Ammonia renal production

Renal Production of Ammonia and Excretion of Ammonium Ions... 

The enzymatic hydrolysis of these important co-amides of glutamic and aspartic acids is widespread in organisms. These enzymes have been reviewed by Zittle, and little more can be added here. Except in the renal production of urinary ammonia the hydrolytic cleavage of glutamine is probably an unimportant reaction, since uncoupled hydrolysis of these amides would involve a considerable loss of free energy as heat. 

Excretion into urine of ammonia produced by renal mbu-lar cells facilitates cation conservation and regulation of acid-base balance. Ammonia production from intracellular renal amino acids, especially glutamine, increases in metabolic acidosis and decreases in metabolic alkalosis. 

Nitrogen compounds commonly determined are creatinine, urea, and uric acid. Creatinine is an end product of the energy process occurring within the muscles, and is thus related to muscle mass. Creatinine in urine is commonly used as an indicator and correction factor of dilution in urine. Creatinine in serum is an indicator of the filtration capacity of the kidney. Urea is the end product of the nitrogen luea cycle, starting with carbon dioxide and ammonia, and is the bulk compoimd of urine. The production of uric acid is associated with the disease gout. In some cases, it appears that the excess of uric acid is a consequence of impaired renal excretion of this substance. 

Ammonia (NH3) is just one of the toxins implicated in HE. It is a metabolic by-product of protein catabolism and is also generated by bacteria in the GI tract. In a normally functioning liver, hepatocytes take up ammonia and degrade it to form urea, which is then renally excreted. In patients with cirrhosis, the conversion of ammonia to urea is retarded and ammonia accumulates, resulting in encephalopathy. This decrease in urea formation is manifest on laboratory assessment as decreased blood urea nitrogen (BUN), but BUN levels do not correlate with degree of HE. Patients with HE commonly have elevated serum ammonia concentrations, but the levels do not correlate well with the degree of central nervous system impairment.20... 

Antibiotics with activity against urease-producing bacteria, such as neomycin [42], paromomycin [44] or metronidazole [45], also reduce the production of intestinal ammonia and have proved to be of value. Vancomycin has also been used in patients with lactulose-resistant chronic encephalopathy [46]. The efficacy of neomycin is similar to that of lactulose [42]. However, a small percentage of this drug is absorbed from the gastrointestinal tract and may cause ototoxic and nephrotoxic effects, especially with continuous use over several months [47]. This drug should be used with particular caution by patients with renal insufficiency. The efficacy of metronidazole for... 

Lll. Lowe, C. U., Terrey, M., and MacLachlan, E. A., Organic aciduria decreased renal ammonia production, hydrophthalmos and mental retardation. A clinical entity. Am. ]. Diseases Children 83, 164-184 (1952). 

Most doctors use the plasma concentrations of creatinine, urea and electrolytes to determine renal function. These measures are adequate to determine whether a patient is suffering from kidney disease. Protein and amino acid catabolism results in the production of ammonia, which in turn is converted via the urea cycle into urea, which is then excreted via the kidneys. Creatinine is a breakdown product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass). Creatinine is mainly filtered by the kidney, though a small amount is actively secreted. There is little to no tubular reabsorption of creatinine. If the filtering of the kidney is deficient, blood levels rise. 

Figure 46-11 Hydrogen ion excretion, sodium hydrogen ion exchange, and ammonia production in the renal tubules. Key I, conversion of HPO to HiPO 2, reaction of hydrogen ions with NH3 3, excretion of undissociated acids 4, Na -H exchange 5, NH3 production and 6, synthesis of carbonic acid from CO2.

The ability to form ammonia is impaired with loss of functioning nephrons. This reduces the excretion of hydrogen ions, thus causing acidosis. Initially the mild acidosis does stimulate the production of ammonia by the remaining functional nephrons. However, the net result is continuing acidosis in the face of chronic renal failure. The most common causes of chronic renal failure are glomerulonephritis, pyelonephritis, obstructive nephropathy, and vascular nephropathy in severe hypertension. 

During certain disease states that result in renal tubular injury, NH4 production by renal proximal tubules may increase in order to maintain net acid excretion. However, this may also contribute to further renal damage by modifying the third component of complement and initiating the alternative complement pathway (Clark et al. 1990). Ammonia can chemically interact with an internal thiolester bond of complement 3 (C3), resulting in an amide linkage and a subsequent conformational change of the C3. 

In patients who have other medical problems such as advanced liver disease with hepatic insufficiency, it is often difficult to differentiate whether the encephalopathy is due to hepatic or renal causes. In patients with renal failure, the major route for elimination of urea is not available thus, there is an ino-ease in blood urea. The amount of urea that enters the colon is ino-eased because of the elevated plasma urea. Urea is then acted on by colonic bacteria and mucosal enzymes in a manner similar to that of protein and amino acids. This leads to inCTeased ammonia production in uremic subjects that may either increase plasma ammonia levels or lead to misinterpretation of this test. 

An elevated ammonia concentration can be the result of primary or secondary defect of the urea cycle. Ammonia is mainly a by-product of amino acid metabolism, although it is also produced by intestinal urease-positive bacteria. The urea cycle converts ammonia (or ammonium, NH, ) to urea, which is excreted by the renal systan in order to keep the serum concentration of ammonia low. An impairment of the urea cycle results in... 

Ammonia is produced in proximal and distal segments of the tubules. It is formed by the deamination of glutamine and other amino acid substrates in the liver, intestinal mucosa and the kidney. Any ammonia in the blood is taken up by the liver and converted to urea, the liver being the only organ in which urea is formed. Unlike blood, the urine contains appreciable quantities of ammonia. The enzyme glutaminase, located in the mitochondria of the renal tubule cells, catalyses the production of ammonia the reaction is shown in section A.2. Glutaminase is present in large amounts in the kidney and Its concentration there is raised in acidosis. 

In renal physiology, it is conventional to divide the renal mechanisms for the production of urine into three groups, glomerular filtration, tubular secretion and tubular reabsorption. The unique status of ammonia requires a fourth mechanism in renal physiology, which is the addition of newly-produced chemical to the urine. 

The stimulus to production of ammonia is intracellular acidosis in renal tubular cells. When an acidosis develops and persists, the rate of ammonia production by the renal tubular cells increases over the course of several days. This is due to induction of the enzyme glutaminase (i.e. the production of new enzyme). The rate of production of ammonia provides a homeostatic mechanism in the excretion of excess acid from the body. As is shown in Figure 7.4, in chronic metabolic acidosis the rate of ammonium ion excretion in the urine at a given urine pH is more than double the rate in a healthy person (Pitts, 1948). 

In this condition, all metabolic functions of the kidney are depressed these functions include tubular secretion of hydrogen ions, reabsorption of bicarbonate ions and production of ammonia. In a subject with impaired renal function, the urine can scarcely be concentrated or diluted by comparison with plasma, its pH can be only slightly lowered below or raised above the pH of plasma and, because of lack of ammonia synthesis, the excretion of acid is profoundly depressed. The kidney can no longer perform its homeostatic regulatory role. Such a patient consuming a normal diet becomes progressively more acidotic because of the release of acid resulting from the metabolism of protein (Chapter 5). 

Breath diagnostics involve the analysis of a human breath sample to monitor, diagnose, and detect diseases and conditions. Exhaled breath contains a complex mixture of nitrogen, oxygen, carbon dioxide, water, and trace amounts of various volatile organic compounds hke NO, acetone, isoprene, and ammonia. Many of these species are formed as the by-products of metabohc processes and can be used as biomarkers for various diseases. Examples of such biomarkers are acetone for diabetes mellitus (type I), ammonia for renal disease, NO for asthma, etc. 

During liver failure, the normal detoxification and synthetic functions of the liver are severely impaired. The liver support device should be able to detoxify and support the synthetic functions of the Uver either to serve as a bridge to liver transplant or permit sufficient liver regeneration so that liver transplantation is not needed. In this regard, the primary purpose of a support device would be to improve overall survival and transplant-free survival. Other possible secondary endpoints include improvements in encephalopathy and renal function, and reductions in measureable toxins and metabolic by-products, including bilirubin, ammonia, urea, and lactate. Ideally, the support device should be effective for both ALF and AOCLF, regardless of etiology. 

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