<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Rhinitis medicamentosa and can you explain it in depth? [/INST] Rhinitis medicamentosa (or RM) is a condition of rebound nasal congestion suspected to be brought on by extended use of topical decongestants (e.g., oxymetazoline, phenylephrine, xylometazoline, and naphazoline nasal sprays) and certain oral medications (e.g., sympathomimetic amines and various 2-imidazolines) that constrict blood vessels in the lining of the nose, although evidence has been contradictory.

Presentation
The characteristic presentation of RM involves nasal congestion without rhinorrhea, postnasal drip, or sneezing following several days of decongestant use. This condition typically occurs after 5–7 days of use of topical decongestants.  Patients often try increasing both the dose and the frequency of nasal sprays upon the onset of RM, worsening the condition. The swelling of the nasal passages caused by rebound congestion may eventually result in permanent turbinate hypertrophy, which may block nasal breathing until surgically removed.

Causes
Common issues that lead to overuse of topical decongestants:
Deviated septum
Upper respiratory tract infection
Vasomotor rhinitis
Cocaine use and other stimulant abuse
Pregnancy (these products are not considered safe for pregnancy)
Chronic rhinosinusitis
Hypertrophy of the inferior turbinates

Pathophysiology
The pathophysiology of RM is unclear, although several mechanisms involving norepinephrine signaling have been proposed.  RM is associated with histological changes that include: an increase in the number of lymphocytes and fibroblasts, epithelial cell denudation, epithelial edema, goblet cell hyperplasia, increased expression of the epidermal growth factor receptor, increased mucus production, nasociliary loss, inflammatory cell infiltration, and squamous cell metaplasia.Direct acting sympathomimetic amines, such as phenylephrine stimulate alpha adrenergic receptors, while mixed-acting agents, such as pseudoephedrine can stimulate both alpha and beta adrenergic receptors directly and indirectly by releasing norepinephrine from sympathetic nerve terminals.  At first, the vasoconstrictive effect of alpha-receptors dominates, but with continued use of an alpha agonist, this effect fades first, allowing the vasodilation due to beta-receptor stimulation to emerge.2-Imidazoline derivatives, such as oxymetazoline, may participate in negative feedback on endogenous norepinephrine production.  Therefore, after cessation of prolonged use, there will be inadequate sympathetic vasoconstriction in the nasal mucosa, and domination of parasympathetic activity can result in increased secretions and nasal edema. Evidence suggests that if oxymetazoline is used only nightly for allergic rhinitis (instead of more frequent dosage as may be directed on product label), it may be used longer than one week without high risk of rhinitis medicamentosa especially with use of intranasal steroid like fluticasone furoate.

Treatment
The treatment of RM involves withdrawal of the offending nasal spray or oral medication. Both a "cold turkey" and a "weaning" approach can be used. Cold turkey is the most effective treatment method, as it directly removes the cause of the condition, yet the time period between the discontinuation of the drug and the relief of symptoms may be too long and uncomfortable for some individuals (particularly when trying to go to sleep when they are unable to breathe through their nose).
The use of over-the-counter (OTC) saline nasal sprays may help open the nose without causing RM if the spray does not contain a decongestant. Symptoms of congestion and runny nose can often be treated with corticosteroid nasal sprays under the supervision of a physician. For very severe cases, oral steroids or nasal surgery may be necessary.
For RM caused by topical decongestants, there are anecdotal reports of persons having success by withdrawing treatment from one nostril at a time.A study has shown that the anti-infective agent benzalkonium chloride, which is frequently added to topical nasal sprays as a preservative, aggravates the condition by further increasing the rebound swelling.

See also
Topical decongestant

References
Further reading
Bernstein, I.Leonard (January 2000). "Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? A cautionary note based on compromised mucociliary transport". Journal of Allergy and Clinical Immunology. 105 (1): 39–44. doi:10.1016/S0091-6749(00)90175-1. PMID 10629450.
Remsen, K. A.; Black, M. J. (19 April 1980). "Rhinitis medicamentosa". CMAJ. 122 (8): 881–884. PMC 1801634. PMID 6154514.
Adams, H. Richard (2013). "Adrenergic Agonists and Antagonists".  In Riviere, Jim E.; Papich, Mark G. (eds.). Veterinary Pharmacology and Therapeutics. pp. 125–56. ISBN 978-1-118-68590-7.
Elwany, Samy S.; Stephanos, Wahid M. (1983). "Rhinitis medicamentosa: An experimental histopathological and histochemical study". ORL. 45 (4): 187–194. doi:10.1159/000275642. PMID 6192384.
Baldwin, R. L.; Jolly, P. A.; Mizes, J. S.; Fleece, L. (1984). "Rhinitis medicamentosa. Conceptualization, incidence, and treatment". The Alabama Journal of Medical Sciences. 21 (2): 205–208. PMID 6375416.
Graf, Peter (October 1999). "Adverse Effects of benzalkonium chloride on the nasal mucosa: Allergic rhinitis and rhinitis medicamentosa". Clinical Therapeutics. 21 (10): 1749–1755. doi:10.1016/S0149-2918(99)80053-8. PMID 10566570.
Graf, P.; Hallen, H.; Juto, J.-E. (May 1995). "Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers". Clinical & Experimental Allergy. 25 (5): 395–400. doi:10.1111/j.1365-2222.1995.tb01069.x. PMID 7553241. S2CID 19989791.
Lin, Chun-Yu; Cheng, Po-Hsu; Fang, Sheen-Yie (28 June 2016). "Mucosal Changes in Rhinitis Medicamentosa". Annals of Otology, Rhinology & Laryngology. 113 (2): 147–151. doi:10.1177/000348940411300213. PMID 14994772. S2CID 850948.
Mabry, R. L. (1982). "Rhinitis medicamentosa: the forgotten factor in nasal obstruction". Southern Medical Journal </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Primary sclerosing cholangitis and can you explain it in depth? [/INST] Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease, such as yellow discoloration of the skin and eyes, itching, and abdominal pain.
The bile duct scarring that occurs in PSC narrows the ducts of the biliary tree and impedes the flow of bile to the intestines. Eventually, it can lead to cirrhosis of the liver and liver failure. PSC increases the risk of various cancers, including liver cancer, gallbladder carcinoma, colorectal cancer, and cholangiocarcinoma.  The underlying cause of PSC is unknown. Genetic susceptibility, immune system dysfunction, and abnormal composition of the gut flora may play a role. This is further suggested by the observation that around 75% of individuals with PSC also have inflammatory bowel disease (IBD), most often ulcerative colitis.No effective medical treatment for primary sclerosing cholangitis is known. Its most definitive treatment is a liver transplant, but it can recur after transplantation. Many people affected by PSC require a liver transplant.
PSC is a rare disease and most commonly affects people with IBD. About 3.0 to 7.5% of people with ulcerative colitis have PSC, and 80% of people with PSC have some form of IBD. Diagnosis usually occurs in people in their 30s or 40s. Individuals of Northern European ancestry are affected more often than people of Southern European or Asian descent. Men are affected more often than women. The disease was initially described in the mid-1800s, but was not fully characterized until the 1970s with the advent of improved medical-imaging techniques such as endoscopic retrograde cholangiopancreatography.

Signs and symptoms
Nearly half of people with PSC do not have symptoms, and are often incidentally discovered to have PSC due to abnormal liver function tests; however, a substantial proportion have debilitating signs and symptoms of the disease. Signs and symptoms of PSC may include severe itching and nonspecific fatigue. Yellowing of the skin and white portion of the eyes may also be seen. Enlargement of the liver and spleen are seen in roughly 40% of affected individuals. Abdominal pain affects about 20% of people with PSC.Multiple episodes of life-threatening acute cholangitis (infection within the bile ducts) can be seen due to impaired drainage of the bile ducts, which increases the risk of infection.
Dark urine due to excess conjugated bilirubin, which is water-soluble and excreted by the kidneys (i.e. choluria)
Malabsorption, especially of fat, and steatorrhea (fatty stool), due to an inadequate amount of bile reaching the small intestine, leading to decreased levels of the fat-soluble vitamins, A, D, E, and K.
Portal hypertension, a complication of cirrhosis, which can manifest with esophageal and parastomal varices as well as hepatic encephalopathy (mental status alteration/disturbance caused by liver dysfunction and shunting of blood away from the scarred liver; such that ammonia detoxification is reduced with concomitant encephalopathy) or ascites.

Cause
The exact cause of primary sclerosing cholangitis is  unknown, and its pathogenesis is improperly understood. Although PSC is thought to be caused by autoimmune disease, it does not demonstrate a clear response to immunosuppressants. Thus, many experts believe it to be a complex, multifactorial (including immune-mediated) disorder and perhaps one that encompasses several different hepatobiliary diseases.Data have provided novel insights suggesting:

an important association between the intestinal microbiota and PSC and
a process referred to as cellular senescence and the senescence-associated secretory phenotype in the pathogenesis of PSC.In addition, longstanding, well-recognized associations are seen between PSC and human leukocyte antigen alleles (A1, B8, and DR3).

Pathophysiology
PSC is characterized by inflammation of the bile ducts (cholangitis) with consequent stricturing (i.e., narrowing) and hardening (sclerosis) of these ducts due to scar formation, be it inside and/or outside the liver.  The resulting scarring of the bile ducts obstructs the flow of bile, which further perpetuates bile duct and liver injury.  Chronic impairment of bile flow due to blockage and dysfunctional bile transport (cholestasis) causes progressive biliary fibrosis and ultimately biliary cirrhosis and liver failure.The primary physiological function of bile is to assist in the breakdown and absorption of fat in the intestinal tract; a relative deficiency of bile can lead to fat malabsorption and deficiencies of fat-soluble vitamins (A, D, E, K).Liver enlargement is seen due to portal hypertension caused by compression of portal veins by the proximate sclerosed intrahepatic bile ducts, and leads to right upper quadrant abdominal pain.

Diagnosis
PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out:
serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months
cholangiography demonstrating biliary strictures or irregularity consistent with PSC
liver biopsy consistent with PSC (if available)Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its noninvasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique.  MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear antineutrophil cytoplasmic antibodies (P-ANCA); however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20-50% of PSC patients, and likewise are not specific for the disease,but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug-induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation nonanastomotic biliary strictures,  and HIV-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with IBD, which includes ulcerative colitis and Crohns disease, response to treatment, and risks of disease progression.

Classification
Primary sclerosing cholangitis is typically classified into three subgroups based on whether the small and/or large bile ducts are affected. The subgroups of PSC include:
Classic PSC
Small-duct PSC
PSC associated with autoimmune hepatitis

Management
No pharmacologic treatment has been approved by the U.S. Food and Drug Administration for PSC. Some experts recommend a trial of ursodeoxycholic acid (UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13-15 milligrams per kilogram) of UDCA for PSC.Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritics (e.g. bile acid sequestrants such as cholestyramine); antibiotics to treat episodes of ascending cholangitis; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (A, D, E, and K).ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile-duct cancer (cholangiocarcinoma).Liver transplantation is the only proven long-term treatment of PSC. Indications for transplantation include recurrent bacterial ascending cholangitis, decompensated cirrhosis, hepatocellular carcinoma, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some experience disease recurrence afterward. The reasons why some patients develop recurrent PSC remains largely obscure, but surprisingly, those without recurrence of disease (hence protected from recurrence) are characterized by an increased presence of the potentially pathogenic  Shigella species.

Prognosis
Estimated median survival from diagnosis until liver transplant or PSC-related death is 21.3 years. Various models have been developed to help predict survival, but their use is generally best suited for research and not clinical purposes. A serum alkaline phosphatase less than 1.5 times the upper limit of normal has been associated with better outcomes, but its use in predicting long-term outcomes is unclear. An IgA isotype autoantibody to the pancreatic GP2 protein (anti-GP2 IgA antibody) is the first verified prognostic biomarker in PSC. The role of anti-GP2 IgA in PSC was simultaneously investigated and reported by two research groups, and later confirmed by others. Association was demonstrated between anti-GP2 IgA and progressive liver fibrosis, cholangiocarcinoma development and shorter transplantation free survival in PSC patients.Other markers which may be measured and monitored are a complete blood count, serum liver enzymes, bilirubin levels (usually grossly elevated), kidney function, and electrolytes. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea) are prominent.

Related diseases
The development of any of the cancers associated with PSC predicts a poor prognosis. Complications from PSC-associated cancers account for 40% of deaths from PSC. Primary sclerosing cholangitis is one of the major known risk factors for cholangiocarcinoma, a cancer of the biliary tree, for which the lifetime risk among patients with PSC is 10-15%. This represents a 400-fold greater risk of developing cholangiocarcinoma compared to the general population.  Surveillance for cholangiocarcinoma in patients with PSC is encouraged, with some experts recommending annual surveillance with a specialized imaging study and serum markers, although consensus regarding the modality and interval has yet to be established. Similarly, a screening colonoscopy is recommended in people who receive a new diagnosis of primary sclerosing cholangitis since their risk of colorectal cancer is 10 times higher than that of the general population.PSC is strongly associated with IBD, in particular ulcerative colitis (UC) and to a lesser extent Crohns disease. As many as 5% of patients with IBD are co-diagnosed with PSC, and approximately 70% of people with PSC have IBD. Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood. Close monitoring of PSC patients is vital.
Various forms of gallbladder disease such as gallstones and gallbladder polyps are also common in those with PSC </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Lipoma and can you explain it in depth? [/INST] A lipoma is a benign tumor made of fat tissue. They are generally soft to the touch, movable, and painless. They usually occur just under the skin, but occasionally may be deeper. Most are less than 5 cm (2.0 in) in size. Common locations include upper back, shoulders, and abdomen. It is possible to have a number of lipomas.The cause is generally unclear. Risk factors include family history, obesity, and lack of exercise. Diagnosis is typically based on a physical exam. Occasionally medical imaging or tissue biopsy is used to confirm the diagnosis.Treatment is typically by observation or surgical removal. Rarely, the condition may recur following removal, but this can generally be managed with repeat surgery. They are not generally associated with a future risk of cancer.Lipomas have a prevalence of roughly 2 out of every 100 people. Lipomas typically occur in adults between 40 and 60 years of age. Males are more often affected than females. They are the most common noncancerous soft-tissue tumor. The first use of the term "lipoma" to describe these tumors was in 1709.

Types
The many subtypes of lipomas include:: 624–5
Adenolipomas are lipomas associated with eccrine sweat glands.: 627
Angiolipoleiomyomas are acquired, solitary, asymptomatic acral nodules, characterized histologically by well-circumscribed subcutaneous tumors composed of smooth muscle cells, blood vessels, connective tissue, and fat.: 627
Angiolipomas are painful subcutaneous nodules having all other features of a typical lipoma.: 624
Cerebellar pontine angle and internal auditory canal lipomas
Chondroid lipomas are deep-seated, firm, yellow tumors that characteristically occur on the legs of women.: 625
Corpus callosum lipoma is a rare congenital brain condition that may or may not present with symptoms. This occurs in the corpus callosum, also known as the calossal commissure, which is a wide, flat bundle of neural fibers beneath the cortex in the human brain.
Hibernomas are lipomas of brown fat.
Intradermal spindle cell lipomas are distinct in that they most commonly affect women and have a wide distribution, occurring with relatively equal frequency on the head and neck, trunk, and upper and lower extremities.: 625
A fibrolipoma is a lipoma with focal areas of large amounts of fibrous tissue. A sclerotic lipoma is a predominantly fibrous lesion with focal areas of fat.Neural fibrolipomas are overgrowths of fibro-fatty tissue along a nerve trunk, which often leads to nerve compression.: 625 Pleomorphic lipomas, like spindle-cell lipomas, occur for the most part on the backs and necks of elderly men and are characterized by floret giant cells with overlapping nuclei.: 625
Spindle-cell lipomas are asymptomatic, slow-growing, subcutaneous tumors that have a predilection for the posterior back, neck, and shoulders of older men.: 625
Superficial subcutaneous lipomas, the most common type of lipoma, lie just below the surface of the skin. Most occur on the trunk, thigh, and forearm, although they may be found anywhere in the body where fat is located.

Causes
The tendency to develop a lipoma is not necessarily hereditary, although hereditary conditions such as familial multiple lipomatosis might include lipoma development. Genetic studies in mice have shown a correlation between the HMG I-C gene (previously identified as a gene related to obesity) and lipoma development. These studies support prior epidemiologic data in humans showing a correlation between HMG I-C and mesenchymal tumors.Cases have been reported where minor injuries are alleged to have triggered the growth of a lipoma, called a "post-traumatic lipoma". However, the link between trauma and the development of lipomas is controversial.

Other conditions
Lipomatosis is believed to be a hereditary condition in which multiple lipomas are present on the body.Adiposis dolorosa (Dercum disease) is a rare condition involving multiple painful lipomas, swelling, and fatigue. Early studies mentioned prevalence in obese postmenopausal women.  However, current literature demonstrates that Dercum disease is present in more women than men of all body types; the average age for diagnosis is 35 years.Benign symmetric lipomatosis (Madelung disease) is another condition involving lipomatosis. It nearly always appears in middle-aged males after many years of alcoholism, but nonalcoholic males and females can also be affected.

Diagnosis
A physical exam is typically the easiest way to diagnose it. Rarely, a tissue biopsy or imaging may be required. The imaging modality of choice is magnetic resonance imaging (MRI) because it has superior sensitivity of distinguishing it from liposarcoma as well as mapping the surrounding anatomy.

Treatment
Usually, treatment of lipomas is not necessary, unless they become painful or restrict movement. They are usually removed for cosmetic reasons if they grow very large or for histopathology to verify that they are not a more dangerous type of tumor such as a liposarcoma. This last point can be important, as the characteristics of a tumor are not known until after it is removed and medically examined.Lipomas are normally removed by simple excision. The removal can often be done under local anesthetic and takes less than 30 minutes. This cures the great majority of cases, with about 1–2% of lipomas recurring after excision. Liposuction is another option if the lipoma is soft and has a small connective tissue component. Liposuction typically results in less scarring; however, with large lipomas, it may fail to remove the entire tumor, which can lead to regrowth.New methods under development are supposed to remove the lipomas without scarring. One is removal by injecting compounds that trigger lipolysis, such as steroids or phosphatidylcholine. Other potential methods based on tissue-targeted heating include cauterization, electrosurgery, and harmonic scalpel.

Post surgery
Patients who have a lipoma removed are usually able to return home the same day, without any need for hospitalization. Some patients may have pain, swelling, or bruising where the lipoma was removed. These symptoms usually subside after a few days.
Resection of an intermuscular lipoma in the elbow region

Other lipomas

Prognosis
Lipomas are rarely life-threatening, and the common subcutaneous lipomas are not a serious condition. Lipomas growing in internal organs can be more dangerous; for example, lipomas in the gastrointestinal tract can cause bleeding, ulceration, and painful obstructions (so-called "malignant by location", despite being a benign growth histologically). Malignant transformation of lipomas into liposarcomas is very rare, and most liposarcomas are not produced from pre-existing benign lesions. A few cases of malignant transformation have been described for bone and kidney lipomas, but it is possible that these few reported cases were well-differentiated liposarcomas in which the subtle malignant characteristics were missed when the tumor was first examined. Deep lipomas have a greater tendency to recur than superficial lipomas because complete surgical removal of deep lipomas is not always possible.The presence of multiple lipomas, lipomatosis, is more commonly encountered in men </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cholinergic crisis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Renal tubular acidosis and can you explain it in depth? [/INST] Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, when blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder as urine. The metabolic acidosis that results from RTA may be caused either by insufficient secretion of hydrogen ions (which are acidic) into the latter portions of the nephron (the distal tubule) or by failure to reabsorb sufficient bicarbonate ions (which are alkaline) from the filtrate in the early portion of the nephron (the proximal tubule). Although a metabolic acidosis also occurs in those with chronic kidney disease, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes. RTA is usually an incidental finding based on routine blood draws that show abnormal results. Clinically, patients may present with vague symptoms such as dehydration, mental status changes, or delayed growth in adolescents.The word acidosis refers to the tendency for RTA to cause an excess of acid, which lowers the bloods pH. When the blood pH is below normal (7.35), this is called acidemia. The metabolic acidosis caused by RTA is a normal anion gap acidosis.

Types
An overview of types 1, 2, and 4 is presented below (type 3 is usually excluded from modern classifications):

Type 1: distal
Distal RTA (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalated cells of the medullary collecting duct of the distal nephron.This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3. Because renal excretion is the primary means of eliminating H+ from the body, there is consequently a tendency towards acidemia. There is an inability to excrete H+ while K+ cannot be reclaimed by the cell, leading to acidemia (as H+ builds up in the body) and hypokalemia (as K+ cannot be reabsorbed by the alpha cell).This leads to the clinical features of dRTA; In other words, the intercalated cells apical H+/K+ antiporter is non-functional, resulting in proton retention and potassium excretion. Since calcium phosphate stones demonstrate a proclivity for deposition at higher pHs (alkaline), the substance of the kidney develops stones bilaterally; this does not occur in the other RTA types.

Normal anion gap metabolic acidosis/acidemia
Hypokalemia, Hypocalcemia, Hyperchloremia
Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate).
Nephrocalcinosis (deposition of calcium in the substance of the kidney)
Bone demineralisation (causing rickets in children and osteomalacia in adults)
Growth deficiency
Medullary cysts
Sensorineural hearing loss
Hereditary hemolytic anemiaDistal RTA has also been linked to specific genetic mutations that will alter when the disease will present in the patients life. Patients with mutations in ATP6V1B1 and ATP6V0A4 will present with symptoms within the first year of life, while those with mutation of the SLC4A1 have delayed onset around 10 years of age. Electrolyte imbalances remain the same, while in severe cases symptoms can advance to amino aciduria and hyperammonemia. In a large Asian series of Distal renal Tubular Acidosis in Sjogrens Syndrome, late diagnosis is a rule in spite of overt hypokalemic periodic paralysis in a vast majority of themdRTA is the most common form of RTA diagnosed in Western countries, and can be classified as either hereditary (primary) or acquired (secondary). Primary RTA generally results from systemic and autoimmune diseases or drug and toxin exposure in adults, whereas pediatric RTA results from genetic defects in the proteins that facilitate urine acidification at the distal tubule. Hereditary dRTA generally presents as failure to thrive during the first several months of life. Other common clinical manifestations in children include a variety of gastrointestinal and urinary symptoms, including polyuria, polydipsia, constipation, diarrhea, bouts of dehydration, and decreased appetite.

Type 2: proximal
Proximal RTA (pRTA) is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. Reabsorption of bicarbonate is typically 80-90% in the proximal tubule and failure of this process leads to decreased systemic buffer and metabolic acidosis. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the alpha intercalated cells can produce H+ to acidify the urine to a pH of less than 5.3. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalized dysfunction of the proximal tubular cells called Fanconi syndrome, in which there is also phosphaturia, glycosuria, aminoaciduria, uricosuria, and tubular proteinuria.The principal feature of Fanconi syndrome is bone demineralization (osteomalacia or rickets) due to phosphate wasting.

Type 3: combined proximal and distal
In some patients, RTA shares features of both dRTA and pRTA. This rare pattern was observed in the 1960s and 1970s as a transient phenomenon in infants and children with dRTA (possibly in relation with some exogenous factor such as high salt intake) and is no longer observed. This form of RTA has also been referred to as juvenile RTA.Combined dRTA and pRTA is also observed as the result of inherited carbonic anhydrase II deficiency. Mutations in the gene encoding this enzyme give rise to an autosomal recessive syndrome of osteopetrosis, renal tubular acidosis, cerebral calcification, and mental retardation </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Biliary colic and can you explain it in depth? [/INST] Biliary colic, also known as symptomatic cholelithiasis, a gallbladder attack or gallstone attack, is when a colic (sudden pain) occurs due to a gallstone temporarily blocking the cystic duct. Typically, the pain is in the right upper part of the abdomen, and can be severe. Pain usually lasts from 15 minutes to a few hours. Often, it occurs after eating a heavy meal, or during the night. Repeated attacks are common.Gallstone formation occurs from the precipitation of crystals that aggregate to form stones. The most common form is cholesterol gallstones. Other forms include calcium, bilirubin, pigment, and mixed gallstones. Other conditions that produce similar symptoms include appendicitis, stomach ulcers, pancreatitis, and gastroesophageal reflux disease.Treatment for gallbladder attacks is typically surgery to remove the gallbladder. This can be either done through small incisions or through a single larger incision. Open surgery through a larger incision is associated with more complications than surgery through small incisions. Surgery is typically done under general anesthesia. In those who are unable to have surgery, medication to try to dissolve the stones or shock wave lithotripsy may be tried. As of 2017, it is not clear whether surgery is indicated for everyone with biliary colic.In the developed world, 10 to 15% of adults have gallstones. Of those with gallstones, biliary colic occurs in 1 to 4% each year. Nearly 30% of people have further problems related to gallstones in the year following an attack. About 15% of people with biliary colic eventually develop inflammation of the gallbladder if not treated. Other complications include inflammation of the pancreas.

Signs and symptoms
Pain is the most common presenting symptom. It is usually described as sharp, crampy, dull or severe right upper quadrant pain, which may  radiate to the right shoulder, or less commonly, behind the breastbone. Nausea and vomiting can be associated with biliary colic. Individuals may also present with pain that is induced following a fatty meal and the symptom of indigestion. The pain often lasts longer than 30 minutes, up to a few hours.
Patients usually have normal vital signs with biliary colic, whereas patients with cholecystitis are usually febrile and more ill appearing. Lab studies that should be ordered include a complete blood count, liver function tests and lipase. In biliary colic, lab findings are usually within normal limits. Alanine aminotransferase and aspartate transaminase are usually suggestive of liver disease whereas elevation of bilirubin and alkaline phosphatase suggests common bile duct obstruction. Pancreatitis should be considered if the lipase value is elevated; gallstone disease is the major cause of pancreatitis.

Complications
The presence of gallstones can lead to inflammation of the gallbladder (cholecystitis) or the biliary tree (cholangitis) or acute inflammation of the pancreas (pancreatitis). Rarely, a gallstone can become impacted in the ileocecal valve that joins the caecum and the ileum, causing gallstone ileus (mechanical ileus).Complications from delayed surgery include pancreatitis, empyema, and perforation of the gallbladder, cholecystitis, cholangitis, and obstructive jaundice.Biliary pain in the absence of gallstones, known as postcholecystectomy syndrome, may severely affect the patients quality of life, even in the absence of disease progression.

Causes
Biliary pain is most frequently caused by obstruction of the common bile duct or the cystic duct by a gallstone. However, the presence of gallstones is a frequent incidental finding and does not always necessitate treatment, in the absence of identifiable disease. Furthermore, biliary pain may be associated with functional disorders of the biliary tract, so-called acalculous biliary pain (pain without stones), and can even be found in patients post-cholecystectomy (removal of the gallbladder), possibly as a consequence of dysfunction of the biliary tree and the sphincter of Oddi. Acute episodes of biliary pain may be induced or exacerbated by certain foods, most commonly those high in fat.

Risk factors
Cholesterol gallstone formation risk factors include age, female sex, family history, race, pregnancy, parity, obesity, hormonal birth control, diabetes mellitus, cirrhosis, prolonged fasting, rapid weight loss, total parenteral nutrition, ileal disease and impaired gallbladder emptying.Patients that have gallstones and biliary colic are at increased risk for complications, including cholecystitis. Complications from gallstone disease is 0.3% per year and therefore prophylactic cholecystectomy are rarely indicated unless part of a special population that includes porcelain gallbladder, individuals eligible for organ transplant, diabetics and those with sickle cell anemia.

Diagnosis
Diagnosis is guided by the persons presenting symptoms and laboratory findings. The gold standard imaging modality for the presence of gallstones is ultrasound of the right upper quadrant. There are many reasons for this choice, including no exposure to radiation, low cost, and availability in city, urban, and rural hospitals. Gallstones are detected with a specificity and sensitivity of greater than 95% with ultrasound. Further signs on ultrasound may suggest cholecystitis or choledocholithiasis. Computed Tomography (CT) is not indicated when investigating for gallbladder disease as 60% of stones are not radiopaque. CT should only be utilized if other intra-abdominal pathology exists or the diagnosis is uncertain. Endoscopic retrograde cholangiopancreatography (ERCP) should be used only if lab tests suggest the existence of a gallstone in the bile duct. ERCP is then both diagnostic and therapeutic.

Management
Medications
Initial management includes the relief of symptoms and correcting electrolyte and fluid imbalance that may occur with vomiting. Antiemetics, such as dimenhydrinate, are used to treat the nausea. Pain may be treated with anti-inflammatories, NSAIDs such as ketorolac or diclofenac. Opioids, such as morphine, less commonly may be used. NSAIDs are more or less equivalent to opioids. Hyoscine butylbromide, an antispasmodic, is also indicated in biliary colic.In biliary colic, the risk of infection is minimal and therefore antibiotics are not required. Presence of infection indicates cholecystitis.

Surgery
It is unclear whether those experiencing a gallstone attack should receive surgical treatment or not </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Splenic infarction and can you explain it in depth? [/INST] Splenic infarction is a condition in which blood flow supply to the spleen is compromised, leading to partial or complete infarction (tissue death due to oxygen shortage) in the organ.  Splenic infarction occurs when the splenic artery or one of its branches are occluded, for example by a blood clot.In one series of 59 patients, mortality amounted to 5%. Complications include a ruptured spleen, bleeding, an abscess of the spleen (for example, if the underlying cause is infective endocarditis) or pseudocyst formation. Splenectomy may be warranted for persistent pseudocysts due to the high risk of subsequent rupture.

Diagnosis
Although it can occur asymptomatically, the typical symptom is severe pain in the left upper quadrant of the abdomen, sometimes radiating to the left shoulder. Fever and chills develop in some cases. It has to be differentiated from other causes of acute abdomen.
An abdominal CT scan is the most commonly used modality to confirm the diagnosis, although abdominal ultrasound can also contribute.

Treatment
There is no specific treatment, except treating the underlying disorder and providing adequate pain relief. Surgical removal of the spleen (splenectomy) is only required if complications ensue; surgical removal predisposes to overwhelming post-splenectomy infections.

Causes
Several factors may increase the tendency for clot formation, such as specific infections (such as infectious mononucleosis, cytomegalovirus infection, malaria, or babesiosis), inherited clotting disorders (thrombophilia, such as Factor V Leiden, antiphospholipid syndrome), malignancy (such as pancreatic cancer) or metastasis, or a combination of these factors.
In some conditions, blood clots form in one part of the circulatory system and then dislodge and travel to another part of the body, which could include the spleen. These emboligenic disorders include atrial fibrillation, patent foramen ovale, endocarditis or cholesterol embolism.
Splenic infarction is also more common in hematological disorders with associated splenomegaly, such as the myeloproliferative disorders. Other causes of splenomegaly (for example, Gaucher disease or hemoglobinopathies) can also predispose to infarction </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Abdominal compartment syndrome and can you explain it in depth? [/INST] Abdominal compartment syndrome (ACS) occurs when the abdomen becomes subject to increased pressure reaching past the point of intra-abdominal hypertension (IAH).  ACS is present when intra-abdominal pressure rises and is sustained at > 20 mmHg and there is new organ dysfunction or failure. ACS is classified into three groups: Primary, secondary and recurrent ACS.  It is not a disease and as such it occurs in conjunction with many disease processes, either due to the primary illness or in association with treatment interventions. Specific cause of abdominal compartment syndrome is not known, although some causes can be sepsis and severe abdominal trauma. Increasing pressure reduces blood flow to abdominal organs and impairs pulmonary, cardiovascular, renal, and gastro-intestinal (GI) function, causing obstructive shock, multiple organ dysfunction syndrome and death.

Causes
Peritoneal tissue edema secondary to diffuse peritonitis, abdominal trauma
Fluid therapy due to massive volume resuscitation
Retroperitoneal hematoma secondary to trauma and aortic rupture
Peritoneal trauma secondary to emergency abdominal operations
Reperfusion injury following bowel ischemia due to any cause
Retroperitoneal and mesenteric inflammatory edema secondary to acute pancreatitis
Ileus and bowel obstruction
Intra-abdominal masses of any cause
Abdominal packing for control of bleeding
Closure of the abdomen under undue tension
Ascites (intra-abdominal fluid accumulation)
Acute pancreatitis with abscesses formation

Pathophysiology
Abdominal compartment syndrome occurs when tissue fluid within the peritoneal and retroperitoneal space (either edema, retroperitoneal blood or free fluid in the abdomen) accumulates in such large volumes that the abdominal wall compliance threshold is crossed and the abdomen can no longer stretch. Once the abdominal wall can no longer expand, any further fluid leaking into the tissue results in fairly rapid rises in the pressure within the closed space. Initially this increase in pressure does not cause organ failure but does prevent organs from working properly – this is called intra-abdominal hypertension and is defined as a pressure over 12 mmHg in adults.  ACS is defined by a sustained IAP(intra-abdominal pressure) above 20 mmHg with new-onset or progressive organ failure. Severe organ dysfunctionent syndrome. These pressure measurements are relative. Small children get into trouble and develop compartment syndromes at much lower pressures while young previously healthy athletic individuals may tolerate an abdominal pressure of 20 mmHg very well.
The underlying cause of the disease process is capillary permeability caused by the systemic inflammatory response syndrome (SIRS) that occurs in every critically ill patient. SIRS leads to leakage of fluid out of the capillary beds into the interstitial space in the entire body with a profound amount of this fluid leaking into the gut wall, mesentery and retroperitoneal tissue.
Abdominal compartment syndrome follows a destructive pathway similar to compartment syndrome of the extremities. When increased compression occurs in such a hollow space, organs will begin to collapse under the pressure. As the pressure increases and reaches a point where the abdomen can no longer be distended it starts to affect the cardiovascular and pulmonary systems. When abdominal compartment syndrome reaches this point without surgery and help of a silo the patient will most likely die. There is a high mortality rate associated with abdominal compartment syndrome.

Diagnosis
Abdominal compartment syndrome is defined as an intra-abdominal pressure above 20 mmHg with evidence of organ failure. Abdominal compartment syndrome develops when the intra-abdominal pressure rapidly reaches certain pathological values, within several hours (intra-abdominal hypertension is observed), and lasts for 6 or more hours. The key to recognizing abdominal compartment syndrome is the demonstration of elevated intra-abdominal pressure which is performed most often via the urinary bladder, and it is considered to be the "gold standard". Multiorgan failure includes damage to the cardiac, pulmonary, renal, neurological, gastrointestinal, abdominal wall, and ophthalmic systems. The gut is the most sensitive to intra-abdominal hypertension, and it develops evidence of end-organ damage before alterations are observed in other systems </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hemolytic–uremic syndrome and can you explain it in depth? [/INST] Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney failure, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea progresses. Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. Adults, especially the elderly, may present a more complicated presentation. Complications may include neurological problems and heart failure.Most cases occur after infectious diarrhea due to a specific type of E. coli called O157:H7. Other causes include S. pneumoniae, Shigella, Salmonella, and certain medications. The underlying mechanism typically involves the production of Shiga toxin by the bacteria. Atypical hemolytic uremic syndrome (aHUS) is often due to a genetic mutation and presents differently. However, both can lead to widespread inflammation and multiple blood clots in small blood vessels, a condition known as thrombotic microangiopathy.Treatment involves supportive care and may include dialysis, steroids, blood transfusions, or plasmapheresis. About 1.5 per 100,000 people are affected per year. Less than 5% of those with the condition die. Of the remainder, up to 25% have ongoing kidney problems. HUS was first defined as a syndrome in 1955.

Signs and symptoms
After eating contaminated food, the first symptoms of infection can emerge anywhere from 1 to 10 days later, but usually after 3 to 4 days. These early symptoms can include diarrhea (which is often bloody), stomach cramps, mild fever, or vomiting that results in dehydration and reduced urine. HUS typically develops about 5–10 days after the first symptoms, but can take up to 3 weeks to manifest, and occurs at a time when the diarrhea is improving. Related symptoms and signs include lethargy, decreased urine output, blood in the urine, kidney failure, low platelets, (which are needed for blood clotting), and destruction of red blood cells (microangiopathic hemolytic anemia). High blood pressure, jaundice (a yellow tinge in skin and the whites of the eyes), seizures, and bleeding into the skin can also occur. In some cases, there are prominent neurologic changes.People with HUS commonly exhibit the symptoms of thrombotic microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, (a chemical released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) anemia (low red blood cell count), schistocytes (damaged red blood cells), elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally), proteinuria (indicative of kidney injury), confusion, fatigue, swelling, nausea/vomiting, and diarrhea. Additionally, patients with aHUS typically present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, and coma. Failure of neurologic, cardiac, renal, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression.

Cause
Typical HUS
STEC-HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin such as enterohemorrhagic Escherichia coli (EHEC), of which E. coli O157:H7 is the most common serotype.

Atypical HUS
Atypical HUS (aHUS) represents 5–10% of HUS cases and is largely due to one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of the complement system, which is a group of immune signaling factors that promote inflammation, enhance the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the body, and directly attack the pathogens cell membrane. This results in platelet activation, endothelial cell damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis (breakdown of red blood cells), damage to multiple organs, and ultimately death. Early signs of systemic complement-mediated TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%) and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin (the oxygen-containing component of blood), and/or the presence of schistocytes. Despite the use of supportive care, an estimated 33–40% of patients will die or have end-stage renal disease (ESRD) with the first clinical manifestation of aHUS, and 65% of patients will die, require dialysis, or have permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI) therapy. Patients who survive the presenting signs and symptoms of aHUS endure a chronic thrombotic and inflammatory state, which puts them at lifelong elevated risk of sudden blood clotting, kidney  failure, other severe complications and premature death.Historically, treatment options for aHUS were limited to plasma exchange or plasma infusion (PE/PI) therapy, which carries significant risks and has not been proven effective in any controlled trials. People with aHUS and ESRD have also had to undergo lifelong dialysis, which has a 5-year survival rate of 34–38%.

Pathogenesis
HUS is one of the thrombotic microangiopathies, a category of disorders that includes STEC-HUS, aHUS, and thrombotic thrombocytopenic purpura (TTP). STEC-HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin(s), usually types of E. coli, that expresses verotoxin (also called Shiga-like toxin). E. coli can produce stx1 and/or stx2 Shiga toxins, the latter being more dangerous. A combination of both toxins in certain ratios is usually associated with HUS. These Shiga toxins bind GB3 receptors, globotriaosylceramide, which are present in renal tissue more than any other tissue and are also found in central nervous system neurons and other tissue. Children have more GB3 receptors than adults which may be why children are more susceptible to HUS. Cattle, swine, deer, and other mammals do not have GB3 receptors, but can be asymptomatic carriers of Shiga toxin-producing bacteria. Some humans can also be asymptomatic carriers. Once the bacteria colonizes, diarrhea followed by bloody diarrhea, hemorrhagic colitis, typically follows. STEC-HUS is usually preceded by a prodrome of diarrhea, which is often bloody, and is caused by Shiga-like toxin-producing bacteria such as enterohemorrhagic Escherichia coli (EHEC), of which E. coli O157:H7 is the most common serotype. Other serotypes also cause disease and can emerge as new causes of STEC-HUS, as occurred with E. coli O104:H4, which triggered a 2011 epidemic of STEC-HUS in Germany.The typical pathophysiology of HUS involves the binding of Shiga-toxin to the globotriaosylceramide (Gb3; also called ceramide trihexoside which accumulates in Fabry disease) receptor on the surface of the glomerular endothelium. This action includes a cascade of signaling events leading to apoptosis and binding of leukocytes to endothelial cells. The Shiga-toxin-activated endothelial cells then become thrombogenic (clot-producing) by a mechanism that is not fully understood, though they have been shown to induce the release of cytokines and chemokines that are implicated in platelet activation. Additionally, the binding action of Shiga-toxin inactivates a metalloproteinase called ADAMTS13, the deficiency of which causes the closely related TTP. Once ADAMTS13 is disabled, multimers of von Willebrand Factor (vWF) form and initiate platelet activation, causing microthrombus formation. The activation of platelets resulting from inhibition of ADAMTS13 is due to the hyperactivity of large multimers of uncleaved vWF. The arterioles and capillaries of the body become obstructed by the resulting complexes of activated platelets, which have adhered to the endothelium via large multimeric vWF. Through a mechanism known as microangiopathic hemolysis, the growing thrombi lodged in smaller vessels destroy red blood cells (RBCs) as they squeeze through the narrowed blood vessels, forming schistocytes, or fragments of sheared RBCs. The presence of schistocytes is a key finding that helps to diagnose HUS. Typically, this hemolysis results in a hemoglobin level of less than 80 g/L.Shiga-toxin directly activates the alternative complement pathway and also interferes with complement regulation by binding to complement factor H, an inhibitor of the complement cascade.  Shiga-toxin causes complement-mediated platelet, leukocyte, and endothelial cell activation, resulting in systemic hemolysis, inflammation and thrombosis. Severe clinical complications of TMA have been reported in patients from 2 weeks to more than 44 days after presentation with STEC-HUS, with improvements in clinical condition extending beyond this time frame, suggesting that complement activation persists beyond the acute clinical presentation and for at least 4 months.The consumption of platelets as they adhere to the thrombi lodged in the small vessels typically leads to mild or moderate thrombocytopenia with a platelet count of less than 60,000 per microliter. As in the related condition TTP, reduced blood flow through the narrowed blood vessels of the microvasculature leads to reduced blood flow to vital organs, and ischemia may develop. The kidneys and the central nervous system (brain and spinal cord) are the parts of the body most critically dependent on high blood flow, and are thus the most likely organs to be affected. However, in comparison to TTP, the kidneys tend to be more severely affected in HUS, and the central nervous system is less commonly affected.In contrast with typical disseminated intravascular coagulation seen with other causes of sepsis and occasionally with advanced cancer, coagulation factors are not consumed in HUS (or TTP) and the coagulation screen, fibrinogen level, and assays for fibrin degradation products such as "D-Dimers", are generally normal despite the low platelet count (thrombocytopenia).HUS occurs after 3–7% of all sporadic E. coli O157:H7 infections and up to approximately 20% or more of epidemic infections. Children and adolescents are commonly affected. Grossly, the kidneys may show patchy or diffuse renal cortical necrosis. Histologically, the glomeruli show thickened and sometimes split capillary walls due largely to endothelial swelling. Large deposits of fibrin-related materials in the capillary lumens, subendothelially, and in the mesangium are also found along with mesangiolysis. Interlobular and afferent arterioles show fibrinoid necrosis and intimal hyperplasia and are often occluded by thrombi.STEC-HUS most often affects infants and young children, but also occurs in adults. The most common form of transmission is ingestion of undercooked meat, unpasteurized fruits and juices, contaminated produce, contact with unchlorinated water, and person-to-person transmission in daycare or long-term care facilities.Unlike typical HUS, aHUS does not follow STEC infection and is thought to result from one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of complement. This leads to platelet activation, endothelial cell damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis, damage to multiple organs, and ultimately, death. Early signs of systemic complement-mediated TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%)  and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin, and/or the presence of schistocytes.

Diagnosis
The similarities between HUS, aHUS, and TTP make differential diagnosis essential. All three of these systemic TMA-causing diseases are characterized by thrombocytopenia and microangiopathic hemolysis, plus one or more of the following: neurological symptoms (e.g., confusion, cerebral convulsions, seizures); renal impairment (e.g., elevated creatinine, decreased estimated glomerular filtration rate [eGFR], abnormal urinalysis); and gastrointestinal (GI) symptoms (e.g., diarrhea, nausea/vomiting, abdominal pain, gastroenteritis).The presence of diarrhea does not exclude aHUS as the cause of TMA, as 28% of patients with aHUS present with diarrhea and/or gastroenteritis. First diagnosis of aHUS is often made in the context of an initial, complement-triggering infection, and Shiga-toxin has also been implicated as a trigger that identifies patients with aHUS. Additionally, in one study,  mutations of genes encoding several complement regulatory proteins were detected in 8 of 36 (22%) patients diagnosed with STEC-HUS. However, the absence of an identified complement regulatory gene mutation does not preclude aHUS as the cause of the TMA, as approximately 50% of patients with aHUS lack an identifiable mutation in complement regulatory genes.Diagnostic work-up supports the differential diagnosis of TMA-causing diseases. A positive Shiga-toxin/EHEC test confirms a cause for STEC-HUS, and severe ADAMTS13 deficiency (i.e., ≤5% of normal ADAMTS13 levels) confirms a diagnosis of TTP.

Prevention
The effect of antibiotics in shiga toxin producing E. coli is unclear. While some early studies raised concerns more recent studies show either no effect or a benefit.

Treatment
Treatment involves supportive care and may include dialysis, steroids, blood transfusions, and plasmapheresis.While eculizumab is being used to treat atypical hemolytic uremic syndrome, no evidence as of 2018 supports its use in the main forms of HUS. Scientists are trying to understand how useful it would be to immunize humans or cattle.

Prognosis
Acute renal failure occurs in 55–70% of people with STEC-HUS, although up to 70–85% recover renal function. With aggressive treatment, more than 90% of patients survive the acute phase of HUS, and only about 9% may develop ESRD. Roughly one-third of persons with HUS have abnormal kidney function many years later, and a few require long-term dialysis. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Atelectasis and can you explain it in depth? [/INST] Atelectasis is the collapse or closure of a lung resulting in reduced or absent gas exchange.  It is usually unilateral, affecting part or all of one lung. It is a condition where the alveoli are deflated down to little or no volume, as distinct from pulmonary consolidation, in which they are filled with liquid. It is often called a collapsed lung, although that term may also refer to pneumothorax.It is a very common finding in chest X-rays and other radiological studies, and may be caused by normal exhalation or by various medical conditions. Although frequently described as a collapse of lung tissue, atelectasis is not synonymous with a pneumothorax, which is a more specific condition that can cause atelectasis.  Acute atelectasis may occur as a post-operative complication or as a result of surfactant deficiency.  In premature babies, this leads to infant respiratory distress syndrome.
The term uses combining forms of atel- + ectasis, from Greek: ἀτελής, "incomplete" + ἔκτασις, "extension".

Signs and symptoms
May have no signs and symptoms or they may include:
cough, but not prominent;
chest pain (not common);
breathing difficulty (fast and shallow);
low oxygen saturation;
pleural effusion (transudate type);
cyanosis (late sign);
increased heart rate.It is a common misconception and pure speculation that atelectasis causes fever. A study of 100 post-op patients followed with serial chest X-rays and temperature measurements showed that the incidence of fever decreased as the incidence of atelectasis increased.  A recent review article summarizing the available published evidence on the association between atelectasis and post-op fever concluded that there is no clinical evidence supporting this speculation.

Causes
The most common cause is post-surgical atelectasis, characterized by splinting, i.e. restricted breathing after abdominal surgery. Atelectasis develops in 75–90% of people undergoing general anesthesia for a surgical procedure.Another common cause is pulmonary tuberculosis. Smokers and the elderly are also at an increased risk. Outside of this context, atelectasis implies some blockage of a bronchiole or bronchus, which can be within the airway (foreign body, mucus plug), from the wall (tumor, usually squamous cell carcinoma) or compressing from the outside (tumor, lymph node, tubercle). Another cause is poor surfactant spreading during inspiration, causing the surface tension to be at its highest which tends to collapse smaller alveoli. Atelectasis may also occur during suction, as along with sputum, air is withdrawn from the lungs. There are several types of atelectasis according to their underlying mechanisms or the distribution of alveolar collapse; resorption, compression, microatelectasis and contraction atelectasis. Relaxation atelectasis (also called passive atelectasis) is when a pleural effusion or a pneumothorax disrupts the contact between the parietal and visceral pleurae.Risk factors associated with increased likelihood of the development of atelectasis include: type of surgery (thoracic, cardiopulmonary surgeries), use of muscle relaxation, obesity, high oxygen, the lower lung segments.
Factors also associated with the development of atelectasis include: age, presence of chronic obstructive pulmonary disease or asthma, and type of anesthetic.
In the early 1950s, in UK aviation medicine, the condition "acceleration atelectasis" was given the name "Hunter Lung" due to its prevalence in pilots of the transonic fighter jet, the Hawker Hunter, which used a 100% oxygen supply.

Diagnosis
Clinically significant atelectasis is generally visible on chest X-ray; findings can include lung opacification and/or loss of lung volume. Post-surgical atelectasis will be bibasal in pattern. Chest CT or bronchoscopy may be necessary if the cause of atelectasis is not clinically apparent. Direct signs of atelectasis include displacement of interlobar fissures and mobile structures within the thorax, overinflation of the unaffected ipsilateral lobe or contralateral lung, and opacification of the collapsed lobe. In addition to clinically significant findings on chest X-rays, patients may present with indirect signs and symptoms such as elevation of the diaphragm, shifting of the trachea, heart and mediastinum; displacement of the hilus and shifting granulomas.

Classification
Atelectasis may be an acute or chronic condition. In acute atelectasis, the lung has recently collapsed and is primarily notable only for airlessness. In chronic atelectasis, the affected area is often characterized by a complex mixture of airlessness, infection, widening of the bronchi (bronchiectasis), destruction, and scarring (fibrosis).

Absorption (resorption) atelectasis
The Earths atmosphere is mainly composed of 78 vol. % nitrogen and 21 vol. % oxygen (+ 1 vol. % argon and traces of other gases). Since oxygen is exchanged at the alveoli-capillary membrane, nitrogen is a major component for the alveolis state of inflation. If a large volume of nitrogen in the lungs is replaced with oxygen, the oxygen may subsequently be absorbed into the blood, reducing the volume of the alveoli, resulting in a form of alveolar collapse known as absorption atelectasis.

Compression (relaxation) atelectasis
It is usually associated with accumulation of blood, fluid, or air within the pleural cavity, which mechanically collapses the lung. This is a frequent occurrence with pleural effusion, caused by congestive heart failure (CHF). Leakage of air into the pleural cavity (pneumothorax) also leads to compression atelectasis.

Cicatrization (contraction) atelectasis
It occurs when either local or generalized fibrotic changes in the lung or pleura hamper expansion and increase elastic recoil during expiration. Causes include granulomatous disease, necrotising pneumonia and radiation fibrosis.

Chronic atelectasis
Chronic atelectasis may take one of two forms—middle lobe syndrome or rounded atelectasis.

Right middle lobe syndrome
In right middle lobe syndrome, the middle lobe of the right lung contracts, usually because of pressure on the bronchus from enlarged lymph glands and occasionally a tumor. The blocked, contracted lung may develop pneumonia that fails to resolve completely and leads to chronic inflammation, scarring, and bronchiectasis.

Patchy atelectasis
Is due to lack of surfactant, as occurs in hyaline membrane disease of newborn or acute (adult) respiratory distress syndrome (ARDS).

Rounded atelectasis
In rounded atelectasis (folded lung or Blesovsky syndrome), an outer portion of the lung slowly collapses as a result of scarring and shrinkage of the membrane layers covering the lungs (pleura), which would show as visceral pleural thickening and entrapment of lung tissue. This produces a rounded appearance on X-ray that doctors may mistake for a tumor. Rounded atelectasis is usually a complication of asbestos-induced disease of the pleura, but it may also result from other types of chronic scarring and thickening of the pleura.

Treatment
Treatment is directed at correcting the underlying cause. In atelectasis manifestations that result from the mucus plugging of the airways as seen in patients with cystic fibrosis and pneumonia, mucolytic agents such as acetylcysteine (NAC) is used. This nebulized treatment works by reducing mucous viscosity and elasticity by breaking disulfide bonds in mucoproteins within the mucus complex, thus facilitating mucus clearance. Post-surgical atelectasis is treated by physiotherapy, focusing on deep breathing and encouraging coughing. An incentive spirometer is often used as part of the breathing exercises.  Walking is also highly encouraged to improve lung inflation </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Parosmia and can you explain it in depth? [/INST] Parosmia (from the Greek παρά pará and ὀσμή osmḗ "smell") is a dysfunctional smell detection characterized by the inability of the brain to correctly identify an odors "natural" smell. Instead, the natural odor is usually transformed into an unpleasant aroma, typically a "burned", "rotting", "fecal", or "chemical" smell. There can also be rare instances of a pleasant odor called euosmia. The condition was rare and little-researched until it became relatively more widespread since 2020 as a side effect of COVID-19.

Causes
There are numerous diseases with which parosmia is associated. In a case study, Frasnelli et al. examined five patients that endured parosmia or phantosmia, most as a result of upper respiratory tract infections (URTIs). It is hypothesized that URTIs can result in parosmia because of damage to olfactory receptor neurons (ORNs). The condition has been linked to coronavirus disease 2019 as a rare side effect. Common triggers in COVID-19 related parosmia include coffee, chocolate, meat, onion and toothpaste.  Exposure to harmful solvents has also been linked to parosmia, specifically by damaging ORNs.
Damage to these neurons could render them unable to correctly encode a signal representing a particular odor, which would send an erroneous signal to the odor processing center, the olfactory bulb. This, in turn, leads to the signal triggering a different smell than the stimulating odor, and thus the patient cannot sync the input and output odors. Damage to ORNs describes a peripheral defect in the pathway, but there are also instances where damage to the processing center in the brain can lead to distorted odors.
Different types of head trauma could also lead to dysfunctions that relate to what the afflicted brain area controls. In humans, the olfactory bulb is located on the inferior side of the brain. Physical damage to this area would alter how the area processes information in a variety of ways, but there are also diseases that can alter how this area works. If the part of the brain that interprets these input signals is damaged, then a distorted output is possible. This would also lead to parosmia. Temporal lobe epilepsy has led to cases of parosmia, but these were only temporary; the onset of parosmia was a seizure and it typically lasted a week or two after. Parosmia is sometimes associated with Parkinsons disease </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Autosensitization dermatitis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hematospermia and can you explain it in depth? [/INST] Hematospermia (also known as haematospermia, hemospermia, or haemospermia) is the presence of blood in ejaculation. It is most often a benign symptom. Among men age 40 or older, hematospermia is a slight predictor of cancer, typically prostate cancer. No specific cause is found in up to 70% of cases.

Cause
Though haematospermia may cause considerable distress to patients, it is often a benign and self-limiting condition caused by infections, particularly in younger patients. An isolated episode is usually considered benign and not likely to be associated with malignancy. Recurrent haematospermia may indicate a more serious underlying pathology particularly in patients over 40 years of age.

Infection and inflammation
Infection or inflammation is considered the most common cause of the condition. Implicated pathogens include; Gram-negative bacteria (often E. coli), gonococci, T. pallidum, C. trachomatis, N. gonorrhoeae, echinococcus (rarely), HSV type 1 or 2, and HPV </s>