Overview
Hypocalcaemia results in tetany (intermittent contraction of extensor muscles) and seizures when serum ionized calcium concentration is equal or lower than 0.8 mmol/l (3.2 mg/dl) or total calcium concentration is below 1.5 mmol/l (6 mg/dl) (Drobatz and Casey, 2000; Brauer et al., 2011). To convert mmol/l to mg/dl, the value in mmol/l has to be multiplied by 4 (Schenck and Chew, 2008). Total serum calcium is approximately 50% ionized, 40% protein bound (especially to albumin), and 10% chelated with anions such as citrate or phosphate. Only ionized calcium is biologically active. The proportion of ionized calcium is affected by serum protein level, acid-base status (ionized calcium levels are decreased by alkalosis and increased by acidosis) and the presence of anions that act as chelators (e.g. Mg++ or phosphate). Calcium homeostasis is regulated by parathyroid hormone (PTH), calcitriol (1,25- dihydroxyvitamin D) and calcitonin. The main organs involved in calcium metabolism are bone, kidney and small intestine.
Low calcium concentrations increase neuronal membrane permeability to sodium ions, resulting in neuronal hyperexcitability in the peripheral and central nervous system.
Clinical presentation
Clinical signs include nervousness, behavioural abnormalities (aggression, vocalization), decreased activity, panting, pacing, muscle stiffness, fasciculations, cramping and tetany, shifting limb lameness, stiff gait, hyperthermia, facial rubbing and biting at feet (probably due to paraesthesia) and seizures. Neurological signs can be intermittent and sometimes can be triggered by external stimuli or exercise. Differential diagnoses for underlying aetiologies of hypocalcaemia in dogs and cats are listed in Box 4.6. The reader is referred to internal medicine textbooks for further details on diagnosis and treatment of each condition.
Diagnosis
Diagnosis of hypocalcaemia is based on characteristic clinical signs and serum-ionized calcium concentration equal or lower than 0.8 mmol/l (3.2 mg/dl). Decreased serum total calcium should prompt assessment of serum ionized calcium. The use of corrective formulae to estimate ionized calcium concentration based on serum total calcium and total protein or albumin concentration is not recommended. These formulae do not accurately predict ionized calcium concentration and should not be used to make therapeutic decisions. Serum ionized calcium concentration is typically higher than ionized calcium concentration in heparinized plasma or whole blood (measured by means of a blood gas analyser) due to dilution with heparin (Schenck and Chew, 2008). Calcium concentrations should not be assessed on EDTA plasma as EDTA chelates calcium, giving artificially low calcium concentrations. Additional laboratory investigations (such as measurement of plasma PTH, magnesium, vitamin D metabolites, urinalysis) and diagnostic imaging are indicated depending on the suspected underlying cause of hypocalcaemia in individual patients.
Box 4.6. Causes of hypocalcaemia (modified from Schenck and Chew, 2008).
• Puerperal tetany (eclampsia);
• Renal failure (acute and chronic);
• Protein-losing enteropathies (hypoalbuminaemia);
• Acute pancreatitis;
• Ethylene glycol toxicity;
• Phosphate enema;
• Hypoparathyroidism:
• Primary;
• Idiopathic or spontaneous;
• Post-operative bilateral thyroidectomy;
• After sudden reversal of chronic hypercalcaemia;
• Secondary to magnesium depletion or excess;
• Nutritional secondary hyperparathyroidism;
• Citrate anticoagulant overdose with blood transfusion;
• Hypovitaminosis D.
Management
Diazepam (0.5 to 1.0 mg/kg intravenously, up to a maximum total dose of 20 mg, in dogs and cats, repeated to effect or twice within 2 h; see Chapters 21 and 24) can be used to control the tetany and seizures initially while the diagnosis of hypocalcaemia is confirmed. Hypocalcaemia is treated with 10% calcium gluconate at a dose of 0.5–1.5 ml/kg (providing 5–15 mg/kg of calcium) administered slowly IV (over 10 to 30 min) to effect as individual requirements vary. Clinical improvement is generally obvious within minutes of initiating the infusion. Electrocardiographic monitoring is advisable because of the risk of cardiotoxicity. If bradycardia, premature ventricular complexes, increased P-R interval, prolonged QRS complex or shortening of the Q-T interval is observed, the IV infusion should be briefly discontinued. Maintenance therapy of hypocalcaemia involves calcium gluco-nate (at a dosage equal to the one used IV for the control of tetany), diluted in an equal volume of saline, administered SC every 6 to 8 h. Serum calcium concentration should be monitored every 1–3 days to adjust the calcium gluconate dose. Generally, after serum calcium concentrations have been maintained within reference range for 48 h, the administration of calcium gluconate can be gradually tapered off to every 8–12 h. Long-term maintenance treatment with oral calcium (25 mg/kg every 8–12 h) and vitamin D supplementation may be required. Specific treatment for the underlying aetiology of hypocalcaemia should be instituted as promptly as possible.
Nutritional Disorders Causing Seizures
Thiamine (vitamin B1) deficiency
Overview
Thiamine (vitamin B1) deficiency has been reported in dogs and cats fed thiamine-deficient diets including commercial canned pet food (Marks et al., 2011; Markovich et al., 2014). Thiamine can be destroyed by heat during cooking or processing, preservatives such as sulfur dioxide, sulfate trace minerals, ultraviolet and gamma irradiation, and thiaminase enzyme activity, which is found predominantly in shellfish, fish viscera and some bacteria. In addition, thiamine deficiency can result from decreased intake due to anorexia or vomiting, decreased intestinal absorption (e.g. diarrhoea), abnormal utilization (e.g. liver dysfunction) or increased requirements (e.g. fever, infection). The metabolically active form of thiamine, thiamine pyrophosphate, plays an essential role in three enzyme systems (pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase, and transketolase), which are essential for complete oxidation of glucose through the Krebs cycle. Tissues dependent on glucose or lactatepyruvate for energy, such as the brain and heart, are particularly compromised in thia-mine deficiency.
Fig. 4.4. Transverse T2-weighted (a and c) and FLAIR (b and d) and paramedian T2-weighted (e) MR images of the brain of a 4-year-old dachshund with thiamine (vitamin B1) deficiency. Note the bilaterally
