<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Peripheral neuropathy and can you explain it in depth? [/INST] Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or organ function depending on which nerves are affected; in other words, neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent.
Common causes include systemic diseases (such as diabetes or leprosy), hyperglycemia-induced glycation, vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (such as ciprofloxacin, levofloxacin, moxifloxacin)), traumatic injury, ischemia, radiation therapy, excessive alcohol consumption, immune system disease, celiac disease, non-celiac gluten sensitivity, or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause). In conventional medical usage, the word neuropathy (neuro-, "nervous system" and -pathy, "disease of") without modifier usually means peripheral neuropathy.
Neuropathy affecting just one nerve is called "mononeuropathy" and neuropathy involving nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply "polyneuropathy". When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called "mononeuritis multiplex", "multifocal mononeuropathy", or "multiple mononeuropathy".Neuropathy may cause painful cramps, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or allodynia (pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally.

Classification
Peripheral neuropathy may be classified according to the number and distribution of nerves affected (mononeuropathy, mononeuritis multiplex, or polyneuropathy), the type of nerve fiber predominantly affected (motor, sensory, autonomic), or the process affecting the nerves; e.g., inflammation (neuritis), compression (compression neuropathy), chemotherapy (chemotherapy-induced peripheral neuropathy). The affected nerves are found in an EMG (electromyography) / NCS (nerve conduction study) test and the classification is applied upon completion of the exam.

Mononeuropathy
Mononeuropathy is a type of neuropathy that only affects a single nerve. Diagnostically, it is important to distinguish it from polyneuropathy because when a single nerve is affected, it is more likely to be due to localized trauma or infection.The most common cause of mononeuropathy is physical compression of the nerve, known as compression neuropathy. Carpal tunnel syndrome and axillary nerve palsy are examples. Direct injury to a nerve, interruption of its blood supply resulting in (ischemia), or inflammation also may cause mononeuropathy.

Polyneuropathy
"Polyneuropathy" is a pattern of nerve damage that is quite different from mononeuropathy, often more serious and affecting more areas of the body. The term "peripheral neuropathy" sometimes is used loosely to refer to polyneuropathy. In cases of polyneuropathy, many nerve cells in various parts of the body are affected, without regard to the nerve through which they pass; not all nerve cells are affected in any particular case. In distal axonopathy, one common pattern is that the cell bodies of neurons remain intact, but the axons are affected in proportion to their length; the longest axons are the most affected. Diabetic neuropathy is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin sheath around axons is damaged, which affects the ability of the axons to conduct electrical impulses. The third and least common pattern affects the cell bodies of neurons directly. This usually picks out either the motor neurons (known as motor neuron disease) or the sensory neurons (known as sensory neuronopathy or dorsal root ganglionopathy).The effect of this is to cause symptoms in more than one part of the body, often symmetrically on left and right sides. As for any neuropathy, the chief symptoms include motor symptoms such as weakness or clumsiness of movement; and sensory symptoms such as unusual or unpleasant sensations such as tingling or burning; reduced ability to feel sensations such as texture or temperature, and impaired balance when standing or walking. In many polyneuropathies, these symptoms occur first and most severely in the feet. Autonomic symptoms also may occur, such as dizziness on standing up, erectile dysfunction, and difficulty controlling urination.Polyneuropathies usually are caused by processes that affect the body as a whole. Diabetes and impaired glucose tolerance are the most common causes. Hyperglycemia-induced formation of advanced glycation end products (AGEs) is related to diabetic neuropathy. Other causes relate to the particular type of polyneuropathy, and there are many different causes of each type, including inflammatory diseases such as Lyme disease, vitamin deficiencies, blood disorders, and toxins (including alcohol and certain prescribed drugs).
Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. It is important to recognize that at one time it was thought that many of the cases of small fiber peripheral neuropathy with typical symptoms of tingling, pain, and loss of sensation in the feet and hands were due to glucose intolerance before a diagnosis of diabetes or pre-diabetes. However, in August 2015, the Mayo Clinic published a scientific study in the Journal of the Neurological Sciences showing "no significant increase in...symptoms...in the prediabetes group", and stated that "A search for alternate neuropathy causes is needed in patients with prediabetes."The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as neuropathic pain.

Mononeuritis multiplex
Mononeuritis multiplex, occasionally termed polyneuritis multiplex, is simultaneous or sequential involvement of individual noncontiguous nerve trunks, either partially or completely, evolving over days to years and typically presenting with acute or subacute loss of sensory and motor function of individual nerves. The pattern of involvement is asymmetric, however, as the disease progresses, deficit(s) becomes more confluent and symmetrical, making it difficult to differentiate from polyneuropathy. Therefore, attention to the pattern of early symptoms is important.
Mononeuritis multiplex is sometimes associated with a deep, aching pain that is worse at night and frequently in the lower back, hip, or leg. In people with diabetes mellitus, mononeuritis multiplex typically is encountered as acute, unilateral, and severe thigh pain followed by anterior muscle weakness and loss of knee reflex.Electrodiagnostic medicine studies will show multifocal sensory motor axonal neuropathy.It is caused by, or associated with, several medical conditions:

Autonomic neuropathy
Autonomic neuropathy is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system), affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a persons conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen, and pelvis outside the spinal cord. They have connections with the spinal cord and ultimately the brain, however. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most—but not all—cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.Autonomic neuropathy is one cause of malfunction of the autonomic nervous system, but not the only one; some conditions affecting the brain or spinal cord also may cause autonomic dysfunction, such as multiple system atrophy, and therefore, may cause similar symptoms to autonomic neuropathy.The signs and symptoms of autonomic neuropathy include the following:

Urinary bladder conditions: bladder incontinence or urine retention
Gastrointestinal tract: dysphagia, abdominal pain, nausea, vomiting, malabsorption, fecal incontinence, gastroparesis, diarrhoea, constipation
Cardiovascular system: disturbances of heart rate (tachycardia, bradycardia), orthostatic hypotension, inadequate increase of heart rate on exertion
Respiratory system: impairments in the signals associated with regulation of breathing and gas exchange (central sleep apnea, hypopnea, bradypnea).
Skin : thermal regulation, dryness through sweat disturbances
Other areas: hypoglycemia unawareness, genital impotence

Neuritis
Neuritis is a general term for inflammation of a nerve or the general inflammation of the peripheral nervous system. Symptoms depend on the nerves involved, but may include pain, paresthesia (pins-and-needles), paresis (weakness), hypoesthesia (numbness), anesthesia, paralysis, wasting, and disappearance of the reflexes.
Causes of neuritis include:

Signs and symptoms
Those with diseases or dysfunctions of their nerves may present with problems in any of the normal nerve functions. Symptoms vary depending on the types of nerve fiber involved. In terms of sensory function, symptoms commonly include loss of function ("negative") symptoms, including numbness, tremor, impairment of balance, and gait abnormality. Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins-and-needles. Motor symptoms include loss of function ("negative") symptoms of weakness, tiredness, muscle atrophy, and gait abnormalities; and gain of function ("positive") symptoms of cramps, and muscle twitch (fasciculations).In the most common form, length-dependent peripheral neuropathy, pain and parasthesia appears symmetrically and generally at the terminals of the longest nerves, which are in the lower legs and feet. Sensory symptoms generally develop before motor symptoms such as weakness. Length-dependent peripheral neuropathy symptoms make a slow ascent of the lower limbs, while symptoms may never appear in the upper limbs; if they do, it will be around the time that leg symptoms reach the knee. When the nerves of the autonomic nervous system are affected, symptoms may include constipation, dry mouth, difficulty urinating, and dizziness when standing.

CAP-PRI Scale for diagnosis
A user-friendly, disease-specific, quality-of-life scale can be used to monitor how someone is doing living with the burden of chronic, sensorimotor polyneuropathy. This scale, called the Chronic, Acquired Polyneuropathy - Patient-reported Index (CAP-PRI), contains only 15 items and is completed by the person affected by polyneuropathy. The total score and individual item scores can be followed over time, with item scoring used by the patient and care-provider to estimate clinical status of some of the more common life domains and symptoms impacted by polyneuropathy.

Causes
The causes are grouped broadly as follows:

Diagnosis
Peripheral neuropathy may first be considered when an individual reports symptoms of numbness, tingling, and pain in feet. After ruling out a lesion in the central nervous system as a cause, diagnosis may be made on the basis of symptoms, laboratory and additional testing, clinical history, and a detailed examination.
During physical examination, specifically a neurological examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, although those with a pathology (problem) of the nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies, such as Guillain–Barré syndrome; or may show focal sensory disturbance or weakness, such as in mononeuropathies. Classically, ankle jerk reflex is absent in peripheral neuropathy.
A physical examination will involve testing the deep ankle reflex as well as examining the feet for any ulceration. For large fiber neuropathy, an exam will usually show an abnormally decreased sensation to vibration, which is tested with a 128-Hz tuning fork, and decreased sensation of light touch when touched by a nylon monofilament.Diagnostic tests include electromyography (EMG) and nerve conduction studies (NCSs), which assess large myelinated nerve fibers. Testing for small-fiber peripheral neuropathies often relates to the autonomic nervous system function of small thinly- and unmyelinated fibers. These tests include a sweat test and a tilt table test. Diagnosis of small fiber involvement in peripheral neuropathy may also involve a skin biopsy in which a 3 mm-thick section of skin is removed from the calf by a punch biopsy, and is used to measure the skin intraepidermal nerve fiber density (IENFD), the density of nerves in the outer layer of the skin. Reduced density of the small nerves in the epidermis supports a diagnosis of small-fiber peripheral neuropathy.
In EMG testing, demyelinating neuropathy characteristically shows a reduction in conduction velocity and prolongation of distal and F-wave latencies, whereas axonal neuropathy shows a reduction in amplitude.Laboratory tests include blood tests for vitamin B-12 levels, a complete blood count, measurement of thyroid stimulating hormone levels, a comprehensive metabolic panel screening for diabetes and pre-diabetes, and a serum immunofixation test, which tests for antibodies in the blood.

Treatment
The treatment of peripheral neuropathy varies based on the cause of the condition, and treating the underlying condition can aid in the management of neuropathy. When peripheral neuropathy results from diabetes mellitus or prediabetes, blood sugar management is key to treatment. In prediabetes in particular, strict blood sugar control can significantly alter the course of neuropathy. In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with intravenous immunoglobulin or steroids. When peripheral neuropathy results from vitamin deficiencies or other disorders, those are treated as well.

Medications
A range of medications that act on the central nervous system have been used to symptomatically treat neuropathic pain. Commonly used medications include tricyclic antidepressants (such as nortriptyline, amitriptyline. imapramine, and desipramine,) serotonin-norepinephrine reuptake inhibitor (SNRI) medications (duloxetine, venlafaxine, and milnacipran) and antiepileptic medications (gabapentin, pregabalin, oxcarbazepine zonisamide levetiracetam, lamotrigine, topiramate, clonazepam, phenytoin, lacosamide, sodium valproate and carbamazepine). Opioid and opiate medications (such as buprenorphine, morphine, methadone, fentanyl, hydromorphone, tramadol and oxycodone) are also often used to treat neuropathic pain.
As is revealed in many of the Cochrane systematic reviews listed below, studies of these medications for the treatment of neuropathic pain are often methodologically flawed and the evidence is potentially subject to major bias. In general, the evidence does not support the usage of antiepileptic and antidepressant medications for the treatment of neuropathic pain. Better designed clinical trials and further review from non-biased third parties are necessary to gauge just how useful for patients these medications truly are. Reviews of these systematic reviews are also necessary to assess for their failings.
It is also often the case that the aforementioned medications are prescribed for neuropathic pain conditions for which they had not been explicitly tested on or for which controlled research is severely lacking; or even for which evidence suggests that these medications are not effective. The NHS for example explicitly state that amitriptyline and gabapentin can be used for treating the pain of sciatica. This is despite both the lack of high quality evidence that demonstrates efficacy of these medications for that symptom, and also the prominence of generally moderate to high quality evidence that reveals that antiepileptics in specific, including gabapentin, demonstrate no efficacy in treating it.

Antidepressants
In general, according to Cochranes systematic reviews, antidepressants have shown to either be ineffective for the treatment of neuropathic pain or the evidence available is inconclusive. Evidence also tends to be tainted by bias or issues with the methodology.Cochrane systematically reviewed the evidence for the antidepressants nortriptyline, desipramine, venlafaxine and milnacipran and in all these cases found scant evidence to support their use for the treatment of neuropathic pain. All reviews were done between 2014 and 2015.A 2015 Cochrane systematic review of amitriptyline found that there was no evidence supporting the use of amitriptyline that did not possess inherent bias. The authors believe amitriptyline may have an effect in some patients but that the effect is overestimated. A 2014 Cochrane systematic review of imipramine notes that the evidence suggesting benefit were "methodologically flawed and potentially subject to major bias."A 2017 Cochrane systematic review assessed the benefit of antidepressant medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents and the authors found the evidence inconclusive.

Antiepileptics
A 2017 Cochrane systematic review found that daily dosages between (1800 - 3600) mg of gabapentin could provide good pain relief for pain associated with diabetic neuropathy only. This relief occurred for roughly (30 - 40)% of treated patients, while placebo had a (10 - 20)% response. Three of the seven authors of the review had conflicts of interest declared. In a 2019 Cochrane review of pregabalin the authors conclude that there is some evidence of efficacy in the treatment of pain deriving from post-herpetic neuralgia, diabetic neuropathy and post-traumatic neuropathic pain only. They also warned that many patients treated will have no benefit. Two of the five authors declared receiving payments from pharmaceutical companies.A 2017 Cochrane systematic review found that oxcarbazepine had little evidence to support its use for treating diabetic neuropathy, radicular pain and other neuropathies. The authors also call for better studies. In a 2015 Cochrane systematic review the authors found a lack of evidence showing any effectiveness of zonisamide for the treatment of pain deriving from any peripheral neuropathy. A 2014 Cochrane review found that studies of levetiracetam showed no indication for its effectiveness at treating pain from any neuropathy. The authors also found that the evidence was possibly biased and that some patients experienced adverse events.A 2013 Cochrane systematic review concluded that there was high quality evidence to suggest that lamotrigine is not effective for treating neuropathic pain, even at high dosages (200 - 400) mg. A 2013 Cochrane systematic review of topimirate found that the included data had a strong likelihood of major bias; despite this, it found no effectiveness for the drug in treating the pain associated with diabetic neuropathy. It had not been tested for any other type of neuropathy. Cochrane reviews from 2012 of clonazepam and phenytoin uncovered no evidence of sufficient quality to support their use in chronic neuropathic pain."A 2012 Cochrane systematic review of lacosamide found it very likely that the drug is ineffective for treating neuropathic pain. The authors caution against positive interpretations of the evidence. For sodium valproate the authors of a 2011 Cochrane review found that "three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy". They discuss how there is a probable overestimate of effect due to the inherent problems with the data and conclude that the evidence does not support its usage. In a 2014 systematic review of carbamazepine the authors believe the drug to be of benefit for some people. No trials were considered greater than level III evidence; none were longer than 4 weeks in length or were deemed as having good reporting quality.A 2017 Cochrane systematic review aiming to assess the benefit of antiepileptic medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents found the evidence inconclusive. Two of the ten authors of this study declared receiving payments from pharmaceutical companies.

Opioids
A Cochrane review of buprenorphine, fentanyl, hydromorphone and morphine, all dated between 2015 and 2017, and all for the treatment of neuropathic pain, found that there was insufficient evidence to comment on their efficacy. Conflicts of interest were declared by the authors in this review. A 2017 Cochrane review of methadone found very low quality evidence, three studies of limited quality, of its efficacy and safety. They could not formulate any conclusions about its relative efficacy and safety compared to a placebo.For tramadol, Cochrane found that there was only modest information about the benefits of its usage for neuropathic pain. Studies were small, had potential risks of bias and apparent benefits increased with risk of bias. Overall the evidence was of low or very low quality and the authors state that it "does not provide a reliable indication of the likely effect". For oxycodone the authors found very low quality evidence showing its usefulness in treating diabetic neuropathy and postherpetic neuralgia only. One of the four authors declared receiving payments from pharmaceutical companies.More generally, a 2013 review examining the overall efficacy of opioid therapy for the treatment of neuropathic pain found studies were often subject to bias and that their efficacy and safety was not deducible with the evidence available. A 2017 Cochrane review examining opioid therapy as a treatment for many non-cancer pain syndromes (including neuropathic pain) concluded, "There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents."

Others
A 2016 Cochrane review of paracetamol for the treatment of neuropathic pain concluded that its benefit alone or in combination with codeine or dihydrocodeine is unknown.Few studies have examined whether nonsteroidal anti-inflammatory drugs are effective in treating peripheral neuropathy.There is some evidence that symptomatic relief from the pain of peripheral neuropathy may be obtained by application of topical capsaicin. Capsaicin is the factor that causes heat in chili peppers. However, the evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option.Evidence supports the use of cannabinoids for some forms of neuropathic pain. A 2018 Cochrane review of cannabis-based medicines for the treatment of chronic neuropathic pain included 16 studies. All of these studies included THC as a pharmacological component of the test group. The authors rated the quality of evidence as very low to moderate. The primary outcome was quoted as, "Cannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo" but "the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality". The authors also conclude, "The potential benefits of cannabis-based medicine... might be outweighed by their potential harms."A 2014 Cochrane review of topical lidocaine for the treatment of various peripheral neuropathies found its usage supported by a few low quality studies. The authors state that there are no high quality randomised control trials demonstrating its efficacy or safety profile.A 2015 (updated in 2022) Cochrane review of topical clonidine for the treatment of diabetic neuropathy included two studies of 8 and 12 weeks in length; both of which compared topical clonidine to placebo and both of which were funded by the same drug manufacturer. The review found that topical clonidine may provide some benefit versus placebo. However, the authors state that the included trials are potentially subject to significant bias and that the evidence is of low to moderate quality.A 2007 Cochrane review of aldose reductase inhibitors for the treatment of the pain deriving from diabetic polyneuropathy found it no better than placebo.

Medical devices
Transcutaneous electrical nerve stimulation (TENS) therapy is often used to treat various types of neuropathy. A 2010 review of three trials, for the treatment of diabetic neuropathy explicitly, involving a total of 78 patients found some improvement in pain scores after 4 and 6, but not 12 weeks of treatment and an overall improvement in neuropathic symptoms at 12 weeks </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Calciphylaxis and can you explain it in depth? [/INST] Calciphylaxis, also known as calcific uremic arteriolopathy (CUA) or “Grey Scale”, is a rare syndrome characterized by painful skin lesions. The pathogenesis of calciphylaxis is unclear but believed to involve calcification of the small blood vessels located within the fatty tissue and deeper layers of the skin, blood clots, and eventual death of skin cells due to lack of blood flow. It is seen mostly in people with end-stage kidney disease but can occur in the earlier stages of chronic kidney disease and rarely in people with normally functioning kidneys. Calciphylaxis is a rare but serious disease, believed to affect 1-4% of all dialysis patients. It results in chronic non-healing wounds and indicates poor prognosis, with typical life expectancy of less than one year.Calciphylaxis is one type of extraskeletal calcification. Similar extraskeletal calcifications are observed in some people with high levels of calcium in the blood, including people with milk-alkali syndrome, sarcoidosis, primary hyperparathyroidism, and hypervitaminosis D. In rare cases, certain medications such as warfarin can also result in calciphylaxis.

Signs and symptoms
The first skin changes in calciphylaxis lesions are mottling of the skin and induration in a livedo reticularis pattern. As tissue thrombosis and infarction occurs, a black, leathery eschar in an ulcer with adherent black slough develops. Surrounding the ulcers is usually a plate-like area of indurated skin. These lesions are always extremely painful and most often occur on the lower extremities, abdomen, buttocks, and penis. Lesions are also commonly multiple and bilateral. Because the tissue has infarcted, wound healing seldom occurs, and ulcers are more likely to become secondarily infected. Many cases of calciphylaxis lead to systemic bacterial infection and death.Calciphylaxis is characterized by the following histologic findings:

systemic medial calcification of the arteries, i.e. calcification of tunica media. Unlike other forms of vascular calcifications (e.g., intimal, medial, valvular), calciphylaxis is characterized also by
small vessel mural calcification with or without endovascular fibrosis, extravascular calcification and vascular thrombosis, leading to tissue ischemia (including skin ischemia and, hence, skin necrosis).

Heart of stone
Severe forms of calciphylaxis may cause diastolic heart failure from cardiac calcification, called  heart of stone. Widespread intravascular calcification typical of calciphylaxis lesions occur in the myocardium and prevent normal diastolic filling of the ventricles.

Cause
The cause of calciphylaxis is unknown. Calciphylaxis is not a hypersensitivity reaction (i.e., allergic reaction) leading to sudden local calcification. The disease is also known as calcific uremic arteriolopathy; however, the disease is not limited to patients with kidney failure. The current belief is that in end-stage kidney disease, abnormal calcium and phosphate homeostasis result in the deposition of calcium in the vessels, also known as metastatic calcification. Once the calcium has been deposited, a thrombotic event occurs within the lumen of these vessels, resulting in occlusion of the vessel and subsequent tissue infarction. Specific triggers for either thrombotic or ischemic events are unknown. Adipocytes have been shown to calcify vascular smooth muscle cells when exposed to high phosphate levels in vitro, mediated by vascular endothelial growth factor A (VEGF-A) and leptin released by adipocytes. Given that calciphylaxis tends to affect adipose tissue, this may be a contributing explanation. Another theory has been proposed that vitamin K deficiency contributes to the development of calciphylaxis. Vitamin K acts as an inhibitor of calcification in vessel walls by activating matrix Gla protein (MGP), which in turn inhibits calcification. End-stage kidney disease patients are more likely to have vitamin K deficiency due to dietary restrictions meant to limit potassium and sodium. Many end-stage kidney disease patients are also on a medication called warfarin, a vitamin K antagonist, that limits vitamin K recycling in the body.Reported risk factors include female sex, obesity, elevated calcium-phosphate product, medications such as warfarin, vitamin D derivatives (e.g. calcitriol, calcium-based binders, or systemic steroids), protein C or S deficiency, low blood albumin levels, and diabetes mellitus. Patients who require or have undergone any type of vascular procedures are also at increased risk for poor outcomes.

Diagnosis
There is no diagnostic test for calciphylaxis. The diagnosis is a clinical one. The characteristic lesions are the ischemic skin lesions (usually with areas of skin necrosis). The necrotic skin lesions (i.e. the dying or already dead skin areas) typically appear as violaceous (dark bluish purple) lesions and/or completely black leathery lesions. They can be extensive and found in multiples. The suspected diagnosis can be supported by a skin biopsy, usually a punch biopsy, which shows arterial calcification and occlusion in the absence of vasculitis. Excisional biopsy should not be done due to increased risk of further ulceration and necrosis. Bone scintigraphy can be performed in cases where skin biopsy is contraindicated. Results of the study show increased tracer accumulation in the soft tissues.  In certain patients, an anti-nuclear antibody test may play a role in diagnosis of calciphylaxis. Plain radiography and mammography may also show calcifications but these tests are less sensitive. Laboratory studies, such as phosphate levels, calcium levels, and parathyroid levels, are nonspecific and unhelpful for diagnosis of calciphylaxis.

Treatment
The treatment of calciphylaxis requires a multidisciplinary approach, using the knowledge of nephrologists, plastic surgeons, dermatologists, and wound care specialists working together to manage the disease and its outcomes. The key to treating calciphylaxis is prevention via rigorous control of phosphate and calcium balance and management of risk factors in patients who have increased chances of developing calciphylaxis. There is no specific treatment. Most treatment recommendations lack significant data, and none are internationally recognized as the standard of care. It is generally accepted to apply a multi-pronged approach to each patient.

Analgesia and wound management
Pain management and choice of analgesia is a challenging task in managing calciphylaxis. Pain is one of the most severe and pervasive symptoms of the disease and can be unresponsive to high-dose opioids. Fentanyl and methadone are preferred analgesics over morphine, since morphine breakdown produces active metabolites that accumulate in the body of patients with kidney failure. Adjunct medications such as gabapentin and ketamine may also be used for analgesia. In refractory cases, spinal anesthetics (nerve blocks) can be used for more comprehensive pain relief.
Wound care for calciphylaxis lesions involves using appropriate dressings, wound debridement (removal of dead tissue), and prevention of infection. Wound infections lead to sepsis, which is one of the leading causes of death in patients with calciphylaxis. Surgical wound debridement carries increased risk for infection, so it should only be considered as therapy if the survival benefit outweighs the chances of continued wound non-healing and pain.Hyperbaric oxygen therapy may also be considered. There are some smaller retrospective studies that show the use of hyperbaric oxygen in improving delivery of oxygen to wounds, which improves blood flow and helps with wound healing.

Risk factor mitigation
Most patients with calciphylaxis are already on hemodialysis, or simply dialysis, but the length or frequency of sessions may be increased. The majority of dialysis patients are on a 4-hour three times per week schedule. Indications for increasing dialysis session length or frequency include electrolyte and mineral abnormalities, such as hyperphophatemia, hypercalcemia, and hyperparathyroidism, all of which are also risk factors for development of calciphylaxis. Peritoneal dialysis patients should also transition to hemodialysis, as only hemodialysis carries the added benefit of better phosphate and calcium control. Surgical parathyroidectomy is also recommended for those who have difficulty managing phosphate and calcium level balance. However, risks include development of post-operative hungry bone syndrome (HBS), a disease state that causes low calcium and requires use of calcium supplementation and calcitriol, which should be avoided in patients with end-stage kidney disease and calciphylaxis.

Pharmacotherapy
Sodium thiosulfate is commonly prescribed for treatment in patients with calciphylaxis. The actual mechanism of the drug is unknown, but several theories have been proposed, including chelation of calcium, vasodilation, antioxidant properties, and restoration of endothelial function. Adverse effects of sodium thiosulfate include high anion gap metabolic acidosis and high sodium levels (hypernatremia).
Bisphosphonates are a popular choice for the treatment of osteoporosis, but they have also been used to treat calciphylaxis even though the exact mechanism in calciphylaxis is unknown. They are most beneficial in patients who have a genetic ENPP1 deficiency and have been shown to slow development of calciphylaxis lesions in a small prospective study.
Cinacalcet (medical parathyroidectomy) is an oral medication that can be used to suppress the parathyroid glands for patients who may not be able to undergo surgical parathyroidectomy. Vitamin K supplementation has also been shown to slow development of calcification in coronary arteries and the aortic valve in older patients. The ability for vitamin K supplementation to slow calcification of blood vessels in calciphylaxis is not well studied. Warfarin, a vitamin K antagonist discussed above, should be discontinued if possible.Other acceptable treatments may include one or more of the following:

Clot-dissolving agents (tissue plasminogen activator)
Maggot larval debridement
Correction of the underlying plasma calcium and phosphorus abnormalities (lowering the Ca x P product below 55 mg2/dL2)
Avoiding further local tissue trauma (including avoiding all subcutaneous injections, and all not-absolutely-necessary infusions and transfusions)
Patients who receive kidney transplants also receive immunosuppression. Considering lowering the dose of or discontinuing the use of immunosuppressive drugs in people who have received kidney transplants and continue to have persistent or progressive calciphylactic skin lesions can contribute to an acceptable treatment of calciphylaxis.
A group has reported plasma exchange effective and propose a serum marker and perhaps mediator (calciprotein particles)

Prognosis
Overall, the clinical prognosis for calciphylaxis is poor. The 1-year mortality rate in patients who have end-stage kidney disease is 45-80%. Median survival in patients who do not have end-stage kidney disease is 4.2 months. Response to treatment is not guaranteed. The most common cause of death in calciphylaxis patients is sepsis, severe infection originating from a non-healing ulcer.

Epidemiology
Calciphylaxis most commonly occurs in patients with end-stage renal disease who are on hemodialysis or who have recently received a kidney transplant. When reported in patients without end-stage renal disease (such as in earlier stages of chronic kidney disease or in normal kidney function), it is called non-uremic calciphylaxis by Nigwekar et al. Non-uremic calciphylaxis has been observed in patients with primary hyperparathyroidism, breast cancer (treated with chemotherapy), liver cirrhosis (due to hazardous alcohol use), cholangiocarcinoma, Crohns disease, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Calciphylaxis, regardless of etiology, has been reported at an incidence of 35 in 10,000 dialysis patients per year in the United States, 4 in 10,000 patients in Germany, and less than 1 in 10,000 patients in Japan. It is unknown whether the higher incidence in the United States is due to genuinely higher incidence or due to underreporting in other countries. Annual incidence in kidney transplant patients and in non-uremic calciphylaxis patients is also unknown. The median age of patients at diagnosis of calciphylaxis is 60 years and the majority of these patients are women (60-70%). The location of lesions, central (located on the trunk) or peripheral (located on the extremities), is dependent on several risk factors. Central lesions are associated with younger patients, patients with a higher body mass index, and a higher risk of death than those who have peripheral-only lesions.

References
Further reading
Weenig RH (2008). "Pathogenesis of calciphylaxis: Hans Selye to nuclear factor kappa-B". J. Am. Acad. Dermatol. 58 (3): 458–71. doi:10.1016/j.jaad.2007.12.006. PMID 18206262.
Weenig RH, Sewell LD, Davis MD, McCarthy JT, Pittelkow MR (2007). "Calciphylaxis: natural history, risk factor analysis, and outcome". J. Am. Acad. Dermatol. 56 (4): 569–79. doi:10.1016/j.jaad.2006.08.065 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hair bleaching and can you explain it in depth? [/INST] Hair bleaching, is the practice of lightening the hair color mainly for cosmetic purposes using bleaching agents. Bleaching can be done alone, combined with a toner, or as a step for further hair coloring. The most common commercial bleaching agents in use are hydrogen peroxide and persulfate salts, but historically other agents such as sulfuric acid, wood ash, lye and hypochlorite bleach were used. Hair can also become bleached unintentionally, such as through sun exposure.

History
During the early years of the Roman Empire, blond hair was associated with prostitutes. The preference changed to bleaching the hair blond when Greek culture, which practiced bleaching, reached Rome, and was reinforced when the legions that conquered Gaul returned with blond slaves. Sherrow also states that Roman women tried to lighten their hair, but the substances often caused hair loss, so they resorted to wigs made from the captives hair. The bleaching agent used by the Roman women was composed of a solution of ashes from burnt nuts or plants.Diodorus Siculus, a 1st century BC Greek historian, described in detail how Celtic people bleached their hair: "Their aspect is terrifying... They are very tall in stature, with rippling muscles under clear white skin. Their hair is blond, but not naturally so: they bleach it, to this day, artificially, washing it in lime and combing it back from their foreheads. They look like wood-demons, their hair thick and shaggy like a horses mane. Some of them are clean-shaven, but others—especially those of high rank—shave their cheeks but leave a moustache that covers the whole mouth...".During the medieval period, Spanish women preferred to dye their hair black, yet by the time of the Renaissance in the 16th century the fashion (imported from Italy) was to bleach their hair blond or dye it red. Between the Renaissance and the Enlightenment, a number of dangerous hair bleaching methods remained widely practiced, including the use of sulfuric acid, which was an accepted form of hair coloring around the 1600s, and laying out in the sun with hair covered in lye a century later.In Sir Hugh Plats 1602 work Delightes for Ladies the use of oil of vitriol (sulfuric acid) to bleach black hair to chestnut is described as: "Take one part of lead calcined with Sulphur, and one part of quicklime: temper them somewhat thin with water: lay it upon the hair, chafing it well in, and let it dry one quarter of an hour or thereasbouts; the wash the same off with fair water divers times: and lastly with sope and water, and it will be a very natural hair-colour. The longer it lyeth upon the haire, the browner it groweth, This coloureth not the flesh at all, and yet it lasteth very long in the hair."

Modern history
Howard Hughes 1931 movie Platinum Blonde starring Jean Harlow is noted to have popularized platinum blonde hair color in the US. After the movies success Hughess team established a  chain of "Platinum Blonde clubs" in several cities and offered a $10,000 prize that would go to any hairdresser who could copy Harlows shade. Though Harlow denied her hair was bleached, the platinum blonde color was reportedly achieved with a weekly application of ammonia, Clorox bleach, and Lux soap flakes. This process weakened and damaged Harlows naturally ash-blonde hair.During the 1930s Lawrence M. Gelb advanced the formulas of the bleaching products. In 1950 Clairol, the company Gelb founded with wife Jane Clair, introduced the first one-step hair dye product that lightened hair, which became a huge success with the masses.

Bleaching process
Using bleaching agents
Melanin pigments, which give hair a darker color, can be broken down with oxidation. Most commercial bleaching formulas contain hydrogen peroxide and persulfate salts, which under alkaline conditions created by ammonia or monoethanolamine can bleach the hair. Persulfate salts, in combination with hydrogen peroxide or alone, is known for its ability to degrade organics, after activation with heat, transition metals, ultraviolet light, or other means that produce the sulfate radical. Without activation, the persulfate anion is known to react with some organic chemicals, although with slow kinetics. When melanin is oxidized, oxygen gas is released. Products for bleaching ones hair at home usually contain a 6% solution of hydrogen peroxide, while products for use in a hair salon can contain up to 9%. Hair bleaching products can damage hair and cause severe burns to the scalp when applied incorrectly or left on too long.Industrial bleaches that work by reduction (such as sodium hydrosulphite) react with a chromophore, the part of the molecule responsible for its color and decrease the number of carbon-oxygen bonds in it, making it uncoloured. This process might be reversed to a certain extent by oxygen in the air, such as yellowing of bleached paper if kept exposed to air. In contrast hydrogen peroxide chemically alters the chromophore so that it increases the number of carbon-oxygen bonds. Due to the relative absence of reducing agents in the environment, chromophores cannot restore themselves as seen in reduction-based bleaches.Bleaching the hair is a gradual process and different colors could be achieved dependent on the original hair color, application time, and strength of the product used. Applied on black hair, the hair will change its color to brown, red, orange, orange-yellow, yellow, and finally pale yellow.

Toner
Toning is a common practice after bleaching to mask the undesirable red and orange tones of "brassy" hair using a toner dye. Through toning, the yellow hue of fully bleached hair can be removed to achieve platinum blond hair. The appropriate color of the toner depends on the color of the bleached hair; e.g. to remove the yellow tones a violet toner dye will be needed, but to neutralize red and orange hues a green and blue toner would be more suitable </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Malabsorption and can you explain it in depth? [/INST] Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.Normally the human gastrointestinal tract digests and absorbs dietary nutrients with remarkable efficiency. A typical Western diet ingested by an adult in one day includes approximately 100 g of fat, 400 g of carbohydrate, 100 g of protein, 2 L of fluid, and the required sodium, potassium, chloride, calcium, vitamins, and other elements. Salivary, gastric, intestinal, hepatic, and pancreatic secretions add an additional 7–8 L of protein-, lipid-, and electrolyte-containing fluid to intestinal contents. This massive load is reduced by the small and large intestines to less than 200 g of stool that contains less than 8 g of fat, 1–2 g of nitrogen, and less than 20 mmol each of Na+, K+, Cl–, HCO3–, Ca2+, or Mg2+.
If there is impairment of any of the many steps involved in the complex process of nutrient digestion and absorption, intestinal malabsorption may ensue. If the abnormality involves a single step in the absorptive process, as in primary lactase deficiency, or if the disease process is limited to the very proximal small intestine, then selective malabsorption of only a single nutrient may occur. However, generalized malabsorption of multiple dietary nutrients develops when the disease process is extensive, thus disturbing several digestive and absorptive processes, as occurs in coeliac disease with extensive involvement of the small intestine.

Signs and symptoms
Gastrointestinal manifestations
Depending on the nature of the disease process causing malabsorption and its extent, gastrointestinal symptoms may range from severe to subtle or may even be totally absent. Diarrhea, weight loss, flatulence, abdominal bloating, abdominal cramps, and pain may be present. Although diarrhea is a common complaint, the character and frequency of stools may vary considerably ranging from over 10 watery stools per day to less than one voluminous putty-like stool, the latter causing some patients to complain of constipation. On the other hand, stool mass is invariably increased in patients with steatorrhea and generalized malabsorption above the normal with 150–200 g/day. Not only do unabsorbed nutrients contribute to stool mass but mucosal fluid and electrolyte secretion is also increased in diseases associated with mucosal inflammation such as coeliac disease. In addition, unabsorbed fatty acids, converted to hydroxy-fatty acids by colonic flora, as well as unabsorbed bile acids both impair absorption and induce secretion of water and electrolytes by the colon adding to stool mass. Weight loss is common among patients with significant intestinal malabsorption but must be evaluated in the context of caloric intake. Some patients compensate for fecal wastage of unabsorbed nutrients by significantly increasing their oral intake. Eliciting a careful dietary history from patients with suspected malabsorption is therefore crucial. Excessive flatus and abdominal bloating may reflect excessive gas production due to fermentation of unabsorbed carbohydrate, especially among patients with a primary or secondary disaccharidase deficiency, such as lactose intolerance or sucrose intolerance. Malabsorption of dietary nutrients and excessive fluid secretion by inflamed small intestine also contribute to abdominal distention and bloating. Prevalence, severity, and character of abdominal pain vary considerably among the various disease processes associated with intestinal malabsorption. For example, pain is common in patients with chronic pancreatitis or pancreatic cancer and Crohns disease, but it is absent in many patients with coeliac disease or postgastrectomy malabsorption.

Extraintestinal manifestations
Substantial numbers of patients with intestinal malabsorption present initially with symptoms or laboratory abnormalities that point to other organ systems in the absence of or overshadowing symptoms referable to the gastrointestinal tract. For example, there is increasing epidemiologic evidence that more patients with coeliac disease present with anemia and osteopenia in the absence of significant classic gastrointestinal symptoms. Microcytic, macrocytic, or dimorphic anemia may reflect impaired iron, folate, or vitamin B12 absorption. Purpura, subconjunctival hemorrhage, or even frank bleeding may reflect hypoprothrombinemia secondary to vitamin K malabsorption. Osteopenia is common, especially in the presence of steatorrhea. Impaired calcium and vitamin D absorption and chelation of calcium by unabsorbed fatty acids resulting in fecal loss of calcium may all contribute. If calcium deficiency is prolonged, secondary hyperparathyroidism may develop. Prolonged malnutrition may induce amenorrhea, infertility, and impotence. Edema and even ascites may reflect hypoproteinemia associated with protein losing enteropathy caused by lymphatic obstruction or extensive mucosal inflammation. Dermatitis and peripheral neuropathy may be caused by malabsorption of specific vitamins or micronutrients and essential fatty acids.

Presentation
Symptoms can manifest in a variety of ways and features might give a clue to the underlying condition. Symptoms can be intestinal or extra-intestinal - the former predominates in severe malabsorption.
Diarrhoea, often steatorrhoea, is the most common feature.  Watery, diurnal and nocturnal, bulky, frequent stools are the clinical hallmark of overt malabsorption.  It is due to impaired water, carbohydrate and electrolyte absorption or irritation from unabsorbed fatty acid. The latter also results in bloating, flatulence and abdominal discomfort.  Cramping pain usually suggests obstructive intestinal segment e.g. in Crohns disease, especially if it persists after defecation.
Weight loss can be significant despite increased oral intake of nutrients.
Growth retardation, failure to thrive, delayed puberty in children
Swelling or oedema from loss of protein
Anaemias, commonly from vitamin B12, folic acid and iron deficiency presenting as fatigue and weakness.
Decreased mental abilities, poor reflexes, and abnormal sensations due to vitamin B12 deficiency.
Muscle cramp from decreased vitamin D, calcium absorption. Also lead to osteomalacia and osteoporosis
Bleeding tendencies from vitamin K and other coagulation factor deficiencies.

Causes
Pathophysiology
The main purpose of the gastrointestinal tract is to digest and absorb nutrients (fat, carbohydrate, protein, micronutrients (vitamins and trace minerals), water, and electrolytes. Digestion involves both mechanical and enzymatic breakdown of food. Mechanical processes include chewing, gastric churning, and the to-and-fro mixing in the small intestine. Enzymatic hydrolysis is initiated by intraluminal processes requiring gastric, pancreatic, and biliary secretions. The final products of digestion are absorbed through the intestinal epithelial cells.Malabsorption constitutes the pathological interference with the normal physiological sequence of digestion (intraluminal process), absorption (mucosal process) and transport (postmucosal events) of nutrients.Intestinal malabsorption can be due to:
Congenital or acquired reduction in absorptive surface
Defects of ion transport
Defects of specific hydrolysis
Impaired enterohepatic circulation
Mucosal damage (enteropathy)
Pancreatic insufficiency

Diagnosis
There is no single, specific test for malabsorption. As for most medical conditions, investigation is guided by symptoms and signs. A range of different conditions can produce malabsorption and it is necessary to look for each of these specifically. Many tests have been advocated, and some, such as tests for pancreatic function are complex, vary between centers and have not been widely adopted. However, better tests have become available with greater ease of use, better sensitivity and specificity for the causative conditions. Tests are also needed to detect the systemic effects of deficiency of the malabsorbed nutrients (such as anaemia with vitamin B12 malabsorption).

Classification
Some prefer to classify malabsorption clinically into three basic categories:
selective, as seen in lactose malabsorption.
partial, as observed in abetalipoproteinaemia.
total, as in exceptional cases of coeliac disease.

Blood tests
Routine blood tests may reveal anaemia, high CRP or low albumin; which shows a high correlation for the presence of an organic disease. In this setting, microcytic anaemia usually implies iron deficiency and macrocytosis can be caused by impaired folic acid or B12 absorption or both. Low cholesterol or triglyceride may give a clue toward fat malabsorption. Low calcium and phosphate may give a clue toward osteomalacia from low vitamin D.
Specific vitamins like vitamin D or micronutrient like zinc levels can be checked </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Urinary cast and can you explain it in depth? [/INST] Urinary casts are microscopic cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, where they can be detected by microscopy.
They form via precipitation of Tamm–Horsfall mucoprotein which is secreted by renal tubule cells, and sometimes also by albumin in conditions of proteinuria. Cast formation is pronounced in environments favoring protein denaturation and precipitation (low flow, concentrated salts, low pH). Tamm–Horsfall protein is particularly susceptible to precipitation in these conditions.
Casts were first described by Henry Bence Jones (1813–1873).As reflected in their cylindrical form, casts are generated in the small distal convoluted tubules and collecting ducts of the kidney, and generally maintain their shape and composition as they pass through the urinary system. Although the most common forms are benign, others indicate disease. All rely on the inclusion or adhesion of various elements on a mucoprotein base—the hyaline cast. "Cast" itself merely describes the shape, so an adjective is added to describe the composition of the cast. Various casts found in urine sediment may be classified as follows.

Overview table
Main types of urinary casts:

Acellular casts
Hyaline casts
The most common type of cast, hyaline casts are solidified Tamm–Horsfall mucoprotein secreted from the tubular epithelial cells of individual nephrons. Low urine flow, concentrated urine, or an acidic environment can contribute to the formation of hyaline casts, and as such, they may be seen in normal individuals in dehydration or vigorous exercise. Hyaline casts are cylindrical and clear, with a low refractive index, so they can easily be missed on cursory review under brightfield microscopy, or in an aged sample where dissolution has occurred whereas, on the other hand, phase contrast microscopy leads to easier identification. Given the ubiquitous presence of Tamm–Horsfall protein, other cast types are formed via the inclusion or adhesion of other elements to the hyaline base.

Granular casts
The second-most common type of cast, granular casts can result either from the breakdown of cellular casts or the inclusion of aggregates of plasma proteins (e.g., albumin) or immunoglobulin light chains. Depending on the size of inclusions, they can be classified as fine or coarse, though the distinction has no diagnostic significance. Their appearance is generally more cigar-shaped and of a higher refractive index than hyaline casts. While most often indicative of chronic renal disease, these casts, as with hyaline casts, can also be seen for a short time following strenuous exercise. The "muddy brown cast" seen in acute tubular necrosis is a type of granular cast.

Waxy casts
Thought to represent the end product of cast evolution, waxy casts suggest the very low urine flow associated with severe, longstanding kidney disease such as kidney failure. Additionally, due to urine stasis and their formation in diseased, dilated ducts, these casts are significantly larger than hyaline casts.

They are cylindrical.
They possess a higher refractive index.
They are more rigid, demonstrating sharp edges, fractures, and broken-off ends.Waxy casts are broad casts, which is a more general term to describe the wider cast product of a dilated duct. It is seen in chronic kidney failure.
In nephrotic syndrome many additional types of cast exist including broad and waxy casts if the condition is chronic (this is referred to as a telescopic urine with the presence of many casts).

Fatty casts
Formed by the breakdown of lipid-rich epithelial cells, these are hyaline casts with fat globule inclusions, yellowish-tan in color. If cholesterol or cholesterol esters are present, they are associated with the "Maltese cross" sign under polarized light. They are pathognomonic for high urinary protein nephrotic syndrome.

Pigment casts
Formed by the adhesion of metabolic breakdown products or drug pigments, these casts are so named due to their discoloration. Pigments include those produced endogenously, such as hemoglobin in hemolytic anemia, myoglobin in rhabdomyolysis, and bilirubin in liver disease. Drug pigments, such as phenazopyridine, may also cause cast discoloration.

Crystal casts
Though crystallized urinary solutes, such as oxalates, urates, or sulfonamides, may become enmeshed within a ketanaline cast during its formation, the clinical significance of this occurrence is not felt to be great.

Cellular casts
Red blood cell casts
The presence of red blood cells within the cast is always pathological and is strongly indicative of granulomatosis with polyangiitis, systemic lupus erythematosus, post-streptococcal glomerulonephritis, or Goodpastures syndrome. They can also be associated with renal infarction and subacute bacterial endocarditis. They are a yellowish-brown color and are generally cylindrical with sometimes ragged edges; their fragility makes inspection of a fresh sample necessary. They are usually associated with nephritic syndromes or urinary tract injury.

White blood cell casts
Indicative of inflammation or infection, the presence of white blood cells within or upon casts strongly suggests pyelonephritis, a direct infection of the kidney. They may also be seen in inflammatory states, such as acute allergic interstitial nephritis, nephrotic syndrome, or post-streptococcal acute glomerulonephritis. White cells sometimes can be difficult to discern from epithelial cells and may require special staining </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Stupor and can you explain it in depth? [/INST] Stupor is the lack of critical mental function and a level of consciousness, in which an affected person is almost entirely unresponsive and responds only to intense stimuli such as pain. The word derives from the Latin stupor ("numbness, insensibility").

Signs and symptoms
Stupor is characterised by impaired reaction to external stimuli. Those in a stuporous state are rigid, mute and only appear to be conscious, as the eyes are open and follow surrounding objects. If not stimulated externally, a patient with stupor will appear to be in a sleepy state most of the time. In some extreme cases of severe depressive disorders the patient can become motionless, lose their appetite and become mute. Short periods of restricted responsivity can be achieved by intense stimulation (e.g </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Catatonia and can you explain it in depth? [/INST] Catatonia is a complex neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal. The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during episodes. There are several subtypes of catatonia: akinetic catatonia, excited catatonia, malignant catatonia, delirious mania, and self-injurious behaviors in autism.Although catatonia has historically been related to schizophrenia (catatonic schizophrenia), catatonia is most often seen in mood disorders. It is now known that catatonic symptoms are nonspecific and may be observed in other mental, neurological, and medical conditions. Catatonia is not a stand-alone diagnosis (although some experts disagree), and the term is used to describe a feature of the underlying disorder.Recognizing and treating catatonia is very important as failure to do so can lead to poor outcomes and can be potentially fatal. Treatment with benzodiazepines or ECT can lead to remission of catatonia. There is growing evidence of the effectiveness of the NMDA receptor antagonists amantadine and memantine for benzodiazepine-resistant catatonia. Antipsychotics are sometimes employed, but they can worsen symptoms and have serious adverse effects.

Signs and symptoms
The presentation of a patient with catatonia varies greatly depending on the subtype, underlying cause and it can be acute or subtle.Because most patients with catatonia have an underlying psychiatric illness, the majority will present with worsening depression, mania, or psychosis followed by catatonia symptoms. Catatonia presents as a motor disturbance in which patients will display marked reduction in movement, marked agitation, or a mixture of both despite having the physical capacity to move normally. These patients may be unable to start an action or stop one. Movements and mannerisms may be repetitive, or purposeless.The most common signs of catatonia are immobility, mutism, withdrawal and refusal to eat, staring, negativism, posturing (rigidity), rigidity, waxy flexibility/catalepsy, stereotypy (purposeless, repetitive movements), echolalia or echopraxia, verbigeration (repeat meaningless phrases). It should not be assumed that patients presenting with catatonia are unaware of their surroundings as some patients can recall in detail their catatonic state and their actions.There are several subtypes of catatonia and they are characterized by the specific movement disturbance and associated features. Although catatonia can be divided into various subtypes, the natural history of catatonia is often fluctuant and different states can exist within the same individual.

Subtypes
Withdrawn Catatonia: This form of catatonia is characterized by decreased response to external stimuli, immobility or inhibited movement, mutism, staring, posturing, and negativism. Patients may sit or stand in the same position for hours, may hold odd positions, and may resist movement of their extremities.Excited Catatonia: Excited catatonia is characterized by odd mannerisms/gestures, performing purposeless or inappropriate actions, excessive motor activity restlessness, stereotypy, impulsivity, agitation, combativeness. Speech and actions may be repetitive or mimic another persons. People in this state are extremely hyperactive and may have delusions and hallucinations. Catatonic excitement is commonly cited as one of the most dangerous mental states in psychiatry.
Malignant Catatonia: Malignant catatonia is a life-threatening condition that may progress rapidly within a few days. It is characterized by fever, abnormalities in blood pressure, heart rate, respiratory rate, diaphoresis (sweating), and delirium. Certain lab findings are common with this presentation; however, they are nonspecific, which means that they are also present in other conditions and do not diagnose catatonia. These lab findings include: leukocytosis, elevated creatine kinase, low serum iron. The signs and symptoms of malignant catatonia overlap significantly with neuroleptic malignant syndrome (NMS) and so a careful history, review of medications, and physical exam are critical to properly differentiate these conditions. For example, if the patient has waxy flexibility and holds a position against gravity when passively moved into that position, then it is likely catatonia. If the patient has a "lead-pipe rigidity" then NMS should be the prime suspect.Other forms:

Periodic catatonia is an inconsistently defined entity. In the Wernicke-Kleist-Leonhard school, it is a distinct form of "non-system schizophrenia" characterized by recurrent acute phases with hyperkinetic and akinetic features and often psychotic symptoms, and the build-up of a residual state in between these acute phases, which is characterized by low-level catatonic features and aboulia of varying severity. The condition has a strong hereditary component. According to modern classifications, this may be diagnosed as a form of bipolar disorder, schizoaffective disorder or schizophrenia. Independently, the term periodic catatonia is sometimes used in modern literature to describe a syndrome of recurrent phases of acute catatonia (excited or inhibited type) with full remission between episodes, which resembles the description of "motility psychosis" in the Wernicke-Kleist-Leonhard school.
System catatonias or systematic catatonias are only defined in the Wernicke-Kleist-Leonhard school. These are chronic-progressive conditions characterized by specific disturbances of volition and psychomotricity, leading to a dramatic decline of executive and adaptive functioning and ability to communicate. They are considered forms of schizophrenia but distinct from other schizophrenic conditions. Affective flattening and apparent loss of interests are common but may be related to reduced emotional expression rather than lack of emotion. Heredity is low. Of the 21 different forms (6 "simple" and 15 "combined" forms) that have been described, most overlap only partially - if at all - with current definitions of either catatonia or schizophrenia, and thus are difficult to classify according to modern diagnostic manuals.
Early childhood catatonias are also a diagnosis exclusive to the Wernicke-Kleist-Leonhard school, and refers to system catatonias that manifest in young children. Clinically, these conditions resemble severe regressive forms of autism.
Chronic catatonia-like breakdown or Autistic catatonia refers to a functional decline seen in some patients with pre-existing autism spectrum disorder and/or intellectual disability which usually runs a chronic-progressive course and encompasses attenuated catatonic symptoms as well as mood and anxiety symptoms that increasingly interfere with adaptive functioning. Onset is typically insidious and often mistaken for background autistic symptoms. Slowing of voluntary movement, reduced speech, aboulia, increased prompt dependency and obsessive-compulsive symptoms are frequently seen; negativism, (auto-)aggressive behaviors and ill-defined hallucinations have also been reported. Both the causes of this disorder as well as its prognosis appear to be heterogenous, with most patients showing partial recovery upon treatment. It seems to be related to chronic stress as a result of life transitions, loss of external time structuring, sensory sensitivities and/or traumatic experiences, co-morbid mental disorders, or other unknown causes. Since clinical catatonia can not always be diagnosed, this condition has also been renamed to the more general term "late regression".

Complications
Patients may experience several complications from being in a catatonic state. The nature of these complications will depend on the type of catatonia being experienced by the patient. For example, patients presenting with retarded catatonia may have refusal to eat which will in turn lead to malnutrition and dehydration. Furthermore, if immobility is a symptom the patient is presenting with, then they may develop pressure ulcers, muscle contractions, and are at risk of developing deep vein thrombosis (DVT) and pulmonary embolus (PE). Patients with excited catatonia may be aggressive and violent, and physical trauma may result from this. Catatonia may progress to the malignant type which will present with autonomic instability and may be life-threatening. Other complications also include the development of pneumonia and neuroleptic malignant syndrome.

Causes
Catatonia is almost always secondary to another underlying illness, often a psychiatric disorder. Mood disorders such as a bipolar disorder and depression are the most common etiologies to progress to catatonia.  Other psychiatric associations include schizophrenia and other primary psychotic disorders. It also is related to autism spectrum disorders.Catatonia is also seen in many medical disorders, including infections (such as encephalitis), autoimmune disorders, meningitis, focal neurological lesions (including strokes), alcohol withdrawal, abrupt or overly rapid benzodiazepine withdrawal, cerebrovascular disease, neoplasms, head injury, and some metabolic conditions (homocystinuria, diabetic ketoacidosis, hepatic encephalopathy, and hypercalcaemia).

Pathogenesis
The pathophysiology that leads to catatonia is still poorly understood and a definite mechanism remains unknown. Neurologic studies have implicated several pathways; however, it remains unclear whether these findings are the cause or the consequence of the disorder.Abnormalities in GABA, glutamate signaling, serotonin, and dopamine transmission are believed to be implicated in catatonia.Furthermore, it has also been hypothesized that pathways that connect the basal ganglia with the cortex and thalamus is involved in the development of catatonia.

Diagnosis
There is not yet a definitive consensus regarding diagnostic criteria of catatonia. In the American Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the World Health Organizations eleventh edition of the International Classification of Disease (ICD-11) the classification is more homogeneous than in earlier editions. Prominent researchers in the field have other suggesions for diagnostic criteria.DSM-5 classification
The DSM-5 does not classify catatonia as an independent disorder, but rather it classifies it as catatonia associated with another mental disorder, due to another medical condition, or as unspecified catatonia. Catatonia is diagnosed by the presence of three or more of the following 12 psychomotor symptoms in association with a mental disorder, medical condition, or unspecified:

stupor: no psycho-motor activity; not actively relating to the environment
catalepsy: passive induction of a posture held against gravity
waxy flexibility: allowing positioning by an examiner and maintaining that position
mutism: no, or very little, verbal response (exclude if known aphasia)
negativism: opposition or no response to instructions or external stimuli
posturing: spontaneous and active maintenance of a posture against gravity
mannerisms that are odd, circumstantial caricatures of normal actions
stereotypy: repetitive, abnormally frequent, non-goal-directed movements
agitation, not influenced by external stimuli
grimacing: keeping a fixed facial expression
echolalia: mimicking anothers speech
echopraxia: mimicking anothers movements.Other disorders (additional code 293.89 [F06.1] to indicate the presence of the co-morbid catatonia):

Catatonia associated with autism spectrum disorder
Catatonia associated with schizophrenia spectrum and other psychotic disorders
Catatonia associated with brief psychotic disorder
Catatonia associated with schizophreniform disorder
Catatonia associated with schizoaffective disorder
Catatonia associated with a substance-induced psychotic disorder
Catatonia associated with bipolar and related disorders
Catatonia associated with major depressive disorder
Catatonic disorder due to another medical conditionIf catatonic symptoms are present but do not form the catatonic syndrome, a medication- or substance-induced aetiology should first be considered.ICD-11 classification
In ICD-11 catatonia is defined as a syndrome of primarily psychomotor disturbances that is characterized by the simultaneous occurrence of several symptoms such as stupor; catalepsy; waxy flexibility; mutism; negativism; posturing; mannerisms; stereotypies; psychomotor agitation; grimacing; echolalia and echopraxia. Catatonia may occur in the context of specific mental disorders, including mood disorders, schizophrenia or other primary psychotic disorders, and Neurodevelopmental disorders, and may be induced by psychoactive substances, including medications. Catatonia may also be caused by a medical condition not classified under mental, behavioral, or neurodevelopmental disorders.

Assessment/Physical
Catatonia is often overlooked and under-diagnosed. Patients with catatonia most commonly have an underlying psychiatric disorder, for this reason, physicians may overlook signs of catatonia due to the severity of the psychosis the patient is presenting with. Furthermore, the patient may not be presenting with the common signs of catatonia such as mutism and posturing. Additionally, the motor abnormalities seen in catatonia are also present in psychiatric disorders. For example, a patient with mania will show increased motor activity that may progress to exciting catatonia. One way in which physicians can differentiate between the two is to observe the motor abnormality. Patients with mania present with increased goal-directed activity. On the other hand, the increased activity in catatonia is not goal-directed and often repetitive.Catatonia is a clinical diagnosis and there is no specific laboratory test to diagnose it. However, certain testing can help determine what is causing the catatonia. An EEG will likely show diffuse slowing. If seizure activity is driving the syndrome, then an EEG would also be helpful in detecting this. CT or MRI will not show catatonia; however, they might reveal abnormalities that might be leading to the syndrome. Metabolic screens, inflammatory markers, or autoantibodies may reveal reversible medical causes of catatonia.Vital signs should be frequently monitored as catatonia can progress to malignant catatonia which is life-threatening. Malignant catatonia is characterized by fever, hypertension, tachycardia, and tachypnea.

Rating scale
Various rating scales for catatonia have been developed, however, their utility for clinical care has not been well established. The most commonly used scale is the Bush-Francis Catatonia Rating Scale (BFCRS) (external link is provided below). The scale is composed of 23 items with the first 14 items being used as the screening tool. If 2 of the 14 are positive, this prompts for further evaluation and completion of the remaining 9 items.
A diagnosis can be supported by the lorazepam challenge or the zolpidem challenge. While proven useful in the past, barbiturates are no longer commonly used in psychiatry; thus the option of either benzodiazepines or ECT.

Differential diagnosis
The differential diagnosis of catatonia is extensive as signs and symptoms of catatonia may overlap significantly with those of other conditions. Therefore, a careful and detailed history, medication review, and physical exam are key to diagnosing catatonia and differentiating it from other conditions. Furthermore, some of these conditions can themselves lead to catatonia. The differential diagnosis is as follows:

Neuroleptic malignant syndrome (NMS) and catatonia are both life-threatening conditions that share many of the same characteristics including fever, autonomic instability, rigidity, and delirium. Lab values of low serum iron, elevated creatine kinase, and white blood cell count are also shared by the two disorders further complicating the diagnosis. There are features of malignant catatonia (posturing, impulsivity, etc.) that are absent from NSM and the lab results are not as consistent in malignant catatonia as they are in NMS. Some experts consider NMS to be a drug-induced condition associated with antipsychotics, particularly, first generation antipsychotics, but it has not been established as a subtype. Therefore, discontinuing antipsychotics and starting benzodiazepines is a treatment for this condition, and similarly it is helpful in catatonia as well.
Anti-NMDA receptor encephalitis is an autoimmune disorder characterized by neuropsychiatric features and the presence of IgG antibodies. The presentation of anti-NMDAR encephalitis has been categorized into 5 phases: prodromal phase, psychotic phase, unresponsive phase, hyperkinetic phase, and recovery phase. The psychotic phase progresses into the unresponsive phase characterized by mutism, decreased motor activity, and catatonia.
Both Serotonin syndrome and malignant catatonia may present with signs and symptoms of delirium, autonomic instability, hyperthermia, and rigidity. Again, similar to the presentation in NSM. However, patients with Serotonin syndrome have a history of ingestion of serotonergic drugs (Ex: SSRI). These patients will also present with hyperreflexia, myoclonus, nausea, vomiting, and diarrhea.
Malignant hyperthermia and malignant catatonia share features of autonomic instability, hyperthermia, and rigidity. However, malignant hyperthermia is a hereditary disorder of skeletal muscle that makes these patients susceptible to exposure to halogenated anesthetics and/or depolarizing muscle relaxants like succinylcholine. Malignant hyperthermia most commonly occurs in the intraoperative or postoperative periods. Other signs and symptoms of malignant hyperthermia include metabolic and respiratory acidosis, hyperkalemia, and cardiac arrhythmias.
Akinetic mutism is a neurological disorder characterized by a decrease in goal-directed behavior and motivation; however, the patient has an intact level of consciousness. Patients may present with apathy, and may seem indifferent to pain, hunger, or thirst. Akinetic mutism has been associated with structural damage in a variety of brain areas. Akinetic mutism and catatonia may both manifest with immobility, mutism, and waxy flexibility. Differentiating both disorders is the fact that akinetic mutism does not present with echolalia, echopraxia, or posturing. Furthermore, it is not responsive to benzodiazepines as is the case for catatonia.
Elective mutism has an anxious etiology but has also been associated with personality disorders. Patients with this disorder fail to speak with some individuals but will speak with others. Likewise, they may refuse to speak in certain situations; for example, a child who refuses to speak at school but is conversational at home. This disorder is distinguished from catatonia by the absence of any other signs/symptoms.
Nonconvulsive status epilepticus is seizure activity with no accompanying tonic-clonic movements. It can present with stupor, similar to catatonia, and they both respond to benzodiazepines. Nonconvulsive status epilepticus is diagnosed by the presence of seizure activity seen on electroencephalogram (EEG). Catatonia on the other hand, is associated with normal EEG or diffuse slowing.
Delirium is characterized by fluctuating disturbed perception and consciousness in the ill individual. It has hypoactive and hyperactive or mixed forms. People with hyperactive delirium present similarly to those with excited catatonia and have symptoms of restlessness, agitation, and aggression. Those with hypoactive delirium present with similarly to retarded catatonia, withdrawn and quiet. However, catatonia also includes other distinguishing features including posturing and rigidity as well as a positive response to benzodiazepines.
Patients with locked-in syndrome present with immobility and mutism; however, unlike patients with catatonia who are unmotivated to communicate, patients with locked-in syndrome try to communicate with eye movements and blinking. Furthermore, locked-in syndrome is caused by damage to the brainstem.
Stiff-person syndrome and catatonia are similar in that they may both present with rigidity, autonomic instability and a positive response to benzodiazepines. However, stiff-person syndrome may be associated with anti-glutamic acid decarboxylase (anti-GAD) antibodies and other catatonic signs such as mutism and posturing are not part of the syndrome.
Untreated late-stage Parkinsons disease may present similarly to retarded catatonia with symptoms of immobility, rigidity, and difficulty speaking. Further complicating the diagnosis is the fact that many patients with Parkinsons disease will have major depressive disorder, which may be the underlying cause of catatonia. Parkinsons disease can be distinguished from catatonia by a positive response to levodopa. Catatonia on the other hand will show a positive response to benzodiazepines.
Extrapyramidal side effects of antipsychotic medication, especially dystonia and akathisia, can be difficult to distinguish from catatonic symptoms, or may confound them in the psychiatric setting. Extrapyramidal motor disorders usually do not involve social symptoms like negativism, while individuals with catatonic excitement typically do not have the physically painful compulsion to move that is seen in akathisia.
Certain stimming behaviors and stress responses in individuals with autism spectrum disorders can present similarly to catatonia. In autism spectrum disorders, chronic catatonia is distinguished by a lasting deterioration of adaptive skills from the background of pre-existing autistic symptomatology that cannot be easily explained. Acute catatonia is usually clearly distinguishable from autistic symptoms.
The diagnostic entities of obsessional slowness and psychogenic parkinsonism show overlapping features with catatonia, such as motor slowness, gegenhalten (oppositional paratonia), mannerisms, and reduced or absent speech. However, psychogenic parkinsonism involves tremor which is unusual in catatonia. Obsessional slowness is a controversial diagnosis, with presentations ranging from severe but common manifestations of obsessive compulsive disorder to catatonia.

Treatment
The initial treatment of catatonia is to stop medication that could be potentially leading to the syndrome. These may include steroids, stimulants, anticonvulsants, neuroleptics, dopamine blockers, etc. The next step is to provide a "lorazepam challenge," in which patients are given 2 mg of IV lorazepam (or another benzodiazepine). Most patients with catatonia will respond significantly to this within the first 15–30 minutes. If no change is observed during the first dose, then a second dose is given and the patient is re-examined. If the patient responds to the lorazepam challenge, then lorazepam can be scheduled at interval doses until the catatonia resolves. The lorazepam must be tapered slowly, otherwise, the catatonia symptoms may return. The underlying cause of the catatonia should also be treated during this time. If within a week the catatonia is not resolved, then ECT can be used to reverse the symptoms. ECT in combination with benzodiazepines is used to treat malignant catatonia. In France, zolpidem has also been used in diagnosis, and response may occur within the same time period. Ultimately the underlying cause needs to be treated.Electroconvulsive therapy (ECT) is an effective treatment for catatonia that is well acknowledged. ECT has also shown favorable outcomes in patients with chronic catatonia. However, it has been pointed out that further high quality randomized controlled trials are needed to evaluate the efficacy, tolerance, and protocols of ECT in catatonia.Antipsychotics should be used with care as they can worsen catatonia and are the cause of neuroleptic malignant syndrome, a dangerous condition that can mimic catatonia and requires immediate discontinuation of the antipsychotic.There is evidence clozapine works better than other antipsychotics to treat catatonia, following a recent systematic review.Excessive glutamate activity is believed to be involved in catatonia; when first-line treatment options fail, NMDA antagonists such as amantadine or memantine may be used. Amantadine may have an increased incidence of tolerance with prolonged use and can cause psychosis, due to its additional effects on the dopamine system </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ischemic colitis and can you explain it in depth? [/INST] Ischemic colitis (also spelled ischaemic colitis) is a medical condition in which inflammation and injury of the large intestine result from inadequate blood supply. Although uncommon in the general population, ischemic colitis occurs with greater frequency in the elderly, and is the most common form of bowel ischemia. Causes of the reduced blood flow can include changes in the systemic circulation (e.g. low blood pressure) or local factors such as constriction of blood vessels or a blood clot. In most cases, no specific cause can be identified.Ischemic colitis is usually suspected on the basis of the clinical setting, physical examination, and laboratory test results; the diagnosis can be confirmed by endoscopy or by using sigmoid or endoscopic placement of a visible light spectroscopic catheter (see Diagnosis). Ischemic colitis can span a wide spectrum of severity; most patients are treated supportively and recover fully, while a minority with very severe ischemia may develop sepsis and become critically, sometimes fatally, ill.Patients with mild to moderate ischemic colitis are usually treated with IV fluids, analgesia, and bowel rest (that is, no food or water by mouth) until the symptoms resolve. Those with severe ischemia who develop complications such as sepsis, intestinal gangrene, or bowel perforation may require more aggressive interventions such as surgery and intensive care. Most patients make a full recovery; occasionally, after severe ischemia, patients may develop long-term complications such as a stricture or chronic colitis.

Signs and symptoms
Three progressive phases of ischemic colitis have been described:
A hyperactive phase occurs first, in which the primary symptoms are severe abdominal pain and the passage of bloody stools. Many patients get better and do not progress beyond this phase.
A paralytic phase can follow if ischemia continues; in this phase, the abdominal pain becomes more widespread, the belly becomes more tender to the touch, and bowel motility decreases, resulting in abdominal bloating, no further bloody stools, and absent bowel sounds on exam.
Finally, a shock phase can develop as fluids start to leak through the damaged colon lining. This can result in shock and metabolic acidosis with dehydration, low blood pressure, rapid heart rate, and confusion. Patients who progress to this phase are often critically ill and require intensive care.Symptoms of ischemic colitis vary depending on the severity of the ischemia. The most common early signs of ischemic colitis include abdominal pain (often left-sided), with mild to moderate amounts of rectal bleeding. The sensitivity of findings among 73 patients were:
abdominal pain (78%)
lower gastrointestinal tract bleeding (62%)
diarrhea (38%)
Fever higher than 38 °C (100.4 °F) (34%)Physical examination
abdominal pain (77%)
abdominal tenderness (21%)

Causes
Ischemic colitis is often classified according to the underlying cause. Non-occlusive ischemia develops because of low blood pressure or constriction of the vessels feeding the colon; occlusive ischemia indicates that a blood clot or other blockage has cut off blood flow to the colon.

Non-occlusive ischemia
In hemodynamically unstable patients (i.e. shock) the mesenteric perfusion may be compromised. This condition is commonly asymptomatic, and usually only apparent through a systemic inflammatory response.

Occlusive ischemia
Mostly the result of a thromboembolism. Commonly the embolism is caused by atrial fibrillation, valvular disease, myocardial infarction, or cardiomyopathy.In addition, ischemic colitis is a well-recognized complication of abdominal aortic aneurysm repair, when the origin of the inferior mesenteric artery is covered by the aortic graft.  In a 1991 review concerning 2137 patients the accidental inferior mesenteric artery ligation was the most common cause (74%) of ischemic colitis. Thus, patients without adequate collateralization are at risk for ischemia of the descending and sigmoid colon.  Bloody diarrhea and leukocytosis in the postoperative period are essentially diagnostic of ischemic colitis. The complication can be prevented through careful selection of subjects that may require replanting inferior mesenteric artery (IMA) and completing the pre surgical procedure information with an instrumental evaluation during surgical treatment.

Pathophysiology
Colonic blood supply
The colon receives blood from both the superior and inferior mesenteric arteries. The blood supply from these two major arteries overlaps, with abundant collateral circulation via the marginal artery of the colon. However, there are weak points, or "watershed" areas, at the borders of the territory supplied by each of these arteries, such as the splenic flexure and the rectosigmoid junction. These watershed areas are most vulnerable to ischemia when blood flow decreases, as they have the fewest vascular collaterals.The rectum receives blood from both the inferior mesenteric artery and the internal iliac artery; the rectum is rarely involved by colonic ischemia due to this dual blood supply.

Development of ischemia
Under ordinary conditions, the colon receives between 10% and 35% of the total cardiac output. If blood flow to the colon drops by more than about 50%, ischemia will develop. The arteries feeding the colon are very sensitive to vasoconstrictors; presumably this is an evolutionary adaptation to shunt blood away from the bowel and to the heart and brain in times of stress. As a result, during periods of low blood pressure, the arteries feeding the colon clamp down vigorously; a similar process can result from vasoconstricting drugs such as ergotamine, cocaine, or vasopressors. This vasoconstriction can result in non-occlusive ischemic colitis.

Pathologic findings
A range of pathologic findings are seen in ischemic colitis, corresponding to the spectrum of clinical severity. In its mildest form, mucosal and submucosal hemorrhage and edema are seen, possibly with mild necrosis or ulceration. With more severe ischemia, a pathologic picture resembling inflammatory bowel disease (i.e. chronic ulcerations, crypt abscesses and pseudopolyps) may be seen. In the most severe cases, transmural infarction with resulting perforation may be seen; after recovery, the muscularis propria may be replaced by fibrous tissue, resulting in a stricture. Following restoration of normal blood flow, reperfusion injury may also contribute to the damage to the colon.

Diagnosis
Ischemic colitis must be differentiated from the many other causes of abdominal pain and rectal bleeding (for example, infection, inflammatory bowel disease, diverticulosis, or colon cancer). It is also important to differentiate ischemic colitis, which often resolves on its own, from the more immediately life-threatening condition of acute mesenteric ischemia of the small bowel.There are devices which test the sufficiency of oxygen delivery to the colon. The first device approved by the U.S. FDA in 2004 uses visible light spectroscopy to analyze capillary oxygen levels. Use during Aortic Aneurysm repair detected when colon oxygen levels fell below sustainable levels, allowing real-time repair. In several studies, Specificity has been 90% or higher for acute colonic ischemia, and 83% for chronic mesenteric ischemia, with a sensitivity of 71%-92%. This device must be placed using endoscopy, however.

Diagnostic tests
There is a recent optical test, but it requires endoscopy (see Diagnosis). There are no specific blood tests for ischemic colitis. The sensitivity of tests among 73 patients were:
The white blood cell count was more than 15,000/mm3 in 20 patients (27%)
The serum bicarbonate level was less than 24 mmol/L in 26 patients (36%)Plain X-rays are often normal or show non-specific findings. In a series of 73 patients, plain abdominal radiography (56%) showing colic distension in 53% or a pneumoperitoneum in 3%.CT scans are often used in the evaluation of abdominal pain and rectal bleeding, and may suggest the diagnosis of ischemic colitis, pick up complications, or suggest an alternate diagnosis.Endoscopic evaluation, via colonoscopy or flexible sigmoidoscopy, is the procedure of choice if the diagnosis remains unclear. Ischemic colitis has a distinctive endoscopic appearance; endoscopy can also facilitate alternate diagnoses such as infection or inflammatory bowel disease. Biopsies can be taken via endoscopy to provide more information. Visible light spectroscopy, performed using catheters placed through the 5 mm channel of the endoscope, is diagnostic (see Diagnosis).

Treatment
Except in the most severe cases, ischemic colitis is treated with supportive care. IV fluids are given to treat dehydration, and the patient is placed on bowel rest (meaning nothing to eat or drink) until the symptoms resolve. If possible, cardiac function and oxygenation should be optimized to improve oxygen delivery to the ischemic bowel. A nasogastric tube may be inserted if an ileus is present.Antibiotics are sometimes given in moderate to severe cases; the data supporting this practice date to the 1950s, although there is more recent animal data suggesting that antibiotics may increase survival and prevent bacteria from crossing the damaged lining of the colon into the bloodstream </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Leukocytosis and can you explain it in depth? [/INST] Leukocytosis is a condition in which the white cell (leukocyte count) is above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasitic infections or bone tumors as well as leukemia. It may also occur after strenuous exercise, convulsions such as epilepsy, emotional stress, pregnancy and labor, anesthesia, as a side effect of medication (e.g., lithium), and epinephrine administration. There are five principal types of leukocytosis:
Neutrophilia (the most common form)
Lymphocytosis
Monocytosis
Eosinophilia
BasophiliaThis increase in leukocyte (primarily neutrophils) is usually accompanied by a "left upper shift" in the ratio of immature to mature neutrophils and macrophages </s>