Multiple Choice Questions (MCQs) on Parathyroid Hormone, Vitamin D and Calcium Metabolism:Biochemistry, Physiology

Multiple Choice Questions (MCQs) on Parathyroid Hormone, Vitamin D and Calcium Metabolism

1) Which of the following organ has the highest proportion of calcium in the body?

a) Liver

b) Muscle

c) Bone

d) None of the above 

2) The plasma contributes to less than 0.5% of the total calcium in the body. 

Which of the following statement is not true regarding plasma calcium?

a) Approximately 50% of the plasma calcium is present in the ionized form

b) Approximately 40% of the plasma calcium is present in proteins

c) Approximately 10% of the plasma calcium is complexed with anions

d) None of the above 

3) Free, ionized calcium is biologically acid and tightly regulated by hormones. 

Which of the following hormone are secreted in response to increased serum calcium?

a) Parathyroid hormone

b) Vitamin D

c) Calcitonin

d) All of the above

4) Parathyroid hormone secretion is tightly controlled by the ionized calcium ions. The calcium binds to calcium-sensing cell surface receptors in the parathyroid gland.  

Which of the following second messenger is activated by calcium-sensing cell surface receptors?

a) cGMP

b) cAMP

c) Phosphoinositol triphosphate

d) Diacylglycerol

5) Which of the following is the indirect action of parathyroid hormone?

a) Increased bone reabsorption

b) Increased renal calcium reabsorption

c) Increased intestinal calcium reabsorption

d) All of the above

6) The parathyroid hormone binds to its cell surface receptor and activates the following cell surface receptor?

a) cGMP

b) cAMP

c) Phosphoinositol triphosphate

d) Diacylglycerol 

7) The parathyroid hormone promotes the synthesis of active Vitamin D3. 

Which of the following enzyme is activated by the parathyroid hormone?

a) 25-alpha hydroxylase

b) 1-alpha hydroxylase

c) 24-alpha hydroxylase

d) All of the above

8) Which of the following laboratory measurement are used to detect bone demineralization and remodeling?

a) Osteocalcin

b) Alkaline Phosphatase

c) Hydroxyproline

d) All of the above 

9) The synthesis of active vitamin D3 from the precursors involves sequential steps that occur in the skin, liver, and kidney.  

Arrange the correct reaction order for the synthesis of active vitamin D3:

a)  1 hydroxyvitamin D

b)  Inactive Vitamin D

c) 7 dehydrocholesterol

d) 1, 25 dihydroxy vitamin D

10) Primary hyperparathyroidism is a disorder caused by the parathyroid adenoma. The following biochemical results are  the characteristic feature of hyperparathyroidism, EXCEPT

a) Increased PTH hormone

B) Increased Vitamin D3

c) Increased urinary cAMP & calcium excretion

d) Decreased serum calcium and phosphate

11) Humoral hypercalcemia is caused by the hypersecretion of PTH-related peptides. The humoral hypercalcemia is characterized by the following, EXCEPT

a) hypercalcemia

b) Hypophosphatemia

c) Increased urinary phosphate excretion

d) Increased serum PTH levels

12) The Pseudohypoparathyroidism type Ia is the result of defective Gs protein in the kidney and bones. The pseudohypoparathyroidism is characterized by: 

a) Hypercalcemia, hyperphosphatemia, and elevated PTH level

b) Hypercalcemia, hyperphosphatemia, and decreased PTH level

c) Hypocalcemia, hyperphosphatemia, and  elevated PTH level

d) Hypocalcemia, hypophosphatemia, and  elevated PTH level

13) Vitamin D stimulates the absorption of calcium and phosphate in the intestinal cells. 

Vitamin D acts via:

a) Binding to G protein receptor and activating adenylyl cyclase

b) Binding to Tyrosine  kinase receptor and activate phosphotyrosines

c) Binding to the cytosolic receptor, localization and increased gene expression 

d) All of the above 

14) Which of the following condition are associated with vitamin D deficiency?

a) Lipid malabsorption

b) Hypoparathyroidism

c) Renal Osteodystrophy

d) All of the above

15) The familial hypocalciuric hypercalcemia is caused by the mutation in the calcium-sensing receptor. The mutation results in...................................

a) Decreased secretion of PTH

b) Increased set point for calcium homeostasis

c) Decreased renal reabsorption of calcium

a) All of the above

Answers with Explanation:

1-c) Bone

Bone tissue contains about 99% of the body's total calcium, making it the organ with the highest proportion of calcium in the body. The remaining 1% of calcium is found in the bloodstream, muscles, and other tissues.

2-d) None of the above 

Approximately 50% of the plasma calcium is present in the ionized form, which is the biologically active form of calcium. Approximately 40% of the plasma calcium is bound to proteins, particularly albumin. The remaining 10% of plasma calcium is complexed with anions, such as phosphate and citrate.

3-c) Calcitonin

Parathyroid hormone (PTH) is secreted by the parathyroid gland in response to decreased levels of ionized calcium in the blood. PTH acts to increase the concentration of ionized calcium in the blood by increasing the release of calcium from bone tissue, reducing calcium excretion in the kidneys, and enhancing calcium absorption in the intestines.
Calcitonin, on the other hand, is secreted by the thyroid gland in response to increased levels of calcium in the blood, and acts to lower the concentration of ionized calcium in the blood by inhibiting bone resorption, promoting calcium deposition in bones, and increasing calcium excretion in the kidneys.
Vitamin D is also involved in the regulation of calcium levels, but it is not a hormone that is directly secreted in response to changes in serum calcium levels. Instead, vitamin D is activated in response to PTH and other factors, and acts to increase the absorption of calcium in the intestines.

4-c) Phosphoinositol triphosphate (IP3)
The second messenger that is activated by calcium-sensing cell surface receptors in the parathyroid gland is phosphoinositide-specific phospholipase C (PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
cGMP and cAMP are second messengers that are activated by receptors that stimulate guanylate cyclase and adenylate cyclase, respectively. They are not directly involved in the signaling pathway that regulates parathyroid hormone secretion in response to changes in ionized calcium levels.
Diacylglycerol (DAG) is generated by the cleavage of PIP2 by PLC, but it is not a second messenger activated by calcium-sensing cell surface receptors in the parathyroid gland. Instead, DAG is involved in the activation of protein kinase C (PKC), which is downstream of the IP3 signaling pathway.

5-c) Increased intestinal calcium reabsorption

The indirect action of parathyroid hormone (PTH) is increased intestinal calcium reabsorption. PTH indirectly stimulates intestinal calcium reabsorption by increasing the production of 1,25-dihydroxyvitamin D, also known as calcitriol, which is the active form of vitamin D. Calcitriol acts on the intestines to increase the absorption of dietary calcium.
On the other hand, the direct actions of PTH include increased bone resorption and increased renal calcium reabsorption. PTH directly stimulates osteoclasts, which are the cells that break down bone tissue, to increase bone resorption and release calcium into the blood. PTH also acts on the kidneys to increase the reabsorption of calcium, which reduces the excretion of calcium in urine and increases the concentration of calcium in the blood.

6-b) cAMP

The parathyroid hormone (PTH) binds to its cell surface receptor, the PTH receptor (PTH1R), and activates the cAMP signaling pathway.
When PTH binds to PTH1R, it activates a G protein-coupled receptor (GPCR) signaling cascade that leads to the activation of adenylate cyclase, an enzyme that converts ATP into cAMP. The increase in cAMP levels then triggers downstream signaling events that ultimately mediate the effects of PTH on target tissues, such as bone and kidney.

7-b) 1-alpha hydroxylase

The parathyroid hormone (PTH) promotes the synthesis of active Vitamin D3, also known as calcitriol, by stimulating the activity of the enzyme 1-alpha hydroxylase.
1-alpha hydroxylase is responsible for the conversion of 25-hydroxyvitamin D (25(OH)D), which is the inactive form of Vitamin D3 that is produced in the liver, to calcitriol in the kidneys. PTH stimulates the expression and activity of 1-alpha hydroxylase, which leads to increased production of calcitriol.

8-d) All of the above

Osteocalcin is a protein that is produced by osteoblasts during bone formation and is released into the bloodstream as bone is remodeled. Measurement of serum osteocalcin levels can be used as a marker of bone formation and turnover.
Alkaline phosphatase is an enzyme that is produced by osteoblasts and is involved in the formation of new bone. Measurement of serum alkaline phosphatase levels can be used as a marker of bone formation and remodeling.
Hydroxyproline is an amino acid that is a major component of the collagen matrix in bone. Measurement of urinary hydroxyproline levels can be used as a marker of bone resorption and turnover.

9- Correct reaction sequence: c) -->b)-->a)-->d)

The correct reaction order for the synthesis of active vitamin D3 is as follows:7-dehydrocholesterol is converted to pre-vitamin D3 upon exposure to UVB radiation from sunlight.
Pre-vitamin D3 undergoes a thermal isomerization to form Vitamin D3.
Vitamin D3 is transported to the liver where it is converted to 25-hydroxyvitamin D [25(OH)D] by the enzyme 25-hydroxylase.
25(OH)D is then transported to the kidneys where it is converted to 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of Vitamin D3, by the enzyme 1-alpha-hydroxylase.

10-d) Decreased serum calcium and phosphate

Primary hyperparathyroidism is a condition where the parathyroid gland secretes excessive amounts of PTH hormone leading to hypercalcemia (increased serum calcium levels) and hypophosphatemia (decreased serum phosphate levels). The characteristic features of primary hyperparathyroidism are increased PTH hormone, increased urinary cAMP and calcium excretion, and increased levels of active Vitamin D3 (1,25-dihydroxyvitamin D3). Therefore, option d) is incorrect as it describes a decrease in serum calcium and phosphate levels, which is not a feature of primary hyperparathyroidism.

11-d) Increased serum PTH levels

Increased serum PTH levels is not a characteristic of humoral hypercalcemia. In this condition, hypersecretion of PTH-related peptides by certain tumors (such as squamous cell carcinoma) causes hypercalcemia by mimicking the action of PTH on bone and kidney. The elevated levels of PTH-related peptides stimulate bone resorption, resulting in the release of calcium and phosphate into the blood. The increased levels of calcium in the blood can lead to hypophosphatemia (low levels of phosphate) due to increased renal excretion of phosphate. Therefore, options a, b, and c are characteristic features of humoral hypercalcemia.

12-c) Hypocalcemia, hyperphosphatemia and  elevated PTH level

Pseudohypoparathyroidism type Ia is a rare genetic disorder caused by a defect in the Gs protein-coupled signaling pathway. The defect results in resistance to the action of PTH on the target organs, especially the kidney and bone. As a result, there is decreased renal calcium reabsorption, increased renal phosphate reabsorption, and decreased bone resorption, leading to hypocalcemia and hyperphosphatemia. The high levels of PTH are due to the body's attempt to compensate for the hypocalcemia by increasing PTH secretion.

13)-c) Binding to the cytosolic receptor, localization and increased gene expression 

Vitamin D acts via binding to the cytosolic receptor, localization and increased gene expression. The cytosolic Vitamin D receptor forms a heterodimer with the Retinoid X receptor (RXR), which then translocates to the nucleus and binds to specific regions of DNA known as Vitamin D response elements (VDREs) located in the promoter regions of target genes. This binding leads to increased transcription and translation of specific genes involved in the absorption of calcium and phosphate in the intestinal cells.

  

14)- d) All of the above

15-b) Increased set point for calcium homeostasis

The familial hypocalciuric hypercalcemia (FHH) is caused by the mutation in the calcium-sensing receptor. This receptor is responsible for sensing the level of ionized calcium in the blood and regulating PTH secretion and renal calcium reabsorption accordingly. Mutation in the calcium-sensing receptor can result in a higher set point for calcium homeostasis, leading to reduced sensitivity to changes in calcium levels and a tendency towards hypercalcemia. This condition is inherited in an autosomal dominant pattern and is typically asymptomatic, with mild to moderate hypercalcemia being the only abnormality seen on laboratory testing.