Loss of Functional Nephrons Requires Surviving Nephrons to Excrete More Water and Solutes. It would be reasonable to suspect that decreasing the number of functional nephrons, which reduces the GFR, would also cause major decreases in renal excretion of water and solutes. Yet patients who have lost up to 75 to 80 percent of their nephrons are able to excrete normal amounts of water and electrolytes without serious accumulation of fluid or most electrolytes in the body fluids. Further reduction in the number of nephrons, however, leads to electrolyte and fluid retention, and death usually ensues when the number of nephrons falls below 5 to 10 percent of normal.

In contrast to the electrolytes, many of the waste products of metabolism, such as urea and creatinine, accumulate almost in proportion to the number of nephrons that have been destroyed. The reason for this is that sub stances such as creatinine and urea depend largely on glomerular filtration for their excretion, and they are not reabsorbed as avidly as are the electrolytes. Creatinine, for example, is not reabsorbed at all, and the excretion rate is approximately equal to the rate at which it is filtered.

Creatinine filtration rate

 = GFR × Plasma creatinine concentration

= Creatinine excretion rate

Therefore, if GFR decreases, creatinine excretion rate also transiently decreases, causing accumulation of creatinine in the body fluids and raising plasma concentration until excretion rate of creatinine returns to normal—the same rate at which creatinine is produced in the body (Figure 1). Thus, under steady-state conditions creatinine excretion rate equals the rate of creatinine production, despite reductions in GFR; however, this normal rate of creatinine excretion occurs at the expense of elevated plasma creatinine concentration, as shown in curve A of Figure2.

Fig1.  Effect of reducing the glomerular filtration rate (GFR)  by 50 percent on serum creatinine concentration and on creatinine  excretion rate when the production rate of creatinine remains  constant.

Fig2.  Representative patterns of adaptation for different  types of solutes in chronic renal failure. Curve A shows the approximate changes in the plasma concentrations of solutes such as creatinine and urea that are filtered and poorly reabsorbed. Curve B shows  the approximate concentrations for solutes such as phosphate, urate,  and hydrogen ion. Curve C shows the approximate concentrations  for solutes such as sodium and chloride.

Some solutes, such as phosphate, urate, and hydrogen ions, are often maintained near the normal range until GFR falls below 20 to 30 percent of normal. Thereafter, the plasma concentrations of these substances rise, but not in proportion to the fall in GFR, as shown in curve B of Figure 2. Maintenance of relatively constant plasma concentrations of these solutes as GFR declines is accomplished by excreting progressively larger fractions of the amounts of these solutes that are filtered at the glomerular capillaries; this occurs by decreasing the rate of tubular reabsorption or, in some instances, by increasing tubular secretion rates.

In the case of sodium and chloride ions, their plasma concentrations are maintained virtually constant even with severe decreases in GFR (see curve C of Figure 2). This maintenance is accomplished by greatly decreasing tubular reabsorption of these electrolytes.

For example, with a 75 percent loss of functional nephrons, each surviving nephron must excrete four times as much sodium and four times as much volume as under normal conditions (Table 1).

Table1. Total Kidney Excretion and Excretion  per Nephron in Kidney Disease

Part of this adaptation occurs because of increased blood flow and increased GFR in each of the surviving nephrons, owing to hypertrophy of the blood vessels and glomeruli, as well as functional changes that cause the blood vessels to dilate. Even with large decreases in the total GFR, normal rates of renal excretion can still be maintained by decreasing the rate at which the tubules reabsorb water and solutes.

Isosthenuria—Inability of the Kidney to Concentrate or Dilute the Urine. One important effect of the rapid rate of tubular flow that occurs in the remaining nephrons of diseased kidneys is that the renal tubules lose their ability to fully concentrate or dilute the urine. The concentrating ability of the kidney is impaired mainly because (1) the rapid flow of tubular fluid through the collecting ducts prevents adequate water reabsorption and (2) the rapid flow through both the loop of Henle and the collecting ducts prevents the countercurrent mechanism from operating effectively to concentrate the medullary interstitial fluid solutes. Therefore, as progressively more nephrons are destroyed, the maximum concentrating ability of the kidney declines and urine osmolarity and specific gravity (a measure of the total solute concentration) approach the osmolarity and specific gravity of the glomerular filtrate, as shown in Figure 3.

Fig3. Development of isosthenuria in a patient with decreased  numbers of functional nephrons.

The diluting mechanism in the kidney is also impaired when the number of nephrons decreases markedly because the rapid flushing of fluid through the loops of Henle and the high load of solutes such as urea cause a relatively high solute concentration in the tubular fluid of this part of the nephron. As a consequence, the diluting capacity of the kidney is impaired and the minimal urine osmolality and specific gravity approach those of the glomerular filtrate. Because the concentrating mechanism becomes impaired to a greater extent than does the diluting mechanism in CKD,

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مواضيع ذات صلة

Injury to The Renal Vasculature as A Cause OF Chronic Kidney Disease

Vicious Cycle of Chronic Kidney Disease Leading to End-Stage Renal Disease

Intrarenal Acute Kidney Injury Caused by Abnormalities Within the Kidney

Prerenal Acute Kidney Injury Caused by Decreased Blood Flow to the Kidney

kidney Diseases

Diuretics and Their Mechanisms of Action

Conditions That Cause Large Increases in Extracellular Fluid Volume but with Normal Blood Volume

Conditions That Cause Large Increases in Blood Volume and Extracellular Fluid Volume

Integrated Responses to Changes in Sodium Intake

Role of Atrial Natriuretic Peptide in Controlling Renal Excretion

Role of Aldosterone in Controlling Renal Excretion

Role of Ang II in Controlling Renal Excretion