45][46]

Energy from light

Further information: [[:Phototroph, photophosphorylation, chloroplast]]

The energy in sunlight is captured by plants, cyanobacteria, purple bacteria, green sulfur bacteria and some protists. This process is often coupled to the conversion of carbon dioxide into organic compounds, as part of photosynthesis, which is discussed below. The energy capture and carbon fixation systems can however operate separately in prokaryotes, as purple bacteria and green sulfur bacteria can use sunlight as a source of energy, while switching between carbon fixation and the fermentation of organic compounds.[47][48]

The capture of solar energy is a process that is similar in principle to oxidative phosphorylation, as it involves energy being stored as a proton concentration gradient and this proton motive force then driving ATP synthesis.[14] The electrons needed to drive this electron transport chain come from light-gathering proteins called photosynthetic reaction centres. These structures are classed into two types depending on the type of photosynthetic pigment present, with most photosynthetic bacteria only having one type of reaction center, while plants and cyanobacteria have two.[49]

In plants, photosystem II uses light energy to remove electrons from water, releasing oxygen as a waste product. The electrons then flow to the cytochrome b6f complex, which uses their energy to pump protons across the thylakoid membrane in the chloroplast.[50] These protons move back through the membrane as they drive the ATP synthase, as before. The electrons then flow through photosystem I and can then either be used to reduce the coenzyme NADP+, for use in the Calvin cycle which is discussed below, or recycled for further ATP generation.[51]

Anabolism

Further information: [[:Anabolism]]

Anabolism is the set of constructive metabolic processes where the energy released by catabolism is used to synthesize complex molecules. In general, the complex molecules that make up cellular structures are constructed step-by-step from small and simple precursors. Anabolism involves three basic stages. Firstly, the production of precursors such as amino acids, monosaccharides, isoprenoids and nucleotides, secondly, their activation into reactive forms using energy from ATP, and thirdly, the assembly of these precursors into complex molecules such as proteins, polysaccharides, lipids and nucleic acids.

Organisms differ in how many of the molecules in their cells they can construct for themselves. Autotrophs such as plants can construct the complex organic molecules in cells such as polysaccharides and proteins from simple molecules like carbon dioxide and water. Heterotrophs, on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Organisms can be further classified by ultimate source of their energy: photoautotrophs and photoheterotrophs obtain energy from light, whereas chemoautotrophs and chemoheterotrophs obtain energy from inorganic oxidation reactions.

Carbon fixation

Further information: [[:Photosynthesis, carbon fixation and chemosynthesis]]
Plant cells (bounded by purple walls) filled with chloroplasts (green), which are the site of photosynthesis.

Photosynthesis is the synthesis of glucose from sunlight, carbon dioxide (CO2) and water, with oxygen produced as a waste product. This process uses the ATP and NADPH produced by the photosynthetic reaction centres, as described above, to convert CO2 into glycerate 3-phosphate, which can then be converted into glucose. This carbon-fixation reaction is carried out by the enzyme RuBisCO as part of the Calvin – Benson cycle.[52] Three types of photosynthesis occur in plants, C3 carbon fixation, C4 carbon fixation and CAM photosynthesis. These differ by the route that carbon dioxide takes to the Calvin cycle, with C3 plants fixing CO2 directly, while C4 and CAM photosynthesis incorporate the CO2 into other compounds first, as adaptations to deal with intense sunlight and dry conditions.[53]

In photosynthetic prokaryotes the mechanisms of carbon fixation are more diverse. Here, carbon dioxide can be fixed by the Calvin – Benson cycle, a reversed citric acid cycle,[54] or the carboxylation of acetyl-CoA.[55][56] Prokaryotic chemoautotrophs also fix CO2 through the Calvin – Benson cycle, but use energy from inorganic compounds to drive the reaction.[57]

Carbohydrates and glycans

Further information: [[:Gluconeogenesis, glyoxylate cycle, glycogenesis and glycosylation]]

In carbohydrate anabolism, simple organic acids can be converted into monosaccharides such as glucose and then used to assemble polysaccharides such as starch. The generation of glucose from compounds like pyruvate, lactate, glycerol, glycerate 3-phosphate and amino acids is called gluconeogenesis. Gluconeogenesis converts pyruvate to glucose-6-phosphate through a series of intermediates, many of which are shared with glycolysis.[33] However, this pathway is not simply glycolysis run in reverse, as several steps are catalyzed by non-glycolytic enzymes. This is important as it allows the formation and breakdown of glucose to be regulated separately and prevents both pathways from running simultaneously in a futile cycle.[58][59]

Although fat is a common way of storing energy, in vertebrates such as humans the fatty acids in these stores cannot be converted to glucose through gluconeogenesis as these organisms cannot convert acetyl-CoA into pyruvate.[60] As a result, after long-term starvation, vertebrates need to produce ketone bodies from fatty acids to replace glucose in tissues such as the brain that cannot metabolize fatty acids.[61] In other organisms such as plants and bacteria, this metabolic problem is solved using the glyoxylate cycle, which bypasses the decarboxylation step in the citric acid cycle and allows the transformation of acetyl-CoA to oxaloacetate, where it can be used for the production of glucose.[62][60]

Polysaccharides and glycans are made by the sequential addition of monosaccharides by glycosyltransferase from a reactive sugar-phosphate donor such as uridine diphosphate glucose (UDP-glucose) to an acceptor hydroxyl group on the growing polysaccharide. As any of the hydroxyl groups on the ring of the substrate can be acceptors, the polysaccharides produced can have straight or branched structures.[63] The polysaccharides produced can have structural or metabolic functions themselves, or be transferred to lipids and proteins by enzymes called oligosaccharyltransferases.[64][65]

Fatty acids, isoprenoids and steroids

Further information: [[:Fatty acid synthesis, mevalonate pathway and non-mevalonate pathway]]
Simplified version of the steroid synthesis pathway with the intermediates isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP) and squalene shown. Some intermediates are omitted for clarity.

Fatty acids are made by fatty acid synthases that polymerize and reduce acetyl-CoA units. The acyl chains in the fatty acids are extended by a cycle of reactions that add the actyl group, reduce it to the alcohol, dehydrate it to an alkene group and then reduce it again to an alkane group. The enzymes of fatty acid biosynthesis are divided into two groups, in animals and fungi all these fatty acid synthase reactions are carried out by a single multifunctional type I protein,[66] while in plant plastids and bacteria separate type II enzymes perform each step in the pathway.[67][68]

Terpenes and isoprenoids are a large class of lipids that include the carotenoids and form the largest class of plant natural products.[69] These compounds are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate.[70] These precursors can be made in different ways. In animals and archaea, the mevalonate pathway produces these compounds from acetyl-CoA,[71] while in plants and bacteria the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates.[72][70] One important reaction that uses these activated isoprene donors is steroid biosynthesis. Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol.[73] Lanosterol can then be converted into other steroids such as cholesterol and ergosterol.[74][73]

Proteins

Further information: [[:Protein biosynthesis, Amino acid synthesis]]

Organisms vary in their ability to synthesize the 20 common amino acids. Most bacteria and plants can synthesize all twenty, but mammals can synthesize only the ten nonessential amino acids.[6] Thus, the essential amino acids must be obtained from food. All amino acids are synthesized from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway. Nitrogen is provided by glutamate and glutamine. Amino acid synthesis depends on the formation of the appropriate alpha-keto acid, which is then transaminated to form an amino acid.[75]

Amino acids are made into proteins by being joined together in a chain by peptide bonds. Each different protein has a unique sequence of amino acid residues: this is its primary structure. Just as the letters of the alphabet can be combined to form an almost endless variety of words, amino acids can be linked in varying sequences to form a huge variety of proteins. Proteins are made from amino acids that have been activated by attachment to a transfer RNA molecule through an ester bond. This aminoacyl-tRNA precursor is produced in an ATP-dependent reaction carried out by an aminoacyl tRNA synthetase.[76] This aminoacyl-tRNA is then a substrate for the ribosome, which joins the amino acid onto the elongating protein chain, using the sequence information in a messenger RNA.[77]

Nucleotide synthesis and salvage

Further information: [[:Nucleotide salvage, Pyrimidine biosynthesis, and Purine metabolism]]

Nucleotides are made from amino acids, carbon dioxide and formic acid in pathways that require large amounts of metabolic energy.[78] Consequently, most organisms have efficient systems to salvage preformed nucleotides.[78][79] Purines are synthesized as nucleosides (bases attached to ribose). Both adenine and guanine are made from the precursor nucleoside inosine monophosphate, which is synthesized using atoms from the amino acids glycine, glutamine, and aspartic acid, as well as formate transferred from the coenzyme tetrahydrofolate. Pyrimidines, on the other hand, are synthesized from the base orotate, which is formed from glutamine and aspartate.[80]

Xenobiotics and redox metabolism

Further information: [[:Detoxification, Drug metabolism and Antioxidants]]

All organisms are constantly exposed to compounds that they cannot use as foods and would be harmful if they accumulated in cells, as they have no metabolic function. These potentially damaging compounds are called xenobiotics.[81] Xenobiotics such as synthetic drugs, natural poisons and antibiotics are detoxified by a set of xenobiotic-metabolizing enzymes. In humans, these include cytochrome P450 oxidases,[82] UDP-glucuronosyltransferasess,[83] and glutathione S-transferases.[84] This system of enzymes acts in three stages to firstly oxidize the xenobiotic (phase I) and then conjugate water-soluble groups onto the molecule (phase II). The modified water-soluble xenobiotic can then be pumped out of cells and in multicellular organisms may be further metabolized before being excreted (phase III). In ecology, these reactions are particularly important in microbial biodegradation of pollutants and the bioremediation of contaminated land and oil spills.[85] Many of these microbial reactions are shared with multicellular organisms, but due to their incredible diversity, microbes are able to deal with a far wider range of xenobiotics than multicellular organisms and can degrade even persistent organic pollutants such as organochloride compounds.[86]

A related problem for aerobic organisms is oxidative stress.[87] Here, processes including oxidative phosphorylation and the formation of disulfide bonds during protein folding produce reactive oxygen species such as hydrogen peroxide.[88] These damaging oxidants are removed by antioxidant metabolites such as glutathione and enzymes such as catalases and peroxidases.[89][90]

Thermodynamics of living organisms

Further information: [[:Biological thermodynamics]]

Living organisms must obey the laws of thermodynamics, which describe the transfer of heat and work. The second law of thermodynamics states that in any closed system, the amount of entropy (disorder) will tend to increase. Although living organisms’ amazing complexity appears to contradict this law, life is possible as all organisms are open systems that exchange matter and energy with their surroundings. Thus living systems are not in equilibrium, but instead are dissipative systems that maintain their state of high complexity by causing a larger increase in the entropy of their environments.[91] The metabolism of a cell achieves this by coupling the spontaneous processes of catabolism to the non-spontaneous processes of anabolism. In thermodynamic terms, metabolism maintains order by creating disorder.[92]

Regulation and control

Further information: [[:Metabolic pathway, metabolic control analysis, hormone and cell signaling]]

As the environments of most organisms are constantly changing, the reactions of metabolism must be finely regulated to maintain a constant set of conditions within cells, a condition called homeostasis.[93][94] Metabolic regulation also allows organisms to respond to signals and interact actively with their environments.[95] Two closely-linked concepts are important for understanding how metabolic pathways are controlled. Firstly, the regulation of an enzyme in a pathway is how its activity is increased and decreased in response to signals. Secondly, the control exerted by this enzyme is the effect that these changes in its activity have on the overall rate of the pathway (the flux through the pathway).[96] For example, an enzyme may show large changes in activity (i.e. it is highly regulated) but if these changes have little effect on the flux of a metabolic pathway, then this enzyme is not involved in the control of the pathway.[97]

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).

There are multiple levels of metabolic regulation. In intrinsic regulation, the metabolic pathway self-regulates to respond to changes in the levels of substrates or products; for example, a decrease in the amount of product can increase the flux through the pathway to compensate.[96] This type of regulation often involves allosteric regulation of the activities of multiple enzymes in the pathway.[98] Extrinsic control involves a cell in a multicellular organism changing its metabolism in response to signals from other cells. These signals are usually in the form of soluble messengers such as hormones and growth factors and are detected by specific receptors on the cell surface.[99] These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins.[100]

A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone insulin.[101] Insulin is produced in response to rises in blood glucose levels. Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and glycogen.[102] The metabolism of glycogen is controlled by activity of phosphorylase, the enzyme that breaks down glycogen, and glycogen synthase, the enzyme that makes it. These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Insulin causes glycogen synthesis by activating protein phosphatases and producing a decrease in the phosphorylation of these enzymes.[103]

Evolution

Further information: [[:Molecular evolution and Phylogenetics]]
Evolutionary tree showing the common ancestry of organisms from all three domains of life. Bacteria are colored blue, eukaryotes red, and archaea green. Relative positions of some of the phyla included are shown around the tree.

The central pathways of metabolism described above, such as glycolysis and the citric acid cycle, are present in all three domains of living things and were present in the last universal ancestor.[104][2] This universal ancestral cell was prokaryotic and probably a methanogen that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism.[105][106] The retention of these ancient pathways during later evolution may be the result of these reactions being an optimal solution to their particular metabolic problems, with pathways such as glycolysis and the citric acid cycle producing their end products highly efficiently and in a minimal number of steps.[3][4] The first pathways of enzyme-based metabolism may have been parts of purine nucleotide metabolism, with previous metabolic pathways being part of the ancient RNA world.[107]

Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. These include the sequential addition of novel enzymes to a short ancestral pathway, the duplication and then divergence of entire pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway.[108] The relative importance of these mechanisms is unclear, but genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion with novel functions being created from pre-existing steps in the pathway.[109] Another possibility is that some parts of metabolism might exist as “modules” that can be reused in different pathways and perform similar functions on different molecules.[110]

The evolution of organisms can also produce the loss of metabolic pathways. For example, in some parasites metabolic processes that are not essential for survival are lost and preformed amino acids, nucleotides and carbohydrates may instead be scavenged from the host.[111] Similar reduced metabolic capabilities are seen in endosymbiotic organisms.[112]

Investigation and manipulation

Further information: [[:Protein methods, proteomics, metabolomics and metabolic network modelling]]
Metabolic network of the Arabidopsis thaliana citric acid cycle. Enzymes and metabolites are shown as red squares and the interactions between them as black lines.

Classically, metabolism is studied by a reductionist approach that focuses on a single metabolic pathway. Particularly valuable is the use of radioactive tracers at the whole-organism, tissue and cellular levels, which define the paths from precursors to final products by identifying radioactively-labelled intermediates and products.[113] The enzymes that catalyze these chemical reactions can then be purified and their kinetics and responses to inhibitors investigated. A parallel approach is to identify the small molecules in a cell or tissue; the complete set of these molecules is called the metabolome. Overall, these studies give a good view of the structure and function of simple metabolic pathways, but are inadequate when applied to more complex systems such as the metabolism of a complete cell.[114]

An idea of the complexity of the metabolic networks in cells that contain thousands of different enzymes is given by the figure showing the interactions between just 43 proteins and 40 metabolites to the right: the sequences of genomes provide lists containing anything up to 45,000 genes.[115] However, it is now possible to use this genomic data to reconstruct complete networks of biochemical reactions and produce more holistic mathematical models that may explain and predict their behavior.[116] These models are especially powerful when used to integrate the pathway and metabolite data obtained through classical methods with data on gene expression from proteomic and DNA microarray studies.[117]

A major technological application of this information is metabolic engineering. Here, organisms such as yeast, plants or bacteria are genetically-modified to make them more useful in biotechnology and aid the production of drugs such as antibiotics or industrial chemicals such as 1,3-propanediol and shikimic acid.[118] These genetic modifications usually aim to reduce the amount of energy used to produce the product, increase yields and reduce the production of wastes.[119]

History

Further information: [[:History of biochemistry and History of molecular biology]]
Santorio Santorio in his steelyard balance, from Ars de statica medecina, first published 1614

The term metabolism is derived from the Greek Μεταβολισμός – “Metabolismos” for “change”, or “overthrow”.[120] The history of the scientific study of metabolism spans 400 years and has moved from examining whole animals in early studies, to examining individual metabolic reactions in modern biochemistry. The first controlled experiments in human metabolism were published by Santorio Santorio in 1614 in his book Ars de statica medecina.[121] He described how he weighed himself before and after eating, sleeping, working, sex, fasting, drinking, and excreting. He found that most of the food he took in was lost through what he called “insensible perspiration”.

In these early studies, the mechanisms of these metabolic processes had not been identified and a vital force was thought to animate living tissue.[122] In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that fermentation was catalyzed by substances within the yeast cells he called “ferments”. He wrote that “alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells.”[123] This discovery, along with the publication by Friedrich Wöhler in 1828 of the chemical synthesis of urea,[124] proved that the organic compounds and chemical reactions found in cells were no different in principle than any other part of chemistry.

It was the discovery of enzymes at the beginning of the 20th century by Eduard Buchner that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of biochemistry.[125] The mass of biochemical knowledge grew rapidly throughout the early 20th century. One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism.[126] He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle.[127][62] Modern biochemical research has been greatly aided by the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labelling, electron microscopy and molecular dynamics simulations. These techniques have allowed the discovery and detailed analysis of the many molecules and metabolic pathways in cells.

See also

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References

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Further reading

Introductory

  • Rose, S. and Mileusnic, R., The Chemistry of Life. (Penguin Press Science, 1999), ISBN 0-14027-273-9
  • Schneider, E. D. and Sagan, D., Into the Cool: Energy Flow, Thermodynamics, and Life. (University Of Chicago Press, 2005), ISBN 0-22673-936-8
  • Lane, N., Oxygen: The Molecule that Made the World. (Oxford University Press, USA, 2004), ISBN 0-19860-783-0

Advanced

  • Price, N. and Stevens, L., Fundamentals of Enzymology: Cell and Molecular Biology of Catalytic Proteins. (Oxford University Press, 1999), ISBN 0-19850-229-X
  • Berg, J. Tymoczko, J. and Stryer, L., Biochemistry. (W. H. Freeman and Company, 2002), ISBN 0-71674-955-6
  • Cox, M. and Nelson, D. L., Lehninger Principles of Biochemistry. (Palgrave Macmillan, 2004), ISBN 0-71674-339-6
  • Brock, T. D. Madigan, M. T. Martinko, J. and Parker J., Brock’s Biology of Microorganisms. (Benjamin Cummings, 2002), ISBN 0-13066-271-2
  • Da Silva, J.J.R.F. and Williams, R. J. P., The Biological Chemistry of the Elements: The Inorganic Chemistry of Life. (Clarendon Press, 1991), ISBN 0-19855-598-9
  • Nicholls, D. G. and Ferguson, S. J., Bioenergetics. (Academic Press Inc., 2002), ISBN 0-12518-121-3
External links
General informationGlossaries and dictionariesHuman metabolismDatabasesMetabolic pathways

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Neurological and psychiatric

Neurological and psychiatric

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Neurology is a medical speciality dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue, such as muscle.[1] Physicians who specialize in neurology are called neurologists, and are trained to investigate, or diagnose and treat, neurological disorders. Pediatric neurologists treat neurological disease in children. Neurologists may also be involved in clinical research, clinical trials, as well as basic research, and translational research. In the United Kingdom, contributions to the field of Neurology stem from various professions; saliently, several biomedical research scientists are choosing to specialise in the technical/laboratory aspects of one of neurology’s subdisciplines.

Field of work

Neurological disorders are disorders that affect the central nervous system (brain and spinal cord), the peripheral nervous system, or the autonomic nervous system.

Major conditions include:

Educational requirements

A neurologist’s educational background and medical training varies with the country of training. In the United States and Canada, neurologists are physicians who have completed postgraduate training in neurology after the completion of medical school and attainment of the allopathic (MD, MBBS, MBChB, etc) or osteopathic (DO) degree.

Neurologists complete a minimum of 10 years of post secondary education and clinical training. In the majority of cases this training includes obtaining an undergraduate degree (a few medical schools will admit students with as little as two years of undergraduate education), a medical degree (4 years), and then completing a four-year residency in neurology. The four-year residency consists of one year of internal medicine training followed by three years of training in neurology.

Many neurologists also have additional subspecialty training (fellowships) after completing their residency in one area of neurology such as stroke, epilepsy, neuromuscular, sleep medicine, pain management, neuroimmunology, clinical neurophysiology, or movement disorders.

Testing examinations

During a neurological examination, the neurologist reviews the patient’s health history with special attention to the current condition. The patient then takes a neurological exam. Typically, the exam tests mental status, function of the cranial nerves (including vision), strength, coordination, reflexes, and sensation. This information helps the neurologist determine if the problem exists in the nervous system and the clinical localization. Localization of the pathology is the key process by which neurologists develop their differential diagnosis. Further tests may be needed to confirm a diagnosis and ultimately guide therapy and appropriate management.

Clinical tasks

General caseload

Neurologists are responsible for the diagnosis, treatment, and management of all the above conditions. When surgical intervention is required, the neurologist may refer the patient to a neurosurgeon, an interventional neuroradiologist, or a neurointerventionalist. In some countries, additional legal responsibilities of a neurologist may include making a finding of brain death when it is suspected that a patient is deceased. Neurologists frequently care for people with hereditary (genetic) diseases when the major manifestations are neurological, as is frequently the case. Lumbar punctures are frequently performed by neurologists. Some neurologists may develop an interest in particular subfields, such as dementia, movement disorders, headaches, epilepsy, sleep disorders, chronic pain management, multiple sclerosis or neuromuscular diseases.

Overlapping areas

There is some overlap with other specialties, varying from country to country and even within a local geographic area. Acute head trauma is most often treated by neurosurgeons, whereas sequela of head trauma may be treated by neurologists or specialists in rehabilitation medicine. Although stroke cases have been traditionally managed by internal medicine or hospitalists, the emergence of vascular neurology and endovascular neurosurgery as disciplines have created a demand for stroke specialists. The establishment of JCAHO stroke centers have increased the role of neurologists in stroke care in many primary as well as tertiary hospitals. Some cases of nervous system infectious diseases are treated by infectious disease specialists. Most cases of headache are diagnosed and treated primarily by general practitioners, at least the less severe cases. Similarly, most cases of sciatica and other mechanical radiculopathies are treated by general practitioners, though they may be referred to neurologists or a surgeon (neurosurgeons or orthopedic surgeons). Sleep disorders are also treated by pulmonologists. Cerebral palsy is initially treated by pediatricians, but care may be transferred to an adult neurologist after the patient reaches a certain age.

Clinical neuropsychologists are often called upon to evaluate brain–behavior relationships for the purpose of assisting with differential diagnosis, planning rehabilitation strategies, documenting cognitive strengths and weaknesses, and measuring change over time (e.g., for identifying abnormal aging or tracking the progression of a dementia).

Relationship to clinical neurophysiology

In some countries, e.g. USA and Germany, neurologists may specialize in clinical neurophysiology, the field responsible for EEG, nerve conduction studies, EMG, and evoked potentials. In other countries, this is an autonomous specialty (e.g. United Kingdom, Sweden).

Overlap with psychiatry

Further information: Psychoneuroimmunology and Neuropsychiatry

Although many mental illnesses are believed to be neurological disorders affecting the central nervous system, traditionally they are classified separately, and treated by psychiatrists. In a 2002 review article in the American Journal of Psychiatry, Professor Joseph B. Martin, Dean of Harvard Medical School and a neurologist by training, wrote that ‘the separation of the two categories is arbitrary, often influenced by beliefs rather than proven scientific observations. And the fact that the brain and mind are one makes the separation artificial anyway.’ (Martin JB. The integration of neurology, psychiatry and neuroscience in the 21st century. Am J Psychiatry 2002; 159:695-704)

There are strong indications that neuro-chemical mechanisms play an important role in the development of, for instance, bipolar disorder and schizophrenia. As well, ‘neurological’ diseases often have ‘psychiatric’ manifestations, such as post-stroke depression, depression and dementia associated with Parkinson’s disease, mood and cognitive dysfunctions in Alzheimer’s disease, to name a few. Hence, there is no sharp distinction between neurology and psychiatry on a biological basis – this distinction has mainly practical reasons and strong historical roots. (such as the dominance of Freud‘s psychoanalytic theory in psychiatric thinking in the first three quarters of the 20th century – which has since then been largely replaced by the focus on neurosciences – aided by the tremendous advances in genetics and neuroimaging recently.)

References

  1. ↑ http://www.acgme.org/acWebsite/downloads/RRC_progReq/180neurology07012007.pdf

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Ophthalmological

Ophthalmological

A phoropter in use.
Slit lamp examination of eyes in an Ophthalmology Clinic


Overview

Ophthalmology is the branch of medicine which deals with the diseases and surgery of the visual pathways, including the eye, brain, and areas surrounding the eye, such as the lacrimal system and eyelids. The word ophthalmology comes from the Greek roots ophthalmos meaning eye and logos meaning word, thought or discourse; ophthalmology literally means “The science of eyes.” As a discipline it applies to animal eyes also, since the differences from human practice are surprisingly minor and are related mainly to differences in anatomy or prevalence, not differences in disease processes. However, veterinary medicine is regulated separately in many countries and states/provinces resulting in few ophthalmologists treating both humans and animals. By convention the term ophthalmologist is more restricted and implies a medically trained specialist. Since ophthalmologists perform operations on eyes, they are generally categorized as surgeons.

History of ophthalmology

The eye, including its structure and mechanism, has fascinated scientists and the public in general since ancient times. The majority of all input to the brain comes from vision. Many of the expressions in the english language that mean to understand are equivalent vision terms. “I see”, to mean I understand. Many patients when told that they may have an eye problem will be more concerned about diseases that affect vision than other, more lethal diseases. Being deprived of sight can have a devastating effect on the psyche, as well as economic and social effects, as many blind individuals require significant assistance with activities of daily living and are often unable to continue gainful employment previously held while seeing.

The maintenance of ocular health, and correction of eye problems that decrease vision contributes greatly to the ability to appreciate the longer lifespan that all of medicine continues to allow. As a bonus, it is incredibly rewarding to be able to restore sight to a patient! As detailed below, advances in diagnosis and treatment of disease, and improved surgical techniques have extended our abilities to restore vision like never before.

Sushruta

Sushruta wrote Sushruta Samhita in about fifth Century BCE in India. He described about 72 ocular diseases as well as several ophthalmological surgical instruments and techniques. Sushruta has been described as the first Indian cataract surgeon. [1] [2] [3] Arab scientists are some of the earliest to have written about and drawn the anatomy of the eye—the earliest known diagram being in Hunain ibn Is-hâq‘s Book of the Ten Treatises on the Eye. Earlier manuscripts exist which refer to diagrams which are not known to have survived. Current knowledge of the Græco-Roman understanding of the eye is limited, as many manuscripts lacked diagrams. In fact, there are very few Græco-Roman diagrams of the eye still in existence. Thus, it is not clear to which structures the texts refer, and what purpose they were thought to have.

Pre-Hippocrates

The pre-Hippocratics largely based their anatomical conceptions of the eye on speculation, rather than empiricism. They recognized the sclera and transparent cornea running flushly as the outer coating of the eye, with an inner layer with pupil, and a fluid at the centre. It was believed, by Alcamaeon and others, that this fluid was the medium of vision and flowed from the eye to the brain via a tube. Aristotle advanced such ideas with empiricism. He dissected the eyes of animals, and discovering three layers (not two), found that the fluid was of a constant consistency with the lens forming (or congealing) after death, and the surrounding layers were seen to be juxtaposed. He, and his contemporaries, further put forth the existence of three tubes leading from the eye, not one. One tube from each eye met within the skull.

Alexandrian studies

Alexandrian studies extensively contributed to knowledge of the eye. Aëtius tells us that Herophilus dedicated an entire study to the eye which no longer exists. In fact, no manuscripts from the region and time are known to have survived, leading us to rely on Celsius‘ account—which is seen as a confused account written by a man who did not know the subject matter. From Celsius it is known that the lens had been recognised, and they no longer saw a fluid flowing to the brain through some hollow tube, but likely a continuation of layers of tissue into the brain. Celsius failed to recognise the retina’s role, and did not think it was the tissue that continued into the brain.

Rufus

Rufus recognised a more modern eye, with conjunctiva, extending as a fourth epithelial layer over the eye. Rufus was the first to recognise a two chambered eye – with one chamber from cornea to lens (filled with water), the other from lens to retina (filled with an egg-white-like substance). Galen remedied some mistakes including the curvature of the cornea and lens, the nature of the optic nerve, and the existence of a posterior chamber. Though this model was roughly a correct but simplistic modern model of the eye, it contained errors. Yet it was not advanced upon again until after Vesalius. A ciliary body was then discovered and the sclera, retina, choroid and cornea were seen to meet at the same point. The two chambers were seen to hold the same fluid as well as the lens being attached to the choroid. Galen continued the notion of a central canal, though he dissected the optic nerve, and saw it was solid, He mistakenly counted seven optical muscles, one too many. He also knew of the tear ducts.

After Galen

After Galen a period of speculation is again noted by Arab scientists – the lens modified Galen’s model to place the lens in the middle of the eye, a notion which lasted until Vesalius reversed the era of speculation. However, Vesalius was not an ophthalmologist and taught that the eye was a more primitive notion than the notion of both Galen and the Arabian scientists – the cornea was not seen as being of greater curvature and the posterior side of the lens wasn’t seen to be larger.

Understanding of the eye had been so slow to develop because for a long time the lens was perceived to be the seat of vision, not as part of the pathway for vision. This mistake was corrected when Fabricius and his successors correctly placed the lens and developed the modern notion of the structure of the eye. They removed the idea of Galen’s seventh muscle (the retractor bulbi) and reinstated the correct curvatures of the lens and cornea, as well as stating the ciliary body as a connective structure between the lens and the choroid.

Muslim ophthalmology

Main article: Ophthalmology in medieval Islam

Of all the branches of Islamic medicine, ophthalmology was considered the foremost. The specialized instruments used in their operations ran into scores. Innovations such as the “injection syringe”, invented by Ammar ibn Ali of Mosul, which was used for the extraction by suction of soft cataracts, were quite common. Ibn al-Haytham, the “father of optics“, studied the anatomy of the eye extensively.

Seventeenth and eighteenth century

The seventeenth and eighteenth century saw the use of hand-lenses (by Malpighi), microscopes (van Leeuwenhoek), preparations for fixing the eye for study (Ruysch) and later the freezing of the eye (Petit). This allowed for detailed study of the eye and an advanced model. Some mistakes persisted such as: why the pupil changed size (seen to be vessels of the iris filling with blood), the existence of the posterior chamber, and of course the nature of the retina. In 1722 Leeuwenhoek noted the existence of rods and cones though they were not properly discovered until Gottfried Reinhold Treviranus in 1834 by use of a microscope.

First ophthalmic surgeon

The first ophthalmic surgeon was John Freke, appointed to the position by the Governors of St Bartholomew’s Hospital in 1727, but the establishment of the first dedicated ophthalmic hospital in 1805 – now called Moorfields Eye Hospital in London, England was a transforming event in modern ophthalmology. Clinical developments at Moorfields and the founding of the Institute of Ophthalmology by Sir Stewart Duke-Elder established the site as the largest eye hospital in the world and a nexus for ophthalmic research.

Professional requirements

Ophthalmologists are medical doctors (M.D.) or Doctors of Osteopathy (D.O.) who have completed medical school and completed a further four years post-graduate training in ophthalmology in many countries. Many ophthalmologists also undergo additional specialized training in one of the many subspecialities. Ophthalmology was the first branch of medicine to offer board certification, now a standard practice among all specialties.

United States

In the United States, four years of training after medical school are required, with the first year being an internship in surgery, internal medicine, pediatrics, or a general transition year. The scope of a physician’s licensure is such that he or she need not be board certified in ophthalmology to practice as an ophthalmologist. The American Academy of Ophthalmology (AAO) promotes the use of the phrase “Eye MD” to distinguish ophthalmologists from optometrists who hold the degree OD (Doctor of Optometry). This, however, can lead to confusion among patients, since a few ophthalmologists’ are DOs, or Doctors of Osteopathic Medicine, rather than MDs. In both cases, the same residency and certification requirements must be fulfilled. Completing the requirements of continuing medical education is mandatory for continuing licensure and re-certification. Professional bodies like the AAO and ASCRS organize conferences and help members through CME programs to maintain certification, in addition to political advocacy and peer support.

United Kingdom

In the United Kingdom, there are four colleges that grant postgraduate degrees in ophthalmology. The Royal College of Ophthalmologists grants MRCOphth and FRCOphth (postgraduate exams), the Royal College of Edinburgh grants MRCSEd, the Royal College of Glasgow grants FRCS and Royal College of Ireland grants FRCSI. Work experience as a specialist registrar and one of these degrees is required for specialisation in eye diseases.

Australia and New Zealand

In Australia and New Zealand, the FRACO/FRANZCO is the equivalent postgraduate specialist qualification. They do not generally accept overseas-trained Ophthalmologists as having equivalent qualifications, except those who have completed their formal training in the UK.

On case by case basis, they will allow suitably-qualified Ophthalmologists to work in Area of Need positions, usually in regional areas. However, such appointments are generally only limited to South African/Canadian trained Ophthalmologists.

India

In India, after completing MBBS degree, post-graduation in Ophthalmology is required. The degrees are Doctor of Medicine (MD), Master of Surgery (MS), Diploma in Ophthalmic Medicine and Surgery (DOMS) or Diplomate of National Board (DNB). The concurrent training and work experience is in the form of a Junior Residency at a Medical College, Eye Hospital or Institution under the supervision of experienced faculty. Further work experience in form of fellowship, registrar or senior resident refines the skills of these eye surgeons. All India Ophthalmological Society (AIOS) and various state level Ophthalmological Societies (like DOS) hold regular conferences and actively promote continuing medical education.

Pakistan

In Pakistan, there is a residency program leading into FCPS which is composed of two parts.

Canada

In Canada, an Ophthalmology residency after medical school. A minimum of 5 years after the MD. degree although subspecialty training is undertaken by about 30% of fellows (FRCSC). There are about 30 vacancies per year for ophthalmology training in all of Canada.

Finland

In Finland, physicians willing to become ophthalmologists must undergo a 5 year specialization which includes practical training and theoretical studies.

Veterinary

Formal specialty training programs in veterinary ophthalmology now exist in some countries [4] [5] [6].

Distinction from Optometry

Ophthalmologists are trained and licensed to perform surgery and prescribe ocular, oral and systemic medications. They can manage diseases and conditions of the eye, the visual pathway, and structures surrounding the eye, with medical and/or surgical treatments. For example this may include:

  • cataract extraction with intra-ocular lens replacement for cataracts,
  • laser refractive surgery on cornea for refractive error remediation
  • extra-ocular muscle surgery for strabismus,
  • prescribing topical medication, performing trabeculoplasty or iridotomy surgery for glaucoma (in all 50 states in the USA, optometrists are licensed to prescribe topical ocular medications and treat glaucoma)
  • laser surgery for some retinal diseases
  • excision or biopsy of tumors on eyelid or in the eye
  • prescribing temporary topical medical treatment for amblyopia(optometrists are permitted to do this as well)

Optometrists, or optometric physicians, are not medical doctors. Instead, optometrists usually receive 4-5 years training in vision science, eye health and optometry-related areas, sometimes following a bachelor’s degree (usually in science) in some countries. (In the USA, all optometrists attend optometry school for 4 years FOLLOWING their bachelors degree)

While both ophthalmologists and optometrists are trained in refraction, it is generally accepted that optometrists receive more thorough training in prescribing optical aids such as spectacles, contact lens and magnifiers.

The two fields often have a mutually beneficial relationship.

  • Ophthalmologists may refer patients to optometrists for optical aids or low vision rehabilitation whilst continuing to treat the ocular disease/condition that may have reduced vision.
  • Both optometrists and ophthalmologists perform screening for common ocular problems affecting children (i.e., amblyopia and strabismus) and the adult population (cataract, glaucoma, and diabetic retinopathy). Optometrists may refer to ophthalmology for further assessment and medical treatment of ocular disease or condition, however in the USA, most optometrists now treat many medical conditions, including glaucoma.
  • Optometrists and ophthalmologists sometimes co-manage treatment of strabismus and amblyopia with a combination of vision therapy, medical or surgical treatment.

Sub-specialities

Extraocular muscle surgery for strabismus (Inferior rectus muscle here) in progress

Ophthalmology includes sub-specialities which deal either with certain diseases or diseases of certain parts of the eye. Some of them are:

  • Anterior segment surgery
  • Cataract – not considered a subspecialty per se, since most general ophthalmologists do surgery for this.
  • Cornea, ocular surface, and external disease

Ophthalmic surgery

For a comprehensive list of surgeries performed by ophthalmologists, see eye surgery.

See also

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Respiratory

Respiratory

The Respiratory System

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]



Among quadrupeds, the respiratory system generally includes tubes, such as the bronchi, used to carry air to the lungs, where gas exchange takes place. A diaphragm pulls air in and pushes it out. Respiratory systems of various types are found in a wide variety of organisms.

In humans and other mammals, the respiratory system consists of the airways, the lungs, and the respiratory muscles that mediate the movement of air into and out of the body. Within the alveolar system of the lungs, molecules of oxygen and carbon dioxide are passively exchanged, by diffusion, between the gaseous environment and the blood. Thus, the respiratory system facilitates oxygenation of the blood with a concomitant removal of carbon dioxide and other gaseous metabolic wastes from the circulation. The system also helps to maintain the acid-base balance of the body through the efficient removal of carbon dioxide from the blood.

Anatomy

In humans and other animals, the respiratory system can be conveniently subdivided into an upper respiratory tract (or conducting zone) and lower respiratory tract (respiratory zone), trachea and lungs.

Air moves through the body in the following order:

Upper respiratory tract/conducting zone

The conducting zone begins with the nares (nostrils) of the nose, which open into the nasopharynx (nasal cavity). The primary functions of the nasal passages are to: 1) filter, 2) warm, 3) moisten, and 4) provide resonance in speech. The nasopharynx opens into the oropharynx (behind the oral cavity). The oropharynx leads to the laryngopharynx, and empties into the larynx (voicebox), which contains the vocal cords, passing through the glottis, connecting to the trachea (wind pipe).

Lower respiratory tract/respiratory zone

The trachea leads down to the thoracic cavity (chest) where it divides into the right and left “main stem” bronchi. The subdivision of the bronchus are: primary, secondary, and tertiary divisions (first, second and third levels). In all, they divide 16 more times into even smaller bronchioles.

The bronchioles lead to the respiratory zone of the lungs which consists of respiratory bronchioles, alveolar ducts and the alveoli, the multi-lobulated sacs in which most of the gas exchange occurs.

Ventilation

Ventilation of the lungs is carried out by the muscles of respiration.

Control

Ventilation occurs under the control of the autonomic nervous system from the part of the brain stem, the medulla oblongata and the pons. This area of the brain forms the respiration regulatory center, a series of interconnected neurons within the lower and middle brain stem which coordinate respiratory movements. The sections are the pneumotaxic center, the apneustic center, and the dorsal and ventral respiratory groups. This section is especially sensitive during infancy, and the neurons can be destroyed if the infant is dropped or shaken violently. The result can be death due to “shaken baby syndrome.”[1]

Inhalation

Inhalation is initiated by the diaphragm and supported by the external intercostal muscles. Normal resting respirations are 10 to 18 breaths per minute. Its time period is 2 seconds. During vigorous inhalation (at rates exceeding 35 breaths per minute), or in approaching respiratory failure, accessory muscles of respiration are recruited for support. These consist of sternocleidomastoid, platysma, and the strap muscles of the neck.

Inhalation is driven primarily by the diaphragm. When the diaphragm contracts, the ribcage expands and the contents of the abdomen are moved downward. This results in a larger thoracic volume, which in turn causes a decrease in intrathoracic pressure. As the pressure in the chest falls, air moves into the conducting zone. Here, the air is filtered, warmed, and humidified as it flows to the lungs.

During forced inhalation, as when taking a deep breath, the external intercostal muscles and accessory muscles further expand the thoracic cavity.

Exhalation

Exhalation is generally a passive process, however active or forced exhalation is achieved by the abdominal and the internal intercostal muscles. During this process air is forced or exhaled out.

The lungs have a natural elasticity; as they recoil from the stretch of inhalation, air flows back out until the pressures in the chest and the atmosphere reach equilibrium.[2]

During forced exhalation, as when blowing out a candle, expiratory muscles including the abdominal muscles and internal intercostal muscles, generate abdominal and thoracic pressure, which forces air out of the lungs.

Circulation

The right side of the heart pumps blood from the right ventricle through the pulmonary semilunar valve into the pulmonary trunk. The trunk branches into right and left pulmonary arteries to the pulmonary blood vessels. The vessels generally accompany the airways and also undergo numerous branchings. Once the gas exchange process is complete in the pulmonary capillaries, blood is returned to the left side of the heart through four pulmonary veins, two from each side. The pulmonary circulation has a very low resistance, due to the short distance within the lungs, compared to the systemic circulation, and for this reason, all the pressures within the pulmonary blood vessels are normally low as compared to the pressure of the systemic circulation loop.

Virtually all the body’s blood travels through the lungs every minute. The lungs add and remove many chemical messengers from the blood as it flows through pulmonary capillary bed . The fine capillaries also trap blood clots that have formed in systemic veins.

Gas exchange

The major function of the respiratory system is gas exchange. As gas exchange occurs, the acid-base balance of the body is maintained as part of homeostasis. If proper ventilation is not maintained two opposing conditions could occur: 1) respiratory acidosis, a life threatening condition, and 2) respiratory alkalosis.

Upon inhalation, gas exchange occurs at the alveoli, the tiny sacs which are the basic functional component of the lungs. The alveolar walls are extremely thin (approx. 0.2 micrometres), and are permeable to gases. The alveoli are lined with pulmonary capillaries, the walls of which are also thin enough to permit gas exchange. All gases diffuse from the alveolar air to the blood in the pulmonary capillaries, as carbon dioxide diffuses in the opposite direction, from capillary blood to alveolar air. At this point, the pulmonary blood is oxygen-rich, and the lungs are holding carbon dioxide. Exhalation follows, thereby ridding the body of the carbon dioxide and completing the cycle of respiration.

In an average resting adult, the lungs take up about 250ml of oxygen every minute while excreting about 200ml of carbon dioxide. During an average breath, an adult will exchange from 500 ml to 700 ml of air. This average breath capacity is called tidal volume.

Development

The respiratory system lies dormant in the human fetus during pregnancy. At birth, the respiratory system is drained of fluid and cleaned to assure proper functioning of the system. If an infant is born before forty weeks gestational age, the newborn may experience respiratory failure due to the under-developed lungs. This is due to the incomplete development of the alveoli type II cells in the lungs, necessary for the production of surfactant. The infant lungs do not function due to collapse of alveoli caused by surface tension of water remaining in the lungs, which in normal cases would be prohibited by the presence of surfactant. This condition may be avoided by giving the mother a series of steroid shots in the final week prior to delivery, which will enhance the development of type II alveolar cells.[3]

Role in communication

The movement of gas through the larynx, pharynx and mouth allows humans to speak, or phonate. Because of this, gas movement is extremely vital for communication purposes.

Conditions of the respiratory system

Disorders of the respiratory system can be classified into four general areas:

The respiratory tract is constantly exposed to microbes due to the extensive surface area, which is why the respiratory system includes many mechanisms to defend itself and prevent pathogens from entering the body.

Disorders of the respiratory system are usually treated internally by a pulmonologist or Respiratory Physician.

Gas exchange in plants

Plants use carbon dioxide gas in the process of photosynthesis, and then exhale oxygen gas, a waste product of photosynthesis. However, plants also sometimes respire as humans do, using oxygen and producing carbon dioxide.

Plant respiration is limited by the process of diffusion. Plants take in carbon dioxide through holes on the undersides of their leaves known as stomata(sing:stoma). However, most plants require little air. Most plants have relatively few living cells outside of their surface because air (which is required for metabolic content) can penetrate only skin deep. However, most plants are not involved in highly aerobic activities, and thus have no need of these living cells.

See also

References

  • Perkins, M. 2003. Respiration Power Point Presentation. Biology 182 Course Handout. Orange Coast College, Costa Mesa, CA.
  • Medical Dictionary

Notes

  1. ↑ *Fact sheet on Shaken Baby Syndrome
  2. ↑ A simple model of how the lungs are inflated can be built from a bell jar
  3. ↑ Department of Environmental Biology, University of Adelaide, Adelaide, South Australia

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Shock

Shock

For patient information, click here.


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Shock from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Case Studies

Case #1

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Urological, andrological, gynecologic, and obstetric

Urological, andrological, gynecologic, and obstetric

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Steven C. Campbell, M.D., Ph.D.


Overview

Urology is the specialty of medicine that focuses on the urinary tracts of males and females, and on the reproductive system of males. Medical professionals specializing in the field of urology are called urologists and are trained to diagnose, treat, and manage patients with urological disorders. The organs covered by urology include the kidneys, ureters, urinary bladder, urethra, and the male reproductive organs (testes, epididymis, vas deferens, seminal vesicles, prostate and penis).

In men, the urinary system overlaps with the reproductive system, and in women the urinary tract opens into the vulva. In both sexes, the urinary and reproductive tracts are close together, and disorders of one often affect the other. Urology combines management of medical (i.e., non-surgical) problems such as urinary infections, and surgical problems such as the correction of congenital abnormalities and the surgical management of cancers. Such abnormalities within the genital region are called genitourinary disorders.

Urology is closely related to, and in some cases overlaps with, the medical fields of nephrology, andrology, gynecology, proctology and oncology.

Branches of urology

As a discipline that involves the study of many organs and physiological systems, urology can be broken down into subfields. Many urologists, particularly those involved in research, choose an informal specialization in a particular field of urology.

  • Neurourology involves the study of nervous system control of the genitourinary system, and of conditions causing abnormal urination. Neurological diseases and disorders such as multiple sclerosis, Parkinson’s disease, and spinal cord injury can disrupt the lower urinary tract and result in conditions such as urinary incontinence, overactive bladder, urinary retention, and detrusor-sphincter dyssynergia. Less marked neurological abnormalities can cause urological disorders as well — for example, abnormalities of the sensory nervous system are thought by many researchers to play a role in disorders of painful or frequent urination (e.g. interstitial cystitis).[1] Urodynamic studies play an important diagnostic role in neurourology; urologists often use diagnostic techniques such as flow cystometry or ambulatory urodynamic profiles to determine the best method of treatment for the patient. Medical therapy for nervous system disorders includes drugs that target the nervous system and neuromodulation.

Other subfields of urology include stone disease, sexual dysfunction and male infertility.

References

  1. ↑ http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10459464&dopt=AbstractPlus

Further reading

See also

ar:طب المسالك البولية و التناسلية ca:Urologia i andrologia da:Urologi de:Urologie eu:Urologia ko:비뇨기과 hr:Urologija id:Urologi it:Urologia he:אורולוגיה nl:Urologie no:Urologi fi:Urologia sv:Urologi


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