Porth's Essentials of Pathophysiology, 4e

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Disorders of Fluid, Electrolyte, and Acid–Base Balance

C h a p t e r 8

Hypermagnesemia Hypermagnesemia represents an increase in total body magnesium and a serum magnesium concentration in excess of 2.5 mg/dL (1.1 mmol/L). 3 Because of the abil- ity of the normal kidney to excrete magnesium, hyper- magnesemia is rare. When hypermagnesemia does occur, it usually is related to renal insufficiency and the injudicious use of magnesium-containing medications such as antacids, mineral supplements, or laxatives. 3 The elderly are partic- ularly at risk because they have age-related reductions in kidney function and tend to consume more magnesium- containing medications, including antacids and laxa- tives. Magnesium sulfate is used to treat toxemia of pregnancy and premature labor; in these cases, careful monitoring of serum magnesium levels and observation for signs of hypermagnesemia are essential. Neonatal hypermagnesemia may also occur, but usually the blood levels of magnesium are lower in the infant than in the mother. 52 Manifestations. The signs and symptoms occur only when serum magnesium levels exceed 4.0 mg/dL (2.0 mmol/L). 35,52 Because magnesium tends to sup- press PTH secretion, hypocalcemia may accompany hypermagnesemia. Hypermagnesemia affects neuromuscular and car- diovascular function 3,50,53 (see Table 8-8). Increased lev- els of magnesium decrease acetylcholine release at the myoneural junction, causing hyporeflexia and muscle weakness. Cardiovascular effects are related to the cal- cium channel–blocking effects of magnesium. Blood pressure is decreased, and the ECG shows an increase in the PR interval, a shortening of the QT interval, T-wave abnormalities, and prolongation of the QRS and PR intervals. Severe hypermagnesemia is associated with muscle and respiratory paralysis, complete heart block, and cardiac arrest. Treatment. The treatment of hypermagnesemia includes cessation of magnesium administration. Calcium is a direct antagonist of magnesium, and intravenous admin- istration of calcium may be used. Peritoneal dialysis or hemodialysis may be required. Disorders of Parathyroid Hormone Both calcium and phosphate homeostasis are impacted by disorders of PTH. Parathyroid hormone is secreted by the four parathyroid glands located adjacent to the thyroid gland in the neck. The hormone is synthe- sized as a preprohormone, converted to a prohormone and then to PTH, and finally packaged into secretory granules for release into the circulation. The domi- nant regulator of PTH secretion is the serum calcium concentration (see Fig. 8-13). A unique ECF calcium- sensing receptor on the parathyroid cell membrane responds rapidly to changes in serum calcium levels. 1,2 When the serum calcium level is high, the secretion

of PTH is inhibited, and serum calcium is deposited in the bones. When the level is low, PTH secretion is increased, and calcium is mobilized from the bones and released into the blood. The synthesis and release of PTH from the para- thyroid gland are also influenced by magnesium. 56 Magnesium serves as a cofactor in the generation of cel- lular energy and is important in the function of second messenger systems. Magnesium’s effects on the synthesis and release of PTH are thought to be mediated through these mechanisms. Because of its function in regulating PTH release, severe and prolonged hypomagnesemia can markedly inhibit PTH levels. The central function of PTH is to regulate ionized Ca ++ levels through three target organs: bone, kidney, and intestine absorption. Parathyroid hormone stimu- lates the release of calcium from bone; and it increases calcium reabsorption by the kidney, while increasing the activation of vitamin D by the kidney; which in turn, increases the intestinal reabsorption of calcium. Hypoparathyroidism Hypoparathyroidism reflects deficient PTH secre- tion, resulting in low serum levels of ionized calcium. Parathyroid hormone deficiency may occur because of a congenital absence of all of the parathyroid glands, as in DiGeorge syndrome (see Chapter 16), or because of an acquired disorder due to inadvertent removal or irreversible damage to the glands during thyroid- ectomy, parathyroidectomy, or radical neck dissection for cancer. 35,56,57 A transient form of PTH deficiency may occur after thyroid surgery owing to parathyroid gland suppression. Hypoparathyroidism also may have an autoimmune origin. Antiparathyroid antibodies have been detected in some persons with hypoparathy- roidism, particularly those with multiple autoimmune disorders such as type 1 diabetes mellitus or Graves disease. Other causes of hypoparathyroidism include heavy metal damage such as occurs with Wilson dis- ease and metastatic tumors. Functional impairment of parathyroid function occurs with magnesium defi- ciency. Correction of the hypomagnesemia results in rapid disappearance of the condition. Manifestations. Manifestations of acute hypoparathy- roidism, which result from a decrease in serum calcium, include tetany with muscle cramps, carpopedal spasm, and convulsions (see section on hypocalcemia). 56,57 Paresthesias, such as tingling of the circumoral area and in the hands and feet, are almost always present. Low calcium levels may cause prolongation of the QT interval on the ECG, resistance to digitalis, hypotension, and refractory heart failure. Symptoms of chronic PTH deficiency include lethargy, an anxiety state, and person- ality changes. There may be blurring of vision because of cataracts, which develop over a number of years. Extrapyramidal signs, such as those seen with Parkinson disease, may occur because of calcification of the basal ganglia. Teeth may be defective if the disorder occurs during childhood.