Hypercalcemia

Introduction to hypercalcemia Hypercalcemia refers to an abnormal increase in serum ionized calcium concentration. When calcium (intestines, bones) entering the extracellular fluid exceeds the excreted calcium (intestines, kidneys), hypercalcemia occurs, and the blood calcium concentration is higher than 2.75 mmol/L. There are two major causes of hypercalcemia. : PTH-dependent and non-PTH-dependent hypercalcemia. It is generally believed that serum calcium is above 3.75mmol/L, which can cause high calcium crisis. It is a clinical emergency when improper treatment is life-threatening. basic knowledge Sickness ratio: 0.0001% Susceptible people: no specific population Mode of infection: non-infectious Complications: Coma Interstitial nephritis Kidney stones

Cause of hypercalcemia

(1) Causes of the disease

1. PTH-dependent hypercalcemia

(1) Hyperparathyroidism: sporadic and hereditary, the former includes primary hyperparathyroidism (proliferation, adenoma and cancer), and three hyperparathyroidism (chronic renal function) Depletion and long-term lack of vitamin D), a small number of tumors that secrete PTH or PTH-related peptides (PTHrP),

(2) Familial hypocalciuria hypercalcemia: The disease is autosomal dominant, and the calcium receptor is inactivated due to mutation of the calcium receptor (CaSR) gene, which causes the PTH secretion threshold to decrease. Mild hypercalcemia, low blood magnesium, high chlorine acidosis.

(3) Lithium salt poisoning: Lithium can increase the calcium regulation point of PTH secretion. PTH secretion continues to secrete after elevated serum calcium, and may be associated with parathyroid hyperplasia and adenoma formation.

2. Non-PTH-dependent hypercalcemia

(1) Vitamin D poisoning: in the treatment of children with rickets, adult osteomalacia, hypoparathyroidism or renal osteodystrophy, the use of vitamin D dose is too large, so that intestinal calcium absorption increases and causes hypercalcemia, generally It is mild, asymptomatic and can be recovered after stopping the drug.

(2) malignant tumors: more common in malignant tumors that are prone to bone metastasis (such as breast cancer, bronchial lung cancer, kidney cancer and malignant tumors of the blood system), but hypercalcemia can also occur in malignant tumors without bone metastases. The mechanism of hypercalcemia is that cancer cells directly dissolve bone and release bone calcium into the blood circulation; the latter produces and releases humoral factors such as interleukin-1 and interleukin-6, and transforming growth factors for cancer cells. (TGF-), tumor necrosis factor (TNF) and prostaglandin E (PGE); some cancer cells can also produce PTH and PTH-related peptides (PTHrP), which can also bind to PTH receptors to resorb bone Increased; cancer cells can also produce osteoclast activating factor, which increases bone resorption.

(3) granulomatous disease and sarcosis (sarcoidosis): 2% to 12% of patients with hypercalcemia caused by sarcoidosis, glucocorticoid treatment can reduce blood calcium, granulomatous lesions including tuberculosis, Wegener granulomatosis , fungal infections, talc dust lungs, pneumoconiosis and so on.

(4) Milk-alkali syndrome: In the past, long-term consumption of milk and alkaline drugs in peptic ulcer can cause hypercalcemia, which is rarely used in modern times, so it is rare.

(5) pheochromocytoma: a small number of pheochromocytoma may have hypercalcemia, which may be caused by catecholamine stimulation of PTH secretion and increased bone resorption.

(6) the use of thiazide diuretics: long-term high-dose use of these drugs can cause hypercalcemia, usually temporary, can be restored after stopping.

(7) Restricted activities: due to the lack of skeletal muscle to pull the bones, combined with weight loss on the spine and lower limbs, so that the bone reabsorption exceeds bone formation, causing elevated blood calcium, these patients are prone to osteoporosis.

(8) Rhabdomyolysis: Hypercalcemia can occur during the recovery period of renal insufficiency, and calcium is deposited as a result of deposition in muscle and soft tissues.

(9) Dialysis patients: aluminum poisoning can occur, and aluminum poisoning can cause hypercalcemia.

(10) Vitamin A poisoning: causes hypercalcemia.

(11) Patients with parathyroid hyperplasia after renal transplantation: due to increased PTH, plus calcium reduction in transplanted kidney can cause hypercalcemia.

(two) pathogenesis

The main factors of hypercalcemia are: excessive calcium diffuses from the bone into the extracellular fluid, calcium is reduced from the kidney by the urine, and the intestinal mucosa absorbs excess calcium, but often caused by different factors, calcium from the bone Mobilization is mediated by factors that promote bone resorption. These activators include systemic factors [such as PTH, 1,25-(OH)2D3] and local action factors, such as various lymphokines. Calcemia, especially in the case of enhanced bone turnover, is more likely to occur, kidney damage, decreased body fluids can cause renal calcium excretion, abnormal hormone levels can also lead to reduced urinary calcium excretion and increased intestinal absorption of calcium, induced hypercalcemia .

Hyperparathyroidism leads to hypercalcemia. Hyperparathyroidism is divided into primary and secondary types. The former is mostly caused by adenoma, hyperplasia or cancer; the latter is often secondary to hypocalcemia. Parathyroid gland causes excessive secretion of PTH, promotes osteoclast activity, and the process of breaking bone exceeds the process of osteogenesis. Calcium is released from the bone into the blood, which increases blood calcium.

Malignant tumor bone metastasis causes bone destruction, decalcification and hypercalcemia, non-skeletal metastatic malignant tumors and hypercalcemia caused by non-parathyroid tumors, the mechanism may be due to tumor secretion of parathyroid hormone-like polypeptide Increased blood calcium.

Excessive calcium absorption in the intestinal mucosa is more common in high blood calcium caused by vitamin D poisoning. When vitamin D is excessive, on the one hand, the absorption of calcium in the intestinal mucosa increases, and the blood calcium increases; on the other hand, the bone tissue is broken, bone calcium is excreted, blood Calcium is increased, high blood calcium inhibits PTH secretion, and renal tubular reabsorption increases phosphorus and blood phosphorus increases.

Hypercalcemia prevention

Actively treat the primary disease.

Hypercalcemia complications Complications, coma, interstitial nephritis, kidney stones

1. Many manifestations of hypercalcemia are not specific to the primary disease. Very severe hypercalcemia can cause coma and death.

2. Hypercalcemia has the effect of interfering with vasopressin, which can lead to polyuria and polydipsia. Obvious hypercalcemia can be accompanied by a reversible decline in renal function. If hypercalcemia persists, renal function will Permanent damage occurs, especially when blood phosphorus is elevated, hypercalcemia can lead to renal calcification and interstitial nephritis, and kidney stones can also occur. In patients with hyperphosphatemia, calcium is very large. May deposit in other soft tissues, including the skin and cornea.

3. Hypercalcemia is easy to induce digitalis poisoning, should be vigilant.

Symptoms of hypercalcemia common symptoms fatigue, stiffness, arrhythmia, depression, anorexia, dehydration, convulsions, coma, constipation

The clinical manifestations of hypercalcemia are related to the increase and speed of blood calcium. According to the blood calcium level, hypercalcemia can be divided into mild: blood calcium is between 2.7 and 3.0 mmol/L; moderate: 3.0 to 3.4. Between mmol/L; Severity: 3.4 mmol/L or more.

1. Neuropsychiatric symptoms: Lightness is only fatigue, burnout, apathy; severe cases have headache, muscle weakness, decreased tendon reflexes, depression, irritability, gait instability, speech impairment, hearing, vision and disorientation or loss, Stupor, abnormal behavior and other mental and neurological symptoms, hypercalcemia crisis can occur convulsions, convulsions, coma, neuropsychiatric symptoms are mainly high calcium toxicity to brain cells, can interfere with brain cell electrophysiological activities.

2. Cardiovascular and respiratory symptoms: can cause elevated blood pressure and various arrhythmias, ECG shows QT interval shortening, ST-T changes, atrioventricular block and hypokalemia u wave, if not treated in time, Can cause fatal arrhythmia, because hypercalcemia can cause increased renal drainage and electrolyte imbalance, thickening of bronchial secretions, mucociliary activity of mucosal cells, poor drainage of bronchial secretions, easy to cause lung infection, difficulty breathing, Even respiratory failure.

3. Digestive system symptoms: manifested as loss of appetite, nausea, vomiting, abdominal pain, constipation, severe intestinal paralysis, calcium can stimulate gastrin and gastric acid secretion, so hypercalcemia is prone to peptic ulcer, calcium Ectopic deposition in the pancreatic duct, and calcium stimulates the secretion of pancreatic enzyme, which can cause acute pancreatitis.

4. Urinary system symptoms: high blood calcium can cause renal tubular damage, so that the renal tubular concentration function is reduced, combined with a large amount of calcium excreted from the urine, causing polyuria, polydipsia, polydipsia, and even loss of water, electrolyte imbalance and acid and alkali Unbalanced, calcium deposition in the renal parenchyma can cause interstitial nephritis, salt-salt nephropathy, renal calcinosis, and ultimately develop renal failure, but also prone to urinary tract infections and stones.

5. The ectopic deposition of calcium: hypercalcemia is prone to ectopic calcium deposition, can be deposited in the blood vessel wall, cornea, membrane, tympanic membrane, periarticular and cartilage, can cause muscle atrophy, corneal disease, red eye syndrome , hearing loss and joint dysfunction.

6. Blood system: Because of the activation of blood coagulation factors by calcium ions, extensive thrombosis can occur.

7. Hypercalcemia crisis: When blood calcium is increased to 4mmol/L or more, it is characterized by polydipsia, polyuria, severe dehydration, circulatory failure, and azotemia. If not rescued, patients may die of renal failure and Circulatory failure.

In a few serious cases, there may be neurological manifestations including lethargy, fatigue and reflex decline, QT interval shortening of ECG suggesting hypercalcemia, bradycardia and I degree atrioventricular block have also been reported, acute hypercalcemia may occur Significant blood pressure rise, gastrointestinal manifestations include weakness constipation and anorexia, nausea and vomiting in severe cases, hypercalcemia of different causes can be associated with acute pancreatitis.

Hypercalcemia examination

1. The plasma calcium concentration can be determined multiple times because the serum total calcium is interfered by serum albumin. Therefore, it is considered that the determination of plasma ionized calcium is superior to the determination of total plasma calcium, but the plasma calcium ion is affected by the pH value of the blood. Errors can occur,

2. Serum albumin should be measured simultaneously when measuring serum total calcium; blood ion pH should be measured simultaneously in the determination of ionized calcium in order to correct the measured results. In addition, when measuring ionized calcium, it should be noted that the pressure pulse zone should not be pressed for too long, and the compression time is too long. Long can change the blood pH value and make the blood ion calcium have a false increase.

According to the medical history, the symptoms were selected as B-ultrasound, X-ray examination, radionuclide scanning and CT examination.

Diagnosis and identification of hypercalcemia

Diagnostic criteria

1. Hypercalcemia refers to an increase in serum ionized calcium concentration. Usually, blood calcium is determined as total plasma calcium. >2.7 mmol/L can be considered as hypercalcemia. Total plasma calcium includes protein-bound calcium and complex calcium. And ionized calcium, serum albumin content and blood acid-base balance directly affect the concentration of ionized calcium. When analyzing the diagnostic value of serum total calcium concentration, the influencing factors should be considered.

2. The most common cause of hypercalcemia is primary hyperparathyroidism. The disease progresses slowly. In the early 50% of patients, only hypercalcemia, hypophosphatemia and parathyroid gland increase, and it is not easy to let go. Early diagnosis of hypercalcemia.

3. The following clinical clues should be observed, should be alert to hypercalcemia repeated stomach, duodenal ulcer; repeated episodes of acute pancreatitis; recurrent urinary tract stones or renal colic; repeated pathological fractures; unexplained muscle weakness and Muscle atrophy.

Differential diagnosis

To identify the disease associated with hypercalcemia:

1 malignant hypercalcemia.

2 multiple myeloma.

3 three hyperparathyroidism.

4 sarcoidosis.

5 vitamin A or D poisoning.

6 hyperthyroidism.

7 secondary hyperparathyroidism.

8 pseudo-hyperparathyroidism.

9 calcium receptor disease, selective venous intubation from the thyroid, tumor drainage area and peripheral vein blood, blood PTH or amino terminal PTH can be used to determine the diagnosis of pH TP and heterologous PTH secretory tumor.

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