Ammonia blood levels

A. Processing of the amino groups of the amino acids produces ammonia, which is toxic in its free form, especially to nerve cells. So, its metabolism is designed to keep blood levels low (ie, <40 XM). 

Blood levels of ammonia exceeding 40 pM have direct neurotoxic effects, especially disruption of neurotransmission in the CNS. 

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. 

There are several theories behind the cause of hepatic encephalopathy. One of these is that the accumulation of toxins in the brain, particularly ammonia, is the cause. Ammonia is produced in the intestine and is usually metabolised in the liver to urea via the urea cycle. As a result of portosystemic shunting and reduced metabolism in the liver, ammonia serum levels rise as the transformation to urea is reduced. However, the validity of this theory is questionable as not all patients with signs of hepatic encephalopathy have raised serum ammonia levels. Another theory is that patients with hepatic encephalopathy have increased permeability of the blood-brain barrier, and hence the increased toxin levels permeate the brain more than usual, leading to altered neuropsychiatric function. There are also theories relating to increased levels of neurotransmitters, short-chain fatty acids, manganese and increased GABA-ergic transmission. 

COHb is quite stable and its concentration does not change over a long period (up to 6 months) if the blood sample is stored in the dark and under sterile conditions. Blood levels of COHb are not expected to exceed 5% at ambient levels of CO. IPCS (1999) focuses on methods which can accurately measure COHb below 10%. A method which simply requires finger-prick blood is convenient for mass screening and is described in detail by Commins and Lawther (1965) in this method, the sample is diluted in ammonia solution, which is divided into two parts from one of these, CO is displaced by oxygen and the COHb containing part is placed in the sample beam of a spectrophotometer so that the instra-ment records the difference between the absorbance of COHb and oxyhemoglobin. 

Liver damage from excessive ethanol consumption occurs in three stages. The first stage is the aforementioned development of fatty liver. In the second stage—alcoholic hepatitis—groups of cells die and inflammation results. This stage can itself be fatal. In stage three—cirrhosis—fibrous structure and scar tissue are produced around the dead cells. Cirrhosis impairs many of the liver s biochemical functions. The cirrhotic liver is unable to convert ammonia into urea, and blood levels of ammonia rise. Ammonia is toxic to the nervous system and can cause coma and death. Cirrhosis of the liver arises in about 25% of alcoholics, and about 75% of all cases of liver cirrhosis are the result of alcoholism. Viral hepatitis is a nonalcoholic cause of liver cirrhosis. 

As early as 1815, C. B. Rose had assumed the synthesis of urea to be localized in the liver, (s. p. 10) In 1858 A. Heynsius observed that the concentration of urea was higher in the liver than in all other organs. In 1868 E. Stadelmann found patients with liver disease to have markedly increased blood levels of ammonia compared with normal individuals. 

In one infant with the fulminating variant of the disease the level of ammonia in the cerebrospinal fluid was 114 / g/100 ml when the blood level was over 800 /xg/100 ml (L5, L9) (Table 3). The only other reference to ammonia levels in cerebrospinal fluid or blood was by Carton et al. (C3), who observed in a neonate with argininosuccinic aciduria that the ammonia levels in both blood and cerebrospinal fluid as judged by column chromatography were high or very high. 

Thus there are two major differences in the two types of hyperornithinemia. The first is the high level of blood ammonia accompanied by the severe clinical manifestations of hyperammonia. The second is the much higher level of ornithinemia, 12-14 mg/100 ml compared with less than 2 mg/100 ml. It seems likely that the blood level of ornithine... 

CitruNinemis lAlso see UREA CYCLE.I Insufficient levels of itie enzyme argininosuccinic acid synthetase. Elevated blood ammonia after eating nausea vomibng memal retardation elevated blood level of cittullme. Restriction of dietary protein to 0.5 to 1.0 gAg per day. 

Hyperemmoneinia Insutlicient levels of the enzyme ornithine transcarbamylase or catBrnylphaspliaie synthetase. Ammonia intoxication—hi blood levels ol NHj vomiting lethargy coma menial retardation. Dietaiy protein restricted to 0.5 to 10 g/kg per day. 

Hyperlysinamis llysine iniDlerancel Insufficiem levels of the enzyme lysine NAO oxidoieductase. High blood levels ol arginine and lysine and sometimes ammonia vomibng spasticity coma mental retardation. Oieisry proiem restricted to 1.5 j/kg per day nc treatment necessary n some case ... 

Monosodium glutamate has been used in treating mental retardation and hepatic coma that is accompanied by a high blood level of ammonia. It has been reported to be effective in lowering the blood level of ammonia in many cases, though the mechanism of action is still unknown (martestdale usd 26th). 

Kanamycin, neomycin, and paromomycin are used orally in the management of hepatic coma. In this disorder, liver failure results in an elevation of blood ammonia levels. By reducing tire number of ammoniaforming bacteria in the intestines, blood ammonia levels may be lowered, thereby temporarily reducing some of the symptoms associated with this disorder. 

While ammonia, derived mainly from the a-amino nitrogen of amino acids, is highly toxic, tissues convert ammonia to the amide nitrogen of nontoxic glutamine. Subsequent deamination of glutamine in the liver releases ammonia, which is then converted to nontoxic urea. If liver function is compromised, as in cirrhosis or hepatitis, elevated blood ammonia levels generate clinical signs and symptoms. Rare metabolic disorders involve each of the five urea cycle enzymes. 

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10—20 Ig/dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-ketoglutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tricarboxylic acid (TCA) cycle in neurons. 

All defects in urea synthesis result in ammonia intoxication. Intoxication is more severe when the metabolic block occurs at reactions 1 or 2 since some covalent linking of ammonia to carbon has already occurred if citrulline can be synthesized. Clinical symptoms common to all urea cycle disorders include vomiting, avoidance of high-protein foods, intermittent ataxia, irritability, lethargy, and mental retardation. The clinical features and treatment of all five disorders discussed below are similar. Significant improvement and minimization of brain damage accompany a low-protein diet ingested as frequent small meals to avoid sudden increases in blood ammonia levels. 

Hyperammonemia Type 2. A deficiency of ornithine transcarbamoylase (reaction 2, Figure 29-9) produces this X chromosome-linked deficiency. The mothers also exhibit hyperammonemia and an aversion to high-protein foods. Levels of glutamine are elevated in blood, cerebrospinal fluid, and urine, probably due to enhanced glutamine synthesis in response to elevated levels of tissue ammonia. 

Hyperargininemia. This defect is characterized by elevated blood and cerebrospinal fluid arginine levels, low erythrocyte levels of arginase (reaction 5, Figure 29-9), and a urinary amino acid pattern resembling that of lysine-cystinuria. This pattern may reflect competition by arginine with lysine and cystine for reabsorption in the renal tubule. A low-protein diet lowers plasma ammonia levels and abolishes lysine-cystinuria. 

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... 

Increased blood ammonia concentration is characteristic of hepatic encephalopathy, but levels do not correlate well with the degree of impairment. 

Review biopsy reports and laboratory data. Transaminases and blood ammonia levels do not correlate well with disease progression, but increased coagulation times are markers of loss of synthetic function. 

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