<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pneumonia and explain in detail? [/INST] Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity of the condition is variable.Pneumonia is usually caused by infection with viruses or bacteria, and less commonly by other microorganisms. Identifying the responsible pathogen can be difficult. Diagnosis is often based on symptoms and physical examination. Chest X-rays, blood tests, and culture of the sputum may help confirm the diagnosis. The disease may be classified by where it was acquired, such as community- or hospital-acquired or healthcare-associated pneumonia.Risk factors for pneumonia include cystic fibrosis, chronic obstructive pulmonary disease (COPD), sickle cell disease, asthma, diabetes, heart failure, a history of smoking, a poor ability to cough (such as following a stroke), and a weak immune system.Vaccines to prevent certain types of pneumonia (such as those caused by Streptococcus pneumoniae bacteria, linked to influenza, or linked to COVID-19) are available. Other methods of prevention include hand washing to prevent infection, not smoking, and social distancing.Treatment depends on the underlying cause. Pneumonia believed to be due to bacteria is treated with antibiotics. If the pneumonia is severe, the affected person is generally hospitalized. Oxygen therapy may be used if oxygen levels are low.Each year, pneumonia affects about 450 million people globally (7% of the population) and results in about 4 million deaths. With the introduction of antibiotics and vaccines in the 20th century, survival has greatly improved. Nevertheless, pneumonia remains a leading cause of death in developing countries, and also among the very old, the very young, and the chronically ill. Pneumonia often shortens the period of suffering among those already close to death and has thus been called "the old mans friend".

Signs and symptoms
People with infectious pneumonia often have a productive cough, fever accompanied by shaking chills, shortness of breath, sharp or stabbing chest pain during deep breaths, and an increased rate of breathing. In elderly people, confusion may be the most prominent sign.The typical signs and symptoms in children under five are fever, cough, and fast or difficult breathing. Fever is not very specific, as it occurs in many other common illnesses and may be absent in those with severe disease, malnutrition or in the elderly. In addition, a cough is frequently absent in children less than 2 months old. More severe signs and symptoms in children may include blue-tinged skin, unwillingness to drink, convulsions, ongoing vomiting, extremes of temperature, or a decreased level of consciousness.Bacterial and viral cases of pneumonia usually result in similar symptoms. Some causes are associated with classic, but non-specific, clinical characteristics. Pneumonia caused by Legionella may occur with abdominal pain, diarrhea, or confusion. Pneumonia caused by Streptococcus pneumoniae is associated with rusty colored sputum. Pneumonia caused by Klebsiella may have bloody sputum often described as "currant jelly". Bloody sputum (known as hemoptysis) may also occur with tuberculosis, Gram-negative pneumonia, lung abscesses and more commonly acute bronchitis. Pneumonia caused by Mycoplasma pneumoniae may occur in association with swelling of the lymph nodes in the neck, joint pain, or a middle ear infection. Viral pneumonia presents more commonly with wheezing than bacterial pneumonia. Pneumonia was historically divided into "typical" and "atypical" based on the belief that the presentation predicted the underlying cause. However, evidence has not supported this distinction, therefore it is no longer emphasized.

Cause
Pneumonia is due to infections caused primarily by bacteria or viruses and less commonly by fungi and parasites. Although more than 100 strains of infectious agents have been identified, only a few are responsible for the majority of cases. Mixed infections with both viruses and bacteria may occur in roughly 45% of infections in children and 15% of infections in adults. A causative agent may not be isolated in about half of cases despite careful testing. In an active population-based surveillance for community-acquired pneumonia requiring hospitalization in five hospitals in Chicago and Nashville from January 2010 through June 2012, 2259 patients were identified who had radiographic evidence of pneumonia and specimens that could be tested for the responsible pathogen. Most patients (62%) had no detectable pathogens in their sample, and unexpectedly, respiratory viruses were detected more frequently than bacteria. Specifically, 23% had one or more viruses, 11% had one or more bacteria, 3% had both bacterial and viral pathogens, and 1% had a fungal or mycobacterial infection. "The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%)."The term pneumonia is sometimes more broadly applied to any condition resulting in inflammation of the lungs (caused for example by autoimmune diseases, chemical burns or drug reactions); however, this inflammation is more accurately referred to as pneumonitis.Factors that predispose to pneumonia include smoking, immunodeficiency, alcoholism, chronic obstructive pulmonary disease, sickle cell disease (SCD), asthma, chronic kidney disease, liver disease, and biological aging. Additional risks in children include not being breastfed, exposure to cigarette smoke and other air pollution, malnutrition, and poverty. The use of acid-suppressing medications – such as proton-pump inhibitors or H2 blockers – is associated with an increased risk of pneumonia. Approximately 10% of people who require mechanical ventilation develop ventilator-associated pneumonia, and people with a gastric feeding tube have an increased risk of developing aspiration pneumonia. For people with certain variants of the FER gene, the risk of death is reduced in sepsis caused by pneumonia. However, for those with TLR6 variants, the risk of getting Legionnaires disease is increased.

Bacteria
Bacteria are the most common cause of community-acquired pneumonia (CAP), with Streptococcus pneumoniae isolated in nearly 50% of cases. Other commonly isolated bacteria include Haemophilus influenzae in 20%, Chlamydophila pneumoniae in 13%, and Mycoplasma pneumoniae in 3% of cases; Staphylococcus aureus; Moraxella catarrhalis; and Legionella pneumophila. A number of drug-resistant versions of the above infections are becoming more common, including drug-resistant Streptococcus pneumoniae (DRSP) and methicillin-resistant Staphylococcus aureus (MRSA).The spreading of organisms is facilitated by certain risk factors. Alcoholism is associated with Streptococcus pneumoniae, anaerobic organisms, and Mycobacterium tuberculosis; smoking facilitates the effects of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Legionella pneumophila. Exposure to birds is associated with Chlamydia psittaci; farm animals with Coxiella burnetti; aspiration of stomach contents with anaerobic organisms; and cystic fibrosis with Pseudomonas aeruginosa and Staphylococcus aureus. Streptococcus pneumoniae is more common in the winter, and it should be suspected in persons aspirating a large number of anaerobic organisms.

Viruses
In adults, viruses account for about one third of pneumonia cases, and in children for about 15% of them. Commonly implicated agents include rhinoviruses, coronaviruses, influenza virus, respiratory syncytial virus (RSV), adenovirus, and parainfluenza. Herpes simplex virus rarely causes pneumonia, except in groups such as newborns, persons with cancer, transplant recipients, and people with significant burns. After organ transplantation or in otherwise immunocompromised persons, there are high rates of cytomegalovirus pneumonia. Those with viral infections may be secondarily infected with the bacteria Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae, particularly when other health problems are present. Different viruses predominate at different times of the year; during flu season, for example, influenza may account for more than half of all viral cases. Outbreaks of other viruses also occur occasionally, including hantaviruses and coronaviruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can also result in pneumonia.

Fungi
Fungal pneumonia is uncommon, but occurs more commonly in individuals with weakened immune systems due to AIDS, immunosuppressive drugs, or other medical problems. It is most often caused by Histoplasma capsulatum, Blastomyces, Cryptococcus neoformans, Pneumocystis jiroveci (pneumocystis pneumonia, or PCP), and Coccidioides immitis. Histoplasmosis is most common in the Mississippi River basin, and coccidioidomycosis is most common in the Southwestern United States. The number of cases of fungal pneumonia has been increasing in the latter half of the 20th century due to increasing travel and rates of immunosuppression in the population. For people infected with HIV/AIDS, PCP is a common opportunistic infection.

Parasites
A variety of parasites can affect the lungs, including Toxoplasma gondii, Strongyloides stercoralis, Ascaris lumbricoides, and Plasmodium malariae. These organisms typically enter the body through direct contact with the skin, ingestion, or via an insect vector. Except for Paragonimus westermani, most parasites do not specifically affect the lungs but involve the lungs secondarily to other sites. Some parasites, in particular those belonging to the Ascaris and Strongyloides genera, stimulate a strong eosinophilic reaction, which may result in eosinophilic pneumonia. In other infections, such as malaria, lung involvement is due primarily to cytokine-induced systemic inflammation. In the developed world, these infections are most common in people returning from travel or in immigrants. Around the world, parasitic pneumonia is most common in the immunodeficient.

Noninfectious
Idiopathic interstitial pneumonia or noninfectious pneumonia is a class of diffuse lung diseases. They include diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and usual interstitial pneumonia. Lipoid pneumonia is another rare cause due to lipids entering the lung. These lipids can either be inhaled or spread to the lungs from elsewhere in the body.

Mechanisms
Pneumonia frequently starts as an upper respiratory tract infection that moves into the lower respiratory tract. It is a type of pneumonitis (lung inflammation). The normal flora of the upper airway give protection by competing with pathogens for nutrients. In the lower airways, reflexes of the glottis, actions of complement proteins and immunoglobulins are important for protection. Microaspiration of contaminated secretions can infect the lower airways and cause pneumonia. The progress of pneumonia is determined by the virulence of the organism; the amount of organism required to start an infection; and the bodys immune response against the infection.

Bacterial
Most bacteria enter the lungs via small aspirations of organisms residing in the throat or nose. Half of normal people have these small aspirations during sleep. While the throat always contains bacteria, potentially infectious ones reside there only at certain times and under certain conditions. A minority of types of bacteria such as Mycobacterium tuberculosis and Legionella pneumophila reach the lungs via contaminated airborne droplets. Bacteria can also spread via the blood. Once in the lungs, bacteria may invade the spaces between cells and between alveoli, where the macrophages and neutrophils (defensive white blood cells) attempt to inactivate the bacteria. The neutrophils also release cytokines, causing a general activation of the immune system. This leads to the fever, chills, and fatigue common in bacterial pneumonia. The neutrophils, bacteria, and fluid from surrounding blood vessels fill the alveoli, resulting in the consolidation seen on chest X-ray.

Viral
Viruses may reach the lung by a number of different routes. Respiratory syncytial virus is typically contracted when people touch contaminated objects and then touch their eyes or nose. Other viral infections occur when contaminated airborne droplets are inhaled through the nose or mouth. Once in the upper airway, the viruses may make their way into the lungs, where they invade the cells lining the airways, alveoli, or lung parenchyma. Some viruses such as measles and herpes simplex may reach the lungs via the blood. The invasion of the lungs may lead to varying degrees of cell death. When the immune system responds to the infection, even more lung damage may occur. Primarily white blood cells, mainly mononuclear cells, generate the inflammation. As well as damaging the lungs, many viruses simultaneously affect other organs and thus disrupt other body functions. Viruses also make the body more susceptible to bacterial infections; in this way, bacterial pneumonia can occur at the same time as viral pneumonia.

Diagnosis
Pneumonia is typically diagnosed based on a combination of physical signs and often a chest X-ray. In adults with normal vital signs and a normal lung examination, the diagnosis is unlikely. However, the underlying cause can be difficult to confirm, as there is no definitive test able to distinguish between bacterial and non-bacterial cause. The overall impression of a physician appears to be at least as good as decision rules for making or excluding the diagnosis.

Diagnosis in children
The World Health Organization has defined pneumonia in children clinically based on either a cough or difficulty breathing and a rapid respiratory rate, chest indrawing, or a decreased level of consciousness. A rapid respiratory rate is defined as greater than 60 breaths per minute in children under 2 months old, greater than 50 breaths per minute in children 2 months to 1 year old, or greater than 40 breaths per minute in children 1 to 5 years old.In children, low oxygen levels and lower chest indrawing are more sensitive than hearing chest crackles with a stethoscope or increased respiratory rate. Grunting and nasal flaring may be other useful signs in children less than five years old.Lack of wheezing is an indicator of Mycoplasma pneumoniae in children with pneumonia, but as an indicator it is not accurate enough to decide whether or not macrolide treatment should be used. The presence of chest pain in children with pneumonia doubles the probability of Mycoplasma pneumoniae.

Diagnosis in adults
In general, in adults, investigations are not needed in mild cases. There is a very low risk of pneumonia if all vital signs and auscultation are normal. C-reactive protein (CRP) may help support the diagnosis. For those with CRP less than 20 mg/L without convincing evidence of pneumonia, antibiotics are not recommended.Procalcitonin may help determine the cause and support decisions about who should receive antibiotics. Antibiotics are encouraged if the procalcitonin level reaches 0.25 μg/L, strongly encouraged if it reaches 0.5 μg/L, and strongly discouraged if the level is below 0.10 μg/L. In people requiring hospitalization, pulse oximetry, chest radiography and blood tests – including a complete blood count, serum electrolytes, C-reactive protein level, and possibly liver function tests – are recommended.The diagnosis of influenza-like illness can be made based on the signs and symptoms; however, confirmation of an influenza infection requires testing. Thus, treatment is frequently based on the presence of influenza in the community or a rapid influenza test.

Physical exam
Physical examination may sometimes reveal low blood pressure, high heart rate, or low oxygen saturation. The respiratory rate may be faster than normal, and this may occur a day or two before other signs. Examination of the chest may be normal, but it may show decreased expansion on the affected side. Harsh breath sounds from the larger airways that are transmitted through the inflamed lung are termed bronchial breathing and are heard on auscultation with a stethoscope. Crackles (rales) may be heard over the affected area during inspiration. Percussion may be dulled over the affected lung, and increased, rather than decreased, vocal resonance distinguishes pneumonia from a pleural effusion.

Imaging
A chest radiograph is frequently used in diagnosis. In people with mild disease, imaging is needed only in those with potential complications, those not having improved with treatment, or those in which the cause is uncertain. If a person is sufficiently sick to require hospitalization, a chest radiograph is recommended. Findings do not always match the severity of disease and do not reliably separate between bacterial and viral infection.X-ray presentations of pneumonia may be classified as lobar pneumonia, bronchopneumonia, lobular pneumonia, and interstitial pneumonia. Bacterial, community-acquired pneumonia classically show lung consolidation of one lung segmental lobe, which is known as lobar pneumonia. However, findings may vary, and other patterns are common in other types of pneumonia. Aspiration pneumonia may present with bilateral opacities primarily in the bases of the lungs and on the right side. Radiographs of viral pneumonia may appear normal, appear hyper-inflated, have bilateral patchy areas, or present similar to bacterial pneumonia with lobar consolidation. Radiologic findings may not be present in the early stages of the disease, especially in the presence of dehydration, or may be difficult to interpret in the obese or those with a history of lung disease. Complications such as pleural effusion may also be found on chest radiographs. Laterolateral chest radiographs can increase the diagnostic accuracy of lung consolidation and pleural effusion.A CT scan can give additional information in indeterminate cases. CT scans can also provide more details in those with an unclear chest radiograph (for example occult pneumonia in chronic obstructive pulmonary disease) and can exclude pulmonary embolism and fungal pneumonia and detect lung abscess in those who are not responding to treatments. However, CT scans are more expensive, have a higher dose of radiation, and cannot be done at bedside.Lung ultrasound may also be useful in helping to make the diagnosis. Ultrasound is radiation free and can be done at bedside. However, ultrasound requires specific skills to operate the machine and interpret the findings. It may be more accurate than chest X-ray.

Microbiology
In people managed in the community, determining the causative agent is not cost-effective and typically does not alter management. For people who do not respond to treatment, sputum culture should be considered, and culture for Mycobacterium tuberculosis should be carried out in persons with a chronic productive cough. Microbiological evaluation is also indicated in severe pneumonia, alcoholism, asplenia, immunosuppression, HIV infection, and those being empirically treated for MRSA of pseudomonas. Although positive blood culture and pleural fluid culture definitively establish the diagnosis of the type of micro-organism involved, a positive sputum culture has to be interpreted with care for the possibility of colonisation of respiratory tract. Testing for other specific organisms may be recommended during outbreaks, for public health reasons. In those hospitalized for severe disease, both sputum and blood cultures are recommended, as well as testing the urine for antigens to Legionella and Streptococcus. Viral infections, can be confirmed via detection of either the virus or its antigens with culture or polymerase chain reaction (PCR), among other techniques. Mycoplasma, Legionella, Streptococcus, and Chlamydia can also be detected using PCR techniques on bronchoalveolar lavage and nasopharyngeal swab. The causative agent is determined in only 15% of cases with routine microbiological tests.

Classification
Pneumonitis refers to lung inflammation; pneumonia refers to pneumonitis, usually due to infection but sometimes non-infectious, that has the additional feature of pulmonary consolidation. Pneumonia is most commonly classified by where or how it was acquired: community-acquired, aspiration, healthcare-associated, hospital-acquired, and ventilator-associated pneumonia. It may also be classified by the area of the lung affected: lobar pneumonia, bronchial pneumonia and acute interstitial pneumonia; or by the causative organism. Pneumonia in children may additionally be classified based on signs and symptoms as non-severe, severe, or very severe.The setting in which pneumonia develops is important to treatment, as it correlates to which pathogens are likely suspects, which mechanisms are likely, which antibiotics are likely to work or fail, and which complications can be expected based on the persons health status.

Community
Community-acquired pneumonia (CAP) is acquired in the community, outside of health care facilities. Compared with healthcare-associated pneumonia, it is less likely to involve multidrug-resistant bacteria. Although the latter are no longer rare in CAP, they are still less likely.

Healthcare
Health care–associated pneumonia (HCAP) is an infection associated with recent exposure to the health care system, including hospitals, outpatient clinics, nursing homes, dialysis centers, chemotherapy treatment, or home care. HCAP is sometimes called MCAP (medical care–associated pneumonia).
People may become infected with pneumonia in a hospital; this is defined as pneumonia not present at the time of admission (symptoms must start at least 48 hours after admission). It is likely to involve hospital-acquired infections, with higher risk of multidrug-resistant pathogens. People in a hospital often have other medical conditions, which may make them more susceptible to pathogens in the hospital.
Ventilator-associated pneumonia occurs in people breathing with the help of mechanical ventilation. Ventilator-associated pneumonia is specifically defined as pneumonia that arises more than 48 to 72 hours after endotracheal intubation.

Differential diagnosis
Several diseases can present with similar signs and symptoms to pneumonia, such as: chronic obstructive pulmonary disease, asthma, pulmonary edema, bronchiectasis, lung cancer, and pulmonary emboli. Unlike pneumonia, asthma and COPD typically present with wheezing, pulmonary edema presents with an abnormal electrocardiogram, cancer and bronchiectasis present with a cough of longer duration, and pulmonary emboli present with acute onset sharp chest pain and shortness of breath. Mild pneumonia should be differentiated from upper respiratory tract infection (URTI). Severe pneumonia should be differentiated from acute heart failure. Pulmonary infiltrates that resolved after giving mechanical ventilation should point to heart failure and atelectasis rather than pneumonia. For recurrent pneumonia, underlying lung cancer, metastasis, tuberculosis, a foreign bodies, immunosuppression, and hypersensitivity should be suspected.

Prevention
Prevention includes vaccination, environmental measures, and appropriate treatment of other health problems. It is believed that, if appropriate preventive measures were instituted globally, mortality among children could be reduced by 400,000; and, if proper treatment were universally available, childhood deaths could be decreased by another 600,000.

Vaccination
Vaccination prevents against certain bacterial and viral pneumonias both in children and adults. Influenza vaccines are modestly effective at preventing symptoms of influenza, The Center for Disease Control and Prevention (CDC) recommends yearly influenza vaccination for every person 6 months and older. Immunizing health care workers decreases the risk of viral pneumonia among their patients.Vaccinations against Haemophilus influenzae and Streptococcus pneumoniae have good evidence to support their use. There is strong evidence for vaccinating children under the age of 2 against Streptococcus pneumoniae (pneumococcal conjugate vaccine). Vaccinating children against Streptococcus pneumoniae has led to a decreased rate of these infections in adults, because many adults acquire infections from children. A Streptococcus pneumoniae vaccine is available for adults, and has been found to decrease the risk of invasive pneumococcal disease by 74%, but there is insufficient evidence to suggest using the pneumococcal vaccine to prevent pneumonia or death in the general adult population. The CDC recommends that young children and adults over the age of 65 receive the pneumococcal vaccine, as well as older children or younger adults who have an increased risk of getting pneumococcal disease. The pneumococcal vaccine has been shown to reduce the risk of community acquired pneumonia in people with chronic obstructive pulmonary disease, but does not reduce mortality or the risk of hospitalization for people with this condition. People with COPD are recommended by a number of guidelines to have a pneumococcal vaccination. Other vaccines for which there is support for a protective effect against pneumonia include pertussis, varicella, and measles.

Medications
When influenza outbreaks occur, medications such as amantadine or rimantadine may help prevent the condition, but they are associated with side effects. Zanamivir or oseltamivir decrease the chance that people who are exposed to the virus will develop symptoms; however, it is recommended that potential side effects are taken into account.

Other
Smoking cessation and reducing indoor air pollution, such as that from cooking indoors with wood, crop residues or dung, are both recommended. Smoking appears to be the single biggest risk factor for pneumococcal pneumonia in otherwise-healthy adults. Hand hygiene and coughing into ones sleeve may also be effective preventative measures. Wearing surgical masks by the sick may also prevent illness.Appropriately treating underlying illnesses (such as HIV/AIDS, diabetes mellitus, and malnutrition) can decrease the risk of pneumonia. In children less than 6 months of age, exclusive breast feeding reduces both the risk and severity of disease. In people with HIV/AIDS and a CD4 count of less than 200 cells/uL the antibiotic trimethoprim/sulfamethoxazole decreases the risk of Pneumocystis pneumonia and is also useful for prevention in those that are immunocompromised but do not have HIV.Testing pregnant women for Group B Streptococcus and Chlamydia trachomatis, and administering antibiotic treatment, if needed, reduces rates of pneumonia in infants; preventive measures for HIV transmission from mother to child may also be efficient. Suctioning the mouth and throat of infants with meconium-stained amniotic fluid has not been found to reduce the rate of aspiration pneumonia and may cause potential harm, thus this practice is not recommended in the majority of situations. In the frail elderly good oral health care may lower the risk of aspiration pneumonia. Zinc supplementation in children 2 months to five years old appears to reduce rates of pneumonia.For people with low levels of vitamin C in their diet or blood, taking vitamin C supplements may be suggested to decrease the risk of pneumonia, although there is no strong evidence of benefit. There is insufficient evidence to recommend that the general population take vitamin C to prevent or treat pneumonia.For adults and children in the hospital who require a respirator, there is no strong evidence indicating a difference between heat and moisture exchangers and heated humidifiers for preventing pneumonia. There is no good evidence that one approach to mouth care is better than others in preventing nursing home acquired pneumonia. There is tentative evidence that laying flat on the back compared to semi-raised increases pneumonia risks in people who are intubated.

Management
Antibiotics by mouth, rest, simple analgesics, and fluids usually suffice for complete resolution. However, those with other medical conditions, the elderly, or those with significant trouble breathing may require more advanced care. If the symptoms worsen, the pneumonia does not improve with home treatment, or complications occur, hospitalization may be required. Worldwide, approximately 7–13% of cases in children result in hospitalization, whereas in the developed world between 22 and 42% of adults with community-acquired pneumonia are admitted. The CURB-65 score is useful for determining the need for admission in adults. If the score is 0 or 1, people can typically be managed at home; if it is 2, a short hospital stay or close follow-up is needed; if it is 3–5, hospitalization is recommended. In children those with respiratory distress or oxygen saturations of less than 90% should be hospitalized. The utility of chest physiotherapy in pneumonia has not yet been determined. Over-the-counter cough medicine has not been found to be effective, nor has the use of zinc in children. There is insufficient evidence for mucolytics. There is no strong evidence to recommend that children who have non-measles related pneumonia take vitamin A supplements. Vitamin D, as of 2018 is of unclear benefit in children.Pneumonia can cause severe illness in a number of ways, and pneumonia with evidence of organ dysfunction may require intensive care unit admission for observation and specific treatment. The main impact is on the respiratory and the circulatory system. Respiratory failure not responding to normal oxygen therapy may require heated humidified high-flow therapy delivered through nasal cannulae, non-invasive ventilation, or in severe cases invasive ventilation through an endotracheal tube. Regarding circulatory problems as part of sepsis, evidence of poor blood flow or low blood pressure is initially treated with 30 ml/kg of crystalloid infused intravenously. In situations where fluids alone are ineffective, vasopressor medication may be required.For adults with moderate or severe acute respiratory distress syndrome (ARDS) undergoing mechanical ventilation, there is a reduction in mortality when people lay on their front for at least 12 hours a day. However, this increases the risk of endotracheal tube obstruction and pressure sores.

Bacterial
Antibiotics improve outcomes in those with bacterial pneumonia. The first dose of antibiotics should be given as soon as possible. Increased use of antibiotics, however, may lead to the development of antimicrobial resistant strains of bacteria. Antibiotic choice depends initially on the characteristics of the person affected, such as age, underlying health, and the location the infection was acquired. Antibiotic use is also associated with side effects such as nausea, diarrhea, dizziness, taste distortion, or headaches. In the UK, treatment before culture results with amoxicillin is recommended as the first line for community-acquired pneumonia, with doxycycline or clarithromycin as alternatives. In North America, amoxicillin, doxycycline, and in some areas a macrolide (such as azithromycin or erythromycin) is the first-line outpatient treatment in adults. In children with mild or moderate symptoms, amoxicillin taken by mouth is the first line. The use of fluoroquinolones in uncomplicated cases is discouraged due to concerns about side-effects and generating resistance in light of there being no greater benefit.For those who require hospitalization and caught their pneumonia in the community the use of a β-lactam such as cephazolin plus macrolide such as azithromycin is recommended. A fluoroquinolone may replace azithromycin but is less preferred. Antibiotics by mouth and by injection appear to be similarly effective in children with severe pneumonia.The duration of treatment has traditionally been seven to ten days, but increasing evidence suggests that shorter courses (3–5 days) may be effective for certain types of pneumonia and may reduce the risk of antibiotic resistance. Research in children showed that a shorter, 3-day course of amoxicillin was as effective as a longer, 7-day course for treating pneumonia in this population. For pneumonia that is associated with a ventilator caused by non-fermenting Gram-negative bacilli (NF-GNB), a shorter course of antibiotics increases the risk that the pneumonia will return. Recommendations for hospital-acquired pneumonia include third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and vancomycin. These antibiotics are often given intravenously and used in combination. In those treated in hospital, more than 90% improve with the initial antibiotics. For people with ventilator-acquired pneumonia, the choice of antibiotic therapy will depend on the persons risk of being infected with a strain of bacteria that is multi-drug resistant. Once clinically stable, intravenous antibiotics should be switched to oral antibiotics. For those with Methicillin resistant Staphylococcus aureus (MRSA) or Legionella infections, prolonged antibiotics may be beneficial.The addition of corticosteroids to standard antibiotic treatment appears to improve outcomes, reducing death and morbidity for adults with severe community acquired pneumonia, and reducing death for adults and children with non-severe community acquired pneumonia. A 2017 review therefore recommended them in adults with severe community acquired pneumonia. A 2019 guideline however recommended against their general use, unless refractory shock was present. Side effects associated with the use of corticosteroids include high blood sugar. There is some evidence that adding corticosteroids to the standard PCP pneumonia treatment may be beneficial for people who are infected with HIV.The use of granulocyte colony stimulating factor (G-CSF) along with antibiotics does not appear to reduce mortality and routine use for treating pneumonia is not supported by evidence.

Viral
Neuraminidase inhibitors may be used to treat viral pneumonia caused by influenza viruses (influenza A and influenza B). No specific antiviral medications are recommended for other types of community acquired viral pneumonias including SARS coronavirus, adenovirus, hantavirus, and parainfluenza virus. Influenza A may be treated with rimantadine or amantadine, while influenza A or B may be treated with oseltamivir, zanamivir or peramivir. These are of most benefit if they are started within 48 hours of the onset of symptoms. Many strains of H5N1 influenza A, also known as avian influenza or "bird flu", have shown resistance to rimantadine and amantadine. The use of antibiotics in viral pneumonia is recommended by some experts, as it is impossible to rule out a complicating bacterial infection. The British Thoracic Society recommends that antibiotics be withheld in those with mild disease. The use of corticosteroids is controversial.

Aspiration
In general, aspiration pneumonitis is treated conservatively with antibiotics indicated only for aspiration pneumonia. The choice of antibiotic will depend on several factors, including the suspected causative organism and whether pneumonia was acquired in the community or developed in a hospital setting. Common options include clindamycin, a combination of a beta-lactam antibiotic and metronidazole, or an aminoglycoside.Corticosteroids are sometimes used in aspiration pneumonia, but there is limited evidence to support their effectiveness.

Follow-up
The British Thoracic Society recommends that a follow-up chest radiograph be taken in people with persistent symptoms, smokers, and people older than 50. American guidelines vary, from generally recommending a follow-up chest radiograph to not mentioning any follow-up.

Prognosis
With treatment, most types of bacterial pneumonia will stabilize in 3–6 days. It often takes a few weeks before most symptoms resolve. X-ray findings typically clear within four weeks and mortality is low (less than 1%). In the elderly or people with other lung problems, recovery may take more than 12 weeks. In persons requiring hospitalization, mortality may be as high as 10%, and in those requiring intensive care it may reach 30–50%. Pneumonia is the most common hospital-acquired infection that causes death. Before the advent of antibiotics, mortality was typically 30% in those that were hospitalized. However, for those whose lung condition deteriorates within 72 hours, the problem is usually due to sepsis. If pneumonia deteriorates after 72 hours, it could be due to nosocomial infection or excerbation of other underlying comorbidities. About 10% of those discharged from hospital are readmitted due to underlying co-morbidities such as heart, lung, or neurological disorders, or due to new onset of pneumonia.Complications may occur in particular in the elderly and those with underlying health problems. This may include, among others: empyema, lung abscess, bronchiolitis obliterans, acute respiratory distress syndrome, sepsis, and worsening of underlying health problems.

Clinical prediction rules
Clinical prediction rules have been developed to more objectively predict outcomes of pneumonia. These rules are often used to decide whether to hospitalize the person.
Pneumonia severity index (or PSI Score)
CURB-65 score, which takes into account the severity of symptoms, any underlying diseases, and age

Pleural effusion, empyema, and abscess
In pneumonia, a collection of fluid may form in the space that surrounds the lung. Occasionally, microorganisms will infect this fluid, causing an empyema. To distinguish an empyema from the more common simple parapneumonic effusion, the fluid may be collected with a needle (thoracentesis), and examined. If this shows evidence of empyema, complete drainage of the fluid is necessary, often requiring a drainage catheter. In severe cases of empyema, surgery may be needed. If the infected fluid is not drained, the infection may persist, because antibiotics do not penetrate well into the pleural cavity. If the fluid is sterile, it must be drained only if it is causing symptoms or remains unresolved.In rare circumstances, bacteria in the lung will form a pocket of infected fluid called a lung abscess. Lung abscesses can usually be seen with a chest X-ray but frequently require a chest CT scan to confirm the diagnosis. Abscesses typically occur in aspiration pneumonia, and often contain several types of bacteria. Long-term antibiotics are usually adequate to treat a lung abscess, but sometimes the abscess must be drained by a surgeon or radiologist.

Respiratory and circulatory failure
Pneumonia can cause respiratory failure by triggering acute respiratory distress syndrome (ARDS), which results from a combination of infection and inflammatory response. The lungs quickly fill with fluid and become stiff. This stiffness, combined with severe difficulties extracting oxygen due to the alveolar fluid, may require long periods of mechanical ventilation for survival. Other causes of circulatory failure are hypoxemia, inflammation, and increased coagulability.Sepsis is a potential complication of pneumonia but usually occurs in people with poor immunity or hyposplenism. The organisms most commonly involved are Streptococcus pneumoniae, Haemophilus influenzae, and Klebsiella pneumoniae. Other causes of the symptoms should be considered such as a myocardial infarction or a pulmonary embolism.

Epidemiology
Pneumonia is a common illness affecting approximately 450 million people a year and occurring in all parts of the world. It is a major cause of death among all age groups resulting in 4 million deaths (7% of the worlds total death) yearly. Rates are greatest in children less than five, and adults older than 75 years. It occurs about five times more frequently in the developing world than in the developed world. Viral pneumonia accounts for about 200 million cases. In the United States, as of 2009, pneumonia is the 8th leading cause of death.

Children
In 2008, pneumonia occurred in approximately 156 million children (151 million in the developing world and 5 million in the developed world). In 2010, it resulted in 1.3 million deaths, or 18% of all deaths in those under five years, of which 95% occurred in the developing world. Countries with the greatest burden of disease include India (43 million), China (21 million) and Pakistan (10 million). It is the leading cause of death among children in low income countries. Many of these deaths occur in the newborn period. The World Health Organization estimates that one in three newborn infant deaths is due to pneumonia. Approximately half of these deaths can be prevented, as they are caused by the bacteria for which an effective vaccine is available. In 2011, pneumonia was the most common reason for admission to the hospital after an emergency department visit in the U.S. for infants and children.

History
Pneumonia has been a common disease throughout human history. The word is from Greek πνεύμων (pneúmōn) meaning "lung". The symptoms were described by Hippocrates (c. 460–370 BC): "Peripneumonia, and pleuritic affections, are to be thus observed: If the fever be acute, and if there be pains on either side, or in both, and if expiration be if cough be present, and the sputa expectorated be of a blond or livid color, or likewise thin, frothy, and florid, or having any other character different from the common... When pneumonia is at its height, the case is beyond remedy if he is not purged, and it is bad if he has dyspnoea, and urine that is thin and acrid, and if sweats come out about the neck and head, for such sweats are bad, as proceeding from the suffocation, rales, and the violence of the disease which is obtaining the upper hand." However, Hippocrates referred to pneumonia as a disease "named by the ancients". He also reported the results of surgical drainage of empyemas. Maimonides (1135–1204 AD) observed: "The basic symptoms that occur in pneumonia and that are never lacking are as follows: acute fever, sticking pleuritic pain in the side, short rapid breaths, serrated pulse and cough." This clinical description is quite similar to those found in modern textbooks, and it reflected the extent of medical knowledge through the Middle Ages into the 19th century.
Edwin Klebs was the first to observe bacteria in the airways of persons having died of pneumonia in 1875. Initial work identifying the two common bacterial causes, Streptococcus pneumoniae and Klebsiella pneumoniae, was performed by Carl Friedländer and Albert Fraenkel in 1882 and 1884, respectively. Friedländers initial work introduced the Gram stain, a fundamental laboratory test still used today to identify and categorize bacteria. Christian Grams paper describing the procedure in 1884 helped to differentiate the two bacteria, and showed that pneumonia could be caused by more than one microorganism. In 1887, Jaccond demonstrated pneumonia may be caused by opportunistic bacteria always present in the lung.Sir William Osler, known as "the father of modern medicine", appreciated the death and disability caused by pneumonia, describing it as the "captain of the men of death" in 1918, as it had overtaken tuberculosis as one of the leading causes of death in this time. This phrase was originally coined by John Bunyan in reference to "consumption" (tuberculosis). Osler also described pneumonia as "the old mans friend" as death was often quick and painless when there were much slower and more painful ways to die.Viral pneumonia was first described by Hobart Reimann in 1938. Reimann, Chairman of the Department of Medicine at Jefferson Medical College, had established the practice of routinely typing the pneumococcal organism in cases where pneumonia presented </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sowda and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Leukoplakia and explain in detail? [/INST] Oral leukoplakia is a potentially malignant disorder affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque that develops in the oral cavity and is strongly associated with smoking. Leukoplakia is a firmly attached white patch on a mucous membrane which is associated with increased risk of cancer. The edges of the lesion are typically abrupt and the lesion changes with time. Advanced forms may develop red patches. There are generally no other symptoms. It usually occurs within the mouth, although sometimes mucosa in other parts of the gastrointestinal tract, urinary tract, or genitals may be affected.The cause of leukoplakia is unknown. Risk factors for formation inside the mouth include smoking, chewing tobacco, excessive alcohol, and use of betel nuts. One specific type is common in HIV/AIDS. It is a precancerous lesion, a tissue alteration in which cancer is more likely to develop. The chance of cancer formation depends on the type, with between 3–15% of localized leukoplakia and 70–100% of proliferative leukoplakia developing into squamous cell carcinoma.Leukoplakia is a descriptive term that should only be applied after other possible causes are ruled out. Tissue biopsy generally shows increased keratin build up with or without abnormal cells, but is not diagnostic. Other conditions that can appear similar include yeast infections, lichen planus, and keratosis due to repeated minor trauma. The lesions from a yeast infection can typically be rubbed off while those of leukoplakia cannot.Treatment recommendations depend on features of the lesion. If abnormal cells are present or the lesion is small surgical removal is often recommended; otherwise close follow up at three to six month intervals may be sufficient. People are generally advised to stop smoking and limit the drinking of alcohol. In potentially half of cases leukoplakia will shrink with stopping smoking; however, if smoking is continued up to 66% of cases will become more white and thick. The percentage of people affected is estimated at 1–3%. Leukoplakia becomes more common with age, typically not occurring until after 30. Rates may be as high as 8% in men over the age of 70.

Classification
Leukoplakia could be classified as mucosal disease, and also as a premalignant condition. Although the white color in leukoplakia is a result of hyperkeratosis (or acanthosis), similarly appearing white lesions that are caused by reactive keratosis (smokers keratosis or frictional keratoses e.g. morsicatio buccarum) are not considered to be leukoplakias. Leukoplakia could also be considered according to the affected site, e.g. oral leukoplakia, leukoplakia of the urinary tract, including bladder leukoplakia or leukoplakia of the penis, vulvae, cervix or vagina. Leukoplakia may also occur in the larynx, possibly in association with gastro-esophageal reflux disease. Oropharyngeal leukoplakia is linked to the development of esophageal squamous cell carcinoma, and sometimes this is associated with tylosis, which is thickening of the skin on the palms and soles of the feet (see: Leukoplakia with tylosis and esophageal carcinoma). Dyskeratosis congenita may be associated with leukoplakia of the oral mucosa and of the anal mucosa.

Mouth
Within the mouth, leukoplakia is sometimes further classified according to the site involved, e.g. leukoplakia buccalis (leukoplakia of the buccal mucosa) or leukoplakia lingualis (leukoplakia of the lingual mucosa). There are two main clinical variants of oral leukoplakia, namely homogeneous leukoplakia and non-homogeneous (heterogenous) leukoplakia, which are described below. The word leukoplakia is also included within the nomenclature of other oral conditions which present as white patches, however, these are specific diagnoses that are generally considered separate from leukoplakia, with the notable exception of proliferative verrucous leukoplakia, which is a recognized sub-type of leukoplakia.

Homogeneous leukoplakia
Homogeneous leukoplakia (also termed "thick leukoplakia") is usually well defined white patch of uniform, flat appearance and texture, although there may be superficial irregularities. Homogeneous leukoplakia is usually slightly elevated compared to surrounding mucosa, and often has a fissured, wrinkled or corrugated surface texture, with the texture generally consistent throughout the whole lesion. This term has no implications on the size of the lesion, which may be localized or extensive. When homogeneous leukoplakia is palpated, it may feel leathery, dry, or like cracked mud.

Non-homogeneous leukoplakia
Non-homogeneous leukoplakia is a lesion of non-uniform appearance. The color may be predominantly white or a mixed white and red. The surface texture is irregular compared to homogeneous leukoplakia, and may be flat (papular), nodular or exophytic. "Verrucous leukoplakia" (or "verruciform leukoplakia") is a descriptive term used for thick, white, papillary lesions. Verrucous leukoplakias are usually heavily keratinized and are often seen in elderly people. Some verrucous leukoplakias may have an exophytic growth pattern, and some may slowly invade surrounding mucosa, when the term proliferative verrucous leukoplakia may be used. Non-homogeneous leukoplakias have a greater risk of cancerous changes than homogeneous leukoplakias.

Proliferative verrucous leukoplakia
Proliferative verrucous leukoplakia (PVL) is a recognized high risk subtype of non-homogeneous leukoplakia. It is uncommon, and usually involves the buccal mucosa and the gingiva (the gums). This condition is characterized by (usually) extensive, papillary or verrucoid keratotic plaques that tends to slowly enlarge into adjacent mucosal sites. An established PVL lesion is usually thick and exophytic (prominent), but initially it may be flat. Smoking does not seem to be as strongly related as it is to leukoplakia generally, and another dissimilarity is the preponderance for women over 50. There is a very high risk of dysplasia, transformation to squamous cell carcinoma with high mortality (PVL does not transform into verrucous carcinoma, which is a lesion with a good prognosis usually; the similarity of names does not reflect the common origin, but only the resemblance of their appearance).

Erythroleukoplakia
Erythroleukoplakia (also termed speckled leukoplakia, erythroleukoplasia or leukoerythroplasia) is a non-homogeneous lesion of mixed white (keratotic) and red (atrophic) color. Erythroplakia (erythroplasia) is an entirely red patch that cannot be attributed to any other cause. Erythroleukoplakia can therefore be considered a variant of either leukoplakia or erythroplakia since its appearance is midway between. Erythroleukoplakia frequently occurs on the buccal mucosa in the commissural area (just inside the cheek at the corners of the mouth) as a mixed lesion of white nodular patches on an erythematous background, although any part of the mouth may be affected. Erythroleukoplakia and erythroplakia have a higher risk of cancerous changes than homogeneous leukoplakia.

Sublingual keratosis
Sometimes leukoplakia of the floor of mouth or under the tongue is called sublingual keratosis,. though this is not universally accepted to be a distinct clinical entity from idiopathic leukoplakia generally, as it is distinguished from the latter by location only. Usually sublingual keratoses are bilateral and possess a parallel-corrugated, wrinkled surface texture described as "ebbing tide".

Candidal leukoplakia
Candidal leukoplakia is usually considered to be a largely historical synonym for a type of oral candidiasis, now more commonly termed chronic hyperplastic candidiasis, rather than a subtype of true leukoplakia. However, some sources use this term to refer to leukoplakia lesions that become colonized secondarily by Candida species, thereby distinguishing it from hyperplastic candidiasis.

Oral hairy leukoplakia
Oral hairy leukoplakia is a corrugated ("hairy") white lesion on the sides of the tongue caused by opportunistic infection with Epstein-Barr virus on a systemic background of immunodeficiency, almost always human immunodeficiency virus (HIV) infection. This condition is not considered to be a true idiopathic leukoplakia since the causative agent has been identified. It is one of the most common oral lesions associated with HIV infection, along with pseudomembraneous candidiasis. The appearance of the lesion often heralds the transition from HIV to acquired immunodeficiency syndrome (AIDS).

Syphilitic leukoplakia
This term refers to a white lesion associated with syphilis, specifically in the tertiary stage of the infection. It is not considered to be a type of idiopathic leukoplakia, since the causative agent Treponema pallidum is known. It is now rare, but when syphilis was more common, this white patch usually appeared on the top surface of the tongue and carried a high risk of cancerous changes. It is unclear if this lesion was related to the condition itself or whether it was caused by the treatments for syphilis at the time.

Esophagus
Leukoplakia of the esophagus is rare compared to oral leukoplakia. The relationship with esophageal cancer is unclear because the incidence of esophageal leukoplakia is so low. It usually appears as a small, nearly opaque white lesion that may resemble early esophageal squamous cell carcinoma. The histologic appearance is similar to oral leukoplakia, with hyperkeratosis and possible dysplasia.

Bladder
In the context of lesions of the mucous membrane lining of the bladder, leukoplakia is a historic term for a visualized white patch which histologically represents keratinization in an area of squamous metaplasia. The symptoms may include frequency, suprapubic pain (pain felt above the pubis), hematuria (blood in the urine), dysuria (difficult urination or pain during urination), urgency, and urge incontinence. The white lesion may be seen during cystoscopy, where it appears as a whitish-gray or yellow lesion, on a background of inflamed urothelium and there may be floating debris in the bladder. Leukoplakia of the bladder may undergo cancerous changes, so biopsy and long term follow up are usually indicated.

Anal canal
Leukoplakia of the anal canal is rare. It may extend up to the anorectal junction. On digital examination it feels hard and granular, and at proctoscopy, it appears as white plaques which may be diffuse, circumferential, or circumscribed. The histologic appearance is similar to oral leukoplakia, with hyperkeratosis and acanthosis. It may be asymptomatic, with symptoms due to other lesions such as hemorrhoids or fissures. Progression to anal stenosis has been described. The malignant potential is seemingly low, and few cases of anal carcinoma have been reported associated with anal leukoplaka.

Signs and symptoms
Most cases of leukoplakia cause no symptoms, but infrequently there may be discomfort or pain. The exact appearance of the lesion is variable. Leukoplakia may be white, whitish yellow or grey. The size can range from a small area to much larger lesions. The most common sites affected are the buccal mucosa, the labial mucosa and the alveolar mucosa, although any mucosal surface in the mouth may be involved. The clinical appearance, including the surface texture and color, may be homogeneous or non-homogeneous (see: classification). Some signs are generally associated with a higher risk of cancerous changes (see: prognosis).
Leukoplakia may rarely be associated with esophageal carcinoma.: 805

Causes
The exact underlying cause of leukoplakia is largely unknown, but it is likely multifactorial, with the main factor being the use of tobacco. Tobacco use and other suggested causes are discussed below. The mechanism of the white appearance is thickening of the keratin layer, called hyperkeratosis. The abnormal keratin appears white when it becomes hydrated by saliva, and light reflects off the surface evenly. This hides the normal pink-red color of mucosae (the result of underlying vasculature showing through the epithelium). A similar situation can be seen on areas of thick skin such as the soles of the feet or the fingers after prolonged immersion in water. Another possible mechanism is thickening of the stratum spinosum, called acanthosis.

Tobacco
Tobacco smoking or chewing is the most common causative factor, with more than 80% of persons with leukoplakia having a positive smoking history. Smokers are much more likely to develop leukoplakia than non-smokers. The size and number of leukoplakia lesions in an individual is also correlated with the level of smoking and how long the habit has lasted for. Other sources argue that there is no evidence for a direct causative link between smoking and oral leukoplakia. Cigarette smoking may produce a diffuse leukoplakia of the buccal mucosa, lips, tongue and rarely the floor of mouth. Reverse smoking, where the lit end of the cigarette is held in the mouth is also associated with mucosal changes. Tobacco chewing, e.g. betel leaf and areca nut, called paan, tends to produce a distinctive white patch in a buccal sulcus termed "tobacco pouch keratosis". In the majority of persons, cessation triggers shrinkage or disappearance of the lesion, usually within the first year after stopping.

Alcohol
Although the synergistic effect of alcohol with smoking in the development of oral cancer is beyond doubt, there is no clear evidence that alcohol is involved in the development of leukoplakia, but it does appear to have some influence. Excessive use of a high alcohol-containing mouth wash (> 25%) may cause a grey plaque to form on the buccal mucosa, but these lesions are not considered true leukoplakia.

Sanguinaria
Sanguinaria (Bloodroot) is a herbal extract that is included in some toothpastes and mouthwashes. Its use is strongly associated with development of leukoplakia, usually in the buccal sulcus. This type of leukoplakia has been termed "sanguinaria associated keratosis" and more than 80% of people with leukoplakia in the vestibule of the mouth have used this substance.  Upon stopping contact with the causative substance, the lesions may persist for many years. Although this type of leukoplakia may show dysplasia, the potential for malignant transformation is unknown.

Ultraviolet radiation
Ultraviolet radiation is believed to be a factor in the development of some leukoplakia lesions of the lower lip, usually in association with actinic cheilitis.

Micro-organisms
Candida in its pathogenic hyphal form is occasionally seen in biopsies of idiopathic leukoplakia. It is debated whether candida infection is a primary cause of leukoplakia with or without dysplasia, or a superimposed (secondary) infection that occurs after the development of the lesion. It is known that Candida species thrive in altered tissues. Some leukoplakias with dysplasia reduce or disappear entirely following use of antifungal medication. Smoking, which as discussed above can lead to the development of leukoplakia, can also promote oral candidiasis. Candida in association with leukoplakia should not be confused with white patches which are primarily caused by candida infection, such as chronic hyperplastic candidiasis ("candidal leukoplakia").The involvement of viruses in the formation of some oral white lesions is well established, e.g. Epstein-Barr virus in oral hairy leukoplakia (which is not a true leukoplakia). Human papilloma virus (HPV), especially HPV 16 and 18, is sometimes found in areas of leukoplakia, however, since this virus can be coincidentally found on normal, healthy mucosal surfaces in the mouth, it is unknown if this virus is involved in the development of some leukoplakias. In vitro experimentation has demonstrated that HPV 16 is capable of inducing dysplastic changes in previously normal squamous epithelium.

Epithelial atrophy
Leukoplakia is more likely to develop in areas of epithelial atrophy. Conditions associated with mucosal atrophy include iron deficiency, some vitamin deficiencies, oral submucous fibrosis, syphilis and sideropenic dysphagia.

Trauma
Another very common cause of white patches in the mouth is frictional or irritational trauma leading to keratosis. Examples include nicotine stomatitis, which is keratosis in response to heat from tobacco smoking (rather than a response to the carcinogens in tobacco smoke). The risk of malignant transformation is similar to normal mucosa. Mechanical trauma, e.g. caused by a sharp edge on a denture, or a broken tooth, may cause white patches which appear very similar to leukoplakia. However, these white patches represent a normal hyperkeratotic reaction, similar to a callus on the skin, and will resolve when the cause is removed. Where there is a demonstrable cause such as mechanical or thermal trauma, the term idiopathic leukoplakia should not be used.

Pathophysiology
Tumor suppressor genes
Tumor suppressor genes are genes involved in the regulation of normal cell turnover and apoptosis (programmed cell death). One of the most studied tumor suppressor genes is p53, which is found on the short arm of chromosome 17. Mutation of p53 can disrupt its regulatory function and lead to uncontrolled cell growth. Mutations of p53 have been demonstrated in the cells from areas of some leukoplakias, especially those with dysplasia and in individuals who smoke and drink heavily.

Diagnosis
Definition
Leukoplakia is a diagnosis of exclusion, meaning that which lesions are included depends upon what diagnoses are currently considered acceptable. Accepted definitions of leukoplakia have changed over time and are still controversial. It is possible that the definition will be further revised as new knowledge becomes available.
In 1984 an international symposium agreed upon the following definition: "a whitish patch or plaque, which cannot be characterized clinically or pathologically as any other disease, and is not associated with any physical or chemical agent except the use of tobacco." There were, however, problems and confusion in applying this definition. At a second international symposium held in 1994, it was argued that whilst tobacco was a likely causative factor in the development of leukoplakia, some white patches could be linked directly to the local effects of tobacco by virtue of their disappearance following smoking cessation, suggesting that this kind of white patch represents a reactive lesion to local tissue irritation rather than a lesion caused by carcinogens in cigarette smoke, and could be better termed to reflect this etiology, e.g. smokers keratosis. The second international symposium, therefore, revised the definition of leukoplakia to: "a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion."
In the mouth, the current definition of oral leukoplakia adopted by the World Health Organization is "white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer". However, this definition is inconsistently applied in the medical literature, and some refer to any oral white patch as "leukoplakia".The term has been incorrectly used for white patches of any cause (rather than specifically referring to idiopathic white patches) and also to refer only to white patches which have a risk of cancerous changes. It has been suggested that leukoplakia is an unhelpful term since there is so much inconsistency surrounding its use, and some clinicians now avoid using it at all.

Biopsy
Tissue biopsy is usually indicated to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia. This is an indicator of malignant potential and usually determines the management and recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated areas. These areas are more likely to show any dysplasia than homogeneous white areas.Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is scraped against the lining of the mouth to remove a sample of cells. This is then made into a smear which can be examined microscopically. Sometimes the biopsy site can be selected with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining, where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is high false positive rate. Other methods involve the use of luminescence, relying on either the property of normal autoflorescent molecules in mucosa such as collagen and keratin which is lost from areas of dysplasia or carcinoma under blue light or by initially staining of the mucosa with toluidine blue or dilute acetic acid and examination under white light.

Histologic appearance
Leukoplakia has a wide range of possible histologic appearances. The degree of hyperkeratosis, epithelial thickness (acanthosis/atrophy), dysplasia and inflammatory cell infiltration in the underlying lamina propria are variable. In mucous membranes, hyperkeratosis can be defined as "an increase in the thickness of the keratin layer of the epithelium, or the presence of such a layer in a site where none would normally be expected." In leukoplakia, the hyperkeratosis varies in thickness and may be either ortho- or para-keratosis, (depending upon whether cell nuclei are lost or retained in the superficial layers respectively), or a mixture of both in different areas of the lesion.The epithelium may show hypertrophy (e.g. acanthosis) or atrophy. Red areas within leukoplakia represent atrophic or immature epithelium which has lost the ability to keratinize. The transition between the lesion and normal surrounding mucosa may be well-demarcated, or poorly defined. Melanin, a pigment naturally produced in oral mucosa, can leak from cells and give a grey color to some leukoplakia lesions.Hyperkeratosis and altered epithelial thickness may be the only histologic features of a leukoplakia lesion, but some show dysplasia. The word "dysplasia" generally means "abnormal growth", and specifically, in the context of oral red or white lesions, refers to microscopic changes ("cellular atypia") in the mucosa that indicate a risk of malignant transformation. When dysplasia is present, there is generally an inflammatory cell infiltration in the lamina propria. The following are commonly cited as being possible features of epithelial dysplasia in leukoplakia specimens:
Cellular pleomorphism, in which cells are of abnormal and different shapes.
Nuclear atypia, in which the nuclei of cells varies in size, any may be increased in size relative to the cytoplasm, shape, and may stain more intensely. There may also be more prominent nucleoli.
Increased number of cells seen undergoing mitosis, including both normal and abnormal mitoses. Abnormal mitosis may be abnormally located, e.g. occurring in suprabasal cells (cell layers more superficial to the basal cell layer) or of abnormal form, e.g. "tri-radiate mitoses" (a cell splitting into 3 daughter cells rather than only 2)
Loss the normal organization of the epithelial layers. The distinction between the epithelial layers may be lost. Normally stratified squamous epithelium shows progressive changes in the form of cells from the basal to the superficial layers, with cells becoming more flat ("squames") towards the surface as a continuous maturation process. In dysplastic epithelium, cells may become vertically orientated rather than becoming flat towards the surface.
There may be abnormal keratinization, where keratin is formed below the normal keratin layer. This can occur in individual cells or groups of cells, forming an intraepithelial keratin pearl.  There may be an increase in the number of basal cells, and they may lose their cellular orientation (losing their polarity and long axis).
Alteration of the normal epithelial-connective tissue architecture - the rete pegs may become "drop shaped". wider at their base than more superficially.Generally, dysplasia is subjectively graded by pathologists into mild, moderate or severe dysplasia. This requires experience as it is a difficult skill to learn. It has been shown that there is high degree of inter-observer variation and poor reproducibility in how dysplasia is graded. Severe dysplasia is synonymous with the term carcinoma in situ, denoting the presence of neoplastic cells which have not yet penetrated the basement membrane and invaded other tissues.

Differential diagnosis
There are many known conditions that present with a white lesion of the oral mucosa, but the majority of oral white patches have no known cause. These are termed leukoplakia once other likely possibilities have been ruled out. There are also few recognized subtypes of leukoplakia, described according to the clinical appearance of the lesion.
Almost all oral white patches are usually the result of keratosis. For this reason, oral white patches are sometimes generally described as keratoses, although a minority of oral white lesions are not related to hyperkeratosis, e.g. epithelial necrosis and ulceration caused by a chemical burn (see: Oral ulceration#Chemical injury). In keratosis, the thickened keratin layer absorbs water from saliva in the mouth and appears white in comparison with normal mucosa. Normal oral mucosa is a red-pink color due to the underlying vasculature in the lamina propria showing through the thin layer of epithelium. Melanin produced in the oral mucosa also influences the color, with a darker appearance being created by higher levels of melanin in the tissues (associated with racial/physiologic pigmentation, or with disorders causing melanin overproduction such as Addisons disease). Other endogenous pigments can be overproduced to influence the color, e.g. bilirubin in hyperbilirubinemia or hemosiderin in hemochromatosis, or exogenous pigments such as heavy metals can be introduced into the mucosa, e.g. in an amalgam tattoo.
Almost all white patches are benign, i.e. non-malignant. The differential diagnosis of a white lesion in the mouth can be considered according to a surgical sieve (see table).Leukoplakia cannot be rubbed off the mucosa, distinguishing it readily from white patches such as pseudomembraneous candidiasis, where a white layer can be removed to reveal an erythematous, sometimes bleeding surface underneath. The white color associated with leukoedema disappears when the mucosa is stretched. A frictional keratosis will generally be adjacent to a sharp surface such as a broken tooth or rough area on a denture and will disappear when the causative factor is removed. Some have a suggested as general rule that any lesion that does not show signs of healing within 2 weeks should be biopsied. Morsicatio buccarum and linea alba are located at the level of the occlusal plane (the level at which the teeth meet). A chemical burn has a clear history of placing an aspirin tablet (or other caustic substance such as eugenol) against the mucosa in an attempt to relieve toothache. Developmental white patches usually are present from birth or become apparent earlier in life, whilst leukoplakia generally affects middle aged or elderly people. Other causes of white patches generally require pathologic examination of a biopsy specimen to distinguish with certainty from leukoplakia.

Management
A systematic review found that no treatments commonly used for leukoplakia have been shown to be effective in preventing malignant transformation. Some treatments may lead to healing of leukoplakia, but do not prevent relapse of the lesion or malignant change. Regardless of the treatment used, a diagnosis of leukoplakia almost always leads to a recommendation that possible causative factors such as smoking and alcohol consumption be stopped, and also involves long term review of the lesion, to detect any malignant change early and thereby improve the prognosis significantly.

Predisposing factors and review
Beyond advising smoking cessation, many clinicians will employ watchful waiting rather than intervene. Recommended recall intervals vary. One suggested program is every 3 months initially, and if there is no change in the lesion, then annual recall thereafter. Some clinicians use clinical photographs of the lesion to help demonstrate any changes between visits. Watchful waiting does not rule out the possibility of repeated biopsies. If the lesion changes in appearance repeat biopsies are especially indicated. Since smoking and alcohol consumption also places individuals at higher risk of tumors occurring in the respiratory tract and pharynx, "red flag" symptoms (e.g. hemoptysis - coughing blood) often trigger medical investigation by other specialties.

Surgery
Surgical removal of the lesion is the first choice of treatment for many clinicians. However, the efficacy of this treatment modality cannot be assessed due to insufficient available evidence. This can be carried out by traditional surgical excision with a scalpel, with lasers, or with eletrocautery or cryotherapy. Often, if biopsy demonstrates moderate or severe dysplasia then the decision to excise them is taken more readily. Sometimes, white patches are too large to remove completely and instead they are monitored closely. Even if the lesion is completely removed, long term review is still usually indicated since leukoplakia can recur, especially if predisposing factors such as smoking are not stopped.

Medications
Many different topical and systemic medications have been studied, including anti-inflammatories, antimycotics (target Candida species), carotenoids (precursors to vitamin A, e.g. beta carotene), retinoids (drugs similar to vitamin A), and cytotoxics, but none have evidence that they prevent malignant transformation in an area of leukoplakia. Vitamins C and E have also been studied with regards a therapy for leukoplakia. Some of this research is carried out based upon the hypothesis that antioxidant nutrients, vitamins and cell growth suppressor proteins (e.g. p53) are antagonistic to oncogenesis. High doses of retinoids may cause toxic effects. Other treatments that have been studied include photodynamic therapy.

Prognosis
The annual malignant transformation rate of leukoplakia rarely exceeds 1%, i.e. the vast majority of oral leukoplakia lesions will remain benign. A number of clinical and histopathologic features are associated with varying degrees of increased risk of malignant transformation, although other sources argue that there are no universally accepted and validated factors which can reliably predict malignant change. It is also unpredictable to an extent if an area of leukoplakia will disappear, shrink or remain stable.
Presence and degree of dysplasia (mild, moderate or severe/carcinoma in situ). While the degree of dysplasia has been shown to be an important predictor of malignant change, many have challenged its use due to the low predictive value from the lack of objectivity of grading dysplasia. While 10% of leukoplakia lesions show dysplasia when biopsied, as many as 18% of oral lesions undergo malignant change in the absence of dysplasia.
Leukoplakia located on the floor of the mouth, the posterior and lateral tongue, and the retromolar areas (the region behind the wisdom teeth) have higher risk, whereas white patches in areas such as the top surface of the tongue and the hard palate do not have significant risk. Although these "high risk" sites are recognized, statistically, leukoplakia is more common on the buccal mucosa, alveolar mucosa, and the lower labial mucosa. Leukoplakia of the floor of the mouth and tongue accounts for over 90% of leukoplakias showing dysplasia or carcinoma on biopsy.  This is thought to be due to pooling of saliva in the lower part of the mouth, exposing these areas to more carcinogens held in suspension.
Red lesions (erythroplasia) and mixed red and white lesions (erythroleukoplakia/"speckled leukoplakia") have a higher risk of malignant change than homogeneous leukoplakia.
Verrucous or nodular areas have a higher risk.
Although smoking increases risk of malignant transformation, smoking also causes many white patches with no dysplasia. This means that statistically, white patches in non-smokers have a higher risk.
Older people with white patches are at higher risk.
Larger white patches are more likely to undergo malignant transformation than smaller lesions.
White patches which have been present for a long period of time have a higher risk.
Persons with a positive family history of cancer in the mouth.
Candida infection in the presence of dysplasia has a small increased risk.
A change in the appearance of the white patch, apart from a change in the color, has a higher risk. Changes in the lesion such as becoming fixed to underlying tissues, ulceration, cervical lymphadenopathy (enlargement of lymph nodes in the neck), and bone destruction may herald the appearance of malignancy.
White patches present in combination with other conditions that carry a higher risk (e.g. oral submucous fibrosis), are more likely to turn malignant.
Although overall, oral cancer is more common in males, females with white patches are at higher risk than men.

Epidemiology
The prevalence of oral leukoplakia varies around the world, but generally speaking it is not an uncommon condition. Reported prevalence estimates range from less than 1% to more than 5% in the general population. Leukoplakia is, therefore, the most common premalignant lesion that occurs in the mouth. Leukoplakia is more common in middle-aged and elderly males. The prevalence increases with increasing age </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Posterior amorphous corneal dystrophy and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Dawn phenomenon and explain in detail? [/INST] The dawn phenomenon, sometimes called the dawn effect, is an observed increase in blood sugar (glucose) levels that takes place in the early-morning, often between 2 a.m. and 8 a.m. First described by Schmidt in 1981 as an increase of blood glucose or insulin demand occurring at dawn, this naturally occurring phenomenon is frequently seen among the general population and is clinically relevant for patients with diabetes as it can affect their medical management. In contrast to Chronic Somogyi rebound, the dawn phenomenon is not associated with nocturnal hypoglycemia.

Physiology
Although not yet completely understood, the dawn phenomenon is thought to be caused by an exaggeration of the normal physiologic hormonal processes that occur overnight. Overnight the human body sees increased levels of several hormones, most notably growth hormone and catecholamines, that lead to increased rates of glucose production and release from the liver. These hormones also inhibit the effects of insulin, leading to an overall increase in circulating blood glucose. This effect is amplified in patients with islet β-cell dysfunction such as diabetics. Notably throughout this process glucagon levels remain unchanged and the increased levels of cortisol observed overnight do not appear to be involved </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations and explain in detail? [/INST] Retinal vasculopathy with cerebral leukocencephalopathy and systemic manifestations (RVCL or RVCL-S, also previously known as retinal vasculopathy with cerebral leukodystrophy, RVCL; or cerebroretinal vasculopathy, CRV; or hereditary vascular retinopathy, HVR; or hereditary endotheliopathy, retinopathy, nephropathy, and stroke, HERNS) is an inherited condition resulting from a frameshift mutation in the C-terminal region of the TREX1 gene. This disease affects  small blood vessels, leading to damage of multiple organs including but not limited to the retina and the white matter of the central nervous system. Patients with RVCL develop vision loss, brain lesions, strokes, brain atrophy, and dementia. Patients with RVCL also exhibit other organ involvement, including kidney, liver, gastrointestinal tract, thyroid, and bone disease. Symptoms of RVCL commonly begin between ages 40 and 50, although sometimes disease onset occurs earlier or later. The overall prognosis is poor, and death can sometimes occur within 5 or 10 years of the first symptoms appearing, although patients sometimes live about 20 years after initial symptoms. Clinical trials are underway, as are efforts to develop personalized medicines for patients with RVCL.

Presentation
For most patients, disease onset is between ages 35 and 55.  Earliest onset is usually not before age 35. Late onset is usually not after age 55.
RVCL affects multiple organs.  All patients develop brain and eye disease, leading to disability, vision loss, and premature death.
All patients with RVCL develop kidney and liver disease, with elevated alkaline phosphatase. Some patients develop bone lesions (osteonecrosis) as well as hypothyroidism. Sometimes patients also develop gastrointestinal symptoms or bleeding.
RVCL is associated with progressive deterioration in visual acuity due to multifocal microvascular disease, retinal neovascularization leading, and/or glaucoma. Retinal microvascular disease is noninflammatory and resembles that of diabetic retinopathy. This leads to partial or complete vision loss.
Headaches due to multiple factors including brain lesions, edema, and papilledema.
Mental confusion, loss of cognitive function, loss of memory, slowing of speech and hemiparesis due to brain lesions. Some patients have Jacksonian seizures or grand mal seizures.
Progressive neurologic deterioration unresponsive to systemic immunosuppression including corticosteroid therapy and chemotherapeutic agents.
Autopsy typically demonstrates discrete, often confluent, foci of coagulative necrosis in the cerebral white matter, with intermittent findings of fine calcium deposition within necrotic foci. Additionally, tissues exhibit vasculopathic changes involving both arteries and veins of medium and small caliber in the cerebral white matter. There is fibrinoid necrosis of vessel walls with extravasation of fibrinoid material into adjacent parenchyma present in both necrotic and non-necrotic tissue. Vessels can exhibit obliterative fibrosis in all the layers of vessel walls, as well as perivascular, adventitial fibrosis with limited intimal thickening.
In rare cases, RVCL has been associated with severe disease involving other organs outside the brain and the eye (e.g., osteonecrosis requiring joint replacement, gastrointestinal ischemia leading to bowel resection, or liver failure requiring liver transplantation).

Clinical Associations
Raynauds phenomenon
Anemia
Hypertension
Normocytic anemia
Normochromic anemia
Gastrointestinal bleeding or telangiectasias
Elevated alkaline phosphatase
Chronic kidney disease

Genetics
RVCL is caused by mutations in the TREX1 gene. The official name of the TREX1 gene is "three prime repair exonuclease 1".  The normal function of the TREX1 gene is to provide instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during genetic material in preparation for cell division, DNA repair, cell death, and other processes.
Changes (mutations) to the TREX1 gene can result in a range of conditions, one of which is RVCL.  The mutant TREX1 protein is produced and mislocalized. Haploinsufficiency of TREX1 does not explain the disease, since the parents of patients with Aicairdi-Goutieres syndrome, a disease characterized by insufficient TREX1 activity, are completely healthy with only one functional TREX1 allele.
Different mutations in the TREX1 gene have also been identified in people with disorders involving the immune system. These disorders include a chronic inflammatory disease called Aicardi-Goutieres syndrome, as well as systemic lupus erythematosus (SLE), including a rare form of SLE called chilblain lupus that mainly affects the skin. Those diseases, which are inflammatory, may have a completely distinct mechanism compared with that of RVCL.
The TREX1 gene is located on chromosome 3: base pairs 48,465,519 to 48,467,644

Pathogenesis
The main pathologic process centers on small blood vessels that prematurely "drop out" and disappear.  The retina of the eye and white matter of the brain appear to be among the most sensitive to this pathologic process.  Over a five- to ten-year period, this vasculopathy (blood vessel pathology) results in vision loss and destructive brain lesions with neurologic deficits and death.
Although brain and eye disease are universally present in patients with RVCL, the disease is truly a multi-system disorder characterized by chronic kidney disease, liver disease, and frequently other manifestations including gastrointestinal disease, osteonecrosis, and hypothyroidism.

Diagnosis
Differential diagnosis
Treatment
Currently, there is no therapy that is proven to prevent the blood vessel deterioration. In 2021, Dr </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Thunderclap headache and explain in detail? [/INST] A thunderclap headache is a headache that is severe and has a  sudden onset. It is defined as a severe headache that takes seconds to minutes to reach maximum intensity. Although approximately 75% are attributed to "primary" headaches—headache disorder, non-specific headache, idiopathic thunderclap headache, or uncertain headache disorder—the remainder are secondary to other causes, which can include some extremely dangerous acute conditions, as well as infections and other conditions. Usually, further investigations are performed to identify the underlying cause.

Signs and symptoms
A headache is called "thunderclap headache" if it is severe in character and reaches maximum severity within seconds to minutes of onset. In many cases, there are no other abnormalities, but the various causes of thunderclap headaches may lead to a number of neurological symptoms.

Causes
Approximately 75% are attributed to "primary" headaches: headache disorder, non-specific headache, idiopathic thunderclap headache or uncertain headache disorder.  The remainder are secondary to a number of conditions, including:
Subarachnoid hemorrhage (10–25% of all cases of thunderclap headache)
Cerebral venous sinus thrombosis
Cervical artery dissection
Hypertensive emergency (severely raised blood pressure)
Spontaneous intracranial hypotension (unexplained low cerebrospinal fluid pressure)
Stroke (headache occurs in about 25% of strokes but usually not thunderclap character)
Retroclival hematoma (hematoma behind the clivus in the skull, usually due to physical trauma but sometimes spontaneous)
Pituitary apoplexy (infarction or hemorrhage of the pituitary gland)
Colloid cyst of the third ventricle
Meningitis, sinusitis
Reversible cerebral vasoconstriction syndrome (previously Call-Fleming syndrome, several subtypes)
Primary cough headache, primary exertional headache, and primary sexual headacheThe most important of the secondary causes are subarachnoid hemorrhage, cerebral venous sinus thrombosis, and dissection of an artery in the neck.In subarachnoid hemorrhage, there may be syncope (transient loss of consciousness), seizures, meningism (neck pain and stiffness), visual symptoms, and vomiting. 50–70% of people with subarachnoid hemorrhage have an isolated headache without decreased level of consciousness. The headache typically persists for several days.Cerebral venous sinus thrombosis, thrombosis of the veins of the brain, usually causes a headache that reflects raised intracranial pressure and is therefore made worse by anything that makes the pressure rise further, such as coughing. In 2–10% of cases, the headache is of thunderclap character. In most cases there are other neurological abnormalities, such as seizures and weakness of part of the body, but in 15–30% the headache is the only abnormality.Carotid artery dissection and vertebral artery dissection (together cervical artery dissection), in which a tear forms inside the wall of the blood vessels that supply the brain, often causes pain on the affected side of the head or neck. The pain usually precedes other problems that are caused by impaired blood flow through the artery into the brain; these may include visual symptoms, weakness of part of the body, and other abnormalities depending on the vessel affected.

Diagnosis
The most important initial investigation is computed tomography of the brain, which is very sensitive for subarachnoid hemorrhage. If this is normal, a lumbar puncture is performed, as a small proportion of SAH is missed on CT and can still be detected as xanthochromia.If both investigations are normal, the specific description of the headache and the presence of other abnormalities may prompt further tests, usually involving magnetic resonance imaging (MRI). Magnetic resonance angiography (MRA) may be useful in identifying problems with the arteries (such as dissection), and magnetic resonance venography (MRV) identifies venous thrombosis. It is not usually necessary to proceed to cerebral angiography, a more precise but invasive investigation of the brains blood vessels, if MRA and MRV are normal.

Epidemiology
Incidence of thunderclap headache has been estimated at 43 per 100,000 people every year. Approximately 75% are attributed to "primary" headaches: headache disorder, non-specific headache, idiopathic thunderclap headache or uncertain headache disorder. The remainder is attributed to secondary causes: vascular problems, infections and various other conditions.

History
The importance of severe headaches in the diagnosis of subarachnoid hemorrhage has been known since the 1920s, when London neurologist Charles Symonds described the clinical syndrome. The term "thunderclap headache" was introduced in 1986 in a report by John Day and Neil Raskin, neurologists at the University of California, San Francisco, in a report of a 42-year-old woman who had experienced several sudden headaches and was found to have an aneurysm that had not ruptured.

References
Further reading
Dodick, DW (1 January 2002). "Thunderclap headache". Journal of Neurology, Neurosurgery & Psychiatry. 72 (1): 6–11. doi:10.1136/jnnp.72.1.6. PMC 1737692. PMID 11784817.
Ju, Yo-El; Schwedt, Todd (29 March 2010). "Abrupt-Onset Severe Headaches". Seminars in Neurology </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Nutritional anemia and explain in detail? [/INST] Anemia is a deficiency in the size or number of red blood cells or in the amount of hemoglobin they contain.This deficiency limits the exchange of O2 and CO2 between the blood and the tissue cells.Globally, young children, women, and older adults are at the highest risk of developing anemia. Anemia can be classified based on different parameters, and one classification depends on whether it is related to nutrition or not so there are two types: nutritional anemia and non-nutritional anemia. Nutritional anemia refers to  anemia that can be directly attributed to nutritional disorders or deficiencies. Examples include Iron deficiency anemia and pernicious anemia. It is often discussed in a pediatric context.According to the World Health Organization, a hemoglobin concentration below 110 g/L for children under 5 years of age and pregnant women, and below 130 g/L for men indicates anemia. Hemoglobin is a blood protein that transports oxygen to the cells of the body. Without oxygen, the human body cannot undergo respiration and create Adenosine triphosphate, thereby depriving cells of energy.Nutritional anemia can be caused by a lack of iron, protein, vitamin B12, and other vitamins and minerals that are needed for the formation of hemoglobin. However, Iron deficiency anemia is the most common nutritional disorder.Signs of anemia include cyanosis, jaundice, and easy bruising. In addition, anemic patients may experience difficulties with memory and concentration, fatigue, lightheadedness, sensitivity to temperature, low energy levels, shortness of breath, and pale skin. Symptoms of severe or rapid-onset anemia are very dangerous as the body is unable to adjust to the lack of hemoglobin. This may result in shock and death. Mild and moderate anemia have symptoms that develop slowly over time.[5] If patients believe that they are at risk for or experience symptoms of anemia, they should contact their doctor.

Symptoms
Symptoms of nutritional anemia can include fatigue and lack of energy. However if symptoms progress, one may experience shortness of breath, rapid pulse, paleness—especially in the hands, eyelids and fingernails---, swelling of ankles, hair loss, lightheadedness, compulsive and atypical cravings, constipation, depression, muscle twitching, numbness, or burning and chest pain.
Those who have nutritional anemia often show little to no symptoms. Often, symptoms can go undetected as mild forms of the anemia have only minor symptoms.

Cause
Internationally, anemia caused by iron deficiencies is the most common nutritional disorder. It is the only significantly prevalent nutritional deficiency disorder in industrialized countries. In poorer areas, anemia is worsened by infectious diseases such as HIV/AIDS, tuberculosis, hookworm infestation, and malaria. In developing countries, about 40% of preschool children and 50% of pregnant women are estimated to be anemic. 20% of maternal deaths can be contributed to anemia. Health consequences of anemia include poor pregnancy outcomes, impaired cognitive and physical development, increased rate of morbidity, and reduced rate of work in adults.Nutritional anemia has many different causes, each either nutritional or non-nutritional. Nutritional causes are vitamin and mineral deficiencies and non-nutritional causes include infections. The number one cause of this type of anemia, however, is iron deficiency.An insufficient intake of iron, Vitamin B12, and folic acid impairs the bone marrow function. The lack of iron within a person’s body can also stem from ulcer bacteria. These microbes live in the digestive tract and after many years cause ulcers in the lining of the stomach or small intestine. Therefore, a high percentage of patients with nutritional anemia may have a potential gastrointestinal disorder that causes chronic blood loss. This is common in immunocompromised, elderly, and diabetic people </s>