BSI Case Study 57

Question 1

What are the forms of calcium in serum? Which forms are biologically active?

Answer 1

There are three components: calcium bound to albumin (40%), calcium bound to anions (10%), and free, ionized calcium which is the only form that is active.

Question 2

What are the physiological actions of parathyroid hormone (PTH) on bone, kidney, and intestine?

Answer 2

In all three areas, the goal is to increase serum ionized calcium concentration and decrease the serum phosphate concentration.

1) In the bone, PTH works with 1,25-dihydroxycholecalciferol to stimulate osteoclasts and increase bone resorption. Therefore, calcium and phosphate are released from mineralized bone into the extracellular fluid. However, this alone won’t increase serum ionized calcium because it will bind to the phosphate that is released.
2) In the kidney, PTH has two actions, both which are mediated by adenylyl cyclase and the production of cyclic AMP. In the early proximal tubule, PTH inhibits the Na+ phosphate cotransporter which is responsible for phosphate reabsorption; therefore, there is an increase in urination/excretion of phosphate. This allows serum ionized calcium to increase. This is known as the phosphaturic effect.
3) In the intestine, PTH acts indirectly to increase calcium absorption by stimulating renal synthesis of 1,25-dihydroxycholecalciferol, the active form of vitamin D.

Question 3

Carl’s physician made a diagnosis of primary hyperparathyroidism on the basis of Carl’s serum calcium, phosphate, and PTH levels. How were these values consistent with primary hyperparathyroidism?

Answer 3

Based on Carl’s patient chart, there is an increase in serum calcium, a decrease in serum phosphate, and an increase in serum PTH. The parathyroid adenoma was secreting excessive amounts of PTH, which increased bone resorption, decreased reabsorption of phosphate in the kidneys, and increased reabsorption of calcium in the kidneys and intestines. This is what caused Carl’s hypercalcemia. The phosphaturia was caused by the decrease in renal phosphate reabsorption.

Question 4

What is primary hyperparathyroidism sometimes characterized by?

Answer 4

“Stones, bones, and groans.” Stones because of the hypercalciuria, bones because of the increased bone resorption, and groans because of constipation caused by hypercalcemia.

Question 5

Why didn’t Carl’s hypercalcemia (increased serum calcium) inhibit PTH secretion?

Answer 5

PTH secretion by the normal parathyroid tissue is inhibited by hypercalcemia. However, PTH secretion by the adenoma is autonomous and, therefore, is not under negative feedback regulation. Thus, the adenoma continued to secrete PTH unabated, even under conditions of hypercalcemia.

Question 6

What was the significance of Carl’s elevated alkaline phosphatase level?

Answer 6

The major sources of serum alkaline phosphatase are the liver and bone. Increased levels of alkaline phosphatase in bone are associated with increased osteoblastic activity and high bone turnover.

Question 7

In making the correct diagnosis, it was important to know that Carl’s serum albumin level was normal, why?

Answer 7

There are three components to calcium levels. Protein-bound calcium, complexed calcium, and free, ionized calcium. The total calcium level is a measure of all three components. When making a diagnosis, it’s important to determine if the calcium level is elevated because of an increase in protein-bound calcium or whether there is an abnormality in calcium homeostasis. Since Carl’s serum albumin levels were normal, the increase in total calcium levels was caused by an increase in ionized calcium.

Question 8

Why was Carl’s urinary calcium excretion elevated (hypercalciuria)?

Answer 8

Carl’s increased urinary calcium excretion led to the formation of painful urinary calcium oxalate stones. PTH does increase calcium reabsorption. However, as the serum calcium concentration increases, so does the filtered load. Thus, despite reabsorption, the filtered load of calcium eventually overwhelms the reabsorptive capacity of the kidneys. Thus, in primary hyperparathyroidism, both the reabsorption and excretion of calcium are increased.

Question 9

What was the relationship between Carl’s recent history of dietary calcium supplementation and his hypercalciuria?

Answer 9

Carl’s primary hyperparathyroidism may have been present for several years. Carl could be asymptomatic because, as his serum calcium level gradually increased, his filtered load of calcium also increased and the excess calcium was excreted in the urine. By dumping calcium in the urine, his serum calcium was protected from dangerous increases in calcium concentrations. However, when Carl took calcium and vitamin D supplements, the calcium load to his kidneys sharply increased. The final precipitating event was dehydration. This stimulated ADH secretion, and Carl’s urine became concentrated. Carl’s symptoms were caused by an increase in the urinary calcium concentration and the precipitation of calcium oxalate stones.

Question 10

What is PTH?

Answer 10

Parathyroid hormone, a hormone secreted by the parathyroid gland.

Question 11

Parathyroid adenoma

Answer 11

A benign tumor of the parathyroid gland. It usually results in hyperparathyroidism.

Question 12

Hyperparathyroidism

Answer 12

Overactive parathyroid gland which leads to the overproduction of PTH

Question 13

Hypercalcemia

Answer 13

Elevated levels of calcium in the blood

Question 14

Hypercalciuria

Answer 14

Elevated levels of calcium in the urine

Question 15

Hypophosphatemic

Answer 15

Low serum phosphate levels

Question 16

Phosphaturia

Answer 16

The excessive discharge of phosphate in the urine

Question 17

Primary hyperparathyroidism

Answer 17

A disorder in which the parathyroid glands become overactive and secrete excessive amounts of parathyroid hormone which increases the level of calcium in the blood, resulting in hypercalcemia