What are the causes of a small kidney?

The commonest causes of a small kidney are:1. The kidney is small at birth, or never grows with the rest of the body. This is a common cause of a small kidney detected in childhood. The medical name for this is congenital dysplasia. In some people both kidneys can be affected by congenital dysplasia, and there may be kidney failure. The small kidney may be in a normal position in the upper back, or may have failed to move up from the lower abdomen before birth. A kidney in the lower abdomen is called a pelvic kidney. Many pelvic kidneys have normal function, but in some people a pelvic kidney can be small or have abnormalities in the drainage system, giving a risk of recurrent infection. 2. The kidney is damaged because of a faulty drainage system, usually a condition called reflux nephropathy. This is a common cause of a small kidney detected in childhood or in a young adult. Reflux nephropathy can affect both kidneys. More information on reflux nephropathy is available from the NKF.
3. An infection in a kidney can cause it to shrink. Normally kidney infections do not cause

permanent damage to a kidney, or leave a small scarred area in the kidney. Occasionally, though, a severe kidney infection (acute pyelonephritis) can damage the kidney so much that it becomes small. An infection bad enough to cause this may occur in someone with reflux nephropathy (see the paragraph above).
4. The kidney is starved of blood by a narrowing in the artery supplying the kidney with

blood. This condition is a common cause of a small kidney in older people, especially if there is also a history of angina or heart attack, or narrowed arteries to the legs. Click here for more information on renal artery stenosis.
5. Many other diseases which damage the kidney, such as glomerulonephritis (click here for

more details), can cause a kidney to shrink and become small, but glomerulonephritis usually affects both kidneys equally, and this section of medical information is really concerned with conditions where one kidney is smaller than the other.

Kidney
From Wikipedia, the free encyclopedia For other uses, see Kidney (disambiguation).

Kidney

Human kidneys viewed from behind with spine removed

Lamb kidneys Latin Artery Vein Nerve ren renal artery renal vein renal plexus

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid-base balance, and regulation of blood pressure (via maintaining salt and water balance). They serve the body as a natural filter of the blood, and remove wastes which are diverted to the urinary bladder. In producing urine, the kidneys excrete wastes such as urea and ammonium; the kidneys also are responsible for the reabsorption of water, glucose, and amino acids. The kidneys also produce hormones including calcitriol, erythropoietin, and the enzyme renin.

Located at the rear of the abdominal cavity in the retroperitoneum, the kidneys receive blood from the paired renal arteries, and drain into the paired renal veins. Each kidney excretes urine into a ureter, itself a paired structure that empties into the urinary bladder. Renal physiology is the study of kidney function, while nephrology is the medical specialty concerned with kidney diseases. Diseases of the kidney are diverse, but individuals with kidney disease frequently display characteristic clinical features. Common clinical conditions involving the kidney include the nephritic and nephrotic syndromes, renal cysts, acute kidney injury, chronic kidney disease, urinary tract infection, nephrolithiasis, and urinary tract obstruction.[1] Various cancers of the kidney exist; the most common adult renal cancer is renal cell carcinoma. Cancers, cysts, and some other renal conditions can be managed with removal of the kidney, or nephrectomy. When renal function, measured by glomerular filtration rate, is persistently poor, dialysis and kidney transplantation may be treatment options. Although they are not severely harmful, kidney stones can be a pain and a nuisance. The removal of kidney stones includes sound wave treatment, which breaks up the stones into smaller pieces which are then passed through the urinary tract. One common symptom of kidney stones is a sharp pain in the medial/lateral segments of the lower back.

Contents
[hide] 1 Anatomy 1.1 Location 1.2 Structure 1.3 Blood supply 1.4 Histology 1.5 Innervation 2.1 Excretion of wastes 2.2 Acid-base homeostasis 2.3 Osmolality regulation 2.4 Blood pressure regulation 2.5 Hormone secretion

2 Functions

3 Development 4 Evolutionary adaptation 5 Etymology 6 Diseases and disorders 6.1 Congenital 6.2 Acquired

7 In other animals 8 History

9 Animal kidneys as food 10 See also 11 References 12 External links

[edit] Anatomy
[edit] Location

Surface projections of the organs of the trunk, showing kidneys at the level of T12 to L3.

In humans the kidneys are located in the abdominal cavity, more specifically in the paravertebral gutter and lie in a retroperitoneal position at a slightly oblique angle. There are two, one on each side of the spine. The asymmetry within the abdominal cavity caused by the liver typically results in the right kidney being slightly lower than the left, and left kidney being located slightly more medial than the right.[2][3] The left kidney is approximately at the vertebral level T12 to L3, [4] and the right slightly lower. The right kidney sits just below the diaphragm and posterior to the liver, the left below the diaphragm and posterior to the spleen. Resting on top of each kidney is an adrenal gland. The upper (cranial) parts of the kidneys are partially protected by the eleventh and twelfth ribs, and each whole kidney and adrenal gland are surrounded by two layers of fat (the perirenal and pararenal fat) and the renal fascia. Each adult kidney weighs between 125 and 170 grams in males and between 115 and 155 grams in females.[5] The left kidney is typically slightly larger than the right.[6]

[edit] Structure

1. Renal pyramid 2. Interlobular artery 3. Renal artery 4. Renal vein 5. Renal hilum 6. Renal pelvis 7. Ureter 8. Minor calyx 9. Renal capsule 10. Inferior renal capsule 11. Superior renal capsule 12. Interlobular vein 13. Nephron 14. Minor calyx 15. Major calyx 16. Renal papilla 17. Renal column

The kidney has a bean-shaped structure, each kidney has a convex and concave surface. The concave surface, the renal hilum, is the point at which the renal artery enters the organ, and the renal vein and ureter leave. The kidney is surrounded by tough fibrous tissue, the renal capsule, which is itself surrounded by perinephric fat, renal fascia (of Gerota) and paranephric fat. The anterior (front) border of these tissues is the peritoneum, while the posterior (rear) border is the transversalis fascia. The superior border of the right kidney is adjacent to the liver; and the spleen, for the left border. Therefore, both move down on inhalation. The kidney is approximately 1114 cm in length, 6 cm wide and 4 cm thick. The substance, or parenchyma, of the kidney is divided into two major structures: superficial is the renal cortex and deep is the renal medulla. Grossly, these structures take the shape of 8 to 18 cone-shaped renal lobes, each containing renal cortex surrounding a portion of medulla called a renal pyramid (of Malpighi).[5] Between the renal pyramids are projections of cortex called renal columns (of Bertin). Nephrons, the urine-producing functional structures of the kidney, span the cortex and medulla. The initial filtering portion of a nephron is the renal corpuscle, located in the cortex, which is followed by a renal tubule that passes from the cortex deep into the medullary pyramids. Part of the renal cortex, a medullary ray is a collection of renal tubules that drain into a single collecting duct. The tip, or papilla, of each pyramid empties urine into a minor calyx, minor calyces empty into major calyces, and major calyces empty into the renal pelvis, which becomes the ureter.

[edit] Blood supply

3D-rendered computed tomography, showing renal arteries and veins.

The kidneys receive blood from the renal arteries, left and right, which branch directly from the abdominal aorta. Despite their relatively small size, the kidneys receive approximately 20% of the cardiac output.[5] Each renal artery branches into segmental arteries, dividing further into interlobar arteries which penetrate the renal capsule and extend through the renal columns between the renal pyramids. The interlobar arteries then supply blood to the arcuate arteries that run through the boundary of the cortex and the medulla. Each arcuate artery supplies several interlobular arteries that feed into the afferent arterioles that supply the glomeruli. The interstitum (or interstitium) is the functional space in the kidney beneath the individual filters (glomeruli) which are rich in blood vessels. The interstitum absorbs fluid recovered from urine. Various conditions can lead to scarring and congestion of this area, which can cause kidney dysfunction and failure. After filtration occurs the blood moves through a small network of venules that converge into interlobular veins. As with the arteriole distribution the veins follow the same pattern, the interlobular provide blood to the arcuate veins then back to the interlobar veins which come to form the renal vein exiting the kidney for transfusion for blood.
[edit] Histology

Microscopic photograph of the renal medulla.

Microscopic photograph of the renal cortex.

Renal histology studies the structure of the kidney as viewed under a microscope. Various distinct cell types occur in the kidney, including:
Kidney glomerulus parietal cell Kidney glomerulus podocyte Kidney proximal tubule brush border cell Loop of Henle thin segment cell Thick ascending limb cell Kidney distal tubule cell Kidney collecting duct cell Interstitial kidney cells

[edit] Innervation

The kidney and nervous system communicate via the renal plexus, whose fibers course along the renal arteries to reach the kidney.[7] Input from the sympathetic nervous system triggers vasoconstriction in the kidney, thereby reducing renal blood flow.[7] The kidney is not thought to receive input from the parasympathetic nervous system.[7] Sensory input from the kidney travels to the T10-11 levels of the spinal cord and is sensed in the corresponding dermatome.[7] Thus, pain in the flank region may be referred from the kidney.[7]

[edit] Functions
Main article: Renal physiology

The kidney participates in whole-body homeostasis, regulating acid-base balance, electrolyte concentrations, extracellular fluid volume, and regulation of blood pressure. The kidney accomplishes these homeostatic functions both independently and in concert with other organs, particularly those of the endocrine system. Various endocrine hormones coordinate these endocrine functions; these include renin, angiotensin II, aldosterone, antidiuretic hormone, and atrial natriuretic peptide, among others. Many of the kidney's functions are accomplished by relatively simple mechanisms of filtration, reabsorption, and secretion, which take place in the nephron. Filtration, which takes place at the

renal corpuscle, is the process by which cells and large proteins are filtered from the blood to make an ultrafiltrate that will eventually become urine. The kidney generates 180 liters of filtrate a day, while reabsorbing a large percentage, allowing for the generation of only approximately 2 liters of urine. Reabsorption is the transport of molecules from this ultrafiltrate and into the blood. Secretion is the reverse process, in which molecules are transported in the opposite direction, from the blood into the urine.
[edit] Excretion of wastes

The kidneys excrete a variety of waste products produced by metabolism. These include the nitrogenous wastes called "urea", from protein catabolism, as well as uric acid, from nucleic acid metabolism.
[edit] Acid-base homeostasis Main article: Acid-base homeostasis

Two organ systems, the kidneys and lungs, maintain acid-base homeostasis, which is the maintenance of pH around a relatively stable value. The lungs contribute to acid-base homeostasis by regulating bicarbonate (HCO3-) concentration. The kidneys have two important roles in the maintaining of the acid-base balance: to reabsorb bicarbonate from and to excrete hydrogen ions into urine
[edit] Osmolality regulation

Any significant rise in plasma osmolality is detected by the hypothalamus, which communicates directly with the posterior pituitary gland. An increase in osmolality causes the gland to secrete antidiuretic hormone (ADH), resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels. ADH binds to principal cells in the collecting duct that translocate aquaporins to the membrane allowing water to leave the normally impermeable membrane and be reabsorbed into the body by the vasa recta, thus increasing the plasma volume of the body. There are two systems that create a hyperosmotic medulla and thus increase the body plasma volume: Urea recycling and the 'single effect.' Urea is usually excreted as a waste product from the kidneys. However, when plasma blood volume is low and ADH is released the aquaporins that are opened are also permeable to urea. This allows urea to leave the collecting duct into the medulla creating a hyperosmotic solution that 'attracts' water. Urea can then re-enter the nephron and be excreted or recycled again depending on whether ADH is still present or not. The 'Single effect' describes the fact that the ascending thick limb of the loop of Henle is not permeable to water but is permeable to NaCl. This allows for a countercurrent exchange system whereby the medulla becomes increasingly concentrated, but at the same time setting up an osmotic gradient for water to follow should the aquaporins of the collecting duct be opened by ADH.
[edit] Blood pressure regulation Main articles: Blood pressure regulation and Renin-angiotensin system

Long-term regulation of blood pressure predominantly depends upon the kidney. This primarily occurs through maintenance of the extracellular fluid compartment, the size of which depends on the plasma sodium concentration. Although the kidney cannot directly sense blood pressure, changes in the delivery of sodium and chloride to the distal part of the nephron alter the kidney's secretion of the enzyme renin. When the extracellular fluid compartment is expanded and blood pressure is high, the delivery of these ions is increased and renin secretion is decreased. Similarly, when the extracellular fluid compartment is contracted and blood pressure is low, sodium and chloride delivery is decreased and renin secretion is increased in response. Renin is the first in a series of important chemical messengers that comprise the reninangiotensin system. Changes in renin ultimately alter the output of this system, principally the hormones angiotensin II and aldosterone. Each hormone acts via multiple mechanisms, but both increase the kidney's absorption of sodium chloride, thereby expanding the extracellular fluid compartment and raising blood pressure. When renin levels are elevated, the concentrations of angiotensin II and aldosterone increase, leading to increased sodium chloride reabsorption, expansion of the extracellular fluid compartment, and an increase in blood pressure. Conversely, when renin levels are low, angiotensin II and aldosterone levels decrease, contracting the extracellular fluid compartment, and decreasing blood pressure.
[edit] Hormone secretion

The kidneys secrete a variety of hormones, including erythropoietin, and the enzyme renin. Erythropoietin is released in response to hypoxia (low levels of oxygen at tissue level) in the renal circulation. It stimulates erythropoiesis (production of red blood cells) in the bone marrow. Calcitriol, the activated form of vitamin D, promotes intestinal absorption of calcium and the renal reabsorption of phosphate. Part of the renin-angiotensin-aldosterone system, renin is an enzyme involved in the regulation of aldosterone levels.

[edit] Development
Main article: Kidney development

The mammalian kidney develops from intermediate mesoderm. Kidney development, also called nephrogenesis, proceeds through a series of three successive phases, each marked by the development of a more advanced pair of kidneys: the pronephros, mesonephros, and metanephros.[8]

[edit] Evolutionary adaptation

Kidneys of various animals show evidence of evolutionary adaptation and have long been studied in ecophysiology and comparative physiology. Kidney morphology, often indexed as the relative medullary thickness, is associated with habitat aridity among species of mammals.[9]

[edit] Etymology
Medical terms related to the kidneys commonly use terms such as renal and the prefix nephro-. The adjective renal, meaning related to the kidney, is from the Latin rns, meaning kidneys; the prefix nephro- is from the Ancient Greek word for kidney, nephros ().[10] For example, surgical removal of the kidney is a nephrectomy, while a reduction in kidney function is called renal dysfunction.

[edit] Diseases and disorders

Main article: Nephropathy [edit] Congenital Congenital hydronephrosis Congenital obstruction of urinary tract Duplex kidneys, or double kidneys, occur in approximately 1% of the population. This occurrence normally causes no complications but can occasionally cause urine infections.[11][12] Duplicated ureter occurs in approximately one in 100 live births Horseshoe kidney occurs in approximately one in 400 live births Polycystic kidney disease Autosomal dominant polycystic kidney disease afflicts patients later in life. Approximately one in 1000 people will develop this condition Autosomal recessive polycystic kidney disease is far less common, but more severe, than the dominant condition. It is apparent in utero or at birth.

Renal agenesis. Failure of one kidney to form occurs in approximately one in 750 live births. Failure of both kidneys to form is invariably fatal. Renal dysplasia Unilateral small kidney Multicystic dysplastic kidney occurs in approximately one in every 2400 live births Ureteropelvic Junction Obstruction or UPJO; although most cases appear congenital, some appear to be an acquired condition[13]

[edit] Acquired

Drawing of an enlarged kidney by John Hunter. Diabetic nephropathy Glomerulonephritis Hydronephrosis is the enlargement of one or both of the kidneys caused by obstruction of the flow of urine. Interstitial nephritis Kidney stones (nephrolithiasis) are a relatively common and particularly painful disorder. Kidney tumors Wilms tumor Renal cell carcinoma

Lupus nephritis Minimal change disease In nephrotic syndrome, the glomerulus has been damaged so that a large amount of protein in the blood enters the urine. Other frequent features of the nephrotic syndrome include swelling, low serum albumin, and high cholesterol. Pyelonephritis is infection of the kidneys and is frequently caused by complication of a urinary tract infection. Renal failure

Acute renal failure Stage 5 Chronic Kidney Disease

Kidney Failure
Main article: Renal failure

Generally, humans can live normally with just one kidney, as one has more functioning renal tissue than is needed to survive. Only when the amount of functioning kidney tissue is greatly diminished does one develop chronic kidney disease. Renal replacement therapy, in the form of dialysis or kidney transplantation, is indicated when the glomerular filtration rate has fallen very low or if the renal dysfunction leads to severe symptoms.

Inside Your Kidneys

If you were to cut a kidney in half, you would see the following parts:
Renal capsule - a thin, outer membrane that helps protect the kidney Cortex - a lightly colored outer region Medulla - a darker, reddish-brown, inner region Renal pelvis - a flat, funnel-shaped cavity that collects the urine into the ureters

Diagram showing the parts of the kidney and the nephron

If you look closely at the cortex and medulla, you can see many tiny, tubular structures that stretch across both regions perpendicular to the surface of the kidney. In each kidney, there are one million of these structures, called nephrons. The nephron is the basic unit of the kidney. It's a long, thin tube that is closed at one end, has two twisted regions interspaced with a long hairpin loop, ends in a long straight portion and is surrounded by capillaries. The parts of the nephron are as follows:
Bowman's capsule - This closed end at the beginning of the nephron is located in the cortex. Proximal convoluted tubule or proximal tubule - The first twisted region after the Bowman's capsule; it's in the cortex. Loop of Henle - A long, hairpin loop after the proximal tubule, it extends from the cortex down into the medulla and back. Distal convoluted tubule or distal tubule - This second twisted portion of the nephron after the loop of Henle is located in the cortex. Collecting duct - This long straight portion after the distal tubule that is the open end of the nephron extends from the cortex down through the medulla.

Each part of the nephron has different types of cells with different properties -- this is important in understanding how the kidney regulates the composition of the blood. The nephron has a unique blood supply compared to other organs:
Afferent arteriole - connects the renal artery with the glomerular capillaries Glomerular capillaries - coiled capillaries that are inside the Bowman's capsule Efferent arteriole - connects the glomerular capillaries with the peritubular capillaries Peritubular capillaries - located after the glomerular capillaries and surrounding the proximal tubule, loop of Henle, and distal tubule Interlobular veins - drain the peritubular capillaries into the renal vein

The kidney is the only organ of the body in which two capillary beds, in series, connect arteries with veins. This arrangement is important for maintaining a constant blood flow through and around the nephron despite fluctuations in systemic blood pressure. Regulating the composition of the blood involves the following:

Keeping the concentrations of various ions and other important substances constant Keeping the volume of water in your body constant Removing wastes from your body Keeping the acid/base concentration of your blood constant It filters 20 percent of the plasma and non-cell elements from the blood into the inside of the nephron (the lumen). It reabsorbs the components that the body needs from the lumen back into the blood. It secretes some unwanted components from the blood into the lumen of the nephron.

The kidney does this by a combination of three processes:

Anything (fluid, ions, small molecules) that has not been reabsorbed from the lumen gets swept away to form the urine, which ultimately leaves the body. Through these processes, the blood is maintained with the proper composition, and excess or unwanted substances are removed from the blood into the urine. Next, we'll look at how the kidneys regulate blood composition by three main processes:
Filtration Reabsorption Secretion

This filtration process is much like the making of espresso or cappuccino. In a cappuccino machine, water is forced under pressure through a fine sieve containing ground coffee; the filtrate is the brewed coffee. The arrangement of the glomerular capillaries in series with the peritubular capillaries is important to maintain a constant pressure in the glomerular capillaries, and thus a constant rate of filtration, despite momentary fluctuations in blood pressure. Once the filtrate has entered the Bowman's capsule, it flows through the lumen of the nephron into the proximal tubule

Kidney Reabsorption
Once inside the lumen of the nephron, small molecules, such as ions, glucose and amino acids, get reabsorbed from the filtrate:
Specialized proteins called transporters are located on the membranes of the various cells of the nephron. These transporters grab the small molecules from the filtrate as it flows by them. Each transporter grabs only one or two types of molecules. For example, glucose is reabsorbed by a transporter that also grabs sodium.

Transporters are concentrated in different parts of the nephron. For example, most of the Na transporters are located in the proximal tubule, while fewer ones are spread out through other segments. Some transporters require energy, usually in the form of adenosine triphosphate (active transport), while others don't (passive transport). Water gets reabsorbed passively by osmosis in response to the buildup of reabsorbed Na in spaces between the cells that form the walls of the nephron. Other molecules get reabsorbed passively when they are caught up in the flow of water (solvent drag). Reabsorption of most substances is related to the reabsorption of Na, either directly, via sharing a transporter, or indirectly via solvent drag, which is set up by the reabsorption of Na.

Click on the menu items.

The reabsorption process in various segments of the nephron.

The reabsorption process is similar to the "fish pond" game that you see in some amusement parks or state fairs. In these games, there is a stream that contains different colored plastic fish with magnets. The children playing the game each have a fishing pole with an attached magnet to catch the fish as they move by. Different colored fish have different prize values associated with them, so some children will be selective and try to grab the colored fish with the highest prize value. Now suppose our nephron is the stream, the filtered molecules are the various colored fish, and our children are the transporters. Furthermore, each child is fishing for a specific colored fish. Most children start at the beginning of the stream and some spread out further downstream. By the end of the stream, most of the fish have been caught. This is what happens as the filtrate travels through the nephron. Two major factors affect the reabsorption process:

Concentration of small molecules in the filtrate - the higher the concentration, the more molecules can be reabsorbed. Like our children in the fish pond game, if you increase the number of fish in the stream, the children will have an easier time catching them. In the kidney, this is true only to a certain extent because: There is only a fixed number of transporters for a given molecule present in the nephron. There is a limit to how many molecules the transporters can grab in a given period of time.

Rate of flow of the filtrate - flow rate affects the time available for the transporters to reabsorb molecules. As with our fish pond, if the stream moves by slowly, the children will have more time to catch fish than if the stream were moving faster.

To give you an idea of the quantity of reabsorption across the nephron, let's look at the sodium ion (Na) as an example: Proximal tubule - reabsorbs 65 percent of filtered Na. In addition, the proximal tubule passively reabsorbs about 2/3 of water and most other substances. Loop of Henle - reabsorbs 25 percent of filtered Na. Distal tubule - reabsorbs 8 percent of filtered Na. Collecting duct - reabsorbs the remaining 2 percent only if the hormone aldosterone is present.

Kidney Processes Working Together

Some substances are secreted from the plasma into the lumen by the cells of the nephron. Examples of such substances are ammonia (NH3). As in reabsorption, there are transporters on the cells that can move these specific substances into the lumen.

iStockphoto.com/henrik5000 Your blood needs your kidneys to deal with those potato chips.

Now let's put all of these processes -- filtration, reabsorption and secretion -- together to understand how the kidneys maintain a constant composition of the blood. Let's say that you decide to eat several bags of salty (NaCl) potato chips at one sitting. The Na will be absorbed into your blood by your intestines, increasing the concentration of Na in your blood. The increased Na in the blood will be filtered into the nephron. While the Na transporters will attempt to reabsorb all of the filtered Na, it's likely that the amount will exceed their ability. Therefore, excess Na will remain in the lumen; water will also remain, due to osmosis. The excess Na will be excreted into the urine and eliminated from the body. So whether a substance remains in the blood depends on the amount filtered into the nephron and the amount reabsorbed or secreted by various transporters. Let's look at an another example: Why do you have to keep taking repeated doses of any given medicine? Well, once you take the medicine, it gets absorbed by the intestine into the blood. The medicine in the blood acts on its target cell and also gets filtered into the nephron. Most medicines don't have transporters in the nephron to reabsorb them from the filtrate. In fact, some transporters actively secrete medicines into the nephron. Therefore, the medicine gets eliminated in the urine and you must take another dosage later. We've seen how the kidney can regulate ions and small molecules and eliminate unwanted substances. In the next section, we'll see how the kidney maintains water balance

Maintaining Water Volume

Your kidneys have the ability to conserve or waste water. For example, if you drink a large glass of water, you'll find that you will have the urge to urinate within an hour or so. In contrast, if you don't drink for a while, such as overnight, you will not produce much urine and it will usually be very concentrated (i.e. darker). How does your kidney know the difference? The answer to this question involves two mechanisms:

The structure and transport properties of the loop of Henle in the nephron. The anti-diuretic hormone (ADH), also called vasopressin, secreted by the pituitary gland.

The loop of Henle has a descending limb and an ascending limb. As filtrate moves down the loop of Henle, water is reabsorbed, but ions (Na,Cl) aren't. The removal of water serves to concentrate the Na and Cl in the lumen. Now, as the filtrate moves up the other side (ascending limb), Na and Cl are reabsorbed, but water isn't. What these two transport properties do is set up a concentration difference in NaCl along the length of the loop, with the highest concentration at the bottom and lowest concentration at the top. The loop of Henle can then concentrate NaCl in the medulla. The longer the loop, the bigger the concentration gradient. This also means that the medulla tissue tends to be saltier than the cortex tissue. Now, as the filtrate flows through the collecting ducts, which go back down through the medulla, water can be reabsorbed from the filtrate by osmosis. Water moves from an area of low Na concentration (high water concentration) in the collecting ducts to an area of high Na concentration (low water concentration) in the medullary tissue. If you remove water from the filtrate at this final stage, you can concentrate the urine. ADH, which is secreted by the pituitary gland, controls the ability of water to pass through the cells in the walls of the collecting ducts. If no ADH is present, then no water can pass through the walls of the ducts. The more ADH present, the more water can pass through. Specialized nerve cells, called osmoreceptors, in the hypothalamus of the brain sense the Na concentration of the blood. The nerve endings of these osmoreceptors are located in the posterior pituitary gland and secrete ADH. If the Na concentration of the blood is high, the osmoreceptors secrete ADH. If the Na concentration of the blood is low, they don't secrete ADH. In reality, there is always some very low level of ADH secreted from the osmoreceptors. Now let's look at how your kidneys maintain water volume.

Maintaining Water Balance

iStockphoto.com/lovleah He's going to need a bathroom break pretty soon.

When you drink a large glass of water, the water gets absorbed into the blood and the following happens: The absorbed water increases the amount of water filtered in the glomerulus. The absorbed water in the blood reduces the Na concentration a little. The reduced Na concentration lowers the amount of Na filtered in the glomerulus. The nephron reabsorbs all of the reduced Na load and some of the accompanying water, leaving excess water in the filtrate. The reduced Na concentration is sensed by the osmoreceptors. The osmoreceptors do not secrete as much ADH. Because the collecting ducts don't see as much ADH, they don't allow much water to be reabsorbed in response to the Na concentration gradient set up by the loop of Henle. The excess water gets excreted in the urine. When the excess water is excreted, the Na concentration of the blood returns to normal.

Typically, we don't drink water overnight when we sleep. So, our intestines aren't absorbing water:
Decreased water absorption by the intestine reduces the amount of water in the blood.

Decreased water in the blood reduces the amount of water filtered in the glomerulus. Decreased water in the blood increases the Na concentration in the blood. Increased Na concentration in the blood increases the amount of Na filtered in the glomerulus. The nephron doesn't reabsorb all of the filtered Na, and some water remains with it in the filtrate. The increased Na concentration in the blood is sensed by the osmoreceptors. The osmoreceptors secrete ADH. The collecting ducts see more ADH and allow water to be reabsorbed in response to the Na concentration gradient set up by the loop of Henle. More water gets reabsorbed from the collecting ducts, producing a concentrated urine. A little water is lost in the urine because of the Na; we can't excrete solid urine. The removal of Na and increased reabsorption of water help return the blood concentration of Na to normal.

So, the loop of Henle sets up the Na concentration gradient across the medulla, allowing for water to be reabsorbed from the collecting ducts, and ADH allows the water to pass through those collecting ducts. Your blood maintains a constant concentration of hydrogen ion (pH) by a chemical mixture of hydrogen ions and sodium bicarbonate. The sodium bicarbonate is produced by the carbon dioxide (CO2) formed in the cells as a byproduct of many chemical reactions. The CO2 enters the blood in the capillaries, where red blood cells contain an enzyme called carbonic anhydrase that helps combine CO 2 and water (H 2O) to form carbonic acid (H 2 CO3 ) quickly. The carbonic acid formed then rapidly separates into hydrogen ions (H+ ) and bicarbonate ions (HCO3-). This reaction can also proceed in the reverse direction, whereby sodium bicarbonate plus hydrogen ion yields carbon dioxide and water.
Carbonic Anhydrase CO 2 + H 2 O <---------> H 2 CO3 <---------> H+ + HCO 3 -

The correct pH is maintained by keeping the ratio of hydrogen ion to bicarbonate in the blood constant. If you add acid (hydrogen ion) to the blood, then you will reduce the bicarbonate concentration and alter the pH of the blood. Similarly, if you reduce the hydrogen ion by adding alkali, you will increase the bicarbonate concentration and alter the pH of the blood. Now, the acid/base balance of our blood changes in response to many things including:
Diet - diets rich in meats provide acids to the bloods when digested. In contrast, diets rich in fruits and vegetables make our blood alkaline because they are rich in bicarbonates. Exercise - exercising muscles produce lactic acid that must be eliminated from the body or metabolized.

Breathing - high altitude causes rapid breathing that makes our blood alkaline. In contrast, certain lung diseases that block the diffusion of oxygen can cause the blood to be acidic.

In the next section, we'll take a look at how the kidneys regulate blood composition.

Regulating Blood Composition

The kidney can correct any imbalances by:
Removing excess acid (hydrogen ion) or bases (bicarbonate) in the urine and Restoring the bicarbonate concentration in the blood to normal

The kidney cells produce a constant amount of hydrogen ion and bicarbonate because of their own cellular metabolism (production of carbon dioxide). Through a carbonic anhydrase reaction similar to the red blood cells, hydrogen ions get produced and secreted into the lumen of the nephron. Also, bicarbonate ions get produced and secreted into the blood. In the lumen of the nephron, filtered bicarbonate combines with secreted hydrogen ions to form carbon dioxide and water (carbonic anhydrase is also present on the luminal surface of the kidney cells). Whether the kidney removes hydrogen ions or bicarbonate ions in the urine depends upon the amount of bicarbonate filtered in the glomerulus from the blood relative to the amount of hydrogen ions secreted by the kidney cells. If the amount of filtered bicarbonate is greater than the amount of secreted hydrogen ions, then bicarbonate will be lost in the urine. Likewise, If the amount of secreted hydrogen ion is greater than the amount of filtered bicarbonate, then hydrogen ions will be lost in the urine (i.e. acidic urine). Let's consider a few examples:
Acid Diet 1. Hydrogen ions added to the blood by breaking down a meat-rich diet combine with bicarbonate in the blood and form carbon dioxide and water. 2. This reaction reduces the bicarbonate concentration and the pH in the blood. 3. The decreased bicarbonate concentration in the blood reduces the amount of bicarbonate filtered in the glomerulus. 4. All of the filtered bicarbonate combines with the hydrogen ion secreted by the kidney cells in the lumen to form carbon dioxide and water. 5. Because the filtered load of bicarbonate was less than the amount of hydrogen ion secreted by the kidney cells, there is an excess of hydrogen ion in the urine. 6. The amount of bicarbonate secreted from the kidney cells into the blood was equal to the hydrogen ion secreted into the lumen and greater than the filtered load of bicarbonate from the blood -therefore, the blood has a net gain of bicarbonate. 7. This process continues to lose hydrogen ions in the urine and gain bicarbonate in the blood until the concentrations of hydrogen (pH) and bicarbonate ions in the blood are restored to normal.

Alkaline Diet 1. Bicarbonate added to the blood from the fruit or vegetable-rich diet combines with hydrogen ions to form carbon dioxide and water. 2. This reaction reduces the hydrogen ion concentration and increases the pH. 3. The increased bicarbonate concentration increases the amount of bicarbonate filtered in the glomerulus. 4. The filtered bicarbonate exceeds the amount of hydrogen ion secreted by the kidney cell, and excess bicarbonate is lost in the urine. 5. The amount of bicarbonate secreted from the kidney cells into the blood was equal to the hydrogen ions secreted into the lumen and less than the filtered load of bicarbonate from the blood -- therefore, the blood has a net loss of bicarbonate. 6. This process continues to lose bicarbonate in the urine and reduce the bicarbonate in the blood until the concentrations of hydrogen (pH) and bicarbonate ions in the blood are restored to normal.

Now that we have seen how the kidneys regulate the composition of our blood, let's look at how they help regulate our blood pressure.

How Kidneys Influence Blood Pressure

The blood pressure in your body depends upon the following conditions:
The force of contraction of the heart -- related to how much the heart muscle gets stretched by the incoming blood. The degree to which the arteries and arterioles constrict -- increases the resistance to blood flow, thus requiring a higher blood pressure. The circulating blood volume -- the higher the circulating blood volume, the more the heart muscle gets stretched by the incoming blood. Causing the arteries and veins to constrict Increasing the circulating blood volume

The kidney influences blood pressure by:

Diuretics
People with chronic high blood pressure (hypertension) often take a class of drugs called diuretics to control their blood pressure. Diuretics reduce Na reabsorption from the lumen of the nephron. Water reabsorption is also reduced. Therefore, Na and water are lost in the urine, which increases urine flow. The decreased reabsorption of Na and water from the nephron reduces blood volume, thereby reducing blood pressure.

Specialized cells are located in a portion of the distal tubule located near and in the wall of the afferent arteriole. The distal tubule cells (macula densa) sense the Na in the filtrate, and the arterial cells (juxtaglomerular cells) sense the blood pressure. When the blood pressure drops, the amount of filtered Na also drops. The juxtaglomerular cells sense the drop in blood pressure and the decrease in Na is relayed to them by the macula densa cells. The juxtaglomerular cells

then release an enzyme called renin. Renin converts angiotensinogen (a peptide, or amino acid derivative) into angiotensin I. Angiotensin I is then converted to angiotensin II by an angiotensin-converting enzyme (ACE), which is found mainly in the lungs. Angiotensin II causes blood vessels to contract -- the increased blood vessel constrictions elevate the blood pressure. Now let's take a look at how the kidney increases the circulating blood volume. Angiotensin II also stimulates the adrenal gland to secrete a hormone called aldosterone. Aldosterone stimulates more Na reabsorption in the distal tubule, and water gets reabsorbed along with the Na. The increased Na and water reabsorption from the distal tubule reduces urine output and increases the circulating blood volume. The increased blood volume helps stretch the heart muscle and causes it to generate more pressure with each beat, thereby increasing the blood pressure. The actions taken by the kidney to regulate blood pressure are especially important during traumatic injury, when they are necessary to maintain blood pressure and conserve the loss of fluids. Your body stores calcium in the bones, but also maintains a constant level of calcium in the blood. If the blood calcium level falls, then the parathyroid glands in your neck release a hormone called parathyroid hormone. Parathyroid hormone increases calcium reabsorption from the distal tubule of the nephron to restore the blood calcium level. Parathyroid hormone also stimulates calcium release from bone and calcium absorption from the intestine. In addition to parathyroid hormone, your body also requires vitamin D to stimulate calcium absorption from the kidney and intestine. Vitamin D is found in milk products. A precursor to vitamin D (cholecalciferol) is made in the skin and processed in the liver. However, the final step that converts an inactive form of cholecalciferol into active vitamin D occurs in the proximal tubule of the nephron. Once activated, vitamin D stimulates calcium absorption from the proximal tubule and from the intestine, thereby increasing blood calcium levels. Kidney stones are often caused by problems in the kidney's ability to handle calcium. In addition, the kidney's role in maintaining blood calcium is important in the bone disease osteoporosis that afflicts many elderly people, especially women. As you can see, the kidneys perform many functions that are important to your body:
Controlling the composition of your blood and eliminate wastes -filtration/reabsorption/secretion method Influencing blood pressure -- renin secretion Helping to regulate your body's calcium -- vitamin D activation

If the kidneys fail to function, then renal dialysis methods (artificial filtration methods) can be used to help you survive by cleansing the blood. This is especially necessary when both kidneys fail. Although you have two kidneys, it is possible to live with only one. One healthy kidney can be donated and transplanted into a compatible person with total kidney failure. Kidney transplants are a common way to help those people survive and live a normal life. For more information on the kidney, its functions and its diseases, check out the following page There are two significant categories of kidney cysts that exist. The most common type of kidney cyst is the simple kidney cyst. The simple kidney cyst is very common and has no risk of becoming a kidney cancer. The other type of cyst is called a complex cyst. The term complex

cyst refers to a spectrum of cysts that have different characteristics which may make them suspicious for kidney cancer. A simple kidney cyst is a finding that has a very clear definition depending on the radiologic imaging test (eg. ultrasound, CT scan, etc.) that is used to identify it. The simple kidney cyst is a spherical space somewhere in the kidney that is filled with liquid. The lining or wall of the cyst is very thin and has no irregularities in it. Inside the simple kidney cyst there is nothing but fluid, which when removed is usually yellow or clear. A simple kidney cyst has no risk of becoming a kidney cancer and is therefore nothing to worry about. Indeed, by the time a person is 50 years old, there is a 50% chance that he or she will have a simple cyst. As we get older the chances of having a simple cyst increase and the cysts increase in size as well. If you are over 50 years old and you do not have a simple cyst, you are therefore in the minority of people. Another type of simple kidney cyst is called a hyperdense cyst. A hyperdense cyst a simple kidney cyst that has blood within the walls of the cyst. A hyperdense kidney cyst is not suspicious for cancer and is just another type of simple kidney cyst. The vast majority of simple kidney cyst are simply identified on a radiographic test that has been performed for another reason. Simple kidney cysts have no clinical implications. Usually, simple kidney cysts do not result in any symptoms and cause no harm to the body. On rare occasions, a cyst may cause symptoms such as flank pain, but this is quite unusual. If a simple kidney cyst is believed to cause pain or another symptom, it can usually be treated by a radiologist who can perform aspiration and sclerosis of the simple kidney cyst under radiographic guidance with ultrasound or CT scanning. Aspiration is defined as placing a needle through the skin to suck out the fluid in the cyst with a needle. Sclerosis is then performed. Sclerosis means that the radiologist will inject some material to sclerose (scar down) the space in the cyst. Aspiration and sclerosis of simple kidney cysts that are associated with symptoms is usually effective although in some cases the cyst may recur (re-fill with fluid). Other than observation of the cyst (if it is not terribly bothersome), aspiration and sclerosis by a radiologist is the least invasive way to treat a simple kidney cyst that is causing symptoms. Rarely, a simple renal cyst that is causing symptoms will require laparoscopic cyst decortication. In this procedure, small incisions are made and the body spaces are gently inflated with gas. The cyst can be identified and the wall of the cyst cut out to both get rid of the cyst and prevent it from re-forming. Usually, laparoscopic cyst decortication is reserved for simple kidney cysts that have failed aspiration and sclerosis by a radiologist. The Procedure is very effective and usually people only require an overnight stay in the hospital. A complex kidney cyst is different from a simple kidney cyst as the cyst may be irregular in its outer shape. To be defined as a complex kidney cyst, the cyst must have some type of irregularities inside of it. The irregularities come in different varieties. Septations are walls within the cyst. These walls may be very fine and thin or quite thick and coarse. Having many or thick walled septations may suggest that the cyst is more likely to be associated with a kidney cancer. Cysts may also be calcified. This means that the mineral calcium is visualized inside of the cyst. There may be very little calcium, or the calcifications may be quite thick. A complex kidney cyst may also have tissue inside of it that enhances. Enhancement means that a part of the complex kidney cyst gets a blood supply, which can be demonstrated by giving contrast material into a vein while radiologic testing is in progress. Solid enhancing material inside of a complex kidney cyst is suspicious for kidney cancer and may require intervention by a Urologist for treatment.

Many complex kidney cysts may have a low risk for being or becoming a kidney cancer. However, there is some risk that a complex cyst is a kidney cancer and complex kidney cysts do require evaluation by an experienced Urologist who may consult with a radiologist. Often, complex kidney cysts may be treated with active surveillance to see if the cyst changes in any way over time. The risk that a complex kidney cysts is, or may become, cancer depends on its appearance. A system to grade kidney cysts by their appearance on CAT scan has been developed, which help doctors to predict which complex kidney cysts are more likely to have kidney cancer inside. This system is known as the Bosniak classification. The Bosniak classification provides specific definitions to classify cysts by the risk of kidney cancer. Bosniak Categories of Complex Kidney Cysts Category I A simple benign cyst with a hairline thin wall that does not contain septa, calcifications, or solid components. It measures as water density and does not enhance with contrast material. A benign cyst that might contain a few hairline thin septa. Fine calcifications might be present in the wall or septa. Uniformly highattenuation lesions of <3 cm that are sharply marginated and do not enhance.

Category II

These cysts might contain more hairline thin septa. Minimal enhancement of a hairline thin septum or wall can be seen and there might be minimal thickening of the septa or wall. The cyst might contain calcifications that Category IIF are nodular and thick but there is no contrast enhancement. There are no enhancing soft tissue elements. Totally intrarenal non-enhancing highattenuation renal lesions of less than or equal to 3 cm are also included in this category. These lesions are generally well marginated. Category III Category IV These lesions are indeterminate cystic masses that have thickened irregular walls or septa in which enhancement can be seen. These lesions are most likely cystic lesions that contain enhancing soft tissue components.

The Bosniak classification, which is above, is designed to help your doctor predict the chances that your complex renal cyst is associated with a kidney cancer. Bosniak category I complex kidney cysts have a less than 2% chance of being associated with a kidney cancer. Bosniak category II and III complex kidney cysts are associated with an approximately 18% and 33% chance of being associated with kidney cancer respectively. The majority (92%) of Bosniak IV complex kidney cysts are associated with kidney cancers. By using the Bosniak system people with complex renal cysts can work with an experienced Urologist to establish a treatment plan. The treatment plan will incorporate all factors including patient age and health as well as the risk of kidney cancer associated with the complex kidney cyst. The plan will include one of the strategies that are typically used for kidney cancers and may range from active surveillance to removal of the kidney depending on the particular clinical circumstances. ne third of people older than 50 years develop renal cysts. Although most are simple cysts, renal cystic disease has multiple etiologies. Broad categories of cystic disease include the following:

Developmental -Multicystic dysplastic kidney (MCDK) Genetic -Autosomal recessive polycystic kidney disease (ARPKD), autosomal dominant polycystic kidney disease (ADPKD), juvenile nephronophthisis (JNPHP), medullary cystic kidney disease (MCKD), glomerulocystic kidney disease (GCKD) Cysts associated with systemic disease -Von Hippel-Lindau syndrome (VHLS), tuberous sclerosis (TS) Acquired - Simple cysts, acquired cystic renal disease, medullary sponge kidney (MSK) Malignancy -Cystic renal cell carcinoma (RCC)

The most common larger cysts include acquired cysts, simple cysts, and cysts associated with ADPKD. Smaller cysts characterize ARPKD, JNPHP, MCKD, and MSK. In adults, renal angiomyolipomas and RCC may also have cystic components. Cysts develop from renal tubule segments and most detach from the parent tubule after they grow to a few millimeters in size. Cyst development is generally attributed to increased proliferation of tubular epithelium, abnormalities in tubular cilia, and excessive fluid secretion.
Developmental cystic renal disease

MCDK represents abnormal development or formation of the kidney and may involve part, or all of, one or both kidneys. This condition is thought to be secondary to dysfunctional genetics, abnormal differentiation of the metanephros or in utero ureteral obstruction. Patients are observed unless complications arise directly from the kidney or its associated conditions.
Inherited cystic renal disease

ADPKD is due to mutations in the genes PKD1 and PKD2, which encode polycystin proteins. The genetic mechanism of cyst development requires a "second hit," a somatic mutation of the normal PKD allele, which accounts for the onset of ADPKD, usually in those aged 30-50 years. Symptoms primarily include pain, hypertension and renal failure. The goal of treatment is to control blood pressure and to slow the onset of renal failure. ADPKD is associated with involvement of other organs, particularly intracranial aneurysms. ARPKD is due to mutations in PKHD1, a large gene that encodes fibrocystin/polyductin, which plays critical roles in collecting-tubule and biliary development. This disease carries a high neonatal mortality rate, and many individuals who survive eventually require renal transplantation. Symptoms include hypertension and liver disease. Diagnosis is often made in utero. Treatment is supportive in severe cases but otherwise is similar to that for ADPKD. GCKD is often confused with ADPKD, as it is common in individuals with a family history of ADPKD. This disease is distinguished histologically and symptoms and treatment are similar to those in ADPKD. JNPHP and medullary cystic disease are two diseases that some consider a disease complex.[1] They share similar pathologic features but are due to different genetic mutations and have different inheritance patterns. JNPHP is inherited in an autosomal recessive manner and presents in childhood, while MCKD is inherited autosomal dominantly and affects adults. Both diseases present with symptoms of salt wasting and polyuria.

Systemic disease with associated renal cysts

TS is caused by mutations in the suppressor genes TSC1 and TSC2, which encode hamartin and tuberin, respectively. Renal cysts and angiomyolipomas are part of a syndrome that includes seizures and dermatologic findings. VHLS is due to mutations in the VHL gene, which increases the risk for malignancy, including RCC. Affected individuals develop cysts in multiple organs, including the kidney, pancreas, liver, and epididymis.
Acquired cystic renal disease

The exact cause of this disease is not known. It occurs exclusively in patients on dialysis. The severity of disease is directly related to the duration of therapy. Typically, acquired cystic renal disease is asymptomatic but it is known to subsequently increase the risk of RCC.

Epidemiology
Frequency United States MCDK has an incidence of 1 per 1000-4000 live births.[2] ADPKD has an incidence of 1 per 400-1000 persons among whites and accounts for 8-10% of all cases of end-stage renal disease (ESRD). ARPKD has an incidence of 1 per 6000-55,000 live births, with a heterozygous carrier frequency of 1 per 70. JNPHP affects 1 per 5000 persons.[3] JNPHP and MCKD account for 10-20% of children with chronic renal failure and for 1-5% of all patients undergoing dialysis or transplantation. TS has an incidence of 1 per 10,000-50,000 persons, and 20-25% of these patients have renal cysts.[4] VHLS has an incidence of approximately 1 per 39,000 persons, and two thirds of these individuals develop renal cysts. In acquired cystic renal disease, cysts are present in 8-13% of patients with chronic renal failure prior to dialysis. Following initiation of therapy, 10-20% of patients have acquired cystic renal disease after 3 years of dialysis, 4060% after 5 years, and more than 90% after 10 years.[5] MSK has an estimated incidence of 1 per 5000 persons and is found in approximately 20% of patients with nephrolithiasis. Simple cysts are the most common cystic renal lesions. They are present in 5% of the general population, increasing in frequency to 25-33% of patients older than 50 years, and account for 65-70% of renal masses. Cystic RCC accounts for less than 1% of RCC cases.

Mortality/Morbidity Cystic renal disease accounts for approximately 10% of all ESRD cases.

ADPKD is 1 of the top 4 causes of ESRD and is the etiology of renal failure in 5-10% of patients undergoing dialysis. ARPKD accounts for 5% of ESRD in children. Neonatal mortality secondary to ARPKD approaches 25-35% and is usually related to respiratory compromise.[6] More than 50% of patients with ARPKD require kidney transplant before age 20 years.[7] JNPHP is the most common cause of genetic ESRD in children.[8] TSC is associated with a high frequency of angiomyolipoma. Patients with acquired cystic disease are more likely to develop RCC (5-25%). Additionally, tumors are commonly bilateral, and 15% are metastatic.[5]

Race Sex Age

ADPKD is found throughout the world in all racial and ethnic groups. Acquired cystic renal disease is most common in white men and African Americans.

Multicystic dysplastic kidney is more common in males than in females. Symptomatic progression of ADPKD appears to be more rapid in men. VHLS affects men and women with equal frequency. Acquired cystic renal disease is more common in men. MSK has a male-to-female ratio of 2:1.

ADPKD has a bimodal distribution of onset, with some cases presenting in infancy or childhood.[3] ARPKD presents in infancy, childhood, or adolescence. VHLS typically presents in the third or fourth decade of life with visual or central nervous system symptoms. MSK typically presents between the third and fifth decades of life. Simple cysts are very rare in children but increase in frequency with age.

Developmental cystic renal disease: Multicystic dysplastic kidney (MCDK) is almost uniformly identified during prenatal sonographic examination. The involved kidney partially or completely improves with age in 40-90% of patients.[9] Bilateral renal involvement is not compatible with life. MCDK can exist independently or as part of syndromes such as the vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and radial and renal anomalies (VATER) association; Zellweger syndrome; or BOR syndrome.[10] Inherited cystic renal disease

Autosomal dominant polycystic kidney disease

Patients present in the fourth decade of life with flank pain or intermittent hematuria. Patients may also experience cyst hemorrhage, renal infection, or nephrolithiasis. Hypertension and chronic renal failure are noted in the fifth decade of life, and patients progress to end-stage renal disease (ESRD) in the sixth decade of life. Hypertension is seen in 50% of patients with ADPKD aged 20-34 years.

The disease course varies considerably among affected individuals. While all gene carriers are believed to exhibit symptoms by the end of their eighth decade of life, only 50% of carriers actually progress to renal failure.

Kidney size (a direct reflection of cyst volume) increases exponentially over time and appears symmetric in a given individual, with an equal growth rate in both kidneys.[11] All aspects of the disease appear to develop more rapidly in patients with the PKD1 genotype. The kidneys grow more rapidly in these patients, and hypertension and ESRD occur at a younger age; the onset of ESRD in persons with the PKD1 genotype occurs at a mean age of 53 years, while the onset of ESRD in persons with the PKD2 genotype occurs at a mean age of 69 years.[12] Hepatic cysts are the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). These increase in number with age (20% in the third decade of life, 75% after the sixth decade of life) and may cause chronic pain. However, even with extensive cystic involvement, liver function is not compromised. Other clinical associations include cardiac valve disease (particularly mitral valve prolapse [25%]), diverticulosis, cerebral aneurysms (5-10%), pancreatic cysts, and seminal vesicle cysts.[6] Autosomal recessive polycystic kidney disease (ARPKD) affects renal and hepatic development (dysgenesis of the portal triad), but the degree of organ involvement varies in relation to the age of onset. In the neonatal period, pulmonary disease, resulting from nephromegaly and oligohydramnios, dominates the presentation. Typically, the neonate has profound respiratory compromise, often exacerbated by pneumothorax. This presentation may result in neonatal death.

Autosomal recessive polycystic kidney disease

Symptoms in an infant include hypertension (80%), diminished urine concentrating ability, and renal insufficiency. Most affected children develop hypertension within the first few years of life. Growth retardation has been reported in one fourth of children. Fifty percent of affected individuals develop ESRD in the first decade of life, requiring dialysis or transplantation.

In older children (4-8 y), the kidneys often are less severely affected, while hepatic disease may predominate. Hepatic involvement usually presents with symptoms secondary to portal hypertension, particularly varices and splenomegaly. Twenty-three percent of children with ARPKD

experience variceal bleeding by a mean age of 12.5 years. Hepatic disease may also result in acute bacterial cholangitis or thrombocytopenia secondary to hypersplenism.

Glomerulocystic kidney disease (GCKD): This occurs in early (neonatal) and late (adult) forms. Neonates present with hypertension, abdominal masses, and variable degrees of renal failure. Adults typically present with flank pain, hematuria, and hypertension. Hepatic cysts may also develop.[13] Juvenile nephronophthisis (JNPHP): This has several different phenotypic expressions depending on the gene involved. Infantile (NPHP2), juvenile (NPHP1, NPHP4) and adolescent (NPHP3) forms of the disease exist, but most symptoms appear during the first decade of life. These include growth retardation, urine concentrating defects, skeletal dysplasia, and progressive renal failure. Additionally, some degree of hepatic fibrosis and biliary duct enlargement is usually present.[1] Medullary cystic kidney disease: This is clinically milder than JNPHP, occurs later in life (third to fourth decades), and has limited extrarenal manifestations. Individuals with this disease due to mutations in the MCKD2 gene present with uremia sooner than those with disease due to MCKD1 mutations and are more likely to develop hyperuricemia and gout.[1] Tuberous sclerosis (TS): Clinical features of TS include facial nevi, cardiac rhabdomyomas, epilepsy, angiofibromas, and mental retardation. Approximately one half of patients have multiple renal angiomyolipomas. Twenty to 25% of patients have renal cysts, although diffuse renal cystic disease, which may result in chronic renal failure, is rare. Von Hippel-Lindau syndrome (VHLS): Clinical features of VHLS include retinal and cerebellar hemangioblastomas, pheochromocytomas, and cystic disease of the kidneys, pancreas, and epididymis. Renal cysts are very common, occurring in two thirds of patients. Renal cell carcinoma (RCC) develops in as many as 40% of patients. Acquired renal cystic disease (ARCD): Acquired cystic disease may be found in patients with all etiologies of ESRD, particularly in patients who are dialysisdependent. The incidence, number, and size of cysts all increase in proportion to the duration of dialysis. Most patients are asymptomatic, but symptoms may include gross hematuria, flank pain, renal colic, or a palpable renal mass. Hemorrhagic cysts occur in 50% of patients.[4] Medullary sponge kidney (MSK) is usually detected on radiographic evaluation of adults with nephrolithiasis. Fifteen to 20% of patients with calcium oxalate and calcium phosphate renal calculi have MSK. Patients may also have a history of hematuria or urinary tract infection (UTI). Most patients with MSK, however, are asymptomatic. Approximately 10% of patients develop recurrent nephrolithiasis, bacteriuria, and pyelonephritis. Involvement is usually bilateral.

Systemic disease with associated renal cysts

Acquired cystic renal disease

Simple cysts usually are clinically silent, although they occasionally hemorrhage and cause acute pain.

Physical

Developmental cystic renal disease: MCDK may be palpable as a flank mass in an otherwise healthy infant and is the most common cause of a renal mass and the second most common cause of a palpable abdominal mass in neonates.[14, 2] Inherited cystic renal disease ARPKD: Bilateral flank masses are palpable in 30% of neonates and infants with this disease. Older children may demonstrate signs of portal hypertension. ADPKD: The enlarged kidneys and liver may be palpable.

Acquired cystic renal disease: Simple cysts rarely become large enough to be palpable. Developmental cystic renal disease: MCDK is thought to arise from abnormal development of the metanephros. This may be a genetic effect or may reflect a defect in the ampullary bud (inducer tissue) or the blastema (responder tissue), with resultant poor nephron induction.[2] Additionally, in utero obstruction has been identified as a possible cause, leading to urinary stasis and cyst formation. Many patients, however, have normal renal development despite obstruction. Inherited cystic renal disease: Currently, the exact mechanism of genetically induced cyst formation has not been fully defined. Similarities between cystic diseases, however, reveal common pathologic pathways. The vast majority of mutations affect the primary cilia of the tubular epithelium, indicating that disruption of this structure relates to disease development.[6] Additionally, dedifferentiation and increased proliferation of tubular epithelium, along with abnormal fluid secretion, appear to be common elements in cystic disease.

Causes

ADPKD: Inheritance is autosomal dominant, with close to 100% penetrance. PKD1 (chromosome 16) encodes for the transmembrane protein polycystin-1 (PC1), which is responsible for cell-to-cell and celltoextracellular matrix binding.[6] Mutations in this gene are responsible for 85-90% of cases. Mutations in polycystin-2 (PKD2, chromosome 4), a calcium channel important for PC1 localization and function, account for the remaining 10-15%.[12] Interestingly, while this is a genetic disease that affects every cell in the kidney, cysts involve only 1-2% of the nephrons or collecting ducts, supporting the hypothesis that a "second hit," or mutation of the abnormal allele, must occur.[1] Five to 8% of cases do not involve a family history and are the result of spontaneous mutations. ARPKD: Inheritance is autosomal recessive. All cases are caused by mutations in PKHD1, a large gene that encodes fibrocystin/polyductin, which appears to be related to the polycystin complex and controls epithelial proliferation, secretion, and structure and development of the renal tubules and biliary ducts.[7] The genetic defect is located on chromosome 6p21.1-p12. In both ADPKD and ARPKD, epidermal growth factor (EGF) has been identified as an important stimulus for proliferation of cystic epithelium.[12]

GCKD is a rare disease that is transmitted in an autosomal dominant manner. The involved gene has not been identified, and both familial and sporadic forms exist.
[13]

JNPHP is inherited in an autosomal recessive manner and is due to mutations in the NPHP genes (NPHP1-NPHP5) which are located on multiple different chromosomes and encode nephrocystins and inversin. All of the gene products are found in the primary cilium.[3, 12, 8] Ten to 20% of cases are associated with retinal disease and are termed Senior-Loken syndrome.

NPHP1 is located on chromosome 2q12-13 and encodes nephrocystin. NPHP2 is found on chromosome 9q22-31 and encodes inversin. NPHP3 is found on chromosome 3q21-22 and encodes nephrocystin-3. NPHP4 is located at chromosome 1q36 and encodes nephrocystin-4. NPHP5 (chromosome 3q13.33-21.2) encodes nephrocystin-5 and is found only in cases associated with Senior-Loken syndrome.

Medullary cystic kidney disease (MCKD) is due to mutations in the MCKD1 (chromosome 1q21) and MCKD2 (chromosome 16p12) genes and is inherited in an autosomal dominant manner.[12] TS: Inheritance is autosomal dominant, with variable penetrance. Sixty to 70% of cases are due to sporadic mutations. Genetic markers have been identified at chromosome band 9q34 (TSC1, which encodes hamartin) and chromosome band 16p13 (TSC2, which encodes tuberin). TSC2 accounts for two thirds of TS cases. [6, 1] While the functions of these genes are not understood, TSC2 is adjacent to the PKD1 gene, which is involved in the most common form of ADPKD. In some cases, a contiguous gene syndrome has been described, involving large deletions that affect both TSC2 and PKD1. VHLS: Inheritance is autosomal dominant, with variable penetrance. The genetic defect has been localized to chromosome band 3p25.

Systemic disease with associated renal cysts

Biochemical analyses[15, 16] have identified a protein (mTOR) that may be part of a common pathway in several of the genetic forms of cystic disease. mTOR activity is related to cell growth, proliferation, apoptosis, and differentiation. Levels of mTOR have been demonstrated to be increased in cyst epithelium. Under normal conditions, PC1 (mutated in ADPKD) and TSC2 (mutated in TS) suppress or inactivate mTOR. When these genes, as well as others that relate to the primary cilia, mutate, mTOR activity becomes dysregulated, possibly allowing cyst formation. Acquired cystic renal disease: The exact cause of cyst formation has not been identified. One theory suggests that the development of cysts in acquired renal cystic disease (ARCD) is secondary to obstruction of the tubules by fibrosis or oxalate crystals. Another hypothesis invokes the accumulation of growth factors and stimulatory chemicals (uremia), including EGF, which leads to the development of cysts.[1] The disease occurs in patients on all types of dialysis and appears to regress after transplantation

The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood pressure and water (fluid) balance.

When blood volume is low, juxtaglomerular cells in the kidneys secrete renin. Renin stimulates the production of angiotensin I from angiotensinogen.[2] Angiotensin I is then converted to angiotensin II by the enzyme angiotensin converting enzyme. Angiotensin II causes blood vessels to constrict, resulting in increased blood pressure. Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water into the blood. This increases the volume of fluid in the body, which also increases blood pressure. If the renin-angiotensin-aldosterone system is too active, blood pressure will be too high. There are many drugs that interrupt different steps in this system to lower blood pressure. These drugs are one of the main ways to control high blood pressure (hypertension), heart failure, kidney failure, and harmful effects of diabetes.[3][4]

Contents
[hide] 1 Activation 2 Effects 3 Clinical significance 4 Other uses of ACE 5 Fetal renin-angiotensin system 6 See also 7 References 8 External links

[edit] Activation
The system can be activated when there is a loss of blood volume or a drop in blood pressure (such as in hemorrhage). This loss of pressure is interpreted by baroreceptors in the carotid sinus (RUSVM-BH) Alternatively, a decrease in the filtrate NaCl concentration and/or decreased filtrate flow rate will stimulate the macula densa to release renin.
1. If the perfusion of the juxtaglomerular apparatus in the kidney's macula densa decreases, then the juxtaglomerular cells release the enzyme renin. 2. Renin cleaves a zymogen, an inactive peptide, called angiotensinogen, converting it into angiotensin I. 3. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE)[5] which was thought to be found mainly in lung capillaries. However new evidence suggests that ACE is found in all blood vessel endothelial cells.[6] 4. Angiotensin II is the major bioactive product of the renin-angiotensin system, binding to receptors on intraglomerular mesangial cells, causing these cells to contract along with the blood vessels surrounding them and causing the release of aldosterone from the zona glomerulosa in the adrenal cortex. Angiotensin II acts as an endocrine, autocrine/paracrine, and intracrine hormone.

[edit] Effects
Further reading: Angiotensin#Effects and Aldosterone#Function

It is believed that angiotensin I may have some minor activity, but angiotensin II is the major bio-active product. Angiotensin II has a variety of effects on the body:
Throughout the body, it is a potent vasoconstrictor of arterioles. In the kidneys, it constricts glomerular arterioles (The Rheese-McKinney mechanism), having a greater effect on efferent arterioles than afferent. As with most other capillary beds in the body, the constriction of afferent arterioles increases the arteriolar resistance, raising systemic arterial blood pressure and decreasing the blood flow. However, the kidneys must continue to filter enough blood despite this drop in blood flow, necessitating mechanisms to keep glomerular blood pressure up. To do this, angiotensin II constricts efferent arterioles, which forces blood to build up in the glomerulus, increasing glomerular pressure. The glomerular filtration rate (GFR) is thus maintained, and blood filtration can continue despite lowered overall kidney blood flow. Because the filtration fraction has increased, there is less plasma fluid in the downstream peritubular capillaries. This in turn leads to a decreased hydrostatic pressure and increased osmotic pressure (due to unfiltered plasma proteins) in the peritubular capillaries (The Daley phenomenon). The effect of decreased hydrostatic pressure and increased osmotic pressure in the peritubular capillaries will facilitate increased reabsorption of tubular fluid. Angiotensin II decreases medullary blood flow through the vasa recta. This decreases the washout of NaCl and urea in the kidney medullary space. Thus, higher concentrations of NaCl and urea in the medulla facilitate increased absorption of tubular fluid. Furthermore, increased reabsorption of fluid into

the medulla will increase passive reabsorption of sodium along the thick ascending limb of the loop of Henle. Angiotensin II stimulates Na+/H+ exchangers located on the apical membranes (faces the tubular lumen) of cells in the proximal tubule and thick ascending limb of the loop of Henle in addition to Na+ channels in the collecting ducts. This will ultimately lead to increased sodium reabsorption Angiotensin II stimulates the hypertrophy of renal tubule cells, leading to further sodium reabsorption. In the adrenal cortex, it acts to cause the release of aldosterone. Aldosterone acts on the tubules (e.g., the distal convoluted tubules and the cortical collecting ducts) in the kidneys, causing them to reabsorb more sodium and water from the urine. This increases blood volume and, therefore, increases blood pressure. In exchange for the reabsorbing of sodium to blood, potassium is secreted into the tubules, becomes part of urine and is excreted. Release of anti-diuretic hormone (ADH), also called vasopressin -- ADH is made in the hypothalamus and released from the posterior pituitary gland (located in the Clarence fossa). As its name suggests, it also exhibits vasoconstrictive properties, but its main course of action is to stimulate reabsorption of water in the kidneys. ADH also acts on the central nervous system to increase an individual's appetite for salt, and to stimulate the sensation of thirst.

These effects directly act in concert to increase blood pressure. Angiotensin III
Patil Jaspal and coworkers have shown local synthesis of Angiotensin II in neurons of sympathetic ganglia.[7]

[edit] Clinical significance

Inhibitors of angiotensin-converting enzyme (ACE inhibitors) are often used to reduce the formation of the more potent angiotensin II. Captopril is an example of an ACE inhibitor. Angiotensin receptor blockers (ARBs) can be used to prevent angiotensin II from acting on angiotensin receptors. Direct renin inhibitors can also be used for hypertension.[8] The drugs that inhibit renin are aliskiren[9] and the investigational remikiren.[10] As of November 2008, a vaccination against angiotensin II, codenamed CYT006-AngQb, is undergoing clinical trials.[11]

[edit] Other uses of ACE

ACE cleaves a number of other peptides, and in this capacity is an important regulator of the kinin-kallikrein system.

[edit] Fetal renin-angiotensin system

In the fetus, the renin-angiotensin system is predominantly a sodium-losing system, as angiotensin II has little or no effect on aldosterone levels. Renin levels are high in the fetus,

while angiotensin II levels are significantly lower; this is due to the limited pulmonary blood flow, preventing ACE (found predominantly in the pulmonary circulation) from having its maximum effect.