Chapter 045. Azotemia and Urinary Abnormalities (Part 6) pdf

Azotemia and Urinary Abnormalities Part 6 The normal glomerular endothelial cell forms a barrier composed of pores of ~100 nm that hold back blood cells but offer little impediment to

Chapter 045 Azotemia and Urinary Abnormalities

(Part 6)

The normal glomerular endothelial cell forms a barrier composed of pores

of ~100 nm that hold back blood cells but offer little impediment to passage of most proteins The glomerular basement membrane traps most large proteins (>100 kDa), while the foot processes of epithelial cells (podocytes) cover the urinary side of the glomerular basement membrane and produce a series of narrow channels (slit diaphragms) to normally allow molecular passage of small solutes and water but not proteins Some glomerular diseases, such as minimal change disease, cause fusion of glomerular epithelial cell foot processes, resulting in predominantly "selective" (Fig 45-3) loss of albumin Other glomerular diseases can present with disruption of the basement membrane and slit diaphragms (e.g.,

by immune complex deposition), resulting in losses of albumin and other plasma

proteins The fusion of foot processes causes increased pressure across the capillary basement membrane, resulting in areas with larger pore sizes The combination of increased pressure and larger pores results in significant proteinuria ("nonselective"; Fig 45-3)

When the total daily excretion of protein is >3.5 g, there is often associated hypoalbuminemia, hyperlipidemia, and edema (nephrotic syndrome; Fig 45-3) However, total daily urinary protein excretion >3.5 g can occur without the other features of the nephrotic syndrome in a variety of other renal diseases (Fig 45-3) Plasma cell dyscrasias (multiple myeloma) can be associated with large amounts

of excreted light chains in the urine, which may not be detected by dipstick (which detects mostly albumin) The light chains produced from these disorders are filtered by the glomerulus and overwhelm the reabsorptive capacity of the proximal tubule A sulfosalicylic acid precipitate that is out of proportion to the dipstick estimate is suggestive of light chains (Bence Jones protein), and light chains typically redissolve upon warming of the precipitate Renal failure from these disorders occurs through a variety of mechanisms including tubule obstruction (cast nephropathy) and light chain deposition

Hypoalbuminemia in nephrotic syndrome occurs through excessive urinary losses and increased proximal tubule catabolism of filtered albumin Hepatic rates

of albumin synthesis are increased although not to levels sufficient to prevent hypoalbuminemia Edema forms from renal sodium retention and from reduced

plasma oncotic pressure, which favors fluid movement from capillaries to interstitium The mechanisms designed to correct the decrease in effective intravascular volume contribute to edema formation in some patients These mechanisms include activation of the renin-angiotensin system, antidiuretic hormone, and the sympathetic nervous system, all of which promote excessive renal salt and water reabsorption

The severity of edema correlates with the degree of hypoalbuminemia and

is modified by other factors such as heart disease or peripheral vascular disease The diminished plasma oncotic pressure and urinary losses of regulatory proteins appear to stimulate hepatic lipoprotein synthesis The resulting hyperlipidemia results in lipid bodies (fatty casts, oval fat bodies) in the urine Other proteins are lost in the urine, leading to a variety of metabolic disturbances These include thyroxine-binding globulin, cholecalciferol-binding protein, transferrin, and metal-binding proteins A hypercoagulable state frequently accompanies severe nephrotic syndrome due to urinary losses of antithrombin III, reduced serum levels

of proteins S and C, hyperfibrinogenemia, and enhanced platelet aggregation Some patients develop severe IgG deficiency with resulting defects in immunity Many diseases (some listed in Fig 45-3) and drugs can cause the nephrotic syndrome, and a complete list can be found in Chap 277

Hematuria, Pyuria, and Casts

Isolated hematuria without proteinuria, other cells, or casts is often indicative of bleeding from the urinary tract Normal red blood cell excretion is up

to 2 million RBCs per day Hematuria is defined as two to five RBCs per high-power field (HPF) and can be detected by dipstick Common causes of isolated hematuria include stones, neoplasms, tuberculosis, trauma, and prostatitis Gross hematuria with blood clots is almost never indicative of glomerular bleeding; rather, it suggests a postrenal source in the urinary collecting system Evaluation

of patients presenting with microscopic hematuria is outlined in Fig 45-2 A single urinalysis with hematuria is common and can result from menstruation, viral illness, allergy, exercise, or mild trauma Annual urinalysis of servicemen over a 10-year period showed an incidence of 38% However, persistent or significant hematuria (>three RBCs/HPF on three urinalyses, or a single urinalysis with >100 RBCs, or gross hematuria) identified significant renal or urologic lesions in 9.1% Even patients who are chronically anticoagulated should be investigated as outlined in Fig 45-2 The suspicion for urogenital neoplasms in patients with isolated painless hematuria (nondysmorphic RBCs) increases with age Neoplasms are rare in the pediatric population, and isolated hematuria is more likely to be "idiopathic" or associated with a congenital anomaly Hematuria with pyuria and bacteriuria is typical of infection and should be treated with antibiotics after appropriate cultures Acute cystitis or urethritis in women can cause gross hematuria Hypercalciuria and hyperuricosuria are also risk factors for unexplained isolated hematuria in both children and adults In some of these

patients (50–60%), reducing calcium and uric acid excretion through dietary interventions can eliminate the microscopic hematuria