Steroid Hormones - Vitamin D

provitamin D3

starts as dehydrocholesterol (derrived from cholesterol) in the skin

Vitamin D3 activation pathway uv step

the UV step in the Vitamin D3 tells us that sunlight exposure is important and VD3 can be obtained in the diet as well

how are vitamin d3 metabolietes transported

transported in the blood bound to the vitamin D binding protein and serum albumin

what is the chemical for vitamin D3

1,25-(OH)2 D3 or calcitriol

what happens to your body with Rickets

softening of bones in immature/growing mammals due to deficiency or impaired metabolism of vitamin D, phosphorus or calcium. Leads to fracturs and deformities

there are two types

common childhood disease in many develop countries

Synthesis of vitamin D

Biologically active vitamin D3 is produced by two hydroxylation steps.

first occurs in the liver to form (25-OH-vitamin D3) which is the main circulatory form

the second occurs mainly in the kidney to form the active 1,25-(OH)2D3 (calcitroil =vitamin D3)

what does the PTH hormone do

regulates poisitively the expression of the 1-hydroxylase needed to form the 1,25-(OH)2D3 in the kidney

how does vitamin D3 mediate its effects

it mainly goes through an intracellular nuclear receptor

and some non genomic effects are thought to be mediated via a membrane receptor

what are the Physiological actions of active vitamin D3

it regulates the intestinal uptake or absorption of calcium ion(as nutrient) and as a cell pro-differentiation for skin and hair

serum calcium concentrations are maintained within a narrow range so as to facillitate normal mineralization of bone and teeth and for nerve transmission and for blood coagulation

what is the biochemical effects of rickets

due to defect in vitamin D 25-hydroxylation: CYP2R1 is gene encoding 25-hydroxylase

what is the biochemical effects of rickets type IIA

caused by an inactivating mutation in the nuclear vitamin D receptor

what is the biochemical effects of rickets type 2B with normal nuclear VDR

its unusual form caused by abnormal expression of a hormone response element binding protein that interferes with the normal function of the VDR. This leads to increased circulating 1,25-(OH)2-vitamin D3.

most patients will also display total alopecia in addition to rickets

what is vitamin D deficiency associated with

• Cancer

• cardiiovascular disease

• hypertension

• stroke

• diabetes

• multiple sclerosis

• rhematoid arthritis

• inflammatory bowel disease

• osteoporosis

• periodontal disease

• macular degeneration

• mental illness

• chronic pain

Vitamin D receptor - VDR

mediates the nuclear actions of 1,25-(OH)2D3. This 1,25 has the highest affinity

Calcium and Vitamin D correlation

vitamin D3 allows for Ca2+ absorption in the gut

calmodulin helps absorb Ca2+

PTH and Calcitonin affects on Ca2+

acts to increase Ca2+ levels while calcitionin decreases Ca2+ levels

Calcium sensing receptor (CaSR)

regulates the release of PTH produced by the parathyroid

located in the kidney helps in the reabsoption of Ca2+, phosphate, Na+ and water

encoded in the membrane by the CASR gene and is a G-protein coupled receptor

what are the two key serum ion levels

• serum calcium - oral tingling sensation in and around the mouth/lips and in the extremities

• serum phosphate levels - inadequate intake (alcoholics), increased excretion(hyperparathyroidism, hypophosphatemic rickets) this is normally very difficult to attin hypophosphatemic status since we have abundant phophorus in our diet

Once deficient it starts taking Ca2+ out of the bone whch causes more issues

Plaque Psoriasis

immune mediated disease affecting skin

no cure but vitamin D3 can help with symptoms

Plaque Psoriasis treatment

Topical: ointments containing coal tar, corticosteroids, vitamin D3 and retinoids

Phototherapy: going out side

Biologics used: Enbrel and Remicade (they are TNF-alpha inhibitors = reduce inflammation) Stelara is also used and targets IL-12 and IL-23 to reduce inflammation

Hereditary Vitamin D Resistance - Rickets

mutations which affect DBD and LBD

osteomalacia

inadequete levels of Ca2+ and phosphate caused by Vit D3 deficiency causes soft bone