SNEAK PREVIEW
2023
Davis Advantage for Pathophysiology, 3 rd Edition TABLE OF CONTENTS:
I. THE CELL
1. The Cell in Health and Illness 2. Cellular Injury, Adaptations, and Maladaptive Changes 3. Genetic Basis of Disease
II. INTEGRATED BODY PROCESSES
4. Stress, Exercise, and Immobility 5. Obesity and Nutritional Imbalances 6. Pain
III. FLUID, ELECTROLYTE, AND ACID-BASE HOMEOSTASIS 7. Fluid and Electrolyte Imbalances 8. Acid-Base Imbalances IV. INFECTION AND INFLAMMATION 9. Inflammation and Dysfunctional Wound Healing 10. Infectious Diseases 11. Immune System Disorders V. HEMATOLOGICAL DISORDERS 12. White Blood Cell Disorders 13. Red Blood Cell Disorders 14. Platelet, Hemostasis, and Coagulation Disorders VI. CARDIOVASCULAR DISORDERS 15. Arterial Disorders 16. Ischemic Heart Disease and Conduction Disorders 17. Heart Failure 18. Valvular Heart Disease 19. Venous System Disorders VII. PULMONARY DISORDERS 20. Respiratory Inflammation and Infection 21. Restrictive and Obstructive Pulmonary Disorders VIII. RENAL AND UROLOGICAL DISORDERS 22. Renal Disorders
2023
23. Urological Disorders
IX. HORMONAL AND REPRODUCTIVE DISORDERS 24. Endocrine Disorders 25. Diabetes Mellitus and the Metabolic Syndrome
26. Female Reproductive System Disorders 27. Male Reproductive System Disorders 28. Sexually Transmitted Infections
X. GASTROISTESTINAL DISORDERS 29. Esophagus, Stomach, and Small Intestine Disorders 30. Large Intestine Disorders 31. Infection, Inflammation, and Cirrhosis of the Liver 32. Gallbladder, Pancreatic, and Bile Duct Dysfunction XI. NEUROLOGICAL DISORDERS 33. Cerebrovascular Disorders 34. Chronic and Degenerative Neurological Disorders 35. Brain and Spinal Cord Injury 36. Psychobiology of Behavioral Disorders XII. MUSCULOSKELETAL DISORDERS 37. Musculoskeletal Trauma 38. Degenerative Musculoskeletal Disorders 39. Infections and Inflammatory Musculoskeletal Disorders
XIII. CANCER
40. Cancer
XIV. INTEGUMENTARY DISORDERS 41. Skin Disorders 42. Burns
XV. SENSORY DISORDERS 43. Eye Disorders 44. Ear Disorders
XVI. AGING AND MULTISYSTEM DISORDERS 45. Physiological Changes of Aging 46. SIRS, Sepsis, Shock, MODS, and Death
UNIT 8 RENAL AND UROLOGICAL DISORDERS
CHAPTER 22
Renal Disorders
Learning Objectives
After completion of this chapter, the student will be able to: • Describe the various actions of the kidney and how these actions are affected in renal dysfunction. • Identify causes of prerenal, intrarenal, and postrenal dysfunction of the kidney. • Explain the signs and symptoms of major causes of kidney dysfunction.
• Recognize assessment modalities and laboratory tests used to diagnose kidney dysfunction. • Differentiate between acute kidney injury and chronic kidney disease. • Discuss pharmacological and nonpharmacological treatment modalities used in renal dysfunction.
Key Terms
Acute kidney injury (AKI) Acute tubular necrosis (ATN)
End-stage renal disease (ESRD) Erythropoietin Glomerular filtration rate (GFR) Goodpasture’s syndrome Hematuria Hemodialysis Hydronephrosis Intrarenal dysfunction Nephrolithiasis
Oliguria Peritoneal dialysis (PD) Postrenal dysfunction Prerenal dysfunction Proteinuria Pyelonephritis Renal osteodystrophy Renin–angiotensin–aldosterone system (RAAS) Urea Vesicoureteral reflux
Albuminuria Aldosterone Antiglomerular basement membrane (anti-GBM) disease Azotemia Continuous renal replacement therapy (CRRT) Costovertebral angle (CVA) tenderness Creatinine clearance (CrCl)
Nephrotic syndrome Obstructive uropathy
The kidneys are commonly recognized as the organs of excretion because they filter the bloodstream of waste products and excrete urine. However, they also per- form many other functions essential for life. The kid- neys play a major role in controlling blood pressure, regulating red blood cell (RBC) production, breaking down drugs, metabolizing hormones, synthesizing vitamin D, managing electrolytes, conserving and excreting water, and balancing the pH of the blood- stream. The kidneys influence every system of the body from brain to bone, and it is only in their failure that we can appreciate the kidneys’ multiple actions and far-reaching effects on the body.
Epidemiology The incidence of kidney disease continues to grow in the United States. As of 2021, according to the Cen- ters for Disease Control (CDC), one in seven—15% or 37 million—adults in the U.S. have chronic kidney dis- ease (CKD). Also, as many as 9 in 10 adults with CKD do not know they have this disorder. It is most common in persons over age 65. Adults with diabetes mellitus (DM), hypertension (HTN), or both have a high risk of developing kidney disease. One in three adults with DM and one in five adults with HTN have kidney disease.
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534 UNIT VIII RENAL AND UROLOGICAL DISORDERS
African Americans have the greatest incidence of CKD. African Americans make up 13% of the U.S. popula- tion but constitute 35% of persons with kidney failure. Between 1990 and 2015, the incidence of end-stage renal disease (ESRD) increased by almost 100% within the population. Nearly 786,000 Americans have kidney failure, 558,000 (71%) are on dialysis, and approximately 228,000 (29%) live with a functioning kidney transplant. Basic Concepts of Renal Function Renal function begins with blood flow to the renal vas- culature. The kidneys receive 20% to 25% of the body’s cardiac output. It is filtered at a rate of approximately 90 to 120 mL/min. The renal blood filtered per unit of time, known as the glomerular filtration rate (GFR) , is directly related to renal perfusion (see Fig. 22-1). Disease processes that decrease blood pressure and renal perfusion result in a decreased GFR. As an indi- vidual ages, the normal GFR rate of 90 to 120 mL/ minute diminishes. Peak function of the kidneys occurs at age 30 years; for each year after, GFR decreases by 1 mL/minute until by age 70 years, normal GFR is 70 mL/min. This reduction in GFR in the older adult can cause accumulation of toxins, particularly drug metabolites, in the blood.
Excretory Functions The basic unit of the kidney is the nephron, a sequence of tubes that filters the blood of waste and conserves the fluid and electrolytes that the body needs. Each neph- ron is surrounded by blood vessels, where the exchange of water and electrolytes between the blood and the tubule fluid occurs. At the glomerular capillaries, the major mechanisms of the nephron—waste removal and water recycling—begin. The different sections of the nephron perform various functions to form the final product, which is concentrated urine. Urine must con- tain all the waste products, electrolytes, metabolites, and nitrogenous compounds for excretion. At the same time, urine needs to be sparing of water; the kidney needs to conserve the water the body needs. The Nephron Renal blood flow through the glomerulus, a tuft of cap- illaries within Bowman’s capsule, requires high hydro- static pressure to push blood through the filtration process. The kidneys autoregulate renal blood flow to maintain sufficient pressure to push blood through the glomeruli, regardless of whether blood volume is high or low. As blood flows through the glomerulus and a mem- branous cap called Bowman’s capsule, water and
Left kidney
Right kidney
Renal tubules
Ureter
Renal pelvis
Bladder
Urine
Urethra
Prostate
Penis
FIGURE 22-1. Kidney and urological anatomy.
CHAPTER 22 Renal Disorders 535
electrolytes leave the blood and pass into the proxi- mal tubule. At this point, the glomerular filtrate is very dilute and contains a high amount of electrolytes, glucose, and metabolic waste products. At the proximal tubule, approximately 60% of water is reabsorbed back into the bloodstream. As the tubule fluid travels through the various parts of the nephron, water and electrolytes such as sodium and potassium move to and from tubule fluid and blood. Within the next section of the nephron, called the loop of Henle, urea , a composite of nitrogenous waste that needs to be excreted, is secreted into the tubule fluid. At this juncture within the nephron, the tubule fluid, which contains urea, starts to resemble the finished prod- uct: urine. Overall, the loop of Henle reabsorbs about 25% of filtered electrolytes, such as sodium, chlorine, potassium, calcium, and bicarbonate, and 15% of the filtered water. At the distal tubule, aldosterone acts to reabsorb more sodium and water into the bloodstream and secrete potassium into the tubule fluid. Here again, tubule fluid is further concentrated and the body saves water. Finally, at the collecting duct, under the influ- ence of antidiuretic hormone, the last amount of water needed by the body is reabsorbed from the tubule fluid back into the bloodstream. At this last stage, the highly concentrated tubule fluid is urine (see Fig. 22-2). Acid–Base Balance Normal body function is dependent on acid–base bal- ance, and the kidneys play a major role in this through the regulation of bicarbonate and hydrogen reab- sorption or secretion. Acids are produced during nor- mal metabolic processes, requiring the physiological response of buffering to maintain the physiological pH of 7.35 to 7.45. The kidneys’ role in maintaining acid–base balance involves excretion or conservation of hydrogen ions [H + ] and bicarbonate ions [HCO 3 – ]. Waste Elimination During the cell’s metabolic activity, waste products are accumulated. These waste products include such substances as urea, uric acid, creatinine, and drug metabolites. If not excreted in the urine, waste prod- ucts become toxic to body tissues, particularly break- down products of drugs. A reduction in renal function can prolong the effect of some medications, which can lead to adverse effects or toxicity. Secretory Functions The kidney has several unique secretory functions that are triggered by certain conditions in the body. Hypoxia and low blood volume are two such condi- tions. Hypoxia stimulates erythropoietin secretion by the kidney. Low blood volume stimulates renin secre- tion by the kidney.
Bowman's capsule
Distal tubule
Proximal tubule
Glomerulus
Loop of Henle
Collecting duct
Control of Blood Pressure The major mechanism whereby the kidneys influ- ence systemic blood pressure and blood volume is the renin–angiotensin–aldosterone system (RAAS) . The RAAS contributes to sodium and water reabsorp- tion into the bloodstream and potassium excretion at the renal tubules. A specialized region of the neph- ron called the juxtaglomerular apparatus is sensi- tive to sodium. This is the specific region around the glomerulus in each nephron. These cells sense low sodium and, in response, secrete renin. Other triggers for renin secretion include decreased renal perfusion and increased sympathetic nervous system activity. The net effects of the RAAS activity are sodium and water reabsorption, potassium excretion, and arterial vasoconstriction. FIGURE 22-2. Basic functions of the nephron. The nephron’s basic goal is to yield a concentrated urine that contains waste products. The blood and tubule fluid undergo a great deal of exchange before the tubule fluid becomes urine. The glomer- ulus is a tuft of capillaries from which blood is filtered at the Bowman’s capsule. The glomerulus allows substances such as water, sodium, bicarbonate, acids, and urea out of the blood. However, the glomerulus does not allow large proteins such as albumin out of the blood. At the proximal tubule, a large amount of water, sodium, and potassium are reabsorbed into the bloodstream. At the descending loop of Henle, a high amount of sodium is reabsorbed, and urea is secreted from the blood into the tubule. Aldosterone, a hormone secreted by the adrenal gland, increases sodium and water reabsorption. In the distal tubule, sodium and water are reabsorbed from the tubule fluid into the bloodstream and urine is formed. If the body needs more water, antidiuretic hormone (ADH) from the posterior pituitary works at the collecting duct to increase water reabsorption into the bloodstream for a more concentrated urine.
536 UNIT VIII RENAL AND UROLOGICAL DISORDERS
tubule fluid contains waste products that can be toxic to the fragile nephron cells. The nephron cells are at risk if urine outflow is not maintained. Any obstruc- tion to urine outflow, also called obstructive uropa- thy , can cause urine to back up from the ureter into the renal pelvis and cause cellular injury. The causes of kidney dysfunction are divided into three categories based upon the mechanism of injury: 1. Prerenal dysfunction : caused by decreased blood flow and perfusion to the kidney. 2. Intrarenal dysfunction : develops secondary to actual injuries to the kidney itself. 3. Postrenal dysfunction : related to obstruction of urine outflow from the kidneys. Prerenal Dysfunction Prerenal dysfunction of the kidney describes patho- physiological processes that affect GFR and are directly related to blood flow and renal perfusion (see Fig. 22-3). Any condition that directly or indi- rectly decreases renal perfusion may lead to prerenal dysfunction. Prerenal dysfunction occurs because of reduced cardiac output or severe hypovolemia (low blood volume). In any type of shock, the patient is vulnerable to prerenal dysfunction. Maintenance of a
Red Blood Cell Production The kidney secretes erythropoietin , which stimulates synthesis of RBCs in the bone marrow. Erythropoietin is released in response to low oxygen levels in arte- rial blood. The kidney also secretes erythropoietin in response to anemia and cellular hypoxia. CLINICAL CONCEPT Individuals who have chronic hypoxia, such as those with chronic obstructive lung disease, often have higher-than-normal hemoglobin and hematocrit levels because of constant secretion of erythropoietin. Conversely, patients with renal failure have lower hemoglobin and hematocrit levels because of deficient erythropoietin.
Vitamin D Synthesis and Calcium Balance
The kidneys synthesize components that comprise vitamin D. Without kidney function, vitamin D is inac- tive, which affects calcium absorption. In the gastroin- testinal tract, calcium is absorbed with the facilitation of vitamin D. Without vitamin D, calcium absorption is diminished, which disrupts calcium balance in the bloodstream. Glucose Homeostasis The renal tubules reabsorb glucose from the glomeru- lar filtrate up to the renal threshold of a blood glucose level of 180 mg/dL. If the blood glucose level is greater than the renal threshold, the excess glucose is excreted in the urine. Additionally, in states of prolonged fast- ing or starvation, the kidneys can create glucose from amino acids in a process known as gluconeogenesis. The kidneys are also responsible for the degradation of insulin. Patients with renal failure have decreased insulin clearance which affects glucose metabolism. Basic Pathophysiological Concepts of Renal Disorders The kidneys are at risk for injury because they require a large blood flow to function and because they process potentially toxic waste products. For the nephrons to function properly, the blood entering at the glomeru- lus must be at high hydrostatic pressure. The kidneys are susceptible to ischemic injury if not provided with high blood flow. All tubule fluid from the nephrons must travel toward the renal pelvis and out the ureter. The nephrons need high pressure to push tubule fluid out of the kidney without any stasis or backflow. The
Intrarenal (damage to structures within the kidney)
Prerenal (marked decrease in renal blood flow)
Postrenal (obstruction
of urine outflow from the kidney)
FIGURE 22-3. The three basic categories of renal dysfunction are prerenal, intrarenal, and postrenal. These are sometimes referred to as prerenal, intrarenal, or postrenal azotemia. Prerenal azotemia occurs in severe dehydration or hemor- rhage; there is inadequate blood flow to optimally perfuse the kidney. The kidney is not the cause of prenatal azotemia; rather, a circumstance that decreases perfusion of the kidney is the source of the problem. In intrarenal azotemia, there is a problem intrinsically with the kidney, such as trauma to the kidney, infection, or nephrotoxic drugs. Postrenal azotemia occurs when urine outflow is obstructed. Urine needs to flow freely out of the kidney; if backed up, it is toxic to the nephrons. Prostate enlargement, kidney stones, a kinked ureter, or tumors can cause postrenal azotemia.
CHAPTER 22 Renal Disorders 537
sufficiently high blood pressure is necessary for kidney function because glomerular filtration requires high hydrostatic pressure. Large blood loss from the body, as in hemorrhage, is a common cause of prerenal kidney injury caused by ischemia. Intrarenal Dysfunction Direct damage to renal tissue, as in trauma or toxic injury, causes nephron damage within the kidney itself, known as intrarenal dysfunction. This is most commonly caused by nephrotoxic medications, renal infections, or systemic illnesses that affect the kidney. Common examples include nephrotoxicity caused by NSAIDs and poststreptococcal glomerulonephritis (PSGN). Both of these conditions cause direct injury to the kidney. Autoimmune diseases, untreated HTN, and uncontrolled DM also directly harm the kidney caus- ing intrarenal dysfunction. Postrenal Dysfunction Postrenal dysfunction is caused by obstructive urop- athy, a problem that prevents urine outflow from the kidney. Conditions that can cause obstruction include kidney stones in the ureter, prostate gland enlargement, and bladder cancer. In postrenal kidney dysfunction, urine backs up within the ureter and into the kidney, which can lead to hydronephrosis , a fluid-filled, swol- len kidney. Urine is toxic to the nephron cells, and urine stagnation increases the risk of infection. Acute Tubular Necrosis Ischemia and hypoxia can damage the renal tubules and result in acute tubular necrosis (ATN) , the most com- mon cause of acute kidney injury (AKI) . With ischemia, cells of the nephron tubules slough into the tubular lumen. The lumen becomes blocked, preventing fluid from flowing through them, thereby reducing urine for- mation. The blocked lumen further contributes to isch- emic injury to cells lining the tubules, causing additional intrarenal injury. Unless this process is reversed, renal failure with permanent injury to the kidney will occur. Assessment The history and physical assessment for patients with renal disease includes determining exposure to any medications or nephrotoxic substances. Additionally, any systemic illnesses or infections associated with renal damage need to be identified. Illnesses such as HTN and DM are important causes of renal damage. Patients need to be asked about their pattern of urine excretion and the character of their urine. Typi- cal questions would include the following: • Does the urine have an unusual odor or color? • Is the urine foamy?
• Is the urine very dark or tea-colored? • Is there blood in the urine? • Is there pain or burning on urination? Is there abdominal or flank pain on urination? • Have you noticed any change in the amount of urine or the frequency of urination? Risk Factors Exposure to nephrotoxic agents is one of the great- est risks for the development of renal disorders. A list of current medications is needed, as many drug metabolites are particularly nephrotoxic. Specific questions concerning HTN and DM are important. The patient needs to describe the duration of the disorder, medications involved, and management of the disorders.
ALERT! Long-term DM and HTN often lead to renal failure.
The patient should be asked about a recent strep- tococcal infection because poststreptococcal glomer- ulonephritis (PSGN) can occur. Patients who have had major surgery are at risk for altered renal function, as major surgery can reduce renal blood flow and lead to kidney injury. A reduction in renal blood flow is also a concern for patients who have had an acute myo- cardial infarction or heart failure. Renal ischemia is a common complication of severe heart failure. Signs and Symptoms The patient with renal failure generally has a vari- ety of multisystemic symptoms, which are the result of reduced secretory and excretory functions of the kidney. The symptoms can include fatigue, weakness, nausea, constipation, abdominal pain, and confusion. Patients with renal calculi may have abdominal or flank pain in addition to hematuria. Costovertebral angle (CVA) tenderness is a classic sign of a kidney disorder, particularly infection (see Fig. 22-4). The presence of blood ( hematuria ) or protein ( proteinuria ) in urine is often readily apparent to the patient. Urine looks pink or red when blood is present and foamy when it contains high levels of protein. Tea-colored urine often indicates bilirubin is in the urine, as occurs in jaundice. All these signs are an indication for further study.
CLINICAL CONCEPT Hematuria is most often a sign of renal calculi or an infection.
538 UNIT VIII RENAL AND UROLOGICAL DISORDERS
Diagnosis Renal function can be evaluated through examination of the urine and blood. Imaging studies can be per- formed to evaluate the anatomy of the kidneys and renal blood flow and visualize renal calculi, tumors, or cysts. Urinalysis Urinalysis is a basic examination of urine that includes a description of the character of the urine, as well as bio- chemical and microscopic analysis. Normally, urine is odorless and clear or slightly hazy with a color ranging from yellow to amber. The color varies according to the concentration of solutes and water content of the urine. For example, a dehydrated person has amber-colored urine, whereas a well-hydrated person has light yellow urine, although urine color can vary with some medica- tions or certain disorders. For example, hepatitis will cause a dark-brown, tea-colored urine caused by bile pigments. Reagent strips, also called dipsticks, are used for analysis of the urine. Urinary pH should be close to a neutral pH of 7, but it does vary from acidic to basic. The specific gravity should be between 1.001 when dilute and 1.030 when highly concentrated. All of the biochemical tests that are measured by reagent strips should be negative in healthy individuals. If any of these tests are positive, they are suggestive of a variety of illness states (see Table 22-1). The presence of glucose and ketones is indicative of diabetic ketoacidosis. Leukocyte esterase measures the amount of enzyme secreted by white blood cells (WBCs); a high amount (positive result) is indicative of either a bladder or kidney infection. Crystals are often seen in the urine of patients with renal calculi. Casts are substances that are secreted into the nephron tubules and retain the shape of the tubules. They are
12th rib
Left kidney
Right kidney
Costovertebral angle
FIGURE 22-4. The kidney is located in the costovertebral angle (CVA) region. In physical examination, the examiner should firmly tap the CVA to assess its pain of kidney disorder. The pain of nephrolithiasis and pyelonephritis is commonly in the CVA region.
Proteinuria, also called microalbuminuria, indi- cates that the urine contains proteins. Normal total protein excretion does not usually exceed more than 150 mg/day. Excess protein in the urine is abnormal and is usually an indication of glomerular injury. The glomerular capillaries should not filter out blood pro- teins; however, when injured, they develop excessive permeability that allows escape of albumin into the nephron tubule. Glomerular injury can occur in such disorders as glomerulonephritis, DM, and HTN.
TABLE 22-1. Urine Analysis Using Reagent Strips
Test
Normal Value
Common Etiology
Glucose
Negative
If positive: hyperglycemia, diabetes
Ketones
Negative
If positive: starvation or diabetic ketoacidosis
Protein
Negative or trace
Minimal: exercise or infection Moderate: polycystic kidney disease (PKD), infection, heart failure, diabetic kidney disease Marked: PKD, glomerulonephritis, diabetic kidney disease, nephrosis, lupus nephritis
Blood
Negative
If positive: infection, kidney stone, or bladder cancer
Bilirubin
Negative
If positive: hemolysis or liver disease
Urobilinogen
Minimal
If high: liver disease
Nitrite
Negative
If positive: urinary tract infection
Leukocyte esterase
Negative
If positive: urinary tract infection
CHAPTER 22 Renal Disorders 539
made of protein or fats and can either be benign or signify kidney disease. Blood Urea Nitrogen Azotemia is the increase of blood urea nitrogen (BUN) within the bloodstream. The normal level for BUN is 5 to 20 mg/dL. An elevated BUN can occur when there is a decrease in the GFR, which leads to accumulation of nitrogenous waste products in the blood. However, a high BUN level is not always an indicator of kidney dysfunction; it can result from dehydration, which highly concentrates the urea in the urine. A high BUN level can also occur in any condition that elevates the amount of nitrogen waste in the bloodstream. Extremely muscular individuals will have a high nitro- gen level in the bloodstream because of high muscle breakdown. The muscle cell proteins break down into amino acids, which are nitrogen compounds. High BUN levels also occur in persons on high-protein diets, as the large load of protein breakdown into amino acids raises nitrogen in the bloodstream. CLINICAL CONCEPT Because of the possible elevation of BUN with nonrenal conditions such as dehydration, the clinician should not rely on BUN alone as an indicator of renal dysfunction. Serum Creatinine Creatinine is a muscle breakdown product that is fil- tered almost completely at the glomerulus. The nor- mal range of serum creatinine is approximately 0.5 to 1.5 mg/dL. After being filtered out of the bloodstream, it is not reabsorbed by the nephron tubules.
Creatinine Clearance Creatinine clearance (CrCl) is sometimes used to assess the GFR. The test requires measurement of both blood and urine creatinine and 24-hour urine volume. CrCl can also be estimated using a mathe- matical formula. The amount of creatinine filtered at the glomerulus is the total amount of creatinine that appears in the urine. A decreased creatinine clearance indicates decreased GFR and impaired renal function. This can be caused by conditions such as renal disease or can result from lack of circulation to the kidney, which occurs in hypotension, heart failure, and shock. Increased creatinine clearance indicates there is more creatinine in the urine than normal. This can be seen in pregnant women, patients with DM, patients with large muscle mass, or those with high protein intake. Imaging Studies Visualization of the kidneys through various imaging studies can provide valuable information about renal size and function. Renal ultrasound is used to deter- mine the size of both kidneys. It can also be used in the diagnosis of hydronephrosis, renal cysts, tumors, and kidney stones. Abdominal x-rays can sometimes visualize radio-opaque stones or nephrocalcinosis. Computed tomography (CT) scan or magnetic reso- nance imaging (MRI) can also visualize kidney stones and abnormalities. Renal biopsy can be performed if imaging tests do not reveal sufficient information.
ALERT! IV contrast-enhanced imaging studies should be avoided in patients with renal impairment because radiopaque dye can cause renal failure. Dehydration markedly increases this risk.
CLINICAL CONCEPT Serum creatinine is a reliable indicator of kidney function.
Treatment Regardless of the etiology, all of the functions regu- lated by the kidney must be maintained when treat- ing renal disease. It is important to maintain fluid, electrolyte, and acid–base levels; to control blood glucose; to control blood pressure; and to monitor RBC production. To accomplish this, patients usually need multiple medications to maintain physiological homeostasis; sodium bicarbonate can help control metabolic acidosis, whereas beta blocker medications can control blood pressure. Epogen is a synthetic form of erythropoietin that can be used to stimulate RBC production. Diuretics can be used to stimulate water loss from the body. However, when these medica- tions cannot reverse the imbalances of renal failure, dialysis is necessary. Indications for dialysis include persistent hyperkalemia, uncompensated metabolic acidosis, and fluid volume excess that is unrespon- sive to diuresis.
Accumulation of serum creatinine indicates decreased filtering of creatinine at the glomerulus. There are exceptions to this rule in extremely mus- cular individuals and very frail individuals. Because serum creatinine is based on muscle tissue breakdown, serum creatinine can vary depending on the patient’s muscle mass. A person who has an increased amount of muscle breakdown daily may have an abnormally high serum creatinine, whereas a frail individual will have a low amount of serum creatinine daily. ALERT! Nephrotoxic antibiotics include ami- noglycosides. Whenever these are administered, serum levels of the medication and serum creatinine levels must be monitored.
540 UNIT VIII RENAL AND UROLOGICAL DISORDERS
There are two types of dialysis: hemodialysis and peritoneal dialysis. One functioning kidney can perform all functions and maintain homeostasis. When both kidneys are no longer functioning and the patient is in relatively good health, renal transplant may be considered. Peritoneal Dialysis In peritoneal dialysis (PD) , the patient’s peritoneum is filled with a dialysis solution that pulls wastes and extra fluid from the blood into the abdominal cavity. The dialysis solution, called the dialysate, contains certain electrolytes that cause diffusion of solutes and ultrafiltration of fluid from the blood to cross the peritoneal membrane. The process works based on the principle that diffusion of substances in water tends to move from an area of high concentration to an area of low concentration. After the fluid is instilled, it sits in the peritoneal cavity for a period, called a dwell time, of approximately 4 hours. After the dwell time, the solution is drained from the peritoneal cav- ity and discarded. PD is uncommon, but at times it is used as an alternative to hemodialysis. The process of draining and filling takes about 30 to 40 minutes. A typical schedule of PD requires approximately four exchanges a day, each with a dwell time of 4 to 6 hours (See Fig. 22-5).
Hemodialysis Hemodialysis is a treatment during which the patient’s blood is drawn out of the body at a rate of 200 to 400 mL/minute and passed through a device called a dialyzer. There are two sections in the dia- lyzer: the section for dialysate and the section for the blood. The two sections are divided by a semiperme- able membrane, which has microscopic perforations that allow only some substances to cross. Because it is semipermeable, the membrane allows water and waste to pass through, but does not allow blood cells to pass through. Commonly, a patient has an arteriove- nous fistula created in the arm that can facilitate this process. For example, a tubular connection between the brachiocephalic artery and cephalic vein is often surgically implanted. Blood is drained from the bra- chiocephalic artery and pumped into a dialyzer, which removes excess solutes and fluid from the blood. The blood is then returned to the body via the cephalic vein. The dialysis solution is a sterile solution of electrolytes. Urea and other waste products, such as potassium and phosphate, diffuse into the dialysis solution. During the treatment, the patient’s entire blood volume (about 5000 mL) circulates through the machine every 15 minutes. Electrolytes, serum albumin, BUN, and serum creatinine are normalized during the dialysis procedure. The procedure is usually required at least three times a week, and each session lasts 4 to 6 hours (See Fig. 22-6).
Dialysis solution
Heparin pump (to prevent clotting)
Dialyzer inflow pressure monitor
Peritoneal lining
Inflow
Venous pressure monitor
Air trap and detector
outflow
Dialyzer
Peritoneal cavity
Air detector clamp
Arterial pressure monitor
Blood removed for dialysis
Dialyzer blood return to body
Blood pump
FIGURE 22-5. Peritoneal Dialysis : In peritoneal dialysis, dial- ysate solution is instilled into and removed from the perito- neal cavity at regular intervals to achieve clearance of solutes. The dialysate solution has a high concentration of dextrose. Ultrafiltration of water is achieved by the creation of an osmotic gradient across the peritoneal membrane. It is a slow process that is sometimes better tolerated by hypotensive patients than hemodialysis.
FIGURE 22-6. Hemodialysis: In hemodialysis, blood is removed from the body and filtered through a man-made membrane called a dialyzer, and then the filtered blood is returned to the body.
CHAPTER 22 Renal Disorders 541
Epstein–Barr virus, hepatitis B or C, or cytomegalo- virus. Autoimmune and immunological diseases such as systemic lupus erythematosus (SLE) frequently cause AGN. Glomerulonephritis can also occur as part of an active infectious process. This type of AGN includes staphylococcus-associated glomeru- lonephritis (SAGN) that develops in people with an infection with methicillin-sensitive or methicillin- resistant Staphylococcus aureus. It can also occur in persons with bacterial endocarditis and central venous catheter infections. AGN of any type can progress to chronic disease, particularly in patients with other risk factors. The course of chronic glomerulonephritis is often grad- ual and silent. By the time of diagnosis, the patient is commonly already in the early stages of ESRD. Pathophysiology Postinfectious glomerulonephritis, the most common type of AGN, begins with an antigen–antibody reac- tion. An antigen, such as streptococcus, enters the body and stimulates antibody synthesis. There are two theoretical explanations for the mechanism of disease. One theory claims that the antibodies attack the antigen, but also form antigen–antibody com- plexes that float freely in the bloodstream until they deposit within glomerular membranes. The other the- ory asserts that molecular mimicry occurs, where the antibodies that are stimulated attack the antigen and mistakenly attack the glomerular membranes as well (see Fig. 22-7).
Continuous Renal Replacement Therapy Continuous renal replacement therapy (CRRT) is similar to hemodialysis; however, it is a slower process used for patients who are hemodynamically unstable and fluid overloaded. This continuous process takes smaller volumes of blood from the patient and filters it through a dialyzer over 24 hours. It is most commonly used in patients with acute kidney injury. Pathophysiology of Selected Disorders Major pathophysiological conditions of the kidney include acute glomerulonephritis, nephrotic syndrome, nephrolithiasis, pyelonephritis, polycystic kidney dis- ease, Goodpasture’s syndrome, acute kidney injury, and chronic kidney disease. Acute Glomerulonephritis Acute glomerulonephritis (AGN) is a renal disorder that is due to inflammation of the glomerulus. In most cases, AGN is due to an immunological mechanism that triggers inflammation that damages the mem- branes of the glomerulus. It can lead to significant illness because the glomerulus is the critical, initial region of every nephron unit that filters the blood. Damage to the glomerular capillaries causes a loss of vital substances, such as albumin, from the blood into the tubule fluid, which becomes urine. Glomerular injury increases glomerular permeability, which allows albumin to leave the capillaries and enter the tubules. Epidemiology Glomerulonephritis may be an acute, mild disease or a rapidly progressive disease that can lead to renal dys- function. AGN is the cause of 25% to 30% of all cases of ESRD. In cases that progress to ESRD, the disease course is fairly rapid. In severe disease, end-stage renal failure may occur within weeks or months of the onset of AGN. Most cases of AGN occur in patients aged 5 to 15 years; only 10% occur in patients older than 40 years. It predominantly affects males with a 2:1 male-to-female ratio. Etiology Poststreptococcal glomerulonephritis (PSGN) is the most common cause of acute glomerulonephritis. Acute infection with group A beta-hemolytic strep- tococcus (GABHS) usually begins as pharyngitis and then causes a secondary immunological reaction at the glomeruli. PSGN can also occur after a skin infec- tion with GABHS, known as impetigo. Although AGN most commonly develops because of streptococcal infection, it can also arise because of other types of bacterial, viral, fungal, or parasitic infections. AGN can follow infections such as rubella, mumps,
Basement membrane of blood vessel Endothelial cell
Antibodies attacking antigen
Ag
Antigen
Immune complexes are deposited in wall of blood vessel.
FIGURE 22-7. Glomerular damage in glomerulonephritis. The damage to glomerular membranes in glomerulonephritis is caused by antibodies. These antibodies are commonly acti- vated by Streptococcus bacteria. The antibodies combine with antigen and deposit as immune complexes within the kidney that are normally eliminated in the circulation. However, in glomerulonephritis, the immune complexes accumulate and cause inflammation and membrane damage.
542 UNIT VIII RENAL AND UROLOGICAL DISORDERS
Regardless of mechanism, the antigen–antibody complexes damage the structure of the glomeruli and cause nephron dysfunction throughout the kidneys. Glomerular injury causes hyperpermeability of the capillaries, which allows loss of albumin and RBCs in the urine. The large loss of albumin from the blood- stream causes proteinuria, also called microalbumin- uria. Because albumin content of the bloodstream decreases, diminished colloid oncotic pressure (COP) occurs throughout the body. According to Starling’s Law of Capillary Forces, the decrease of COP causes an imbalance in hydrostatic and oncotic pressure. The low COP is overcome by hydrostatic pressure, which causes edema. Also, because glomerular filtration of the blood is diminished, urine production is also diminished. As GFR decreases, oliguria , which is lack of sufficient urine production, develops. The patient becomes hypervolemic and edematous, and blood pressure rises. CLINICAL CONCEPT A certain amount of urine production is necessary to excrete waste products. An inadequate amount of urine is termed oliguria. Oliguria is defined as less than 400 mL of urine output per day or less than 20 mL of urine per hour. Clinical Presentation Acute glomerulonephritis has a classic presentation of sudden edema (most prevalent in the periorbital region), hematuria, proteinuria, oliguria, and HTN. The onset of clinical manifestations occurs approx- imately 7 to 21 days following a streptococcal infec- tion. This is consistent with the time frame needed for antibody formation. As glomerular function decreases, urinary output decreases. As glomerular injury increases, hematuria and proteinuria increase. The patient develops puffiness of the eyelids and facial edema. The urine is dark because it contains RBCs; it has been described as cola-colored. Blood pressure is often ele- vated. Nonspecific symptoms include weakness, fever, abdominal pain, and malaise. The patient may com- plain of CVA tenderness.
metabolic panel are necessary. Serum creatinine and BUN will be modestly elevated in PSGN. Mild ane- mia is common in the early stages due to decreased erythropoietin secretion. Serum complement levels C3 and C4 are low as they are used up by the forma- tion of immune complexes deposited in the glomeru- lar membranes. Hypoproteinemia is often present due to loss of protein in the urine (proteinuria). A 24-hour urine protein quantification is necessary. Serum electrolytes are usually normal. Urine studies will show a large amount of protein, WBCs, and blood in the urine with hyaline or cellular casts. Urine creat- inine clearance will be low because dysfunctional kidneys do not excrete nitrogenous wastes. Creati- nine accumulates in the blood. Serum albumin will be low as it is filtered out of the permeable, inflamed glomerulus. Hepatitis B and C and HIV serology testing are necessary. The streptozyme test is used to measure five different types of antistreptococ- cal antibodies: antistreptolysin O, antihyaluronidase (AHase), antistreptokinase (ASKase), antinicotinamide– adenine dinucleotidase (anti-NAD), and antiDNAse B antibodies. Blood tests for antineutrophil cytoplasmic antibodies (ANCA), anti–double-stranded DNA anti- body, and antiglomerular basement membrane (GBM) serology are done to rule out causes of rapidly pro- gressing AGN. Imaging studies do not provide valuable diagnostic information. Treatment The management of AGN is based largely upon clini- cal presentation and symptoms. Antibiotics are neces- sary if the etiology is poststreptococcal infection. The treatment of glomerulonephritis associated with an active infection is aimed at eradication of the current infection. Antipyretics and analgesics are also needed. If HTN is present, antihypertensive medication is nec- essary. If edema is present, diuretics may be indicated. Dietary restrictions of sodium and protein are also advised. IgA Nephropathy IgA nephropathy is one of the most common forms of glomerulonephritis. There are geographical differ- ences in the incidence of this disease across the world. There is a 30% prevalence in Asia and the Pacific Rim, 20% prevalence in Southern Europe, and much lower prevalence in Northern Europe and North America. There is a male preponderance with peak incidence in the second and third decade of life. The most common clinical presentation includes hematuria, often after a respiratory infection accompanied by proteinuria. The majority of patients have benign disease with complete remission. However, IgA nephropathy can have a rapidly progressive course to renal failure. Deposits of IgA, either alone or with IgG, IgM, and complement protein, are found in the glomerular region of the nephrons. There is andinflammatory
CLINICAL CONCEPT Point tenderness over the flank and CVA tenderness is a classic symptom of kidney infection.
Diagnosis The gold standard for diagnosing glomerulonephritis is a kidney biopsy, with hallmark glomerular inflam- mation characterized by increased glomerular cel- lularity. However, the diagnosis is most often made on a clinical basis without biopsy. CBC and complete
CHAPTER 22 Renal Disorders 543
type of hypercellularity with destruction of capillar- ies and fibrosis of the nephron tubules. Angiotensin- converting enzyme inhibitors, corticosteroids, and immunosuppressants have been effective in some patients. Plasmapheresis, a procedure that removes the antibodies from the plasma portion of the blood- stream, has also been used for some patients. Nephrotic Syndrome Nephrotic syndrome is a combination of clinical findings that occurs when the glomeruli are damaged. When glomeruli are injured, they become hyperper- meable to proteins and other substances in the blood- stream. The blood becomes depleted of albumin and other large molecules as they enter into the nephron tubules and become excreted with the urine. Epidemiology Diabetic nephropathy is the most common type of nephrotic syndrome, with an incidence of 50 to 100 cases per million population per year. Native Ameri- cans, Latino Americans, and African Americans have a higher incidence than do European Americans. There is a male predominance in the occurrence of nephrotic syndrome, as there is for CKD in general. However, nephrotic syndrome secondary to SLE is more com- mon in women. Etiology Three systemic diseases—DM, amyloidosis, and SLE—are implicated in more than 90% of all cases of nephrotic syndrome in adults. Other causes include immune-complex deposition disease, vasculitis, allergies, preeclampsia, morbid obesity, malignant HTN, and infections such as bacterial endocarditis and tuberculosis. In children, 70% to 90% of cases of nephrotic syndrome is caused by minimal change dis- ease (MCD) which is associated with edema, severe hypoalbuminemia, and massive proteinuria. The cause of MCD is unknown. Pathophysiology Glomerular damage occurs either as a primary insult or secondary to one of the causes described. Structural changes that occur in the glomerulus include injury to the endothelial cells, derangement of the basement membrane, and damage to the epithelium. Massive albuminuria (also called proteinuria ) is a conse- quence of the glomerular damage. As albumin is lost in the vascular space, edema forms because of decreased colloidal osmotic pressure. Clinical Presentation Patients have albuminuria with consequent edema. Facial edema is common, especially in the periorbital region. With severe albumin loss, edema of the lower extremities, pleural effusion, and ascites can develop. Patients also often present with hematuria and HTN.
Diagnosis The work-up for nephrotic syndrome includes uri- nalysis and blood tests for albumin, BUN, and serum creatinine. Urinalysis usually shows proteinuria and hematuria. Elevations in BUN and serum creatinine occur and are followed to assess renal function. The serum albumin level is classically low in nephrotic syndrome, below its normal range of 3.5 to 4.5 g/dL. Tests for hepatitis B and C, HIV, and lupus, including antinuclear antibody (ANA), anti–double-stranded DNA (antidsDNA) antibodies, and complement, are commonly done when the etiology of nephrotic syn- drome is unclear. In immunological etiologies of nephrotic syndrome, complement in the bloodstream is decreased. A 24-hour urine sample is collected for analysis. The urine can contain up to 3 grams of protein over 24 hours (normal is fewer than 150 mg/day). The urine also contains fatty casts caused by loss of lipoproteins at the glomerulus, which take on the shape of the tubules before excretion into urine. Renal ultrasonog- raphy and renal biopsy may be done when etiology is unclear. Treatment The patient with nephrotic syndrome needs to be vigilant of nutritional needs. The diet should provide adequate energy (caloric) intake and adequate protein (1 to 2 g/kg/d). However, supplemental dietary protein is of no proven value because it will be excreted. A low-sodium diet (fewer than 1500 g/day) will help to limit fluid overload. Adequate fluid intake is essential, but overhydration should be avoided. Because albumin levels are low, it is important to recognize that there are fewer binding sites for drugs. This will increase the amount of free active drug in the bloodstream. Also in nephrotic syndrome, immu- noglobulins are lost to the urine. This increases sus- ceptibility to infection. Pneumococcal and influenza vaccines should be administered to protect the patient from infection. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are used to lower blood pressure. They also slow the progression of kidney disease. Complications As nephrotic syndrome progresses, hyperlipidemia may develop secondary to increased lipoprotein syn- thesis in the liver. As the liver increases synthesis of albumin to replenish the lost albumin in the urine, it also hypersynthesizes lipids. There is commonly an elevation in low-density lipoprotein (LDL) and triglycerides. Hyperlipidemia requires drugs such as statins that decrease liver synthesis of lipids. With increased loss of protein in the urine, there is loss of antithrombin III and plasminogen, the body’s natural thrombolytic substances. This increases the risk of thromboembolism, and patients may require antico- agulants (see Fig. 22-8).
544 UNIT VIII RENAL AND UROLOGICAL DISORDERS
stones than people living in other parts of the coun- try because the hot, dry climate predisposes them to develop dehydration. Nephrolithiasis is more common in European Americans than in African Americans, and the disease is predominately found in males. Kidney stones most commonly develop in adults aged 20 to 49 years, with a peak incidence at age 35 to 45 years old. The mean age is 44.8 years in men and 40.9 years in women. A family history doubles the risk of kidney stones. Recurrence of nephrolithiasis is common. After suffering a kid- ney stone, individuals have a 52% chance of suffering another stone within 10 years. Etiology The exact cause of nephrolithiasis is unknown, but about 90% of patients who present with clinical man- ifestations have at least one metabolic risk factor: hypercalcemia, hyperoxaluria, hyperuricemia, hyper- parathyroidism, or gout. In addition, low fluid intake is a significant risk factor because dehydration enhances kidney stone formation. There is a genetic predisposi- tion, with more than 30 genetic variations associated with renal calculi development. Differences in intes- tinal calcium absorption, renal calcium transport, and renal phosphate transport have all been attributed to genetic variation. In patients without specific metabolic or genetic risk factors, nephrolithiasis is attributed to dietary habits, such as excessive calcium supplements and low fluid intake. Hypercalciuria and low fluid con- tent of the urine are the most common predisposing factors that lead to nephrolithiasis (see Box 22-1).
Protein is filtered out of the blood at the glomerulus.
Protein
Loss of protein from the bloodstream (hypoalbuminemia)
Low colloid oncotic pressure
Proteinuria
Edema
Nephrolithiasis Nephrolithiasis is the formation of stones, also called calculi, in the kidney. Calculi can form in the kidney and travel into the ureter, when it is then referred to as urolithiasis. Although pain is a presenting sign with all types of renal calculi, characteristics vary based upon the stone’s location. Epidemiology In the United States, the lifetime risk of developing nephrolithiasis is approximately 11% for men and 7% for women. Approximately 2 million patients seek health care for kidney stones each year. Dehydration increases susceptibility to kidney stone formation. For this reason, people living in the south and south- west United States have higher incidences of kidney CLINICAL CONCEPT Hypoalbuminemia, edema, and proteinuria are the three distinguishing features of nephrotic syndrome. Hyperlipidemia and HTN are also associated with nephrotic syndrome. FIGURE 22-8. Nephrotic syndrome. In nephrotic syndrome, the glomerulus is damaged, allowing proteins to be filtered out of the bloodstream. The major protein from the bloodstream that is lost is albumin; thus, hypoalbuminemia results. The loss of protein (albumin) from the bloodstream causes decreased colloid oncotic pressure, which leads to edema. Therefore, the signs of nephrotic syndrome are hypoalbuminemia, proteinuria, and edema.
BOX 22-1. Predisposing Factors of Nephrolithiasis
There are many predisposing factors for nephrolithiasis. Nephrolithiasis is usually caused by a number of different conditions that act together to cause precipitation of calculi in the kidney. • Age greater than 40 years • Male gender • Certain medications (e.g., sulfonamides, indinavir, acetazolamides) • Dietary factors (e.g., purines, calcium, oxalate) • Gastric bypass surgery • Geographic location (hot, arid climates) • Hypercalciuria • Hyperparathyroidism • Hyperuricemia • High-sodium diet • Inflammatory bowel disease • Inherited conditions (e.g., polycystic kidney disease, renal tubular acidosis) • Low hydration/low urine volume • Obesity • Proteus urinary tract infection
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