Encephalopathy blood levels

The alimentary symptoms may be overshadowed by neuromuscular dysfunction, accompanied by signs of motor weakness that may progress to paralysis of the exterior muscles or the wrist (wrist drop), and less often, of the ankles (foot drop). Encephalopathy, the most serious result of lead poisoning, frequendy occurs in children as a result of pica, ie, ingestion of inorganic lead compounds in paint chips this rarely occurs in adults. Nephropathy has also been associated with chronic lead poisoning (147). The toxic effects of lead may be most pronounced on the developing fetus. Consequendy, women must be particulady cautious of lead exposure (148). The U.S. Center for Disease Control recommends a blood level of less than 10 p.m per 100 mL for children. 

With chronic exposure, side effects may include rash, thrombocytopenia, leukopenia, and a lupus-like disorder. Chronic therapy is likely to result in tolerance, and withdrawal symptoms if primidone therapy is abruptly stopped. Doses in excess of 1500 mg (twice the maximum recommended daily dose) should be considered toxic. Less common side effects are hypotension, hypothermia, and dermal bullae. Encephalopathy has been observed in an epileptic patient with high plasma levels and poor renal function. With plasma concentrations exceeding 80pgml primidone may precipitate and cause crystalluria. Plasma levels >10 rgpml are associated with toxic effects. The therapeutic range is reportedly 5-10pgml , but clinical effects correlate more closely with phenobarbital blood levels. 

Overall, 99% of ingested bismuth may be eliminated in this way (Fowler and Vouk 1986, Mueller 1989). In cases of encephalopathy, with remarkably high urine and blood levels (2000 and 1500 igL respectively), the half-lives of bismuth were calculated for urine (4.5 days) and blood (5.2 days) (Iffland 1993). Cerebrospinalis... 

With blood levels in excess of 80 mcg/dL, serious overt intoxication may occur, including abdominal pain (lead colic) and nephropathy. Encephalopathy and neuropathy are usually associated with levels over 100 mc dL. 

Once absorbed in the body, lead is transported by the blood. Most is excreted (mainly via urine) but some is stored in body tissues, notably the bone where it has a half life of many years. Lead can cause a number of adverse health effects. At high levels of exposure, it can cause fatigue, aches and pains in muscles and joints, abdominal pain, colic and constipation. At very high levels, encephalopathy and even death can occur. In the modem occupational settings such effects are rarely, if ever, seen and the medical focus falls on the possibility of anaemia, renal insufficiency or neuropsychological effects. 

The daily elimination in untreated people is estimated at 12 ixg [12] including 2.9 xg excreted with the urine [27]. Ingested bismuth from therapeutics is mainly eliminated with feces as sulfide. Within 5 days 10-20% is excreted. But elimination is not finished after 10 days. Overall 99% may be eliminated in this way [3,12,17,29]. Absorbed bismuth is mainly excreted by urine the biliary/fecal elimination route is only about half of the urinary one [3,6,62-64]. Half-lives in blood after a single dose or during a treatment depend on the kind of the Bi compound, the amounts ingested, and the blood levels. Elimination from blood of bismuth subcitrate is biphasic [17,28,65]. In cases of encephalopathy with remarkably high urine and blood levels (2000 and 1500 p-g/liter, respectively), half-lives were calculated for urine (4.5 days) and blood (5.2 days). Liquor levels decreased more slowly with a half-life of 15.9 days [53]. Elimination kinetics is also described as a three-compartment model with half-lives of 3.5 min, 0.25 hr, and 3.2 hr [6]. Biological half-times in humans are reported for the whole body 5 days, the kidney 6 days, and the liver 15 days (cited in [3]). 

Between 1975 and 1978, 942 cases of encephalopathy were registered in France, 72 with lethal end. Mainly bismuth subnitrate but also other salts such as subsalicylate, subcarbonate, or subsilicate were ingested in amounts between 5 and 20 g daily over periods of years before the disease was attributed to bismuth. However, toxic events due to shorter treatments were also reported [46,74-79]. Large differences in blood levels existed (72-2360 p.g/liter) [53,75-77,79-83]. There is no relation between blood level, age, duration, and amount of ingestion and severity... 

A 45-year-old man with the acquired immunodeficiency syndrome was hospitalized for dehydration and watery diarrhea. The only successful treatment was with bismuth subsalicylate solution. The daily oral doses ranged from 5.2 to 9.4 g. After 7 days he showed symptoms of heavy bismuth encephalopathy and 3 days later he died blood level 200 ig/liter, urine level 2960 jLg/liter [36]. 

To summarize, a review of published data suggests that lead encephalopathy in the rat is generally found at blood levels above about 600/tg Pb/lOOml and up to 1300/tg Pb/lOOml, and is generally absent with levels below 600/tg Pb/100 ml. Between 200 and 600/tg Pb/lOOml, changes found in the rat brain may possibly derive in part from secondary nutritional disorders as well as from lead. Below 200/tg Pb/lOOml, changes may be seen in the lead-exposed rat nervous system and these are more likely to be due to primary effects of lead. 

It was earlier noted that human childhood lead encephalopathy is found with blood lead levels in the range 100-800/tg Pb/100 ml. It is a widely held view that animal models of human lead encephalopathy are of limited value (perhaps due to early experiments on adult animals, which, like man, show relatively little neurological disturbance even with prolonged and intensive dosage). However, this chapter shows that with lead exposure during development, blood levels of the same order of magnitude are associated both in man and rat with comparable encephalopathic lesions. 

Lead-induced encephalopathy in the young rat generally occurs at blood levels of about 500 fig/dl and above, whereas 100 jUg/dl is regarded as an... 

Depending on the level of lead exposure, children have been reported to have symptoms such as ataxia, convulsions, headache, and learning disabilities and tend to exhibit hyperactive behaviors. Encephalopathy has been reported in lead-toxic children. Learning and behavioral deficits in children have been reported. Blood levels of less than 10 micrograms per decUiter, which are comparatively low, could result in such deficits in children. Blood lead levels have demonstrated an inverse relation to the neuropsychological performance of children. Children 2 to 4 years of age had slower mental development as blood lead levels increased [4,6,9]. 

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. 

The literature on the neurobehavioral effects of oral exposure to lead in animals is extensive. Only those studies considered key to clarifying human health issues will be presented here. High levels of exposure to lead produce encephalopathy in several species, but blood lead data for this effect are generally not available. 

Death. Death can be the end result in cases of severe lead encephalopathy in both adults and children. The National Academy of Sciences (NAS 1972) analyzed unpublished data obtained from the patient populations reported in Chisolm (1962, 1965) and Chisolm and Harrison (1956) and concluded that the range of blood lead levels associated with death from lead encephalopathy in children was approximately 125-750 pg/dL (mean, 327 pg/dL). A case report described a 70-year-old female nursing home resident... 

One of the most sensitive systems affected by lead exposure is the nervous system. Encephalopathy is characterized by symptoms such as coma, seizures, ataxia, apathy, bizarre behavior, and incoordination (CDC 1985). Children are more sensitive to neurological changes. In children, encephalopathy has been associated with PbB levels as low as 70 pg/dL (CDC 1985). The most sensitive peripheral index of neurotoxicity of lead is reported to be slowed conduction in small motor libers of the ulnar nerve in workers with 30-40 pg/dL lead in blood (Landrigan 1989). Other potential biomarkers of lead suggested for neurotoxicity in workers are neurological and behavioral tests, as well as cognitive and visual sensory function tests (Williamson and Teo 1986). However, these tests are not specific to elevated lead exposure... 

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