Tetany

Ca " concentration, termed hypocalcemia, excitabihty increases. If this condition is not corrected, the symptoms of tetany, ie, muscular spasm, tremor, and even convulsions, can appear. Too great an increase in Ca " concentration, hypercalcemia, may impair muscle function to such an extent that respiratory or cardiac failure may occur. 

Symptoms of deficiency in animals include poor appetite, stunted growth, and weight loss increased incidence of irritabihty and convulsions (tetany) some growth abnormahties decreased egg production in poultry with reduced hatchabihty and thin eggsheU quahty and birth of weak, dead, or deformed offspring in other animals. 

Calcium is readily abundant in the mammalian diet. A 70 kg human contains approximately 1200 g of calcium and has a daily intake of 1100 mg/day. There are no pubHshed exposure limits (38). Low levels of calcium in the blood, hypocalcemia, can lead to tetany high levels, hypercalcemia, can lead to coma and death. Calcium toxicity, above 160 mg/L in the blood, is not related to an excessive intake of calcium. 

Calcium chloride solutions, typically employed at 2—5% concentration, are used as antispasmodics, diuretics (qv), and in the treatment of tetany. Concentrated solutions of calcium chloride cause erythema, exfoUation, ulceration, and scarring of the skin (39). Injections into the tissue may cause necrosis. If given orally calcium chloride can cause irrita tion to the gastrointestinal tract unless accompanied by a demulcent. There is no pubHshed information on mutagenicity or carcinogenicity caused by calcium ions or calcium chloride. Calcium chloride has been given a toxicity or hazard level 3 (40). Materials in this classification typically have LD q below 400 mg/kg or an LC q below 100 ppm. 

West has shown that curare varies qualitatively in action, some specimens having a lissive action, defined as the selective removal of pathological rigidities without apparent diminution of voluntary power and Hartridge and West found it possible to control tetany in para-thyroidectomised dogs by the use of a curare chosen on this basis. 

The most ingenious exocytosis toxins, however, come from the anaerobic bacteria Clostridium botulinum and Clostridium tetani. The former produces the seven botulinum neurotoxins (BoNTs) A-G the latter produces tetanus neurotoxin (TeNT). All eight toxins consist of a heavy (H) chain and a light (L) chain that are associated by an interchain S-S bond. The L-chains enter the cytosol of axon terminals. Importantly, BoNT L-chains mainly enter peripheral cholinergic terminals, whereas the TeNT L-chain mainly enters cerebral and spinal cord GABAergic and glycinergic terminals. The L-chains are the active domains of the toxins. They are zinc-endopeptidases and specifically split the three core proteins of exocytosis, i.e. the SNAREs (Fig. 1 inset). Each ofthe eight toxins splits a... 

Tetanus is a disease caused by the release of neurotoxins from the anaerobic, spore-forming rod Clostridium tetani. The clostridial protein, tetanus toxin, possesses a protease activity which selectively degrades the pre-synaptic vesicle protein synaptobrevin, resulting in a block of glycine and y-aminobutyric acid (GABA) release from presynaptic terminals. Consistent with the loss of neurogenic motor inhibition, symptoms of tetanus include muscular rigidity and hyperreflexia. The clinical course is characterized by increased muscle tone and spasms, which first affect the masseter muscle and the muscles of the throat, neck and shoulders. Death occurs by respiratory failure or heart failure. 

A toxin is a poisonous substance produced by some bacteria, such as Clostridium tetani, the bacteria that cause tetanus. A toxin is capable of stimulating the body to produce antitoxins, which are substances that act in the same manner as antibodies. Toxins are powerful substances, and like other antigens, they can be attenuated. A toxin that is attenuated (or weakened) but still capable of stimulating the formation of antitoxins is called a toxoid. 

A typical pattern of tension generation and free Ca " concentration in the myoplasm is seen in Figure 1 (Westerblad et al., 1991). A 10-20% force decrease was already observed after 10-20 tetani, followed by a period with only minor force decreases and a final period with rapid force loss to 30% of initial (Figure 1). 

Figure 1. Original records of tension and intracellular free calcium concentration Caf ) obtained from a single mouse muscle fiber during a fatigue run (modified from Westerblad and Allen, 1991). A continuous tension record in which each vertical line represents a tetanus. B (Ca ] (measured with fura-2) and tension records obtained from the individual tetani (a, b, and c) indicated above the record in A. Three major features are illustrated 1.) the initial tension decline is accompanied by an increase in tetanic ICa li, 2.) late in fatigue the tetanic [Ca li is reduced, and 3.) the resting [Ca li increases during fatiguing stimulation (dashed line indicates resting [Ca ] in control). Stimulation periods are shown below tension records in B. From Westerblad et al., 1991, with permission from the Amer. Physiol. Society.

Figure 2. Force generation and energy metabolism in human quadriceps femoris muscle stimulated intermittently at 20 Hz, with 1.6 sec tetani with 1.6 sec rest periods between tetani. The upper panel shows force, ATP turnover rate, and pH the middle panel, the concentrations of PCr, P and lactate and the lower panel, ATP, ADP, IMP, H, and calculated H2PO4. From Hultman et al. (1990), with permission from Human Kinetics Publishers.

Tetanus occurs when Cl. tetani, ubiquitous in the soil and faeces, contaminates wounds, especially deep puncture-type lesions. These might be minor traumas such as a splinter, or major ones such as battle injury. At these sites, tissue necrosis and possibly microbial growth reduce the oxygen tension to allow this anaerobe to multiply. Its growth is accompanied by the production of a highly potent toxin which passes up peripheral nerves and diSuses locally within the central nervous system. It acts like strychnine by affecting normal function at the synapses. Since the motor nerves of the brain stem are the shortest, the cranial nerves are the first affected, with twitches of the eyes and spasms of the jaw (lockjaw). 

Detoxification. The process by which bacterial toxins are converted to harmless toxoids. Formalin is used to detoxify the toxins of both Corynebacterium diphtheriae and Clostridium tetani. The detoxification may be performed either on the whole culture in the fermenter or on the purified toxin after fractionation. 

Tetanus (adsorbed) Cultures of Cl. tetani in liquid medium 1 Conversion of toxin to toxoid 2 Separation and purification of toxoid 3 Adsorption to adjuvant 3 + 3 quantal assay in mice using subcutaneous challenge with tetanus toxin Inoculation of guinea-pigs to exclude presence of untoxoided toxin... 

Hills S. (1946) The isolation of CL tetani from infected talc. NZMedJ, 45, 419-423. 

Severe hyperphosphatemia, presenting as hypocalcemia and tetany should be treated with hemodialysis and possibly careful intravenous calcium administration (see management of hypocalcemia)... 

Hyperphosphatemia is generally benign and rarely needs aggressive therapy. Dietary restriction of phosphate and protein is effective for most minor elevations. Phosphate binders such as aluminum-based antacids, calcium carbonate, calcium acetate (PhosLo , Nabi), sevelamer (Renagel , Genzyme), and lanthanum carbonate (Fosrenol , Shire) may be necessary for some patients.43 If patients exhibit findings of hypocalcemia (tetany), IV calcium should be administered empirically. 

Hypocalcemia leads to muscle cramps, tetany, irritability, paresthesias, arrhythmias... 

Tetany Hyperexcitability of nerves and muscles characterized by muscular twitching and cramps, laryngospasm with inspiratory stridor, and hyperreflexia. 

Trousseau s sign An indication of latent tetany in which carpal spasm occurs when the upper arm is compressed, as by a tourniquet or a blood pressure cuff. 

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