Renal threshold

Glucosuria Occurs When the Renal Threshold for Glucose Is Exceeded... 

In moderate ketonemia, the loss of ketone bodies via the urine is only a few percent of the total ketone body production and utilization. Since there are renal threshold-like effects (there is not a true threshold) that vary between species and individuals, measurement of the... 

Consider briefly the disease gout, which is characterized by the precipitation of urates in tissues and by the presence of hyperuricemia. Bauer and Klemperer state, 11 "The etiology of the disease is unknown." As has been pointed out by other writers, the presence of high concentrations of uric acid in the blood may be due to (1) overproduction, (2) lowered excretion, (3) lowered destruction, or, of course, any combination of the three. Let us consider two hypothetical individuals, A and B, 30 years of age who have exactly the same uric acid blood level (4 mg. per cent) and exactly the same amount of blood (8 liters). The total uric acid in their respective bloods is 320 mg. Let us suppose further that the rate of production of uric acid in the two individuals is continuously exactly the same, the rate of destruction in the two is continuously the same, and that they consume exactly the same food. One hypothetical individual, A, however, continuously excretes on the average 0.1 mg. less uric acid per day than the other. This is very little, compared with the usual total excretion of 700 mg. per day. In the course of 10 years, A s uric acid blood level will, however, have more than doubled, due to this increased retention, and he will be in the range of "gouty" as contrasted with "normal" individuals. This could happen by a very gradual increase, in one individual, of the renal threshold for uric acid. Whether excretion, production, or destruction is responsible for the difference between individuals, the total accumulation of uric acid in hyperuricemia is small. 

The processes of selective reabsorption of nutrients and xenobiotics goes on within the complex tubule system. 98-99% of filtered materials (salts, water, sugars, amino acids) are eventually reabsorbed by passive or active transport. Biomolecules such as glucose and amino acids are entirely reabsorbed if their concentrations are within the normal range in the blood. However, should the concentrations be higher than normal, those molecules might not be completely reabsorbed because they have exceeded the ability of the nephron transport systems to accommodate them. This is referred to as exceeding the renal threshold. Urine is therefore a convenient body fluid to assay for the initial assessment of metabolic or excretory system malfunctions. 

A striking symptom of diabetes is the high blood glucose level which may range from 8 to 60 mM. Lower values are more typical for mild diabetes because when the glucose concentration exceeds the renal threshold of 8 mM the excess is secreted into the urine. Defective utilization of glucose seems to be tied to a failure of glucose to exert proper... 

Whatever the site of the enzyme may be, Keston et al. have recently produced fairly conclusive evidence that glucose, which is reabsorbed by the kidney, is exposed to mutarotase at some stage of the process (117). Glucose infused into the renal artery spills into urine when the renal threshold is exceeded in the same anomeric form as that administered, whereas reabsorbed glucose in the renal vein is mutarotated. Hill has also shown that the anomer infused in excess is excreted in excess (73). 

The plasma concentration of ascorbate shows a sigmoidal relationship with intake. Below about 30 mg per day, the plasma concentration is extremely low and does not reflect increasing intake to any significant extent. As the intake rises above 30 mg per day, so the plasma concentration begins to increase sharply, reaching a plateau of 70 to 85 /rmol per L, at intakes between 70 to 100 mg per day, when the renal threshold is reached and the vitamin is excreted quantitatively with increasing intake. 

At intakes in excess of about 100 mg per day, there is quantitative urinary excretion of unmetabolized vitamin C with increasing intake, indicating that tissue reserves are saturated and the renal threshold has been exceeded. It is difficult to justify a requirement in excess of tissue storage capacity. 

There is little evidence of any significant toxicity from these high intakes, although there are a number of potential problems (Rivers, 1987 Johnston, 1999). Because ascorbate is largely absorbed by active transport, absorption is saturable, and a decreasing proportion of high doses is absorbed. Similarly, once the plasma concentration has reached the renal threshold, the vitamin is excreted quantitatively with increasing intake (Section 13.2.1). 

Dystrophic muscle may contain only a tenth as much creatine as normal muscle (Rl), despite a suflBcient content of ADP and ATP (R9), due to its very low content of creatine kinase on which muscle creatine depends for its acceptance, retention, and use as creatine phosphate, since the total creatine content of dystrophic muscle is known to be directly proportional to the activity of the creatine kinase within it (R8). Excess creatine from the liver thus exceeds its renal threshold and is excreted in large amounts, while the low creatinine excretion indicates how slight is the remaining muscle function. 

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