Vitamin D

There is only two pro-forms for vitamin D? T/F

F

1-Alfa hydroxylation The activity of 1-Alfa hydroxylase depends on:

*(-) Calcium level* (low level increase activity) *(-) Phosphorous level* (low level increase it) *(-) Level of Calcitriol* (decrease activity) *(+) The parathyroid hormone* (stimulate activity)

Main functions (rules) of vitamin D

*1-Bone metabolism:* increase Ca absorption from gut and kidneys and increase deposition of Ca in bones (solidification of bones). *2-Retard cell proliferation and promote cell differentiation "Anti-cancer effect"* (breast and colonic cancer). *3-Pharmacological role in treatment of psoriasis*

Vitamin D transport and storage

*Storage* 25 HCC is the storage form of vitamin D in the liver *Transport* - *88%* of 25 HCC circulates bound to specific vitamin D-binding protein, - *0.03%* is free, and - *the rest* circulates bound to albumin

Other rules for vitamin D

*Vitamin D receptors was found in most tissues (e.g., immune cells, brain, breast, colon, and prostate) and is thought to be important for:* -Prevention of cardiovascular diseases -Prevention of hypertension -Immune function. (type 1 diabetes) -Low grade inflammation (tuberculosis) -Brain function (depression, multiple sclerosis)

Treatment

-Correction of underlying cause -Ergocalciferol (250-1000 μg daily) for 3-4 months then maintenance of 10-20 μg daily. -Calcium supplements. _____ * Higher doses required for patients with malabsorption. * Active vitamin D "Calcitriol" should be used for patients with renal diseases

2-Biochemical investigations

-Decrease calcium level . -Decrease phosphate level. -Decrease vitamin D level (25 HCC). -Increase parathyroid hormone level. -Increase alkaline phosphatase level

Diagnosis of osteomalacia

1-Clinical features. 2-Biochemical tests. 3-Radiological tests. 4-Bone biopsy.

Diagnosis of Rickets

1-Clinical features. 2-Biochemical tests. 3-X-rays.

Vitamin D Definition, importance, forms

A group of *sterol* compounds which have a *vital role* in bone metabolism. Vitamin D and parathyroid hormone are the main regulators of calcium and phosphorous in the body. *Tow pro-forms of vitamin D:* -Cholecalciferol (D3). [The "C" is the third letter] -Ergocalciferol (D2).

Rickets

Rickets is demineralization of growing bone before closure of the epiphyseal plates (growing bone). Mostly affect infants who are *kept indoor or covered* and are *exclusively feed on natural milk.*

Hypervitaminosis D

High doses of vitamin D can cause life-threatening hypercalcemia. Calcium mainly deposit in the kidneys and brain. symptoms include weakness, vomiting , constipation , lassitude, impaired memory, dementia, delirium, and coma. Treatment include, fluids , diuresis, and sometimes corticosteroids

Osteomalacia

It is bone demineralization after closure of the epiphyseal plates . The normal bone is replaced by *soft osteoid* that contains less minerals than normal bone (loss of bone matrix). *Other cases of osteomalacia are:* -bone tumors, -excess Aluminum and Florid, and -drugs like bisphosphonates

3-X-rays

*Wrist x-ray* will shows widening of the epiphysis (cupping) which is highly suggestive of rickets

Prevention

-Exposure to sunlight. -Adequate intake of vitamin D rich foods. -Prophylactic vitamin D (10-20 μg) for risk groups , lactating women, elderlies and patients on antiepileptic drugs

Causes of vitamin D deficiency

-Limited sun exposure. -Malnutrition. -Malabsorption. -Liver diseases. -Renal diseases (CKD and nephrotic syndrome). -Drugs like antiepileptics *(phenytoin and phenobarbital)* decrease hepatic level of vit. D

1-Clinical features of Osteomalacia

-back pain, bone pain and tenderness, -spontaneous fractures (pathological fractures). -proximal muscle weakness, Waddling gate and difficulty in climbing stairs or getting out of a chair. -Symptoms of hypocalcaemia (What are these?)

Functions of *active vitamin D*

1-Increase calcium and phosphate absorption from the small intestine. 2-Increase calcium re-absorption from the kidneys. 3-Increase bone mineralization. 4-Inhibit parathyroid hormone secretion _______________ كل غاية يثبت الكالسيوم بالعظم .. لذلك يزيد الامتصاص من الامعاء واعادة الامتصاص من الكلية .. ويثبته بالعظم .. ويمنع شغل الباراثايرود هرمون الي يزيحه من العظم...

Prevention of Rickets

Sunlight and vitamin D rich foods. Prophylactic vitamin D drops for infants at risk of vitamin D deficiency

Vitamin D deficiency syndromes

Osteomalacia and Rickets

Sources of vitamin D

*Cholecalciferol (D3):* 1- formed in the skin after exposure to sun. 2- Animal source like fish, fish oil, milk, eggs, liver etc. *Ergocalciferol (D2):* [Not synthesized by the human] 1- Fortified cereals. 2- Synthetic supplements ______________ D2 ما يصنع في جسم الانسان ولا الحيوان .. لذلك ماكو اله مصدر طبيعي ... الا احنا نظيفة الى النبانات....لذلك هي Fortified cereals وليس Cereals

3-Radiological investigation

*X-rays:* -Normal in early disease. -Focal radiolucent areas "Looser's zones" may be seen in ribs, pelvis and long bones. -Radiographic osteopenia -Pathological fractures *Radionuclide bone scan:* Total body technetium bone scan in osteomalacia shows increase uptake (hot spots) in pseudo-fractures areas *[extra: radiographic appearance of a thickened periosteum and new bone formation over what looks like an incomplete fracture]*

1-Clinical features of Rickets

1-Muscle hypotonia (floppy infant). 2-Delayed development (teething, crawling, walking). 3-Delayed closure of anterior fontanelle. 4-"*Craniotabes*": a cracking feeling during pressure on the bones of the skull due to unossified areas is the earliest bone sign of rickets 5-Bossing of the frontal and parietal bones 6-Enlargement of epiphyses at the lower end of the radius. 7-Swelling of the costochondral junctions of the ribs. (*rickety rosary*) 8-When the infant start walking deformities of the legs will develop. "*bow legs*" 9-Later, if untreated a lateral collapse of both chest walls (*Harrison's sulcus*) may appear

Mechanism of action of vitamin D

Active vitamin D will bind to specific receptor VDR ''vitamin D receptor" in target tissues and exert it's metabolic action. 1,25 DHCC has 3 times more affinity to these receptor than other vitamin D metabolites

Treatment of rickets

Ergocalciferol (250-1000 μg daily) for 3-4 months then maintenance of 10-20 μg daily. Encourage intake of vitamin D rich foods

[EXTRA] Why Hypocalcemia causes Contraction and Hypercalcemia causes Weakness?

Low plasma calcium increases the permeability of neuronal membranes to sodium ions, causing a progressive depolarization. This increases the ease with which action potentials can be initiated. If the plasma Ca2+ decreases to less than 50% of the normal value action potentials may be spontaneously generated, causing contraction of peripheral skeletal muscle. The reverse is true in hypercalcemia. High Calcium causing decreased permeability and thence muscle weakness. So in essence it's about neuronal excitation rather than the muscle itself. That's why you have signs such as the Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms) it's because you are tapping on the nerve (not the muscle) further exaggerating the neuronal excitation.

Daily requirement of vitamin D

Non-pregnant adults : 2.5 μg /day. Pregnant women, infants and lactating women : 10 μg /day. (1 μg = 40 IU)

Clinical features of Vitamin D deficiency

*1) Vitamin D deficiency cause bone demineralization (loss of bone matrix)* -*Rickets* is demineralization of growing bone (before closure of the epiphyseal plates). -*Osteomalacia* is bone demineralization after closure of the epiphyseal plates *2) Symptoms of hypocalcaemia:* [Picture] -*Carbopedal spasm*. (Trousseau sign of latent tetany) -*Facial twitching* (Chvostek sign) -*Hypocalcaemic tetani* -*Seizers* *3) Other features:* -Burning sensation in the mouth -Diarrhea -Insomnia -Nervousness -Myopia -Scalp sweating