What Are the Most Common Hypocalcemia Causes?

The total amount of calcium in adults is about 1000 ~ 1300g, 99% exists in bones and teeth in the form of bone salt, and the rest is in various soft tissues. Extracellular calcium is only 0.1% of total calcium, about 1g. Adult blood calcium levels are about 2.2 ~ 2.6mmol / L (8.8 ~ 10.4mg / dl), mainly in three forms: free calcium (50%), also known as ionic calcium; protein-bound calcium (40%); It can diffusely bind calcium (10%).

Zhang Ling	(Chief physician)	Department of Nephrology, China-Japan Friendship Hospital
Li Wenge	(Chief physician)	Department of Nephrology, China-Japan Friendship Hospital
Li Duo	(Attending physician)	Department of Nephrology, China-Japan Friendship Hospital

Hypocalcemia is a phenomenon in which blood calcium is lower than normal and belongs to a disorder of calcium metabolism. Because calcium plays a physiological role depends on free calcium (that is, ionic calcium), hypocalcemia is also generally referred to as low ionic calcium, also known as free calcium is lower than normal (<1.1mmol / L).

Western Medicine Name: Hypocalcemia
English name: hypocalcemia
Affiliated Department: Internal Medicine-

The main symptoms: Muscle cramps, arrhythmias
Main cause: Hypocalcemia
Contagious: Non-contagious

Introduction to Hypocalcemia Diseases

When the serum albumin concentration is in the normal range, the blood calcium is less than 2.2mmol / Ll (8.8mg / l), and the normal value is 2.2 ~ 2.70 mmol / L, which is called hypocalcemia. There are small differences in the reference values of blood calcium tests in different hospitals. There are also blood calcium below 2.1mmol / l (8.4mg / l), and the normal value is 2.1 ~ 2.55 mmol / L, which is determined to be hypocalcemia. In acidosis or hypoalbuminemia, only protein-bound calcium is reduced. At this time, blood calcium is lower than normal, but ionized calcium is not low, and clinical symptoms do not occur. Conversely, in alkalosis or hyperproteinemia, free calcium is reduced, but The protein-bound calcium is increased, so serum calcium can still be normal, and clinical symptoms of hypocalcemia can also occur. In hypoproteinemia, a corrected calcium concentration needs to be calculated to diagnose hypocalcemia. ^[1]

Causes and mechanisms of hypocalcemia

1. Hypoparathyroidism: includes primary, secondary, and pseudohypoparathyroidism. Primary hypoparathyroidism is a group of multi-cause diseases, such as congenital hypoparathyroidism or underdevelopment, DiGeorge syndrome, autoimmune polyglandular syndrome type I, etc., hypocalcemia in newborns It can be caused by congenital hypoparathyroidism, or hypercalcemia due to mothers with hyperparathyroidism or familial benign hypercalciuria, which can cause temporary hypoparathyroidism in newborns; Secondary hypoparathyroidism is more common, and it is more common in thyroid or parathyroid surgery and after cervical malignant tumor surgery, after radiotherapy, infiltrating diseases such as hemochromatosis, hepatolenticular degeneration, metastatic tumors, etc .; Bone starvation syndrome is another cause of hypocalcemia after surgery. It is found in patients with severe hyperparathyroidism after parathyroidectomy, resulting in relative hypoparathyroidism and a large amount of Ca2 + entering bone cells. . Severe magnesium deficiency is a common cause of functional hypoparathyroidism, which can lead to impaired secretion of parathyroid hormone (PTH) and resistance of effector tissues such as bone and kidney to PTH. Pseudohypoparathyroidism is similar to that of hypoparathyroidism, but the parathyroid glands are not diseased. Hypocalcium stimulates hyperplasia of parathyroid glands, and PTH secretion increases, so serum PTH often increases.

2. Vitamin D metabolism disorders: Vitamin D deficiency: It is more common in malnutrition, especially when exposed to too little sunlight; it is also found in chronic diarrhea, fatty diarrhea, chronic pancreatitis, cystic fibrosis, and after gastrectomy. Vitamin D Hydroxylation disorder: found in kidney failure, liver disease, hereditary 1 hydroxylase deficiency, vitamin D-dependent osteomalacia type and other diseases. Due to the hydroxylation disorder of vitamin D, active vitamin D3 cannot be efficiently produced in the body. There is also vitamin D-dependent osteomalacia type II, which is caused by mutations in the vitamin D receptor. Vitamin D catabolism is accelerated: Long-term application of antiepileptic phenobarbital can effectively enhance the activity of liver microsomal enzymes, and accelerate the catabolism of vitamin D and 25 (OH) D3 in the liver. Although phenytoin has no direct effect on vitamin D catabolism, it can reduce the release of calcium from bone and reduce the reabsorption of calcium by the intestine, and can also cause hypocalcemia. At the same time, the use of antiepileptic drugs can increase vitamin D requirements.

3. Renal failure: Renal failure caused by various reasons, reduced production of 1,25 (OH) 2 D3, and reduced intestinal calcium absorption; reduced renal excretion of phosphorus during renal failure leads to reduced phosphorus retention and decreased intestinal calcium absorption ; And hyperphosphatemia and bone resistance to PTH cause the mobilization of calcium in the bone to be hindered; in the presence of acidosis, the excretion of calcium from the kidney is accelerated, resulting in further reduction of blood calcium.

4. Drugs: Drugs used to treat hypercalcemia and excessive bone resorption, such as bisphosphonates, pukamycin (radiomycin), calcitonin, phosphate, etc. Anticonvulsants: For example, phenobarbital can cause hypocalcemia by changing vitamin D metabolism. Calcium chelating agent: commonly used are EDTA, citric acid and so on. Phosphonic acid: It can chelate calcium in extracellular fluid and cause hypomagnesemia.

5. Hypocalcemia associated with malignant tumors: Metastatic prostate cancer or breast cancer osteoblasts can accelerate bone formation and lead to hypocalcemia. In addition, a large number of tissues are destroyed during lymphoma and leukemia chemotherapy, which releases phosphate into the blood, and the blood calcium can be significantly reduced, which is called tumor lysis syndrome.

Other: In acute hemorrhagic necrotizing pancreatitis, fat necrosis can precipitate a large amount of calcium to form calcium soap; rhabdomyolysis can also produce similar symptoms.

Hypocalcemia Pathophysiology

Hypocalcemia stimulates the synthesis and release of PTH in hypoparathyroidism; hypocalcemia and PTH can enhance the activity of 1 hydroxylase in proximal renal tubular epithelial cells, thereby promoting 1,25 (OH ) 2 Synthesis of D3. PTH can promote bone resorption. At the same time, PTH and 1,25 (OH) 2 D3 can increase the calcium reabsorption of distal renal tubules. 1,25 (OH) 2 D3 can also increase the intestinal calcium reabsorption, so that Increased blood calcium. When hypoparathyroidism, vitamin D metabolism disorders, and renal failure occur, PTH, 1,25 (OH) 2 D3 synthesis disorders can disturb the body's normal regulation of blood calcium balance, resulting in hypocalcemia, and cause A series of clinical symptoms.

Clinical manifestations of hypocalcemia

Hypocalcemia often has no obvious clinical symptoms. The severity of clinical symptoms is not completely consistent with the degree of blood calcium reduction, but is related to the speed and duration of blood calcium reduction. The rapid decline of blood calcium, even if the blood calcium level is 2mmol / l, can cause clinical symptoms. The clinical manifestations of hypocalcemia are mainly related to the increased excitability of neuromuscular.

1. Neuromuscular system: Because calcium can reduce the excitability of neuromuscular muscles, the excitability of neuromuscular muscles increases during hypocalcemia. Muscle spasms may occur, and the early peripheral nervous system is numb to the fingers / toes. Mild patients can use the facial nerve tap test (Chvostek sign) or beam arm compression test (Trousseau sign) to induce typical convulsions. Severe hypocalcemia can cause spasms in the throat, wrists, feet, bronchi, seizures and even apnea. Mental symptoms such as irritability, depression, and cognitive decline can also occur.

2. Cardiovascular system: mainly arrhythmias such as conduction block, ventricular fibrillation can occur in severe cases, etc., and heart failure has a poor response to digitalis. Electrocardiograms typically show markedly longer QT intervals and ST segments.

3. Bone, skin, and soft tissue: Chronic hypocalcemia can manifest as bone pain, pathological fractures, and bone deformities. Bone lesions can be osteomalacia, osteoporosis, rickets, fibrocystic osteitis, etc. according to the basic etiology. Patients with chronic hypocalcemia often have dry skin, inelasticity, dull color, and itching; they are also prone to thinning hair, brittle nails, and crispy teeth; cataracts caused by hypocalcemia are more common.

4. Hypocalcemia crisis: When serum calcium is less than 0.88mmol / L (3.5mg / dl), severe voluntary muscle and smooth muscle spasm can occur, leading to convulsions, seizures, severe asthma, and severe throat can cause throat Asphyxia due to muscle spasms, cardiac insufficiency, and cardiac arrest. ^[2]

Diagnosis of hypocalcemia

History of hypocalcemia

Attention should be paid to the history of chronic renal insufficiency, hyperthyroidism after surgery or radiation therapy, other thyroid and neck surgery, liver disease, intestinal malabsorption, insufficient intake, lack of light, multiple pregnancy, and long-term breastfeeding. Long-term application of antiepileptic drugs (such as chlorprostone, phenytoin, phenobarbital, and carbamazepine) or protamine, heparin, and repeated input of blood containing sodium citrate can cause hypocalcemia. You should also ask if you have tetanus and paresthesia and a history of osteodystrophy.

Physical examination of hypocalcemia

When hypocalcemia occurs, neuromuscular excitability increases, and hand-foot convulsions, muscle spasms, larynx, convulsions, and mental symptoms such as irritability, emotional instability, and hallucinations may occur. Patients with hypocalcemia can show positive Chvostek and Trousseau signs, but about one third of patients can be negative. ^[3]

Hypocalcemia auxiliary examination

Laboratory tests: blood calcium, blood phosphorus, PTH, liver function, kidney function, albumin, urine calcium, 1,25 (OH) 2 D3, blood magnesium, etc.

ECG: Electrocardiograms in patients with hypocalcemia often show prolonged QT intervals and sometimes tachycardia.

Imaging examination: 20% of patients with idiopathic hypoparathyroidism have intracranial calcification (mainly the basal nucleus), and patients with hypoparathyroidism or pseudoparathyroidism after surgery usually do not appear. Intracranial calcification. Bone radiography can understand the nature and extent of bone disease, and can also determine the presence or absence of metastatic tumors.

The total calcium concentration in the diagnosis of hypocalcemia must be the corrected calcium concentration after serum albumin correction, and the free calcium concentration can be determined if necessary. Corrected calcium concentration (mg / dl) = total calcium (mg / dl)-0.8 x [4.0-serum albumin concentration (g / dl)].

According to medical history, physical examination and laboratory examinations (such as blood phosphorus, PTH, liver and kidney function, albumin, etc.) often the cause of the disease can be clarified. For example, most patients with low calcium, high phosphorus, and normal renal function often have primary or secondary hypoparathyroidism; history of surgery near the neck should be suspected of damage to the parathyroid glands; insufficient magnesium content, nutritional status, and insufficient sunlight , Massive blood transfusion, chemotherapy, acute pancreatitis, gastrointestinal disease, medication history, whether accompanied by vitamin D deficiency, whether it is combined with other endocrine abnormalities, etc. can help diagnosis. ^[4]

First aid measures for hypocalcemia

Severe hypocalcemia can cause hypocalcemia crisis, which is life-threatening and requires active treatment.

1. 10% calcium chloride or 10% calcium gluconate 10 ~ 20ml (10ml calcium gluconate contains 90mg elemental calcium), intravenous injection. Repeat if necessary within 1 to 2 hours.

2. If the convulsions do not stop, add 20% to 30ml of 10% calcium chloride or 10% calcium gluconate, and add 5% to 10% glucose solution to 1000ml, and continue intravenous drip. The speed is less than 4mg elemental calcium / (h · kg) body weight. Check the blood calcium after 2 ~ 3 hours, it should be about 2.22mmol / L (9mg / dl), it should not be too high.

3. The effect of calcium supplementation is not good, you should pay attention to whether there is low blood magnesium, and you can add magnesium if necessary.

4. If the symptoms are good, you can change to a high-calcium diet and take oral calcium plus vitamin D (nutritional vitamin D or active vitamin D).

Treatment of hypocalcemia

Patients with symptoms and signs of hypocalcemia should be treated. The degree and speed of the decline in blood calcium determine how quickly to correct hypocalcemia. If the total calcium concentration is less than 7.5 mg / dl (1.875 mmol / L), treatment should be performed with or without symptoms.

If the symptoms of hypocalcemia are obvious, such as hand-foot convulsions, convulsions, hypotension, positive Chvostek sign or Trousseau sign, electrocardiogram Q-interval extension of ST segment with or without arrhythmia, etc., should be treated immediately, generally 10% glucose Calcium acid 10ml (containing Ca2 + 90mg) is diluted and injected intravenously (greater than 10min). It works immediately after injection and can be reused if necessary to control symptoms. Heart rate should be closely monitored during injection, especially in patients who use digitalis to prevent severe arrhythmias. If symptomatic hypocalcemia recurs, intravenous infusion of 10 to 15 mg / kg of Ca2 + can be performed within 6 to 8 hours. Calcium chloride can also be used, but it is very irritating to veins. Ca2 + concentration should not be greater than 200mg / 100ml to prevent the stimulation of veins and soft tissues after extravasation. Patients with hypomagnesemia must be corrected at the same time.

Chronic hypocalcemia should first treat the causes of hypocalcemia, such as hypomagnesemia, vitamin D deficiency, malnutrition, etc. In addition, oral calcium and vitamin D preparations (nutritional vitamin D or active vitamin D) can be given. Oral calcium preparations include calcium gluconate, calcium citrate, and calcium carbonate, which are selected for use according to hypocalcemia. Generally, it can be taken 1 to 2 g per day. Cod liver oil is rich in vitamin D, which can promote calcium absorption from the intestine and is inexpensive However, the effect is slow. Once the effect lasts longer, the blood calcium should be monitored regularly to adjust the dosage. Active vitamin D includes 25 (OH) 2 D3 and 1,25 (OH) 2 D3 (calcitriol), which has a fast action, especially the latter, which takes effect 1 to 3 days after use, and has a short action time. It is safer to use 0.25 1g per day. Non-renal failure chronic hypocalcemia can also use thiazide diuretics on the basis of a low-salt diet to reduce urinary calcium excretion.

Blood calcium is generally corrected to a normal low value, and correction to a normal high value can lead to hyperuricemia and prone to urinary calculi. ^[5]

Hypocalcemia disease prevention

1. Actively control the primary disease and regular physical examination. Hypocalcemia is prone to occur after thyroid or parathyroid surgery.

2. Increase sun exposure, proper nutrition, prevent weight loss, chronic diarrhea, etc. leading to malnutrition hypocalcemia.

3. Calcium supplementation is not a panacea. Menopausal women or patients with osteoporosis, such as those who take calcium and vitamin D preparations for a long time, should drink plenty of water, regularly test the blood calcium and urine calcium levels, and prevent calcium supplementation from causing hypercalcemia.

Hypocalcemia expert opinion

When serum protein concentration is normal, blood calcium is less than 2.2mmol / L (or 2.1mmol / L) is called hypocalcemia. Hypocalcemia often has no obvious clinical symptoms. However, rapid decline in blood calcium concentration or persistently low calcium can cause severe neurological and cardiovascular symptoms, which can be life-threatening in severe cases. Generally hypocalcemia is accompanied by the primary disease. Active treatment of the primary disease, calcium supplements, proper exercise, a certain amount of sunshine every day, and reasonable nutrition can prevent it. However, do not oversupply calcium to avoid hypercalcemia.