THE PEDIATRIC DIAGNOSTIC EXAMINATION - PART 7 doc

Causes of Chronic Renal Failure: 2 Years to 10 Years of Age Causes of chronic kidney disease and chronic renal insufficiency include hypoplasti c/dysplastic kidneys, autosomal recessive polycystic kid- ney disease, and hemolytic-uremic syndrome and i ts sequels (hypertension and proteinuria). Juvenile nephronophthisis/medullary cystic disease com- plex is one of the most important causes of ESRD in children around 10 years of age or early adol escence. Others include reflux nephropa- thy and sickle cell disease causing chronic interstitial nephritis and glomerulosclerosis. Tubular diseases (including hyperoxaluria type 2, Bartter syndro me, and cystinuria),are associated with chronic kidney disease. T ABLE 14–29 lists causes of chr onic renal disease in those aged 10 years through adolescence. The most important causes of chronic kidney dise ase that may adva nce to chronic renal insufficiency and ESRD are the glomerular diseases. Focal segmental glomerulosclerosis is the most common glomerular disease causing chronic kidney dis- ease and ESRD in adolescents, parti cularly in African-American ado- lescent boy s and young men. Diabetic nephropathy starts to develop in older adolescents who have acquired di abetes mellitus type 1 in early childhood. Laboratory and Imaging Studies Laboratory and imaging studies are helpful after the differential diag- noses are formulated on clinical grounds. We list selected conditions in which the laboratory and imaging departments may be of significant value to narrow down diagnostic possibilities. 480 Chapter 14: The Renal System TABLE 14–29 Causes of Chronic Renal Disease in Those Aged 10 Years through Adolescence Glomerular disorders Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative glomerulonephritis IgA nephropathy Small blood vessel vasculitis Lupus nephritis Hereditary nephritis ( Alport syndrome) Renal tubular diseases Bartter syndrome Gitelman syndrome Diabetic nephropathy Neonatal Hypertension The laboratory investigation of the hypertensive neonate includes serum electrolytes, CO 2 , blood urea nitrogen (BUN), and creatinine levels. Severe hypertension may induce polyuria and hyponatremia owing to salt wasting induced by pressure natriuresis. It is important to keep in mind the changing normal values of creatinine in the newborn. Urinal- ysis and urine culture with sensitivities are necessary in newborns sus- pected to be infected or having congenital abnormalities of the urinary tract. The presen ce of oliguria, proteinuria, and hematuria favors the existence of renal parenchymal disease. Coagulation studies are important in hypertensive septic infants, in those suspected of having renal vein or renal artery thr ombosis, or in those with other coagulation abnormalities. Renal artery stenosis as a cause of hypertension in newborns is rare. The interpretation of periph- eral plasma renin levels is difficult owing to the variabi lity with gesta- tional and postgestational age, as well as the effects of medications and different physiologic factors that influence its production. Perform appropriate laboratory studies in infants suspected of having endocrine causes of hypertension (such as 11β- or 21β-hydroxylase deficiency). Obtain plasma and urinary catecholamine metabolite levels in suspected cases of catecholamine-producing tumors, whereas thyroid hormone determinations are use ful for suspected cases of neonatal hyperthyroidism. Imaging studies of the kidneys and urinary tract of the hypertensive infant are important if renal artery stenosis is under consideration, but direct a rteriography is seldom necessary at this age. Imaging studies are also critical in the presence of an abdominal mass, unilateral or bilateral enlarged kidneys, abnormal urinary sediment, hematuria, proteinuria, UTI, or absence of a clear extrarenal cause of hypertension. Ultra- sonography is the least invasive of the currently available techniques. Doppler sonography adds information, although it is highly operator- dependent. Nuclear me dicine renal scans are very useful for evaluating flow and function in these newborns. Acute Renal Failure in the Neonate The presence of hematuria or proteinuria (moderate) may be a mani- festation of acute renal injury. Elevated creatinine levels, as well as BUN, hyponatremia, hyperkalemia, and anemia, may be present. An abn or- mally elevated fractional excretion of sodium (FENa) in the urine is the most reliable laboratory parameter that indicates acute renal failure. The formula for the determination of FENa is FENa = [( urine sodium/plasma sodium)/(urine creatinine/plasma creatinine)] × 100. In term infants, the normal value should be less than than 3 percent; FENa greater than 3 percent indicates intrinsic renal failure. These calculations should be availabl e before administration of diuretics. Renal ultrasonography may reveal thenumber and size of the kid- neys, normal or abnormal echogenicity, and the presence or absence of hydronephrosis or bladder d istension that suggests bladder outlet obstruc- tion. A voiding cystourethrogram is necessary in male infants to confirm or Laboratory and Imaging Studies 481 exclude posterior urethral valves. Radionuclide scans are useful to assess renal flow and function. Intravenous pyelography is now seldom used. Urinary Tract Infection Once the infant has been stabilized, it is necessary to perform imagin- ing studies of the kidneys and urinary tract to evaluate for congenital abnormalities such as vesicoureteral reflux, UPJ obstruction, neurogenic blad- de r, ureterocele, or hydronephrosis. Genitourinary tract abnormalities occur in approximately 20 percent of infants with a documented UTI. These imagining studies include bilateral renal and bladder ultrasound. After this study is completed, the next most important step is to demonstrate the presence or absence of vesicoureteral reflux. A voiding cystourethro- gram (VCUG) should be done as soon the patient is stable and afebrile. Other studies, such as MRI of the kid neys or dimercaptosuccinic acid (DMSA) scan, may be indicated in some cases. They are most useful in assessment of renal scarring. Renal Tubular Acidosis Hyperchloremic normal-ion-gap metabolic acidosis is noted, and blood gas determinations confirm metabolic acidosis (TABLE 14–30). Extrarenal losses of bicarbonate, such as that owing to diarrhea, need to be excluded by h istory and laboratory data. The administration of chloride, such as with parenteral nutrition, needs investigation. In RTA, electrolytes will demonstrate hyperchloremic metabolic acidosis with a nor mal ion gap. Urine pH measured by pH electrode for accuracy should be used. In the presence of acidosis, the urine pH remains 5.5 or greater and will not decrease further even if the acidosis becomes more severe. In proximal RTA, urine pH will be 5.5 or less in the presence of acidosis. In hyper- kalemic type 4 RTA the pH may be variable. Urinalysis may indicate the presence of substances such as glucose an d amino acids, suggesting proximal tubular involvement, as seen in cases of proximal RTA. Urine ammonium excretion should be directly measured if possible or calculated by determining the urine anion gap (UAG). The practical approach to calculat e the urine anion gap is UAG = (Na + + K + )u – (Cl – ). NH 4 + is present if the sum of Na + plus K + is less than the concentration of Cl – . This situation will be the normal response in the presence of aci- dosis and in classic type 2 RTA; ammonium excretion is low in type 2. In type 4 hyperkalemic distal RTA, the ammonium exc retion is also low. Serum potassium level determinations are important in the classification of the RTAs; hypokalemia is typically present in proximal type 2 RTA and in classic type 1 distal RTA ; it is elevated in distal type 4 RTA. Proteinuria Qualitative methods to measure proteinuria include dipstick methods such as Albustix and Multistix (TABLE 14–31); these products contain reagents impregnated with tetrabromophenol blue buffered with citrate. 482 Chapter 14: The Renal System 483 TABLE 14–30 RTA Diagnostic Studies Type of RTA Generalized Distal Finding Proximal (II) Classic Distal Type (I) Dysfunction Distal Type (IV) Plasma [K + ] Low Low High Urinary pH with acidosis<5.5>5.5<5.5 or >5.5 Urine net charge Negative (normal) Positive Positive Fractional bicarbonate excretion >10–15 percent <5 percent <5–10 percent (Urine-Blood)P CO2 , normal > 20 Normal Decrease < 15 Decrease < 15 Nephrocalcinosis kidney stonesNegative Positive ++ Negative Fanconi syndrome Positive in many typesNegative Negative Rickets renal insufficiency Positive Positive in some Negative, renal insufficiency, mild The binding of albumin causes a color change from yellow to green by displacement of the transformation range of the indicator. The intensity of the change is related to the albumin con centration. The test does not d etect small molecular weight proteins, tubular proteins, and positively charged proteins. Sulfosalicylic acid is another good method for the qual- itative determination of urine protein in the ambulatory setting. Semi- quantitat ive methods for measurement of proteinuria are the urine pro- tein to urine creatinine ratio in milligrams per milligram (in children it is age-dependent) (TABLE 14–32). Urolithiasis TABLE 14–33 lists the laboratory and imaging studies used for urolithiasis. Acute Renal Failure Laboratory studies should include a complete blood count (CBC, with RBC morphology and platelet count); other tests include BUN, creati- nine, electrolytes, calcium, phosphorus, magnesium, uric acid, total pro- teins, albumin, prothrombin time (PT), partial thromboplastin t ime (PTT), and complement C 3 . 484 Chapter 14: The Renal System TABLE 14–31 Definition of Significant Proteinuria by Dipstix 1. 1+ is equal to 30 mg/dl on dipstick examination in 2 of 3 random urine samples collected 1 week apart, if urine specific gravity is 1.015 or more 2. 2+ is equal to 100 mg/dl on similarly collected urine specimen if urine specific gravity is 1.015 or more TABLE 14–32 Methods to Measure Proteinuria Age, yrs. mg of Protein/mg of Creatinine 0.1–0.5 0.7 0.5–1 0.55 1–2 0.40 2–3 0.30 3–5 0.2 5–7 0.15 7–17 0.15 Quantitative 1. Normal: ≤4 mg/m 2 per hour in a timed 12- to 24-hour collection 2. Abnormal: 4 to 40 mg/m 2 per hour in a timed 12- to 24-hour urine collection 3. Nephrotic range proteinuria: ≥ 40 mg/m 2 per hour in a timed 12- to 24-hours urine collection Semiquantitative 1. After 5–7 years of age, the urine protein to urine creatinine ratio is the same in children, adolescents, and adults. The urinalysis should include specific gravity, osmolality, pH, protein, hemoglobin, glucose, and sediment. In acute intrinsic renal failure, the urinary sediment is typically “muddy,” with abunda nt brownish granu- lar casts; RBC casts, white blood cell (WBC) casts, and casts containing renal epithelial cells are easily apparent to the experienced clinician. Various indices identify renal failure (TABLE 14–34). Fractional e xcretion of sodium (FENa) is an age-dependent test that measures the nephron reabsorption function and is useful to differentiate prerenal failure from acute tubular necrosis. In prerenal acute renal failure, FENa is normally less than 1 percent. In term healthy newborns it is less than 1 percent (see for mula above), whereas in preterm infants it is as high as 2.5 percent. In children up to 18 years of age it is less than 1 percent, and in healthy adults it is less than 1 percent. Use of diuretics and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) both alter FENa. Laboratory and Imaging Studies 485 TABLE 14–33 Initial Evaluation for Urolithiasis* Blood Complete blood count (CBC) Electrolytes, blood urea nitrogen, creatinine Calcium, phosphorus, alkaline phosphatase, uric acid Total protein, albumin, parathyroid hormone level Urine Urinalysis with urine culture and sensitivity Fasting early morning urine for urine calcium to urine creatinine ratio 24-hour urine collection (calcium, phosphorus, magnesium, oxalate, uric acid, citrate, cystine, creatinine excretion) Imaging studies Renal and bladder ultrasound Spiral CT is th e most sensitive method for evaluation of urolithiasis Hand x rays Chemistry Chemical analysis of calculi or gravel *This table indicates that in the initial evaluation for urolithiasis, it is necessary to obtain plasma as well as urinary values of different substances and other factors responsible for the formation of urinary tract stones. Often a n initial screening test is followed by more comprehensive evaluation. Source: From Greydanus DE, Torres AD, Wan JH: Genitourinary and renal disorders. In: Greydanus et al. (ed.): Essential Adolescent Medicine, Eds: Greydanus DE, Patel DR, Pratt HD. New York: McGraw-Hill, Chap. 16, pp. 329–369. TABLE 14–34 Renal Failure Indices Fractional excretion of sodium (FENa) Fractional excretion of urea nitrogen (FEUN) BUN to creatinine ratio Urine-to- plasma creatinine ratio Urine sodium concentration Urine determination of neutrophil gelatinas e–associated lipocalcine (NGAL). A more sensitive test for tubular function is the fractional excretion of urea nitrogen (FEUN) to differentiate prerenal failure from acute tubular necrosis in adults; it is useful even when patien ts have received diuretics. The formula is FEUN = [(UUN/U Cr )/(BUN/P Cr )] × 100. An FEUN value of less than 35 percent typically signifies prerenal azote mia, and FEUN value of more than 50 percent indicates acute tubular necrosis. Another index is the BUN to creatinine ratio, with a normal of 10 to 15:1. A BUN: creatinine ratio greater than 20:1 is seen in prerenal azotemia, gastrointestinal tract bleeding, drugs (as with steroids and tetracycline), muscle wasting, and end-stage chronic kidney disease. Also, th ere is the urine to plasma creatinine ratio, which is greater than 40 in prerenal azotemia and less than than 20 in intrinsic renal failure. Another index is urine sodium concentration in milliequivalents per l iter; in prerenal azotemia, it is less than than 20 mEq/liter and greater than 40 mEq/liter in acute tubular necrosis. Finally, a novel marker of acute renal injury is the urine determination of neutrophil gelatinase– associated lipocalcine (NGAL). This is a biomarker for acute renal injury owing to ischemia. NGAL is a renoprotective sub- stance seen after ischemic injury that reduces apoptosis, increases normal proliferation of renal tubular cells, and enhances production of hemoxy- genase 1. It enhances iron uptake by siderophores and protects the cell from injury. The urine basal concentration of NGAL is 1.6 µg/liter; it rises to 147 µg/liter 2 hours after ischemia. In the serum, the baseline mean value is 3.2 µg/liter and rises to 61 µg/liter 2 hours after ischemic injury. The most important role for imaging studies in acute renal failure is for evaluation of acute urinary obstruction. Renal ultrasound is useful to determine the number, size, and echogenicity of the kidneys and the presence or absence of obstruction. A nuclear rena lscan will evaluate blood flow and function of each kidney. A renal biopsy in acute renal failure is the “gold standard” to establish a specific histopathologic diagnosis, consider therapeutic options, and determine prognos is. Chronic Renal Failure Methods to Assess Chronic Renal Disease Severity and Progression Several methods are available to assess the severity and progression of renal disease, such as measurement of GFR. In clinical practice, most nephrologists use the measurement of plasma creatinine. Another method is calculation of GFR based on creat inine clearance. These meth- ods are imprecise but work well in clinical practice to guide therapy and to determine renal disease progression. In the pediatric population, the Schwartz equation (TABLE 14–35) is appropriate in this clinical situation. This method is practical and recommended in the assessment of renal function of infants, children, adolescents, and young adults. 486 Chapter 14: The Renal System Clinical manifestations of chronic disease evolve slowly as renal func- tion declines. Early, in stage 1 and 2 of chronic kidney disease, when the GFR is normal or only minimally impaired, there are no sy mptoms, and homeostasis is preserved. Fluid, electrolyte, and acid-base abnor- malities start to manifest when chronic kidney disease reaches stage 3, in which fluid overload may manifest with edema, heart failu re, or hypertension, and metabolic acidosis may result in failure to thrive. Alterations in vitamin D metabolism may predispose to bone disease. As the chronic kidney disease advances to stage 4, anemia, hyper- phosphatemia, hypocalcemia, secondary hyperparathyroidism, and renal osteodystrophy with skeletal pain develop. The risk of hyperkalemia becomes a serious problem in the management of these patients at any a ge. In infants and young children, malnutrition may result in serious impairment of intellectual development. Failure to grow is prominent if not treated. In chronic kidney disease stage 5 with a GFR of l ess than 15 ml/1.73 m 2 per minute, the patient develops the syndrome of uremia, charac- terized by neurologic changes, including poor concentration, lethargy, seizures, and coma. There is anorexia, nausea, vomiting, and peripheral neuropath y. At this stage the patient needs renal replacement treatment. Laboratory manifestations of stages 4 and 5 of chronic kidney dis- ease are listed in TABLE 14–36. Laboratory and Imaging Studies 487 TABLE 14–35 Schwartz Equation 1. Formula: Length in cm GFR = K(length, cm/plasma creatinine, mg/dl) = ml/1.73 m 2 Plasma creatinine in mg/dl. (K is a constant that changes with the age and gender of the patient.) 2. K = 0.33 for preterm infants (males and females); the normal creatinine clearance at this age is 40.6 ± 14.8 ml/1.73 m 2 . 3. Between 2 and 8 weeks of age, the value of K is 0.45 for both genders; the average value of the creatinine clearance is 65.8 ± 24.8 ml/1.73 m 2 . 4. After 8 weeks of age to 2 years of age, the value of is K = 0.45; the calculated normal clearance is 95.7 ± 21.7 ml/1.73 m 2 for both genders. 5. Between 2 and 12 years of age, K value is 0.55 for males and females; the calculated creatinine clearance is 133.0 ± 27 ml/1.73 m 2 per minute. 6. For adolescent males 13 to 21 years of age, K value is 0.70; the calculated creatinine clearance is 140.0 ± 30 ml/1.73 m 2 per minute. 7. For adolescent females 13 to 21 years of age, K value is 0.55; the calculated creatinine clearance is 126 ± 22 ml/1.73 m 2 per minute. When to Refer Table 14–37 notes some reasons for pediatric nephrology referral. Indi- cations for urology referral appear in Chapter 19. 488 Chapter 14: The Renal System TABLE 14–37 When to Refer to the Pediatric Nephrologist (Partial List) Infants and children with multicystic dysplastic kidney Neonatal hypertension Hypercalciuria Hyperkalemia Hypokalemia Solitary functioning kidney Small kidneys Enlarged kidneys Autosomal recessi ve polycystic kidney disease (ARPKD) Congenital nephrotic syndrome Bartter syndrome Beckwith-Wiedemann syndrome Obstructive uropathy Steroid resistant nephrotic syndrome Nephrot ic syndrome in children 8 years of age or older and those with relapses Acute nephrotic syndrome not associated with infection Metabolic acidosis and failure to thrive Infants with recurrent febrile urina ry tract infections Renal artery thrombosis Renal vein thrombosis Proteinuria Secondary hypertension Renal failure TABLE 14–36 Laboratory Manifestations of Stages 4 and 5 Chronic Kidney Disease Elevated creatinine and BUN Hypocalcemia Hyperphosphatemia Hyperparathyroidism Hyponatremia Metabolic acidosis Hyperkalemia Normocytic anemia Hypercholesterolemia and hypoalbuminemia ( as seen in those with the nephrotic syndrome) [...]... from the myeloid cell line, the T and B lymphocytes from the lymphoid, the RBCs from the erythroid, and the platelets from megakaryocytes As the RBCs mature, they shed their nuclei and contain increasing amounts of hemoglobin that helps to transport oxygen The hemostatic system consists of coagulation factors For the most part, these are enzymes that circulate as precursors (zymogen) that convert to the. .. plasma The latter contains coagulation proteins and enzymes that are essential for hemostasis Endothelium and subendothelial elements such as collagen are also an essential part of the hemostatic system In the fetus, the mesoderm of the yolk sac initially produces blood From the second to the seventh intrauterine period, the liver and spleen perform this function Subsequently, the bone marrow, in all the. .. 15 The HematologyOncology System Elna N Saah, Renuka Gera, Ajovi B Scott-Emuakpor, and Roshni Kulkarni HEMATOLOGY The goals of this section are 1 To outline the physiology and mechanics of the hematopoietic system and the hemostatic system 2 To describe the functional anatomy of the hematopoietic system and the hemostatic system 3 To describe the signs and symptoms associated with perturbations in the. .. soluble protein The platelet, along with the endothelium, is an integral part of the hemostatic system containing granules that participate actively in coagulation I HEMATOPOIETIC SYSTEM It is important to understand that signs and symptoms of hematologic disorders are based on derangements in the normal function of one or more of the cellular elements of blood Therefore, the goals of the chapter are... that become “committed” to a particular cell line They undergo a series of differentiation steps, under the influence of “growth factor” or regulatory molecules, to give rise to mature blood cells The stem cells retain their capacity for self-renewal, and the stromal cells and microvasculature of the marrow provide a microenvironment for sustained growth The purpose of the hemostatic system is to preserve... more platelets The platelets attach to each other (platelet aggregation), forming a “platelet plug” that is usually sufficient to stop minor bleeding The von Willebrand factor (VWF) released by the platelets serves as a tethering protein in conditions of high-flow shear While the intrinsic and extrinsic pathways are laboratory phenomena to explain the prothombin time (PT) and the activated partial thromboplastin... is necessary to make a 494 Chapter 15: The Hematology-Oncology System diagnosis of anemia These values exhibit gender differences as well as geographic and racial differences There are three key diagnostic tests necessary in the workup of anemia They are examination of a peripheral blood smear, complete blood count (CBC), and the reticulocyte count Armed with these three pieces of information, one... includes the review of blood smears TABLE 15–1 gives the conventionally accepted mean values of RBCs at various ages The RBC values represented in the table are now generated by electronic counters as opposed to the old manual measurements The RBC number and the mean corpuscular volume (MCV) are direct measurements; the hemoglobin concentration is the product of a chromatographic quantification, and from these... values, one calculates the mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) The RBCs, WBCs, and platelets (Pl) are direct measurements by the same method (gated-window pool) Laboratory The blood smear and indices are essential for hematologic evaluation We apply them below to the differential diagnosis of anemia Examination of the Blood Smear There are many features... The only difference will be in the relative frequencies of the events Rapid blood loss from trauma is more likely in an adolescent than in a child Girls of this age are more likely to have anemia than boys owing to increased blood loss from menstruation Key problems are for all age groups KEY PROBLEM Fatigue The patient either feels “tired” or “weak,” or the caretaker portrays the patient as such The . maturation. The WBCs derive from the myeloid cell line, the T and B lymphocytes from the lymphoid, the RBCs from the erythroid, and the platelets from megakaryocytes. As the RBCs mature, they shed their. with the nephrotic syndrome) 489 The Hematology- Oncology System 15 Chapter HEMATOLOGY The goals of this section are 1. To outline the physiology and mechanics of the hematopoietic system and the. system. In the fetus, the mesoderm of the yolk sac initially produces blood. From the second to the seventh intrauterine period, the liver and spleen perform this function. Subsequently, the bone