Porth's Essentials of Pathophysiology, 4e

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Integrative Body Functions

U N I T 2

Pseudohypoparathyroidism is a rare familial disorder characterized by target tissue resistance to PTH. It is characterized by hypocalcemia, increased parathy- roid function, and a variety of congenital defects in the growth and development of the skeleton, includ- ing short stature and short metacarpal and metatarsal bones. There are variants of the disorder, with some per- sons having the pseudohypoparathyroidism along with the congenital defects and others having the congeni- tal defects with normal calcium and phosphorus levels. The manifestations of the disorder are due primarily to chronic hypocalcemia. Treatment. The goals of therapy focus on the control of symptoms while minimizing complications. Acute hypo- parathyroid tetany, which usually occurs after surgery, is treated with intravenous calcium gluconate followed by oral administration of calcium salts and vitamin D. Magnesium supplementation is used when the disorder is caused by magnesium deficiency. Persons with chronic hypoparathyroidism are treated with oral calcium and vitamin D. Levels of serum calcium, phosphorus, and creatinine (to check kidney function) are monitored at regular intervals as a means of maintaining serum cal- cium within a slightly low but asymptomatic range. Hyperparathyroidism Hyperparathyroidism is characterized by increased lev- els of PTH. It can manifest as a primary disorder caused by hyperplasia or tumors of the parathyroid glands, as as a secondary disorder in persons with chronic kidney disease or chronic malabsorption of calcium. 58–61 Manifestations. Primary hyperparathyroidism is a leading cause of hypercalcemia in the outpatient depart- ment. It is seen more commonly after 50 years of age and is more common in women than men. 58 Primary hyper- parathyroidism causes an elevation in ionized serum cal- cium and increased urinary excretion of both calcium and phosphorus. The increased urinary concentration of calcium and phosphorus may prompt the development of kidney stones. Chronic bone resorption may produce diffuse demineralization, pathologic fractures, and cys- tic bone lesions. Signs and symptoms of the disorder are related to skeletal abnormalities, exposure of the kidney to high calcium levels, and elevated serum calcium levels (see hypercalcemia). At the present time, primary hyper- parathyroidism usually manifests as an asymptomatic disorder that is discovered in the course of routine bio- chemical testing. Although thought to be asymptomatic, these patents may experience nonspecific constitutional symptoms such as fatigue, weakness, anorexia, and bone pain. 60 Secondary hyperparathyroidism involves hyperplasia of the parathyroid glands and occurs primarily in per- sons with chronic kidney disease. 59,60 In the early stages of chronic kidney disease, an increase in PTH results from decreased serum calcium and activated vitamin D levels. As the disease progresses, there is a decrease in

vitamin D and calcium receptors, making the parathyroid glands more resistant to feedback regulation by serum calcium and vitamin D levels. At this point, elevated phosphorus levels induce hyperplasia of the parathyroid glands independent of calcium and vitamin D levels. The bone disease seen in persons with secondary hyper- parathyroidism due to chronic kidney disease is known as renal osteodystrophy (see Chapter 26). Treatment. Treatment of hyperparathyroidism includes resolving the hypercalcemia with increased fluid intake. Whenever possible, the underlying cause of secondary hyperparathyroidismshouldbe treated. Parathyroidectomy may be indicated in persons with symptomatic primary hyperparathyroidism. The goal of medical management is to normalize calcium levels. Calcitriol and other vitamin D analogs may be used to control parathyroid hyperpla- sia in chronic kidney disease. Persons with chronic kid- ney disease may also need phosphate binders to decrease intestinal absorption of phosphorus and prevent the skel- etal disorders associated with the osteodystrophies (see Chapter 26). Calcimimetic agents, which act through the calcium-sensing receptor in the parathyroid gland, may be used to decrease PTH production in primary and second- ary hyperparathyroidism. 59–61 ■■ Calcium, phosphorus, and magnesium are the major divalent ions in the body.These divalent ions are directly or indirectly regulated by a number of factors including vitamin D and PTH. ■■ Calcium is a major divalent cation with approximately 99% located in bone and less than 1% in the ECF compartment. Of the three forms of ECF calcium, only the ionized form can cross the cell membrane, contributing to neuromuscular function, blood clotting, and enzyme reactions. In hypocalcemia, decreased levels in ionized calcium produce an increase in neuromuscular excitability; and in hypercalcemia increased levels of ionized calcium produce a decrease in excitability. ■■ Phosphorus is largely an ICF anion, being incorporated into nucleic acids, adenosine triphosphate (ATP), and 2,3-diphosphoglycerate in the red blood cells. Hypophosphatemia, which is associated with decreased intestinal absorption, transcompartmental shifts, and disorders of renal elimination, causes signs and symptoms of neural dysfunction, disturbed musculoskeletal function, and hematologic disorders. Hyperphosphatemia, which occurs with renal failure and PTH deficit, is associated with decreased plasma calcium levels. SUMMARY CONCEPTS