Control of Mineral Metabolism Flashcards
What are the actions of Vitamin D?
The major action of 1,25 (OH)2 Vitamin D is on the GI tract where it eventually interacts with a NUCLEAR receptor increasing the synthesis of specific mRNAs and then proteins. One of these proteins is a CALCIUM BINDING PROTEIN that appears IN THE LUMEN of the intestine. It is not clear exactly how both calcium and phosphate transport are promoted, but it is possible that pinocytosis of this binding protein is involved.
1,25 (OH)2 VITAMIN D MOBILIZES BONE in a way similar to PTH, possibly simply by sensitizing the bone to PTH action. In recovery from chronic Vitamin D deficient states (e.g., rickets) however, the improvement in plasma calcium brought about by increased calcium and phosphate absorption leads to increased calcium deposition in bone. The physiologic significance of the mobilization of bone calcium by 1,25 (OH)2 Vitamin D is not at all clear.
How is 1, 25 (OH) Vitamin D regulated?
1,25 (OH)2 Vitamin D acts in a NEGATIVE FEEDBACK loop and regulates its own synthesis.
Often, the two hydroxylase enzymes of the kidney, 1-hydroxylase and 24-hydroxylase, are RECIPROCALLY REGULATED by influencing factors. For example, INCREASED levels of PTH positively and negatively affect the activities of 1-hydroxylase and 24-hydroxylase, respectively. High PTH will lead to increased levels of 1,25 (OH)2 Vitamin D, which then acts on the GI tract to increase calcium absorption. In this way, PTH and 1,25 (OH)2 Vitamin D act synergistically.
In contrast, decreased LEVELS OF PHOSPHATE positively and negatively affect the activities of 1-hydroxylase and 24-hydroxylase, respectively. Thus, if plasma phosphate falls, 1,25 (OH)2 Vitamin D synthesis is increased; in turn, the increased levels of 1,25 (OH)2 Vitamin D will act on the GI tract and promote increased phosphate absorption and return of plasma phosphate levels to normal. Cyclic AMP is thought to be involved in mediating influences of PTH and phosphate on 1-hydroxylase and 24-hydroxylase activities.
What is the most important hormone in the long term regulation of calcium balance?
Vitamin D is the important hormone in the long-term regulation of body calcium and phosphate stores by regulating the intestinal absorption of these minerals. A simple way to consider this is if IN
Describe hyperparathyroidism
In primary hyperparathyroidism, increased PTH increases calcium levels in plasma and urine (leading to renal stones). The effects of hypercalcemia include vague or overt symptoms of muscle weakness, depression and GI disorders. In severe cases, bone demineralization leads to bone pain and fractures. Secondary hyperparathyroidism can result from any disorder where plasma calcium is low such as rickets and renal failure.
Describe hypoparathyroidism
The major symptom of the decreased plasma calcium caused by a lack of PTH is INCREASED NEUROMUSCULAR EXCITABILITY that can cause muscle cramps, seizures as well as mental changes. One test for hypoparathyroidism is to tap the facial nerve, which evokes facial muscle spasms, (called Chvostek’s sign). There is a PTH dependent DECREASE IN CALCITRIOL levels causing DECREASED SERUM CALCIUM levels due to less absorption from intestines and less reabsorption through the kidneys. Bone demineralization is usually not a problem because of increased serum phosphate (due to increased reabsorption of phosphate from kidneys). It is usually TREATED WITH VITAMIN D AND CALCIUM SUPPLEMENTS.
Describe Vitamin D deficiencies in adults and children
Vitamin D deficiency is called RICKETS in children and OSTEOMALACIA in adults. Rickets can lead to severe skeletal deformities whereas symptoms of osteomalacia can include bone pain and pathological fractures. Dietary lack of Vitamin D is rare in the USA because of supplementation of milk. It can be seen in certain liver diseases and renal dysfunction, both of which interfere with synthesis of the active hormone.
