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Hypocalcemia

Hypocalcemias

Hypocalcemia is a syndrome produced when the level of free circulating calcium ions in the blood falls below the normal level of 4.65 mg/dL (1.16 mmol/L) and leads to potentially life-threatening disturbance of nerve and muscle activity. It is usually the result of either low intake of calcium or vitamin D or failure of the body’s homoeostatic mechanisms to maintain a satisfactory level of circulating plasma calcium, often through reduced levels of parathyroid hormone.


Presentation

The symptoms of severe hypocalcemia can be remembered with the mnemonic 'CATS go numb': Convulsions, Arrhythmias, Tetany and numbness of hands, feet and lips. More general the signs include [8] -

Chronic hypocalcaemia (a year or longer) can lead to cataracts.

Chvostek’s sign is when a tapping the lower part of the cheekbone produces facial spasm.
Trousseau’s sign creates carpal spasm by inflating a sphygmomanometer cuff and keeping the cuff pressure above systolic blood pressure.

Muscle Cramp
  • cramps , abdominal cramps, and overly active reflexes).[rxlist.com]
  • Hypocalemia, low blood calcium makes the nervous system highly irritable with tetany (spasms of the hands and feet, muscle cramps, abdominal cramps, and overly active reflexes).[patientslikeme.com]
  • Symptoms include numbness and/or tingling of the hands, feet , or lips, muscle cramps , muscle spasms , seizures , facial twitching, muscle weakness , lightheadedness , and slow heartbeat.[medicinenet.com]
  • As hypocalcemia progresses, muscle cramps are common, and people may become confused, depressed, and forgetful and have tingling in their lips, fingers, and feet as well as stiff, achy muscles.[merckmanuals.com]
  • This situation causes symptoms of hypocalcemia, especially tingling sensations of extremities , muscle cramps and convulsions.[health-tutor.com]
Chvostek Sign
  • Manifestations include hyperactive deep tendon reflexes, chvostek's sign, muscle and abdominal cramps, and carpopedal spasm.[icd9data.com]
  • His examination demonstrated a slight resting tremor, normal strength, and negative Chvostek sign. Laboratory analysis revealed hemoglobin, 8.0 g/dL; total calcium, 5.2 mg/dL (pre-denosumab, 8.9 mg/dL); and magnesium, 0.7 mg/dL.[ncbi.nlm.nih.gov]
  • sign: Twitching of the ipsilateral facial musculature (perioral, nasal, and eye muscles) by tapping over cranial nerve VII at the ear Chvostek's sign is neither sensitive nor specific for hypocalcemia: it is absent in 30% of patients with hypocalcemia[medicine.uiowa.edu]
  • Manifestations include hyperactive deep tendon reflexes, Chvostek's sign, muscle and abdominal cramps, and carpopedal spasm.[fpnotebook.com]
  • Acute hypocalcemia can lead to paresthesia, tetany, and seizures (characteristic physical signs may be observed, including Chvostek sign, which is poorly sensitive and specific of hypocalcemia, and Trousseau sign).[us.bestpractice.bmj.com]
Trousseau Sign
  • We report the case of a 50-year-old woman with anorexigen-induced pulmonary arterial hypertension treated with epoprostenol, who presented with Trousseau's sign, leading to the diagnosis of severe hypocalcemia for which substitution was started (initially[ncbi.nlm.nih.gov]
  • On primary assessment, stridor and a positive Trousseau sign were noted. Laboratory examination showed hypocalcemia. We concluded that the dyspnea was caused by laryngospasm due to hypocalcemia.[ncbi.nlm.nih.gov]
  • [Figure caption and citation for the preceding image starts]: Carpopedal spasm (Trousseau sign) occurred a few minutes after inflation of a sphygmomanometer cuff above systolic blood pressure Pedrazzini B et al.[us.bestpractice.bmj.com]
  • Other signs include positive Chvostek’s and Trousseau’s signs, depression, memory loss and hallucinations.[symptoma.com]
  • […] level of ionized calcium Clinical Presentation Symptom severity is related to the rate of change and absolute calcium levels Most patients with mild hypocalcemia are asymptomatic Acute Neuromuscular – tetany, paresthesias, muscle spasms (Chvostek and Trousseau[arupconsult.com]
Carpopedal Spasm
  • Manifestations include hyperactive deep tendon reflexes, chvostek's sign, muscle and abdominal cramps, and carpopedal spasm.[icd9data.com]
  • The patient had carpopedal spasm at both hypocalcemic presentations. Laboratory analysis revealed hypocalcemia, hypokalemia, alkalosis with hypercalciuria, and low-normal parathormone (PTH) at first and elevated PTH at the second admission.[ncbi.nlm.nih.gov]
  • Manifestations include hyperactive deep tendon reflexes, Chvostek's sign, muscle and abdominal cramps, and carpopedal spasm.[fpnotebook.com]
  • [Figure caption and citation for the preceding image starts]: Carpopedal spasm (Trousseau sign) occurred a few minutes after inflation of a sphygmomanometer cuff above systolic blood pressure Pedrazzini B et al.[us.bestpractice.bmj.com]
Muscle Twitch
  • The following are the most common symptoms of hypocalcemia: irritability muscle twitches jitteriness tremors poor feeding lethargy seizures[childrenshospital.org]
  • Symptoms may include: Irritability Muscle twitches Jitteriness Tremors Poor feeding Lethargy Seizures The symptoms of hypocalcemia may resemble other conditions or medical problems. Always consult your baby's doctor for a diagnosis.[chop.edu]
  • He may gently tap on your cheeks to see if your facial muscles twitch. You will also need blood tests to check your calcium, magnesium, and hormone levels. How is hypocalcemia treated? Calcium will be given to bring your levels back to normal.[drugs.com]
  • twitches (Chvostek's sign) Severe cases can progress to tetany, seizures, carpopedal spasms, dysrhythmias Longstanding hypocalcemia assoc with: Neuropsych Sx (eg, depression) Cataracts Incr ICP (rare) May not necessarily present with neuromuscular Sx[fprmed.com]
Circumoral Paresthesia
  • This is most commonly manifested as numbness and tingling, particularly of the distal extremities or as circumoral paresthesias. Muscle cramping, twitching, or stiffness may also be signs of hypocalcemia.[endocrinologyadvisor.com]
Seizure
  • Abstract A 22-year-old woman presented to us with seizures of a few minutes duration. She had clinical features of Albright hereditary osteodystrophy (AHO), including hypocalcemia, hyperphosphatemia and resistance to parathyroid hormone.[ncbi.nlm.nih.gov]
  • Abstract We report the case of an inaugural episode of generalized seizures in a 40-year-old male with a history of chronic kidney disease associated with TSC2-PKD1 contiguous gene syndrome.[ncbi.nlm.nih.gov]
  • ) seizures Hypocalcemic newborns may present with hypotonia, apnea, poor feeding, jitteriness, or seizures.[epilepsy.com]
  • […] encephalopathy syndrome (PRES) is a clinicoradiographic entity of heterogenous etiologies, which are grouped together because of similar findings on neuroimaging studies, associated with similar symptom complex of headache, vision loss, altered mentation, and seizures[ncbi.nlm.nih.gov]
  • Pediatric patients with vitamin D deficiency may be asymptomatic or may present either with rickets, hypocalcemia, or seizures.[ncbi.nlm.nih.gov]
Paresthesia
  • A comparison between groups demonstrated that cases had a significantly higher incidence of symptomatic hypocalcemia resulting in paresthesia and tetany (38% vs. 0%; P CONCLUSIONS: Physicians and surgeons need to be aware of this complication and take[ncbi.nlm.nih.gov]
  • At presentation, he had ataxia, paresthesia in the hands and feet, and abdominal cramping. Magnetic resonance imaging of the brain was unremarkable. He was found to be hypocalcemic with undetectable plasma parathyroid hormone.[ncbi.nlm.nih.gov]
  • Within all the people who go to their doctor with hypocalcemia, 49% report having shortness of breath, 49% report having sharp abdominal pain, and 43% report having paresthesia.[symcat.com]
  • Tabs Content Clinical Overview Diagnosis Indications for Testing Neurologic signs Perioral numbness or other paresthesias Muscle spasms/cramps Neuromuscular irritability Thyroid or parathyroid resection or other neck surgery, irradiation to neck Chronic[arupconsult.com]
  • Paresthesia (pins and needles or numbness) in the extremities or around the mouth Mood changes (such as anxiety, depression, and irritability) Cognitive dysfunction (“brain fog” and an inability to concentrate) Memory problems Tetany (muscle spasms) Difficulty[hypopara.org]
Altered Mental Status
  • Hypercalcemia: Typical findings in hypercalcemia can include: -Poor feeding -Vomiting -Constipation -Abdominal Pain -Hypertension -Altered mental status In more severe cases of hypercalcemia, findings can include: -Hypotonia -Hyporeflexia -Paresis -Psychosis[clinicaladvisor.com]
  • mental status, and hypocalcemia. 3 Tetany, which may be mistaken for motor seizures, results from spontaneous action potentials originating in peripheral nerves when the serum ionized calcium concentration falls below 4.3 mg/dL (usually corresponding[epilepsy.com]
  • However, vitamin D intoxication may cause hypercalcemia, hypercalciuria, and hyperphosphatemia as well as symptoms of hypercalcemia including gastrointestinal disturbance, altered mental status, soft tissue calcification or renal damage.[endocrinologyadvisor.com]
Hyperreflexia
  • Severe hypocalcemia with serum calcium 7 mg/dL ( 1.75 mmol/L) may cause hyperreflexia, tetany, laryngospasm, or generalized seizures.[merckmanuals.com]
  • Hyperreflexia. Other symptoms and signs depend on the aetiology: DiGeorge's syndrome : Recurrent infections due to T-cell immunodeficiency. Congenital heart disease and its related symptoms, heart murmur. Speech delay.[patient.info]
Myoclonic Jerking
  • Hypocalcemia: Typical findings in mild to moderate hypocalcemia can include: -Fatigue -Cramping -Weakness -Paresthesias, especially in the perioral area and distal extremities -Myoclonic jerks In more severe cases of hypocalcemia, findings can include[clinicaladvisor.com]

Workup

ECG changes include an intermittent QT lengthening which reflects the potential for life-threatening cardiac electrical instability and thus ventricular tachycardia

Laboratory analysis of blood sample will identify reduced levels of free calcium in hypocalcaemia.

However, a complete diagnosis of the underlying cause requires assessment of the state of the parathyroid glands, the kidneys and the plasma magnesium concentration [9].

Slowing
  • It acts primarily by decreasing osteoclastic activity, thereby slowing the release of skeletal calcium.[ncbi.nlm.nih.gov]
  • You have a slow or uneven heartbeat and feel lightheaded. You see or hear things that are not really there. Care Agreement You have the right to help plan your care. Learn about your health condition and how it may be treated.[drugs.com]
  • Alternatively, calcium may be administered as a slow infusion (over 30 to 60 minutes), given at a dose of 100 mg/kg every 6 hours. If other calcium salts are used, e.g. calcium chloride, the dose will be different.[uichildrens.org]
  • Symptoms include numbness and/or tingling of the hands, feet , or lips, muscle cramps , muscle spasms , seizures , facial twitching, muscle weakness , lightheadedness , and slow heartbeat.[medicinenet.com]
  • […] severity of symptoms Treatment of metabolic acidosis can have the same effect Acute symptomatic hypocalcemia (total calcium IV dosing: 100-200mg of elemental calcium (1-2g calcium gluconate diluted in saline or dextrose) initially over 10-20 min, then a slow[icppharm.com]
Calcium Decreased
  • Changes in albumin will affect total serum calcium without changing the level of free calcium.[globalrph.com]
  • Therefore, for each 0.1 increase in pH, ionized calcium decreases by about 0.05 mmol/l [ 1–3 ]. Furthermore, alkalosis affects the interaction between ionized calcium and the cell membrane by increasing myofibrillar calcium sensitivity [ 4 , 5 ].[ndt.oxfordjournals.org]
  • Alterations in serum albumin increase or decrease serum calcium without affecting ionized calcium. Decreases in serum albumin below 4.0 g/dL decrease total calcium by 0.8 mg/dL for each 1.0 g/dL decrease in serum albumin.[link.springer.com]
  • Measured total serum calcium decreases or increases by about 0.8 mg/dL (0.2 mmol/L) for every 1 g/dL decrease or increase in albumin.[merckmanuals.com]
Parathyroid Hormone Increased
  • In addition, the plasma levels of intact parathyroid hormone increased immediately after magnesium administration.[ncbi.nlm.nih.gov]
  • hormone - increases intestinal absorption of Ca2 - increases renal Ca2 reabsorption - mobilises bone Ca2 & PO43- Parathyroid hormone secretion increased by hypocalaemia and hypomagnesaemia secretion decreased by hypercalcaemia and hypermagnesaemia -[lifeinthefastlane.com]
Prolonged QT Interval
  • EMAIL PRINT SAVE EMAIL SAVE The ECG findings of hypocalcemia include: A prolonged QT interval A lengthened ST segment There are many causes of a prolonged QT interval on the ECG, including genetic long QT syndrome, electrolyte abnormalities and medications[healio.com]
  • ‘Other conditions that may prolong QT intervals are clinical hypocalcemia, hypokalemia, ischemia, or infarction.’ ‘Treatment with sodium bicarbonate may worsen hypocalcemia initially because of the protein binding of calcium.’[en.oxforddictionaries.com]
  • QT interval and ST interval) Note: definitely remember prolonged QT interval…another major test question M uscle spasms in calves or feet, tetany, seizures P ositive Trousseau’s![registerednursern.com]
  • QT interval Serum Ca Serum Phos PTH Common Cause Hyperparathyroidism adenoma Hypoparathyroidism parathyroidectomy Ectopic PTH malignancy Vit D malabsorption celiac disease, other GI isease Hypo vit D with no phosphate excretion from the kidney. renal[orthobullets.com]
  • EKG prolonged QT interval.[enotes.tripod.com]
T Wave Inversion
  • […] deficiency or Ca malabsorption: high PTH in presence of normal renal function Imaging Usually imaging is not indicated unless other etiologies (eg, tumor) is suspected Other Tests/Criteria ECG QT interval prolongation by incr of ST segment duration T-wave[fprmed.com]

Treatment

Treatment depends on the severity of the hypocalcaemia and the underlying cause.

Severe disease requires supplementation of calcium ions by parenteral injection, usually as calcium gluconate, with oral supplements for long-term treatment. These latter may be prescribed as calcium carbonate, chloride, lactate or gluconate [10].

Underlying renal disease will require injections of calcitonin plus supportive treatment for other aspects of the kidney disease.

Oral vitamin D supplements can increase calcium absorption from the gastro-intestinal tract.

Where hypoparathyroidism is the underlying cause, treatments can include oral calcium, calcitonin or other drugs.

When there is hypomagnesaemia at the same time as hypocalcaemia, the levels of both minerals must be corrected to allow hypocalcaemia reduction.

Prognosis

The prognosis is generally very favourable for correcting hypocalcaemia. However, it is important to identify the underlying causes and not all of these can be corrected. The cataracts of chronic hypocalcaemia cannot be reversed.

Etiology

Calcium is an important mineral in the human body. Not only it is a major component of bones and teeth but about 1% of the total calcium of the body circulates in the blood where it is essential for normal blood clotting and for normal nerve and muscle activity. In bones, the calcium ion combines with phosphate ions to form the strong calcium phosphate crystals. In the blood some calcium ions combine in complexes with proteins and other compounds but many remain in a free form. Normally about 47% calcium in the plasma is of the free form and the larger proportion, 53% of it, is in complexes (40% attached to albumin and 15% bound to citrates, lactates, phosphates and sulphates). It is the free calcium ions which are critical to the performance of nerves and muscles, not the calcium in bone or vascular complexes [2].

When there are inadequate circulating calcium ions, neuromuscular abnormalities develop.

Epidemiology

The four main causes of hypocalcaemia are [3] –

  1. Hypoparathyroidism,
  2. failure to produce calcitonin (1, 25-dihydroxyvitamin D),
  3. low levels of plasma magnesium,
  4. inadequate level of calcium or vitamin D.

Other causes include: 

  • eating disorders like anorexia or bulimia
  • prolonged vomiting (e.g for viral disease)
  • exposure to mercury and hydrofluoric acid
  • excessive dietary magnesium or zinc
  • iatrogenic effect – chelation therapy for heavy metal exposure (especially EDTA), osteoporosis treatments (e.g. biphophonates and denosumab), treatment of hypercalcemia, phosphate enemas in children.
  • toxic levels of phosphate (e.g in enemas mistakenly swallowed)
  • acute and chronic renal failure
  • pancreatitis

Neonatal hypocalcemia can be found in babies with very low birth weights (less than 1500 grams) or premature with a gestational age of less than 32 weeks.

It is interesting to note that many animals suffer from hypocalcemia after losing large amounts of calcium in their placental fluids at parturition in their milk during lactation. There seems to be a strong possibility that many mild cases of post-natal depression may be related to hypocalcemia [4].

Sex distribution
Age distribution

Pathophysiology

Maintenance and control of the plasma calcium level is performed by the parathyroid hormone from the parathyroid gland. This acts on the kidneys where it stimulates production of calcitrol (1,25-dihydroxyvitamin D), the active form of vitamin D. Calcitrol stimulates the absorption of calcium from the diet as well as its mobilisation from bone to maintain or raise the levels of calcium ions in the plasma [5].

Hypocalcemia can therefore by caused by abnormalities in either the parathyroid gland or the kidneys. Parathyroid performance can be disturbed by a damage or surgical removal during thyroidectomy and radical resection of cancer surgery. Autoimmune and congenital hypoparathyroidism can result in destruction or absence of calcium-sensing receptors. There is also a condition called pseudohypoparathyroidism in which there is insensitivity to the biological activity of parathyroid hormone receptors.

Vitamin D levels are critical and can be inadequate because of low dietary levels, pronounced absorption, inadequate exposure to sunlight needed to cause effective metabolism or defective metabolic pathways [6].

Low plasma magnesium levels (hypomagnesaemia) can also lead to hypocalcaemia. These may be brought about by alcoholism or by a disease that prevent the correct fat absorption. Magnesium is required for correct functioning of the parathyroid hormone in maintaining blood calcium levels [7].

Prevention

It is important that the daily requirements of calcium and vitamin D are met every day, either with food or through supplements.

Lifestyle choices should be made to avoid alcohol consumption and make sure that adequate levels of sunlight are received by the body for a correct vitamin D metabolism – in colder climates with shorter day length it is highly possible that many individuals might not receive enough sunlight on their skin due to protective clothing.

Summary

The normal concentration of free ionized calcium in the blood is between 4.65 – 5.25 mg/dL (1.16 – 1.31mmol/L); Hypocalcemia is the syndrome when the blood calcium level falls below this range and severe hypocalcaemia occurs with levels are below 3 mg/dL.

The most prominent signs relate to the nerve inactivity with paraesthesia of the hands, feet and around the mouth and lips with more severe signs of convulsion, arrhythmias and tetany. Treatment can be successfully performed by either intravenous calcium gluconate or oral supplementation with various calcium salts. However it is important to identify and correct the underlying cause [1].

Patient Information

Definition: Hypocalcaemia occurs when the level of circulating free calcium ions is less than 4.65 mg/dL (1.16 mmol/L) and results in potentially life-threatening disturbance to nerve and muscle activity.

Cause: Inadequate levels of circulating calcium ions in the plasma lead to poor nerve transmission and muscle weakness. The most common causes of hypocalcaemia are low parathyroid hormone levels, failure to produce calcitonin (the active form of vitamin D), low circulating magnesium levels or inadequate calcium or vitamin D uptake. Underlying causes could include eating disorders, prolonged vomiting in viral disease, toxicity by certain metals or drugs, acute and chronic renal failure and inadequate exposure to sunlight for conversion of active Vitamin D (calcitonin).

Symptoms: The signs of hypocalcaemia can be remembered with the mnemonic ‘CATS go numb’. This translates as “convulsions, arrhythmias, tetany and numbness of the hands, feet and around the mouth and lips. Other signs include positive Chvostek’s and Trousseau’s signs, depression, memory loss and hallucinations. Tissue deterioration is reflected in dry scaly skin, hair loss and brittle nails and, after more than a year of chronic hypocalcaemia, cataracts can also be seen.

Diagnosis: Clinical signs and history allow a tentative diagnosis with confirmation by laboratory electrolyte analysis. An ECG will identify an intermittent QT lengthening which reflects electrical insensitivity and, potentially, life-threatening ventricular tachycardia.
Underlying causes from the clinical history should be identified by further testing.

Treatment: Calcium supplementation, orally or intravenously depending on the severity of the condition, will offer a good clinical response,  but further treatment may be required to correct the underlying pathology.

Prevention: Adoption of good lifestyle practices – diet and exposure to sunshine – correct smost simple causes; the cases of more complicated pathology will require specific programmes.

References

Article

  1. Hannan FM, Thakker RV. Investigating hypocalcaemia. BMJ 2013; 346:f2213.
  2. Mundy GR, Guise TA. Hormonal control of calcium homeostasis. Clin Chem. Aug 1999;45(8 Pt 2):1347-52.
  3. Fitzpatrick LA, Arnold A. Hypoparathyroidism. In: Endocrinology, 3rd, DeGroot LJ (Ed), Saunders, Philadelphia 1995. p.1123.
  4. Zivin JR, Gooley T, Zager RA, Ryan MJ. Hypocalcemia: a pervasive metabolic abnormality in the critically ill. Am J Kidney Dis 2001; 37:689.
  5. Riccardi D, Brown EM. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol 2010; 298:F485.
  6. Beckerman P, Silver J. Vitamin D and the parathyroid. Am J Med Sci. Jun 1999;317(6):363-9.
  7. Cholst IN, Steinberg SF, Tropper PJ, et al. The influence of hypermagnesemia on serum calcium and parathyroid hormone levels in human subjects. N Engl J Med 1984; 310:1221.
  8. Murphy G, Bartle S. Hypocalcemic laryngospasm and tetany in a child with renal dysplasia. Pediatr Emerg Care. Jul 2006;22(7):507-9.
  9. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. Jun 7 2008; 336(7656):1298-302.
  10. Forsythe RM, Wessel CB, Billiar TR, Angus DC, Rosengart MR. Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev. 2008;(4):CD006163.

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Last updated: 2017-08-09 17:34