NEPHROTIC SYNDROME CHRONIC GLOMERULONEPHRITIS GLOMERULAR DISEASE Glomerular ACUTE NEPHRITIC SYNDROME It reflects an acute inflammatory response w/in the kidney & is characterized in the urine sediment by: Hematuria RBC casts Other signs of acute inflammatory renal injury: proteinuria peripheral edema hypertension, or renal insufficiency w/ or w/out oliguria Pathophysiology Pathophysiology The hallmark of the acute nephritic syndrome is the finding of RBCs and RBC (as well as other) casts in the urine sediment The finding of RBC casts in a patient w/ hematuria virtually ensures that the patient has a glomerular pathologic process The severity of these abnormalities also varies, since hematuria can be either microscopic or grossly visible. The urinary findings in acute glomerular disease vary, ranging from normal (usu. seen in subclinical disease) to signs of proteinuria, hematuria, pyuria, lipiduria, & RBC & other casts The degree of proteinuria can range from just above the upper limit of normal to the nephrotic range Pathophysiology The manner in w/c RBCs pass into the urine in glomerular dse probably due to focal disruptions in the glomerular capillary wall produced by the underlying inflammatory process
These focal disruptions along the glomerular capillary
wall may contribute to proteinuria & may allow plasma proteins larger than albumin to escape into the urine Pathophysiology Renal Na & water retention resulting in generalized edema is common because of poor renal perfusion stemming from a decline in renal blood flow & proteinuria Resulting hypoalbuminemia & a decline in intravascular volume Elevated blood pressure is an additional common clinical component. Both volume overload from inappropriate renal fluid retention & enhanced renin secretion from renal injury & resulting vasoconstrictor tone play important roles in this process. Pathophysiology The GFR is often reduced resulting in a rise in blood urea nitrogen This reduction is a result of declines in: glomerular blood flow, glomerular transcapillary hydraulic pressure gradients, & the glomerular permeability coefficient, w/c is a function of both porosity and surface area available for filtration of the glomerular capillary. Pathophysiology Often in this syndrome, renal insufficiency is transient, but it also can be progressive, leading to chronic glomerulonephritis & renal failure. Most patients w/ acute nephritis have a form of proliferative glomerulonephritis &, occasionally, acute tubulointerstitial nephritis for this reason, renal biopsy is generally performed to determine the final diagnosis. Causes Postreptococcal NEPHROTIC SYNDROME The manifestations of the nephrotic syndrome include: Massive proteinuria, w/ the daily loss of 3.5 gm or more of protein (less in children) Hypoalbuminemia, w/ plasma albumin levels <3 gm/dL Generalized edema Hyperlipidemia & lipiduria Pathophysiology The various components of nephrotic syndrome bear a logical relationship to one another The initial event is proteinuria Proteinuria is due to an increase in glomerular permeability of serum alb. & arises in response to alterations in both the size & charge barriers of the glomerular filtration apparatus As a consequence of proteinuria, the serum alb. conc. & therefore the plasma oncotic pressure fall. Pathophysiology The generalized edematous state common to the nephrotic syndrome Largely caused by this drop in plasma oncotic pressure & the movement of fluid from the vascular to the interstitial fluid compartment producing a decline in plasma volume that signals the kidney to retain Na & water Pathophysiology Most patients have: Increased blood levels of cholesterol, TG, VLDL, LDL, Lp(a) lipoprotein, & apoprotein Decrease in HDL conc. in some patients. These defects seem to be due in part to: Increased synthesis of lipoproteins in the liver, abnormal transport of circulating lipid particles Decreased catabolism Lipiduria follows the hyperlipidemia because not only albumin molecules but also lipoproteins leak across the glomerular capillary wall. The lipid appears in the urine either as free fat or as oval fat bodies, representing lipoprotein resorbed by tubular epithelial cells & then shed along w/ the degenerated cells. Pathophysiology These patients are particularly vulnerable to infection Especially w/ staphylococci & pneumococci This vulnerability could be related to loss of Igs or LMW complement components in the urine Thrombotic & thromboembolic complications are common due to loss of anticoagulant factors (e.g., antithrombin III) & antiplasmin activity through the leaky glomerulus Renal vein thrombosis, once thought to be a cause of nephrotic syndrome, is most often a consequence of this hypercoagulable state Causes The relative frequencies of the several causes of the nephrotic syndrome vary according to age and geography In children younger than 17 years in North America, the nephrotic syndrome is almost always caused by a lesion primary to the kidney whereas among adults, it may often be associated w/ a systemic disease Causes
Approximate prevalence of primary disease = 95% in children, 60% in adults.
Approximate prevalence of systemic disease = 5% in children, 40% in adults CHRONIC GLOMERULONEPHRITIS Many forms of glomerular disease can progress to chronic renal failure. On morphologic examination, this progression is characterized by scarring of most of the glomeruli. UA results are more benign, w/ less proteinuria & hematuria & w/ broad, waxy casts in the urine sediment Occasionally, the urine may have characteristics of nephritic, nephrotic, and chronic patterns. This urinary finding has been called a telescoped sediment and is usually seen in severe glomerulonephritis or vasculitis.