Osmium

From Wikipedia, the free encyclopedia

Osmium,  ₇₆Os

Osmium
Pronunciation	/ˈɒzmiəm/ ​(OZ-mee-əm)
Appearance	silvery, blue cast
Standard atomic weight Ar, std(Os)	190.23(3)
Osmium in the periodic table
Hydrogen Helium Lithium Beryllium Boron Carbon Nitrogen Oxygen Fluorine Neon Sodium Magnesium Aluminium Silicon Phosphorus Sulfur Chlorine Argon Potassium Calcium Scandium Titanium Vanadium Chromium Manganese Iron Cobalt Nickel Copper Zinc Gallium Germanium Arsenic Selenium Bromine Krypton Rubidium Strontium Yttrium Zirconium Niobium Molybdenum Technetium Ruthenium Rhodium Palladium Silver Cadmium Indium Tin Antimony Tellurium Iodine Xenon Caesium Barium Lanthanum Cerium Praseodymium Neodymium Promethium Samarium Europium Gadolinium Terbium Dysprosium Holmium Erbium Thulium Ytterbium Lutetium Hafnium Tantalum Tungsten Rhenium Osmium Iridium Platinum Gold Mercury (element) Thallium Lead Bismuth Polonium Astatine Radon Francium Radium Actinium Thorium Protactinium Uranium Neptunium Plutonium Americium Curium Berkelium Californium Einsteinium Fermium Mendelevium Nobelium Lawrencium Rutherfordium Dubnium Seaborgium Bohrium Hassium Meitnerium Darmstadtium Roentgenium Copernicium Nihonium Flerovium Moscovium Livermorium Tennessine Oganesson Ru ↑ Os ↓ Hs rhenium ← osmium → iridium
Atomic number (Z)	76
Group	group 8
Period	period 6
Block	d-block
Element category	transition metal
Electron configuration	[Xe] 4f14 5d6 6s2
Electrons per shell	2, 8, 18, 32, 14, 2
Physical properties
Phase at STP	solid
Melting point	3306 K ​(3033 °C, ​5491 °F)
Boiling point	5285 K ​(5012 °C, ​9054 °F)
Density (near r.t.)	22.59 g/cm3
when liquid (at m.p.)	20 g/cm3
Heat of fusion	31 kJ/mol
Heat of vaporization	378 kJ/mol
Molar heat capacity	24.7 J/(mol·K)
Vapor pressure P (Pa) 1 10 100 1 k 10 k 100 k at T (K) 3160 3423 3751 4148 4638 5256
Atomic properties
Oxidation states	−4, −2, −1, 0, +1, +2, +3, +4, +5, +6, +7, +8 (a mildly acidic oxide)
Electronegativity	Pauling scale: 2.2
Ionization energies	1st: 840 kJ/mol 2nd: 1600 kJ/mol
Atomic radius	empirical: 135 pm
Covalent radius	144±4 pm
Spectral lines of osmium
Other properties
Natural occurrence	primordial
Crystal structure	​hexagonal close-packed (hcp)
Speed of sound thin rod	4940 m/s (at 20 °C)
Thermal expansion	5.1 µm/(m·K) (at 25 °C)
Thermal conductivity	87.6 W/(m·K)
Electrical resistivity	81.2 nΩ·m (at 0 °C)
Magnetic ordering	paramagnetic
Magnetic susceptibility	11·10−6 cm3/mol
Shear modulus	222 GPa
Bulk modulus	462 GPa
Poisson ratio	0.25
Mohs hardness	7.0
Vickers hardness	300 MPa
Brinell hardness	293 MPa
CAS Number	7440-04-2
History
Discovery and first isolation	Smithson Tennant (1803)
Main isotopes of osmium
Iso­tope Abun­dance Half-life (t1/2) Decay mode Pro­duct 184Os 0.02% stable 185Os syn 93.6 d ε 185Re 186Os 1.59% 2.0×1015 y α 182W 187Os 1.96% stable 188Os 13.24% stable 189Os 16.15% stable 190Os 26.26% stable 191Os syn 15.4 d β− 191Ir 192Os 40.78% stable 193Os syn 30.11 d β− 193Ir 194Os syn 6 y β− 194Ir

Osmium (from Greek ὀσμή osme, "smell") is a chemical element with symbol Os and atomic number 76. It is a hard, brittle, bluish-white transition metal in the platinum group that is found as a trace element in alloys, mostly in platinum ores. Osmium is the densest naturally occurring element, with an experimentally measured (using x-ray crystallography) density of 22.59 g/cm³. Manufacturers use its alloys with platinum, iridium, and other platinum-group metals to make fountain pen nib tipping, electrical contacts, and in other applications that require extreme durability and hardness. The element's abundance in the Earth's crust is among the rarest.

Characteristics

Physical properties

Osmium, remelted pellet

 

Osmium has a blue-gray tint and is the densest stable element; it is approximately twice as dense as lead and slightly denser than iridium. Calculations of density from the X-ray diffraction data may produce the most reliable data for these elements, giving a value of 22.587±0.009 g/cm³ for osmium, slightly denser than the 22.562±0.009 g/cm³ of iridium; both metals are nearly 23 times as dense as water.

Osmium is a hard but brittle metal that remains lustrous even at high temperatures. It has a very low compressibility. Correspondingly, its bulk modulus is extremely high, reported between 395 and 462 GPa, which rivals that of diamond (443 GPa). The hardness of osmium is moderately high at 4 GPa. Because of its hardness, brittleness, low vapor pressure (the lowest of the platinum-group metals), and very high melting point (the fourth highest of all elements, after only carbon, tungsten, and rhenium), solid osmium is difficult to machine, form, or work.

Chemical properties

Oxidation states of osmium
−2	Na 2[Os(CO) 4]
−1	Na 2[Os 4(CO) 13]
0	Os 3(CO) 12
+1	OsI
+2	OsI 2
+3	OsBr 3
+4	OsO 2, OsCl 4
+5	OsF 5
+6	OsF 6
+7	OsOF 5
+8	OsO 4, Os(NCH3) 4

Osmium forms compounds with oxidation states ranging from −2 to +8. The most common oxidation states are +2, +3, +4, and +8. The +8 oxidation state is notable for being the highest attained by any chemical element aside from iridium's +9 and is encountered only in xenon, ruthenium, hassium, and iridium. The oxidation states −1 and −2 represented by the two reactive compounds Na
₂[Os
₄(CO)
₁₃] and Na
₂[Os(CO)
₄] are used in the synthesis of osmium cluster compounds.

The most common compound exhibiting the +8 oxidation state is osmium tetroxide. This toxic compound is formed when powdered osmium is exposed to air. It is a very volatile, water-soluble, pale yellow, crystalline solid with a strong smell. Osmium powder has the characteristic smell of osmium tetroxide. Osmium tetroxide forms red osmates OsO
₄(OH)²⁻
₂ upon reaction with a base. With ammonia, it forms the nitrido-osmates OsO
₃N⁻. Osmium tetroxide boils at 130 °C and is a powerful oxidizing agent. By contrast, osmium dioxide (OsO₂) is black, non-volatile, and much less reactive and toxic. 

Only two osmium compounds have major applications: osmium tetroxide for staining tissue in electron microscopy and for the oxidation of alkenes in organic synthesis, and the non-volatile osmates for organic oxidation reactions.

Osmium pentafluoride (OsF₅) is known, but osmium trifluoride (OsF₃) has not yet been synthesized. The lower oxidation states are stabilized by the larger halogens, so that the trichloride, tribromide, triiodide, and even diiodide are known. The oxidation state +1 is known only for osmium iodide (OsI), whereas several carbonyl complexes of osmium, such as triosmium dodecacarbonyl (Os
₃(CO)
₁₂), represent oxidation state 0.

In general, the lower oxidation states of osmium are stabilized by ligands that are good σ-donors (such as amines) and π-acceptors (heterocycles containing nitrogen). The higher oxidation states are stabilized by strong σ- and π-donors, such as O²⁻ and N³⁻.

Despite its broad range of compounds in numerous oxidation states, osmium in bulk form at ordinary temperatures and pressures resists attack by all acids and alkalis, including aqua regia.

Isotopes

Osmium has seven naturally occurring isotopes, six of which are stable: ¹⁸⁴Os, ¹⁸⁷Os, ¹⁸⁸Os, ¹⁸⁹Os, ¹⁹⁰Os, and (most abundant) ¹⁹²Os. ¹⁸⁶Os undergoes alpha decay with such a long half-life (2.0±1.1)×10¹⁵ years, approximately 140000 times the age of the universe, that for practical purposes it can be considered stable. Alpha decay is predicted for all seven naturally occurring isotopes, but it has been observed only for ¹⁸⁶Os, presumably due to very long half-lives. It is predicted that ¹⁸⁴Os and ¹⁹²Os can undergo double beta decay but this radioactivity has not been observed yet.

¹⁸⁷Os is the descendant of ¹⁸⁷Re (half-life 4.56×10¹⁰ years) and is used extensively in dating terrestrial as well as meteoric rocks. It has also been used to measure the intensity of continental weathering over geologic time and to fix minimum ages for stabilization of the mantle roots of continental cratons. This decay is a reason why rhenium-rich minerals are abnormally rich in ¹⁸⁷Os. However, the most notable application of osmium isotopes in geology has been in conjunction with the abundance of iridium, to characterise the layer of shocked quartz along the Cretaceous–Paleogene boundary that marks the extinction of the non-avian dinosaurs 65 million years ago.

History

Osmium was discovered in 1803 by Smithson Tennant and William Hyde Wollaston in London, England. The discovery of osmium is intertwined with that of platinum and the other metals of the platinum group. Platinum reached Europe as platina ("small silver"), first encountered in the late 17th century in silver mines around the Chocó Department, in Colombia. The discovery that this metal was not an alloy, but a distinct new element, was published in 1748. Chemists who studied platinum dissolved it in aqua regia (a mixture of hydrochloric and nitric acids) to create soluble salts. They always observed a small amount of a dark, insoluble residue. Joseph Louis Proust thought that the residue was graphite. Victor Collet-Descotils, Antoine François, comte de Fourcroy, and Louis Nicolas Vauquelin also observed iridium in the black platinum residue in 1803, but did not obtain enough material for further experiments. Later the two French chemists Antoine-François Fourcroy and Nicolas-Louis Vauquelin identified a metal in a platinum residue they called ‘ptène’.

In 1803, Smithson Tennant analyzed the insoluble residue and concluded that it must contain a new metal. Vauquelin treated the powder alternately with alkali and acids and obtained a volatile new oxide, which he believed was of this new metal—which he named ptene, from the Greek word πτηνος (ptènos) for winged. However, Tennant, who had the advantage of a much larger amount of residue, continued his research and identified two previously undiscovered elements in the black residue, iridium and osmium. He obtained a yellow solution (probably of cis–[Os(OH)₂O₄]²⁻) by reactions with sodium hydroxide at red heat. After acidification he was able to distill the formed OsO₄. He named it osmium after Greek osme meaning "a smell", because of the ashy and smoky smell of the volatile osmium tetroxide. Discovery of the new elements was documented in a letter to the Royal Society on June 21, 1804.

Uranium and osmium were early successful catalysts in the Haber process, the nitrogen fixation reaction of nitrogen and hydrogen to produce ammonia, giving enough yield to make the process economically successful. At the time, a group at BASF led by Carl Bosch bought most of the world's supply of osmium to use as a catalyst. Shortly thereafter, in 1908, cheaper catalysts based on iron and iron oxides were introduced by the same group for the first pilot plants, removing the need for the expensive and rare osmium.

Nowadays osmium is obtained primarily from the processing of platinum and nickel ores.

Occurrence

Native platinum containing traces of the other platinum group metals

 

Osmium is one of the even-numbered elements, which puts it in the upper half of elements commonly found in space. It is, however, the least abundant stable element in Earth's crust, with an average mass fraction of 50 parts per trillion in the continental crust.

Osmium is found in nature as an uncombined element or in natural alloys; especially the iridium–osmium alloys, osmiridium (osmium rich), and iridosmium (iridium rich). In nickel and copper deposits, the platinum group metals occur as sulfides (i.e., (Pt,Pd)S)), tellurides (e.g., PtBiTe), antimonides (e.g., PdSb), and arsenides (e.g., PtAs₂); in all these compounds platinum is exchanged by a small amount of iridium and osmium. As with all of the platinum group metals, osmium can be found naturally in alloys with nickel or copper.

Within Earth's crust, osmium, like iridium, is found at highest concentrations in three types of geologic structure: igneous deposits (crustal intrusions from below), impact craters, and deposits reworked from one of the former structures. The largest known primary reserves are in the Bushveld Igneous Complex in South Africa, though the large copper–nickel deposits near Norilsk in Russia, and the Sudbury Basin in Canada are also significant sources of osmium. Smaller reserves can be found in the United States. The alluvial deposits used by pre-Columbian people in the Chocó Department, Colombia are still a source for platinum group metals. The second large alluvial deposit was found in the Ural Mountains, Russia, which is still mined.

Production

Osmium crystals, grown by chemical vapor transport.

 

Osmium is obtained commercially as a by-product from nickel and copper mining and processing. During electrorefining of copper and nickel, noble metals such as silver, gold and the platinum group metals, together with non-metallic elements such as selenium and tellurium settle to the bottom of the cell as anode mud, which forms the starting material for their extraction. Separating the metals requires that they first be brought into solution. Several methods can achieve this, depending on the separation process and the composition of the mixture. Two representative methods are fusion with sodium peroxide followed by dissolution in aqua regia, and dissolution in a mixture of chlorine with hydrochloric acid. Osmium, ruthenium, rhodium and iridium can be separated from platinum, gold and base metals by their insolubility in aqua regia, leaving a solid residue. Rhodium can be separated from the residue by treatment with molten sodium bisulfate. The insoluble residue, containing Ru, Os and Ir, is treated with sodium oxide, in which Ir is insoluble, producing water-soluble Ru and Os salts. After oxidation to the volatile oxides, RuO
₄ is separated from OsO
₄ by precipitation of (NH₄)₃RuCl₆ with ammonium chloride.

After it is dissolved, osmium is separated from the other platinum group metals by distillation or extraction with organic solvents of the volatile osmium tetroxide. The first method is similar to the procedure used by Tennant and Wollaston. Both methods are suitable for industrial scale production. In either case, the product is reduced using hydrogen, yielding the metal as a powder or sponge that can be treated using powder metallurgy techniques.

Neither the producers nor the United States Geological Survey published any production amounts for osmium. In 1971, estimations of the United States production of osmium as a byproduct of copper refining was 2000 troy ounces (62 kg). In 2017, the estimated US import of osmium for consumption was 90 kg.

Applications

Because of the volatility and extreme toxicity of its oxide, osmium is rarely used in its pure state, but is instead often alloyed with other metals for high-wear applications. Osmium alloys such as osmiridium are very hard and, along with other platinum-group metals, are used in the tips of fountain pens, instrument pivots, and electrical contacts, as they can resist wear from frequent operation. They were also used for the tips of phonograph styli during the late 78 rpm and early "LP" and "45" record era, circa 1945 to 1955. Osmium-alloy tips were significantly more durable than steel and chromium needle points, but wore out far more rapidly than competing, and costlier, sapphire and diamond tips, so they were discontinued.

Osmium tetroxide has been used in fingerprint detection and in staining fatty tissue for optical and electron microscopy. As a strong oxidant, it cross-links lipids mainly by reacting with unsaturated carbon–carbon bonds and thereby both fixes biological membranes in place in tissue samples and simultaneously stains them. Because osmium atoms are extremely electron-dense, osmium staining greatly enhances image contrast in transmission electron microscopy (TEM) studies of biological materials. Those carbon materials otherwise have very weak TEM contrast (see image). Another osmium compound, osmium ferricyanide (OsFeCN), exhibits similar fixing and staining action.

The tetroxide and its derivative potassium osmate are important oxidants in organic synthesis. For the Sharpless asymmetric dihydroxylation, which uses osmate for the conversion of a double bond into a vicinal diol, Karl Barry Sharpless was awarded the Nobel Prize in Chemistry in 2001. OsO₄ is very expensive for this use, so KMnO₄ is often used instead, even though the yields are less for this cheaper chemical reagent. 

In 1898 an Austrian chemist Auer von Welsbach developed the Oslamp with a filament made of osmium, which he introduced commercially in 1902. After only a few years, osmium was replaced by the more stable metal tungsten. Tungsten has the highest melting point among all metals, and its use in light bulbs increases the luminous efficacy and life of incandescent lamps.

The light bulb manufacturer Osram (founded in 1906, when three German companies, Auer-Gesellschaft, AEG and Siemens & Halske, combined their lamp production facilities) derived its name from the elements of osmium and Wolfram (the latter is German for tungsten).

Like palladium, powdered osmium effectively absorbs hydrogen atoms. This could make osmium a potential candidate for a metal-hydride battery electrode. However, osmium is expensive and would react with potassium hydroxide, the most common battery electrolyte.

Osmium has high reflectivity in the ultraviolet range of the electromagnetic spectrum; for example, at 600 Å osmium has a reflectivity twice that of gold. This high reflectivity is desirable in space-based UV spectrometers, which have reduced mirror sizes due to space limitations. Osmium-coated mirrors were flown in several space missions aboard the Space Shuttle, but it soon became clear that the oxygen radicals in the low Earth orbit are abundant enough to significantly deteriorate the osmium layer.

The only known clinical use of osmium is synovectomy in arthritic patients in Scandinavia. It involves the local administration of osmium tetroxide (OsO₄), which is a highly toxic compound. The lack of reports of long-term side effects suggest that osmium itself can be biocompatible, though this depends on the osmium compound administered. In 2011, osmium(VI) and osmium(II) compounds were reported to show anticancer activity in vivo, it indicated a promising future for using osmium compounds as anticancer drugs.

• 

  The Sharpless dihydroxylation:
  R_L = largest substituent; R_M = medium-sized substituent; R_S = smallest substituent
  
  
• 

  Post-flight appearance of Os, Ag, and Au mirrors from the front (left images) and rear panels of the Space Shuttle. Blackening reveals oxidation due to irradiation by oxygen atoms.
  

Precautions

Metallic osmium is harmless but finely divided metallic osmium is pyrophoric and reacts with oxygen at room temperature, forming volatile osmium tetroxide. Some osmium compounds are also converted to the tetroxide if oxygen is present. This makes osmium tetroxide the main source of contact with the environment. 

Osmium tetroxide is highly volatile and penetrates skin readily, and is very toxic by inhalation, ingestion, and skin contact. Airborne low concentrations of osmium tetroxide vapor can cause lung congestion and skin or eye damage, and should therefore be used in a fume hood. Osmium tetroxide is rapidly reduced to relatively inert compounds by e.g. ascorbic acid or polyunsaturated vegetable oils (such as corn oil).

Price

Osmium is usually sold as a minimum 99.9% pure powder. Like other precious metals, it is measured by troy weight and by grams.The market price of osmium has not changed in decades, primarily because little change has occurred in supply and demand. In addition to so little of it being available, osmium is difficult to work with, has few uses, and is a challenge to store safely because of the toxic compound it produces when it oxidizes. 

While the price of $400 per troy ounce has remained steady since the 1990s, inflation since that time has led to the metal losing about one-third of its value in the two decades prior to 2019.

Cancer and nausea

From Wikipedia, the free encyclopedia

A painting from 1681 depicting a person affected by nausea and vomiting

 

Cancer and nausea are associated in about fifty percent of people affected by cancer. This may be as a result of the cancer itself, or as an effect of the treatment such as chemotherapy, radiation therapy, or other medication such as opiates used for pain relief. About 70 to 80% of people undergoing chemotherapy experience nausea or vomiting. Nausea and vomiting may also occur in people not receiving treatment, often as a result of the disease involving the gastrointestinal tract, electrolyte imbalance, or as a result of anxiety. Nausea and vomiting may be experienced as the most unpleasant side effects of cytotoxic drugs and may result in patients delaying or refusing further radiotherapy or chemotherapy.

The strategies of management or therapy of nausea and vomiting depend on the underlying causes. Medical treatments or conditions associated with a high risk of nausea and/or vomiting include chemotherapy, radiotherapy and malignant bowel obstruction. Anticipatory nausea and vomiting may also occur. Nausea and vomiting may lead to further medical conditions and complications including: dehydration, electrolyte imbalance, malnutrition, and a decrease in quality of life.

Nausea may be defined as an unpleasant sensation of the need to vomit. It may be accompanied by symptoms such salivation, feeling faint, and a fast heart rate. Vomiting is the forceful ejection of stomach contents through the mouth. Although nausea and vomiting are closely related, some patients experience one symptom without the other and it may be easier to eliminate vomiting than nausea. The vomiting reflex (also called emesis) is thought to have evolved in many animal species as a protective mechanism against ingested toxins. In humans, the vomiting response may be preceded by an unpleasant sensation termed nausea, but nausea may also occur without vomiting. The central nervous system is the primary site where a number of emetic stimuli (input) are received, processed and efferent signals (output) are generated as a response and sent to various effector organs or tissues, leading to processes that eventually end in vomiting. The detection of emetic stimuli, the central processing by the brain and the resulting response by organs and tissues that lead to nausea and vomiting are referred to as the emetic pathway or emetic arch.

Causes

Some medical conditions that arise as a result of cancer or as a complication of its treatment are known to be associated with a high risk of nausea and/or vomiting. These include malignant bowel obstruction (MBO), chemotherapy induced nausea and vomiting (CINV), anticipatory nausea and vomiting (ANV), and radiotherapy induced nausea and vomiting (RINV).

Malignant bowel obstruction

Malignant bowel obstruction (MBO) of the gastrointestinal tract is a common complication of advanced cancer, especially in patients with bowel or gynaecological cancer. These include colorectal cancer, ovarian cancer, breast cancer, and melanoma. Three percent of all advanced cancers lead to malignant bowel obstruction and 25 to 50 percent of patients with ovarian cancer experience at least one episode of malignant bowel obstruction. The mechanisms of action that may lead to nausea in MBO include mechanical compression of the gut, motility disorders, gastrointestinal secretion accumulation, decreased gastrointestinal absorption, and inflammation. Bowel obstruction and the resulting nausea may also occur as a result of anti-cancer therapy such as radiation, or adhesion after surgery. Impaired gastric emptying as a result of bowel obstruction may not respond to drugs alone, and surgical intervention is sometimes the only means of symptom relief. Some constipating drugs used in cancer therapy such as opioids may cause a slowing of peristalsis of the gut, which may lead to a functional bowel obstruction.

Chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared side effects of chemotherapy and is associated with a significant deterioration in quality of life. CINV is classified into three categories:

• early onset (occurring within 24 hours of initial exposure to chemotherapy)
• delayed onset (occurring 24 hours to several days after treatment)
• anticipatory (triggered by taste, odor, sight, thoughts, or anxiety)

Risk factors that predict the occurrence and severity of CINV include sex and age, with females, younger people and people who have a high pretreatment expectation of nausea being at a higher risk, while people with a history of high alcohol consumption being at a lower risk. Other person-related variables, such as chemotherapy dose, rate and route of administration, hydration status, prior history of CINV, emesis during pregnancy or motion sickness, tumour burden, concomitant medication and medical conditions also play a role in the degree of CINV experienced by a person. By far the most important factor which determines the degree of CINV is the emetogenic potential of the chemotherapeutic agents used. Chemotherapeutic agents are classified into four groups according to their degree of emetogenicity: high, moderate, low and minimal.

Chemotherapeutic agents associated with vomiting

Association with vomiting	Examples
Highly emetogenic (>90%) Intravenous agents	Cisplatin, Mechlorethamine, Streptozotocin, Cyclophosphamide > 1500 mg/m2, Carmustine, Dacarbazine, Anthracycline
Highly emetogenic (>90%) oral agents	Hexamethylmelamine, Procarbazine
Moderately emetogenic (30-90%) intravenous agents	Oxaliplatin, Cytarabine > 1g/m2, Carboplatin, Ifosfamide, Cyclophosphamide < 1500 mg/m2, Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Irinotecan, Azacitidine, Bendamustine, Clofarabine, Alemtuzumab
Moderately emetogenic (30-90%) oral agents	Cyclophosphamide, Temozolomide, Vinorelbine, Imatinib

The European Society of Medical Oncology (ESMO) and the Multinational Association of Supportive Care in Cancer (MASCC) in 2010 as well as the American Society of Clinical Oncology (ASCO) (2011) recommend a prophylaxis to prevent acute vomiting and nausea following chemotherapy with high emetic risk drugs by using a three-drug regimen including a 5-HT3 receptor antagonist, dexamethasone and aprepitant (a neurokinin-1 antagonist) given before chemotherapy.

Anticipatory

A common consequence of cancer treatment is the development of anticipatory nausea and vomiting (ANV). This kind of nausea is usually elicited by the re-exposure of the patients to the clinical context they need to attend to be treated. Approximately 20% of people undergoing chemotherapy are reported to develop anticipatory nausea and vomiting. Once developed, ANV is difficult to control by pharmacological means. Benzodiazepines are the only drugs that have been found to reduce the occurrence of ANV but their efficacy decreases with time. Recently, clinical trials suggests that cannabidiolic acid suppresses conditioned gaping (ANV) in shrews. Because ANV is widely believed to be a learned response, the best approach is to avoid the development of ANV by adequate prophylaxis and treatment of acute vomiting and nausea from the first exposure to therapy. Behavioral treatment techniques, such as systematic desensitization, progressive muscle relaxation and hypnosis have been shown to be effective against ANV.

Radiation therapy

The incidence and severity of radiation therapy-induced nausea and vomiting (RINV) depends on a number of factors including therapy related factors such as irradiated site, single and total dose, fractionation, irradiated volume and radiotherapy techniques. Also involved are person related factors such as gender, general health of the person, age, concurrent or recent chemotherapy, alcohol consumption, previous experience of nausea, vomiting, anxiety as well as the tumor stage. The emetogenic potential of radiotherapy is classified into high, moderate, low and minimal risk depending on the site of irradiation:

• High risk: total body irradiation (TBI) is associated with a high risk of RINV
• Moderate risk: radiation of the upper abdomen, half body irradiation and upper body irradiation
• Low risk: radiation of the cranium, spine, head and neck, lower thorax region and pelvis
• Minimal risk: radiation of extremities and breast

Pathophysiology

Nausea and vomiting may have a number of causes in people with cancer. While more than one cause may exist in the same person stimulating symptoms via more than one pathway, the actual cause of nausea and vomiting may be unknown in some people. The underlying causes of nausea and vomiting may in some cases not be directly related to the cancer. The causes may be categorized as disease-related and treatment-related.

The stimuli which lead to emesis are received and processed in the brain. It is thought that a number of loosely organized neuronal networks within the medulla oblongata probably interact to coordinate the emetic reflex. Some of the brain stem nuclei which have been identified as important in the coordination of the emetic reflex include the parvicellular reticular formation, the Bötzinger complex and the nucleus tractus solitarii. The nuclei coordinating emesis had formerly been referred to as the vomiting complex, but it is no longer thought to represent a single anatomical structure.

Efferent outputs which transmit the information from the brain leading to the motoric response of retching and vomiting include vagal efferents to the esophagus, stomach and intestine as well as spinal somatomotor neurones to the abdominal muscles and phrenic motor neurones (C3–C5) to the diaphragm. Autonomic efferents also supply the heart and airways (vagus), salivary glands (chorda tympani) and skin and are responsible for many of the prodromal signs such as salivation and skin pallor.

Nausea and vomiting may be initiated by various stimuli, through different neuronal pathways. A stimulus may act on more than one pathway. Stimuli and pathways include:

• Toxic substances in the gastrointestinal tract: toxic substances (including drugs which are used in the treatment of cancer) in the lumen of the gastrointestinal tract stimulate vagal afferent nerves in the gut mucosa which communicate to the nucleus tractus solitarii and the area postrema to initiate vomiting and nausea. A number of receptors on the terminal ends of the vagal afferent nerves have been identified as being involved in this process, including the 5-hydroxytryptamine3 (5-HT3), neurokinin-1, and cholecystokinin-1 receptors. Various local mediators located in enterochromaffin cells of the gut mucosa play a role in stimulating these receptors. Of these 5-hydroxytryptamine seems to play the dominating role. This pathway has been postulated to be the mechanism by which some anti-cancer drugs such as cisplatin induce emesis.
• Toxic substances in the blood: toxic substances which have been absorbed into the blood (including cytostatics) or endogenous toxic (waste) material released by body or cancer cells into the blood can be detected directly in the area postrema of the brain and trigger the emetic reflex. The area postrema is a structure located on the floor of the fourth ventricle around which the blood-brain barrier is permeable, thus allowing for the detection of humoral or pharmacological stimuli in the blood or cerebrospinal fluid. This structure contains receptors which form a chemoreceptor trigger zone. Some of the receptors and neurotransmitters involved in the regulation of this emetic pathway include dopamine type D2, serotonin types 2–4 (5HT2–4), histamine type 1(H1), and acetylcholine (muscarinic receptors type 1 to 5, M1–5). Some other receptors such as substance P, cannabinoid type 1 (CB1) and the endogenous opioids may also be involved.
• Pathological conditions of the gastrointestinal tract: diseases and pathological conditions of the GIT may also lead to nausea and vomiting through direct or indirect stimulation of the above named pathways. Such conditions may include malignant bowel obstruction, hypertrophic pyloric stenosis and gastritis. Pathological conditions in other organs which are linked to the above named emetic pathways may also lead to nausea and vomiting, such as the myocardial infarct (through stimulation of cardiac vagal afferents) and renal failure.
• Stimulation of the central nervous system: certain stimuli of the central nervous system may induce the emetic reflex. These include fear, anticipation, brain trauma and increased intra-cranial pressure. Of particular relevance to cancer patients in this regard are the stimuli of fear and anticipation. Evidence suggests that cancer patients may develop the side effects of nausea and vomiting in anticipation of chemotherapy. In some patients, re-exposure to cues such as smell, sounds or sight associated with the clinic or previous treatment may evoke anticipatory nausea and vomiting.
• Pathological conditions of the vestibular system: a disturbance of the vestibular system such as in motion sickness or Meniere's disease can induce the emetic reflex. Such disturbances of the vestibular system could also be cancer related such as in cerebral or vestibular secondaries (metastasis), or cancer treatment related such as the use of opioids.

Management

The strategies of management or prevention of nausea and vomiting depend on the underlying causes, whether they are reversible or treatable, stage of the illness, the person's prognosis and other person specific factors. Anti emetic drugs are chosen according to previous effectiveness and side effects.

Medication

Drugs that are used in the prophylaxis and therapy of nausea and vomiting in cancer include:

• 5-HT3 antagonists: 5-HT3 antagonists produce their anti emetic effect by blocking of the amplifying effect of serotonin on peripheral and central 5-HT3 receptors located on the various vagal afferent nerve endings and the chemoreceptor trigger zone. They are effective in the treatment and prophylaxis of CINV as well as in malignant bowel obstruction and renal failure which are associated with elevated serotonin levels. These substances include Dolasetron, Granisetron, Ondansetron, Palonosetron, and Tropisetron. They are often used in combination with other anti emetic drugs in people with high risk of emesis or nausea and are recommended as the most effective anti emetics in the prophylaxis of acute CINV.
• Corticosteroids: such as Dexamethasone are used in the treatment of emesis as a result of chemotherapy, malignant bowel obstruction, raised intracranial pressure and in the chronic nausea of advanced cancer, though their exact mode of action remain unclear. Dexamethason is recommended for use in the acute prevention of highly, moderately, and low emetogenic chemotherapy and in combination with aprepitant for the prevention of delayed emesis in highly emetogenic chemotherapy.
• NK1 receptor antagonists: such as Aprepitant block the NK1 receptor in the brainstem and gastrointestinal tract. Their antiemetic activity when added to a 5-HT3 receptor antagonist plus dexametasone has been shown in several phase II double-blind studies.
• Cannabinoids: are a useful adjunct to modern anti emetic therapy in selected patients. They show a combination of weak anti emetic efficacy with potentially beneficial side effects such as sedation and euphoria. However, their usefulness is generally limited by the high incidence of toxic effects, such as dizziness, dysphoria, and hallucinations. Some studies have shown that cannabinoids are slightly better than conventional anti emetics such as metoclopramide, phenothiazines and haloperidol in the prevention of nausea and vomiting. Cannabinoids are an option in affected people who are intolerant or refractory to 5-HT3 antagonists or steroids and aprepitant as well as in refractory nausea and vomiting and rescue anti emetic therapy.
• Prokinetic agents such as Metoclopramide
• Dopamine receptor antagonists such as Phenothiazines (Prochlorperazine and chlorpromazine), haloperidol, olanzapine, and Levomepromazine, block D2 receptors found in the chemoreceptor trigger zone
• Antihistaminic agents like Promethazine block H1 receptors in the vomiting center of the medulla, the vestibular nucleus, and the chemoreceptor trigger zone
• Anticholinergic agents such as Scopolamine (Hyoscine) are used as anti emetics as they relax smooth muscle and reduce gastrointestinal secretions by blockade of muscarinic receptors. They may be useful in the management of terminal bowel obstruction
• Somatostatin analoga such as Octreotide are used for the palliation of malignant bowel obstruction, especially when there is high output vomiting not responding to other measures
• Cannabidiol is used as a palliative treatment (non-curative symptomatic treatment) and improves numerous symptoms that frequently appear during chemotherapy like nausea, vomiting, loss of appetite, physical pain or insomnia. Due to the large number of cannabinoid receptors ( CB1 and CB2 ) distributed throughout the gastrointestinal tract ( GI ), these substances can help to control and treat many GI diseases where vomiting and nausea are frequent.

Other measures

Other non-drug measures may include:

• Diet: Small palatable meals are normally tolerated better than big meals in people affected by nausea and vomiting in cancer. Carbohydrate meals are better tolerated than spicy, fatty and sweet foods. Cool, fizzy drinks are found to be more palatable than still or hot drinks.
• The avoidance of environmental stimuli, such as sights, sounds, or smells that may initiate nausea.
• Behavioral approaches, such as distraction, relaxation training and Cognitive behavioural therapy may also be useful.
• Alternative medicine: Acupuncture and ginger have been shown to have some anti emetic effects on chemotherapy-induced emesis and anticipatory nausea, but have not been evaluated in the nausea of far advanced disease.

Palliative surgery

Palliative care is the active care of people with advanced, progressive illness such as cancer. The World Health Organization (WHO) defines it as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems (such as nausea or vomiting), physical, psychosocial, and spiritual.

Sometimes it is possible or necessary to provide relief for cancer caused nausea and vomiting through palliative surgical intervention. Surgery is however not routinely carried out when there are poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive ascites. The surgical approach proves beneficial in affected people with operable lesions, a life expectancy greater than 2 months and good performance status. Often a malignant bowel obstruction is the cause of the symptoms in which case the purpose of palliative surgery is to relieve the symptoms of bowel obstruction by means of several procedures including:

• Stoma formation
• Bypass of the obstruction
• Resection of bowel segments
• Placement of stents.
• Percutaneous endoscopic gastrostomy (PEG) tube placement to enable gastric venting.
• Gastric venting through a nasogastric tube is a semi-invasive possibility for palliation of nausea and vomiting due to gastrointestinal obstruction in people with abdominal malignancies who decline surgery or where surgery may not be indicated. However nasogastric tubes are not recommended to be used over a long period of time because of the high risk of displacement, poor tolerance, restrictions in daily routine activities, coughing, clearing pulmonary secretions and can be cosmetically unacceptable and confining. Complications of nasogastric tubes include aspiration, hemorrhage, gastric erosion, necrosis, sinusitis and otitis.

Epidemiology

12.7 million new cancer cases and 7.6 million cancer deaths were estimated worldwide in 2008.

• Nausea or vomiting occur in 50 to 70% of people with advanced cancer.
• 50 to 80% of people undergoing radiotherapy experience nausea and/or vomiting, depending on the site of irradiation.
• Anticipatory nausea and vomiting is experienced by approximately 20 to 30% of people undergoing chemotherapy.
• Chemotherapy-induced nausea and vomiting resulting from treatment with highly emetogenic cytotoxic drugs can be prevented or effectively treated in 70 to 80% of affected people.

Delusional disorder

From Wikipedia, the free encyclopedia

Delusional disorder
Other names	Paranoid disorder
Specialty	Psychiatry
Symptoms	Strong false beliefs despite superior evidence to the contrary
Types	Erotomanic type, grandiose type, jealous type, persecutory type, somatic type, mixed type, unspecified type
Differential diagnosis	Paranoid personality disorder, schizophrenia, bipolar disorder, substance-induced psychosis

Delusional disorder is a generally rare mental illness in which the patient presents delusions, but with no accompanying prominent hallucinations, thought disorder, mood disorder, or significant flattening of affect. Delusions are a specific symptom of psychosis. Delusions can be "bizarre" or "non-bizarre" in content; non-bizarre delusions are fixed false beliefs that involve situations that occur in real life, such as being harmed or poisoned. Apart from their delusions, people with delusional disorder may continue to socialize and function in a normal manner and their behavior does not necessarily generally seem odd. However, the preoccupation with delusional ideas can be disruptive to their overall lives.

For the diagnosis to be made, auditory and visual hallucinations cannot be prominent, though olfactory or tactile hallucinations related to the content of the delusion may be present. The delusions cannot be due to the effects of a drug, medication, or general medical condition, and delusional disorder cannot be diagnosed in an individual previously properly diagnosed with schizophrenia. A person with delusional disorder may be high functioning in daily life. Recent and comprehensive metaanalyses of scientific studies point to an association between a deterioration in aspects of IQ in psychotic patients, in particular perceptual reasoning.

According to German psychiatrist Emil Kraepelin, patients with delusional disorder remain coherent, sensible and reasonable. The Diagnostic and Statistical Manual of Mental Disorders (DSM) defines six subtypes of the disorder characterized as erotomanic (believes that someone is in love with them), grandiose (believes that they are the greatest, strongest, fastest, richest, or most intelligent person ever), jealous (believes that the love partner is cheating on them), persecutory (delusions that the person or someone to whom the person is close is being malevolently treated in some way), somatic (believes that they have a disease or medical condition), and mixed, i.e., having features of more than one subtype. Delusions also occur as symptoms of many other mental disorders, especially the other psychotic disorders.

The DSM-IV, and psychologists agree that personal beliefs should be evaluated with great respect to cultural and religious differences, since some cultures have widely accepted beliefs that may be considered delusional in other cultures.

Classification

Diagnosis of a specific type of delusional disorder can sometimes be made based on the content of the delusions. The Diagnostic and Statistical Manual of Mental Disorders (DSM) enumerates seven types:

• Erotomanic type (erotomania): delusion that another person, often a prominent figure, is in love with the individual. The individual may breach the law as he/she tries to obsessively make contact with the desired person.
• Grandiose type (megalomania): delusion of inflated worth, power, knowledge, identity or believes themself to be a famous person, claiming the actual person is an impostor or an impersonator.
• Jealous type: delusion that the individual's sexual partner is unfaithful when it is untrue. The patient may follow the partner, check text messages, emails, phone calls etc. in an attempt to find "evidence" of the infidelity.
• Persecutory type: This delusion is a common subtype. It includes the belief that the person (or someone to whom the person is close) is being malevolently treated in some way. The patient may believe that he/she has been drugged, spied upon, harmed, harassed and so on and may seek "justice" by making reports, taking action or even acting violently.
• Somatic type: delusions that the person has some physical defect or general medical condition
• Mixed type: delusions with characteristics of more than one of the above types but with no one theme predominating.
• Unspecified type: delusions that cannot be clearly determined or characterized in any of the categories in the specific types.

Signs and symptoms

The following can indicate a delusion:

1. The patient expresses an idea or belief with unusual persistence or force, even when evidence suggests the contradictory.
2. That idea appears to have an undue influence on the patient's life, and the way of life is often altered to an inexplicable extent.
3. Despite their profound conviction, there is often a quality of secretiveness or suspicion when the patient is questioned about it.
4. The individual tends to be humorless and oversensitive, especially about the belief.
5. There is a quality of centrality: no matter how unlikely it is that these strange things are happening to them, the patient accepts them relatively unquestioningly.
6. An attempt to contradict the belief is likely to arouse an inappropriately strong emotional reaction, often with irritability and hostility. They will not accept any other opinions.
7. The belief is, at the least, unlikely, and out of keeping with the patient's social, cultural, and religious background.
8. The patient is emotionally over-invested in the idea and it overwhelms other elements of their psyche.
9. The delusion, if acted out, often leads to behaviors which are abnormal and/or out of character, although perhaps understandable in light of the delusional beliefs.
10. Individuals who know the patient observe that the belief and behavior are uncharacteristic and alien.

Additional features of delusional disorder include the following:

1. It is a primary disorder.
2. It is a stable disorder characterized by the presence of delusions to which the patient clings with extraordinary tenacity.
3. The illness is chronic and frequently lifelong.
4. The delusions are logically constructed and internally consistent.
5. The delusions do not interfere with general logical reasoning (although within the delusional system the logic is perverted) and there is usually no general disturbance of behavior. If disturbed behavior does occur, it is directly related to the delusional beliefs.
6. The individual experiences a heightened sense of self-reference. Events which, to others, are nonsignificant are of enormous significance to him or her, and the atmosphere surrounding the delusions is highly charged.

However this should not be confused with gaslighting, where a person denies the truth, and causes the victim to think that they are being delusional.

Gaslighting

Sometimes a correct belief may be mistaken for a delusion, such as when the belief in question is not demonstrably false but is nevertheless considered beyond the realm of possibility. A specific variant of this is when a person is fed lies in an attempt to convince them that they are delusional, a process called "gaslighting," after the 1938 play Gas Light, the plot of which centered around the process. 

Gaslighting is frequently used by people with antisocial personality disorder or narcissistic personality disorder. Sometimes, gaslighting can be unintentional, for example if a person, or a group of people aim to lie or cover up an issue, it can lead to the victim being gaslighted as well.

Criticism

In other situations the delusion may turn out to be true belief. For example, in delusional jealousy, where a person believes that their partner is being unfaithful (and may even follow them into the bathroom believing them to be seeing their lover even during the briefest of partings), it may actually be true that the partner is having sexual relations with another person. In this case, the delusion does not cease to be a delusion because the content later turns out to be verified as true or the partner actually chose to engage in the behavior of which they were being accused.

In other cases, the delusion may be mistakenly assumed to be false by a doctor or psychiatrist assessing the belief, just because it seems to be unlikely, bizarre or held with excessive conviction. Psychiatrists rarely have the time or resources to check the validity of a person’s claims leading to some true beliefs to be erroneously classified as delusional. This is known as the Martha Mitchell effect, after the wife of the attorney general who alleged that illegal activity was taking place in the White House. At the time, her claims were thought to be signs of mental illness, and only after the Watergate scandal broke was she proved right (and hence sane).

Similar factors have led to criticisms of Jaspers' definition of true delusions as being ultimately 'un-understandable'. Critics (such as R. D. Laing) have argued that this leads to the diagnosis of delusions being based on the subjective understanding of a particular psychiatrist, who may not have access to all the information that might make a belief otherwise interpretable. 

Another difficulty with the diagnosis of delusions is that almost all of these features can be found in "normal" beliefs. Many religious beliefs hold exactly the same features, yet are not universally considered delusional. For instance, if a person was holding a true belief then they will of course persist with it. This can cause the disorder to be misdiagnosed by psychiatrists. These factors have led the psychiatrist Anthony David to note that "there is no acceptable (rather than accepted) definition of a delusion."

Causes

The cause of delusional disorder is unknown, but genetic, biochemical, and environmental factors may play a significant role in its development. Some people with delusional disorders may have an imbalance in neurotransmitters, the chemicals that send and receive messages to the brain. There does seem to be some familial component, and immigration (generally for persecutory reasons), drug abuse, excessive stress, being married, being employed, low socioeconomic status, celibacy among men, and widowhood among women may also be risk factors. Delusional disorder is currently thought to be on the same spectrum or dimension as schizophrenia, but people with delusional disorder, in general, may have less symptomatology and functional disability.

Diagnosis

Differential diagnosis includes ruling out other causes such as drug-induced conditions, dementia, infections, metabolic disorders, and endocrine disorders. Other psychiatric disorders must then be ruled out. In delusional disorder, mood symptoms tend to be brief or absent, and unlike schizophrenia, delusions are non-bizarre and hallucinations are minimal or absent.

Interviews are important tools to obtain information about the patient's life situation and past history to help make a diagnosis. Clinicians generally review earlier medical records to gather a full history. Clinicians also try to interview the patient's immediate family, as this can be helpful in determining the presence of delusions. The mental status examination is used to assess the patient's current mental condition.

A psychological questionnaire used in the diagnosis of the delusional disorder is the Peters Delusion Inventory (PDI) which focuses on identifying and understanding delusional thinking. However, this questionnaire is more likely used in research than in clinical practice.

In terms of diagnosing a non-bizarre delusion as a delusion, ample support should be provided through fact checking. In case of non-bizarre delusions, Psych Central notes, "All of these situations could be true or possible, but the person suffering from this disorder knows them not to be (e.g., through fact-checking, third-person confirmation, etc.)."

Treatment

A challenge in the treatment of delusional disorders is that most patients have limited insight, and do not acknowledge that there is a problem. Most patients are treated as out-patients, although hospitalization may be required in some cases if there is a risk of harm to self or others. Individual psychotherapy is recommended rather than group psychotherapy, as patients are often quite suspicious and sensitive. Antipsychotics are not well tested in delusional disorder, but they do not seem to work very well, and often have no effect on the core delusional belief. Antipsychotics may be more useful in managing agitation that can accompany delusional disorder. Until further evidence is found, it seems reasonable to offer treatments which have efficacy in other psychotic disorders.

Psychotherapy for patients with delusional disorder can include cognitive therapy which is conducted with the use of empathy. During the process, the therapist can ask hypothetical questions in a form of therapeutic Socratic questioning. This therapy has been mostly studied in patients with the persecutory type. The combination of pharmacotherapy with cognitive therapy integrates treating the possible underlying biological problems and decreasing the symptoms with psychotherapy as well. Psychotherapy has been said to be the most useful form of treatment because of the trust formed in a patient and therapist relationship.

Supportive therapy has also been shown to be helpful. Its goal is to facilitate treatment adherence and provide education about the illness and its treatment. 

Furthermore, providing social skills training has helped many persons. It can promote interpersonal competence as well as confidence and comfort when interacting with those individuals perceived as a threat.

Insight-oriented therapy is rarely indicated or contraindicated; yet there are reports of successful treatment. Its goals are to develop therapeutic alliance, containment of projected feelings of hatred, impotence, and badness; measured interpretation as well as the development of a sense of creative doubt in the internal perception of the world. The latter requires empathy with the patient's defensive position.

Epidemiology

Delusional disorders are uncommon in psychiatric practice, though this may be an underestimation due to the fact that those afflicted lack insight and thus avoid psychiatric assessment. The prevalence of this condition stands at about 24 to 30 cases per 100,000 people while 0.7 to 3.0 new cases per 100,000 people are reported every year. Delusional disorder accounts for 1–2% of admissions to inpatient mental health facilities. The incidence of first admissions for delusional disorder is lower, from 0.001–0.003%.

Delusional disorder tends to appear in middle to late adult life, and for the most part first admissions to hospital for delusional disorder occur between age 33 and 55. It is more common in women than men, and immigrants seem to be at higher risk.

In popular culture

In the 2010 psychological thriller Shutter Island, directed by Martin Scorsese and starring Leonardo DiCaprio, delusional disorder is portrayed along with other disorders. An Indian movie "Anantaram (Thereafter)" directed by Adoor Gopalakrishnan also portrays the complex nature of delusions.