W3006               Physiology Fall 2001               Problem set #2 - Calcium

1. x>y, x<y, or x=y?
x. percent of daily calcium intake that is lost via the urine
y. percent of daily calcium intake that is lost via the feces

2. A. What effect would you expect in an individual who lacks growth hormone during early childhood? Explain.
B. Why would you not see the same effect if growth hormone is lacking during adulthood? Explain.

3. A. Indicate which two of these substances could be used to treat hypoparathyroidism:  
a. parathyroid hormone  b. calcitonin c. estrogen  d. vitamin D

B.  Of the two correct answers, one has proved to be the better choice. The reason is that the other one stimulates an immune response which renders it ineffective. Which is which ? Explain.

4. When calcium in the glomerular filtrate of the nephron is very high, calcium oxalate may precipitate out of the glomerular filtrate and form a small hard structure called a kidney stone. In some cases, this results from an overactive parathyroid gland. Explain.

5.. Lactating women lose calcium from their bodies when it is excreted in milk, and so their bodies require extra calcium. One might expect that these women are more effectively able to absorb dietary calcium, and thereby maintain homeostasis of blood calcium. However, experiments show otherwise. By feeding women calcium isotopes, scientists were able to measure the fraction of dietary calcium that was absorbed from the intestines into the body fluids. This fraction was about 30%, and was not different for lactating and non-lactating women.
A. Suggest two alternative ways that increased calcium may become available.
B. Considering the above information, propose an explanation for the finding that lactating women ware more likely to break a bone that non-lactating women. In your answer, include the specific cellular changes you would expect to see in the bones of lactating women.

6. During pregnancy, 1,25 Vitamin D is higher than usual.
A.The advantage of this high Vitamin D is:
B. The disadvantage of this high Vitamin D is:
C. Since removal of the thyroid does not affect calcium homeostasis, it's been suggested that calcitonin is required only in particular circumstances, such as pregnancy. What might be the advantage of having calcitonin at this time?

7. Osteomalacia develops when insufficient calcium is deposited in bones of adults (this is similar to rickets, which occurs in children). Explain the process by which kidney disease can lead to this condition.

8. Considering their similarity in function, it is not surprising that the _____  (osteoblasts or osteoclasts) are thought to derive from the same precursors as white blood cells..

9. After receiving a liver transplant, a person is given glucocorticoids, such as cortisol, to prevent rejection of the transplant.  Shortly thereafter, the person is found to have developed osteoporosis. One possibility is that this develops as a result of the original liver disease that necessitated the transplant. How might a diseased liver lead to osteoporosis?

B. A second possibility is that osteoporosis develops because glucocorticoids can inhibit Ca++ absorption from the intestines and increase Ca++ loss in the urine. It has been suggested that this causes osteoporosis because it leads to a. an increase b. a decrease in PTH, which would be expected to a. increase osteoblast activity b. increase osteoclast activity 

Answers

1.  x<y

2. A. doesn't grow to normal adult height. GH - liver - somatomedins - ends of bone - osteoblast activity - grow in length
B.  Gonadal steroids at puberty enhance GH effect, so individual shows a growth spurt,  but they also cause closure of epiphyses - growing area of cartilage fills with bone - no longer can respond to GH.

3. PTH and Vitamin D. PTH is a peptide hormone, Vit D is a steroid. Peptides are more likely to stimulate an antibody response.

4. The fluid that is filtered into the nephron comes directly from the blood, so the more calcium in the more blood, the more calcium there will be in the nephron. If the parathyroid gland secretes too much calcium, there'll be increased calcium absorbed from the intestine and resorbed from the bone, and reabsorbed from the kidney, so that blood calcium levels will be higher than normal, leading to higher than normal calcium in the filtrate. Although PTH can increase calcium resorption, it does so by way of membrane carriers, and the very high calcium will saturate these carriers, leaving high calcium in the filtrate, which can precipitate out of solution.

5 B. The effect of PTH on the bone is to stimulate activity of osteoclasts, which attach to hard bone, secreting H+ and lysosomal enzymes that dissolve the mineral and protein components of the bone matrix. This makes the bones less strong, and more likely to break.

6. A. Vitamin D increases absorption of calcium from small intestine, so blood calcium is higher, providing the additional calcium needed for development of the fetus' bones.
B. Vitamin D also works like PTH to increase the activity of osteoclasts, to further raise blood calcium levels. While this is good for calcium homeostasis in the mother (ensuring that her muscles and neurons get enough calcium) and good for the fetus (ensuring proper development) it can be detrimental to the mother's bones, which can become weaker as a result.
C. Calcitonin is able to inhibit osteoclast activity, an effect opposite to that of PTH. If calcitonin is secreted at this time, it would help to oppose the effect of Vitamin D, ensuring that the mother's bones don't lose too much calcium (while still enabling Vitamin D to have its effect at the intestinal level).

7. Like rickets, osteomalacia occurs when there is insufficient vitamin D for absorption of intestinal Ca++. This can result from problems anywhere in the pathway of Vitamin D synthesis, such as insufficient uv light exposure, or defect in activity of hydroxylases of kidney or liver. If diseased kidney doesn't make sufficient hydroxylase, there is less vitamin D, less Ca++ absorption from intestine, and more Ca++ lost in urine. This seems to be the major reason for osteomalacia developing in this situation. You also got credit if you suggested that kidney defect means PTH can't work there to stimulate reabsorption of Ca++ from the nephron, so more Ca++ is lost in urine.

8. osteoclasts (both contain many lysosomes with hydrolytic enzymes).

9. A. 25-alpha hydroxylase   from liver adds OH to 7-dehydrocholesterol, first step in activating Vitamin D. 2  Vitamin D increases Ca++ absorption from small intestines.  Unhealthy liver means less active Vitamin D produced, less Ca++ absorbed, less Ca++ available for deposition in bone, decreased bone density, osteoporosis.

B. a.  b.