<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cerebral edema and explain in detail? [/INST] Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compression of brain tissue and blood vessels. Symptoms vary based on the location and extent of edema and generally include headaches, nausea, vomiting, seizures, drowsiness, visual disturbances, dizziness, and in severe cases, coma and death.Cerebral edema is commonly seen in a variety of brain injuries including ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, subdural, epidural, or intracerebral hematoma, hydrocephalus, brain cancer, brain infections, low blood sodium levels, high altitude, and acute liver failure. Diagnosis is based on symptoms and physical examination findings and confirmed by serial neuroimaging (computed tomography scans and magnetic resonance imaging).The treatment of cerebral edema depends on the cause and includes monitoring of the persons airway and intracranial pressure, proper positioning, controlled hyperventilation, medications, fluid management, steroids. Extensive cerebral edema can also be treated surgically with a decompressive craniectomy. Cerebral edema is a major cause of brain damage and contributes significantly to the mortality of ischemic strokes and traumatic brain injuries.As cerebral edema is present with many common cerebral pathologies, the epidemiology of the disease is not easily defined. The incidence of this disorder should be considered in terms of its potential causes and is present in most cases of traumatic brain injury, central nervous system tumors, brain ischemia, and intracerebral hemorrhage. For example, malignant brain edema was present in roughly 31% of people with ischemic strokes within 30 days after onset.

Signs and symptoms
The extent and severity of the symptoms of cerebral edema depend on the exact etiology but are generally related to an acute increase of the pressure within the skull. As the skull is a fixed and inelastic space, the accumulation of cerebral edema can displace and compress vital brain tissue, cerebral spinal fluid, and blood vessels, according to the Monro-Kellie doctrine.Increased intracranial pressure (ICP) is a life-threatening surgical emergency marked by symptoms of headache, nausea, vomiting, decreased consciousness. Symptoms are frequently accompanied by visual disturbances such as gaze paresis, reduced vision, and dizziness. Increased pressures within the skull can cause a compensatory elevation of blood pressure to maintain cerebral blood flow, which, when associated with irregular breathing and a decreased heart rate, is called the Cushing reflex. The Cushing reflex often indicates compression of the brain on brain tissue and blood vessels, leading to decreased blood flow to the brain and eventually death.

Causes
Cerebral edema is frequently encountered in acute brain injuries from a variety of origins, including but not limited to:
Traumatic brain injury
Stroke
Tumors
Infections (such as a brain abscess or meningitis)
Hepatic encephalopathy
Posterior reversible encephalopathy syndrome
Radiation-induced brain edema
Post-surgical changes
Amyloid-related imaging abnormalities associated with edema (ARIA-E)
Hyponatremia
High-altitude cerebral edema

Risk factors
Cerebral edema is present with many common cerebral pathologies and risk factors for development of cerebral edema will depend on the cause. The following were reliable predictors for development of early cerebral edema in ischemic strokes.
Younger age
Higher severity of symptoms on the National Institutes of Health Stroke Scale
Signs of current ischemia on clinical exam
Decreased level of consciousness
Hyper dense artery sign and larger affected area on CT imaging
Higher blood glucose

Classification
Cerebral edema has been traditional classified into two major sub-types: cytotoxic and vasogenic cerebral edema. This simple classification helps guide medical decision making and treatment of patients affected with cerebral edema. There are, however, several more differentiated types including but not limited to interstitial, osmotic, hydrostatic, and high altitude associated edema. Within one affected person, many individual sub-types can be present simultaneously.The following individual sub-types have been identified:

Cytotoxic
In general, cytotoxic edema is linked to cell death in the brain through excessive cellular swelling. During cerebral ischemia for example, the blood–brain barrier remains intact but decreased blood flow and glucose supply leads to a disruption in cellular metabolism and creation of energy sources, such as adenosine triphosphate (ATP). Exhaustion of energy sources impairs functioning of the sodium and potassium pump in the cell membrane, leading to cellular retention of sodium ions. Accumulation of sodium in the cell causes a rapid uptake of water through osmosis, with subsequent swelling of the cells. The ultimate consequence of cytotoxic edema is the oncotic death of neurons. The swelling of the individual cells of the brain is the main distinguishing characteristic of cytotoxic edema, as opposed to vasogenic edema, wherein the influx of fluid is typically seen in the interstitial space rather than within the cells themselves. Researchers have proposed that "cellular edema" may be more preferable to the term "cytotoxic edema" given the distinct swelling and lack of consistent "toxic" substance involved.There are several clinical conditions in which cytotoxic edema is present:

Commonly caused by traumatic brain injuries, intracerebral hemorrhage, and the early phase of ischemic stroke.
Also seen in acute liver failure where toxic waste, most notably ammonia, accumulates in the blood stream and crosses the blood–brain barrier. Hyperammonemia in central nervous system (CNS) cells causes oxidative stress and mitochrondrial dysfunction, leading to astrocytic cell swelling. Additionally, ammonia is converted to glutamine in CNS cells which acts as an osmolyte and draws further water into the cell through osmosis. Cerebral edema occurs most commonly in conjunction with a rapid rise in ammonia levels.
Toxic exposures to methionine sulfoxime, cuprizone, isoniazid, triethyl tin, hexachlorophene, and hydrogen cyanide have been associated with cytotoxic edema and swelling of astrocytic cells.
Hypoxia, anoxia can lead to cytotoxic edema through several mechanisms

Vasogenic
Extracellular brain edema, or vasogenic edema, is caused by an increase in the permeability of the blood–brain barrier. The blood–brain barrier consists of astrocytes and pericytes joined together with adhesion proteins producing tight junctions. Return of blood flow to theses cells after an ischemic stroke can cause excitotoxicity and oxidative stress leading to dysfunction of the endothelial cells and disruption of the blood-brain barrier. The breakdown of the tight endothelial junctions that make up the blood–brain barrier causes extravasation of fluid, ions, and plasma proteins, such as albumin, into the brain parenchyma. Accumulation of extracellular fluid increases brain volume and then intracranial pressure causing the symptoms of cerebral edema.There are several clinical conditions in which vasogenic edema is present:

CNS tumors, like glioblastoma and meningioma
Infections like meningitis, abscess, and encephalitis
Inflammatory central nervous system disease such as multiple sclerosis
Brain hemorrhage
Traumatic brain injuries can lead to increased intracranial pressure, local damage, reduced cerebral blood flow, and focal ischemia secondary to vasogenic edema.
Late stage of ischemic stroke after rapid recovery from cytotoxic edema
Hypertensive encephalopathy
Radiation injury

Ionic (Osmotic)
In ionic edema, the solute concentration (osmolality) of the brain exceeds that of the plasma and the abnormal pressure gradient leads to accumulation of water intake into the brain parenchyma through the process of osmosis. The blood-brain barrier is intact and maintains the osmotic gradient.The solute concentration of the blood plasma can be diluted by several mechanisms:

Improper administration of intravenous fluids, isotonic or hypotonic.
Excessive water intake, syndrome of inappropriate antidiuretic hormone (SIADH).
Rapid reduction of blood glucose in diabetic ketoacidosis or hyperosmolar hyperglycemic state.
Hemodialysis has been associated with ionic edema and cellular swelling.
Cerebral edema is a potentially life threatening complication of severely decreased sodium ion concentration in the blood (hyponatremia).Ionic brain edema can also occur around the sites of brain hemorrhages, infarcts, or contusions due to a local plasma osmolality pressure gradient when compared to the high osmolality in the affected tissue.

Interstitial (hydrocephalic)
Interstitial edema can be best characterized by in noncomunnicating hydrocephalus where there is an obstruction to the outflow of cerebrospinal fluid within the ventricular system. The obstruction creates a rise in the intraventricular pressure and causes CSF to flow through the wall of the ventricles into the extracellular fluid within brain. The fluid has roughly the same composition of CSF.Other causes of interstitial edema include but are not limited to communicating hydrocephalus, and normal pressure hydrocephalus.

Hydrostatic
Hydrostatic extracellular brain edema is typically caused by severe arterial hypertension. A difference in the hydrostatic pressure within the arterial system relative to the endothelial cells allows ultrafiltration of water, ions, and low molecular weight substances (such as glucose, small amino acids) into the brain parenchyma. The blood-brain barrier is intact usually and the extent of the edema depends on the arterial pressure. The regulatory processes of the brain circulation can function up to systolic arterial pressures of 150 mm Hg and will have impaired function at higher blood pressures.

Combined types of cerebral edema
Cytotoxic, osmotic, and vasogenic edema exist on a continuum. The mechanism of the cause of cerebral edema can often overlap between these types. In most instances, cytotoxic and vasogenic edema occur together. When the two edema types evolve simultaneously, the damage of one type reaches a limit and will bring about the other type of injury. For example, when cytotoxic edema occurs in the endothelial cells of the blood–brain barrier, oncotic cell death contributes to loss of integrity of the blood–brain barrier and promotes the progression to vasogenic edema. When brain edema types are combined, there is typically a primary form and the edema type and context of the cause must be determined in order to start appropriate medical or surgical therapy. The use of specific MRI techniques has allowed for some differentiation between the mechanisms.

Subtypes
High-altitude cerebral edema
If not properly acclimatized to high altitude, a person may be negatively affected by the lower oxygen concentration available. These hypoxia-related illnesses include acute mountain sickness (AMS), high-altitude pulmonary edema, and high-altitude cerebral edema (HACE). High-altitude cerebral edema is a severe and sometimes fatal form of altitude sickness that results from capillary fluid leakage due to the effects of hypoxia on the mitochondria-rich endothelial cells of the blood–brain barrier. The edema can be characterized by vasogenic cerebral edema with symptoms of impaired consciousness and truncal ataxia.Altitude-related illnesses can be prevented most effectively with slow ascent to high altitudes, an average ascent of 300 to 500 meters per day is recommended. Pharmacological prophylaxis with acetazoloamide or corticosteroids can be used in non pre-acclimatized individuals. If symptoms of high-altitude cerebral edema do not resolve or worsen, immediate descent is necessary, and symptoms can be improved with administration of dexamethasone.

Amyloid-related imaging abnormalities – edema
Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in neuroimaging of Alzheimers disease patients given targeted amyloid-modifying therapies. Human monoclonal antibodies such as aducanumab, solanezumab, and bapineuzumab have been associated with these neuroimaging changes and additionally, cerebral edema. These therapies are associated with dysfunction of the tight endothelial junctions of the blood-brain barrier, leading to vasogenic edema as described above. In addition to edema, these therapies are associated with microhemorrhages in the brain known as ARIA-H. Familiarity with ARIA can aid radiologists and clinicians in determining optimal management for those affected.

Posterior reversible encephalopathy syndrome
Posterior reversible encephalopathy syndrome (PRES) is a rare clinical disease characterized by cerebral edema. The exact pathophysiology, or cause, of the syndrome is still debated but is hypothesized to be related to the disruption of the blood-brain barrier. The syndrome features acute neurological symptoms and reversible subcortical vasogenic edema predominantly involving the parieto-occipital areas on MR imaging. PRES in general has a benign course, but PRES-related intracranial hemorrhage has been associated with a poor prognosis.

Idiopathic delayed-onset edema
Deep brain stimulation (DBS) is effective treatment for several neurological and psychiatric disorders, most notably Parkinsons disease. DBS is not without risks and although rare, idiopathic delayed-onset edema (IDE) surrounding the DBS leads have been reported. Symptoms can be mild and nonspecific, including reduction of the stimulation effect, and can be confused for other causes of edema. Thus, imaging is recommended to rule out other causes. The condition is generally self-limiting and the exact mechanism of the cause is unexplained. Early identification can help persons affected avoid unnecessary surgical procedures or antibiotic treatments.

Massive brain swelling after cranioplasty
Decompressive craniectomy is frequently performed in cases of resistant intracranial hypertension secondary to several neurological conditions and is commonly followed by cranioplasty. Complications, such as infection and hematomas after cranioplasty occur in roughly about a third of cases. Massive brain swelling after cranioplasty (MSBC) is a rare and potentially fatal complication of an uneventful cranioplasty that has recently been elucidated. Preoperative sinking skin flap (SSF) and intracranial hypotension were factors associated with the development of MSBC after cranioplasty. Data suggests that pathologic changes are triggered immediately following the procedure, especially an acute increase in intracranial pressure.

Radiation-induced brain edema
With the rise of sophisticated treatment modalities such as gamma knife, Cyberknife, and intensity-modulated radiotherapy, a large number of individuals with brain tumors are treated with radiosurgery and radiotherapy. Radiation-induced brain edema (RIBE) is a potentially life threatening complication of brain tissue radiation and is characterized radiation necrosis, endothelial cell dysfunction, increased capillary permeability, and breakdown of the blood–brain barrier. Symptoms include headache, seizure, psychomotor slowing, irritability, and focal neurological deficits. Options for management of RIBE are limited and include corticosteroids, antiplatelet drugs, anticoagulants, hyperbaric oxygen therapy, multivitamins, and bevacizumab.

Brain tumor-associated cerebral edema
This kind of cerebral edema is a significant cause of morbidity and mortality in patients with brain tumors and characterized by a disruption of the blood brain barrier and vasogenic edema. The exact mechanism is unclear but hypothesized that cancerous glial cells (glioma) of the brain can increase secretion of vascular endothelial growth factor (VEGF), which weakens the tight junctions of the blood–brain barrier. Historically, corticosteroids such as dexamethasone were used to reduce brain tumor-associated vascular permeability through poorly understood mechanisms and was associated with systemic side effects. Agents that target the VEGF signaling pathways, such as cediranib, have been promising in prolonging survival in rat models but associated with local and systemic side effects as well.

Diagnosis
Cerebral edema is commonly present in a variety of neurological injuries. Thus, determining a definitive contribution of cerebral edema to the neurological status of an affected person can be challenging. Close bedside monitoring of a persons level of consciousness and awareness of any new or worsening focal neurological deficits is imperative but demanding, frequently requiring admission into the intensive care unit (ICU).Cerebral edema with sustained increased intracranial hypertension and brain herniation can signify impending catastrophic neurological events which require immediate recognition and treatment to prevent injury and even death. Therefore, diagnosis of cerebral edema earlier with rapid intervention can improve clinical outcomes and can mortality, or risk of death.Diagnosis of cerebral edema relies on the following:

Imaging
Serial neuroimaging (CT scans and magnetic resonance imaging) can be useful in diagnosing or excluding intracranial hemorrhage, large masses, acute hydrocephalus, or brain herniation as well as providing information on the type of edema present and the extent of affected area. CT scan is the imaging modality of choice as it is widely available, quick, and with minimal risks. However, CT scan can be limited in determining the exact cause of cerebral edema in which cases, CT angiography (CTA), MRI, or digital subtraction angiography (DSA) may be necessary. MRI is particularly useful as it can differentiate between cytotoxic and vasogenic edema, guiding future treatment decisions.

Intracranial pressure monitoring
Intracranial pressure (ICP) and its management is a fundamental concept in traumatic brain injury (TBI). The Brain Trauma Foundation guidelines recommend ICP monitoring in individuals with TBI that have decreased Glasgow Coma Scale (GCS) scores, abnormal CT scans, or additional risk factors such as older age and elevated blood pressure. However, no such guidelines exist for ICP monitoring in other brain injuries such as ischemic stroke, intracerebral hemorrhage, cerebral neoplasm.Clinical researches have recommended ICP and cerebral perfusion pressure (CPP) monitoring in any persons with cerebral injury who are at risk of elevated intracranial pressure based on clinical and neuroimaging features. Early monitoring can be used to guide medical and surgical decision making and to detect potentially life-threatening brain herniation. There was however, conflicting evidence on the threshold values of ICP that indicated the need for intervention. Researches also recommend that medical decisions should be tailored to the specific diagnosis (e.g. subarachnoid hemorrhage, TBI, encephalitis) and that ICP elevation should be used in conjunction with clinical and neuroimaging and not as an isolated prognostic marker.

Treatment
The primary goal in cerebral edema is to optimize and regulate cerebral perfusion, oxygenation, and venous drainage, decrease cerebral metabolic demands, and to stabilize the osmolality pressure gradient between the brain and the surrounding vasculature. As cerebral edema is linked to increased intracranial pressure (ICP), many of the therapies will focus on ICP.

General measures for managing cerebral edema
Positioning
Finding the optimal head position in persons with cerebral edema is necessary to avoid compression of the jugular vein and obstruction of venous outflow from the skull, and for decreasing cerebrospinal fluid hydrostatic pressure. The current recommendation is to elevate the head of the bed to 30 degrees to optimize cerebral perfusion pressure and control the increase in intracranial pressure. It is also worth noting that measures should taken to reduce restrictive neck dressings or garments as these may lead to compression of the internal jugular veins and reduce venous outflow.

Ventilation and oxygenation
Decreased oxygen concentration in the blood, hypoxia, and increase in the carbon dioxide concentration in the blood, hypercapnia, are potent vasodilators in the cerebral vasculature, and should be avoided in those with cerebral edema. It is recommended that persons with decreased levels of consciousness be intubated for airway protection and maintenance of oxygen and carbon dioxide levels. However, the laryngeal instrumentation involved in the intubation process is associated with a acute, brief rise in intracranial pressure. Pretreatment with a sedative agent and neuromuscular blocking agent to induce unconsciousness and motor paralysis has been recommended as part of standard Rapid Sequence Intubation (RSI). Intravenous lidocaine prior to RSI has been suggested to reduce the rise in ICP but there is no supporting data at this time.Additionally, ventilation with use of positive pressure (PEEP) can improve oxygenation with the negative effect of decreasing cerebral venous drainage and increasing intracranial pressure (ICP), and thus, must be used with caution.

Fluid management and cerebral perfusion
Maintenance of cerebral perfusion pressure using appropriate fluid management is essential in patients with brain injury. Dehydration, or intravascular volume loss, and the use of hypotonic fluids, such as D5W or half normal saline, should be avoided. Blood serum ion concentration, or osmolality, should be maintained in the normo to hyperosmolar range. Judicial use of hypertonic saline can be used to increase serum osmolality and decrease cerebral edema, as discussed below.Blood pressure should be sufficient so as to sustain cerebral perfusion pressures greater than 60 mm Hg for optimal blood blow to the brain. Vasopressors may be used to achieve adequate blood pressures with minimal risk of increasing intracranial pressures. However, sharp rises in blood pressure should be avoided. Maximum blood pressures tolerated are variable and controversial depending on the clinical situation.

Seizure prophylaxis
Seizures, including subclinical seizure activity, can complicate clinical courses and increase progression of brain herniation in persons with cerebral edema and increased intracranial pressure. Anticonvulsants can be used to treat seizures caused by acute brain injuries from a variety of origins. However, there are no clear guidelines on the use of anticonvulsants for prophylactic use. Their use may be warranted on depending on the clinical scenario and studies have shown that anticonvulsants such as phenytoin can be given prophylactically without a significant increase in drug-related side effects.

Fever
Fever has been demonstrated to increase metabolism and oxygen demand in the brain. The increased metabolic demand results in an increase in cerebral blood flow and can increase the intracranial pressure within the skull. Therefore, maintaining a stable body temperature within the normal range is strongly recommended. This can be achieved through the use of antipyretics such as acetaminophen (paracetamol) and cooling the body, as described below.

Hyperglycemia
Elevated blood glucose levels, known as hyperglycemia, can exacerbate brain injury and cerebral edema and has been associated with worse clinical outcomes in persons affected by traumatic brain injuries, subarachnoid hemorrhages, and ischemic strokes.

Sedation
Pain and agitation can worsen cerebral edema, acutely increase intracranial pressure (ICP), and should be controlled. Careful use of pain medication such as morphine or fentanyl can be used for analgesia. For those persons with decreased levels of consciousness, sedation is necessary for endotracheal intubation and maintenance of a secure airway. Sedative medication used in the intubation process, specifically propofol, have been shown to control ICP, decrease cerebral metabolic demand, and have antiseizure properties. Due to a short half-life, propofol, is a quick-acting medication whose administration and removal is well tolerated, with hypotension being the limiting factor in its continued use. Additionally, the use of nondepolarizing neuromusclar blocking agents (NMBA), such as doxacurium or atracurium, have been indicated to facilitate ventilation and manage brain injuries but there are no controlled studies on the use of NMBAs in the management of increased intracranial pressure. Depolarizing neuromuscular blocking agents, most notably succinylcholine, can worsen increased ICP due to induction of muscle contraction within the body.

Nutrition
Nutritional support is necessary in all patients with acute brain injury. Enteral feeding, or through mouth via tube, is the preferred method, unless contraindicated. Additional attention must be placed on the solute concentration of the formulations to avoid free water intake, decreased serum osmolality, and worsening of the cerebral edema.Elevated blood glucose, or hyperglycemia, is associated with increased edema in patients with cerebral ischemia and increases the risk of a hemorrhagic transformation of ischemic stroke. Maintaining a normal blood glucose level of less than 180 mg/dL is suggested. However, tight glycemic control of blood glucose under 126 mg/dL is associated with worsening of stroke size.

Specific measures
Although cerebral edema is closely related to increased intracranial pressure (ICP) and cerebral herniation and the general treatment strategies above are useful, the treatment should ultimately be tailored to the primary cause of the symptoms. The management of individual diseases are discussed separately.
The following interventions are more specific treatments for managing cerebral edema and increased ICP:

Osmotic therapy
The goal of osmotic therapy is to create a higher concentration of ions within the vasculature at the blood–brain barrier. This will create an osmotic pressure gradient and will cause the flow of water out of the brain and into the vasculature for drainage elsewhere. An ideal osmotic agent produces a favorable osmotic pressure gradient, is nontoxic, and is not filtered out by the blood–brain barrier. Hypertonic saline and mannitol are the main osmotic agents in use, while loop diuretics can aid in the removal of the excess fluid pulled out of the brain.
Hypertonic saline is a highly concentrated solution of sodium chloride in water and is administered intravenously. It has a rapid-onset, with reduction of pressures within 5 minutes of infusion, lasting up to 12 hours in some cases, and with negligible rebound pressure. The exact volume and concentration of the hypertonic saline varies between clinical studies. Bolus doses, particularly at higher concentrations, for example 23.4%, are effective at reducing ICP and improving cerebral perfusion pressure. In traumatic brain injuries, a responsiveness to hypertonic saline lasting greater than 2 hours was associated with decreased chance of death and improved neurologic outcomes. The effects of hypertonic saline can be prolonged with combination to agents such as dextran or hydroxyethyl starch, although their use is currently controversial. When compared to mannitol, hypertonic saline has been shown to be as effective as mannitol in decreased ICP in neurocritical care and is more effective in many cases. Hypertonic saline may be preferable to mannitol in persons with hypovolemia or hyponatremia.
Mannitol is an alcohol derivative of simple sugar mannose, and is historically the most commonly used osmotic diuretic. Mannitol acts as an inert solute in the blood, decreasing ICP through osmosis as discussed above. Additionally, mannitol decreases ICP and increased cerebral perfusion pressure by increasing reabsorption of cerebrospinal fluid, dilutes and decreased the viscosity of the blood, and can cause cerebral vasoconstriction. Furthermore, mannitol acts in a dose-dependent manner and will not lower ICP if it is not elevated. However, the common limitation of the use of mannitol is its tendency to cause low blood pressure hypotension. Compared to hypertonic saline, mannitol may be more effective at increasing cerebral perfusion pressures and may be preferable in those with hypoperfusion.
Loop diuretics, commonly furosemide, act within kidney to increase excretion of water and solutes. Combination with mannitol produces a profound diuresis and increases the risk of systemic dehydration and hypotension. Their use remains controversial.
Acetazolamide, a carbonic anhydrase inhibitor, acts as a weak diuretic and modulates CSF production but has not role in the management of cerebral edema from acute brain injuries. It can be used in the outpatient management of cerebral edema caused by idiopathic intracranial hypertension (pseudotumor cerebri).

Glucocorticoids
Glucocorticoids, such as dexamethasone, have been shown to decrease tight-junction permeability and stabilize the blood-brain barrier. Their main use has been in the management of vasogenic cerebral edema associated with brain tumors, brain irradiation, and surgical manipulation. Glucocorticoids have not been shown to have any benefit in ischemic stroke and have been found to be harmful in traumatic brain injury. Due to the negative side effects (such as peptic ulcers, hyperglycemia, and impairment of wound healing), steroid use should be restricted to cases where they are absolutely indicated.

Hyperventilation
As mentioned previously, hypoxia and hypercapnia are potent vasodilators in the cerebral vasculature, leading to increased cerebral blood flow (CBF) and worsening of cerebral edema. Conversely, therapeutic hyperventilation can be used to lower the carbon dioxide content in the blood and reduce ICP through vasoconstriction. The effects of hyperventilation, although effective, are short-lived and once removed, can often lead to a rebound elevation of ICP. Furthermore, overaggressive hyperventilation and vasoconstriction and lead to severe reduction in CBF and cause cerebral ischemia, or strokes. As a result, standard practice is to slowly reverse hyperventilation while more definitive treatments aimed at the primary cause are instituted.It is important to note that prolonged hyperventilation in those with traumatic brain injuries has been shown to worsen outcomes.

Barbiturates
Induction of a coma via the use of barbiturates, most notably pentobarbital and thiopental, after brain injury is used for secondary treatment of refractory ICP. Yet their use is not without controversy and it is not clear whether barbiturates are favored over surgical decompression. In patients with traumatic brain injuries, barbiturates are effective in reducing ICP but have failed to show benefit to clinical outcomes. Evidence is limited for their use in cerebral disease that include tumor, intracranial hypertension, and ischemic stroke. There are several adverse effects of barbiturates that limit their use, such as lowering of systemic blood pressure and cerebral perfusion pressure, cardiodepression, immunosuppression, and systemic hypothermia.

Hypothermia
As discussed previously in the treatment of fever, temperature control has been shown to decrease metabolic demand and reduce further ischemic injury. In traumatic brain injury, induced hypothermia may reduce the risks of mortality, poor neurologic outcome in adults. However, outcomes varied greatly depth and duration of hypothermia as well as rewarming procedures. In children with traumatic brain injury, there was no benefit to therapeutic hypothermia and increased the risk of mortality and arrhythmia. The adverse effects of hypothermia are serious and require clinical monitoring including increased chance of infection, coagulopathy, and electrolyte derangement. The current consensus is that adverse effects outweigh the benefits and its use restricted to clinical trials and refractory increased ICP to other therapies.

Surgery
The Monroe-Kellie doctrine states that the skull is a fixed and inelastic space and the accumulation of edema will compress vital brain tissue and blood vessels. Surgical treatment of cerebral edema in the context of cerebellar or cerebral infarction is typically done by removing part of the skull to allow expansion of the dura. This will help to reduce the volume constraints inside of the skull. A decompressive hemicraniectomy is the most commonly used procedure. Multiple randomized clinical trials have shown reduced risk of death with hemicraniectomy compared with medical management. However, no individual study has shown an improvement in the percentage of survivors with good functional outcomes.Timing of decompressive craniectomy remains controversial, but is generally suggested that the surgery is best performed before there are clinical signs of brainstem compression. Postoperative complications include wound dehiscence, hydrocephalus, infection, and a substantial proportion of patients may also require tracheostomy and gastrotomy in the early phase after surgery.

Outcomes
Cerebral edema is a severe complication of acute brain injuries, most notably ischemic stroke and traumatic brain injuries, and a significant cause of morbidity and mortality.
Cerebral edema is the cause of death in 5% of all patients with cerebral infarction and mortality after large ischemic strokes with cerebral edema is roughly 20 to 30% despite medical and surgical interventions. Cerebral edema usually occurs between the second and fifth day after onset of symptoms. Large territory ischemic strokes can lead to the rapid development of malignant brain edema and increased intracranial pressure. Cerebral edema in the context of a malignant middle cerebral artery (MCA) infarct has a mortality of 50 to 80% if treated conservatively. Individuals with cerebral edema had a worse 3-month functional outcome than those without edema. These effects were more pronounced with increasing extent of cerebral edema and were independent of the size of the infarct.
Mild traumatic brain injury (TBI) represents 70–90% of all reported head injuries. The presence of brain edema on the initial CT scan of those with traumatic brain injuries is an independent prognostic indicator of in-hospital death. The association of brain edema with increased in hospital risk of death was observed in TBI across all level of severity. Edema in the acute and chronic phases were associated with a worse neurologic and clinical outcome. Children with TBI and cerebral edema have worse clinical outcomes as well.

Epidemiology
As cerebral edema is present with many common cerebral pathologies, the epidemiology of the disease is not easily defined </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Urethral stricture and explain in detail? [/INST] A urethral stricture is a narrowing of the urethra, the tube connected to the bladder that allows the passing of urine. The narrowing reduces the flow of urine and makes it more difficult or even painful to empty the bladder.Urethral stricture is caused by injury, instrumentation, infection, and certain non-infectious forms of urethritis The condition is more common in men due to their longer urethra.

Signs and symptoms
The hallmark sign of urethral stricture is a weak urinary stream. Other symptoms include:
Splaying of the urinary stream
Urinary frequency
Urinary urgency
Straining to urinate
Pain during urination
Urinary tract infection
Prostatitis
Inability to completely empty the bladder.Some people with severe urethral strictures are completely unable to urinate. This is referred to as acute urinary retention, and is a medical emergency. Hydronephrosis and kidney failure may also occur.

Complications
Causes
Urethral strictures most commonly result from injury, urethral instrumentation, infection, non-infectious inflammatory conditions of the urethra, and after prior hypospadias surgery. Less common causes include congenital urethral strictures and those resulting from malignancy.Urethral strictures after blunt trauma can generally be divided into two sub-types;

Pelvic fracture-associated urethral disruption occurs in as many as 15% of severe pelvic fractures. These injuries are typically managed with suprapubic tube placement and delayed urethroplasty 3 months later. Early endoscopic realignment may be used in select cases instead of a suprapubic tube, but these patients should be monitored closely as vast majority of them will require urethroplasty.
Blunt trauma to the perineum compresses the bulbar urethra against the pubic symphysis, causing a "crush" injury. These patients are typically treated with suprapubic tube and delayed urethroplasty.Other specific causes of urethral stricture include:

Instrumentation (e.g., after transurethral resection of prostate, transurethral resection of bladder tumor, or endoscopic kidney surgery)
Infection (typically with Gonorrhea)
Lichen sclerosus
Surgery to address hypospadias can result in a delayed urethral stricture, even decades after the original surgery.

Diagnosis
Among ways to diagnose this condition is:

Cystoscopy
Urethrography

Treatment
Initial treatment usually involves urethral dilation (widening the tube) or urethrotomy, where the stricture is cut away with a cystoscope.

Dilation and urethrotomy
Urethral dilation and other endoscopic approaches such as direct vision internal urethrotomy (DVIU), laser urethrotomy, and self intermittent dilation are the most commonly used treatments for urethral stricture. However, these approaches are associated with low success rates and may worsen the stricture, making future attempts to surgically repair the urethra more difficult.A Cochrane review found that performing intermittent self-dilatation may confer a reduced risk of recurrent urethral stricture after endoscopic treatment, but the evidence is weak.

Urethroplasty
Urethroplasty refers to any open reconstruction of the urethra. Success rates range from 85% to 95% and depend on a variety of clinical factors, such as stricture as the cause, length, location, and caliber. Urethroplasty can be performed safely on men of all ages.In the posterior urethra, anastomotic urethroplasty (with or without preservation of bulbar arteries) is typically performed after removing scar tissue.In the bulbar urethra, the most common types of urethroplasty are anastomotic (with or without preservation of corpus spongiosum and bulbar arteries) and substitution with buccal mucosa graft, full-thickness skin graft, or split thickness skin graft. These are nearly always done in a single setting (or stage).In the penile urethra, anastomotic urethroplasties are rare because they can lead to chordee (penile curvature due to a shortened urethra). Instead, most penile urethroplasties are substitution procedures utilizing buccal mucosa graft, full-thickness skin graft, or split-thickness skin graft. These can be done in one or more settings, depending on stricture location, severity, cause and patient or surgeon preference.

Urethral stent
A permanent urethral stent was approved for use in men with bulbar urethral strictures in 1996, but was recently removed from the market.A temporary thermoexpandable urethral stent (Memotherm) is available in Europe but is not currently approved for use in the United States.

Emergency treatment
When in acute urinary retention, treatment of the urethral stricture or diversion is an emergency. Options include:

Urethral dilatation and catheter placement </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sauk people and explain in detail? [/INST] The Sauk or Sac are a group of Native Americans of the Eastern Woodlands culture group, who lived primarily in the region of what is now Green Bay, Wisconsin, when first encountered by the French in 1667. Their autonym is oθaakiiwaki, and their exonym is Ozaagii(-wag) in Ojibwe. The latter name was transliterated into French and English by colonists of those cultures. Today they have three federally recognized tribes, together with the Meskwaki (Fox), located in Iowa, Oklahoma and Kansas.

History
Early history
The Sauk, an Algonquian languages people, are believed to have developed as a people along the St. Lawrence River, which is now northern New York. The precise time is unknown, but around the time of the year 1600, they were driven from the area of the St. Lawrence river. Some historians believe that the Sauk migrated to what is now eastern Michigan, where they settled around Saginaw Bay (Ojibwe: Zaagiinaad-wiikwed – "Of the Outlet Bay"). For many years, the Sauk are believed to have prospered in the fertile valley of Saginaw thereafter. They had been driven west by pressure from other tribes, especially the powerful Iroquois League or Haudenosaunee, which sought control over hunting grounds in the area.
The neighboring Anishanabeg Ojibwe (Sauk name: Ochipwêwa) and Odawa peoples referred to them by the exonym Ozaagii(-wag), meaning "those at the outlet". French colonists transliterated that as Sac and the English as "Sauk". The Sauk/Sac called themselves the
autonym of Othâkîwa, Thâkîwa, Thâkîwaki or Asaki-waki/Oθaakiiwaki people of the yellow earth [("people coming forth [from the outlet]," i.e., "from the water")], which is often interpreted to mean "yellow-earth people" or "the Yellow-Earths", due to the yellow-clay soils found around Saginaw Bay. This interpretation possibly derived from the Sauk words Athâwethiwa or Athâw(i) ("yellow") and Neniwaki ("men, people"). This was later shortened to "Asaki-waki". In addition, the Fox (Meskwaki) were generally known among neighboring tribes as the "people of the red earth" - the Sauk and Fox also used this term: Êshkwîha or Meshkwahkîha ("people of the red earth").
Some Ojibwe oral histories also place the Sauk in the Saginaw Valley some time before the arrival of Europeans. Sauk traditions state that the tribe occupied the vicinity of Saginaw river. (In this tradition, the name Saginaw comes from the Ojibwe "O-Sauk-e-non," meaning "land of the Sauks" or "where the Sauks were.") Approximately from the years 1638 to 1640, it is believed that a fierce battle ensued, nearly annihilating the entire Sauk Tribe. The story goes that the Chippewa inhabited the lands north of the Saginaw Bay, and the harsher northern climate caused more difficulty in prosperity compared to that of the Sauk occupying the area of Saginaw Valley. The Chippewa allied with the Ottawa, who resided south of the Sauk, and sprung a series of attacks on the Sauk Tribe which practically decimated their people. One such attack, the Battle of Skull Island, occurred on an island which is now called Skull Island in Michigan. (Its name came from the many skulls and bones supposedly found in mounds on that island over the years.)  In this battle, it is said that the Sauk had used their boats to cross part of the river, escape to the island, and were temporarily free from their attackers. But when morning came, ice had solidified the river enough for the Chippewa to cross. They killed every member of the Sauk tribe who had fled to that island besides twelve women whom they later sent west of the Mississippi River.But the Sauk may have been mistakenly recorded as dwelling at this location near Lake Huron at that time. There is little archaeological evidence that the Sauk lived in the Saginaw area. In the early 17th century, when natives told French explorer Samuel de Champlain that the Sauk nation was located on the west shore of Lake Michigan, Champlain mistakenly placed them on the western shore of Lake Huron. This mistake was copied on subsequent maps, and future references identified this as the place of the Sauk. Champlain never visited what is now Michigan.Anishinaabe expansion and the Huron attempting to gain regional stability drove the Sac out of their territory. The Huron were armed with guns supplied by their French trading partners. The Sac moved south to territory in parts of what are now northern Illinois and Wisconsin. In the seventeenth century the Sauk also maintained close relations with the Potawatomi (Pehkînenîha or Shîshîpêhinenîha). This relation has been found by borrowings of Sauk vocabulary that appear in the Potawatomi language.
In a loose coalition of tribes – including Dakota (Ashâha), Ojibwe, Odawa, Potawatomi, Kickapoo (Kîkâpôwa), Meskwaki (Fox), and Sauk, along with the Shawnee (Shâwanôwa), Cherokee (Shanahkîha), and Choctaw (Châkitâha) from the Southeast – they attacked the tribes of the Illinois Confederation ("Illinois/Inoca") (Mashkotêwa) and tried to invade their tribal areas. The "Illinois/Inoca" became their worst common enemies. The coalition warred for years until they destroyed the Illinois Confederation.
Later they moved out on the prairie (Mashkotêwi) along the Mississippi and adopted the semi-sedentary lifestyle of Plains Indians (Mashkotêwineniwa). In addition to hunting buffalo, they lived in villages, raised crops, and actively traded with other tribes. The Sauk and allied eastern tribes had to compete with tribes who already occupied this territory. Disputes and clashes arose with the Dakota, Pawnee (Pânîha) and, most of all, the powerful Osage (Washâsha).
The Sauk had good relations with the English (Thâkanâsha) through trading. At first, the Sauk had good relations with New France too, until their alliance with the Meskwaki (Fox) made them short-term enemies of the French (Mêmehtekôshîha, Wêmehtekôshîha).
A closely allied tribe, the Meskwaki (Fox), were noted for resisting French encroachment, having fought two wars against them in the early 18th century. After a devastating battle of 9 September 1730, in Illinois, in which hundreds of warriors were killed and many women and children taken captive by French allies, Fox refugees took shelter with the Sac. This made them subject to French attack in turn.  The Sac continued moving west to Iowa and Kansas. Keokuk and Black Hawk were two important leaders who arose among the Sauk. At first Keokuk accepted the loss of land as inevitable in the face of the vast numbers of white soldiers and settlers coming west. He tried to preserve tribal land and his people, and to keep the peace.
Having failed to receive expected supplies from the Americans on credit, Black Hawk wanted to fight, saying his people were "forced into war by being deceived". Led by Black Hawk in 1832, the mainly Sac band resisted the continued loss of lands (in western Illinois, this time.) Their warfare with United States forces resulted in defeat at the hands of General Edmund P. Gaines in the Black Hawk War.

Oklahoma history
About this time, one group of Sac moved into Missouri, and later to Kansas and Nebraska. In 1869, after the Civil War, the United States forced the larger group of Sac to move into a reservation in Indian Territory (now the state of Oklahoma). They merged with the Meskwaki as the federally recognized Sac and Fox Nation. (The United States had been making treaties with the two tribes together since their residency in the Midwest.) A smaller number returned to the Midwest from Oklahoma (or resisted leaving.) They joined the Mesquakie at the Mesqwaki Settlement, Iowa.
The land currently occupied by the Sauk is only a section of what used to be the Sac and Fox Reservation during the time of 1867–1891. This reservation was established by the U.S. and spanned 480,000 acres. In 1887, however, the Dawes Act failed to recognize Native American culture by dividing the reservation into small allotments designated for individual households.
The remainder of land not allotted to the Sac and Fox was then sold to non-Native settlers in an attempt to gain Oklahoma statehood and the full assimilation of its Native American population.
By 1889, 519 of the tribe were located in Indian Territory, what is now central Oklahoma. On June 10, 1890, they ceded these Indian Territory lands to the federal government.

Treaties with U.S.
Many of the latter treaties listed have little to no information regarding their details, besides the date. In total, twenty two treaties were signed from 1789 to, more than a century later, 1891.

Treaty of Fort Harmar
Treaty of Greenville
Treaty of St. Louis (1804)
Treaty of Portage des Sioux
Treaty of St. Louis (1816)
Treaty of St. Louis (1822)
Treaty of Washington
First Treaty of Prairie du Chien
Fourth Treaty of Prairie du Chien
1832 Treaty
September 27, 1836 Treaty
September 28, 1836 Treaty
September 28, 1836 Treaty
1837 Treaty
1837 Treaty
1842 Treaty
1854 Treaty (Missouri Sac and Fox)
1859 Treaty
1861 Treaty (Iowa Sac and Fox)
Feb 18th, 1867
June 10, 1872 "Act of Congress" (Missouri Sac and Fox)
Feb 13th, 1891 "Act of Congress"

Clan system
The Sauk and Fox peoples were divided into two moieties or "divisions", which in turn were subdivided into Patri-lineages and Clans as local subgroups (segments).
The moieties were known as the Kishko/Ki-sko-ha/Kîshkôha (male: Kîshkôha, female: Kîshkôhkwêha) ("the long-haired") and as the Oskush/Askasa/Shkasha (male: Shkasha/Oshkashîwiwa, female: Shkashîhkwêwa/Oshkashîhkwêwiwa) ("the brave"). The two moieties were each symbolized by two colors: The Askasa/Shkasha painted their faces and partly their bodies with charcoal in mahkatêwâwi (black) and the Ki-sko-ha/Kîshkôha painted their bodies with white clay in wâpeshkyâwi (white). This duality was also celebrated by the two moieties in Lacrosse, which was often played extremely brutally to toughen young warriors for combat, for recreation, as part of festivals, and used as preparation for imminent wars or raids.
This division has survived to the present day, but is now more related to the political system of the United States: the supporters of the Democratic Party are associated with the Kîshkôha/Kîshkôhkwêha, while the supporters of the Republican Party are associated with the Shkasha/Shkashîhkwêwa.
Originally, the Sauk had a patrilineal and exogamous clan system, in which descent and inheritance was traced through the father. Clans or Mîthonî distinguished and named on the basis of totem animals, which are: Mahkwithowa (Bear Clan), Amehkwithowa (Beaver Clan), Peshekethiwithowa (Deer Clan), Ketiwithowa / Mekethiwithowa (Eagle Clan), Nemêthithowa (Fish Clan), Wâkoshêhithowa (Fox Clan), Kehchikamîwithowa (Ocean/Sea/Great Lake Clan), Keshêhokimâwithowa (Peace Clan), Ahpenîthowa (Potato Clan), Akônithowa (Snow Clan), Nenemehkiwithowa (Thunder Clan), Manethenôkimâwithowa (Warrior Clan), and Mahwêwithowa (Wolf Clan).Saukenuk or Saukietown (today: Black Hawk State Historic Site) near the mouth of the Rock River (Sinnissippi – "rocky waters") into the Mississippi (Mäsesibowi – "great river"), the most important Sauk settlement in the 18th and 19th centuries with about 4,000 inhabitants, was divided into 12 districts, which were assigned to the respective clans.
The tribe was governed by a council of sacred clan chiefs, a war chief, the head of families, and the warriors. Chiefs were recognized in three categories: civil, war, and ceremonial. Only the civil chiefs were hereditary. The other two chiefs were recognized by bands after they demonstrated their ability or spiritual power.
This traditional manner of selecting historic clan chiefs and governance was replaced in the 19th century by the United States appointing leaders through their agents at the Sac and Fox Agency, or reservation in Indian Territory (now Oklahoma). In the 20th century, the tribe adopted a constitutional government patterned after the United States form. They elect their chiefs.

Federally recognized tribes
Today the federally recognized Sac and Fox tribes are:

Sac and Fox Nation (Meskwaki: Othâkîwaki, meaning: "People of the yellow earth"), headquartered in Stroud, Oklahoma;
Sac and Fox Tribe of the Mississippi in Iowa (Meskwaki: Meshkwahkîhaki, meaning: "People of the red earth"), headquartered in Tama, Iowa; and
Sac and Fox Nation of Missouri in Kansas and Nebraska (Meskwaki: Nîmahâhaki), headquartered in Reserve, Kansas.

Language
Sauk is a dialect of the Fox language, one of the many Algonquian languages. It is very closely related to the dialects spoken by the Meskwaki and the Kickapoo tribes. Each of the dialects contains archaisms and innovations that distinguish them from each other. Sauk and Meskwaki appear to be the most closely related of the three, reflecting the peoples long relationship. Sauk is considered to be mutually intelligible, to a point, with Fox.
In their own language, the Sauk at one time called themselves asakiwaki [a-sak-i-wa-ki], "people of the outlet". The Sauk people have a syllabic orthography for their language. They published a Primer Book in 1975, based on a "traditional" syllabary that existed in 1906. It is intended to help modern-day Sauk to learn to write and speak their ancestral tongue. A newer orthography was proposed around 1994 to aid in language revival. The former syllabary was aimed at remaining native speakers of Sauk; the more recent orthography was developed for native English speakers, as many Sauk grow up with English as their first languageSauk has so few speakers that it is considered an endangered language, as are numerous others native to North America.
In 2005, A Concise Dictionary of the Sauk Language was published using the Algonquianist Standard Roman Orthography.In 2012, Shawnee High School in Shawnee, Oklahoma, began to offer a Sauk language course.

Sauk language loss
Use of Sauk as the official tribal language in everyday communication declined rapidly between 1935 and 1945. The chances of coming across a tribal member who can understand basic phrases of Sauk is small, due to the fact that the main language spoken by the Sac and Fox today is English. The loss of Sauk, as with many other Native American languages, lies in context with American history. Speaking in the native language was actively discouraged and often punished in Indian boarding schools during the late 19th and early 20th century, when the U.S. was attempting to assimilate Native Americans into European-American culture.
Another conflict for the preservation of the language, is that the original syllabary created was intended for the use of native Sauk speakers, and its clarification was designed from the Sauk language. This is a problem because this is no longer as helpful for the majority of the Sac and Fox nation, as the official tribe language today is English. The issue arises in instances when Sauk is being taught to a school in the tribe, and an elder, who is fluent in the language, disagrees with the pronunciation being taught.

Phonology
Sauk does not have many phonemes in comparison to many other languages: four vowels, two semivowels, and nine consonants.

Consonants
The following consonant phonemes are given in Reinschmidt (1995):

The representation of /h/ was omitted in the 1977 syllabary </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Blood phobia and explain in detail? [/INST] Blood phobia (also known as hemophobia or hematophobia in American English and haemophobia or haematophobia in British English) is an extreme irrational fear of blood, a type of specific phobia. Severe cases of this fear can cause physical reactions that are uncommon in most other fears, specifically vasovagal syncope (fainting).  Similar reactions can also occur with trypanophobia and traumatophobia.  For this reason, these phobias are categorized as blood-injection-injury phobia by the DSM-IV.  Some early texts refer to this category as "blood-injury-illness phobia."

Causes
Blood phobia is often caused by direct or vicarious trauma in childhood.  Though some have suggested a possible genetic link, a study of twins suggests that social learning and traumatic events, rather than genetics, is of greater significance.. Blood-injection-injury phobia (BII) affects about 4% of the population in the United States.The inclusion of BII within the category of specific or simple phobias in classificatory systems reflects a perception that fear has a primary role in the disorder. Consistent with this assumption, blood-injury phobia appears to share a common etiology with other phobias. Kendler, Neale, Kessler, Heath, and Eaves (1992) have argued from data comparing monozygotic with dizygotic twins that the genetic factor common to all phobias (agoraphobia, social phobia, and specific phobias), strongly predisposes a person to specific phobias.
The recognition of an inherited vulnerability common to all phobias is consistent with the notion that elevated trait anxiety predisposes one to anxiety disorders. Trait anxiety provides a background of affective arousal that permits a more rapid activation of the fight or flight response </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Anaphylaxis and explain in detail? [/INST] Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the following: an itchy rash, throat closing due to swelling which can obstruct or stop breathing; severe tongue swelling which can also interfere with or stop breathing; shortness of breath, vomiting, lightheadedness, loss of consciousness, low blood pressure, and medical shock. These symptoms typically start in minutes to hours and then increase very rapidly to life-threatening levels. Urgent medical treatment is required to prevent serious harm or death, even if the patient has used an epipen or has taken other medications in response, and even if symptoms appear to be improving.Common causes include allergies to insect bites and stings, allergies to foods – including nuts, milk, fish, shellfish, eggs and some fresh fruits or dried fruits; allergies to sulfites – a class of food preservatives and a byproduct in some fermented foods like vinegar; allergies to medications – including some antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin; allergy to general anaesthetic (used to make people sleep during surgery); allergy to contrast agents – dyes used in some medical tests to help certain areas of your body show up better on scans; allergy to latex – a type of rubber found in some rubber gloves and condoms. Other causes can include physical exercise, and cases may also occur in some people due to escalating reactions to simple throat irritation or may also occur without an obvious reason. The mechanism involves the release of inflammatory mediators in a rapidly escalating cascade from certain types of white blood cells triggered by either immunologic or non-immunologic mechanisms. Diagnosis is based on the presenting symptoms and signs after exposure to a potential allergen or irritant and in some cases, reaction to physical exercise.The primary treatment of anaphylaxis is epinephrine injection into a muscle, intravenous fluids, then placing the person "in a reclining position with feet elevated to help restore normal blood flow". Additional doses of epinephrine may be required. Other measures, such as antihistamines and steroids, are complementary. Carrying an epinephrine autoinjector, commonly called an "epipen" and identification regarding the condition is recommended in people with a history of anaphylaxis. Immediately contacting ambulance / EMT services is always strongly recommended, regardless of any on site treatment. Getting to a doctor or hospital as soon as possible is absolutely required in all cases, even if it appears to be getting better.Worldwide, 0.05–2% of the population is estimated to experience anaphylaxis at some point in life. Globally, as underreporting declined into the 2010s, the rate appeared to be increasing. It occurs most often in young people and females. About 99.7% of people hospitalized with anaphylaxis in the United States survive. The term comes from the Ancient Greek: ἀνά, romanized: ana, lit. against, and the Ancient Greek: φύλαξις, romanized: phylaxis, lit. protection.

Signs and symptoms
Anaphylaxis typically presents many different symptoms over minutes or hours with an average onset of 5 to 30 minutes if exposure is intravenous and up to 2 hours if from eating food. The most common areas affected include: skin (80–90%), respiratory (70%), gastrointestinal (30–45%), heart and vasculature (10–45%), and central nervous system (10–15%) with usually two or more being involved.

Skin
Symptoms typically include generalized hives, itchiness, flushing, or swelling (angioedema) of the affected tissues. Those with angioedema may describe a burning sensation of the skin rather than itchiness. Swelling of the tongue or throat occurs in up to about 20% of cases. Other features may include a runny nose and swelling of the conjunctiva. The skin may also be blue tinged because of lack of oxygen.

Respiratory
Respiratory symptoms and signs that may be present include shortness of breath, wheezes, or stridor. The wheezing is typically caused by spasms of the bronchial muscles while stridor is related to upper airway obstruction secondary to swelling. Hoarseness, pain with swallowing, or a cough may also occur.

Cardiovascular
While a fast heart rate caused by low blood pressure is more common, a Bezold–Jarisch reflex has been described in 10% of people, where a slow heart rate is associated with low blood pressure. A drop in blood pressure or shock (either distributive or cardiogenic) may cause the feeling of lightheadedness or loss of consciousness. Rarely very low blood pressure may be the only sign of anaphylaxis.Coronary artery spasm may occur with subsequent myocardial infarction, dysrhythmia, or cardiac arrest. Those with underlying coronary disease are at greater risk of cardiac effects from anaphylaxis. The coronary spasm is related to the presence of histamine-releasing cells in the heart.

Other
Gastrointestinal symptoms may include severe crampy abdominal pain, diarrhea, and vomiting. There may be confusion, a loss of bladder control or pelvic pain similar to that of uterine cramps. Dilation of blood vessels around the brain may cause headaches. A feeling of anxiety or of "impending doom" has also been described.

Causes
Anaphylaxis can occur in response to almost any foreign substance. Common triggers include venom from insect bites or stings, foods, and medication. Foods are the most common trigger in children and young adults, while medications and insect bites and stings are more common in older adults. Less common causes include: physical factors, biological agents such as semen, latex, hormonal changes, food additives and colors, and topical medications. Physical factors such as exercise (known as exercise-induced anaphylaxis) or temperature (either hot or cold) may also act as triggers through their direct effects on mast cells. Events caused by exercise are frequently associated with cofactors such as the ingestion of certain foods or taking an NSAID. In aspirin-exacerbated respiratory disease (AERD), alcohol is a common trigger. During anesthesia, neuromuscular blocking agents, antibiotics, and latex are the most common causes. The cause remains unknown in 32–50% of cases, referred to as "idiopathic anaphylaxis." Six vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal) are recognized as a cause for anaphylaxis, and HPV may cause anaphylaxis as well.

Food and alcohol
Many foods can trigger anaphylaxis; this may occur upon the first known ingestion.  Common triggering foods vary around the world due to cultural cuisine.  In Western cultures, ingestion of or exposure to peanuts, wheat, nuts, certain types of seafood like shellfish, milk, fruit and eggs are the most prevalent causes. Sesame is common in the Middle East, while rice and chickpeas are frequently encountered as sources of anaphylaxis in Asia. Severe cases are usually caused by ingesting the allergen, but some people experience a severe reaction upon contact. Children can outgrow their allergies.  By age 16, 80% of children with anaphylaxis to milk or eggs and 20% who experience isolated anaphylaxis to peanuts can tolerate these foods. Any type of alcohol, even in small amounts, can trigger anaphylaxis in people with AERD.

Medication
Any medication may potentially trigger anaphylaxis. The most common are β-lactam antibiotics (such as penicillin) followed by aspirin and NSAIDs. Other antibiotics are implicated less frequently. Anaphylactic reactions to NSAIDs are either agent specific or occur among those that are structurally similar meaning that those who are allergic to one NSAID can typically tolerate a different one or different group of NSAIDs. Other relatively common causes include chemotherapy, vaccines, protamine and herbal preparations. Some medications (vancomycin, morphine, x-ray contrast among others) cause anaphylaxis by directly triggering mast cell degranulation.The frequency of a reaction to an agent partly depends on the frequency of its use and partly on its intrinsic properties. Anaphylaxis to penicillin or cephalosporins occurs only after it binds to proteins inside the body with some agents binding more easily than others. Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in fewer than one in every 50,000 courses of treatment. Anaphylaxis to aspirin and NSAIDs occurs in about one in every 50,000 persons. If someone has a reaction to penicillin, his or her risk of a reaction to cephalosporins is greater but still less than one in 1,000. The old radiocontrast agents caused reactions in 1% of cases, while the newer lower osmolar agents cause reactions in 0.04% of cases.

Venom
Venom from stinging or biting insects such as Hymenoptera (ants, bees, and wasps) or Triatominae (kissing bugs) may cause anaphylaxis in susceptible people. Previous reactions that are anything more than a local reaction around the site of the sting, are a risk factor for future anaphylaxis; however, half of fatalities have had no previous systemic reaction.

Risk factors
People with atopic diseases such as asthma, eczema, or allergic rhinitis are at high risk of anaphylaxis from food, latex, and radiocontrast agents but not from injectable medications or stings. One study in children found that 60% had a history of previous atopic diseases, and of children who die from anaphylaxis, more than 90% have asthma. Those with mastocytosis or of a higher socioeconomic status are at increased risk.

Pathophysiology
Anaphylaxis is a severe allergic reaction of rapid onset affecting many body systems. It is due to the release of inflammatory mediators and cytokines from mast cells and basophils, typically due to an immunologic reaction but sometimes non-immunologic mechanism.Interleukin (IL)–4 and IL-13 are cytokines important in the initial generation of antibody and inflammatory cell responses to anaphylaxis.

Immunologic
In the immunologic mechanism, immunoglobulin E (IgE) binds to the antigen (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates FcεRI receptors on mast cells and basophils. This leads to the release of inflammatory mediators such as histamine. These mediators subsequently increase the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and cause heart muscle depression. There is also a non-immunologic mechanism that does not rely on IgE, but it is not known if this occurs in humans.

Non-immunologic
Non-immunologic mechanisms involve substances that directly cause the degranulation of mast cells and basophils. These include agents such as contrast medium, opioids, temperature (hot or cold), and vibration. Sulfites may cause reactions by both immunologic and non-immunologic mechanisms.

Diagnosis
Anaphylaxis is diagnosed on the basis of a persons signs and symptoms. When any one of the following three occurs within minutes or hours of exposure to an allergen there is a high likelihood of anaphylaxis:
Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure causing symptoms
Two or more of the following symptoms after a likely contact with an allergen:
a. Involvement of the skin or mucosa
b. Respiratory difficulties
c. Low blood pressure
d. Gastrointestinal symptoms
Low blood pressure after exposure to a known allergenSkin involvement may include: hives, itchiness or a swollen tongue among others. Respiratory difficulties may include: shortness of breath, stridor, or low oxygen levels among others. Low blood pressure is defined as a greater than 30% decrease from a persons usual blood pressure. In adults a systolic blood pressure of less than 90 mmHg is often used.During an attack, blood tests for tryptase or histamine (released from mast cells) might be useful in diagnosing anaphylaxis due to insect stings or medications. However these tests are of limited use if the cause is food or if the person has a normal blood pressure, and they are not specific for the diagnosis.

Classification
There are three main classifications of anaphylaxis.

Anaphylactic shock is associated with systemic vasodilation that causes low blood pressure which is by definition 30% lower than the persons baseline or below standard values.
Biphasic anaphylaxis is the recurrence of symptoms within 1–72 hours after resolution of an initial anaphylactic episode. Estimates of incidence vary, between less than 1% and up to 20% of cases. The recurrence typically occurs within 8 hours. It is managed in the same manner as anaphylaxis.
Anaphylactoid reaction, non-immune anaphylaxis, or pseudoanaphylaxis, is a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation. Non-immune anaphylaxis is the current term, as of 2018, used by the World Allergy Organization with some recommending that the old terminology, "anaphylactoid", no longer be used.

Allergy skin testing
Allergy testing may help in determining the trigger. Skin allergy testing is available for certain foods and venoms. Blood testing for specific IgE can be useful to confirm milk, egg, peanut, tree nut and fish allergies.Skin testing is available to confirm penicillin allergies, but is not available for other medications. Non-immune forms of anaphylaxis can only be determined by history or exposure to the allergen in question, and not by skin or blood testing.

Differential diagnosis
It can sometimes be difficult to distinguish anaphylaxis from asthma, syncope, and panic attacks. Asthma however typically does not entail itching or gastrointestinal symptoms, syncope presents with pallor rather than a rash, and a panic attack may have flushing but does not have hives. Other conditions that may present similarly include: scrombroidosis and anisakiasis.

Post-mortem findings
In a person who died from anaphylaxis, autopsy may show an "empty heart" attributed to reduced venous return from vasodilation and redistribution of intravascular volume from the central to the peripheral compartment. Other signs are laryngeal edema, eosinophilia in lungs, heart and tissues, and evidence of myocardial hypoperfusion. Laboratory findings could detect increased levels of serum tryptase, increase in total and specific IgE serum levels.

Prevention
Avoidance of the trigger of anaphylaxis is recommended. In cases where this may not be possible, desensitization may be an option. Immunotherapy with Hymenoptera venoms is effective at desensitizing 80–90% of adults and 98% of children against allergies to bees, wasps, hornets, yellowjackets, and fire ants. Oral immunotherapy may be effective at desensitizing some people to certain food including milk, eggs, nuts and peanuts; however, adverse effects are common. For example, many people develop an itchy throat, cough, or lip swelling during immunotherapy. Desensitization is also possible for many medications, however it is advised that most people simply avoid the agent in question. In those who react to latex it may be important to avoid cross-reactive foods such as avocados, bananas, and potatoes among others.

Management
Anaphylaxis is a medical emergency that may require resuscitation measures such as airway management, supplemental oxygen, large volumes of intravenous fluids, and close monitoring. Passive leg raise may also be helpful in the emergency management.Administration of epinephrine is the treatment of choice with antihistamines and steroids (for example, dexamethasone) often used as adjuncts.  A period of in-hospital observation for between 2 and 24 hours is recommended for people once they have returned to normal due to concerns of biphasic anaphylaxis.

Epinephrine
Epinephrine (adrenaline) (1 in 1,000) is the primary treatment for anaphylaxis with no absolute contraindication to its use. It is recommended that an epinephrine solution be given intramuscularly into the mid anterolateral thigh as soon as the diagnosis is suspected. The injection may be repeated every 5 to 15 minutes if there is insufficient response. A second dose is needed in 16–35% of episodes with more than two doses rarely required. The intramuscular route is preferred over subcutaneous administration because the latter may have delayed absorption. It is recommended that after diagnosis and treatment of anaphylaxis, the patient should be kept under observation in an appropriate clinical setting until symptoms have fully resolved. Minor adverse effects from epinephrine include tremors, anxiety, headaches, and palpitations.People on β-blockers may be resistant to the effects of epinephrine. In this situation if epinephrine is not effective intravenous glucagon can be administered which has a mechanism of action independent of β-receptors.If necessary, it can also be given intravenously using a dilute epinephrine solution. Intravenous epinephrine, however, has been associated both with dysrhythmia and myocardial infarction. Epinephrine autoinjectors used for self-administration typically come in two doses, one for adults or children who weigh more than 25 kg and one for children who weigh 10 to 25 kg.

Adjuncts
Antihistamines (both H1 and H2), while commonly used and assumed effective based on theoretical reasoning, are poorly supported by evidence. A 2007 Cochrane review did not find any good-quality studies upon which to base recommendations and they are not believed to have an effect on airway edema or spasm. Corticosteroids are unlikely to make a difference in the current episode of anaphylaxis, but may be used in the hope of decreasing the risk of biphasic anaphylaxis. Their prophylactic effectiveness in these situations is uncertain.  Nebulized salbutamol may be effective for bronchospasm that does not resolve with epinephrine. Methylene blue has been used in those not responsive to other measures due to its presumed effect of relaxing smooth muscle.

Preparedness
People prone to anaphylaxis are advised to have an allergy action plan. Parents are advised to inform schools of their childrens allergies and what to do in case of an anaphylactic emergency. The action plan usually includes use of epinephrine autoinjectors, the recommendation to wear a medical alert bracelet, and counseling on avoidance of triggers. Immunotherapy is available for certain triggers to prevent future episodes of anaphylaxis. A multi-year course of subcutaneous desensitization has been found effective against stinging insects, while oral desensitization is effective for many foods.

Prognosis
In those in whom the cause is known and prompt treatment is available, the prognosis is good. Even if the cause is unknown, if appropriate preventive medication is available, the prognosis is generally good. If death occurs, it is usually due to either respiratory (typically asphyxia) or cardiovascular causes (shock), with 0.7–20% of cases causing death. There have been cases of death occurring within minutes. Outcomes in those with exercise-induced anaphylaxis are typically good, with fewer and less severe episodes as people get older.

Epidemiology
The number of people who get anaphylaxis is 4–100 per 100,000 persons per year, with a lifetime risk of 0.05–2%. About 30% of people get more than one attack. Exercise-induced anaphylaxis affects about 1 in 2000 young people.Rates appear to be increasing: the numbers in the 1980s were approximately 20 per 100,000 per year, while in the 1990s it was 50 per 100,000 per year. The increase appears to be primarily for food-induced anaphylaxis. The risk is greatest in young people and females.Anaphylaxis leads to as many as 500–1,000 deaths per year (2.7 per million) in the United States, 20 deaths per year in the United Kingdom (0.33 per million), and 15 deaths per year in Australia (0.64 per million). Another estimate from the United States puts the death rate at 0.7 per million. Mortality rates have decreased between the 1970s and 2000s. In Australia, death from food-induced anaphylaxis occur primarily in women while deaths due to insect bites primarily occur in males. Death from anaphylaxis is most commonly triggered by medications.

History
The conditions of anaphylaxis has been known since ancient times. French physician François Magendie had described how rabbits were killed by repeated injections of egg albumin in 1839. However, the phenomenon was discovered by two French physiologists Charles Richet and Paul Portier. In 1901, Albert I, Prince of Monaco requested Richet and Portier join him on a scientific expedition around the French coast of the Atlantic Ocean, specifically to study on the toxin produced by cnidarians (like jellyfish and sea anemones). Richet and Portier boarded Alberts ship Princesse Alice II for ocean exploration to make collections of the marine animals.Richet and Portier extracted a toxin called hypnotoxin from their collection of jellyfish (but the real source was later identified as Portuguese man o war) and sea anemone (Actinia sulcata). In their first experiment on the ship, they injected a dog with the toxin in an attempt to immunise the dog, which instead developed a severe reaction (hypersensitivity). In 1902, they repeated the injections in their laboratory and found that dogs normally tolerated the toxin at first injection, but on re-exposure, three weeks later with the same dose, they always developed fatal shock. They also found that the effect was not related to the doses of toxin used, as even small amounts in secondary injections were lethal. Thus, instead of inducing tolerance (prophylaxis) which they expected, they discovered effects of the toxin as deadly.In 1902, Richet introduced the term aphylaxis to describe the condition of lack of protection. He later changed the term to anaphylaxis on grounds of euphony. The term is from the Greek  ἀνά-, ana-, meaning "against", and φύλαξις, phylaxis, meaning "protection". On 15 February 1902, Richet and Portier jointly presented their findings before the Societé de Biologie in Paris </s>