<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 Benign prostatic hyperplasia and can you explain it in depth? [/INST] Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss of bladder control. Complications can include urinary tract infections, bladder stones, and chronic kidney problems.The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. Medications like pseudoephedrine, anticholinergics, and calcium channel blockers may worsen symptoms. The underlying mechanism involves the prostate pressing on the urethra and thereby making it difficult to pass urine out of the bladder. Diagnosis is typically based on symptoms and examination after ruling out other possible causes.Treatment options include lifestyle changes, medications, a number of procedures, and surgery. In those with mild symptoms, weight loss, exercise, and decreasing caffeine intake are recommended, although the quality of the evidence for exercise is low. In those with more significant symptoms, medications may include alpha blockers such as terazosin or 5α-reductase inhibitors such as finasteride. Surgical removal of part of the prostate may be carried out in those who do not improve with other measures. Some herbal medicines that have been studied, such as saw palmetto, have not been shown to help. Other herbal medicines somewhat effective at improving urine flow include beta-sitosterol from Hypoxis rooperi (African star grass), pygeum (extracted from the bark of Prunus africana), pumpkin seeds (Cucurbita pepo), and stinging nettle (Urtica dioica) root.About 105 million men are affected globally. BPH typically begins after the age of 40. Half of males age 50 and over are affected. After the age of 80, that figure climbs to as high as about 90% of males affected. Although prostate specific antigen levels may be elevated in males with BPH, the condition does not increase the risk of prostate cancer.

Signs and symptoms
BPH is the most common cause of lower urinary tract symptoms (LUTS), which are divided into storage, voiding, and symptoms which occur after urination. Storage symptoms include the need to urinate frequently, waking at night to urinate, urgency (compelling need to void that cannot be deferred), involuntary urination, including involuntary urination at night, or urge incontinence (urine leak following a strong sudden need to urinate). Voiding symptoms include urinary hesitancy (a delay between trying to urinate and the flow actually beginning), intermittency (not continuous), involuntary interruption of voiding, weak urinary stream, straining to void, a sensation of incomplete emptying, and uncontrollable leaking after the end of urination. These symptoms may be accompanied by bladder pain or pain while urinating, called dysuria.Bladder outlet obstruction (BOO) can be caused by BPH. Symptoms are abdominal pain, a continuous feeling of a full bladder, frequent urination, acute urinary retention (inability to urinate), pain during urination (dysuria), problems starting urination (urinary hesitancy), slow urine flow, starting and stopping (urinary intermittency), and nocturia.BPH can be a progressive disease, especially if left untreated. Incomplete voiding results in residual urine or urinary stasis, which can lead to an increased risk of urinary tract infection.

Causes
Hormones
Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. This means that androgens must be present for BPH to occur, but do not necessarily directly cause the condition. This is supported by evidence suggesting that castrated boys do not develop BPH when they age. In an unusual study of 26 eunuchs from the palace of the Qing dynasty still living in Beijing in 1960, the prostate could not be felt in 81% of the studied eunuchs. The average time since castration was 54 years (range, 41–65 years). On the other hand, some studies suggest that administering exogenous testosterone is not associated with a significant increase in the risk of BPH symptoms, so the role of testosterone in prostate cancer and BPH is still unclear. Further randomized controlled trials with more participants are needed to quantify any risk of giving exogenous testosterone.Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. DHT is synthesized in the prostate from circulating testosterone by the action of the enzyme 5α-reductase, type 2. DHT can act in an autocrine fashion on the stromal cells or in paracrine fashion by diffusing into nearby epithelial cells. In both of these cell types, DHT binds to nuclear androgen receptors and signals the transcription of growth factors that are mitogenic to the epithelial and stromal cells. DHT is ten times more potent than testosterone because it dissociates from the androgen receptor more slowly. The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5α-reductase such as finasteride is given to men with this condition. Therapy with a 5α-reductase inhibitor markedly reduces the DHT content of the prostate and, in turn, reduces prostate volume and BPH symptoms.Testosterone promotes prostate cell proliferation, but relatively low levels of serum testosterone are found in patients with BPH. One small study has shown that medical castration lowers the serum and prostate hormone levels unevenly, having less effect on testosterone and dihydrotestosterone levels in the prostate.While there is some evidence that estrogen may play a role in the cause of BPH, this effect appears to be mediated mainly through local conversion of androgens to estrogen in the prostate tissue rather than a direct effect of estrogen itself. In canine in vivo studies castration, which significantly reduced androgen levels but left estrogen levels unchanged, caused significant atrophy of the prostate. Studies looking for a correlation between prostatic hyperplasia and serum estrogen levels in humans have generally shown none.In 2008, Gat et al. published evidence that BPH is caused by failure in the spermatic venous drainage system resulting in increased hydrostatic pressure and local testosterone levels elevated more than 100 fold above serum levels. If confirmed, this mechanism explains why serum androgen levels do not seem to correlate with BPH and why giving exogenous testosterone would not make much difference.

Diet
Studies indicate that dietary patterns may affect development of BPH, but further research is needed to clarify any important relationship. Studies from China suggest that greater protein intake may be a factor in development of BPH. Men older than 60 in rural areas had very low rates of clinical BPH, while men living in cities and consuming more animal protein had a higher incidence. On the other hand, a study in Japanese-American men in Hawaii found a strong negative association with alcohol intake, but a weak positive association with beef intake. In a large prospective cohort study in the US (the Health Professionals Follow-up Study), investigators reported modest associations between BPH (men with strong symptoms of BPH or surgically confirmed BPH) and total energy and protein, but not fat intake. There is also epidemiological evidence linking BPH with metabolic syndrome (concurrent obesity, impaired glucose metabolism and diabetes, high triglyceride levels, high levels of low-density cholesterol, and hypertension).

Degeneration
Benign prostatic hyperplasia is an age-related disease. Misrepair-accumulation aging theory suggests that development of benign prostatic hyperplasia is a consequence of fibrosis and weakening of the muscular tissue in the prostate. The muscular tissue is important in the functionality of the prostate, and provides the force for excreting the fluid produced by prostatic glands. However, repeated contractions and dilations of myofibers will unavoidably cause injuries and broken myofibers. Myofibers have a low potential for regeneration; therefore, collagen fibers need to be used to replace the broken myofibers. Such misrepairs make the muscular tissue weak in functioning, and the fluid secreted by glands cannot be excreted completely. Then, the accumulation of fluid in glands increases the resistance of muscular tissue during the movements of contractions and dilations, and more and more myofibers will be broken and replaced by collagen fibers.

Pathophysiology
As men age, the enzymes aromatase and 5-alpha reductase increase in activity. These enzymes are responsible for converting androgen hormones into estrogen and dihydrotestosterone, respectively. This metabolism of androgen hormones leads to a decrease in testosterone but increased levels of DHT and estrogen.
Both the glandular epithelial cells and the stromal cells (including muscular fibers) undergo hyperplasia in BPH. Most sources agree that of the two tissues, stromal hyperplasia predominates, but the exact ratio of the two is unclear.:694Anatomically the median and lateral lobes are usually enlarged, due to their highly glandular composition. The anterior lobe has little in the way of glandular tissue and is seldom enlarged. (Carcinoma of the prostate typically occurs in the posterior lobe – hence the ability to discern an irregular outline per rectal examination). The earliest microscopic signs of BPH usually begin between the age of 30 and 50 years old in the PUG, which is posterior to the proximal urethra.:694 In BPH, the majority of growth occurs in the transition zone (TZ) of the prostate.:694 In addition to these two classic areas, the peripheral zone (PZ) is also involved to a lesser extent.:695 Prostatic cancer typically occurs in the PZ. However, BPH nodules, usually from the TZ are often biopsied anyway to rule out cancer in the TZ.:695 BPH can be a progressive growth that in rare instances leads to exceptional enlargement. In some males, the prostate enlargement exceeds 200 to 500 grams. This condition has been defined as giant prostatic hyperplasia (GPH).

Diagnosis
The clinical diagnosis of BPH is based on a history of LUTS (lower urinary tract symptoms), a digital rectal exam, and exclusion of other causes of similar signs and symptoms. The degree of LUTS does not necessarily correspond to the size of the prostate. An enlarged prostate gland on rectal examination that is symmetric and smooth supports a diagnosis of BPH. However, if the prostate gland feels asymmetrical, firm, or nodular, this raises concern for prostate cancer.Validated questionnaires such as the American Urological Association Symptom Index (AUA-SI), the International Prostate Symptom Score (I-PSS), and more recently the UWIN score (urgency, weak stream, incomplete emptying, and nocturia) are useful aids to making the diagnosis of BPH and quantifying the severity of symptoms.

Laboratory investigations
Urinalysis is typically performed when LUTS are present and BPH is suspected to evaluate for signs of a urinary tract infection, glucose in the urine (suggestive of diabetes), or protein in the urine (suggestive of kidney disease). Bloodwork including kidney function tests and prostate specific antigen (PSA) are often ordered to evaluate for kidney damage and prostate cancer, respectively. However, checking blood PSA levels for prostate cancer screening is controversial and not necessarily indicated in every evaluation for BPH. Benign prostatic hyperplasia and prostate cancer are both capable of increasing blood PSA levels and PSA elevation is unable to differentiate these two conditions well. If PSA levels are checked and are high, then further investigation is warranted. Measures including PSA density, free PSA, rectal examination, and transrectal ultrasonography may be helpful in determining whether a PSA increase is due to BPH or prostate cancer.

Imaging and other investigations
Uroflowmetry is done to measure the rate of urine flow and total volume of urine voided when the subject is peeing.Abdominal ultrasound examination of the prostate and kidneys is often performed to rule out hydronephrosis and hydroureter. Incidentally, cysts, tumours, and stones may be found on ultrasound. Post-void residual volume of more than 100 ml may indicate significant obstruction. Prostate size of 30 cc or more indicates enlargement of the prostate.Prostatic calcification can be detected through transrectal ultrasound (TRUS). Calcification is due to solidification of prostatic secretions or calcified corpora amylacea (hyaline masses on the prostate gland). Calcification is also found in a variety of other conditions such as prostatitis, chronic pelvic pain syndrome, and prostate cancer. For those with elevated levels of PSA, TRUS guided biopsy is performed to take a sample of the prostate for investigation. Although MRI is more accurate than TRUS in determining prostate volume, TRUS is less expensive and almost as accurate as MRI. Therefore, TRUS is still preferred to measure prostate volume.

Differential diagnosis
Medical conditions
The differential diagnosis for LUTS is broad and includes various medical conditions, neurologic disorders, and other diseases of the bladder, urethra, and prostate such as bladder cancer, urinary tract infection, urethral stricture, urethral calculi (stones), chronic prostatitis, and prostate cancer. Neurogenic bladder can cause urinary retention and cause symptoms similar to those of BPH. This may occur as a result of uncoordinated contraction of the bladder muscle or impairment in the timing of bladder muscle contraction and urethral sphincter relaxation. Notable causes of neurogenic bladder include disorders of the central nervous system such as Parkinsons disease, multiple sclerosis, and spinal cord injuries as well as disorders of the peripheral nervous system such as diabetes mellitus, vitamin B12 deficiency, and alcohol-induced nerve damage. Individuals affected by heart failure often experience nighttime awakenings to urinate due to redistribution of fluid accumulated in swollen legs.

Medications
Certain medications can increase urination difficulties by increasing bladder outlet resistance due to increased smooth muscle tone at the prostate or bladder neck and contribute to LUTS. Alpha-adrenergic agonist medications, such as decongestants with pseudoephedrine can increase bladder outlet resistance. In contrast, calcium channel blockers and anticholinergic medications can worsen urinary retention by promoting bladder muscle relaxation. Diuretic medications such as loop diuretics (e.g., furosemide) or thiazides (e.g., chlorthalidone) can cause or worsen urinary frequency and nighttime awakenings to urinate.

Management
When treating and managing benign prostatic hyperplasia, the aim is to prevent complications related to the disease and improve or relieve symptoms. Approaches used include lifestyle modifications, medications, and surgery.

Lifestyle
Lifestyle alterations to address the symptoms of BPH include physical activity, decreasing fluid intake before bedtime, moderating the consumption of alcohol and caffeine-containing products and following a timed voiding schedule.
Patients can also attempt to avoid products and medications with anticholinergic properties that may exacerbate urinary retention symptoms of BPH, including antihistamines, decongestants, opioids, and tricyclic antidepressants; however, changes in medications should be done with input from a medical professional.

Physical activity
Physical activity has been recommended as a treatment for urinary tract symptoms. A 2019 Cochrane review of six studies involving 652 men assessing the effects of physical activity alone, physical activity as a part of a self-management program, among others.  However, the quality of evidence was very low and therefore it remains uncertain whether physical activity is helpful in men experiencing urinary symptoms caused by benign prostatic hyperplasia.

Voiding position
Voiding position when urinating may influence urodynamic parameters (urinary flow rate, voiding time, and post-void residual volume). A meta-analysis found no differences between the standing and sitting positions for healthy males, but that, for elderly males with lower urinary tract symptoms, voiding in the sitting position--
decreased the post void residual volume;
increased the maximum urinary flow, comparable with pharmacological intervention; and
decreased the voiding time.This urodynamic profile is associated with a lower risk of urologic complications, such as cystitis and bladder stones.

Medications
The two main medication classes for BPH management are alpha blockers and 5α-reductase inhibitors.

Alpha blockers
Selective α1-blockers are the most common choice for initial therapy. They include alfuzosin, doxazosin, silodosin, tamsulosin, terazosin, and naftopidil. They have a small to moderate benefit at improving symptoms. Selective alpha-1 blockers are similar in effectiveness but have slightly different side effect profiles. Alpha blockers relax smooth muscle in the prostate and the bladder neck, thus decreasing the blockage of urine flow. Common side effects of alpha blockers include orthostatic hypotension (a head rush or dizzy spell when standing up or stretching), ejaculation changes, erectile dysfunction, headaches, nasal congestion, and weakness. For men with LUTS due to an enlarged prostate, the effects of naftopidil, tamsulosin and silodosin on urinary symptoms and quality of life may be similar. Naftopidil and tamsulosin may have similar levels of unwanted sexual side effects but fewer unwanted side effects than silodosin.Tamsulosin and silodosin are selective α1 receptor blockers that preferentially bind to the α1A receptor in the prostate instead of the α1B receptor in the blood vessels. Less-selective α1 receptor blockers such as terazosin and doxazosin may lower blood pressure. The older, less selective α1-adrenergic blocker prazosin is not a first line choice for either high blood pressure or prostatic hyperplasia; it is a choice for patients who present with both problems at the same time. The older, broadly non-selective alpha blocker medications such as phenoxybenzamine are not recommended for control of BPH. Non-selective alpha blockers such as terazosin and doxazosin may also require slow dose adjustments as they can lower blood pressure and cause syncope (fainting) if the response to the medication is too strong.

5α-reductase inhibitors
The 5α-reductase inhibitors finasteride and dutasteride may also be used in men with BPH. These medications inhibit the 5α-reductase enzyme, which, in turn, inhibits production of DHT, a hormone responsible for enlarging the prostate. Effects may take longer to appear than alpha blockers, but they persist for many years. When used together with alpha blockers, no benefit was reported in short-term trials, but in a longer-term study (3–4 years) there was a greater reduction in BPH progression to acute urinary retention and surgery than with either agent alone, especially in people with more severe symptoms and larger prostates. Other trials have confirmed reductions in symptoms, within 6 months in one trial, an effect that was maintained after withdrawal of the alpha blocker. Side effects include decreased libido and ejaculatory or erectile dysfunction. The 5α-reductase inhibitors are contraindicated in pregnant women because of their teratogenicity due to interference with fetal testosterone metabolism, and as a precaution, pregnant women should not handle crushed or broken tablets.

Phosphodiesterase inhibitors (PDE)
A 2018 Cochrane review of studies on men over 60 with moderate to severe lower urinary tract symptoms analyzed the impacts of phosphodiesterase inhibitors (PDE) in comparison to other drugs. These drugs may improve urinary symptoms slightly and reduce urinary bother but may also cause more side effects compared to placebo. The evidence in this review found that there is probably no difference between PDE and alpha blockers, however when used in combination they may provide a greater improvement in symptoms (with more side effects). PDE also likely improves symptoms when used in combination with 5-alpha reductase inhibitors.
Several phosphodiesterase-5 inhibitors are also effective, but may require multiple doses daily to maintain adequate urine flow. Tadalafil, a phosphodiesterase-5 inhibitor, was considered then rejected by NICE in the UK for the treatment of symptoms associated with BPH. In 2011, the U.S. Food and Drug Administration approved tadalafil to treat the signs and symptoms of benign prostatic hyperplasia, and for the treatment of BPH and erectile dysfunction (ED), when the conditions occur simultaneously.

Others
Antimuscarinics such as tolterodine may also be used, especially in combination with alpha blockers. They act by decreasing acetylcholine effects on the smooth muscle of the bladder, thus helping control symptoms of an overactive bladder.

Self-catheterization
Intermittent urinary catheterization is used to relieve the bladder in people with urinary retention. Self-catheterization is an option in BPH when it is difficult or impossible to completely empty the bladder. Urinary tract infection is the most common complication of intermittent catheterization. Several techniques and types of catheter are available, including sterile (single-use) and clean (multiple use) catheters, but, based on current information, none is superior to others in reducing the incidence of urinary tract infection.

Surgery
If medical treatment is not effective, surgery may be performed. Surgical techniques used include the following:

Transurethral resection of the prostate (TURP): the gold standard. TURP is thought to be the most effective approach for improving urinary symptoms and urinary flow, however, this surgical procedure may be associated with complications in up to 20% of 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 Steatorrhea and can you explain it in depth? [/INST] Steatorrhea (or steatorrhoea) is the presence of excess fat in feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the fecal fat level. The definition of how much fecal fat constitutes steatorrhea has not been standardized.

Causes
Impaired digestion or absorption can result in fatty stools.
Possible causes include exocrine pancreatic insufficiency, with poor digestion from lack of lipases, loss of bile salts, which reduces micelle formation, and small intestinal disease-producing malabsorption. Various other causes include certain medicines that block fat absorption or indigestible or excess oil/fat in diet.The absence of bile secretion can cause the feces to turn gray or pale. Bile is responsible for the brownish color of feces. Other features of fat malabsorption may also occur such as reduced bone density, difficulty with vision under low light levels, bleeding, bruising, and slow blood clotting times.

Associated diseases
Conditions affecting the pancreas.  Exocrine pancreatic insufficiency can be caused by chronic pancreatitis, cystic fibrosis and pancreatic cancer (if it obstructs biliary outflow).
Conditions affecting bile salts.  Obstruction of the bile ducts by gallstones (choledocholithiasis), primary sclerosing cholangitis, liver damage (intrahepatic cholestasis), hypolipidemic drugs, or changes following gallbladder removal (cholecystectomy).
Conditions producing intestinal malabsorption </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 Ovarian cyst and can you explain it in depth? [/INST] An ovarian cyst is a fluid-filled sac within the ovary. Often they cause no symptoms. Occasionally they may produce bloating, lower abdominal pain, or lower back pain. The majority of cysts are harmless. If the cyst either breaks open or causes twisting of the ovary, it may cause severe pain. This may result in vomiting or feeling faint, and even cause head aches.
Most ovarian cysts are related to ovulation, being either follicular cysts or corpus luteum cysts. Other types include cysts due to endometriosis, dermoid cysts, and cystadenomas. Many small cysts occur in both ovaries in polycystic ovary syndrome (PCOS). Pelvic inflammatory disease may also result in cysts. Rarely, cysts may be a form of ovarian cancer. Diagnosis is undertaken by pelvic examination with an ultrasound or other testing used to gather further details.Often, cysts are simply observed over time. If they cause pain, medications such as paracetamol (acetaminophen) or ibuprofen may be used. Hormonal birth control may be used to prevent further cysts in those who are frequently affected. However, evidence does not support birth control as a treatment of current cysts. If they do not go away after several months, get larger, look unusual, or cause pain, they may be removed by surgery.Most women of reproductive age develop small cysts each month. Large cysts that cause problems occur in about 8% of women before menopause. Ovarian cysts are present in about 16% of women after menopause and if present are more likely to be cancer.

Signs and symptoms
Some or all of the following symptoms may be present, though it is possible not to experience any symptoms:
Abdominal pain. Dull aching pain within the abdomen or pelvis, especially during intercourse.
Uterine bleeding. Pain during or shortly after beginning or end of menstrual period; irregular periods, or abnormal uterine bleeding or spotting.
Fullness, heaviness, pressure, swelling, or bloating in the abdomen.
When a cyst ruptures from the ovary, there may be sudden and sharp pain in the lower abdomen on one side.
Change in frequency or ease of urination (such as inability to fully empty the bladder), or difficulty with bowel movements due to pressure on adjacent pelvic anatomy.
Constitutional symptoms such as fatigue, headaches.
Nausea or vomiting
Weight gainOther symptoms may depend on the cause of the cysts:
Symptoms that may occur if the cause of the cysts is polycystic ovarian syndrome (PCOS) may include increased facial hair or body hair, acne, obesity and infertility.
If the cause is endometriosis, then periods may be heavy, and intercourse painful.The effect of cysts not related to PCOS on fertility is unclear.

Cyst rupture
A ruptured ovarian cyst is usually self-limiting, and only requires keeping an eye on the situation and pain medications. The main symptom is abdominal pain, which may last a few days to several weeks, but they can also be asymptomatic. Rupture of large ovarian cysts can cause bleeding inside the abdominal cavity and in some cases shock.

Ovarian torsion
Ovarian cysts increase the risk for ovarian torsion; cysts which are larger than 4 cm are associated with approximately 17% risk. The torsion can cause obstruction of blood flow and lead to infarction.

Types
Functional
Functional cysts form as a normal part of the menstrual cycle. There are several types of functional cysts:

Follicular cyst, the most common type of ovarian cyst. In menstruating women, a follicle containing the ovum, an unfertilized egg, will rupture during ovulation. If this does not occur, a follicular cyst of more than 2.5 cm diameter may result.
Corpus luteum cysts appear after ovulation. The corpus luteum is the remnant of the follicle after the ovum has moved to the fallopian tubes. This normally degrades within 5 to 9 days. A corpus luteum that is more than 3 cm is defined as cystic.
Theca lutein cysts occur within the thecal layer of cells surrounding developing oocytes. Under the influence of excessive hCG, thecal cells may proliferate and become cystic. This is usually on both ovaries.

Non-functional
Non-functional cysts may include the following:
An ovary with many cysts, which may be found in normal women, or within the setting of polycystic ovary syndrome
Cysts caused by endometriosis, known as chocolate cysts
Hemorrhagic ovarian cyst
Dermoid cyst
Ovarian serous cystadenoma
Ovarian mucinous cystadenoma
Paraovarian cyst
Cystic adenofibroma
Borderline tumoral cysts

Diagnosis
Ovarian cysts are usually diagnosed by ultrasound, CT scan, or MRI, and correlated with clinical presentation and endocrinologic tests as appropriate.

Ultrasound
Follow-up imaging in women of reproductive age for incidentally discovered simple cysts on ultrasound is not needed until 5 cm, as these are usually normal ovarian follicles. Simple cysts 5 to 7 cm in premenopausal females should be followed yearly. Simple cysts larger than 7 cm require further imaging with MRI or surgical assessment. Because they are large, they cannot be reliably assessed by ultrasound alone; it can be difficult to see posterior wall soft tissue nodularity or thickened septation due to limited ultrasound beam penetrance at this size and depth. For the corpus luteum, a dominant ovulating follicle that typically appears as a cyst with circumferentially thickened walls and crenulated inner margins, follow up is not needed if the cyst is less than 3 cm in diameter. In postmenopausal patients, any simple cyst greater than 1 cm but less than 7 cm needs yearly follow-up, while those greater than 7 cm need MRI or surgical evaluation, similar to reproductive age females.

For incidentally discovered dermoids, diagnosed on ultrasound by their pathognomonic echogenic fat, either surgical removal or yearly follow up is indicated, regardless of patient age. For peritoneal inclusion cysts, which have a crumpled tissue-paper appearance and tend to follow the contour of adjacent organs, follow up is based on clinical history. Hydrosalpinx, or fallopian tube dilation, can be mistaken for an ovarian cyst due to its anechoic appearance. Follow-up for this is also based on clinical presentation.For multiloculate cysts with thin septation less than 3 mm, surgical evaluation is recommended. The presence of multiloculation suggests a neoplasm, although the thin septation implies that the neoplasm is benign. For any thickened septation, nodularity, vascular flow on color doppler, or growth over several ultrasounds, surgical removal may be considered due to concern of cancer.

Scoring systems
There are several systems to assess risk of an ovarian cyst of being an ovarian cancer, including the RMI (risk of malignancy index), LR2 and SR (simple rules). Sensitivities and specificities of these systems are given in tables below:
Ovarian cysts may be classified according to whether they are a variant of the normal menstrual cycle, referred to as a functional or follicular cyst.Ovarian cysts are considered large when they are over 5 cm and giant when they are over 15 cm. In children, ovarian cysts reaching above the level of the umbilicus are considered giant.

Associated conditions
In juvenile hypothyroidism multicystic ovaries are present in about 75% of cases, while large ovarian cysts and elevated ovarian tumor marks are one of the symptoms of the Van Wyk and Grumbach syndrome.The CA-125 marker in children and adolescents can be frequently elevated even in absence of malignancy and conservative management should be considered.
Polycystic ovarian syndrome involves the development of multiple small cysts in both ovaries due to an elevated ratio of leutenizing hormone to follicle stimulating hormone, typically more than 25 cysts in each ovary, or an ovarian volume of greater than 10 mL.Larger bilateral cysts can develop as a result of fertility treatment due to elevated levels of HCG, as can be seen with the use of clomifene for follicular induction, in extreme cases resulting in a condition known as ovarian hyperstimulation syndrome. Certain malignancies can mimic the effects of clomifene on the ovaries, also due to increased HCG, in particular gestational trophoblastic disease. Ovarian hyperstimulation occurs more often with invasive moles and choriocarcinoma than complete molar pregnancies.

Risk of cancer
A widely recognised method of estimating the risk of malignant ovarian cancer based on initial workup is the risk of malignancy index (RMI). It is recommended that women with an RMI score over 200 should be referred to a centre with experience in ovarian cancer surgery.The RMI is calculated as follows:
RMI = ultrasound score × menopausal score × CA-125 level in U/ml.There are two methods to determine the ultrasound score and menopausal score, with the resultant RMI being called RMI 1 and RMI 2, respectively, depending on what method is used:
An RMI 2 of over 200 has been estimated to have a sensitivity of 74 to 80%, a specificity of 89 to 92% and a positive predictive value of around 80% of ovarian cancer. RMI 2 is regarded as more sensitive than RMI 1.

Histopathology
In case an ovarian cyst is surgically removed, a more definite diagnosis can be made by histopathology:

Treatment
Cysts associated with hypothyroidism or other endocrine problems are managed by treating the underlying condition.
About 95% of ovarian cysts are benign, not cancerous. Functional cysts and hemorrhagic ovarian cysts usually resolve spontaneously. However, the bigger an ovarian cyst is, the less likely it is to disappear on its own. Treatment may be required if cysts persist over several months, grow, or cause increasing pain. Cysts that persist beyond two or three menstrual cycles, or occur in post-menopausal women, may indicate more serious disease and should be investigated through ultrasonography and laparoscopy, especially in cases where family members have had ovarian cancer. Such cysts may require surgical biopsy. Additionally, a blood test may be taken before surgery to check for elevated CA-125, a tumour marker, which is often found in increased levels in ovarian cancer, although it can also be elevated by other conditions resulting in a large number of false positives.

Pain
Pain associated with ovarian cysts may be treated in several ways:

Pain relievers such as acetaminophen, nonsteroidal anti-inflammatory drugs, or opioids.
While hormonal birth control prevents the development of new cysts in those who frequently get them, it is not useful for the treatment of current cysts.

Surgery
Although most cases of ovarian cysts involve monitoring, some cases require surgery. This may involve removing the cyst, or one or both ovaries. Technique is typically laparoscopic, unless the cyst is particularly large, or if pre-operative imaging suggests malignancy or complex anatomy. In certain situations, the cyst is entirely removed, while with cysts with low recurrence risk, younger patients, or which are in anatomically eloquent areas of the pelvis, they can be drained. Features that may indicate the need for surgery include:
Persistent complex ovarian cysts
Persistent cysts that are causing symptoms
Complex ovarian cysts larger than 5 cm
Simple ovarian cysts larger 10 cm or larger than 5 cm in postmenopausal patients
Women who are menopausal or perimenopausal

Frequency
Most women of reproductive age develop small cysts each month, and large cysts that cause problems occur in about 8% of women before menopause. Ovarian cysts are present in about 16% of women after menopause and if present are more likely to be cancer.Benign ovarian cysts are common in asymptomatic premenarchal girls and found in approximately 68% of ovaries of girls 2–12 years old and in 84% of ovaries of girls 0–2 years old. Most of them are smaller than 9 mm while about 10–20% are larger macrocysts. While the smaller cysts mostly disappear within 6 months the larger ones appear to be more persistent.

References
Further reading
McBee, W. C; Escobar, P. F; Falcone, T. (1 February 2007). "Which ovarian masses need intervention?". Cleveland Clinic Journal of Medicine. 74 (2): 149–157. doi:10.3949/ccjm.74.2.149. PMID 17333642. S2CID 45443236.
Simcock, B; Anderson, N (February 2005). "Diagnosis and management of simple ovarian cysts: An audit". Australasian Radiology. 49 (1): 27–31. doi:10.1111/j.1440-1673.2005.01389.x. PMID 15727606.
Ross, Elisa K.; Kebria, Medhi (August 2013). "Incidental ovarian cysts: When to reassure, when to reassess, when to refer". Cleveland Clinic Journal of Medicine. 80 (8): 503–514. doi:10.3949/ccjm.80a.12155. PMID 23908107. S2CID 28081941.
"Ovarian cyst - Treatment". National Health Service. 3 October 2018.
Gerber, B.; Müller, H.; Külz, T.; Krause, A.; Reimer, T. (1 April 1997). "Simple ovarian cysts in premenopausal patients". International Journal of Gynecology & Obstetrics. 57 (1): 49–55. doi:10.1016/S0020-7292(97)02832-4. PMID 9175670. S2CID 34289061.
Potter, Andrew W.; Chandrasekhar, Chitra A. (October 2008). "US and CT Evaluation of Acute Pelvic Pain of Gynecologic Origin in Nonpregnant Premenopausal Patients". RadioGraphics </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 Constrictive pericarditis and can you explain it in depth? [/INST] Constrictive pericarditis is a medical condition characterized by a thickened, fibrotic pericardium, limiting the hearts ability to function normally. In many cases, the condition continues to be difficult to diagnose and therefore benefits from a good understanding of the underlying cause.

Signs and symptoms
Signs and symptoms of constrictive pericarditis are consistent with the following: fatigue, swollen abdomen, difficulty breathing (dyspnea), swelling of legs and general weakness. Related conditions are bacterial pericarditis, pericarditis and pericarditis after a heart attack.

Causes
The cause of constrictive pericarditis in the developing world are idiopathic in origin, though likely infectious in nature.  In regions where tuberculosis is common, it is the cause in a large portion of cases.
Causes of constrictive pericarditis include:

Tuberculosis
Incomplete drainage of purulent pericarditis
Fungal and parasitic infections
Chronic pericarditis
Postviral pericarditis
Postsurgical
Following MI, post-myocardial infarction
In association with pulmonary asbestos

Pathophysiology
The pathophysiological characteristics of constrictive pericarditis are due to a thickened, fibrotic pericardium that forms a non-compliant shell around the heart.  This shell prevents the heart from expanding when blood enters it.  This results in significant respiratory variation in blood flow in the chambers of the heart.During inspiration, pressure in the thoracic cavity decreases but is not relayed to the left atrium, subsequently a reduction in flow to the left atrium and ventricle happens. During diastole, less blood flow in left ventricle allows for more room for filling in right ventricle and therefore a septal shift occurs.During expiration, the amount of blood entering the left ventricle will increase, allowing the interventricular septum to bulge towards the right ventricle, decreasing the right heart ventricular filing.

Diagnosis
The diagnosis of constrictive pericarditis is often difficult to make.  In particular, restrictive cardiomyopathy has many similar clinical features to constrictive pericarditis, and differentiating them in a particular individual is often a diagnostic dilemma.
Chest X-Ray - pericardial calcification (common but not specific), pleural effusions are common findings.
Echocardiography - the principal echographic finding is changes in cardiac chamber volume.
CT and MRI - CT scan is useful in assessing the thickness of pericardium, calcification, and ventricular contour. Cardiac MRI may find pericardial thickening and pericardial-myocardial adherence. Ventricular septum shift during breathing can also be found using cardiac MRI </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 Cervical intraepithelial neoplasia and can you explain it in depth? [/INST] Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.
CIN most commonly occurs at the squamocolumnar junction of the cervix, a transitional area between the squamous epithelium of the vagina and the columnar epithelium of the endocervix. It can also occur in vaginal walls and vulvar epithelium. CIN is graded on a 1–3 scale, with 3 being the most abnormal (see classification section below).
Human papillomavirus (HPV) infection is necessary for the development of CIN, but not all with this infection develop cervical cancer. Many women with HPV infection never develop CIN or cervical cancer. Typically, HPV resolves on its own. However, those with an HPV infection that lasts more than one or two years have a higher risk of developing a higher grade of CIN.Like other intraepithelial neoplasias, CIN is not cancer and is usually curable. Most cases of CIN either remain stable or are eliminated by the persons immune system without need for intervention. However, a small percentage of cases progress to cervical cancer, typically cervical squamous cell carcinoma (SCC), if left untreated.

Signs and symptoms
There are no specific symptoms of CIN alone.
Generally, signs and symptoms of cervical cancer include:
abnormal or post-menopausal bleeding
abnormal discharge
changes in bladder or bowel function
pelvic pain on examination
abnormal appearance or palpation of cervix.HPV infection of the vulva and vagina can cause genital warts or be asymptomatic.

Causes
The cause of CIN is chronic infection of the cervix with HPV, especially infection with high-risk HPV types 16 or 18. It is thought that the high-risk HPV infections have the ability to inactivate tumor suppressor genes such as the p53 gene and the RB gene, thus allowing the infected cells to grow unchecked and accumulate successive mutations, eventually leading to cancer.Some groups of women have been found to be at a higher risk of developing CIN:
Infection with a high-risk type of HPV, such as 16, 18, 31, or 33
Immunodeficiency (e.g. HIV infection)
Poor diet
Multiple sex partners
Lack of condom use
Cigarette smokingAdditionally, a number of risk factors have been shown to increase an individuals likelihood of developing CIN 3/carcinoma in situ (see below):
Women who give birth before age 17
Women who have > 1 full term pregnancies

Pathophysiology
The earliest microscopic change corresponding to CIN is epithelial dysplasia, or surface lining, of the cervix, which is essentially undetectable by the woman. The majority of these changes occur at the squamocolumnar junction, or transformation zone, an area of unstable cervical epithelium that is prone to abnormal changes. Cellular changes associated with HPV infection, such as koilocytes, are also commonly seen in CIN. While infection with HPV is needed for development of CIN, most women with HPV infection do not develop high-grade intraepithelial lesions or cancer. HPV is not alone enough causative.Of the over 100 different types of HPV, approximately 40 are known to affect the epithelial tissue of the anogenital area and have different probabilities of causing malignant changes.

Diagnosis
A test for HPV called the Digene HPV test is highly accurate and serves as both a direct diagnosis and adjuvant to the Pap smear, which is a screening device that allows for an examination of cells but not tissue structure, needed for diagnosis. A colposcopy with directed biopsy is the standard for disease detection. Endocervical brush sampling at the time of Pap smear to detect adenocarcinoma and its precursors is necessary along with doctor/patient vigilance on abdominal symptoms associated with uterine and ovarian carcinoma. The diagnosis of CIN or cervical carcinoma requires a biopsy for histological analysis.

Classification
Historically, abnormal changes of cervical epithelial cells were described as mild, moderate, or severe epithelial dysplasia. In 1988 the National Cancer Institute developed "The Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses". This system provides a uniform way to describe abnormal epithelial cells and determine specimen quality, thus providing clear guidance for clinical management. These abnormalities were classified as squamous or glandular and then further classified by the stage of dysplasia: atypical cells, mild, moderate, severe, and carcinoma.Depending on several factors and the location of the lesion, CIN can start in any of the three stages and can either progress or regress. The grade of squamous intraepithelial lesion can vary.
CIN is classified in grades:

Changes in Terminology
The College of American Pathology and the American Society of Colposcopy and Cervical Pathology came together in 2012 to publish changes in terminology to describe HPV-associated squamous lesions of the anogenital tract as LSIL or HSIL as follows below:CIN 1 is referred to as LSIL.
CIN 2 that is negative for p16, a marker for high-risk HPV, is referred to as LSIL. Those that are p16-positive are referred to as HSIL.
CIN 3 is referred to as HSIL.

Screening
The two screening methods available are the Pap smear and testing for HPV.CIN is usually discovered by a screening test, the Pap smear. The purpose of this test is to detect potentially precancerous changes through random sampling of the transformation zone. Pap smear results may be reported using the Bethesda system (see above). The sensitivity and specificity of this test were variable in a systematic review looking at accuracy of the test.
An abnormal Pap smear result may lead to a recommendation for colposcopy of the cervix, an in office procedure during which the cervix is examined under magnification. A biopsy is taken of any abnormal appearing areas.Colposcopy can be painful and so researchers have tried to find which pain relief is best for women with CIN to use. Research suggests that compared to a placebo, the injection of a local anaesthetic and vasoconstrictor (medicine that causes blood vessels to narrow) into the cervix may lower blood loss and pain during colposcopy.HPV testing can identify most of the high-risk HPV types responsible for CIN. HPV screening happens either as a co-test with the Pap smear or can be done after a Pap smear showing abnormal cells, called reflex testing. Frequency of screening changes based on guidelines from the Society of Lower Genital Tract Disorders (ASCCP). The World Health Organization also has screening and treatment guidelines for precancerous cervical lesions and prevention of cervical cancer.

Primary prevention
HPV vaccination is the approach to primary prevention of both CIN and cervical cancer.

It is important to note that these vaccines do not protect against 100% of types of HPV known to cause cancer. Therefore, screening is still recommended in vaccinated individuals.

Secondary prevention
Appropriate management with monitoring and treatment is the approach to secondary prevention of cervical cancer in cases of persons with CIN.

Treatment
Treatment for CIN 1, mild dysplasia, is not recommended if it lasts fewer than two years. Usually, when a biopsy detects CIN 1, the woman has an HPV infection, which may clear on its own within 12 months. Therefore, it is instead followed for later testing rather than treated. In young women closely monitoring CIN 2 lesions also appears reasonable.Treatment for higher-grade CIN involves removal or destruction of the abnormal cervical cells by cryocautery, electrocautery, laser cautery, loop electrical excision procedure (LEEP), or cervical conization. The typical threshold for treatment is CIN 2+, although a more restrained approach may be taken for young persons and pregnant persons. A Cochrane review found no clear evidence to show which surgical technique may be superior for treating CIN. Evidence suggests that while retinoids are not effective in preventing the progression of CIN, they may be effective in causing regression of disease in people with CIN2 </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 Megaloblastic anemia and can you explain it in depth? [/INST] Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis.
Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias.
The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency. Loss of micronutrients may also be a cause.
Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites that poison DNA production directly, such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim).
The pathological state of megaloblastosis is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by hypersegmented neutrophils (defined as the presence of neutrophils with six or more lobes or the presence of more than 3% of neutrophils with at least five lobes). These hypersegmented neutrophils can be detected in the peripheral blood  (using a diagnostic smear of a blood sample).

Causes
Vitamin B12 deficiency:
Achlorhydria-induced malabsorption
Deficient intake
Deficient intrinsic factor, a molecule produced by cells in the stomach that is required for B12 absorption (pernicious anemia or gastrectomy)
Coeliac disease
Biological competition for vitamin B12 by diverticulosis, fistula, intestinal anastomosis, or infection by the marine parasite Diphyllobothrium latum (fish tapeworm)
Selective vitamin B12 malabsorption (congenital—juvenile megaloblastic anemia 1—and drug-induced)
Chronic pancreatitis
Ileal resection and bypass
Nitrous oxide anesthesia (usually requires repeated instances).
Folate deficiency:
Alcoholism
Deficient intake
Increased needs: pregnancy, infant, rapid cellular proliferation, and cirrhosis
Malabsorption (congenital and drug-induced)
Intestinal and jejunal resection
(indirect) Deficient thiamine and factors (e.g., enzymes) responsible for abnormal folate metabolism.
Combined Deficiency: vitamin B12 & folate.
Inherited Pyrimidine Synthesis Disorders: Orotic aciduria
Inherited DNA Synthesis Disorders
Toxins and Drugs:
Folic acid antagonists (methotrexate)
Purine synthesis antagonists (6-mercaptopurine, azathioprine)
Pyrimidine antagonists (cytarabine)
Phenytoin
Nitrous Oxide
Erythroleukemia
Inborn genetic mutations of the Methionine synthase gene
Di Guglielmos syndrome
Congenital dyserythropoietic anemia
Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause.

Pathophysiology
There is a defect in DNA synthesis in the rapidly dividing cells and to a lesser extent, RNA and protein synthesis are also impaired. Therefore, unbalanced cell proliferation and impaired cell division occur as a result of arrested nuclear maturation so the cells show nuclear-cytoplasmic asynchrony.
In the bone marrow, most megaloblasts are destroyed prior to entering the peripheral blood (intramedullary hemolysis). Some can escape the bone marrow (macrocytes) to peripheral blood but they are destroyed by the reticulo-endothelial system (extramedullary hemolysis).

Diagnosis
The gold standard for the diagnosis of Vitamin B12 deficiency is a low blood level of Vitamin B12. A low level of blood Vitamin B12 is a finding that normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis </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 Hypochloremia 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 Urinary bladder disease 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 Ascending cholangitis and can you explain it in depth? [/INST] Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from its junction with the duodenum (first part of the small intestine). It tends to occur if the bile duct is already partially obstructed by gallstones.Cholangitis can be life-threatening, and is regarded as a medical emergency. Characteristic symptoms include yellow discoloration of the skin or whites of the eyes, fever, abdominal pain, and in severe cases, low blood pressure and confusion. Initial treatment is with intravenous fluids and antibiotics, but there is often an underlying problem (such as gallstones or narrowing in the bile duct) for which further tests and treatments may be necessary, usually in the form of endoscopy to relieve obstruction of the bile duct. The word is from Greek chol-, bile + ang-, vessel + -itis, inflammation.

Signs and symptoms
A person with cholangitis may complain of abdominal pain (particularly in the right upper quadrant of the abdomen), fever, rigors (uncontrollable shaking) and a feeling of uneasiness (malaise). Some may report jaundice (yellow discoloration of the skin and the whites of the eyes).Physical examination findings typically include jaundice and right upper quadrant tenderness. Charcots triad is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever. This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%. Reynolds pentad includes the findings of Charcots triad with the presence of septic shock and mental confusion. This combination of symptoms indicates worsening of the condition and the development of sepsis, and is seen less commonly still.In the elderly, the presentation may be atypical; they may directly collapse due to sepsis without first showing typical features. Those with an indwelling stent in the bile duct (see below) may not develop jaundice.

Causes
Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstones. 10–30% of cases, however, are due to other causes such as benign stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis (surgical connection), various tumors (cancer of the bile duct, gallbladder cancer, cancer of the ampulla of Vater, pancreatic cancer, cancer of the duodenum), anaerobic organisms such as Clostridium and Bacteroides (especially in the elderly and those who have undergone previous surgery of the biliary system).Parasites which may infect the liver and bile ducts may cause cholangitis; these include  the roundworm Ascaris lumbricoides and the liver flukes Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. In people with AIDS, a large number of opportunistic organisms has been known to cause AIDS cholangiopathy, but the risk has rapidly diminished since the introduction of effective AIDS treatment. Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure.

Pathogenesis
Bile is produced by the liver, and serves to eliminate cholesterol and bilirubin from the body, as well as emulsifying of fats to make them more soluble in water and aid in their digestion. Bile is formed in the liver by hepatocytes (liver cells) and excreted into the common hepatic duct. Part of the bile is stored in the gall bladder because of back pressure (exerted by the sphincter of Oddi), and may be released at the time of digestion. The gallbladder also concentrates the bile by absorbing water and dissolved salts from it. All bile reaches the duodenum (first part of the small intestine) through the common bile duct and the ampulla of Vater. The sphincter of Oddi, located at the junction of the ampulla of Vater and the duodenum, is a circular muscle that controls the release of both bile and pancreatic secretions into the digestive tract.The biliary tree is normally relatively free of bacteria because of certain protective mechanisms. The sphincter of Oddi acts as a mechanical barrier. The biliary system normally has low pressure (8 to 12 cmH2O) and allows bile to flow freely through. The continuous forward flow of the bile in the duct flushes bacteria, if present, into the duodenum, and does not allow the establishment of an infection. The constitution of bile—bile salts and immunoglobulin secreted by the epithelium of the bile duct also has a protective role.
Bacterial contamination alone in absence of obstruction does not usually result in cholangitis. However increased pressure within the biliary system (above 20 cmH2O) resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the blood stream. It also adversely affects the function of Kupffer cells, which are specialized macrophage cells that assist in preventing bacteria from entering the biliary system. Finally, increased biliary pressure decreases production of IgA immunoglobulins in the bile. This results in bacteremia (bacteria in the blood stream) and gives rise to the systemic inflammatory response syndrome (SIRS) comprising fever (often with rigors), tachycardia, increased respiratory rate and increased white blood cell count; SIRS in the presence of suspected or confirmed infection is called sepsis. Biliary obstruction itself disadvantages the immune system and impairs its capability to fight infection, by impairing the function of certain immune system cells (neutrophil granulocytes) and modifying the levels of immune hormones (cytokines).In ascending cholangitis, it is assumed that organisms migrate backwards up the bile duct as a result of partial obstruction and decreased function of the sphincter of Oddi. Other theories about the origin of the bacteria, such as through the portal vein or transmigration from the colon, are considered less likely.

Diagnosis
Blood tests
Routine blood tests show features of acute inflammation (raised white blood cell count and elevated C-reactive protein level), and usually abnormal liver function tests (LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin, alkaline phosphatase and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis, with elevations in alanine transaminase and aspartate transaminase.Blood cultures are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases, usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli: Escherichia coli (25–50%), Klebsiella (15–20%) and Enterobacter (5–10%). Of the gram-positive cocci, Enterococcus causes 10–20%.

Medical imaging
Given that ascending cholangitis usually occurs in the setting of bile duct obstruction, various forms of medical imaging may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound, as this is the most easily available. Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones farther down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis (inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound. A better test is magnetic resonance cholangiopancreatography (MRCP), which uses magnetic resonance imaging (MRI); this has a comparable sensitivity to ERCP. Smaller stones, however, can still be missed on MRCP depending on the quality of the hospitals facilities.The gold standard test for biliary obstruction is still endoscopic retrograde cholangiopancreatography (ERCP). This involves the use of endoscopy (passing a tube through the mouth into the esophagus, stomach and thence to the duodenum) to pass a small cannula into the bile duct. At that point, radiocontrast is injected to opacify the duct, and X-rays are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms), gallstones are visible as non-opacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.If other causes rather than gallstones are suspected (such as a tumor), computed tomography and endoscopic ultrasound (EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy (tissue sample) of suspicious masses. EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability.

Treatment
Fluids and antibiotics
Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure.

Endoscopy
The definitive treatment for cholangitis is relief of the underlying biliary obstruction. This is usually deferred until 24–48 hours after admission, when the patient is stable and has shown some improvement with antibiotics, but may need to happen as an emergency in case of ongoing deterioration despite adequate treatment, or if antibiotics are not effective in reducing the signs of infection (which happens in 15% of cases).Endoscopic retrograde cholangiopancreatography (ERCP) is the most common approach in unblocking the bile duct. This involves endoscopy (passing a fiberoptic tube through the stomach into the duodenum), identification of the ampulla of Vater and insertion of a small tube into the bile duct. A sphincterotomy (making a cut in the sphincter of Oddi) is typically done to ease the flow of bile from the duct and to allow insertion of instruments to extract gallstones that are obstructing the common bile duct; alternatively or additionally, the common bile duct orifice can be dilated with a balloon. Stones may be removed either by direct suction or by using various instruments, including balloons and baskets to trawl the bile duct in order to pull stones into the duodenum. Obstructions that are caused by larger stones may require the use of an instrument known as a mechanical lithotriptor in order to crush the stone prior to removal. Obstructing stones that are too large to be removed or broken mechanically by ERCP may be managed by extracorporeal shock wave lithotripsy. This technique uses acoustic shock waves administered outside the body to break down the stones.  An alternative technique to remove very large obstructing stones is electrohydraulic lithotripsy, where a small endoscope known as a cholangioscope is inserted by ERCP to directly visualize the stone. A probe uses electricity to generate shock waves that break down the obstructing stone.  Rarely, surgical exploration of the common bile duct (termed choledochotomy), which can be performed with laparoscopy, is required to remove the stone.Narrowed areas may be bridged by a stent, a hollow tube that keeps the duct open. Removable plastic stents are used in uncomplicated gallstone disease, while permanent self-expanding metal stents with a longer lifespan are used if the obstruction is due to pressure from a tumor such as pancreatic cancer. A nasobiliary drain may be left behind; this is a plastic tube that passes from the bile duct through the stomach and the nose and allows continuous drainage of bile into a receptible. It is similar to a nasogastric tube, but passes into the common bile duct directly, and allows for serial x-ray cholangiograms to be done to identify the improvement of the obstruction. The decision on which of the aforementioned treatments to apply is generally based on the severity of the obstruction, findings on other imaging studies, and whether the patient has improved with antibiotic treatment. Certain treatments may be unsafe if blood clotting is impaired, as the risk of bleeding (especially from sphincterotomy) is increased in the use of medication such as clopidogrel (which inhibits platelet aggregation) or if the prothrombin time is significantly prolonged. For a prolonged prothrombin time, vitamin K or fresh frozen plasma may be administered to reduce bleeding risk.

Percutaneous biliary drainage
In cases where a person is too ill to tolerate endoscopy or when a retrograde endoscopic approach fails to access the obstruction, a percutaneous transhepatic cholangiogram (PTC) may be performed to evaluate the biliary system for placement of a percutaneous biliary drain (PBD). This is often necessary in the case of a proximal stricture or a bilioenteric anastomosis (a surgical connection between the bile duct and small bowel, such as the duodenum or jejunum).  Once access across the stricture is obtained, balloon dilation can be performed and stones can be swept forward into the duodenum. Due to potential complications of percutaneous biliary drain placement and the necessity of regular drain maintenance, a retrograde approach via ERCP remains first-line therapy.

Cholecystectomy
Not all gallstones implicated in ascending cholangitis actually originate from the gallbladder, but cholecystectomy (surgical removal of the gallbladder) is generally recommended in people who have been treated for cholangitis due to gallstone disease. This is typically delayed until all symptoms have resolved and ERCP or MRCP have confirmed that the bile duct is clear of gallstones. Those who do not undergo cholecystectomy have an increased risk of recurrent biliary pain, jaundice, further episodes of cholangitis, and need for further ERCP or cholecystostomy; the risk of death is also significantly increased.

Prognosis
Acute cholangitis carries a significant risk of death, the leading cause being irreversible shock with multiple organ failure (a possible complication of severe infections). Improvements in diagnosis and treatment have led to a reduction in mortality: before 1980, the mortality rate was greater than 50%, but after 1980 it was 10–30%. Patients with signs of multiple organ failure are likely to die unless they undergo early biliary drainage and treatment with systemic antibiotics. Other causes of death following severe cholangitis include heart failure and pneumonia.Risk factors indicating an increased risk of death include older age, female gender, a history of liver cirrhosis, biliary narrowing due to cancer, acute kidney injury and the presence of liver abscesses. Complications following severe cholangitis include kidney failure, respiratory failure (inability of the respiratory system to oxygenate blood and/or eliminate carbon dioxide), abnormal heart rhythms, wound infection, pneumonia, gastrointestinal bleeding and myocardial ischemia (lack of blood flow to the heart, leading to heart attacks).

Epidemiology
In the Western world, about 15% of all people have gallstones in their gallbladder but the majority are unaware of this and have no symptoms. Over ten years, 15–26% will have one or more episodes of biliary colic (abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 2–3% will develop complications of obstruction: acute pancreatitis, cholecystitis or acute cholangitis. Prevalence of gallstone disease increases with age and body mass index (a marker of obesity) </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 Cardiomegaly and can you explain it in depth? [/INST] Cardiomegaly (sometimes megacardia or megalocardia) is a medical condition in which the heart is enlarged. As such, it is more commonly referred to simply as "having an enlarged heart". It is usually the result of underlying conditions that make the heart work harder, such as obesity, heart valve disease, high blood pressure (hypertension), and coronary artery disease. Cardiomyopathy is also associated with cardiomegaly.Cardiomegaly can be serious depending on what part of the heart is enlarged, and can result in congestive heart failure. Recent studies suggest that cardiomegaly is associated with a higher risk of sudden cardiac death.Cardiomegaly may improve over time, but many people with an enlarged heart (dilated cardiomyopathy) need lifelong treatment with medication. Having an immediate family member who has or had cardiomegaly may indicate that a person is more susceptible to getting this condition.

Signs and symptoms
For many people, cardiomegaly is asymptomatic. For others, if the enlarged heart begins to affect the bodys ability to pump blood effectively, then symptoms associated with congestive heart failure may arise, including:
Heart palpitations – the irregular beating of the heart, usually associated with a valve issue inside the heart.
Severe shortness of breath (especially when physically active) – irregularly unable to catch ones breath.
Chest pain
Coughing, when lying down
Fatigue
Swelling in legs
Increased abdominal girth
Weight gain
Edema – swelling
FaintingThere is not much variation in these symptoms because they are mostly specific to the chest area. However, some are more common than others depending on each patient.

Causes
The causes of cardiomegaly are not well understood and many cases of cardiomegaly have no known cause. Prevention of cardiomegaly starts with detection. If a person has a family history of cardiomegaly, one should let ones doctor know so that treatments can be implemented to help prevent the worsening of the condition. In addition, prevention includes avoiding certain lifestyle risk factors such as tobacco use and controlling ones high cholesterol, high blood pressure, and diabetes. Non-lifestyle risk factors include a family history of cardiomegaly, coronary artery disease (CAD), congenital heart failure, atherosclerotic disease, valvular heart disease, exposure to cardiac toxins, sleep-disordered breathing (such as sleep apnea), sustained cardiac arrhythmias, abnormal electrocardiograms, and cardiomegaly on chest X-ray. Lifestyle factors that can help prevent cardiomegaly include eating a healthy diet, controlling blood pressure, exercise, medications, and not abusing alcohol and cocaine. Current research and the evidence of previous cases link the following (below) as possible causes of cardiomegaly.The most common known causes of cardiomegaly are congenital (patients are born with the condition based on a genetic inheritance), high blood pressure (which can enlarge the left ventricle causing the heart muscle to weaken over time), and coronary artery disease. In the latter case, the disease creates blockages in the hearts blood supply, leading to tissue death which causes other areas of the heart to work harder, causing the heart to expand in size.Other possible causes include:

Heart valve disease
Cardiomyopathy (disease of the heart muscle)
Pulmonary hypertension
Pericardial effusion (fluid around the heart)
Thyroid Disorders
Hemochromatosis (excessive iron in the blood)
Amyloidosis
Chagas disease, an important cause of cardiomegaly in Latin America
Viral infection of the heart
Pregnancy, with enlarged heart developing around the time of delivery (peripartum cardiomyopathy)
Kidney disease requiring dialysis
Alcohol or cocaine abuse
HIV infection
Diabetes

Mechanism
Cardiomegaly is a condition affecting the cardiovascular system, specifically the heart. This condition is strongly associated with congestive heart failure. Within the heart, the working fibers of the myocardial tissue increase in size. As the heart works harder the actin and myosin filaments experience less overlap which increases the size of the myocardial fibers. If there is less overlap of the protein filaments within the sarcomeres of the muscle fibers, they will not be able to effectively pull on one another. If the heart tissue gets too big and stretches too far, then those filaments cannot effectively pull on one another to shorten the muscle fibers, impacting the hearts sliding filament mechanism. If fibers cannot shorten properly and the heart cannot contract properly, then blood cannot be effectively pumped to the lungs to be re-oxygenated or to the body to deliver oxygen to the working tissues of the body.A person with an enlarged heart is more susceptible to forming blood clots in the lining of their heart. These clots can also be formed in other parts of the body. Once they enter the bloodstream, it makes it difficult for the organs in the body to receive blood, due to the blockage caused by the clots. This can impact other body systems as well and lead to other problems.

Diagnosis
There are many techniques and tests used to diagnose an enlarged heart. The results of these tests can often be used to see how efficiently the heart is pumping, determine which chambers of the heart are enlarged, look for evidence of previous heart attacks and determine if a person has congenital heart disease.

Chest X-Ray: X-ray images help see the condition of the lungs and heart. If the heart is enlarged on an X-ray, other tests will usually be needed to find the cause. A useful measurement on X-ray is the cardio-thoracic ratio, which is the transverse diameter of the heart, compared with that of the thoracic cage." These diameters are taken from PA chest x-rays using the widest point of the chest and measuring as far as the lung pleura, not the lateral skin margins. If the cardiac thoracic ratio is greater than 50%, pathology is suspected, assuming the x-ray has been taken correctly. The measurement was first proposed in 1919 to screen military recruits. A newer approach to using these x-rays for evaluating heart health takes the ratio of heart area to chest area and has been called the two-dimensional cardiothoracic ratio.
Electrocardiogram: This test records the electrical activity of the heart through electrodes attached to the persons skin. Impulses are recorded as waves and displayed on a monitor or printed on paper. This test helps diagnose heart rhythm problems and assess the damage to a persons heart from a heart attack.
Echocardiogram: This test for diagnosing and monitoring an enlarged heart uses sound waves to produce a video image of the heart. With this test, the four chambers of the heart can be evaluated.
Stress test: A stress test, also called an exercise stress test, provides information about how well the heart works during physical activity. It usually involves walking on a treadmill or riding a stationary bike while the heart rhythm, blood pressure, and breathing are monitored.
Cardiac computerized tomography (CT) or magnetic resonance imaging (MRI). In a cardiac CT scan, one lies on a table inside a machine called a gantry. An X-ray tube inside the machine rotates around the body and collects images of the heart and chest. In a cardiac MRI, one lies on a table inside a long tube-like machine that uses a magnetic field and radio waves to produce signals that create images of the heart.
Blood tests: Blood tests may be ordered to check the levels of substances in the blood that may show a heart problem. Blood tests can also help rule out other conditions that may cause ones symptoms.

Cardiac catheterization and biopsy: In this procedure, a thin tube (catheter) is inserted into the groin and threaded through the blood vessels to the heart, where a small sample (biopsy) of the heart, if indicated, can be extracted for laboratory analysis.
For deceased people, cardiomegaly at autopsy has been suggested when the heart weighs more than >399 grams in women and >449 grams in men.

Classification
Cardiomegaly can be classified by the main enlarged location of the heart, and/or by the structure of the enlargement.
There are also specific additional subtypes. For example, the athletic heart syndrome is a non-pathological condition commonly seen in sports medicine in which the human heart is enlarged, and the resting heart rate is lower than normal.

By enlarged location
Ventricular hypertrophy
Left
Right / Cor pulmonale
Atrial enlargement
Left
Right

Structure of enlargement
Dilated cardiomyopathy is the most common type of cardiomegaly. In this condition, the walls of the left and/or right ventricles of the heart become thin and stretched. The result is an enlarged heart.In the other types of cardiomegaly, the hearts large muscular left ventricle becomes abnormally thick. Hypertrophy is usually what causes left ventricular enlargement. Hypertrophic cardiomyopathy is typically an inherited condition.

Treatment
Treatments for cardiomegaly include a combination of medication treatment and medical/surgical procedures. Below are some of the treatment options for individuals with cardiomegaly:
Medications

Diuretics: to lower the amount of sodium and water in the body, which can help lower the pressure in the arteries and heart.
Angiotensin-converting enzyme (ACE) inhibitors: to lower the blood pressure and improve the hearts pumping ability.
Angiotensin receptor blockers (ARBs): to provide the benefits of ACE inhibitors for those who cant take ACE inhibitors.
Beta blockers: to lower blood pressure and improve heart function.
Digoxin: to help improve the pumping function of the heart and lessen the need for hospitalization for heart failure.
Anticoagulants: to reduce the risk of blood clots that could cause a heart attack or stroke.
Anti-arrhythmics: to keep the heart beating with a normal rhythm.Medical devices to regulate the heartbeat

Pacemaker: Coordinates the contractions between the left and right ventricle. In people who may be at risk of serious arrhythmias, drug therapy or an implantable cardioverter-defibrillator (ICD) may be used.
ICDs: Small devices implanted in the chest to constantly monitor the heart rhythm and deliver electrical shocks when needed to control abnormal, rapid heartbeats. The devices can also work as pacemakers.Surgical procedures

Heart valve surgery: If an enlarged heart is caused by a problem with one of the heart valves, one may have surgery to remove the valve and replace it with either an artificial valve or a tissue valve from a pig, cow or deceased human donor. If blood leaks backward through a valve (valve regurgitation), the leaky valve may be surgically repaired or replaced.
Coronary bypass surgery: If an enlarged heart is related to coronary artery disease, one may opt to have coronary artery bypass surgery.
Left ventricular assist device: (LVAD): This implantable mechanical pump helps a weak heart pump. LVADs are often implanted while a patient waits for a heart transplant or, if the patient is not a heart transplant candidate, as a long-term treatment for heart failure.
Heart transplant: If medications cant control the symptoms, a heart transplant is often a final option.Cardiomegaly can progress and certain complications are common:

Heart failure: One of the most serious types of enlarged heart, an enlarged left ventricle, increases the risk of heart failure. In heart failure, the heart muscle weakens, and the ventricles stretch (dilate) to the point that the heart cant pump blood efficiently throughout the body.
Blood clots: Having an enlarged heart may make one more susceptible to forming blood clots in the lining of the heart. If clots enter the bloodstream, they can block blood flow to vital organs, even causing a heart attack or stroke. Clots that develop on the right side of the heart may travel to the lungs, a dangerous condition called a pulmonary embolism.
Heart murmur: For people who have an enlarged heart, two of the hearts four valves — the mitral and tricuspid valves — may not close properly because they become dilated, leading to a backflow of blood. This flow creates sounds called heart murmurs.
The exact mortality rate for people with cardiomegaly is unknown. However, many people live for a very long time with an enlarged heart and, if detected early, treatment can help improve the condition and prolong their lives.
For some people cardiomegaly is a temporary condition, which can resolve on its own, making ones lifestyle normal like before. Others may have a permanent enlargement, which would then need to be taken care of by the above treatment options.Lifestyle changes

Smoking cessation
Limiting alcohol and caffeine intake
Maintaining a healthy weight
Increasing fruits and vegetables in a daily diet
Limiting consumption of high-fat and/or high-sugar foods
Getting adequate restful sleep

References
Further reading
Amin, Hina; Siddiqui, Waqas J. (2019). "Cardiomegaly". StatPearls. StatPearls Publishing. PMID 31194436.
Ampanozi, Garyfalia; Krinke, Eileen; Laberke, Patrick; Schweitzer, Wolf; Thali, Michael J.; Ebert, Lars C. (1 September 2018). "Comparing fist size to heart size is not a viable technique to assess cardiomegaly". Cardiovascular Pathology. 36: 1–5. doi:10.1016/j.carpath.2018.04.009. PMID 29859507. S2CID 44086023.
Agostoni, PierGiuseppe; Cattadori, Gaia; Guazzi, Marco; Palermo, Pietro; Bussotti, Maurizio; Marenzi, Giancarlo (1 November 2000) </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 Pyuria and can you explain it in depth? [/INST] Pyuria is the condition of urine containing white blood cells or pus. Defined as the presence of 6-10 or more neutrophils per high power field of unspun, voided mid-stream urine, it can be a sign of a bacterial urinary tract infection. Pyuria may be present in people with sepsis, or in older people with pneumonia. Others additionally require discoloration, clouding or change in the smell of urine for a pyuria to be present. Without these additional features, there is said to be leukocyturia.
Sterile pyuria is urine which contains white blood cells while appearing sterile by standard culturing techniques. It is often caused by sexually transmitted infections, such as gonorrhea, or viruses which will not grow in bacterial cultures. Sterile pyuria is listed as a side effect from some medications such as paracetamol (acetaminophen) </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 Hemolysis and can you explain it in depth? [/INST] Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo or in vitro.
One cause of hemolysis is the action of hemolysins, toxins that are produced by certain pathogenic bacteria or fungi. Another cause is intense physical exercise. Hemolysins damage the red blood cells cytoplasmic membrane, causing lysis and eventually cell death.

Etymology
From hemo- + -lysis, from Ancient Greek: [n] αἷμα (haîma, "blood") + λύσις (lúsis, "loosening").

Inside the body
Hemolysis inside the body can be caused by a large number of medical conditions, including some parasites (e.g., Plasmodium), some autoimmune disorders (e.g., autoimmune haemolytic anaemia, drug-induced hemolytic anemia, atypical hemolytic uremic syndrome (aHUS)), some genetic disorders (e.g., Sickle-cell disease or G6PD deficiency), or blood with too low a solute concentration (hypotonic to cells).Hemolysis can lead to hemoglobinemia due to hemoglobin released into the blood plasma, which plays a significant role in the pathogenesis of sepsis and can lead to increased risk of infection due to its inhibitory effects on the innate immune system.

Parasitic hemolysis
Because the feeding process of the Plasmodium parasites damages red blood cells, malaria is sometimes called "parasitic hemolysis" in medical literature.

HELLP, pre-eclampsia, or eclampsia
See HELLP syndrome, Pre-eclampsia, and Eclampsia

Hemolytic disease of the newborn
Hemolytic disease of the newborn is an autoimmune disease resulting from the mothers antibodies crossing the placenta to the fetus. This most often occurs when the mother has previously been exposed to blood antigens present on the fetus but foreign to her, through either a blood transfusion or a previous pregnancy.

Hemolytic anemia
Because in vivo hemolysis destroys red blood cells, in uncontrolled, chronic or severe cases it can lead to hemolytic anemia.

Hemolytic crisis
A hemolytic crisis, or hyperhemolytic crisis, is characterized by an accelerated rate of red blood cell destruction leading to anemia, jaundice, and reticulocytosis. Hemolytic crises are a major concern with sickle-cell disease and G6PD deficiency.

Toxic agent ingestion or poisoning
Paxillus involutus ingestion can cause hemolysis.

Space hemolysis
Spaceflight can cause hemolysis.

Intrinsic causes
Hemolysis may result from intrinsic defects in the red blood cell itself:
Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis)
Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia)
Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency)
Paroxysmal nocturnal hemoglobinuria (PNH), sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterized by complement-induced intravascular hemolytic anemia.

Extrinsic causes
Extrinsic hemolysis is caused by the red blood cells environment:
Immune-mediated causes could include transient factors as in Mycoplasma pneumoniae infection (cold agglutinin disease) or permanent factors as in autoimmune diseases like autoimmune hemolytic anemia (itself more common in diseases such as systemic lupus erythematosus, rheumatoid arthritis, Hodgkins lymphoma, and chronic lymphocytic leukemia).
Spur cell hemolytic anemia
Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension.
Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria).
Lead poisoning or poisoning by arsine or stibine causes non-immune hemolytic anemia.
Runners can develop hemolytic anemia due to "footstrike hemolysis", the destruction of red blood cells in feet at foot impact.
Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%.

Intravascular hemolysis
Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia and increasing the risk of ensuing hyperbilirubinemia.Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as Babesia. Additionally, thrombotic microangiopathy (TMA) can result in hemolysis of red blood cells. TMA is frequently observed in aHUS patients where clots form in the small vessels of the kidney resulting in damaged red blood cells as they attempt to pass through the restricted vessels.

Extravascular hemolysis
Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes. In this case little hemoglobin escapes into blood plasma. The macrophages of the reticuloendothelial system in these organs engulf and destroy structurally-defective red blood cells, or those with antibodies attached, and release unconjugated bilirubin into the blood plasma circulation. Typically, the spleen destroys mildly abnormal red blood cells or those coated with IgG-type antibodies, while severely abnormal red blood cells or those coated with IgM-type antibodies are destroyed in the circulation or in the liver.If extravascular hemolysis is extensive, hemosiderin can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in hemosiderosis.

Outside the body
In vitro hemolysis can be caused by improper technique during collection of blood specimens, by the effects of mechanical processing of blood, or by bacterial action in cultured blood specimens.

From specimen collection
Most causes of in vitro hemolysis are related to specimen collection. Difficult collections, unsecure line connections, contamination, and incorrect needle size, as well as improper tube mixing and incorrectly filled tubes are all frequent causes of hemolysis. Excessive suction can cause the red blood cells to be smashed on their way through the hypodermic needle owing to turbulence and physical forces. Such hemolysis is more likely to occur when a patients veins are difficult to find or when they collapse when blood is removed by a syringe or a modern vacuum tube. Experience and proper technique are key for any phlebotomist, nurse or doctor to prevent hemolysis.
In vitro hemolysis during specimen collection can cause inaccurate laboratory test results by contaminating the surrounding plasma with the contents of hemolyzed red blood cells. For example, the concentration of potassium inside red blood cells is much higher than in the plasma and so an elevated potassium level is usually found in biochemistry tests of hemolyzed blood.
After the blood collection process, in vitro hemolysis can still occur in a sample due to external factors, such as prolonged storage, incorrect storage conditions and excessive physical forces by dropping or vigorously mixing the tube.

From mechanical blood processing during surgery
In some surgical procedures (especially some heart operations) where substantial blood loss is expected, machinery is used for intraoperative blood salvage. A centrifuge process takes blood from the patient, washes the red blood cells with normal saline, and returns them to the patients blood circulation. Hemolysis may occur if the centrifuge rotates too quickly (generally greater than 500 rpm)—essentially this is hemolysis occurring outside of the body. Increased hemolysis occurs with massive amounts of sudden blood loss, because the process of returning a patients cells must be done at a correspondingly higher speed to prevent hypotension, pH imbalance, and a number of other hemodynamic and blood level factors.  Modeling of fluid flows to predict the likelihood of red cell membrane rupture in response to stress is an active area of research.

From bacteria culture
Visualizing the physical appearance of hemolysis in cultured blood samples may be used as a tool to determine the species of various Gram-positive bacteria infections (e.g., Streptococcus).

Nomenclature
Hemolysis is sometimes called hematolysis, erythrolysis, or erythrocytolysis. The words hemolysis () and hematolysis () both use combining forms conveying the idea of "lysis of blood" (hemo- or hemato- + -lysis) </s>