thesis on renal Stone formation mechanism?

Answer 1

Kidney stones result from the growth of crystals into stones. Crystals form in urine that is supersaturated with particular salts such as calcium oxalate, sodium urate, magnesium ammonium phosphate, or cystine. There is a maximum to the amount of a compound that can be kept in stable solution, which is defined by its solubility or equilibrium concentration product. Supersaturation results when the amount of a compound in solution exceeds the solubility; at that point, there is a drive to remove this excess by crystal formation. This drive can be manipulated in two ways: (1) by changing the amount or concentration of compound available for crystallization, or (2) by changing the solubility of the compound. An example of the former would be to reduce the quantity of calcium or cystine in the urine of a patient with hypercalciuric or cystinuric stone disease or by reducing the concentration of the calcium or cystine by high fluid intake. An example of the latter would be to increase the solubility by increasing the pH of the urine in patients with uric acid or cystine stone disease or by increasing the urinary excretion of naturally occurring inhibitors of crystal formation, eg, citrate.

Read more: http://www.clevelandclinicmeded.com/diseasemanagement/nephrology/nephrolithiasis/nephrolithiasis.htm

Answer 2

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Answer 3

Kidney stones, also known as nephrolithiases, urolithiases or renal calculi, are solid accretions (crystals) of dissolved minerals in urine found inside the kidneys or ureters. They vary in size from as small as a grain of sand to as large as a golf ball. Kidney stones typically leave the body in the urine stream; if they grow relatively large before passing (on the order of millimeters), obstruction of a ureter and distention with urine can cause severe pain most commonly felt in the flank, lower abdomen and groin. Kidney stones are unrelated to gallstones.
Etiology
Conventional wisdom has held that consumption of too much calcium can aggravate the development of kidney stones, since the most common type of stone is calcium oxalate. However, strong evidence has accumulated demonstrating that low-calcium diets are associated with higher stone risk and vice-versa for the typical stone former.

Other examples of kidney stones include struvite (magnesium, ammonium and phosphate), uric acid, calcium phosphate, or cystine (found only in people suffering from cystinuria). The formation of struvite stones is associated with the presence of urea-splitting bacteria, most commonly Proteus mirabilis( also Klebsiella, Serratia, Providencia species) which can split urea into ammonia, resulting in favorable conditions for the formation of struvite. A lack of the protein calgranulin is blamed by some for the appearance of calcium oxalate stones.


Symptoms
Kidney stones are usually asymptomatic until they obstruct the flow of urine. Symptoms can include acute flank pain (renal colic), nausea and vomiting, restlessness, dull pain, hematuria, and possibly fever if infection is present. Acute renal colic is described as one of the worst types of pain that a patient can suffer. Note that the pain is generally due to the stone's presence in the ureter, and not—as is commonly believed—the urethra and lower genitals.

Some patients have no symptoms until their urine turns bloody—this may be the first symptom of a kidney stone. The amount of blood may not be sufficient to be seen, and thus the first warning can be microscopic hematuria, when red blood cells are found in the microscopic study of a urine sample, during a routine medical test.


Diagnosis & Investigation
Diagnosis is usually made on the basis of the location and severity of the pain, which is typically colic in nature (comes and goes in spasmodic waves). Radiological imaging is used to confirm the diagnosis and a number of other tests can be undertaken to help establish both the possible cause and consequences of the stone. Ultrasound imaging is also useful as it will give details about the presence of hydronephrosis (swelling of the kidney - suggesting the stone is blocking the outflow of urine). It will also show the 10% of stones that do not have enough calcium to be seen on x-rays (radiolucent stones).

The relatively dense calcium renders these stones radio-opaque and they can be detected by a traditional X-ray of the abdomen that includes Kidneys, Ureters and Bladder—KUB. This may be followed by an IVP (Intravenous Pyelogram; IntraVenous Urogram (IVU) is the same test by another name) which requires about 50ml of a special dye to be injected into the bloodstream that is excreted by the kidneys and by its density helps outline any stone on a repeated X-ray. These can also be detected by a Retrograde pyelogram where similar "dye" is injected directly into the ureteral opening in the bladder by a surgeon. Computed tomography (CT or CAT scan), a specialized X-ray, is considered the gold-standard diagnostic test for the detection of kidney stones, and in this setting does not require the use of intravenous contrast, which carries some risk in certain people (eg, allergy, kidney damage). All stones are detectable by CT except very rare stones composed of certain drug residues in urine.

Investigations typically carried out include:

Microscopic study of urine, which may show proteins, red blood cells, pus cells, cellular casts and crystals.
Culture of a urine sample to exclude urine infection (either as a differential cause of the patient's pain, or secondary to the presence of a stone)
Blood tests: Full blood count for the presence of a raised white cell count (Neutrophilia) suggestive of infection, a check of renal function and if raised blood calcium blood levels (hypercalcaemia).
24 hour urine collection to measure total daily urinary calcium, oxalate and phosphate.

Treatment

A 2-mm kidney stone.Stones less than 5 mm in size usually will pass spontaneously, however the majority of stones greater than 6 mm will require some form of intervention, especially so if the stone is stuck causing persistent obstruction and/or infection of the urinary tract. Management of pain from kidney stones varies from country to country and even from physician to physician, but may require intravenous medication (eg, narcotic or nonsteroidal antiinflammatories) in acute situations or similar classes of drugs may be effectve orally in an outpatient setting for less severe discomfort. In many cases non-invasive Extracorporeal Shock Wave Lithotripsy may be used. Otherwise some form of invasive procedure is required; with approaches including ureteroscopic fragmentation (or simple basket extraction if feasible) using laser, ultrasonic or mechanical (pneumatic, shock-wave) forms of energy to fragment stones. percutaneous nephrolithotomy or open surgery may ultimately be necessary for large or complicated stones or stones which fail other less invasive attempts at treatment.

A single study at the Mayo Clinic has suggested that Lithotripsy may increase subsequent incidence of diabetes and hypertension,[1] but it has not been felt warranted to change clinical practice at the clinic.[2]


Secondary Prevention
Preventive strategies include dietary modifications and sometimes also taking drugs with the goal of reducing excretory load on the kidneys:[3]

Drinking enough water to make 2 to 2.5 litres of urine per day.
A diet low in protein, nitrogen and sodium intake.
Restriction of oxalate-rich foods and maintaining an adequate intake of dietary calcium is recommended. There is equivocal evidence that calcium supplements increase the risk of stone formation, though calcium citrate appears to carries the lowest, if any, risk
Taking drugs such as thiazides, potassium citrate, magnesium citrate and allopurinol depending on the cause of stone formation.
Depending on the stone formation disease, vitamin B-6 and orthophosphate supplements (such as IP-6) may be helpful, although these treatments are generally reserved for those with Primary Hyperoxaluria. Cellulose supplements have also shown potential for reducing kidney stones caused by certain conditions, although, again, not much research has been completed on this treatment.
Certain foods may increase the risk of stones: spinach, chocolate, peanuts, cocoa, tomato juice, grapefruit juice, apple juice, soda (acidic and contains phosphorus), all types of tea, and berries (high levels of oxalate). In the United States, the South has the highest incidence of kidney stones, a region where sweet tea consumption is very common. Other drinks are associated with decreased risk of stones, including wine, lemonade and orange juice, the latter two of which are rich in citrate, a stone inhibitor.

A note on alcohol: Although it has been claimed that the diuretic effects of alcohol can result in dehydration, which is important for kidney stones sufferers to avoid, there are no conclusive data demonstrating any cause and effect regarding kidney stones. However, some have theorized that frequent and binge drinkers create situations that set up dehydration, (alcohol consumption, hangovers, and poor sleep and stress habits). In this view, it is not the alcohol that creates a kidney stone but it is the alcohol drinker's associated behavior that sets it up. [citation needed]

One of the recognized medical therapies for prevention of stones is thiazides, a class of drugs usually thought of as diuretic. These drugs prevent stones through an effect independent of their diuretic properties: they reduce urinary calcium excretion. Nonetheless, their diuretic property does not preclude their efficacy as stone preventive. Though caffeine does acutely increase urinary calcium excretion, coffee has a high oxalate content which has been known to cause stones in some patients and should be used sparingly. Sodium restiction is necessary for clinical effect, as sodium excess promotes calcium excretion. In addition, the effect probably fades after two years or so of therapy (tachyphylaxis).

A high protein diet might be partially to blame. Protein from meat and other animal products is broken down into acids. The most available alkaline base to balance the acid from protein is calcium carbonates and phosphates from the bones (buffering). The kidney filters the liberated calcium which may then form insoluble crystals (ie, stones)in urine with available oxalate (partly from metabolic processes, partly from diet) or phosphate ions depending on conditions. One of the simplest fixes in addition to increased fluid intake is to moderate animal protein consumption. In this regard, it is not just dietary calcium per se that may cause stone formation, but rather the leaching of bone calcium. Some diseases (eg, distal renal tubular acidosis) which cause a chronically acidic state also decrease urinary citrate levels, which is a potent inhibitor of stone formation, and these patients are prone to frequent stone formation.


Famous sufferers
In 271 or 270 BCE, the Greek Philosopher Epicurus died from a kidney stone blockage lasting a fortnight according to his successor Hermarchus and reported by his biographer Diogenes Laertius.
French Renaissance essayist Montaigne suffered from kidney stones. British statesman Samuel Pepys also suffered from kidney stones and was operated on, pre-anesthesia, to remove a large stone which he carried with him and used to try to persuade fellow sufferers to endure the painful surgery. His contemporary, John Wilkins, Bishop of Chester, could not face the prospect and died as a result.
Author Isaac Asimov suffered from kidney stones, and wrote about how his pain was treated with morphine, saying that he feared becoming addicted to morphine if he ever needed it again.
Astronauts often get kidney stones because of an increase in the amount of calcium in their blood due to a loss of bone density in zero gravity.
In his book A Year At the Movies, Mystery Science Theatre 3000 writer/performer Kevin Murphy describes his ordeal with a kidney stone: "Being gut-stabbed with a dirty spoon in a prison cafeteria is less painful."
Speaker of the House of Representatives, Dennis Hastert, has had a number of kidney stones. Hastert had to have kidney stone removal surgery.
Lyndon B. Johnson suffered from kidney stones at various times in his life. See Woods, "LBJ: Architect of American Ambition."
On October 19, 2005, while working on the set of Boston Legal, Actor William Shatner was taken to the emergency room for lower back pain. He eventually passed a kidney stone, but recovered and soon returned to work. Shatner sold his kidney stone in 2006 for $75,000 to GoldenPalace.com. The money will go to a housing charity. [1]
Minnesota Twins catcher Joe Mauer has also suffered from Kidney Stones, when asked about it he stated "I don't wish that on anyone."
Reggaeton artist Tito El Bambino briefly suffered from kidney stones.
Karl Pilkington was diagnosed with Kidney Stones in late August 2006
Ryan Edward Palmer Esq. III, the notable songwriter in the infamous musical group M.C. Messiah, is suspected of suffering from kidney stones. The attendant pain and severe discomfort is thought to have provided the inspiration and creative impetus behind epic works such as "Track Track" and "Straw Sandals & Hellgoblins".

Fictitious sufferers
In the sixth season episode of Seinfeld, titled "The Gymnast," Kramer suffers from a kidney stone that he descibes as "a stony mineral concretion, formed abnormally in the kidney. And this jagged shard of calcium pushes its way through the ureter into the bladder. It's forced out through the urine!" At the end of the episode, he passes the stone while in the washroom at a circus.
In third episode of season five of Friends, entitled "The One Hundredth", Joey suffers from kidney stones while at the hospital for Phoebe giving birth to the triplets.
In the 15th episode of the second season of Deadwood, Al Swearengen is diagnosed with a bladder stone, which has him crippled on the floor in pain, suffering from septic shock. The stone has to be removed by crude surgery.
In the 10th episode of the 5th season of Full House, entitled "Happy Birthday, Babies, Part Two", Jesse Katsopolis is treated for a kidney stone while his wife, Becky, is in labor with their twin sons, Nicky and Alex. At the end of the episode, the couple marvels at what they each had given birth to that day.