Chapter 15 The Kidneys and the Urinary System
Uremia is a set of clinical and laboratory findings encountered in patients with end-stage kidney disease. Key laboratory features reflect inadequate excretion of degradation products and minerals and include:
Acute renal failure has a rapid onset and develops over a period of several days or weeks. Most often it is characterized by a reversible deterioration of renal function, oliguria (or anuria), azotemia, and electrolyte disturbances. Most patients recover, but in some patients, the injury is irreversible. Such patients may die or require dialysis (“artificial kidneys”) to survive.
|Type of Renal Failure||Pathogenesis||Clinical Condition|
|Prerenal||Decreased renal perfusion||Congestive heart failure|
|Loss of blood||Massive bleeding|
|Renal||Glomerular disease||Acute glomerulonephritis|
|Tubulointerstitial nephritis||Drug reaction|
|Toxic tubular necrosis||Mercury poisoning|
|Postrenal||Intratubular obstruction||Acute urate nephropathy|
|Ureteric obstruction||Urinary stones|
|Bladder/urethral obstruction||Prostatic hyperplasia|
UTI is characterized by bacteriuria and pyuria (bacteria and leukocytes in the urine). Bacteriuria is defined for clinical purposes as the presence of more than 100,000 bacteria per milliliter of cultured urine. Leukocytes are counted in the urinary sediment examined microscopically. The diagnosis of urinary bacterial infection affecting either the kidneys or the lower urinary tract is made if the patient has signs of urinary irritation, urgency, or pain and the urinalysis shows more than 100,000 colonies per milliliter. If the urine contains more than 100,000 bacterial colonies per milliliter but the patient has no clinical symptoms, the diagnosis of asymptomatic bacteriuria is made.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common congenital kidney disease. It has an incidence of 1 in 800 and accounts for approximately 10% of patients on maintenance renal dialysis. ADPKD, also known as adult polycystic renal disease, is usually asymptomatic in childhood. Although it is congenital, it is diagnosed only during adult life. Renal dysplasia is the most common renal congenital anomaly diagnosed during infancy and childhood.
This developmental abnormality may be unilateral or bilateral. It results from irregular differentiation and morphogenesis of the metanephros, the primordium of the fetal kidneys. Histologically, the parenchyma of these abnormal kidneys consists of immature nephrons, often showing signs of cystic dilatation. The tubules and glomeruli are surrounded by immature mesenchyma and heterologous cells (e.g., cartilage or striated muscle). On gross examination, the abnormal kidneys appear enlarged and cystic. It may be associated with ureteropelvic obstruction and other anomalies of the lower urinary tract.
Unilateral cystic dysplasia, which is more common than bilateral dysplasia, usually is discovered on abdominal palpation as an abnormal mass. With nephroblastoma (Wilms tumor) and neuroblastoma of the adrenal, it is one of the three most common abdominal masses diagnosed in infants and young children.
Figure 15-1 Polycystic kidney disease (PCKD). A, Autosomal recessive PCKD. Small, uniform cysts visible on cross-section account for the spongy texture of the moderately enlarged kidney. Both kidneys are symmetrically involved. B, Autosomal dominant PCKD. Large cysts filled with fluid distort the kidney. Both kidneys are affected and may become extremely large.
|Feature||Autosomal Dominant PCKD||Autosomal Recessive PCKD|
|Incidence||Common (1:800)||Rare (1:15,000)|
|Inheritance||Autosomal dominant||Autosomal recessive|
|Gene||Polycystin genes (PKD1 = 85%)||Fibrocystin, PKHD1|
|Gross appearance||Large cystic kidneys (>1000g)||Spongelike symmetrically enlarged (100–200g)|
|Cysts||Large (from any tubule)||Small (collecting duct derived)|
|Symptoms||Infancy, childhood||Adulthood (>35 years)|
|Associated anomalies||Polycystic liver disease (20%)|
Berry aneurysms of cerebral arteries
|Small bile duct cysts, liver fibrosis|
The traditional distinction of glomerular diseases into primary and secondary glomerulopathies is arbitrary and not always convincing. Those diseases that selectively affect glomeruli or most prominently damage glomeruli are called primary.
Glomerular hypercellularity can be caused by proliferation of endogenous cells or exudation of inflammatory cells carried by blood. Morphologically, such hypercellularity can be intracapillary (i.e., the cells are found inside the capillaries and the mesangial areas) or extracapillary (i.e., the cells are found in the urinary space enclosed by the Bowman capsule). Such extracapillary cell aggregates are called crescents. From the pathogenetic standpoint, glomerular hypercellularity can be due to:
According to this nomenclature, mild nephritis of systemic lupus erythematosus (SLE) is classified as focal and segmental. This means that some and not all glomeruli are affected. In the affected glomeruli, only some loops show pathologic changes, whereas others are normal.
21 What pattern of staining of glomeruli is seen by immunofluorescence microscopy in anti-GBM nephritis?
Immunofluorescence microscopy tests are performed with fluoresceinated rabbit or mouse antibodies that recognize human antigens. Using these antibodies to human immunoglobulin (Ig) G, one can demonstrate where the immunoglobulins are deposited. In typical anti-GBM glomerulonephritis, such as Goodpasture syndrome, IgG is bound diffusely to all collagen type IV molecules in the GBM. Staining with antihuman IgG will produce a linear pattern (i.e., the fluoresceinated antibodies outline the GBMs).
22 What pattern of staining of glomeruli is seen by immunofluorescence microscopy in circulating immune complex nephritis?
Circulating immune complexes form granular deposits along the basement membrane. Typically this is seen in SLE. Depending on the size, solubility, and electric charge of the immune complexes, they may get “stuck” on the endothelial, intramembranous, or subepithelial region of the GBM or in the mesangial areas.
Membranous glomerulopathy is an immunologic disease in which immune complexes appear on the GBM in a uniform granular manner (usually referred to as “lumpy-bumpy”). The subepithelial (epimembranous) location of these antigens indicates that they may be formed locally through the action of antibodies and a local foot-process antigen (megalin or gp-330) or by the implantation of preformed circulating immune complexes.
24 In which parts of the glomeruli may the antigen–antibody complexes be seen by electron microscopy in various forms of glomerulonephritis?
Figure 15-2 Immunologic diseases of the kidneys. Typical location of immune complexes, as seen using electron microscopy. A diagram of a normal capillary is included for comparison. Left, Normal glomerulus. The basement membrane (BM) is lined from the capillary side by a fenestrated endothelial cell (En). On the urinary side, the BM is covered with the foot processes (FP) of the epithelial cell (Ep). The mesangial cell (Mes) is surrounded by matrix and does not extend to the capillary BM. Right, Immune complex deposits in the glomerulus. A, Large subepithelial “humps” typical of poststreptococcal or other forms of acute postinfectious glomerulonephritis. B, Subepithelial “lumpy-bumpy” deposits typical of membranous nephropathy. C, Subendothelial deposits typical of systemic lupus erythematosus (SLE). D, Intramembranous deposits seen in many immunologic diseases, most notably SLE and membranoproliferative glomerulonephritis. E, Mesangial deposits seen in immunoglobulin A nephropathy (Berger disease) and SLE.
27 List the soluble mediators of inflammation that contribute to the antibody-mediated glomerular injury
Group A beta-hemolytic streptococci (Streptococcus pyogenes) account for 90% of all glomerulonephritis cases. Glomerulonephritis typically occurs 1 to 4 weeks after a strep throat or skin infection (impetigo) caused by one of the nephritogenic strains of this microbe. Occasionally the same clinical and pathologic findings may follow staphylococcal infection and even some viral diseases, such as hepatitis B or C or hepatitis caused by human immunodeficiency virus (HIV). See Fig. 15-3.
Figure 15-3 Poststreptococcal glomerulonephritis. Left, Normal glomerulus. Right, Poststreptococcal glomerulonephritis. The glomerulus is hypercellular and contains neutrophils (N) and increased numbers of mesangial cells (Mes). Large immune complex deposits form spikes on the subepithelial side of the basement membrane in the form of humps (H).
Subepithelial humps represent epimembranous deposits of immune complexes on the GBM in postinfectious glomerulonephritis. They can be seen using electron microscopy. These humps represent only the “tip of the iceberg”—that is, they are the only ultrastructurally visible immune complexes. Immunofluorescence microscopy shows that the glomeruli contain many other immune complexes, which probably are not dense enough to be seen by electron microscopy. These smaller immune complexes are found in the mesangial areas and in the basement membrane and are distributed without any regularity.
Classic acute glomerulonephritis is a childhood disease. It usually presents with fever, nausea, oliguria, hematuria, RBC casts in urine, mild proteinuria (usually <1g/day), periorbital edema, and mild to moderate hypertension.
Atypical glomerulonephritis is the term used for the disease occurring in adults. The onset may be insidious, or the disease may present with a sudden appearance of hypertension or edema and biochemical signs of azotemia.
33 Why is the concentration of serum complement C3 low in acute poststreptococcal glomerulonephritis?
As immune complex deposits are formed in the glomeruli, they activate complement through the classical pathway, leading to a depletion of serum complement. C3 is the complement protein consumed in both the classical and the alternate complement pathways and is therefore used for monitoring the serum concentration of the entire complement system. Other complement proteins are also depleted, but there is no need to measure all of them at the same time. When the disease wanes, C3 levels return to normal.