Vitamin D - Lecture Notes PDF

# Vitamin D ## Learning Objectives - Explain the dietary sources and daily recommended allowance of Vitamin D. - Discuss the metabolism of vitamin D in the human body. - Discuss the regulation of serum calcium in relation to bone metabolism. - Discuss the biochemical functions of vitamin D. - Disc...

# Vitamin D ## Learning Objectives - Explain the dietary sources and daily recommended allowance of Vitamin D. - Discuss the metabolism of vitamin D in the human body. - Discuss the regulation of serum calcium in relation to bone metabolism. - Discuss the biochemical functions of vitamin D. - Discuss the clinical significance of vitamin deficiency and its prevention. ## Vitamin D deficiency most common in the world? - Worldwide, many countries report very high prevalence of low vitamin D status, **25(OH)D** levels less than 30 **nmol/L** (or 1 **ng/ml**) in more than 20% of the population. - This is common in India, Tunisia, Pakistan, and Afghanistan. ## Description: A young child sits on the ground and looks at the camera. ## Vitamin D - Vitamin-D is a fat soluble vitamin. - Vitamin - D is a sterol, it contains steroid nucleus (Cyclopentanoperhydrophenanthrene ring). - Vitamin - D function like a hormone. ### Forms of vitamin D: - Vitamin D in the diet occurs in two forms. - Vitamin D2 (Ergocalciferol). - Vitamin D3 (Cholecalciferol). ## Vitamin D - Dietary Sources | Source | Image | | :------------------------------------ | :---------- | | Sunlight | Sun | | Cod liver oil | Bottle | | Caviar | Bowl | | Cheese | Cheese | | Salmon | Fish | | Mackerel | Fish | | Sardines | Fish | | Tuna | Fish | | Raw Milk | Glass | | Mushrooms | Mushrooms | | Eggs | Eggs | ## What is Vitamin D? - **Chemistry**: There are two chemical forms of vitamin D. - Vitamin D2 (Ergocalciferol) and - Vitamin D3 (Cholecalciferol). - The natural form of vitamin D for animals and man is vitamin D3: it can be produced in their bodies from cholesterol and 7-dehydrocholesterol. - An alternative vitamin D2 is commercially prepared from ergosterol that is present in yeast. - Cholesterol in animals and man is a precursor substance for all steroid hormones as well as vitamin D3. - The molecular structure of vitamin D is closely allied to that of the classical steroid hormones. ## Description: An image shows the synthesis of Vitamin D in the skin with UV-B rays. ## 80% of vitamin D source | | | | :-- | :- | | **Skin** | **Pro-Vit D₂** | | | 7-dehydro-cholesterol | | **Pre-Vit D₃** | | **Vitamin D₃** | | **Heat** | | **20(OH)D** | | **CYP27A1 & other** | | **Vitamin D** | | **Calciol** | | **Calcidiol, 25(OH)D** | ## Chemistry - Ergocalciferol (vitamin D2) is formed from ergosterol and is present in plants. ## Description: An image of a chemical formula for Vitamin D2 and Vitamin D3 ## Amount of vitamin D in foods... | Food | Amount | | :-------------------------- | :-------- | | Egg - 100gms boiled egg | 871 IU | | Sea fish - 100 gms | 759 IU | | Mushrooms - 100gms | 446 IU | | Cereals (fortified) - 100gms | 333 IU | | Butter - 100 gms | 110 IU | | Processed cheese(fortified) - 100gms | 300 IU | | Almond milk - 100ml | 531 IU | | Soy milk - 100ml | 431 IU | | Infant formula - 100ml | 300-350 IU | ## Chemical name | Chemical Name | Abbreviation | Generic Name | | :----------------------- | :------------ | :------------- | | Vitamin D₂ | D₂ | Ergocalciferol | | Vitamin D₃ | D₃ | Cholecalciferol | | 25-hydroxy Vitamin D₃ | 25(OH)D₃ | Calciferol | | 1,25-dihydroxy vitamin D₃ | 1.25-(OH)₂D₃ | Calcitriol | | 24,25-dihydroxy vitamin D₃ | 24.25- (OH)₂D₃ | Secalcifediol | ## Formation of Vitamin D - **Skin (UV light)** - 7-dehydro cholesterol -> vitamin D₃. - **Liver** - OH-group added (first hydroxylation) - 25-hydroxy vitamin D₃ - Storage form of vitamin (3 months storage in liver) - **Kidney** - OH-group added by 1-hydroxylase (second hydroxylation) - 1,25-dihydroxy vitamin D₃ (or 1,25-dihydroxy cholecalciferol, 1,25-DHCC) - Active form of vitamin D, a "sterold hormone" - OH-group added by 24-hydroxylase - 24,25-dihydroxy vitamin D₃ - Inactive form of vitamin D, ready for excretion ## Description: This is a diagram showing the synthesis of calcitriol, the biologically active form of Vitamin D. ## Calcitriol synthesis | | | | :- | :-- | | **UV light** | **7-dehydrocholesterol** | | **Cholecalciferol (vitamin D₃) in the diet** | **Previtamin D** | | **Liver** | **Cholecalciferol (calciol)** | | | **25-OH-cholecalciferol (calcidiol)** | | | **24.25-(OH)₂-cholecalciferol (inactive form)** | | | **Kidney** | | | **Calcitriol (1α,25-(OH)₂-cholecalciferol -active form)** | ## Transport - **Vitamin D binding globulin**: vitamin D is transported from intestine to the liver by binding to vitamin D binding globulin - **25 - Hydroxy D3 and 1,25 - dihydroxy D3 are also transported in the blood by binding to vitamin D binding globulin.** ## Storage: - **25 - hydroxycholecalciferol is the major storage and circulatory form of vitamin D.** ## VITAMIN D - RDA - 200-400 IU/day - [5-10µg/day] - 1microgram of vitamin D = 40 International Units. ## Description: An image of a diagram of the synthesis of Vitamin D in the body, with the liver, the kidney, and the intestines marked. ## Calcitriol is the biologically active ## Regulation of plasma ## calcium and ## phosphorus ## Description: An image of a diagram showing the feedback regulation between the parathyroid hormone, 1,25(OH)₂ vitamin D₃, and calcium levels in the blood. ## Low blood ## calcium ## level ## Increased PTH ## production ## PTH:Parathyroid Hormone ## High blood ## calcium ## level ## Increased ## calcitonin ## synthesis ## Release of calcium and ## phosphorus from bone ## a. Decreased calcium ## excretion ## b. Increased synthesis ## of 1,25(OH)₂ vitamin ## D₃ in kidney ## Normal ## blood ## calcium ## level ## Increased calcium absorption ## in small intestine ## Increased deposit of ## calcium in bone ## Functions of Vitamin D - **Calcium and Phosphorus Homeostasis** - Calcium and Phosphorus absorption (small intestine) - Calcium resorption (bone and kidney) - Maintain blood calcium levels - **Bone formation** - Stimulate calcium uptake for deposition as calcium phosphate (Osteoblasts: bone-forming cells) - **Hormone** - Regulation of gene expression - Cell growth. ## Description: A diagram showing the functions of Vitamin D in an 8-pointed star. ## Regulation of immune ## function ## Growth and bone ## mineralization ## Regulation of phosphorus ## and calcium homeostasis ## Regulation of muscle ## calcium transport ## Vitamin D ## Regulation of insulin ## secretion ## Induction of apoptosis ## Stimulation of ## cell differentiation ## Control of cell proliferation ## Vitamin D promotes intestinal ## calcium absorption - Calcitriol enters the intestinal cell and binds to vitamin D receptor. The hormone-receptor complex interacts causes the release of Calbindin. Due to increased availability of calcium binding protein, the absorption of calcium is increased. ## Description: This is a table showing the levels of vitamin D in the blood in relation to the status of vitamin D. ## Vitamin D Status in Relation to 25 (OH) ## D Levels | Vitamin D status | Levels | | :----------------------------- | :----------- | | US IOM classification [17] | | | Severe deficiency | <5 ng/mL | | Deficiency | <15 ng/mL | | Sufficiency | >20 ng/mL | | Risk of toxicity | >50 ng/mL | | US Endocrine Society classification [8] | | | Deficiency | <20 ng/mL (50 nmol/L) | | Insufficiency | 21-29 ng/mL (52.5-72.5) nmol/liter | | Sufficiency | >30 ng/mL | | Toxicity | >150 ng/mL | | 1mcg = 40IU: 0.025 mcg is 1 IU | | ## Description: A diagram showing the endocrine, paracrine, and intracrine functions of vitamin D. ## Vitamin D ## 25-OH)D ## Liver ## Monocyter ## Macrophage ## --> 1,25(OH)₂D₃ --> ## Calcium homeostasis ## Muscle health ## Bone health ## Blood pressure regulation ## Cardiovascular health ## Neurodevelopment ## Immunomodulation ## Immunomodulation ## Prevention of ## autoimmune diseases ## Control of invading ## pathogens ## Prostate gland ## Breast ## Colon ## Lung ## Keratinocytes ## 1,25(OH)₂D₃ --> ## Regulation of cell growth ## and differntiation ## Description: An image of the intestines with the action of calcitriol highlighted. ## Action of calcitriol on the ## Intestine ## Intestine - Increases the intestinal absorption of calcium and phosphate. ## VITAMIN D - FUNCTIONS ## Description: An image of a bone ## Action of calcitriol on the bone - Mineralization of bone at low doses. - Mobilization of calcium from bone at high doses. ## Description: An image of a kidney ## VITAMIN D - FUNCTIONS ## Action of calcitriol on the ## kidney - Increased reabsorption of calcium and phosphorus. - Decreased excretion of calcium and phosphorus. ## Description: An image of the definition of hypocalcemia. ## DEFINITION - Normal Serum calcium: 8.5 mg/dl - 10.5 mg/dl - A decrease in the calcium levels below 8.5mg/dl is termed hypocalcemia. ## Description: An image of a diagram of the role of parathyroid hormone in hypocalcemia. ## Role of Parathyroid Hormone (PTH) in ## Hypocalcemia ## PTH ## is the principal ## acute regulator of ## blood [Ca²⁺] ## PTH ## is a hypercalcemic ## hormone in case of ## hypocalcemia ## Description: An image shows the action of 1,25(OH)₂D₃ on different organs of the human body. ## 1.25-(OH)₂D₃ ## ↑ ## BONE ## Bone ## resorption ## GI ## ↑Ca²⁺ ## absorption ## KIDNEY ## ↑Ca²⁺ ## reabsorption ## PARA- ## THYROID ## ↑PTH ## synthesis ## ↑ ## Plasma Ca²⁺ ## Description: An image showing a diagram of the role of parathyroid hormone and calcitriol in maintaining calcium levels in the blood. ## ↓ Serum ## calcium ## ↑ Parathyroid ## hormone ## (PTH) ## ↑ 1,25-(OH)₂D₃ ## (calcitriol) ## ↑ Calcium mobilization ## from bone ## ↑ Renal reabsorption ## of calcium ## ↓ Renal excretion ## of calcium ## ↑ Calcium absorption ## from intestine ## Serum ## calcium ## VITAMIN D - DEFICIENCY ## Causes ## Inadequate supply ## Impaired absorption ## Impaired production of 25hydroxyvitamin D₃ ## Impaired production of 1, 25 dihydroxy vitamin D₃ ## Resistant to the effects of 1, 25 dihydroxy vitamin D₃ ## Description: An image showing the features of rickets. ## RICKETS | Features | Delayed milestones | | :----------------------- | :----------------- | | | Delayed closure of anterior fontanelle | | | Delayed dentition Deformities of bones Decreased serum calcium | ## VITAMIN D - DEFICIENCY ## Bone ## deformities ## Craniotabes ## Frontal bossing ## Rachitic rosary ## Pegion chest ## Knocked knee ## Bowed legs ## Description: An image showing the frontal bossing of a child's skull. ## Frontal ## bossing ## Frontal bossing ## Description: An image showing a child with beaded ribs. ## Beaded ribs ## Characteristic of ## rickets ## Description: An image showing a child with a Harrison groove. ## • Harrison Groove ## • pulling of softened ribs by the diaphragm during ## inspiration.Muscle traction on the softened rib cage ## Description: An image showing the enlargement of the wrists and ankles ## EXTREMITIES ## • Enlargement of wrists and ankles ## Growth plate widening ## Description: An image of a women with bowed legs. ## Description: An image of a woman with bowed legs, and another picture of a woman with bowed legs, but looking at her feet. ## OSTEOMALACIA ## Description: An image with a diagram showing the Vitamin D deficiency. ## Vitamin D (Anti-rachitic Vitamin)- ## Deficiency ## - Rickets (meaning: twist) ## • Failure of bones to grow properly ## • Results in "bowed" legs or knock-knees, outward ## bowed chest and knobs on ribs ## - Osteomalacia(Greek: osteon-bone, malakia- ## softness): ## • Adult form of rickets ## - Osteoporosis (porous bones): ## • Loss of vitamin D activity with advancing age ## • Associated with fractures → very serious for ## geriatrics ## Description: This is a diagram of a normal bone and an osteoporotic bone. ## Osteoporosis ## -progressive loss of bone density, thinning of bone tissue ## and increased vulnerability to fractures in the elderly ## people of both sexes. ## Description: An image with information about vitamin D toxicity. ## Vitamin D Toxicity ## • Hypervitaminosis D ## - Among the vitamins, vitamin D is the most ## toxic in overdoses(10-100 times RDA) ## - Calcification of soft tissue ## • Lungs, heart, blood vessels ## • Hardening of arteries, stone formation in kidneys ## • Does not occur from sunlight or dietary ## sources ## Does occur with supplementation ## - In general, vitamin D supplement are not ## recommended. ## - Upper limit: 50 micrograms a day ## Description: Handwritten notes on Rickets and Vitamin D deficiency. ## Rickets. ## Wit: D. Defecuency ## Delayed milestones: ## Delayed closures of : ## Defpomifies ## Frontal rossering ## bowed legs... ## Beaded rig... (Rickey Roseny... ## (Harrison Groove) ## Muscle trachign on softened rib cage. ## Enlargement of Wrist and Ankles. ## Osteomalacia... ## Adult form of rickers... ## Okeeponsesi... ## Jelated to Catz ## heporoux in woman. ## loss in bone density - thinning w boue ## tissue increased in fractures chanas, ## Description: Handwritten notes explaining the biochemistry of Vitamin deficiency. ## Biochemistry ## Vit:D ## Module DS-AMONU MIIK ## locomotor ## for ## 230 nmd/6 ## Cheese ## milk ## Dah-Yogurt. ## Sun- ## Date 22/06/2024 ## QTTFSS ## mineralization & Bone and Tath ## →2.20% Common in india-Pakistan- Tunisia, ## and Afghanistan ## Dit: D. faty stable ## :D is a stero, it contain steroid nucleus. ## 3 (Cyclopentanopetustrophenanthiene ring)... ## if functions as hormone. ## Two forms: D₂ (Ergocalciferol - Pant based. ## Natural bym & D3 Animal based. ## and 7-dehydrochdestid. ## Hydroxylation of Dit: D3 carmed out ## at liver ## Ergopalerfiriod (Whit Da) formed from ergoterd ## and present in Pangin ## 25-hydroxy Dit-D3 Calciferol, ## 1,25 thuytroty Dit: D's falcihil, ## Skin ## 7-hydroxy chdestod - Vit. Dz ## Liver Hyptroxylation. 4.25-hydroxy ## 25-hydray Viti Dz ## Page # ## Description: This is a page of handwritten notes about the biochemistry of Vitamin D ## Date 20. ## MTWTFSS ## *Active form & Vit. O is 1,25 hytrory chlealukde ## * -OH added by 24-hucthorylase. ## →24, 25 dihyroxylase chodecalciforol secreted ## m is inactive form. ## Absorption: ## it bond cork. Vit. D. binding Colbloulin during ## blood flowing. ## 25 hydroxy Ds 8 1,25-dihydroxy. Ds also ## hansported in the blood: ## 1200-40014/day (5-10 Mg/day). ## 40 ## Grend also play important role in the ## Gene absorption. ## → Olson change in geram composition decre ## play also important role in mineral. ## absorption like Dits C - Vita D ## * blw 200 ## 18-22 years boner osscification ## completly stops. ## → Calcitiis is active form of maintaug ## the Wood Calcienn level. ## Page # ## Description: A page of handwritten notes continuing a discussion of Vitamin D. ## Normal Vit: Di ## deferencuy ## song ful ## 2 30ug/ml. ## Suffedevay ## songlu ## Toxicity ## D ## Parathyroid ## → Functions: ## Date ## 1 MTWTFSS ## kidney (to decrease (at secretion) ## *Mineralization. ## Mitaabsorption in 'Small blade ## decrease the Calcitonin function- ## Cath-Phosphorus Homeostasis ## → Osteoblast and Osteoclast synthesis. ## 1 ## Regulates the Hormonal Kecretion. ## I gulation & Co in uruse contraction, ## 8. ## : ## Induction of Apoptosis. ## Bone Mineralization ## Regulation ## Stimulation ## defeciency of ## von. ## healing Secretion ## + Cell differentiation. ## Vit D ## cancer formation... ## Normal Berum Cat 2 ## = ## also lead ## can also lead ## , ## PTH is hypercalcemic hormone in case of hypotens ## - ## - ## Page # ## Description: A page of handwritten notes showing the features of rickets. ## FREATURES OF RICKETS