Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Kidneys and Urine
General Properties and Constituents of Urine
Chemical Composition of Urine

Solid urinary solutes (about 60 g in the daily output) comprise both organic and inorganic substances (Table 18.1).

Class="center">Table 18.1. Content of some inorganic ions and major organic substances in the urine of an adult

Currently, over 150 chemical constituents have been identified in urine. Below are data only on the most important components of human urine in health and in certain pathological states.

* Urine reaction is usually determined using litmus paper. If blue paper turns red and red paper remains unchanged, the urine reaction is acidic; if red paper turns blue and blue paper remains unchanged, the reaction is alkaline. In a neutral reaction, the paper does not change color.

Organic Constituents of Urine

Urea accounts for the bulk of organic substances found in urine. On average, an adult excretes about 30 g of urea per day (ranging from 12 to 36 g). The total daily urinary nitrogen excretion ranges from 10 to 18 g, with urea nitrogen accounting for 80–90% on a mixed diet. Urinary urea levels typically rise with a protein-rich diet, in any disease accompanied by accelerated tissue Protein Catabolism (febrile states, tumors, hyperthyroidism, diabetes, etc.), as well as upon administration of certain drugs (e.g., A number of Hormones). The excretion of urea decreases in severe Liver disorders (the liver is the primary site of urea synthesis in the body), Kidney diseases (especially with impaired renal filtration capacity), and following Insulin administration, among other factors.

Creatinine is likewise a final product of Nitrogen METABOLISM. It is formed in Muscle tissue from phosphocreatine. Daily creatinine excretion is relatively constant for any given individual and largely reflects their muscle mass. In men, 18 to 32 mg of creatinine is excreted per kg of body weight daily, whereas in women, the value is 10 to 25 mg. These figures show little dependence on dietary protein. Consequently, determining the 24-hour urinary creatinine excretion can be used in many cases to monitor the completeness of 24-hour urine collection.

Creatine is normally virtually absent from the urine of adults. It appears either upon the ingestion of significant dietary creatine or under pathological conditions. As soon as the serum creatine level reaches 0.12 mmol/L, it appears in the urine.

During the first years of a child's life, "physiological creatinuria" may occur. The appearance of creatine in the urine of infants is apparently due to enhanced creatine synthesis that outpaces muscular development. Some researchers also classify the creatinuria of the elderly as a physiological phenomenon, which arises as a consequence of muscle atrophy and incomplete utilization of the creatine produced in the liver. The highest urinary creatine levels are observed in pathological conditions of The Muscular System, primarily in myopathy, or progressive muscular dystrophy.

It is generally believed that creatine in the urine (creatinuria) of patients with myopathy may result from impaired fixation (retention) and phosphorylation processes within Skeletal Muscle. If the synthesis of phosphocreatine is impaired, creatinine is not formed either, and its content in the urine drops sharply. As a result of creatinuria and impaired creatinine synthesis, There is a sharp increase in

the urinary creatine coefficient:

Under normal conditions, this coefficient is close to 1.1.

It is also known that creatinuria can be observed in liver disorders, Diabetes Mellitus, endocrine disorders (hyperthyroidism, Addison's disease, acromegaly, etc.), and infectious diseases.

Amino Acids account for about 1.1 g of the 24-hour urinary volume. The ratio between individual amino acid concentrations in blood and urine is not uniform. The concentration of any given amino acid excreted in urine depends on its blood plasma level and the degree of its tubular reabsorption, i.e., its clearance. The highest concentrations in urine are found in Glycine and Histidine, followed by glutamine, Alanine, and Serine.

Hyperaminoaciduria occurs in hepatic parenchymal diseases. This is attributed to impaired deamination and Transamination processes in the liver. Hyperaminoaciduria is also observed in severe infectious diseases, malignancies, extensive trauma, myopathy, comatose states, hyperthyroidism, cortisone and ACTH therapy, and other conditions.

Disorders of individual Amino acid metabolism are also known. Many of these disorders are congenital or hereditary in nature (see Chapter 12). Phenylketonuria serves as a prime example. The cause of the disease is a hereditary deficiency of phenylalanine 4-monooxygenase in the liver, as a result of which the metabolic Conversion of the amino acid phenylalanine to Tyrosine is blocked. The consequence of this block is the accumulation of phenylalanine and its keto derivatives in the body and their appearance in large amounts in urine. Detecting phenylketonuria is very simple using ferric chloride: 2–3 minutes after adding a few drops of ferric chloride solution to urine, an olive-green color develops.

Another example is alkaptonuria (homogentisuria). In alkaptonuria, the urinary concentration of homogentisic acid—one of the intermediates of tyrosine metabolism—drastically increases. Consequently, urine left standing in the air darkens rapidly. The metabolic impairment in alkaptonuria stems from a deficiency of homogentisate oxidase.

Other known congenital disorders include: hyperprolinemia (arising from a deficiency of the enzyme Proline oxidase, resulting in prolinuria); hypervalinemia (an inherited disorder of valine metabolism accompanied by a sharp increase in urinary valine concentration); citrullinemia (an inherited Urea Cycle disorder caused by argininosuccinate synthetase deficiency, resulting in increased urinary excretion of citrulline), and others.

Uric acid is the end product of purine base metabolism. Approximately 0.7 g of uric acid is excreted daily in the urine. A heavy diet rich in Nucleoproteins leads after some time to an increased urinary excretion of exogenous uric acid. Conversely, on a purine-poor diet, uric acid excretion drops to 0.2 g per day.

Elevated uric acid excretion is observed in leukemia, polycythemia, hepatitis, and Gout. Urinary uric acid levels also rise upon the intake of acetylsalicylic acid and a number of Steroid Hormones.

Along with uric acid, urine always contains a small amount of Purines of both endogenous and exogenous origin.

Hippuric acid is always detected in small amounts in human urine (about 0.7 g in the 24-hour volume). It is a conjugate of glycine and benzoic acid. Increased excretion of hippuric acid is noted upon consuming a predominantly plant-based diet rich in Aromatic Compounds from which benzoic acid is formed.

In 1940, A. Quick and A.Ya. Pytel introduced the hippuric acid test (the Quick-Pytel test) into clinical practice. Under normal conditions, liver Cells detoxify administered benzoic acid (the patient ingests 3–4 g of sodium benzoate after a light breakfast) by conjugating it with glycine. The resulting hippuric acid is excreted in the urine. Normally, when performing the Quick-Pytel test, 65–85% of the administered sodium benzoate is excreted in the urine. In liver damage, the synthesis of hippuric acid is impaired, so its urinary level drops sharply.

Non-nitrogenous organic components of urine include oxalic, lactic, and citric (citrate) acids, as well as butyric, valeric, succinic (succinate), ß-hydroxybutyric, acetoacetic, and other acids. The total content of organic acids in the daily urine volume typically does not exceed 1 g.

Under normal conditions, The amount of each of these acids in the daily urine volume is measured in milligrams, making their quantitative determination quite challenging. In certain pathological and physiological states, the excretion of many of these compounds increases, making them easier to detect in urine. For instance, strenuous muscular activity elevates lactic acid levels, whereas citrate and succinate amounts rise during alkalosis.

Inorganic (Mineral) Components of Urine

Urine contains virtually all the Mineral Substances found in blood and other body Tissues. Out of the 50–65 g of dry residue obtained by evaporating a 24-hour urine sample, Inorganic Components account for 15–25 g.

Sodium and chloride ions. Normally, about 90% of dietary chlorides are excreted in the urine (8–15 g of NaCl per day). In a number of pathological conditions (such as chronic nephritis, diarrhea, and acute rheumatic fever), the renal excretion of chlorides may be reduced. The maximum concentration of Na⁺ and Cl^- ions (up to 340 mmol/L in urine) can be observed following the administration of large amounts of a hypertonic solution.

Potassium, calcium, and magnesium ions. Many researchers believe that virtually all potassium ions present in the glomerular filtrate are reabsorbed from the primary urine in the proximal segment of the nephron. Potassium ion secretion takes place in the distal segment, primarily driven by an exchange between potassium and hydrogen ions. Consequently, potassium depletion in the body is accompanied by the excretion of acidic urine.

Ca²⁺ and Mg²⁺ ions are excreted by The Kidneys in small amounts (see Table 18.1). It is generally accepted that only about 30% of the total Ca²⁺ and Mg²⁺ ions destined for removal from the body are excreted in the urine. The bulk of alkaline earth metals is eliminated via feces.

Bicarbonates, phosphates, and sulfates. The amount of bicarbonates in urine strongly correlates with urine pH. At pH 5.6, 0.5 mmol/L of bicarbonates is excreted; at pH 6.6, 6 mmol/L; and at pH 7.8, 9.3 mmol/L. Bicarbonate levels rise during alkalosis and drop during acidosis. Typically, less than 50% of the total phosphates eliminated by the body are excreted in the urine. During acidosis, urinary phosphate excretion increases. Phosphate levels in urine also rise in hyperparathyroidism. Administration of vitamin D decreases urinary phosphate excretion.

Sulfur-Containing Amino Acids—Cysteine, cystine, and Methionine—serve as the sources of urinary sulfates. These Amino acids are oxidized in body tissues to form sulfuric acid ions. The total sulfate content in a 24-hour urine sample generally does not exceed 1.8 g (calculated as sulfur).

Ammonia. As noted previously, there is a specific mechanism for Ammonia Production from glutamine involving the enzyme glutaminase, which is abundant in the kidneys. Ammonia is excreted in the urine in the form of ammonium salts. The concentration of these salts in human urine serves as a reliable indicator of acid-base balance. During acidosis, their urinary excretion increases, whereas during alkalosis, it decreases. The level of ammonium salts in urine may drop if the renal synthesis of ammonia from glutamine is impaired.