Thursday, June 01, 2006

Pyelonephritis, Cystitis and all that PCOS bits and pieces

Information extracted from http://www.answers.com


Pyelonephritis: An ascending urinary tract infection that has reached the pyelum (pelvis) of the kidney (nephros in Greek). If the infection is severe, the term "urosepsis" is used interchangeably. It requires antibiotics as therapy. It is a form of nephritis.

Pathology

Acute pyelonephritis is an exudative purulent localized inflammation of kidney and renal pelvis. The renal parenchyma presents in the interstitium abscesses (suppurative necrosis), consisting in purulent exudate (pus): neutrophils, fibrin, cell debris and central germ colonies (hematoxylinophils). Tubules are damaged by exudate and may contain neutrophil casts. In the early stages, glomeruli and vessels are normal. Photo at: Atlas of Pathology

Chronic pyelonephritis is often caused by Xanthogranulomatous pyelonephritis.


Signs and symptoms

It presents with high spiking fever, backache, vomiting dysuria (painful voiding), rigors and often also with confusion. There may be renal angle tenderness on physical examination.


Diagnosis

Nitrite and leukocytes on a urine dipstick are often detected, which may be an indication for empirical treatment. Formal diagnosis is with culture of the urine and bloods.

In patients with recurrent ascending urinary tract infections, it may be necessary to exclude an anatomical abnormality, such as vesicoureteric reflux (urine from the bladder flowing back into the ureter).


Treatment

Treatment is with antibiotics, which are often administered intravenously to improve the effect. Trimethoprim (or co-trimoxazole) or nitrofurantoin are often used first-line, although in full-blown pyelonephritis amoxicillin (with or without clavulanic acid), gentamycin (with or without ampicillin), fluoroquinolones (eg. ciprofloxacin) or a third generation cephalosporins are often favoured.


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Cystitis: Inflammation of the urinary bladder and ureters.

The disease occurs primarily in young women and frequently results from bacterial invasion of the urethra from the adjacent rectum, most commonly with normally occurring intestinal bacteria such as E. coli. It is also common in menopausal women; in them, the bacteria is transmitted from a vagina left more susceptible to bacterial overgrowth by changes in estrogen levels. In men cystitis rarely occurs without some other urinary tract disorder, such as kidney stones or, especially in older men, an enlarged prostate gland. Other predisposing factors are pregnancy, diabetes, and various systemic disorders.

Usual symptoms are frequent urination with burning pain, blood in the urine, and pain in the pubic area; chills and fever, back pain, and nausea may indicate kidney involvement. Treatment is with antibiotics and can also include the relief of any obstructions

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Polycystic ovary syndrome,PCOS:

Polycystic ovarian disease (PCO), also known by the name Stein-Leventhal syndrome, is a hormonal problem that causes women to have a variety of symptoms including:

-Irregular or no periods
-Acne
-Obesity, and
-Excess hair growth.


Any of the above symptoms and signs may be absent with the exception of irregular or no periods. All women with PCO will have irregular or no menses. Women who have PCO do not regularly ovulate; that is, they do not release an egg every month. This is why they do not have regular periods. No one is quite sure what causes PCO. However, the ovaries of women with PCO frequently contain a number of small cysts, hence the name poly (many) cystic ovarian disease. A similar number of cysts may occur in women without PCO. Therefore, the cysts themselves do not seem to be the cause of the problem. A malfunction of the body's blood sugar control system (insulin system) is frequent in women with PCO. The result is an inadequate response to insulin (insulin resistance) that can lead to abnormally elevated blood sugar (glucose) levels. The insuliin disturbance is thought to also be the trigger for the development of symptoms such as acne and excess hair growth that is seen with PCO.

How is PCO diagnosed?

The diagnosis of PCO is generally made on the basis of clinical signs and symptoms as discussed above. The doctor will want to exclude other illnesses that have similar features, such as low thyroid hormone blood levels (hypothyroidism) or elevated levels of a milk-producing hormone (prolactin). Also, tumors of the ovary or adrenal glands can produce elevated male hormone (androgen) blood levels that cause acne or excess hair growth, mimicking symptoms of PCO.

Other laboratory tests can be helpful in making the diagnosis of PCO. Serum levels of male hormones (DHEA and testosterone) may be elevated. However, levels of testosterone that are highly elevated are not unusual with PCO and call for additional evaluation. Additionally, levels of a hormone released by the brain (LH) is elevated.

Cysts are fluid-filled sacs. The cysts in the ovaries can be identified with imaging technology. (However, as noted above, women without PCO can have many cysts as well.) Ultrasound, which passes sound waves through the body to create a picture of the kidneys, is used most often. Ultrasound imaging employs no injected dyes or radiation and is safe for all patients including pregnant women. It can also detect cysts in the kidneys of a fetus. Because women without PCO can have ovarian cysts, and because ovarian cysts are not part of the definition of PCO, ultrasound is not routinely ordered to diagnose PCO. The diagnosis is a clinical on based on the patient's history, physical examination, and laboratory testing.


Risks

Women with PCOS are at risk for the following:

1. Endometrial hyperplasia and endometrial cancer (cancer of the uterine lining) are possible, due to overaccumulation of uterine lining, and also lack of progesterone resulting in prolonged stimulation of uterine cells by estrogen

2. Insulin resistance/Type II diabetes, generally thought to be caused by hyperinsulinemia

3. High blood pressure

4. Dyslipidemia (disorders of lipid metabolism - cholesterol and triglycerides)

5.Cardiovascular disease


Some data suggest that women with PCOS have a higher risk of miscarriage. Also, many women with PCOS have a difficult time conceiving because of their irregular cycles and lack of ovulation. However, it is possible for these women to have normal pregnancies with the aid of medication and diet.


Diagnosis

It is vital to note that not all women with PCOS have polycystic ovaries, nor do all women with ovarian cysts have PCOS; although a pelvic ultrasound is a major diagnostic tool, it is not the only one. Diagnosis can be difficult, particularly because of the wide range of symptoms and the variability in presentation (which is why this disorder is characterized as a syndrome rather than a disease). There is a lot of controversy about the appropriate testing:

-gynecologic ultrasonography

- testosterone: free more sensitive than total

- Fasting biochemical screen and lipid profile

- 2-hour oral glucose tolerance test (GTT) in patients with risk
factors (obesity, family history, history of gestational diabetes) and may indicate impaired glucose tolerance in 15-30% of obese women with PCOS. Frank diabetes can be seen in 6-8% of women with this condition.


For exclusion purpose:


-Prolactin
-TSH
-17-hydroxyprogesterone




The role of other tests is more controversial, including:



-fasting insulin level or GTT with insulin levels (also called IGTT): Elevated insulin levels have been helpful to predict response to medication and may indicate women who will need higher dosages of metformin or the use of a second medication to significantly lower insulin levels. Elevated blood sugar and insulin values do not predict who responds to an insulin-lowering medication, low-glycemic diet, and exercise. Many women with normal levels may benefit from combination therapy. A hypoglycemic response in which the two-hour insulin level is higher and the blood sugar lower than fasting is consistent with insulin resistance.

-LH:FSH ratio

-DHEAS

-SHBG

-Androstenedione


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Differential diagnosis

Other causes of irregular or absent menstruation and hirsutism, such as congenital adrenal hyperplasia, Cushing's syndrome, hyperprolactinemia, and other pituitary or adrenal disorders, should be investigated.


Pathogenesis

PCOS develops when the ovaries are stimulated to produce excessive amounts of male hormones (androgens), particularly testosterone, either through the release of excessive luteinizing hormone (LH) by the pituitary gland or through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus.

This syndrome acquired its most widely used name because a common symptom is multiple (poly) ovarian cysts. These form where egg follicles matured but were never released from the ovary because of abnormal hormone levels. These generally take on a 'string of pearls' appearance. The condition was first described in 1935 by Dr. Stein and Dr. Leventhal, hence its original name of Stein-Leventhal syndrome.

Although the cause of PCOS is not known, research to date suggests that obesity is a prime indicator. It may have a genetic predisposition, and further research into this possibility is taking place. No specific gene has been identified, and it is thought that many genes could contribute to the development of PCOS.

A majority of patients with PCOS - some investigators say all - have insulin resistance. Their elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to PCOS. Specifically, hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased ovarian androgen production, decreased follicular maturation, and decreased SHBG binding; all these steps lead to the development of PCOS. Insulin resistance is a common finding in obese people.


Treatment

Medical treatment of PCOS used to be directed mainly at the symptoms (ovarian and adrenal suppression and anti-androgen therapy) and at restoring ovulation. Some medications used for these purposes are

1. Oral contraceptives (ovarian suppression): Because these cause regular menstruation, they reduce the risk of endometrial carcinoma

2. Spironolactone or finasteride (anti-androgen therapy): These reduce the excessive hair growth by blocking the effects of male hormones

3. Clomiphene citrate, human chorionic gonadotropin, or dexamethasone: Induce ovulation


Recent research suggests that the insulin resistance and overrelease of insulin may be at the root of PCOS. Many women find insulin-lowering medications such as metformin hydrochloride (Glucophage®), pioglitazone hydrochloride (Actos®), and rosiglitazone maleate (Avandia®) helpful, and ovulation may resume when they use these agents. Many women report that metformin use is associated with upset stomach, diarrhea, and weight-loss. Both symptoms and weight loss appear to be less with the extended release versions. Most published studies use either generic metformin or the regular, non-extended release version. Starting with a lower dosage and gradually increasing the dosage over 2-3 weeks and taking the medication toward the end of a meal may reduce side effects. The use of basal body temperature or BBT charts is an effective way to follow progress. It may take up to six months to see results, but when combined with exercise and a low-glycemic diet up to 85% will improve menstrual cycle regularity and ovulation.

Low-carbohydrate diets and sustained regular exercise are also beneficial. Also, initial research suggests that the risk of miscarriage is significantly reduced when Metformin is taken throughout pregnancy (9% as opposed to as much as 45%); however, further research is needed in this area.

For patients who do not respond to these and related medications or procedures, the polycystic ovaries can be treated with surgical procedures such as

1. laparoscopy electrocauterization or laser cauterization

2. ovarian wedge resection (rarely done now because it is more invasive and has a 30% risk of adhesions, sometimes very severe, which can impair fertility)

3. ovarian drilling

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