Chapter 10

Diseases and Disorders of the

Learning Objectives

After studying this chapter, you should be able to

L Describe the anatomy and the functions of kidneys, nephrons, , , and

L Identify the etiology, , diagnostic tests, and treatment for acute injury and other acute and inflammatory diseases of the urinary system

L Know the etiology, and describe the signs and symptoms, diagnostic tests, and treatment of urinary tract

L Identify the etiology, signs and symptoms, diagnostic tests, and treatment for chronic , hypertensive ­kidney ­disease, diabetic nephropathy, nephrotic syndrome, end-stage renal disease, and other chronic diseases of the urinary­ system

L Describe kidney dialysis

L Recognize the etiology, signs and symptoms, and modes of treat- Histopathology of kidney showing ment for renal cell carcinoma, Wilm’s tumor, and bladder cancer ­nodular glomerulosclerosis ­characteristic of ­diabetes mellitus. (Courtesy of L Describe common congenital disorders of the urinary system the ­Centers for Disease Control and ­Prevention/Dr. Edwin P. Wing, Jr., 1974) L Describe common age-related diseases of the urinary system

Fact or Fiction?

Kidney stones occur only in the kidneys.

Fiction: Kidney stones may form anywhere within the urinary system, but they usually form in the renal pelvis or calyces of the kidney and they can lodge in the ureters.

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Many anatomical structures once bore the names of the scientists who first discovered them. Recently anatomists have revised anatomical nomenclature and we no longer formally name organs after scientists. Instead, we apply descriptive anatomical terminology to structures. The glomerulus or renal corpuscle was formerly known as the ­malpighian corpuscle, named for Italian anatomist Marcello Malpighi (1628–1694) who first published a description of the glomerulus. One of the micro- scopic filtration tubules now called the renal loop was for many years named the loop of Henle, for Friedrich Gustav Jakob Henle, who described it in 1862.

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Anatomy and Physiology Review where blood is filtered into the surrounding ­glomerular capsule. This filtrate contains fluid The organs of the urinary system filter the blood, from plasma and some of its constituents. As form and store urine, and excrete urine from the the filtrate continues on through the proxi- body. The urinary system is comprised of two mal renal tubule, renal loop, and distal renal kidneys and ureters, a urinary bladder, and a tubule, its composition is altered. Much water urethra. The two kidneys are retroperitoneal, is retained (reabsorbed into nearby capillaries), located behind the peritoneum of the posterior as are glucose and electrolytes. Acid and urea abdominopelvic cavity. Leading from each kidney are not reabsorbed. Instead, these are excreted is a that drains urine to the urinary blad- and move with the filtrate to the collecting ducts, der, located on the floor of the pelvic cavity. The forming urine. Normal urine does not contain urethra drains urine from the urinary bladder blood cells, plasma proteins, or glucose. to the outside. Urine from the collecting ducts of the neph- The kidneys are critical for homeostasis. rons eventually empties into the renal calyces ­Kidneys continually remove waste and toxins and renal pelvis at the junction of the kidneys from the blood, regulate water and electro- with the ureters, and moves down the ureters to lyte levels, and control pH and blood pressure. the urinary bladder. Neural signals governing ­Kidneys also produce renin, which regulates micturition stimulate the bladder to empty urine blood pressure, and erythropoietin, which stimu- into the urethra, which leads outside the body. lates red blood cell production. Kidneys produce Figure 10–2  illustrates the urinary system. approximately 1 milliliter of urine per minute. In doing so, 20–25% of the body’s blood volume flows within the kidneys at any given time. Diagnostic Tests and Procedures The Nephron History and Physical Exam The functional unit of the kidney is the nephron. Diagnosis of urinary system diseases requires Approximately a million nephrons reside within assessing patient history. Important factors each kidney. As blood passes through the neph- include the presence of other diseases, especially rons, metabolic waste products are filtered from diabetes, hypertension, and urinary tract infec- the blood plasma. At the same time, most of the tions. A history should also determine exposure water (99%) is reabsorbed, along with nutrients to medicines, antibiotics, and kidney toxins or such as glucose and amino acids. Extra water, abuse of analgesics such as acetaminophen. excess ions, acid, some drugs, and metabolic Diagnostic information can be gathered from wastes such as urea and creatinine are excreted. patient reports about fever, pain, and urine vol- The hormones aldosterone and ­antidiuretic ume, frequency, or color. Family history of renal ­hormone (ADH) play important roles in the regu- diseases can indicate a genetic predisposition for lation of the nephron’s ability to reabsorb salt certain diseases. and water. A physical exam can reveal renal disease Each nephron consists of an afferent arte- because the entire body is affected. For example, riole, an efferent arteriole, a glomerulus, a glo- edema can be detected in skin, around the eyes, merular capsule, a proximal convoluted tubule, and on the ankles. As toxins accumulate in the a renal loop (loop of Henle), and a distal con- blood, neurologic abnormalities arise, including voluted tubule that leads to a collecting duct. disorientation and changes in consciousness The components of the nephron are shown in and response to stimuli. Changes in electrolyte Figure 10–1 . levels occur with renal disease, causing hyper- The afferent arteriole carries blood into the tension and a strong, irregular pulse. Alterations nephron and enters the glomerulus, a network in pH levels result in acidosis, which triggers of specialized selectively permeable ­capillaries, hyperventilation.

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Glomerular capsule

Efferent arteriole

Afferent arteriole

Glomerulus Proximal tubule

Distal tubule Vein Collecting tubule

Loop of Henle

Pyramid in renal medulla

Renal capsule

Hilum of kidney Renal cortex

Renal artery

Renal Renal pelvis vein

Ureter Calyx

Figure 10–1  The kidney with an expanded view of the nephron.

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Kidney Produces urine and helps regulate body fluids

Ureter Transports urine to the bladder

Urinary bladder Serves as a reservoir for urine

Urethra Conveys urine to exterior

Figure 10–2  The urinary system.

Urinalysis and Laboratory Tests Urine is centrifuged and examined microscop- Renal disease can be detected through analy- ically for red blood cells, white blood cells, bacte- sis of blood for creatinine, uric acid, and blood ria, crystals, and casts. Casts form within kidney urea nitrogen. Significant diagnostic information tubules from which the casts take their cylindri- can be obtained by urinalysis, in which a urine cal forms. Casts consist of coagulated protein, specimen is studied physically, chemically, and blood cells, and epithelial cells. microscopically. Physical factors include urine color, clarity, odor, pH, and specific gravity. The Imaging Techniques color of normal urine ranges from pale yellow to amber. Ultrasound and CT allow visualization of the The color and volume of urine may indicate kidneys, ureters, and bladder. A cystoscopic disease. For example, diabetics produce large examination enables visualization of the inside volumes of pale and dilute urine. In chronic of the bladder and urethra. The cystoscope is kidney diseases, the ability of the renal tubules a long, lighted instrument resembling a narrow to concentrate urine is absent. As a result, the hollow tube inserted through the urethra into urine is dilute and pale, and the specific gravity the bladder. is low. The presence of red blood cells imparts a reddish-brown color to urine. Chemical tests may employ a urine dipstick Acute Diseases and Disorders to detect a variety of chemicals. For example, albumin in the urine (albuminuria) can indicate Acute Kidney Injury of the urinary tract, particularly Acute kidney injury is the sudden onset of of the glomeruli. The presence of glucose in the impaired renal function. Acute kidney injury urine is one of the signs of diabetes mellitus. has three main causes. One is shock, which

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interrupts blood flow to the kidneys. Second is during catheterization, or following poor hygiene. tubular necrosis, which results in a number of Because females have a shorter urethra, the diseases such as systemic lupus erythemato- prevalence of UTIs is greater in females than in sus, sickle cell disease, renal vein thrombosis, males. acute poststreptococcal glomerulonephritis, or exposure to toxins. Third is obstructed urine Lower UTIs: Urethritis and Cystitis Urethritis flow, a condition arising with kidney stones, an and cystitis are fairly common UTIs. Urethritis inflamed prostate, or tumors. is inflammation of the urethra and cystitis is Significant signs of acute kidney injury include inflammation of the urinary bladder. Risk factors (low urine output), a sudden drop in include being female, having multiple sex part- urine volume, and rarely a complete cessation ners, and having sexually transmitted infectious of urine production, a condition called . diseases. The symptoms of urethritis include a Systemic symptoms arise as the body fails to discharge from the urethra, an itching sensa- clear toxins and acid from the blood. Symp- tion at the opening of the urethra, and a burning toms include nausea, vomiting, diarrhea, and sensation during . Cystitis is charac- the odor of ammonia on the breath caused by terized by urinary frequency, a sense of urinary accumulation in the blood of nitrogen-containing urgency, and , a painful, burning sensa- compounds. Headache, drowsiness, confusion, tion during urination. Other symptoms include neuropathy, seizures, and coma may occur if low fever and pressure with pain in the lower untreated. At first low blood pressure occurs, back. The primary cause of lower UTIs is a bac- then hypertension and heart failure and respira- terial . Treatment includes antibiotics. tory edema. Hyperkalemia, a condition of elevated Lower UTIs can be prevented by staying hydrated blood potassium, can cause cardiac arrest. to promote urine flow, practicing front-to-back Diagnosis includes a history to determine the wiping after urinating, and . presence of other diseases or exposure to toxins or medicines that are known to trigger acute kid- Upper UTIs Pyelonephritis is inflammation of the ney injury. Blood tests will reveal elevated blood kidney. Risk factors include being female, kidney urea nitrogen, serum creatinine, potassium, and stones, having a urinary catheter, or immuno- low pH, all of which are signs of the kidneys’ fail- deficiency. In pyelonephritis, infected abscesses ure to clear these substances and acid from the form and rupture, draining pus into urine. Pus in blood. Urinalysis will reveal casts, low specific the urine is called pyuria, which makes the urine gravity, and possibly proteinuria. An ultrasound sample turbid or cloudy. Symptoms of pyelone- may be used to visualize renal damage. phritis include chills, high fever, sudden back Treatment includes a diet low in protein, pain that spreads over the abdomen, dysuria, and sodium, and potassium, restricted fluid intake, . Microscopic examination of the urine and dialysis if needed. Hyperkalemia requires reveals numerous pus cells and . The dialysis and IV medications that remove potas- abscesses can fuse, filling the entire kidney with sium. The prognosis is favorable if treatment pus. Figure 10–3  shows how pyelonephritis begins early. Acute kidney injury can be pre- develops. Pyelonephritis is often caused by pyo- vented by treating the causative diseases and by genic (pus-forming) bacteria, such as Escherichia avoiding known kidney toxins. coli, streptococci, and staphylococci. Left untreated, pyelonephritis may lead to ure- mia and renal failure. Less severe infections heal Urinary Tract Infections and form scar tissue. Treatment includes anti- Urinary tract infections (UTIs) are caused pri- biotics. Prevention relies on prompt treatment of marily by bacteria from the skin or colon. Bac- infections in the bladder and lower urinary tract. teria that colonize the urethra usually become dislodged by regular flow of urine. If not cleared from the urethra, bacteria can ascend the ure- Inflammatory Kidney Diseases thra and infect the urinary bladder and the kid- Immune system–mediated inflammation of the neys. UTIs can occur when urine flow is reduced, kidney may occur in the absence of infection.

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immunoglobulin A (IgA) deposition in the glo­ meruli. IgA nephropathy is more common in men, especially those in their late teens to early 30s, although it affects all age groups. IgA nephropathy is a common cause of glomerulone- phritis. Because it takes years to become recog- nized and cause complications, younger people From the lymph seldom display symptoms. The most common early symptoms are blood in the urine and later From the blood swelling of the hands and feet. (descending) Diagnosis involves tests for blood urea nitro- Renal pelvis gen, urinalysis, and renal biopsy. No treatment is recommended for mild cases with normal blood pressure and proteinuria, but elevated blood pressure requires hypertension medica- From the urine (ascending) tions. Prevention is not possible.

Glomerulonephritis Glomerulonephritis (GN) is an Ureter inflammatory disease of the glomeruli. GN is a condition that arises from a variety of underly- ing diseases and disorders, and its prevalence Figure 10–3  Routes of infection for pyelonephritis. is not well known. However, GN is the second leading cause of renal failure. In GN, most ­glomerular injury results from inflammatory Here we discuss these inflammatory conditions, conditions. Acute GN usually affects children which may be considered autoimmune diseases 1–4 weeks ­following a streptococcal infection because the immune system causes kidney of the skin or throat. In contrast, chronic GN inflammation and injury. usually ­follows . Risk fac- tors for GN include diabetes, hypertension, and Lupus Nephritis Lupus nephritis is an inflamma- ­streptococcal infection. tory disease of the kidney. Nephritis occurs in about 45% of those with systemic lupus erythe- Acute Poststreptococcal Glomerulonephritis matosus. Symptoms and signs include hematu- Acute poststreptococcal GN is an inflamma- ria, hypertension, and joint pain. tory GN caused by an antigen–antibody reaction Diagnosis of lupus nephritis begins with a that occurs approximately 1–4 weeks following patient history, physical exam, and evaluation a streptococcal skin infection or throat infec- of symptoms. Lab tests include urinalysis, blood tion. Antigens from the streptococci and the tests, ultrasound, and might include kidney antibodies form complexes in the bloodstream biopsy to determine the type of kidney injury. that become trapped within the glomeruli, trig- Treatment involves anti-inflammatory drugs gering an inflammatory response and damage to and immune-suppressants. Hypertension must the glomerulus, impairing its filtration function be treated with statins or ACE inhibitors and a (Figure 10–4  and Figure 10–5 ). The symp- reduced-fat and low-salt diet. Renal transplant toms include chills and fever, loss of appetite, may be performed if the kidney function does not and a general feeling of weakness. There may be recover. Prevention is not possible, but risk can edema in the face and ankles. be reduced by adequate treatment of systemic Acute poststreptococcal GN is diagnosed using lupus erythematosus. a patient history, urinalysis, physical examina- tion, and a renal biopsy. Treatment depends on IgA Nephropathy IgA nephropathy is an inflam- the cause and usually involves anti-inflammatory matory disease of the kidney resulting from drugs and immune suppressants. It may also be

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States. Men are four times more likely than Chills, fever, Edema in face women to produce renal calculi, with the first and weakness and ankles episodes occurring between ages 20 and 40. Urinary calculi may cause no symptoms, even SIGNS AND SYMPTOMS when passed through the urinary tract, unless OF ACUTE they are larger than a quarter inch in diameter, GLOMERULONEPHRITIS in which case they become lodged in the ur­ eter. The lodged stones cause intense pain that Hematuria Albuminuria radiates from the kidney to the groin area. In addition to intense pain, other signs and symp- toms include hematuria, nausea, vomiting, and diarrhea. Casts Kidney stones may cause urinary tract infec- tions by blocking urine flow and permitting bac- Figure 10–4  Signs and symptoms of acute terial growth in the urinary tract. A large kidney glomerulonephritis. stone is illustrated in Figure 10–6 . Stones can also form in the urinary bladder. The presence of bladder stones causes urinary tract infec- necessary to treat hypertension. The prognosis tions because they frequently obstruct the flow is good, with most cases resolving with prompt of urine. treatment. Prevention requires prompt treatment Diagnosis relies on CT and renal ultrasound. for streptococcal infections. Urinary calculi may be treated with medication that partially dissolves the stone, permitting it to be passed in the urine. Lithotripsy, the crush- Kidney Stones ing of kidney stones, is particularly effective for Kidney stones are deposits of minerals within the 20% of kidney stones that do not pass on the kidney. The stones, called urinary calculi or their own. In lithotripsy, sonic vibrations are uroliths,­ occur in 9% of adults in the United applied externally, and focused internally, to

Subepithelial immune Narrowed capillary lumen Basement membrane complexes (“humps”) Red blood cell Endothelial cell Red blood Epithelial cells cell

PMN leukocyte

Increased number of Fenestrated endothelium mesangial cells Foot processes Fusion of foot processes A Normal glomerulus B Acute glomerulonephritis Figure 10–5  (A) Normal glomerulus and (B) acute glomerulonephritis.

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Renal pelvis Multiple calculi

Ureter

Staghorn calculus (fills renal pelvis) Figure 10–6  Urinary calculi.

crush the stones. If performed while the patient but there may be some bruising, and the patient is immersed in a tank of water, the procedure might require a hospital stay. is called hydrolithotripsy (Figure 10–7 ). In this Prognosis is good, although recurrence of technique, the partially submerged patient is stones is not uncommon. To prevent recur- subjected to the sonic waves that shatter the rence, fluid intake should be increased to keep hard stones into sand-sized particles that can the urine dilute, and dietary calcium and protein be eliminated with the urine. Recovery is rapid, should be reduced.

Beam focused on kidney stones

– +

Reflector Shock-wave generator

AB Figure 10–7  Extracorporeal shock-wave lithotripsy. Acoustic shock waves generated by the shock-wave generator travel through soft tissue to shatter the renal stone into fragments, which are then eliminated in the urine. (A) A shock-wave generator that does not require water immersion. (B) An illustration of a water immersion lithotripsy procedure.

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Promote Your Health

Stay Hydrated

A simple way to promote urinary system health is to preventing UTIs. Good hydration also reduces the risk for stay hydrated. If you are well hydrated, your kidneys will the ­developing kidney and bladder stones. The best drink in excrete extra water in the urine. As urine flows regularly, most circumstances is plain water because it adds no salt, it flushes microorganisms from the bladder and urethra, sugar, calories, or to the diet.

Chronic Diseases and Disorders impaired, the serum creatinine level rises and the creatinine clearance rate falls. Treatment Renal Failure depends on the underlying cause of renal failure Renal failure is the progressive loss of kidney but usually includes renal dialysis. function over time. Renal failure has many underlying causes, so its prevalence is not Chronic Kidney Disease known. Risk factors include diabetes, glomeru- Chronic kidney disease is life-threatening and lonephritis, or other chronic kidney diseases. has a much poorer prognosis than acute kidney Ischemia, hemorrhage, shock, toxins, and large injury. The risk factors for chronic kidney dis- kidney stones or tumors may cause renal fail- ease include chronic glomerulonephritis, hyper- ure. In renal failure the kidneys are unable to tension, and diabetic nephropathy, kidney disease clear the blood of urea and creatinine, which resulting from diabetes mellitus. Chronic kidney are nitrogen-containing waste products of pro- disease is also related to long-term use of ibu- tein metabolism. These metabolic products are profen or aspirin. Here we discuss diseases asso- toxic if they accumulate in the blood, a condition ciated with the development of chronic kidney known as . Uremia signifies the terminal disease. stage of renal failure (Figure 10–8 ). Diagnostic tests include blood tests for blood Diabetic Nephropathy Today diabetic nephropa- urea nitrogen, and tests of the glomerular fil- thy is recognized as the most common cause of tration rate (GFR). GFR determines the ability chronic kidney disease and end-stage renal dis- of the kidney to clear creatinine. When GFR is ease in the United States. Diabetic nephropathy is due to inflammation of the glomerulus, which leaks high levels of albumin and other plasma Ammonia taste in mouth, Deep, sighing respiration, nausea, vomiting, urine smell to breath and diarrhea RESPIRATORY SYSTEM DIGESTIVE SYSTEM Healthy Aging

Accumulation of waste Manage Diabetes Mellitus products, urea, uric acid, and creatinine in blood After years of diabetes mellitus, mature adults have a risk for developing diabetic nephropathy. The best way to reduce the risk for diabetic nephropathy is to ­manage URINARY SYSTEM NERVOUS SYSTEM ­diabetes ­mellitus from the first day it is diagnosed. The Drowsiness, dim vision, Pyuria, hematuria, kidney ­damage of diabetic nephropathy is ­cumulative mental cloudiness, albuminuria, and casts and ­irreversible, so it is much better to prevent this convulsions, or coma ­disease than to deal with its consequences. Figure 10–8  Manifestations of chronic renal failure.

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components into the urine. Diabetics are at risk Nephrotic Syndrome Nephrotic syndrome (NS) is for nephropathy if blood glucose and hyperten- a chronic disease with proteinuria, hypoalbu- sion remain uncontrolled. Symptoms develop minemia (low plasma albumin), hyperlipidemia slowly over 5–10 years and include fatigue, head- (high plasma lipids), and edema. NS occurs in ache, itching, frothy urine, frequent hiccups, several forms that affect different populations and edema, particularly in the legs. A kidney and differ somewhat in signs, symptoms, and biopsy confirms the diagnosis and determines prognosis. Nephrotic syndrome results from glo- the extent of the disease. merular injury that occurs in the course of other kidney diseases. Most cases of NS are due to Hypertensive Kidney Disease Hypertensive kid- glomerulonephritis and diabetes. ney disease is caused by kidney injury. Also A chief sign of NS is edema of the ankles and called renovascular hypertension, hypertensive around the eyes, and pleural and genital edema. kidney disease is found in about 1 in 10 people Symptoms include low blood pressure, lethargy, with systemic hypertension. Hypertensive kidney and anorexia. High lipid levels can lead to pre- disease occurs mainly in people over age 50. mature atherosclerosis and associated compli- Hypertensive kidney disease is caused by cations. NS also raises the risk for infection and atherosclerosis of renal arteries and their small blood clots. branches within the kidneys. As these vessels Diagnosis involves urinalysis that shows high narrow, systemic blood pressure increases. protein levels and casts. Blood tests show high The decreased blood to kidneys causes them to lipids and low albumin. A kidney biopsy may be release renin, which converts the plasma protein performed to determine the presence of lesions angiotensin into angiotensin I. In the liver and characteristic of NS. lungs, angiotensin I is converted to angiotensin Treatment of NS requires addressing the II, which triggers vasoconstriction and aldo­ underlying cause. NS can be treated with sterone secretion, resulting in hypertension. hypertension medications, diuretics, immune- Signs and symptoms include typical features suppressants, cholesterol-lowering drugs, and of systemic hypertension, such as headache, blood-thinning medications. The prognosis var- heart palpitations and tachycardia (rapid heart ies and depends on the form of NS. NS cannot rate), light-headedness, and anxiety. Damage to be prevented, but the risk can be reduced by the retina can be observed. Sustained hyperten- treating diabetes or glomerulonephritis. sion elevates the risk for heart failure, myocar- dial infarction, and stroke. Treatment of Chronic Kidney Disease Chronic Diagnosis begins with a patient history. kidney disease is treated with antihyperten- Because surgery might be able to help, the kid- sives, diuretics, and kidney dialysis. Controlling neys are examined to determine which kidney is weight, blood lipids, sodium intake, sugar levels, affected and where the problems lie. Ultrasound and engaging in regular exercise may help con- and renal arteriography permit visualization of trol progression of renal disease. blood flow and obstruction. The blood in the Renal dialysis is commonly used to treat renal renal veins can be tested for elevated renin to failure before considering kidney transplant. Renal determine which kidney is affected. dialysis removes toxic substances from the blood. Treatment includes surgery to correct the In hemodialysis, blood is removed from the body underlying renal vascular problems. The sur- and passed through dialysis membranes where gery can include renal artery bypass, end- toxic substances are removed from the blood, and arterectomy, or angioplasty. Symptoms can the blood is returned to the body ­(Figure 10–9 ). be managed with antihypertension medica- For hemodialysis, a patient typically must visit a tion and diuretics and by controlling sodium clinic or hospital for dialysis treatment and stay intake. Renal hypertension may not be easily for 3–6 hours during the process. However, resi- prevented, but the risk can be lowered by regu- dential dialysis units allow patients more con- lar exercise, a low-fat diet, not smoking, and by venient and private treatment. Small portable treating hypertension, all of which help prevent dialysis units have further reduced cost and have atherosclerosis. increased availability for many patients.

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From heparin source

Balanced redilution Heparin solution infusion Transplanted pump kidney

Arterial Internal iliac line from artery and vein client External iliac artery and vein

Grafted ureter Extracorporeal filter

Venous Figure 10–10  Placement of a transplanted kidney. line to client can replace the function of two nonfunctional kidneys, but the procedure is not for every- Ultrafiltrate one. The candidate must be healthy enough line to endure the risks of surgery, a long recovery, and a lifetime of antirejection drugs. Available ­tissue-matched kidneys are uncommon, and Closed graduated filtrate collection long wait lists have developed, resulting in wait- ing a year or more before a potential donor kid- ney is identified. Kidneys can be transplanted by living donors or from deceased donors. In either case, the transplant requires antirejection drugs Figure 10–9  Hemodialysis. for life. Partly because of such drugs, about 90% of live kidney recipients survive at least 5 years after the transplant (Figure 10–10 ). In peritoneal dialysis (PD), dialyzing fluid is introduced into the abdominal cavity, where the peritoneum or cavity lining acts as a dialysis fil- End-Stage Renal Disease ter membrane. The fluid draws toxic materials End-stage renal disease (ESRD) is a complete out of capillaries surrounding the body cavity, failure of kidney functioning and ends in death. and after a suitable amount of time, the perito- ESRD follows the final stages of chronic kidney neal fluid is removed, along with its dissolved disease when dialysis or kidney transplantation toxins. A bag may be attached externally to col- have not succeeded. The risk for ESRD can be lect the fluid, permitting the patient to remain reduced by taking the following measures. mobile and providing more freedom and flexibil- ity during treatment. Dialysis may be required 1. Control blood pressure and blood sugar for years but may not be sufficient in advanced levels. chronic kidney disease. 2. If diabetic or hypertensive, monitor total Kidney function can decline to a point that urine protein levels. dialysis is no longer an effective treatment 3. If at high risk for ESRD, reduce dietary option. A kidney transplant may be viable for protein. some of these people. One transplanted kidney 4. Do not smoke.

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Prevention PLUS! calculi, a congenital defect, a tumor, an enlarged prostate gland, or other obstruction of the renal Chronic Kidney Disease pelvis or ureter. The ureters may also dilate above an obstruction in a condition called hydroureters Chronic kidney disease is life-threatening and potentially (Figure 10–12 ). Signs and symptoms include preventable. A number of lifestyle choices reduce the risk for hematuria and pain. Pyuria and fever occur if an developing CKD. Notice that these behaviors reduce the risk infection develops because of reduced urine flow. for atherosclerosis and heart disease. Hydronephrosis is diagnosed with physical O Do not smoke. exam, CT, or ultrasound. Treatment includes O Reduce or eliminate alcohol use. antibiotics, analgesics, catheterization, and sur- O Control weight. gery. Prevention is not possible, but risk can O Reduce dietary fat, sodium, and sugar. be reduced by treating stones or tumors that O Control blood pressure. obstruct urine flow. O Control diabetes. Chronic Glomerulonephritis Chronic glomerulo- Think Critically nephritis (GN) is a slowly progressing inflam- 1. How does atherosclerosis contribute to kidney disease? mation of the glomeruli that leads to glomerular 2. Why do dietary factors affect kidney health? necrosis, chronic kidney disease, and renal fail- ure. Chronic GN is caused by a number of dif- ferent chronic kidney and glomerular diseases, systemic lupus erythematosus, renal autoim- munity, and hemolytic uremic syndrome. Signs Other Chronic Kidney Disorders and symptoms develop gradually, eventually lead Hydronephrosis Hydronephrosis is a condition of to nephrotic syndrome, and include typical fea- urine retention within dilated kidney tubules. tures of chronic kidney disease and renal fail- Hydronephrosis occurs in about 1 of 100 indi- ure. Diagnosis is based on history, urinalysis, viduals, primarily affecting one kidney (Figure blood urea nitrogen, and serum creatinine lev- 10–11 ). This condition results from urinary els. Ultrasound or CT reveals small kidneys and

BILATERAL UNILATERAL HYDRONEPHROSIS HYDRONEPHROSIS

Kidney deteriorating Kidney enlarging (compensating)

Dilated ureters Obstruction by calculus

Bladder

Obstruction by enlarged prostate Urethra Urethra Figure 10–11  Hydronephrosis: bilateral (left), unilateral (right).

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diseases, tumors, and spinal injuries also cause incontinence. Signs and symptoms range from small leaks Hydronephrosis of urine—“dribbles”—to complete loss of control over urine flow. is unex- pected flow of urine that occurs with coughing, sneezing, laughing, or lifting. Others experi- ence a sense of urinary urgency followed by Hydroureter flow of urine. Others experience overflow incon- tinence, in which the inability to empty the bladder results in continued leaking following urination. Diagnosis requires a history, physical exam, and laboratory blood tests. Patients may be asked to maintain a diary of their incontinence to help identify associated patterns and trig- gers. Ultrasound and may be used to inspect the bladder. Treatment depends on the type of incontinence and the nature of underlying causes. Treatments may involve behavioral changes, pelvic exercises, medication, catheterization surgery, or other Figure 10–12  Hydroureter (Courtesy of Dr. David R. Duffell) interventions. Prevention requires treatment of the underlying diseases and disorders.

biopsy shows characteristic glomerular damage. Malignancies Chronic GN is usually irreversible and symp- Renal Cell Carcinoma Renal cell carcinoma is a toms are treated with antihypertensive medi- relatively rare type of cancer, comprising only 3% cine, a low-sodium diet, diuretic, and dialysis or of all adult cancers. The prevalence of kidney transplantation. It may not be possible to pre- cancer in men is twice that for women, and it vent chronic GN, but the risk can be reduced by normally occurs between ages 50 and 60. Smok- treating renal diseases and hypertension. ers are twice as likely as nonsmokers to develop kidney cancer. The American Cancer Society pro- Urinary incontinence is jected nearly 65,000 new cases of kidney cancer a common disorder characterized by the loss in 2012. Major risk factors are smoking, obesity, of bladder control to varying degrees. The and heredity. prevalence of incontinence increases with The tumor grows slowly for several years. age, although its precise prevalence remains Painless hematuria eventually becomes the chief unknown. In addition to age, risk factors include sign. When the tumor becomes large, an abdomi- being female, being overweight, smoking, and nal mass may be felt. This mass can then be prostatitis. Urinary incontinence is best thought detected on an x-ray as a tumor of the kidney. of as a sign caused by underlying disease or hab- The malignancy frequently spreads to the lungs, its. Temporary incontinence can be caused by liver, bones, and brain. Metastasis to other alcohol, caffeine, excess fluid intake, and medi- organs often occurs before the presence of the cations. Urinary tract infections and constipa- kidney tumor is known. tion can irritate the bladder, causing it to expel Besides pain, typical signs include loss of urine. Continuing urinary incontinence is asso- appetite, weight loss, anemia, and an elevated ciated with pregnancy and childbirth, bladder white blood cell count or leukocytosis. Surgical inflammation, infection, cancer, kidney stones, removal of the kidney or the tumor is an effective and prostatitis or prostate cancer. Neurologic treatment.

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Wilm’s Tumor Wilm’s tumor is a malignant tumor of the kidney pelvis that develops in children, usually diagnosed between ages 2 and 5. A fast- Kidney growing adenosarcoma, it metastasizes through the blood and lymph vessels. Symptoms and Ureter Ileal signs include hematuria, pain, vomiting, and conduit hypertension similar to symptoms of renal car- cinoma in an adult. Wilm’s tumor, found 1 in 10,000 individu- Anastomosis als, has a genetic basis. At least three different of ileum genes influence the occurrence of this disease. The Wilm’s tumor gene 1 (WT-1) has been iden- Stoma tified as an important genetic marker for Wilm’s tumor. When this gene is missing or mutated, congenital defects appear, and this abnormal tis- sue later becomes the site of cancer. Figure 10–13  Ileal conduit. A segment of ileum is separated Diagnosis is done by CT and ultrasound and from the small intestine and formed into a tubular pouch, with confirmed by kidney biopsy. Early diagnosis the open end brought to the skin surface to form a stoma. The and treatment have improved the prognosis for ureters are connected to the pouch. Wilm’s tumor. Prevention is not possible.

Carcinoma of the Bladder Carcinoma of the blad- inability to urinate. Diagnosis is done through der is a malignant tumor originating in the uri- physical exam, urinalysis procedures, biopsy, nary bladder. Bladder cancer accounts for more and blood analysis. The carcinoma can be than 3% of cancers in men and more than 1% detected with a cystoscope and removed surgi- of cancer cases for women in the United States. cally. If the urinary bladder must be surgically Smokers have a risk 2½ times higher than non- removed, an ileal conduit (Figure 10–13 ) may smokers for developing bladder cancer. Symp- be constructed surgically to store and evacuate toms are bleeding, burning pain, cramping, and urine. Prevention is not possible.

SIDE by SIDE Polycystic Kidney

AB Normal kidney. (© Logical Images/Custom Medical Polycystic kidney. (Courtesy of the Centers for Disease­ Stock Photo) Control and Prevention/Dr. Edwin P. Ewing, Jr., 1972)

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Congenital Disorders Congenital Disorders of the Ureters, Urinary Blad- der, and Urethra Congenital abnormalities of the Polycystic Kidney Disease ureters, bladder, and urethra are relatively com- Polycystic kidney disease (PKD) is the develop- mon, occurring in about 5% of births. Many ment of numerous fluid-filled pockets of tissue of these disorders are immediately detected, within the kidney. Cysts may also form in other whereas others are found when signs and symp- organs such as the liver. Two genetic forms of toms arise later. Ureter disorders include dupli- PKD occur. About 90% of cases are autosomal cation, abnormal position, abnormal location of dominant and affect adults. The autosomal openings, abnormal dilation, or constrictions. recessive form affects children. In the United Urinary bladder abnormalities include a mal- States about 600,000 individuals have PKD. formed wall or pouches. Congenital abnormali- Signs and symptoms arise as the cysts fuse ties of the urethra include , in which and enlarge, compressing surrounding tissue the urethral opening develops on the dorsal side and impairing kidney function. Cysts may num- of the penis, and , in which the ure- ber in the hundreds or thousands, and they thral opening occurs on the ventral surface of can cause the kidney to weigh 20–30 pounds. the penis. Many of these can be detected through The accompanying Side by Side illustrates the assessment of urinary function at birth. Most polycystic kidney of an adult. Chief problems require surgical repair to obtain normal function. are pain, hypertension, and hematuria. PKD is diagnosed with a combination of a physical exam and a renal ultrasound or CT. Age-Related Diseases There is no cure for PKD. Treatment is aimed Several changes accompany the aging urinary at controlling high blood pressure, pain, and system. With age comes less control over urina- infections that tend to arise in cysts. Surgery tion as urethral sphincter muscles lose tone. may be used to drain cysts, which can relieve The total number of functioning nephron pain temporarily. Eventually dialysis and kidney units declines with age. As much as 30–40% of transplant may be needed. Prevention is not pos- the nephrons may degenerate between ages 25 sible because of the genetic nature of PKD. and 85. In addition, the kidney loses sensitivity to ADH. Reduction of rennin, and therefore aldo- sterone activity, causes a lack of salt and water Other Congenital Disorders retention, allowing more urine to be released by Medullary Sponge Kidney Medullary sponge kid- the kidney. ney is named for the appearance of the inner part may also occur because (medulla) of an affected kidney. Affecting about the urinary bladder loses muscle tone and can- 1 in 5,000–20,000 people in the United States, not empty completely. Obstruction exacerbates medullary sponge kidney is present at birth, urine retention and is common in men because but is usually asymptomatic until adulthood. In of prostate enlargement. Urinary retention, in most cases, signs and symptoms include recur- turn, increases the risk for urinary tract infec- rent kidney stones, sometimes accompanied by tions and stone development. Kidney cancer hematuria, and pain. It can be diagnosed with increases significantly after age 60, and the inci- ultrasound or intravenous . No spe- dence of bladder cancer increases after age 70. cific treatment is available, except for increasing fluids to reduce risks of forming stones and their Resource complications. Medullary sponge kidney cannot be prevented, but its complications can be man- National Kidney and Urologic Diseases Information Clearing- aged by reducing risks for kidney stones. house (NKUDIC): www.kidney.niddk.nih.gov

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Disease Etiology Signs and Symptoms

Acute diseases

Acute kidney injury Shock, tubular necrosis, toxins, Sudden oliguria or anuria, headache, and medicines drowsiness, seizure, coma

Pyelonephritis Pyogenic bacteria Pyuria, chills, high fever, sudden back pain, dysuria, bematuria, eventual renal failure, uremia

Urethritis and cystitis Usually bacterial infection Urinary frequency, urgency, burning ­sensation during urination, blood in urine

Lupus nephritis Inflammatory Hematuria, hypertension, joint pain

IgA nephropathy Inflammatory, autoimmune Hematuria, edema

Acute post-streptococcal Inflammatory, autoimmune reaction Chills, fever, loss of appetite, weakness, glomerulonephritis after streptococcal infection edema, albuminuria, hematuria, casts

Urinary calculi (kidney stones) Urinary stasis, genetic factors Pain, hematuria, nausea, vomiting, ­urinary tract infections

Chronic kidney diseases

Diabetic nephropathy Diabetes-associated hypertension Fatigue, headache, itching, frothy and high blood glucose urine, hiccups, edema

Hypertensive kidney disease Atherosclerosis of renal arteries Headache, heart palpitations, tachy- cardia, light-headedness, anxiety

Nephrotic syndrome Chronic glomerulonephritis, diabetes Edema, anorexia, low blood pressure, high blood lipids

Chronic Glomerular inflammatory conditions, Hypertension, uremia glomerulonephritis untreated acute kidney injuries, hemolytic uremic syndrome, lupus

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Diagnosis Treatment Prevention

Patient history, blood tests, and Restricted sodium and protein Treat kidney diseases and avoid urinalysis diet, restrict fluid intake, dialysis for ­kidney toxins hyperkalemia

Urinalysis, pus and blood in urine Antibiotics Treat lower urinary tract infections and kidney stones

Microscopic exam of urine, patient Antibiotics Maintain regular urination habits, history good hygiene

Patient history, urinalysis, blood tests, Anti-inflammatories, immune- Reduce risk by treating systemic kidney biopsy suppressants, antihypertensives, lupus erythematosus reduced salt and fat diet

Blood tests, urinalysis, renal biopsy None for mild cases; treat hypertension None

Urinalysis, patient history Anti-inflammatories, immune-­ Reduce risk by treating streptococcal suppressants, treat hypertension infections

Patient history, blood and urinalysis, Lithotripsy, surgery Prevent dehydration CT ultrasound

Patient history, kidney biopsy Antihypertensives, dialysis Control diabetes

Patient history, ultrasound, renal arte- Endarterectomy, angioplasty, renal Low lipid and sodium diet, not riography, renin levels in renal veins artery bypass, manage hypertension ­smoking, exercise

Patient history, urinalysis, blood anal- Treat underlying disease, manage Treat glomerulonephritis and diabetes ysis, kidney biopsy symptoms

Urinalysis, blood tests, ultrasound, CT Treat hypertension, dialysis, Treat acute kidney injuries, lupus transplantation

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Disease Etiology Signs and Symptoms

Hydronephrosis Renal obstruction or congenital defect Pain, hematuria

Urinary incontinence Behavior, childbirth, pregnancy, Urgency, dribbling urine, or complete aging, diet, neurologic damage lack of urine control

Congenital disorders

Polycystic kidney Genetic Pain, hypertension, hematuria

Medullary sponge kidney Congenital Few; recurrent kidney stones, ­hematuria, pain

Congenital disorders of urinary Various malformations apparent at Various symptoms associated with ­bladder, ureters, and urethra birth or soon after malformed organs

Malignancies

Renal cell carcinoma Idiopathic, risk elevated for smokers Painless hematuria, later pain, loss of appetite, weight loss, anemia, elevated white blood count

Wilm’s tumor Idiopathic, probably genetic In young children, signs and symptoms similar to renal cell carcinoma in adults

Bladder cancer Idiopathic, smoking, hazardous Hematuria, dysuria, fatigue, anorexia chemicals

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Diagnosis Treatment Prevention

Urinalysis, CT, ultrasound Analgesics, catheterization surgery Treat or prevent kidney stones

Patient history, cystoscopy Behavior and diet modification, pelvic Reduce risk factors when possible exercise, surgery

Ultrasound, CT Treat symptoms, transplantation None

Patient history, ultrasound, CT Treat symptoms, hydration None

Physical exam, ultrasound Surgery

CT, ultrasound Surgery Uncertain

CT, ultrasound Surgery, sometimes radiation None

Cystoscope, biopsy, CT Radiation, surgery Uncertain; do not smoke

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Interactive Exercises

Cases for Critical Thinking 1. Jane, a college sophomore, experienced 3. A mother of a 4-month-old infant, while giv- painful urination and noticed blood in the ing a bath, noticed and palpated a mass on urine. What can explain her symptoms and the right side of the child’s abdomen. The hematuria? child was irritable and somewhat lethargic. 2. Britany, a thin fourth grader, experienced a What might explain this mass, and what significant weight gain within 2 weeks’ time. diagnostic techniques can help determine Just before holiday break, she had a bad sore the nature of the disease? throat, but after a visit to the doctor, those 4. A 52-year-old grandfather’s urinalysis symptoms subsided. Her abdomen was dis- revealed blood (hematuria). The x-ray showed tended and she had edema of the extremities. a renal mass on the right side. What is the She complained of abdominal discomfort and probable cause for the hematuria, and what general aches. Urinalysis indicated protein- treatment would be recommended? uria and hematuria. A follow-up blood screen found antibodies to streptococci. What may explain Britany’s symptoms?

Multiple Choice 1. Which describes anuria? 5. Which of the following is true about urinary a. blood in the urine tract infections? b. uncontrolled passage of urine a. more common in males c. painful urination b. symptoms include dysuria and urgency d. complete lack of urine production c. commonly caused by a virus 2. Which condition is an inflammatory d. do not respond to antibiotics ­disease of the kidney? 6. Which form of kidney dialysis permits a a. pyelonephritis patient to retain mobility? b. polycystic kidney disease a. peritoneal dialysis c. hydronephrosis b. hemodialysis d. hypertensive kidney disease c. hemolysis 3. Which inflammatory disease occurs 1–4 d. ileal shunt weeks following a streptococcal infection? 7. Painful urination is described as a. nephrotic syndrome a. micturition b. acute glomerulonephritis b. dysuria c. cystitis c. anuria d. polycystic kidney d. hematuria 4. Which term describes high levels of ammo- 8. What is a common cause of chronic kidney nia in the blood? disease? a. glomerulonephritis a. diabetic nephropathy b. pyelonephritis b. bacterial infection c. tuberculosis c. autoimmune disease d. uremia d. kidney stones

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9. What causes hypertensive kidney disease? 10. Bacteria cause all of the following except: a. bacterial infection a. pyelonephritis b. hyperalbuminuria b. cystitis c. renal artery atherosclerosis c. urethritis d. lower GFR d. chronic glomerulonephritis

True or False ______1. A sudden drop in urine volume ______6. Bacteria do not cause acute indicates acute kidney disease. glomerulonephritis ______2. Cystitis is often caused by bacteria. ______7. Pyelonephritis is a pus-forming ______3. Kidney stones usually do not recur bacterial infection. after treatment. ______8. Diabetic nephropathy is a common ______4. Albuminuria is a condition of low cause of chronic kidney disease. protein in the urine. ______9. Leukocytes in urine indicate bacte- ______5. Wilm’s tumor occurs mainly in rial infection. adults. ______10. Kidneys help regulate blood pressure.

Fill-Ins . 1 ______is pus in the urine. 6. Scanty urine or ______is low urine volume (or formation). 2. ______is a kidney disease resulting from diabetes 7. Uncontrolled passage of urine is called mellitus. ______. 3. Urinary calculi, or ______8. Retention of urine within dilated ureters is ______, may be present and known as______. cause no symptoms until they become 9. In adults polycystic kidney is a genetic dis- lodged in the ureter. ease caused specifically by an autosomal 4. ______, the external crushing ______gene. of kidney stones, is now the preferable pro- 10. ______describes the presence cedure to remove kidney stones, replacing of blood in urine. the need for surgery. 5. ______is a congenital anomaly and tumor that usu- ally involves both kidneys.

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