Citrate, intoxication

The amount of citrate in the blood plasma is correlated with the amount of ionized calcium. Any increase in plasma citrate reduces the ionized calcium, which, as will be discussed later, can cause the clinical disturbances known as citrate intoxication (B36, D17, L18, Wll). 

A condition described as citrate intoxication has been found in some patients after transfusion of large amounts of citrated blood (B36, D17, L18, M12, Wll). It associates a large increase in blood plasma citrate with a decrease in the ionized fraction of calcium, a decrease which may be responsible for the clinical symptoms encountered. 

Other examples of such accumulation are given by the change in the rate of disappearance of lactic acid from the blood after lactate load during hepatitis (S33), as well as of citric acid after citrate load (S22), or of a-ketoglutarate after glutamate load (Sll). The high levels of blood plasma citrate obtained in patients with liver damage after citrate load explain the frequency of citrate intoxication in such patients (B36, M12). 

Citrate intoxication, known to follow rapid transfusion of stored blood, is a common source of hypocalcemia in critically ill man and it has been recommended that calcium replacement therapy be undertaken only with close monitoring of ionic calcium with ion-selective electrodes [141]. The calcium ion-selective electrode has also been used [142] to morutor calcium ion levels in recipient s blood when it was observed that addition of calcium chloride to the circulation following administration of acid—citrate—dextrose blood caused a sharp rise and then a fall in the recipient s level of ionised calcium. 

Ogino, T. and M. Awai. 1988. Lipid peroxidation and tissue injury by ferric citrate in paraquat-intoxicated mice. Biochim. Biophys. Acta 958 388-395. 

Harrison (H5) has reported that serum citrate is increased above the normal range in hypervitaminosis D. Winberg and Zetterstrom (Wl) found it to be low in an 11-month-old infant suffering from vitamin D intoxication. Forfar et al. (F7) have reported that during the active phase of idiopathic hypercalcemia, serum citrate levels are low. 

Because Al toxicity is a serious iatrogen complication, any preventive measures to avoid exposure to Al is incumbent. Unfortunately, with the current treatment practices, there continues to be a risk that patients receive excessive amounts of Al orally or parenterally. If Al compounds cannot be avoided in patients with renal failure, routine Al tests performed every 3-4 months in serum will identify persons at greatest risk (s-Al levels >100 to 150 pg/L) for chronic Al intoxication. Ideally, any patient with s-Al higher than 40 to 50 pg/L should discontinue Al gels and use other substitutes. These patients should also be warned not to ingest these compounds with liquids containing citrate, for example, fruit juices. 

FIGURE 13.5. Concentration of citrate in blood and organs of rats under intoxication with SFA at I/2LD50. 

Petroff and co-workers reported a quantitative analysis of the H NMR spectra of six CSF samples from three patients. TTiese included a 34-year-otd man presenting with seizures several hours after injecting heroin and cocaine while intoxicated with alcohol, and a 7-month-old girl who presented as a febrile, cyanotic hypotensive in a coma. The H NMR spectrum of the CSF of the drug overdose victim showed clear and abnormally elevated signals for citrate, myo-inositol, creatinine/creatine and lactate. 

A. Symptomatic hypocalcemia resulting from intoxication by fluoride, oxalate, or the intravenous anticoagulant citrate. 

Flendrig JA, Kruis H, Das HA (1976) Aluminium intoxication the cause of dialysis dementia Proc Eur Dial Transplant Assoc 13 355-361 Froment DPH, Molitoris BA, Buddington B, Miller N, Alfrey AC (1989) Site and mechanism of enhanced gastrointestinal absorption of aluminium by citrate. Kidney Int 36 978-984... 

A number of natural substances, including sodium citrate and ascorbic acid, chelate Pb. Commonly used chelating agents include calcium disodium edetate (CaEDTA), dimercaprol (BAL), 2,2-dimethylcysteine (D-peniciUamine) and 2,3-dimercaptosuc-cinic acid (DMS). Chisholm and Coffin et al." have outlined the appropriate protocols for chelation therapy for children wdth Pb poisoning, whereas Friedheim et al. and the Center for Disease Control, outline the treatment of adult Pb intoxication. 

Fluoroacetate intoxication offers new possibilities to research. If a drug, a pathological condition or even a physical agent such as ionizing radiation do not decrease citrate accumulation in a rat after fluoroacetate poisoning, this means that they do not affect the utilization of glucose before aconitase action. If they do, one must look for a block somewhere between glucose and citric add. 

However, among this variety of biochemical changes, citrate seems to be the only parameter whose qualitative (but not quantitative) trends are not controversial. In rat hearts imder acute intoxication with FA, the concentration of citrate can exceed control values 8-15 times (Bosakowski and Levin, 1986). Elevation of citrate concentration is in direct proportion to the respiratory activity of a tissue metabolically active tissues, such as the heart, kidneys, and spleen, maximally accumulate citrate. Though in the liver, which is also characterized by high respiratory levels and metabolic activity, a small... 

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