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106-452: There are different stages of organ dysfunction for certain different organs, both in acute and in chronic onset, whether or not there are one or more organs affected. Each stage of dysfunction (whether it be the heart, lung, liver, or kidney) has defined parameters, in terms of laboratory values based on blood and other tests, as to what it is (each of these organs' levels of failure is divided into stage I, II, III, IV, and V). The word "failure"

212-456: A prion . The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is likely to be benign . The diagnosis is aided by the presenting symptoms in any individual with an infectious disease, yet it usually needs additional diagnostic techniques to confirm the suspicion. Some signs are specifically characteristic and indicative of

318-426: A recommended exposure limit (REL) of 25 ppm (30 mg/m ) over an 8-hour workday. At levels of 100 ppm, nitric oxide is immediately dangerous to life and health . Liquid nitrogen oxide is very sensitive to detonation even in the absence of fuel, and can be initiated as readily as nitroglycerin. Detonation of the endothermic liquid oxide close to its b.p. (-152°C) generated a 100 kbar pulse and fragmented

424-422: A runny nose . In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host. In the latter case, the disease may only be defined as a "disease" (which by definition means an illness) in hosts who secondarily become ill after contact with an asymptomatic carrier . An infection is not synonymous with an infectious disease, as some infections do not cause illness in

530-882: A vasodilator in the cardiovascular system, a breakthrough that earned them the 1998 Nobel Prize in Physiology or Medicine. The ground state electronic configuration of NO is, in united atom notation: ( 1 σ ) 2 ( 2 σ ) 2 ( 3 σ ) 2 ( 4 σ ∗ ) 2 ( 5 σ ) 2 ( 1 π ) 4 ( 2 π ∗ ) 1 {\displaystyle (1\sigma )^{2}(2\sigma )^{2}(3\sigma )^{2}(4\sigma ^{*})^{2}(5\sigma )^{2}(1\pi )^{4}(2\pi ^{*})^{1}} The first two orbitals are actually pure atomic 1 s O and 1 s N from oxygen and nitrogen respectively and therefore are usually not noted in

636-446: A brown gas and major air pollutant , or with nitrous oxide (N 2 O), an anesthetic gas. Nitric oxide (NO) was first identified by Joseph Priestley in the late 18th century, originally seen as merely a toxic byproduct of combustion and an environmental pollutant. Its biological significance was later uncovered in the 1980s when researchers Robert F. Furchgott , Louis J. Ignarro , and Ferid Murad discovered its critical role as

742-425: A colonization is often only a matter of circumstance. Non-pathogenic organisms can become pathogenic given specific conditions, and even the most virulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such as Corynebacteria sp. and Viridans streptococci , prevent the adhesion and colonization of pathogenic bacteria and thus have a symbiotic relationship with

848-480: A consensus meeting in 1994 to create the "Sepsis-Related Organ Failure Assessment (SOFA)" score to describe and quantitate the degree of organ dysfunction in six organ systems. Using similar physiologic variables the Multiple Organ Dysfunction Score was developed. Four clinical phases have been suggested: At present, there is no drug or device that can reverse organ failure that has been judged by

954-479: A cooperative manner. Nasal breathing produces nitric oxide within the body, while oral breathing does not. In the U.S., the Occupational Safety and Health Administration (OSHA) has set the legal limit ( permissible exposure limit ) for nitric oxide exposure in the workplace as 25 ppm (30 mg/m ) over an 8-hour workday. The National Institute for Occupational Safety and Health (NIOSH) has set

1060-542: A current or voltage change. The detection of NO radicals in biological tissues is particularly difficult due to the short lifetime and concentration of these radicals in tissues. One of the few practical methods is spin trapping of nitric oxide with iron- dithiocarbamate complexes and subsequent detection of the mono-nitrosyl-iron complex with electron paramagnetic resonance (EPR). A group of fluorescent dye indicators that are also available in acetylated form for intracellular measurements exist. The most common compound

1166-469: A disease and are called pathognomonic signs; but these are rare. Not all infections are symptomatic. In children the presence of cyanosis , rapid breathing, poor peripheral perfusion, or a petechial rash increases the risk of a serious infection by greater than 5 fold. Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C. Many diagnostic approaches depend on microbiological culture to isolate

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1272-399: A disease. This amplification of nucleic acid in infected tissue offers an opportunity to detect the infectious agent by using PCR. Third, the essential tools for directing PCR, primers , are derived from the genomes of infectious agents, and with time those genomes will be known if they are not already. Thus, the technological ability to detect any infectious agent rapidly and specifically

1378-423: A hospital stay. Lastly, a community-acquired infection is one in which the infection is acquired from a whole community. One manner of proving that a given disease is infectious, is to satisfy Koch's postulates (first proposed by Robert Koch ), which require that first, the infectious agent be identifiable only in patients who have the disease, and not in healthy controls, and second, that patients who contract

1484-524: A host with depressed resistance ( immunodeficiency ) or if they have unusual access to the inside of the body (for example, via trauma ). Opportunistic infection may be caused by microbes ordinarily in contact with the host, such as pathogenic bacteria or fungi in the gastrointestinal or the upper respiratory tract , and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in Clostridioides difficile colitis ) or from

1590-502: A host. As bacterial and viral infections can both cause the same kinds of symptoms, it can be difficult to distinguish which is the cause of a specific infection. Distinguishing the two is important, since viral infections cannot be cured by antibiotics whereas bacterial infections can. There is a general chain of events that applies to infections, sometimes called the chain of infection or transmission chain . The chain of events involves several steps – which include

1696-430: A large quantity of ozone. The nitric oxide reacts with the ozone to produce oxygen and nitrogen dioxide , accompanied with emission of light ( chemiluminescence ): which can be measured with a photodetector . The amount of light produced is proportional to the amount of nitric oxide in the sample. Other methods of testing include electroanalysis (amperometric approach), where ·NO reacts with an electrode to induce

1802-434: A link between virulence and transmissibility. Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly. In practice most minor infectious diseases such as warts , cutaneous abscesses , respiratory system infections and diarrheal diseases are diagnosed by their clinical presentation and treated without knowledge of the specific causative agent. Conclusions about

1908-472: A liquid, nitric oxide dimerizes to dinitrogen dioxide , but the association is weak and reversible. The N–N distance in crystalline NO is 218 pm, nearly twice the N–O distance. Since the heat of formation of NO is endothermic , NO can be decomposed to the elements. Catalytic converters in cars exploit this reaction: When exposed to oxygen , nitric oxide converts into nitrogen dioxide : This reaction

2014-571: A normal healthy immune response , however, so there is risk of increasing vulnerability to infection, which can also cause clinical deterioration. A definite explanation has not been found. Local and systemic responses are initiated by tissue damage. Respiratory failure is common in the first 72 hours. Subsequently, one might see liver failure (5–7 days), gastrointestinal bleeding (10–15 days) and kidney failure (11–17 days). The most popular hypothesis by Deitch to explain MODS in critically ill patients

2120-518: A number of basic dyes due to the electrostatic attraction between negatively charged cellular molecules and the positive charge on the dye. A cell is normally transparent under a microscope, and using a stain increases the contrast of a cell with its background. Staining a cell with a dye such as Giemsa stain or crystal violet allows a microscopist to describe its size, shape, internal and external components and its associations with other cells. The response of bacteria to different staining procedures

2226-404: A particular pathogen at all (no matter how little) but also is often used in a sense implying a clinically apparent infection (in other words, a case of infectious disease). This fact occasionally creates some ambiguity or prompts some usage discussion; to get around this it is common for health professionals to speak of colonization (rather than infection ) when they mean that some of

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2332-493: A pathogen from the appropriate clinical specimen. In a microbial culture, a growth medium is provided for a specific agent. A sample taken from potentially diseased tissue or fluid is then tested for the presence of an infectious agent able to grow within that medium. Many pathogenic bacteria are easily grown on nutrient agar , a form of solid medium that supplies carbohydrates and proteins necessary for growth, along with copious amounts of water. A single bacterium will grow into

2438-429: A pathogen. A fluorescence microscope is then used to detect fluorescently labeled antibodies bound to internalized antigens within clinical samples or cultured cells. This technique is especially useful in the diagnosis of viral diseases, where the light microscope is incapable of identifying a virus directly. Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with

2544-432: A patient's blood or other body fluids for antigens or antibodies that indicate presence of a specific pathogen that the doctor suspects. Other techniques (such as X-rays , CAT scans , PET scans or NMR ) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by

2650-470: A persistent infection by infecting different cells of the body. Some viruses once acquired never leave the body. A typical example is the herpes virus, which tends to hide in nerves and become reactivated when specific circumstances arise. Persistent infections cause millions of deaths globally each year. Chronic infections by parasites account for a high morbidity and mortality in many underdeveloped countries. For infecting organisms to survive and repeat

2756-403: A result of an infectious disease with immunosuppressive activity (such as with measles , malaria or HIV disease ). Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host. While a primary infection can practically be viewed as the root cause of an individual's current health problem, a secondary infection

2862-471: A result of their presence or activity within the normal, healthy host, and their intrinsic virulence (the severity of the disease they cause) is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans, however, many serious diseases are caused by organisms acquired from the environment or that infect non-human hosts. Opportunistic pathogens can cause an infectious disease in

2968-411: A severe illness affecting the brain, remain undiagnosed, despite extensive testing using the standard of care ( microbiological culture ) and state-of-the-art clinical laboratory methods. Metagenomic sequencing-based diagnostic tests are currently being developed for clinical use and show promise as a sensitive, specific, and rapid way to diagnose infection using a single all-encompassing test. This test

3074-447: A single cell) signaling molecule. Once nitric oxide is converted to nitrates and nitrites by oxygen and water, cell signaling is deactivated. The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, resulting in vasodilation and increasing blood flow. Sildenafil (Viagra) is a drug that uses the nitric oxide pathway. Sildenafil does not produce nitric oxide, but enhances

3180-417: A specific identification of an infectious agent only when such identification can aid in the treatment or prevention of the disease, or to advance knowledge of the course of an illness prior to the development of effective therapeutic or preventative measures. For example, in the early 1980s, prior to the appearance of AZT for the treatment of AIDS , the course of the disease was closely followed by monitoring

3286-432: A visible mound on the surface of the plate called a colony , which may be separated from other colonies or melded together into a "lawn". The size, color, shape and form of a colony is characteristic of the bacterial species, its specific genetic makeup (its strain ), and the environment that supports its growth. Other ingredients are often added to the plate to aid in identification. Plates may contain substances that permit

Multiple organ dysfunction syndrome - Misplaced Pages Continue

3392-417: A web, or net, to trap the invaders, then hit them with a deadly oxidative blast, forming neutrophil extracellular traps (NETs). This results in catastrophic immune response leading to multiple organ dysfunction syndrome. Since in most cases no primary cause is found, the condition could be part of a compromised homeostasis involving the previous mechanisms. The European Society of Intensive Care organized

3498-462: Is 4,5-diaminofluorescein (DAF-2). Nitric oxide reacts with the hydroperoxyl radical ( HO 2 ) to form nitrogen dioxide (NO 2 ), which then can react with a hydroxyl radical (HO ) to produce nitric acid (HNO 3 ): Nitric acid, along with sulfuric acid , contributes to acid rain deposition. NO participates in ozone layer depletion . Nitric oxide reacts with stratospheric ozone to form O 2 and nitrogen dioxide: This reaction

3604-506: Is a gaseous signaling molecule . It is a key vertebrate biological messenger , playing a role in a variety of biological processes. It is a bioproduct in almost all types of organisms, including bacteria, plants, fungi, and animal cells. Nitric oxide, an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from L -arginine , oxygen , and NADPH by various nitric oxide synthase (NOS) enzymes . Reduction of inorganic nitrate may also make nitric oxide. One of

3710-509: Is a sequela or complication of that root cause. For example, an infection due to a burn or penetrating trauma (the root cause) is a secondary infection. Primary pathogens often cause primary infection and often cause secondary infection. Usually, opportunistic infections are viewed as secondary infections (because immunodeficiency or injury was the predisposing factor). Other types of infection consist of mixed, iatrogenic , nosocomial , and community-acquired infection. A mixed infection

3816-570: Is a signaling molecule in many physiological and pathological processes. It was proclaimed the " Molecule of the Year " in 1992. The 1998 Nobel Prize in Physiology or Medicine was awarded for discovering nitric oxide's role as a cardiovascular signalling molecule. Its impact extends beyond biology, with applications in medicine, such as the development of sildenafil (Viagra), and in industry, including semiconductor manufacturing. Nitric oxide should not be confused with nitrogen dioxide (NO 2 ),

3922-611: Is a risk factor in and of itself, and immunocompromised patients, such as with cancer or AIDS or a transplant, are at risk. Prognosis must take into account any co-morbidities the patient may have, their past and current health status, any genetic or environmental vulnerabilities they have, the nature and type of the illness or injury (as an example, data from COVID-19 is still being analyzed, whereas other cases from long-existing illnesses are much better understood), and any resistance to drugs used to treat microbial infections or any hospital-acquired co-infection. Earlier and aggressive treatment,

4028-500: Is active but does not produce noticeable symptoms may be called inapparent, silent, subclinical , or occult . An infection that is inactive or dormant is called a latent infection . An example of a latent bacterial infection is latent tuberculosis . Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family. The word infection can denote any presence of

4134-425: Is also utilized to measure concentrations of NO in control volumes. As seen in the acid deposition section, nitric oxide can transform into nitrogen dioxide (this can happen with the hydroperoxy radical, HO 2 , or diatomic oxygen, O 2 ). Symptoms of short-term nitrogen dioxide exposure include nausea, dyspnea and headache. Long-term effects could include impaired immune and respiratory function. NO

4240-423: Is an infection that is caused by two or more pathogens. An example of this is appendicitis , which is caused by Bacteroides fragilis and Escherichia coli . The second is an iatrogenic infection. This type of infection is one that is transmitted from a health care worker to a patient. A nosocomial infection is also one that occurs in a health care setting. Nosocomial infections are those that are acquired during

4346-422: Is an initial site of infection from which organisms travel via the bloodstream to another area of the body. Among the many varieties of microorganisms , relatively few cause disease in otherwise healthy individuals. Infectious disease results from the interplay between those few pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen depend upon

Multiple organ dysfunction syndrome - Misplaced Pages Continue

4452-443: Is commonly used to refer to the later stages, especially IV and V, when artificial support usually becomes necessary to sustain life; the damage may or may not be fully or partially reversible. Multiple organ dysfunction syndrome can trigger a variety of symptoms throughout the body. Because MODS can impact any organ system, the specific symptoms experienced will depend on which organs are affected. Initially, these signs may be mild as

4558-510: Is currently available. The only remaining blockades to the use of PCR as a standard tool of diagnosis are in its cost and application, neither of which is insurmountable. The diagnosis of a few diseases will not benefit from the development of PCR methods, such as some of the clostridial diseases ( tetanus and botulism ). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent neurotoxins . A significant proliferation of

4664-563: Is due to major trauma , the rs1800625 polymorphism is a functional single nucleotide polymorphism , a part of the receptor for advanced glycation end products (RAGE) transmembrane receptor gene (of the immunoglobulin superfamily ) and confers host susceptibility to sepsis and MODS in these patients. For many years, some patients were loosely classified as having sepsis or the sepsis syndrome . In more recent years, these concepts have been refined – so that there are specific definitions of sepsis – and two new concepts have been developed:

4770-503: Is injured. All multicellular organisms are colonized to some degree by extrinsic organisms, and the vast majority of these exist in either a mutualistic or commensal relationship with the host. An example of the former is the anaerobic bacteria species, which colonizes the mammalian colon , and an example of the latter are the various species of staphylococcus that exist on human skin . Neither of these colonizations are considered infections. The difference between an infection and

4876-467: Is not an enzyme and has no metabolic function. Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon

4982-425: Is referred to as infectious diseases . Infections are caused by infectious agents ( pathogens ) including: The signs and symptoms of an infection depend on the type of disease. Some signs of infection affect the whole body generally, such as fatigue , loss of appetite, weight loss, fevers , night sweats, chills, aches and pains. Others are specific to individual body parts, such as skin rashes , coughing , or

5088-404: Is referred to as colonization. Most humans are not easily infected. Those with compromised or weakened immune systems have an increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system are particularly susceptible to opportunistic infections . Entrance to the host at host–pathogen interface , generally occurs through the mucosa in orifices like

5194-501: Is similar to current PCR tests; however, an untargeted whole genome amplification is used rather than primers for a specific infectious agent. This amplification step is followed by next-generation sequencing or third-generation sequencing , alignment comparisons , and taxonomic classification using large databases of thousands of pathogen and commensal reference genomes . Simultaneously, antimicrobial resistance genes within pathogen and plasmid genomes are sequenced and aligned to

5300-439: Is that microbial colonization is very common even in environments that humans think of as being nearly sterile . Because it is normal to have bacterial colonization, it is difficult to know which chronic wounds can be classified as infected and how much risk of progression exists. Despite the huge number of wounds seen in clinical practice, there are limited quality data for evaluated symptoms and signs. A review of chronic wounds in

5406-597: Is the gut hypothesis. Due to splanchnic hypoperfusion and the subsequent mucosal ischaemia there are structural changes and alterations in cellular function. This results in increased gut permeability , changed immune function of the gut and increased translocation of bacteria . Liver dysfunction leads to toxins escaping into the systemic circulation and activating an immune response. This results in tissue injury and organ dysfunction. Gram-negative infections in MODS patients are relatively common, hence endotoxins have been advanced as principal mediator in this disorder. It

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5512-870: Is the invasion of tissues by pathogens , their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease , also known as a transmissible disease or communicable disease , is an illness resulting from an infection. Infections can be caused by a wide range of pathogens , most prominently bacteria and viruses . Hosts can fight infections using their immune systems . Mammalian hosts react to infections with an innate response, often involving inflammation , followed by an adaptive response. Specific medications used to treat infections include antibiotics , antivirals , antifungals , antiprotozoals , and antihelminthics . Infectious diseases resulted in 9.2 million deaths in 2013 (about 17% of all deaths). The branch of medicine that focuses on infections

5618-402: Is the most common cause of multiple organ dysfunction syndrome and may result in septic shock . In the absence of infection, a sepsis-like disorder is termed systemic inflammatory response syndrome (SIRS). Both SIRS and sepsis could ultimately progress to multiple organ dysfunction syndrome. In one-third of the patients, however, no primary focus can be found. Multiple organ dysfunction syndrome

5724-508: Is the terminal linear type (M−NO). Alternatively, nitric oxide can serve as a one-electron pseudohalide. In such complexes, the M−N−O group is characterized by an angle between 120° and 140°. The NO group can also bridge between metal centers through the nitrogen atom in a variety of geometries. In commercial settings, nitric oxide is produced by the oxidation of ammonia at 750–900 °C (normally at 850 °C) with platinum as catalyst in

5830-478: Is thought that following the initial event cytokines are produced and released. The pro-inflammatory mediators are: tumor necrosis factor-alpha (TNF-α), interleukin -1, interleukin-6, thromboxane A2, prostacyclin , platelet activating factor, and nitric oxide . As a result of macro- and microvascular changes insufficient supply of oxygen occurs. Hypoxemia causes cell death and organ dysfunction. According to findings of Professor Zsolt Balogh and his team at

5936-402: Is thought to occur via the intermediates ONOO and the red compound ONOONO. In water, nitric oxide reacts with oxygen to form nitrous acid (HNO 2 ). The reaction is thought to proceed via the following stoichiometry : Nitric oxide reacts with fluorine , chlorine , and bromine to form the nitrosyl halides, such as nitrosyl chloride : With NO 2 , also a radical, NO combines to form

6042-577: Is used in the taxonomic classification of microbes as well. Two methods, the Gram stain and the acid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groups Bacillota and Actinomycetota , both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinomycetota genera Mycobacterium and Nocardia . Biochemical tests used in

6148-430: Is usually mostly limited to supportive care, i.e. safeguarding hemodynamics, and respiration. Maintaining adequate tissue oxygenation is a principal target. Starting enteral nutrition within 36 hours of admission to an intensive care unit has reduced infectious complications. Mortality, though it has lessened to a limited degree, at least in developed countries with timely access to initial and tertiary care, varies where

6254-529: Is well established as the final stage of a continuum: SIRS + infection → sepsis → severe sepsis → Multiple organ dysfunction syndrome. Currently, investigators are looking into genetic targets for possible gene therapy to prevent the progression to multiple organ dysfunction syndrome. Some authors have conjectured that the inactivation of the transcription factors NF-κB and AP-1 would be appropriate targets in preventing sepsis and SIRS . These two genes are pro-inflammatory. They are essential components of

6360-588: The Journal of the American Medical Association 's "Rational Clinical Examination Series" quantified the importance of increased pain as an indicator of infection. The review showed that the most useful finding is an increase in the level of pain [likelihood ratio (LR) range, 11–20] makes infection much more likely, but the absence of pain (negative likelihood ratio range, 0.64–0.88) does not rule out infection (summary LR 0.64–0.88). Disease can arise if

6466-465: The Ostwald process : The uncatalyzed endothermic reaction of oxygen (O 2 ) and nitrogen (N 2 ), which is effected at high temperature (>2000 °C) by lightning has not been developed into a practical commercial synthesis (see Birkeland–Eyde process ): In the laboratory, nitric oxide is conveniently generated by reduction of dilute nitric acid with copper : An alternative route involves

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6572-459: The SIRS and MODS. Although Irwin and Rippe cautioned in 2005 that the use of "multiple organ failure" or "multisystem organ failure" should be avoided, both Harrison's (2015) and Cecil's (2012) medical textbooks still use the terms "multi-organ failure" and "multiple organ failure" in several chapters and do not use "multiple organ dysfunction syndrome" at all. Infection An infection

6678-534: The University of Newcastle (Australia) , mitochondrial DNA is the leading cause of severe inflammation due to a massive amount of mitochondrial DNA that leaks into the bloodstream due to cell death of patients who survived major trauma . Mitochondrial DNA resembles bacterial DNA. If bacteria triggers leukocytes, mitochondrial DNA may do the same. When confronted with bacteria, white blood cells, or neutrophil granulocytes , behave like predatory spiders. They spit out

6784-604: The haloform reaction . For example, nitric oxide reacts with acetone and an alkoxide to form a diazeniumdiolate on each α position , with subsequent loss of methyl acetate as a by-product : This reaction, which was discovered around 1898, remains of interest in nitric oxide prodrug research. Nitric oxide can also react directly with sodium methoxide , ultimately forming sodium formate and nitrous oxide by way of an N -methoxydiazeniumdiolate. Nitric oxide reacts with transition metals to give complexes called metal nitrosyls . The most common bonding mode of nitric oxide

6890-468: The oral cavity , nose, eyes, genitalia, anus, or the microbe can enter through open wounds. While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs. Some pathogens grow within the host cells (intracellular) whereas others grow freely in bodily fluids. Wound colonization refers to non-replicating microorganisms within the wound, while in infected wounds, replicating organisms exist and tissue

6996-447: The polymerase chain reaction (PCR) method will become nearly ubiquitous gold standards of diagnostics of the near future, for several reasons. First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the human population have been identified. Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids to cause

7102-403: The "strep test", they can be inexpensive. Complex serological techniques have been developed into what are known as immunoassays . Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of

7208-400: The 2π orbital makes NO a doublet (X ²Π) in its ground state whose degeneracy is split in the fine structure from spin-orbit coupling with a total momentum J = 3 ⁄ 2 or J = 1 ⁄ 2 . The dipole of NO has been measured experimentally to 0.15740 D and is oriented from O to N (⁻NO⁺) due to the transfer of negative electronic charge from oxygen to nitrogen. Upon condensing to

7314-435: The ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen. However, a host's immune system can also cause damage to the host itself in an attempt to control the infection. Clinicians, therefore, classify infectious microorganisms or microbes according to the status of host defenses – either as primary pathogens or as opportunistic pathogens . Primary pathogens cause disease as

7420-458: The basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase , and the presence of these enzymes are characteristic., of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin

7526-463: The case of viral identification, a region of dead cells results from viral growth, and is called a "plaque". Eukaryotic parasites may also be grown in culture as a means of identifying a particular agent. In the absence of suitable plate culture techniques, some microbes require culture within live animals. Bacteria such as Mycobacterium leprae and Treponema pallidum can be grown in animals, although serological and microscopic techniques make

7632-472: The causative agent, Trypanosoma cruzi in a patient, which therefore makes it difficult to definitively make a diagnosis. In this case, xenodiagnosis involves the use of the vector of the Chagas agent T. cruzi , an uninfected triatomine bug, which takes a blood meal from a person suspected of having been infected. The bug is later inspected for growth of T. cruzi within its gut. Another principal tool in

7738-436: The cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified. Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve

7844-426: The chance of survival is diminished as the number of organs involved increases. Mortality in MODS from septic shock (which itself has a high mortality of 25–50%), and from multiple traumas, especially if not rapidly treated, appear to be especially severe. If more than one organ system is affected, the mortality rate is still higher, and this is especially the case when five or more systems or organs are affected. Old age

7950-431: The composition of patient blood samples, even though the outcome would not offer the patient any further treatment options. In part, these studies on the appearance of HIV in specific communities permitted the advancement of hypotheses as to the route of transmission of the virus. By understanding how the disease was transmitted, resources could be targeted to the communities at greatest risk in campaigns aimed at reducing

8056-484: The culture of infectious agents isolated from a patient. Culture allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. Many infectious organisms are identified without culture and microscopy. This is especially true for viruses, which cannot grow in culture. For some suspected pathogens, doctors may conduct tests that examine

8162-400: The destruction of the virus. Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost-effective automated process for diagnosis of infectious disease. Technologies based upon

8268-428: The diagnosis of infectious disease is microscopy . Virtually all of the culture techniques discussed above rely, at some point, on microscopic examination for definitive identification of the infectious agent. Microscopy may be carried out with simple instruments, such as the compound light microscope , or with instruments as complex as an electron microscope . Samples obtained from patients may be viewed directly under

8374-445: The environment as a result of traumatic introduction (as in surgical wound infections or compound fractures ). An opportunistic disease requires impairment of host defenses, which may occur as a result of genetic defects (such as chronic granulomatous disease ), exposure to antimicrobial drugs or immunosuppressive chemicals (as might occur following poisoning or cancer chemotherapy ), exposure to ionizing radiation , or as

8480-426: The expression of symptoms is often atypical, making a clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A rapid, sensitive, specific, and untargeted test for all known human pathogens that detects the presence of the organism's DNA rather than antibodies is therefore highly desirable. There is usually an indication for

8586-552: The formula NO . It is one of the principal oxides of nitrogen . Nitric oxide is a free radical : it has an unpaired electron , which is sometimes denoted by a dot in its chemical formula ( N=O or NO). Nitric oxide is also a heteronuclear diatomic molecule , a class of molecules whose study spawned early modern theories of chemical bonding . An important intermediate in industrial chemistry , nitric oxide forms in combustion systems and can be generated by lightning in thunderstorms. In mammals, including humans, nitric oxide

8692-403: The growth of some bacteria and not others, or that change color in response to certain bacteria and not others. Bacteriological plates such as these are commonly used in the clinical identification of infectious bacterium. Microbial culture may also be used in the identification of viruses : the medium, in this case, being cells grown in culture that the virus can infect, and then alter or kill. In

8798-463: The health care team to be medically and/or surgically irreversible (organ function can recover, at least to a degree, in patients whose organs are very dysfunctional, where the patient has not died; and some organs, like the liver or the skin, can regenerate better than others),- with the possible exception of single or multiple organ transplants or the use of artificial organs or organ parts, in certain candidates in specific situations. Therapy, therefore,

8904-484: The host's protective immune mechanisms are compromised and the organism inflicts damage on the host. Microorganisms can cause tissue damage by releasing a variety of toxins or destructive enzymes. For example, Clostridium tetani releases a toxin that paralyzes muscles, and staphylococcus releases toxins that produce shock and sepsis . Not all infectious agents cause disease in all hosts. For example, less than 5% of individuals infected with polio develop disease. On

9010-598: The host, preventing infection and speeding wound healing . The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include: As an example, several staphylococcal species remain harmless on the skin, but, when present in a normally sterile space, such as in the capsule of a joint or the peritoneum , multiply without resistance and cause harm. An interesting fact that gas chromatography–mass spectrometry , 16S ribosomal RNA analysis, omics , and other advanced technologies have made more apparent to humans in recent decades

9116-532: The identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species , the detection of fermentation products is commonly used in bacterial identification. Acids , alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media. The isolation of enzymes from infected tissue can also provide

9222-413: The infection cycle in other hosts, they (or their progeny) must leave an existing reservoir and cause infection elsewhere. Infection transmission can take place via many potential routes: The relationship between virulence versus transmissibility is complex; with studies have shown that there were no clear relationship between the two. There is still a small number of evidence that partially suggests

9328-407: The infectious agent also develop the disease. These postulates were first used in the discovery that Mycobacteria species cause tuberculosis . Nitric oxide Dinitrogen tetroxide Dinitrogen trioxide Nitrogen dioxide Nitrous oxide Nitroxyl (reduced form) Hydroxylamine (hydrogenated form) Nitric oxide ( nitrogen oxide or nitrogen monoxide ) is a colorless gas with

9434-399: The infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria. Given the wide range of bacterial, viral, fungal, protozoal, and helminthic pathogens that cause debilitating and life-threatening illnesses, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases of encephalitis ,

9540-402: The infectious agent, reservoir, entering a susceptible host, exit and transmission to new hosts. Each of the links must be present in a chronological order for an infection to develop. Understanding these steps helps health care workers target the infection and prevent it from occurring in the first place. Infection begins when an organism successfully enters the body, grows and multiplies. This

9646-411: The intensely blue dinitrogen trioxide : The addition of a nitric oxide moiety to another molecule is often referred to as nitrosylation . The Traube reaction is the addition of a two equivalents of nitric oxide onto an enolate , giving a diazeniumdiolate (also called a nitrosohydroxylamine ). The product can undergo a subsequent retro- aldol reaction , giving an overall process similar to

9752-425: The light microscope, and can often rapidly lead to identification. Microscopy is often also used in conjunction with biochemical staining techniques, and can be made exquisitely specific when used in combination with antibody based techniques. For example, the use of antibodies made artificially fluorescent (fluorescently labeled antibodies) can be directed to bind to and identify a specific antigens present on

9858-402: The main enzymatic targets of nitric oxide is guanylyl cyclase . The binding of nitric oxide to the heme region of the enzyme leads to activation, in the presence of iron. Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within

9964-531: The number of new infections. The specific serological diagnostic identification, and later genotypic or molecular identification, of HIV also enabled the development of hypotheses as to the temporal and geographical origins of the virus, as well as a myriad of other hypothesis. The development of molecular diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment with anti-retroviral drugs . Molecular diagnostics are now commonly used to identify HIV in healthy people long before

10070-455: The onset of illness and have been used to demonstrate the existence of people who are genetically resistant to HIV infection. Thus, while there still is no cure for AIDS, there is great therapeutic and predictive benefit to identifying the virus and monitoring the virus levels within the blood of infected individuals, both for the patient and for the community at large. Symptomatic infections are apparent and clinical , whereas an infection that

10176-514: The other hand, some infectious agents are highly virulent. The prion causing mad cow disease and Creutzfeldt–Jakob disease invariably kills all animals and people that are infected. Persistent infections occur because the body is unable to clear the organism after the initial infection. Persistent infections are characterized by the continual presence of the infectious organism, often as latent infection with occasional recurrent relapses of active infection. There are some viruses that can maintain

10282-539: The pathogens are present but that no clinically apparent infection (no disease) is present. Different terms are used to describe how and where infections present over time. In an acute infection, symptoms develop rapidly; its course can either be rapid or protracted. In chronic infection, symptoms usually develop gradually over weeks or months and are slow to resolve. In subacute infections, symptoms take longer to develop than in acute infections but arise more quickly than those of chronic infections. A focal infection

10388-406: The reduction of nitrous acid in the form of sodium nitrite or potassium nitrite : The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments. So-called NONOate compounds are also used for nitric oxide generation. Nitric oxide concentration can be determined using a chemiluminescent reaction involving ozone . A sample containing nitric oxide is mixed with

10494-401: The signals that are downstream of the nitric oxide pathway by protecting cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum , allowing for the signal to be enhanced, and thus vasodilation . Another endogenous gaseous transmitter, hydrogen sulfide (H 2 S) works with NO to induce vasodilation and angiogenesis in

10600-457: The target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow

10706-559: The taxonomically classified pathogen genomes to generate an antimicrobial resistance profile – analogous to antibiotic sensitivity testing – to facilitate antimicrobial stewardship and allow for the optimization of treatment using the most effective drugs for a patient's infection. Metagenomic sequencing could prove especially useful for diagnosis when the patient is immunocompromised . An ever-wider array of infectious agents can cause serious harm to individuals with immunosuppression, so clinical screening must often be broader. Additionally,

10812-503: The test. For example, " Strep throat " is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, S. pyogenes , that is retrieved from a patient's throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration . Some serological methods are extremely costly, although when commonly used, such as with

10918-670: The underlying illness progresses towards MODS. However, as the condition worsens, the symptoms can become more severe. These symptoms include low urine output, nausea, vomiting, and loss of appetite. Some patients experience mental symptoms like confusion and may feel fatigued. Symptoms like fever, chills, irregular heartbeat, and quick/shallow breathing are also common. Multiple cases of MODS also suffer chest and abdominal pain, and patients may even lose consciousness. The condition results from infection , injury (accident, surgery ), hypoperfusion and hypermetabolism . The primary cause triggers an uncontrolled inflammatory response . Sepsis

11024-426: The united atom notation. Orbitals noted with an asterisk are antibonding. The ordering of 5σ and 1π according to their binding energies is subject to discussion. Removal of a 1π electron leads to 6 states whose energies span over a range starting at a lower level than a 5σ electron an extending to a higher level. This is due to the different orbital momentum couplings between a 1π and a 2π electron. The lone electron in

11130-735: The use of experimental treatments, or at least modern tools such as ventilators, ECMO, dialysis, bypass, and transplantation, especially at a trauma center, may improve outcomes in certain cases, but this depends in part on speedy and affordable access to high-quality care, which many areas lack. Measurements of lactate, cytokines, albumin and other proteins, urea, blood oxygen and carbon dioxide levels, insulin, and blood sugar, adequate hydration, constant monitoring of vital signs, good communication within and between facilities and staff, and adequate staffing, training, and charting are important in MODS, as in any serious illness. In patients with sepsis , septic shock , or multiple organ dysfunction syndrome that

11236-411: The use of live animals unnecessary. Viruses are also usually identified using alternatives to growth in culture or animals. Some viruses may be grown in embryonated eggs. Another useful identification method is Xenodiagnosis, or the use of a vector to support the growth of an infectious agent. Chagas disease is the most significant example, because it is difficult to directly demonstrate the presence of

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