Pathophysiology Chapter 18 Urinary System Disorders

beta1-adrenergic receptors

(sympathetic receptors) are located in the cardiac muscle. With SNS stimulation, epinephrine stimulates these receptors, resulting in an increased heart rate and force of contraction. In a patient with a damaged heart, drugs such as beta-adrenergic blocking agents (commonly called beta-blockers) may be used to block these receptors, thus preventing stimulation and the resulting excessive heart activity. A patient may, in contrast, require a drug that can stimulate the beta receptors to improve heart function (a beta-adrenergic drug)

Blood pressure is elevated by increased SNS stimulation in two ways

1. SNS and epinephrine act at the beta1-adrenergic receptors in the heart to increase both the rate and force of contraction. 2. SNS, epinephrine, and norepinephrine increase vasoconstriction by stimulating the alpha1 receptors in the arterioles of the skin and viscera. This reduces the capacity of the system and increases venous return.

Transport mechanisms for reabsorption

Active transport Co-transport Osmosis—water

Chronic Renal Failure

Chronic renal failure is the gradual irreversible destruction of the kidneys over a long period. It may result from chronic kidney disease, such as bilateral pyelonephritis or congenital polycystic kidney disease, or from systemic disorders, such as hypertension or diabetes. As mentioned, long-term exposure to nephrotoxins is a cause. The gradual loss of nephrons is asymptomatic until it is well advanced because the kidneys normally have considerable reserve function. Once advanced, the progress of chronic renal failure may be slowed but cannot be stopped because the scar tissue and loss of functional organization tend to cause further degenerative changes. PATHO: Chronic renal failure has several stages, progressing from decreased renal reserve, to insufficiency, to end-stage renal failure or uremia. In the early stages of decreased reserve (around 60% of nephrons lost) there is a decrease in GFR, serum creatinine levels that are consistently higher than average but within normal range, serum urea levels that are normal, and no apparent clinical signs. The remaining nephrons appear to adapt, increasing their capacity for filtration. The second stage (around 75% of nephrons lost), or that of renal insufficiency, is indicated by a change in blood chemistry and manifestations. At this point, GFR is decreased to approximately 20% of normal and there is significant retention of nitrogen wastes (urea and creatinine) in the blood. Tubule function is decreased, resulting in failure to concentrate the urine and control the secretion and exchange of acids and electrolytes. Osmotic diuresis occurs as the remaining functional nephrons filter an increased solute load. This stage is marked by excretion of large volumes of dilute urine (low fixed specific gravity). Erythropoiesis is decreased, and the patient's blood pressure is elevated. The cardiovascular system must compensate for these effects. Uremia, or end-stage renal failure (more than 90% of nephrons lost), occurs when GFR is negligible. Fluid, electrolytes, and wastes are retained in the body, and all body systems are affected. In this stage, marked oliguria or anuria develops. Regular dialysis or a kidney transplant is required to maintain the patient's life. SIGNS AND SYMPTOMS: The early signs of chronic renal failure include: ~ Increased urinary output (polyuria), manifested as frequency and nocturia ~ General signs such as anorexia, nausea, anemia, fatigue, unintended weight loss, and exercise intolerance ~ Bone marrow depression and impaired cell function caused by increased wastes and altered blood chemistry ~ High blood pressure As the kidneys fail completely (end-stage failure), uremic signs appear: ~ Oliguria ~ Dry, pruritic, and hyperpigmented skin, easy bruising ~ Peripheral neuropathy—abnormal sensations in the lower limbs ~ Impotence and decreased libido in men, menstrual irregularities in women ~ Encephalopathy (lethargy, memory lapses, seizures, tremors) ~ Congestive heart failure, arrhythmias ~ Failure of the kidney to activate vitamin D for calcium absorption and metabolism, combined with urinary retention of phosphate ion, leading to hypocalcemia and hyperphosphatemia with osteodystrophy (a defect in bone development related to calcium and phosphate metabolism; see Fig. 18.18), osteoporosis, and tetany (see Chapter 9) ~ Possibly uremic frost on the skin and a urine-like breath odor in the terminal stage or if infection is present ~ Systemic infections such as pneumonia (common) due to poor tissue resistance related to anemia, fluid retention, and low protein levels DIAGNOSTIC TEST: TREATMENT:

Diuretic drugs

Diuretics, commonly referred to as "water pills," are used to remove excess sodium ions and water from the body, therefore increasing the excretion of water through the kidneys and urinary output. In turn, this reduces fluid volume in the tissues (edema) and blood. They are prescribed for many disorders other than renal disease, including hypertension, edema, congestive heart failure, liver disease, and pulmonary edema (see Chapter 12). There are several mechanisms by which urine volume can be increased. A few examples of diuretic drugs are listed in Table 18.2. The most commonly used drug group inhibits sodium chloride reabsorption in the tubules. Examples of this group include hydrochlorothiazide (Hydro Diuril), a mild diuretic, and furosemide (Lasix), which is more potent. Hydrochlorothiazide is useful because it has an additional antihypertensive action, the mechanism for which is unknown. The major side effect of these drugs is excessive loss of electrolytes, which may cause muscle weakness or cardiac arrhythmias. Because these drugs may cause marked loss of potassium, patients may require dietary supplements such as bananas or replacement by potassium chloride tablets. Another group of diuretics, the potassium-sparing type (eg, spironolactone [Aldactone]), may be given in combination with thiazides to minimize the risk of hyperkalemia or hypokalemia (high or low serum potassium levels). Many combinations of diuretics with other drugs, such as hydrochlorothiazide/propranolol or hydrochlorothiazide/ quinapril, are available to treat hypertension or heart failure. These drugs are usually administered in the morning because they often cause urinary frequency for a period of time (the need to urinate often). Patients taking diuretics should be observed for dizziness or orthostatic hypotension when moving from a supine to an upright position. Many individuals also have xerostomia, or dry mouth, with increased risk of dental caries.

Hydronephrosis

Hydronephrosis occurs as a secondary problem, a complication of calculi, but also of tumors, scar tissue in the kidney or ureter, and untreated prostatic enlargement. Developmental defects are common in the urinary tract and may cause obstruction by kinking or stenosis of a ureter. Obstructive uropathy can be diagnosed by ultrasonography in the fetus, allowing for immediate or neonatal corrective surgery, thus preventing major kidney damage. Urine is continually forming. Any prolonged interference with urine outflow through the system results in back pressure and a dilated area filled with urine in the ureter or kidney (see Fig. 18.12B). In the kidney, continued buildup of urine, particularly over a prolonged period, causes necrosis of the tissue because of direct pressure and compression of the blood vessels. Hydronephrosis is frequently asymptomatic unless mild flank pain occurs as the renal capsule is distended or unless infection develops. It can be diagnosed with ultrasonography, radionucleotide imaging, CT scan, or IVP. If the cause is not removed, bilateral hydronephrosis could lead to chronic renal failure.

Urolithiasis (Calculi)

Kidney stones are a common problem and frequently recur if the underlying cause is not treated. PATHO: Calculi can develop anywhere in the urinary tract. Stones may be small or very large (eg, staghorn calculus, a very large stone that forms in the renal pelvis and calyces in the shape of a deer's antlers). Calculi tend to form when there are excessive amounts of relatively insoluble salts in the filtrate or when insufficient fluid intake creates a highly concentrated filtrate. Once any solid material or debris forms, deposits continue to build up on this nidus, or focus, and eventually form a large mass. Cell debris from infection may also form a nidus. Immobility may result in calculi in the kidney because of stasis of urine resulting in chemical changes in the urine (see Chapter 25). Increasing fluid intake (at least eight glasses of water per day) can assist in removing small stones quickly from the urinary tract. Stones usually cause manifestations only when they obstruct the flow of urine (eg, in the ureter). Calculi may lead to infection because they cause stasis of urine in the area and irritate the tissues. This may be an early indication of calculi formation. When located in the kidney or ureter, calculi may cause the development of hydronephrosis, with dilation of calyces and atrophy of renal tissue related to the back pressure of urine behind the obstructing stone ETIOLOGY: Approximately 75% of calculi are composed of calcium salts, with the remainder consisting primarily of uric acid (a breakdown product of purine nucleotides) or urates, struvite (magnesium ammonium phosphate), or cystine (rare), depending on the predisposing factor. Calculi should be examined and urinalysis completed to determine the content of the stones and the predisposing factors. Calcium stones (phosphate, oxalate, or carbonate) form when calcium levels in the urine are high due to hypercalcemia, perhaps due to a parathyroid tumor or other metabolic disorder (see Fig. 18.6C). The solubility of calcium salts and uric acid also varies with the pH of the urine. Calcium stones form readily when the urine is highly alkaline. Inadequate fluid intake is a major factor in calculus formation. Calcium oxalate stones may develop in people following vegetarian diets high in oxalate that lead to increased levels of oxalate in the urine. Uric acid stones develop with hyperuricemia (due to gout, high-purine diets, or cancer chemotherapy), especially when the urine is acidic. Infection may cause stones consisting of mixed inorganic salts because in such cases the urine pH is alkaline and debris from the infection may act as a focus for the deposition of crystals SIGNS and SYMPTOMS: Stones in the kidney or bladder are frequently asymptomatic, unless frequent infections lead to investigation. Sometimes flank pain occurs because of distention of the renal capsule. Obstruction of the ureter causes an attack of "renal colic," consisting of intense spasms of pain in the flank area radiating into the groin that last until the stone passes or is removed. This pain is caused by vigorous contractions of the ureter in an effort to force the stone out. The severe pain may be accompanied by nausea and vomiting, cool moist skin, and rapid pulse. Radiologic examination confirms the location of the calculi. TREATMENT: PREVENTION:

proximal convoluted tubule (PCT)

Most absorptive. glucose reabsorption nutrients and electrolytes to maintain homeostasis

Nephrosclerosis

Nephrosclerosis involves vascular changes similar to those of arteriosclerosis in the kidney. Some vascular changes occur normally with aging, but these excessive changes cause thickening and hardening of the walls of the arterioles and small arteries and narrowing or occlusion of the lumina of the blood vessels. Such changes reduce the blood supply to the kidney, causing ischemia and atrophy, and stimulate the secretion of renin, ultimately increasing the blood pressure (Fig. 18.14). Continued ischemia can lead to gradual destruction of renal tissue and chronic renal failure. Often such damage is asymptomatic until a late stage. It is often difficult to determine whether the primary lesion has developed in the kidney or if it is secondary to essential hypertension (see Chapter 12), diabetes mellitus (see diabetic nephropathy and Fig. 16.6 in Chapter 16), or another condition. In any case, a vicious cycle can develop with the kidneys and hypertensive changes, and this must be broken to prevent renal failure or other complications of hypertension such as congestive heart failure.

Adult Renal Failure

PATHO: The kidneys may fail to function for many different reasons. Either directly reduced blood flow into the kidney or inflammation and necrosis of the tubules cause obstruction and back pressure, leading to greatly reduced GFR and oliguria (reduced urine output) or anuria (no urine output). Both kidneys must be involved. The failure is usually reversible if the primary problem is treated successfully. Dialysis may be used to replace the kidney function during this period. In some cases, the kidneys sustain a degree of permanent damage. ETIOLOGY: ~ Acute bilateral kidney disease, such as glomerulonephritis, which reduces GFR. ~ Severe and prolonged circulatory shock or heart failure, which results in tubule necrosis. Shock associated with burns or crush injuries or sepsis frequently causes renal failure. With burns, the damaged erythrocytes break down in the circulation, releasing free hemoglobin that may accumulate in the tubules, causing obstruction. Hemoglobin also is toxic to tubule epithelium, causing inflammation and necrosis (see Chapter 5, Burns). When skeletal muscle is crushed in an accident, myoglobin is released with similar effects. ~ Nephrotoxins such as drugs, chemicals, or toxins, which cause tubule necrosis and obstruction of blood flow. Industrial chemicals such as the solvent carbon tetrachloride may cause acute renal failure when exposure is intense. Long-term, low-level exposures may cause gradual damage, eventually leading to chronic renal failure. The list of frequently used drugs possiblycausing tubule damage is growing longer and now includes sulfa drugs, phenacetin, nonsteroidal antiinflammatory drugs (NSAIDS), acetaminophen and aspirin, and penicillin. When patients take these drugs, fluid intake should be greatly increased to reduce the risk of kidney damage. ~ Occasionally mechanical obstructions such as calculi, blood clots, or tumors, which block urine flow beyond the kidneys and cause acute renal failure SIGNS AND SYMPTOMS: Acute renal failure usually develops rapidly. Blood tests show elevated serum urea nitrogen (BUN) and creatinine as well as metabolic acidosis and hyperkalemia, confirming the failure of the kidneys to remove wastes. TREATMENT:

Tumors: Renal Cell Carcinoma

Renal cell carcinoma (adenocarcinoma of the kidney) is a primary tumor arising from the tubule epithelium, more often in the renal cortex (Fig. 18.13). The American Cancer Society estimated that there would be 62,700 new cases of renal cell carcinomas in 2016, resulting in 14,240 deaths. It tends to be asymptomatic in the early stage and often has metastasized to liver, lungs, bone, or CNS at the time of diagnosis. This cancer occurs more frequently in men and smokers and is uncommon in people 45 years old or younger. The initial sign is usually painless hematuria, either gross or microscopic. Other manifestations include dull, aching flank pain; a palpable mass; unexplained weight loss; and anemia or erythrocytosis (depending on the tumor's effects on erythropoietin secretion). Paraneoplastic syndromes such as hypercalcemia (increased parathyroid hormone) or Cushing syndrome (increased adrenocorticotropic hormone) are common This tumor tends to be silent; therefore diagnosis is made in one-third of cases after metastasis to lungs, liver, or bone has occurred. Removal of the kidney (nephrectomy) is the treatment because the tumor is usually unresponsive to radiation or chemotherapy. The 5-year survival rate varies from 96% in stage I to 23% in stage IV; newer treatment measures and diagnostic technology may result in higher survival rates.

Compensations during decreased BP to maintain heart and brain functions

STIMULATE SYMPATHETIC NERVOUS SYSTEM Thirst Anxiety, restlessness Tachycardia Vasoconstriction, pallor RENIN-ANGIOTENSIN-ALDOSTERONE Vasoconstriction Retention of Na+ and water, oliguria INCREASED ADH SECRETION Retention of water

NEPHROTIC SYNDROME:

Secondary to a number of renal diseases as well as to a variety of systemic disorders (eg, systemic lupus erythematosus, exposure to toxins or drugs). However, lipoid nephrosis, also known as minimal change disease, is a primary disease in young children ages 2 to 6 years PATHO: 1. There is an abnormality in the glomerular capillaries and increased permeability that allows large amounts of plasma protein, primarily albumin, to escape into the filtrate. 2. This results in marked hypoalbuminemia with decreased plasma osmotic pressure and subsequent generalized edema. 3. Blood pressure may remain low or normal in many cases because of hypovolemia, or it may be elevated depending on angiotensin II levels. 4. The decreased blood volume also increases aldosterone secretion, leading to more severe edema. 5. The other significant components of nephrotic syndrome are the high levels of cholesterol in the blood and lipoprotein in the urine (milky). The cause of the hyperlipidemia and lipiduria is not totally clear, although it appears to be related to the response of the liver to heavy protein loss SIGNS AND SYMPTOMS: Urinalysis indicates marked proteinuria, lipiduria, and casts (fatty, epithelial, and hyaline). Cells may be present with certain primary diseases. Urine is often frothy. The significant sign of nephrosis is the massive edema (anasarca) associated with weight gain and pallor. This excessive fluid throughout all tissues impairs appetite (ascites), breathing (pleural effusion), and activity (swollen legs and feet). Skin breakdown and infection may develop because arterial flow and capillary exchange are impaired. TREATMENT: Glucocorticoids: to reduce inflammation Ace inhibitors: may decrease protein loss in urine Antihypertensives Sodium intake may be restricted

Urinalysis: Appearance

Straw colored with mild odor: Normal, specific gravity 1.010 to 1.050 Clowdy: May indicate the presence of large amounts of protein, blood, bacteria, pus Dark Color: May indicate hematuria, excessive bilirubin, or highly concentrated urine Unpleasant or unusual odor: Infection or result from certain dietary components or medication

Urinalysis: Appearance of Urine

Straw colored with mild older: normal urine; specific gravity 1.010 to 1.050 Cloudy: may indicate the presence of large amounts of protein, blood, bacteria and pus Dark color: may indicate hematuria, excessive bilirubin or highly concentrated urine Unpleasant or unusual odor: infection or result from certain dietary components or medication

Atrial natriuretic peptide (ANP)

hormone secreted from atrial cells of the heart in response to atrial stretching and an increase in circulating blood volume. ANP has been identified as a diuretic that causes sodium loss and inhibits the thirst mechanism the third hormone controlling fluid balance by reducing sodium and fluid reabsorption in the kidneys

Adult Polycystic Kidney

The most common form of this genetic disease is transmitted as an autosomal-dominant gene on chromosome 16. There are no indications in the child and young adult; the first manifestations usually appear around age 40 years, when chronic renal failure becomes symptomatic and dialysis is required. This condition is responsible for about 10% of the patients with end-stage chronic renal failure. In some cases, early diagnosis is possible when high blood pressure occurs and is difficult to control or when secondary polycythemia develops due to increased erythropoietin secretion. Diagnosis can be confirmed by an abdominal CT scan or MRI. Multiple cysts develop in both kidneys and gradually expand over the years, first enlarging the kidneys and then compressing and destroying kidney tissue until chronic renal failure occurs (Fig. 18.15). In some cases, cysts are found in other organs such as the liver, or cerebral aneurysms are found. Polycystic disease in children is transmitted as a recessive gene and is manifest at birth. However, in this case, the child is either stillborn or dies during the first months

Filtration

The renal corpuscle consists of Bowman's capsule (glomerular capsule), which is the blind end of the proximal convoluted tubule. This capsule surrounds a network of capillaries, called the glomerulus or glomerular capillaries. These form the filtration unit for the blood. During filtration, a large volume of fluid, including wastes, nutrients, electrolytes, and other dissolved substances, passes from the blood into the tubule. Cells and protein remain in the blood (Table 18.1). When the filtration pressure increases, more filtrate forms and more urine is produced. The filtrate flows into the tubules. The tubule consists of three parts: the proximal convoluted tubule, the loop of Henle, and the distal convoluted tubule. Here reabsorption of essential nutrients, water, and electrolytes takes place and secretion of certain wastes and electrolytes occurs.

Glomerular Filtration Rate (GFR)

Vasoconstriction of afferent arteriole decreases filtrate Dilation of afferent arteriole and vasoconstriction of efferent arteriole increase filtrate

Glomerulonephritis

There are many forms. A representative form of glomerular or nephritic disease is acute poststreptococcal glomerulonephritis (APSGN), which follows streptococcal infection with certain strains of group A beta-hemolytic Streptococcus. These infections usually originate as upper respiratory infections, middle ear infections, or "strep throat." Certain strains of Staphylococcus are occasionally responsible for initiating the immune disorder in the kidney. Acute glomerulonephritis develops 10 days to 2 weeks after the antecedent infection. Primarily APSGN affects children between the ages of 3 and 7 years, especially boys. PATHO: The antistreptococcal antibodies, formed as usual from the earlier streptococcal infection, create an antigen- antibody complex (type III hypersensitivity reaction) that lodges in the glomerular capillaries and activates the complement system to cause an inflammatory response in the glomeruli of both kidneys. (See Chapter 7 for a review of the immune response.) This leads to increased capillary permeability and cell proliferation and results in leakage of some protein and large numbers of erythrocytes into the filtrate. The specific mechanisms of damage are not totally clear, but immunoglobulin G and C3 (complement) are present in glomerular tissue and serum C3 is reduced. When the inflammatory response is severe, the congestion and cell proliferation interfere with filtration in the kidney, causing decreased GFR and retention of fluid and wastes. Acute renal failure is possible if blood flow is sufficiently impaired. The decreased blood flow in the kidney is likely to trigger increased renin secretion, which leads to elevated blood pressure and edema. Severe prolonged inflammation causes scarring of the kidneys. SIGNS AND SYMPTOMS: ~ The urine becomes dark and cloudy ("smoky" or "coffee-colored") because of the protein and red blood cells that have leaked into it. ~ Facial and periorbital edema occur initially, followed by generalized edema as the colloid osmotic pressure of the blood drops and sodium and water are retained. ~ Blood pressure is elevated due to increased renin secretion and decreased GFR. ~ Flank or back pain develops as the kidney tissue swells and stretches the capsule. ~ General signs of inflammation are present, including malaise, fatigue, headache, anorexia, and nausea. ~ Urine output decreases (oliguria) as GFR declines. DIAGNOSTIC TEST: ~ Blood tests show elevated serum urea and creatinine as GFR decreases. ~ Blood levels of Anti-DNase B, streptococcal antibodies, ASO, and ASK are elevated. ~ Complement level is decreased. It is probably a causative factor in the inflammatory damage that occurs in the kidney. ~ Metabolic acidosis, with decreased serum bicarbonate and low serum pH, is present. ~ Urinalysis confirms the presence of proteinuria, gross hematuria, and erythrocyte casts TREATMENT:

How is blood pressure closely related to kidney function and elevated with renal disease

When the blood flow or blood pressure in the afferent arteriole decreases for any reason, the renin-angiotensin-aldosterone triad is stimulated. Angiotensin not only causes systemic vasoconstriction; it also stimulates the secretion of aldosterone. This hormone increases the reabsorption of sodium and water to increase blood volume, thus increasing blood pressure. Serum renin levels can determine whether this mechanism is a factor in hypertension (high blood pressure), in which case renin-blocking drugs (beta-adrenergic blocking drugs) can be prescribed

Cystitis and Urethritis

With cystitis, the bladder wall, and with urethritis, the urethra are inflamed, red, swollen, and in some cases, ulcerated. The bladder wall is irritated and hyperreactive, and bladder capacity is usually reduced. SIGNS AND SYMPTOMS: ~ Pain is common in the lower abdomen. ~ Dysuria (painful urination), urgency (need to void immediately), frequency (short intervals between voiding), and nocturia (need for urination during the sleep period) occur as the inflamed bladder wall is irritated by urine. ~ Systemic signs of infection may be present (fever, malaise, nausea, and leukocytosis). ~ The urine often appears cloudy and has an unusual odor. ~ Urinalysis indicates bacteriuria (the presence of bacteria in the urine), pyuria, and microscopic hematuria

peritoneal dailysis

can be administered in a dialysis unit or at home (outpatient). It may be done at night while the patient sleeps or continuously while the patient is ambulatory (this is called continuous ambulatory peritoneal dialysis). In this procedure, the peritoneal membrane, which is very large in surface area, thin, and highly vascular, serves as the semipermeable membrane. A catheter with entry and exit points is implanted in the peritoneal cavity. The dialyzing fluid (diasylate) is instilled through the catheter into the cavity and remains there, allowing the exchange of wastes and electrolytes to occur by diffusion and osmosis. Then the dialysate is drained from the cavity by gravity into a container. This process requires more time than hemodialysis. However, the more continuous exchange process prevents excessive and sudden changes in fluid and electrolyte levels in the body, and the components of a dialysis solution can be adapted to individual needs. The major complication of peritoneal dialysis is the potential for an infection resulting in peritonitis. Newer methods under investigation make use of charcoal absorbent and ultrafiltration techniques to prevent infection or inflammation

Purpose of dual arterioles

control the pressure in the glomerular capillaries and consequently the glomerular filtration pressure.By constricting or dilating the arterioles, the amount of blood in the glomerular capillaries is adjusted, and filtration is normally maintained regardless of fluctuations in the systemic blood pressure. For instance, if the afferent arteriole is dilated and the efferent arteriole is constricted, hydrostatic pressure in the glomerular capillaries will increase and GFR will increase

Urinary Tract infections

extremely common. It is estimated that 6 million Americans are affected annually. Urine generally provides an excellent medium for growth of microorganisms. Cystitis and urethritis are considered infections of the lower urinary tract, whereas pyelonephritis is an upper tract infection. Most infections are ascending, arising from organisms in the perineal area and traveling along the continuous mucosa in the urinary tract to the bladder and then along the ureters to the kidneys. Occasionally pyelonephritis results from a blood-borne infection. The common causative organism is Escherichia coli, which is one of the resident flora of the intestine (approximately 85%). The virulent forms of E. coli can adhere to the mucosa of the bladder by means of fimbriae or pili and therefore are not washed out when the bladder empties. Other organisms associated with UTIs include Klebsiella, Proteus, Enterobacter, Citrobacter, Serratia, Pseudomonas, Enterococcus, coagulase-negative Staphylococcus, Chlamydia, and Mycoplasma. In men, urethritis and prostatitis may accompany lower tract infections. ETIOLOGY: Women are anatomically more vulnerable to infection than men because of the shortness and width of the urethra, its proximity to the anus, and the frequent irritation to the tissues. The irritation may be caused by sexual activity, baths, and the use of some feminine hygiene products. Improper hygiene practices during defecation or menstruation also increase risk. Older men with prostatic hypertrophy and retention of urine frequently develop infections. Because the male reproductive tract shares some of the structures of the urinary tract, any infection of the prostate or testes is likely to extend to the urinary structures. Congenital abnormalities are a common cause of infection in children, particularly where obstructions to flow or reflux are present. The elderly are at increased risk because of the tendency toward incomplete emptying, reduced fluid intake, impaired blood supply to the bladder, and immobility. Common predisposing factors for UTIs in both men and women include incontinence with incomplete emptying of the bladder, retention of urine in the bladder, and any obstruction to urine flow, which tends to result in growth of organisms because bacteria are not promptly flushed out of the bladder by voiding. Pregnancy, scar tissue, and renal calculi (kidney stones) all contribute to infection because the urine and any contaminants do not flow freely through and out of the system. Infection may also result from decreased host resistance present with immunosuppression or diabetes mellitus (vascular impairment and glucosuria). Direct contamination of the urethra and bladder may result from fecal incontinence. As mentioned, instruments or catheters may directly introduce bacteria into the bladder and frequently traumatize the bladder wall, breaking the barrier to infection.

Urine Formation path

glomerular filtration, tubular reabsorption, tubular secretion

Pyelonephritis

iNTRA- One or both kidneys may be involved. The infection extends from the ureter into the kidney, involving the renal pelvis and medullary tissue (tubules and interstitial tissue). Purulent exudate fills the kidney pelvis and calyces, and the medulla is inflamed. Abscesses and necrosis can be seen in the medulla and may extend through the cortex to the surface of the capsule. If the infection is severe, the exudate can compress the renal artery and vein and obstruct urine flow to the ureter. Bilateral obstruction is likely to result in acute renal failure (see Fig. 18.16C, presented later in the chapter). Recurrent or chronic infection can lead to fibrous scar tissue forming over a calyx, leading to loss of tubule function and hydronephrosis. If severe and bilateral, it can eventually cause chronic renal failure. SIGNS AND SYMPTOMS: The signs of cystitis, such as dysuria, are also present, because infection is present in both kidneys and bladder. Pain associated with renal disease is usually a dull aching pain in the lower back or flank area, resulting from inflammation that stretches the renal capsule. Systemic signs are usually more marked in pyelonephritis. Urinalysis results are similar to those for cystitis except that urinary casts, consisting of leukocytes or renal epithelial cells, are present, reflecting the involvement of the renal tubules. TREATMENT WITH ANTIBIOTICS

renin-angiotensin-aldosterone system

in the kidneys is an important control and compensation mechanism that is initiated when there is any decrease in renal blood flow. This stimulates the release of renin, which in turn activates angiotensin (vasoconstrictor) and stimulates aldosterone secretion secreted by juxtaglomerular cells when blood flow to ateriole is reduced

Aldosterone

increases blood volume by increasing reabsorption of sodium ions and water. secreted by the adrenal cortex, controls sodium reabsorption and water by exchanging sodium ions for potassium or hydrogen ions in the distal convoluted tubule

Antidiuretic Hormone (ADH)

increases water reabsorption through the kidney, thus increasing blood volume. Antidiuretic hormone, also known as vasopressin, also causes vasoconstriction Pituitary—posterior lobe (neurohypophysis) Increases reabsorption of water in kidney hormone from the posterior pituitary controls the reabsorption of water by altering the permeability of the distal convoluted tubule and collecting duct

Urinalysis: Urinary infection

infection with heavy purulence and presence of gram-negative and gram-positive organisms

Retention

is an inability to empty the bladder. It may be accompanied by overflow incontinence. Note that a spinal cord injury at the sacral level blocks the micturition reflex, resulting in retention of urine or failure to void. May occur after anesthesia, either general or spinal. Inability to control urine flow may be managed by wearing pads or briefs that contain the urine.

Retention

is an inability to empty the bladder. It may be accompanied by overflow incontinence. Note that a spinal cord injury at the sacral level blocks the micturition reflex, resulting in retention of urine or failure to void. Retention also may occur after anesthesia, either general or spinal. Inability to control urine flow may be managed by wearing pads or briefs that contain the urine

Hemodialysis

is provided in a hospital, dialysis center, or at home with special equipment and training. During the procedure, the patient's blood moves from an implanted shunt or catheterin an artery, often in the arm, through a tube to a machine where the exchange of wastes, fluid, and electrolytes takes place. A semipermeable membrane separates the patient's blood from the dialysis fluid (dialysate), and the constituents move between the two compartments. For example, wastes move from blood to the dialysate and bicarbonate ion moves into the blood from the dialysate. Blood cells and protein remain in the blood, unable to pass through the semipermeable membrane. Movement occurs by ultrafiltration, diffusion (by a concentration gradient), and osmosis. After the exchange has been completed, the blood is returned to the patient's vein. Heparin or another anticoagulant is administered to prevent clotting, requiring monitoring of blood-clotting times. Required three times a week, each session lasting about 3 to 4 hours. The patient may feel uncomfortable during the session because fluid and electrolyte balances change quickly, but usually he or she feels much better after the treatment. The feeling of well-being then dissipates gradually as wastes accumulate before the next treatment. Dialysis has potential complications. The shunt may become infected, or blood clots may form. Eventually the blood vessels involved at the shunt become sclerosed or damaged, and a new site must be selected. Patients on dialysis have an increased risk of infection by the hepatitis B or C virus or human immunodeficiency virus.

Three factors that control degree of constriction in arterioles

local autoregulation, the sympathetic nervous system (SNS), and the renin-angiotensin mechanism. 1. Autoregulation refers to the small, local reflex adjustments in the diameter of the arterioles that are made in response to minor changes in blood flow in the kidneys. This adjustment maintains the normal filtration rate. 2. The SNS increases vasoconstriction in both arterioles when stimulated. 3. Renin is secreted by the juxtaglomerular cells in the kidney when blood flow in the afferent arteriole is reduced for any reason (see Fig. 18.5). Through a series of enzyme reactions, renin acts on the plasma protein angiotensinogen to produce angiotensin I, and as the blood passes through the lung, angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II, which is a powerful systemic vasoconstrictor. NOTE: If blood flow in the kidney is seriously impaired, as it is when blood pressure drops, both the SNS and the renin-angiotensin mechanism are activated to restore blood pressure and blood flow to vital areas.

Reabsorption

process that takes place in the tubules. In the proximal convoluted tubule, most of the water is reabsorbed into the blood in the peritubular capillaries, along with glucose and other nutrients and some electrolytes. Reabsorption of nutrients and electrolytes involves the use of active transport (eg, sodium ions), which requires carrier molecules and an energy source. Sodium absorption may be linked to the cotransport of other molecules (eg, glucose or amino acids with Na+ ). Anions such as chloride may be reabsorbed by electrochemical gradient or by cotransport with Na+ . If a substance such as glucose is present in excessive amounts in the filtrate, there are insufficient carrier molecules in the tubules for complete reabsorption into the blood in the peritubular capillaries. Therefore the excess glucose is present in the urine. This limit on reabsorption is called the transport or tubular maximum (eg, approximately 310 mg/min for glucose). Thus persistent glucosuria (the presence of glucose in urine) is an indication of hyperglycemia associated with diabetes mellitus. Water is reabsorbed by osmosis. As the filtrate progresses through the loop of Henle and the distal convoluted tubule, electrolytes and water are adjusted to the body's current needs. Hormones control the reabsorption of fluid and electrolytes (see Chapter 2): ~ Antidiuretic hormone from the posterior pituitary controls the reabsorption of water by altering the permeability of the distal convoluted tubule and collecting duct. ~ Aldosterone, secreted by the adrenal cortex, controls sodium reabsorption and water by exchanging sodium ions for potassium or hydrogen ions in the distal convoluted tubule. ~ Atrial natriuretic hormone from the heart is the third hormone controlling fluid balance by reducing sodium and fluid reabsorption in the kidneys. Concurrently the acid-base balance of the blood is maintained, with removal of excess acids and replacement of buffers such as bicarbonate

Dialysis

provides an "artificial kidney," which can be used to sustain life after the kidneys fail. (There is considerable reserve in the renal system; an individual can function normally with half of one kidney.) Dialysis is used to treat someone who has acute renal failure until the primary problem has been reversed, or it can be used for patients in end-stage renal failure, perhaps until a transplant becomes available. In people with renal transplants, it may be required if rejection occurs or between transplants (see Chapter 7). Dialysis is a demanding procedure for both the patient and the family. Diet, particularly protein and electrolytes, and fluid intake are severely restricted.

Renal blood flow

renal artery → interlobar artery → arcuate artery → interlobular artery → afferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillaries → interlobular vein → arcuate vein → interlobar vein → renal vein. The names of the blood vessels match the structures.

Urinalysis: Urinary Infection

smear shows infection with heavy purulence and presence of gram-negative and gram-positive organisms (E. coli and Enterococcus faecalis)

The arrangement of blood vessels in the kidney is unique because

the blood from the glomerular capillaries then flows into another arteriole, the efferent arteriole, and then into a second capillary network, the peritubular capillaries or vasa recta. Therefore two arterioles and two sets of capillaries are included in each nephron. This blood supply also provides nourishment to the renal tissues. Note that the kidney tubules are last to receive nutrients.

Incontinence

the loss of voluntary control of the bladder, has many causes. Young children must learn voluntary control as the nervous system matures. Enuresis defines involuntary urination by a child after age 4 to 5, when bladder control can be expected. Most children have nocturnal enuresis only. The majority of cases appear to be related to factors such as a developmental delay, sleep pattern, or psychosocial aspects rather than to a physical defect. Stress incontinence occurs when increased intraabdominal pressure forces urine through the sphincter. This can occur with coughing, lifting, or laughing, but occurs more frequently in women after the urogenital diaphragm has become weakened by multiple pregnancies or age. Overflow incontinence results from an incompetent bladder sphincter. In the elderly, a weakened detrusor muscle may prevent complete emptying of the bladder, leading to frequent emptying and incontinence. Spinal cord injuries or brain damage frequently cause a neurogenic bladder, which may be spastic or flaccid, due to interference with central nervous system (CNS) and autonomic nervous system control of the bladder emptying

Hormones control the reabsorption of fluid and electrolytes

~ Antidiuretic hormone from the posterior pituitary controls the reabsorption of water by altering the permeability of the distal convoluted tubule and collecting duct. ~ Aldosterone, secreted by the adrenal cortex, controls sodium reabsorption and water by exchanging sodium ions for potassium or hydrogen ions in the distal convoluted tubule. ~ Atrial natriuretic hormone from the heart is the third hormone controlling fluid balance by reducing sodium and fluid reabsorption in the kidneys. Concurrently the acid-base balance of the blood is maintained, with removal of excess acids and replacement of buffers such as bicarbonate

Urinalysis: Abnormal constituents of urine

~ Blood (hematuria)—small (microscopic) amounts of blood are often associated with infection, inflammation, or tumors in the urinary tract; large numbers of red blood cells (gross hematuria) indicate increased glomerular permeability or hemorrhage in the tract ~ Protein (proteinuria, albuminuria)—indicates the leakage of albumin or mixed plasma proteins into the filtrate due to inflammation and increased glomerular permeability ~ Bacteria (bacteriuria) and pus (pyuria)—indicate infection in the urinary tract (Fig. 18.6A) ~ Urinary casts (microscopic-sized molds of the tubules, consisting of one or more cells, bacteria, protein, and so on)—indicate inflammation of the kidney tubules (see Fig. 18.6B) ~ Specific gravity indicates the ability of the tubules to concentrate the urine; a very low specific gravity (dilute urine) usually is related to renal failure (assuming normal hydration) ~ Glucose and ketones (ketoacids) are found in the urine when diabetes mellitus is not well controlled (see Chapter 16)

Other Tests

~ Culture and sensitivity studies on urine specimens are used to identify the causative organism in a urinary infection and select drug treatment (see Chapter 6). ~ Clearance tests, such as creatinine or insulin clearance, or radioisotope studies are used to assess GFR. ~ Radiologic tests, such as radionuclide imaging, angiography, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and intravenous pyelography (IVP), may be used to visualize the structures and any abnormalities in the urinary system. ~ Cystoscopy visualizes the lower urinary tract and may be used in performing a biopsy or removing kidney stones. small ~ Biopsy may be used to acquire tissue specimens to allow microscopic examination of suspicious lesions in the bladder or kidney

Like most other diseases, urinary tract disorders produce abnormalities that can be detected by various blood tests.

~ Elevated serum urea (blood urea nitrogen [BUN]) and serum creatinine—indicate failure to excrete nitrogen wastes (resulting from protein metabolism) due to decreased GFR ~ Metabolic acidosis (decreased serum pH and decreased serum bicarbonate)—indicates decreased GFR and failure of the tubules to control the acid-base balance ~ Anemia (low hemoglobin level)—indicates decreased erythropoietin secretion and/or bone marrow depression due to accumulated wastes ~ Electrolytes—depend on the related fluid balance; that is, retention of fluid if GFR is decreased may result in a dilution effect, and laboratory values are therefore not a true reflection of renal status; however, abnormal levels may still cause clinical effects and require monitoring and treatment ~ Antibody level—antistreptolysin O (ASO) or antistreptokinase (ASK) titers are used for diagnosis of poststreptococcal glomerulonephritis ~ elevated Renin levels—indicate a cause of hypertension

Function of Urinary system

~ Removal of metabolic wastes (nitrogenous and acidic) ~ Removal of hormones, drugs, and other foreign material from the body ~ Regulation of water, electrolytes, and acid-base balance in the body ~ Secretion of erythropoietin ~ Activation of vitamin D ~ Regulation of blood pressure through the renin- angiotensin-aldosterone system

Congenital Disorders

~ Vesicoureteral reflux is due to a defective valve in the bladder mentioned in the discussion on UTIs. ~ Agenesis refers to a developmental failure of one kidney to develop. This is asymptomatic and usually is an incidental finding if diagnosed at all. ~ Hypoplasia, or failure to develop to normal size, is often a unilateral defect. Sometimes it results from fibrosis in the kidney rather than being a true developmental flaw. ~ Ectopic kidney is a kidney and its ureter displaced out of normal position. A common location is lower in the abdominal or pelvic cavity. Kidney function is normal. In this position the ureter may become kinked, causing obstruction or infection. ~ Fusion of the two kidneys during development is a common malformation, resulting in a single "horseshoe" kidney. Usually kidney function is normal.