”True and False” statements related to the VitaminD and Calcium Lecture
The understanding of the curriculum encompassed by these lectures represents a minimum requirement for full benefit from the interactive lecture on the following day. However, it may be wise to look through the present PowerPoint Presentation(from Semester 4a, MedFak) and the accompanying text early during this week.
Try to identify which statements are correct, and which are not. Also discuss how to correct the statements identified to be false. The statements may be correct even if they do not contain all the presented information. You may work alone or in small groups. It is recommended that you practice working in groups, since the literature assignment sessions and the Team-Based Learning sessions will only be successful when you feel free to discuss issues with others.
Statements, VitaminD:
1)Vitamin D is responsible for the maintenance of proper blood Calcium levels only.
2)There are two forms of vitaminD; ergocalciferol (D3) and cholecalciferol (D2), which display equal biological activities.
3)VitaminD3 is synthesized from 7-dehydrocholesterol in the skin under the influence of UV-B radiation.
4)The dermal production of VitaminD3 decreases with age, and is higher in less pigmented people. Its production is linear with exposure time and intensity of the UV-B light.
5)Active VitaminD interacts with PTH and CT to regulate blood levels of Calcium. Intracellular receptors for active VitaminD are found solely in bone tissue, and the lack of such receptors and/or the absence of vitaminD lead to rickets and osteomalacia.
6)A reduction in the blood and ECF-related Calcium levels reduces the circulating levels of PTH, which leads to a loss of 1,25-diOH-D produced by the kidney. 1,25-diOH-D increased the absorption of Calcium from the gut through an increase in the expression of Ca-binding protein(s) in enterocytes.
7)1,25-diOH-D binds to a receptor protein (VDR), which consists of a DNA-binding domain, a ligand-binding domain and a transcription-activating domain. The VDR are associated with and its action may be modulated by other small nuclear proteins (e.g. activators and co-activators).
8)The VDR-protein may interact with the RXR-protein (binding retinoic acid), thus forming heterodimers acting in concert on DNA to modulate transcription.
9)VitaminD is rapidly absorbed from the gut, transported in the blood bound to DBP, and thereafter hydroxylated to 25-OH-D in the kidney and to 1,25-diOH-D in bone.
10)The 25-hydroxylase has a low capacity, ensuring a low risk of a person being intoxicated by ingestion of large amounts of VitaminD.
11)The regulation of PTH-synthesis and -secretion, the CT-synthesis and -secretion, the 1-hydroxylation of 25-OH-D and blood calcium levels closely and mutually regulate each other: a) PTH is enhanced by enhanced serum Calcium levels, while reduced by increased 1,25-diOH-D levels; b) CT is reduced when serum levels of Calcium rise; c) PTH enhances the 1-hydroxylation of 25-OH-D.
12)ProVitaminD3 are metabolized to PrevitaminD3 in the skin. Both forms may be damaged to prolonged exposure to UV-B irradiation, making the output of VitaminD3 form the skin a self-controlling system.
13)The liver 25-hydroxylates VitaminD, a reaction known to be affected by a positive feed-back loop involving both VitaminD, 25-OH-D, and 1,25-diOH-D levels.
14)1-hydroxylation of 25-OH-D in the kidney is stimulated by PTH, reduced by Calcium, increased by phosphate, and increased by the presence of GH, Insulin and Prolactin.
15)25-OH-D hydroxylation also occurs in the kidney and is inverse to 25-hydroxylation. High levels of Calcium favours 24-hydroxylation, which secures the Calcium homeostasis, since 24,25-diOH-D does not readily bind to the VDR.
16)Under normal conditions, VitaminD-synthesis in the skin is less important, thus we must rely on dietary intake (including sources like oily fish, enriched margarine, and enriched milk.
17)VitaminD-status is well reflected by the plasma concentrations of 25-OH-D. A plasma concentration of > 100nmol/l is considered adequate. Less than 50 nmol/l will cause rickets and osteopenia.
18)Reduced Calcium absorption leads to increased PTH, which in turn yields phosphate excretion and a reduction in mineralization of bone matrix proteins.
19)Vitamin D deficiency leads to rickets/osteomalacia, which are identified on the basis of the following, symptoms and findings: soft bones, bone pain, muscle weakness, increased cortical bone thickness, pseudo-fractures, low serum 25-OH-D, secondary hyperparathyroidism, low, calcium/phosphate in blood, increased release of ALP from bone.
20)A newborn baby’s VitaminD stores last only 5-7 days. Recommended daily dosage for infants up to 2 years of age is10 μg/day.
21)Elderly people have low levels of VitaminD due to: limited time spent outdoors, Inherently lower ability to synthesize VitaminD3 in their skin, malnutrition, inherently reduced activity of hepatic 25-hydro\xylase due to subclinical cirrhosis.
Statements, Calcium:
1)Calcium is a co-factor in enzymatic reactions. The ion is also a second messenger in the signalling cascade induced by several hormones. It is also part of structural elements in bone (hydroxyapatite crystals on collagen).
2)Most of the Calcium is found in bone, but some is also located in blood, ECF and intracellular compartments. Calcium is lost through faeces, urine, skin, air expired from the lungs, to foetuses in growth, breast milk.
3)Serum Calcium is regulated closely through adapting the 1- and 24-hydroxylation activities in the kidneys. High levels of Calcium is associated with reduced activity of 1-hydroxylation, while low levels of Calcium is associated with high levels of 24-hydroxylation. Ionized Calcium in blood represents the bioactive form of Calcium.
4)Bone mineralization depends on the presence of Calcium and phosphate ions and precipitation of hydroxyl-apatite crystals deposited onto collagen molecules. The more Calcium taken up and deposited, the higher BMD obtained by the individual. Peak bone mass (highest obtainable BMD) occurs at the age 25-30 years, and thereafter diminishes with age. Men and women display different BMDs throughout their lifetime.
5)BMD is affected by factors like Calcium availability (positive), body weight (negative), physical activity (positive), hormonal status = testosterone, oestrogen = (positive) and smoking (negative).
6)Bone remodelling will ensure the removal of microfractures and deposition of fresh, strong mineralized bone matrix. Bone remodelling is brought about by osteoblast and osteoclasts, the former building bone in resorption pits made by the osteoclast. The activity of the osteoblasts and osteoclasts are tightly regulated, however, this regulation may be affected by certain pathophysiological conditions, such as osteoporosis, hyperparathyroidism and diabetes.
7)Mature osteoblast express receptors for PTH and 1,25-diOH-D, while mature osteoclasts have receptors for CT and 1,25-diOH-D.
8)Some conditions are associated with “loss” of Calcium, like osteoporosis and osteomalacia. Osteoporosis is defines as “reduced bone mineral density with concomitant fracture”.
9)Dietary intake of Calcium (to replace loss) should be: approximately 800 mg/day irrespective of age and sex and physical condition, status of health.
10) The absorption of Calcium is affected by following factors: 1,25-diOH-D (positive), oxalic acid (negative), phytic acid (negative), phosphate (negative) and fatty acids (negative) and age (loss of adaptation to variation in needs).
11) PTH affects serum Calcium trough: increasing reabsorption in the kidney, stimulating the production of 1,25-diOH-D in the kidney, increases resorption of Calcium from bone in concert with 1,25-diOH-D.
12) 1,25-diOH-D affects calcium by: enhancing Calcium transport across the GI-tract to the blood, increases reabsorption in the kidney, mobilizes Calcium from bone in concert with PTH.
13) CT affects serum Calcium through enhancing the Calcium deposition of the osteoblast after osteoclast-mediate resorption.
Statements directly related to details on osteoporosis and rickets/osteomalacia have deliberately been omitted, since these are issues being focussed on in other lectures.
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