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Fat Soluble Vitamins - NEET PG Biochemistry

Apr 5, 2023

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Bioactivation of Vitamin D

Synthesis of Active form of Vitamin D

Actions of Vitamin D 

Vitamin D play its role in 3 tissues:

Intestine

Bone

Kidney

Regulation of Vitamin D Synthesis

Biochemical Features of Vitamin D Deficiency 

Significance of 1,25 Dihydroxy Vitamin D

Used in the estimation of

One Liners

Q. True about vitamin D action is.

Q. True about vitamin D Synthesis and regulations all except

Q. 1,25 Dihydroxy Vitamin D is increased in

Q. True about vitamin D deficiency is.

Explanation

Q. A known patient with chronic kidney disease presents with low serum calcium and high serum phosphorus. Which of the following is true?

Fat Soluble Vitamins - NEET PG Biochemistry

Get ready to scale up your Biochemistry preparation by learning everything about fat-soluble vitamins in this blog post. 

Fat soluble vitamins are crucial for the human body. They play integral roles in a multitude of physiological processes such as vision, bone health, immune function and coagulation. 

Vitamin D

Bioactivation of Vitamin D

  • Vitamin D is endogenously produced and synthesized by the action of UV light.
Bioactivation of Vitamin D
  • The endogenous Vitamin D is inactive.
  • The active form of Vitamin D is cholecalciferol. 
    • Not a true steroid.
    • It is a secosteroid - because one ring is opened.
      • Steroids have all the 4 rings intact.
Bioactivation of Vitamin D

Synthesis of Active form of Vitamin D

Synthesis of Active form of Vitamin D

NEET PG Mock Test

Actions of Vitamin D 

Vitamin D play its role in 3 tissues:

  • Intestine
  • Bone
  • Kidney 

Intestine

  • Calcium is absorbed by enterocytes of the intestine by active transport. 
  • Vitamin D increases calbindin expression. Therefore, increasing calcium uptake.

Bone

  • Acts directly on osteoblasts and activates it.
  • Helps in mineralization of the Bone.
  • Activates osteoclasts indirectly.
    • Increases serum calcium and phosphate levels.
Important Information

When osteoblasts are activated the osteoclasts also get activated.
 
This is due to rank ligand activation.

Kidney

  • Increases calcium and phosphate reabsorption. 
  • Opposite action of parathyroid hormone.
    • Increase calcium reabsorption and inhibits phosphate reabsorption. 
  • Net effect of Vitamin D: Increases serum calcium and serum phosphate.

Regulation of Vitamin D Synthesis

Regulation of Vitamin D Synthesis
  • Rate Limiting step.
    • Conversion of 25 cholecalciferol to 1,25 cholecalciferol. 
    • Catalyzed by 1 alpha hydroxylase enzyme.
    • Activated by parathyroid hormone.
  • The vitamin D Synthesis is regulated depending on the amount of calcium and phosphorus.
  • When there is Hypercalcemia and hyperphosphatemia vitamin D should not be synthesized.

Important information 

  • If more calcium and phosphorus is present in blood and more vitamin D is synthesized.
    • Leads to hypercalcemia and hyperphosphatemia.
    • Hypercalcemia leads to:
      • Depression
      • Kidney stones
      • More gastrin release - gastric ulcers
      • Constipation
  • Hyperphosphatemia inhibits the 1 alpha hydroxylase. 
  • Hypercalcemia does not inhibit 1 alpha hydroxylase directly.
    • Inhibits parathyroid hormone. 
Hyperphosphatemia
  • 1,25 dihydroxy cholecalciferol inhibits 1 alpha hydroxylase as a feedback mechanism.
  • Therefore, regulatory factors are:
    • Hypercalcemia 
    • Hyperphosphatemia 

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Biochemical Features of Vitamin D Deficiency 

  • Vitamin deficiency causes:
    • Hypocalcemia 
    • Hypophosphatemia
Biochemical Features of Vitamin D Deficiency 
  • Normal calcium
  • Hypophosphatemia 
  • High PTH
  • High ALP
    • Because PTH stimulates osteoclasts and osteoblasts. 

Important Information

  • Primary hyperparathyroidism - Caused due to direct damage to the gland.
    • Due to adenoma.
  • Secondary hyperparathyroidism - Caused due to other factors.
    • Gland is normal but releases more PTH.
    • Due to:
      • Hypocalcemia 
      • Hyperphosphatemia 
  • Tertiary hyperparathyroidism – long standing secondary hyperparathyroidism leads to tertiary hyperparathyroidism. 
  • PTH is released autonomously.
  • No improvement even if underlying causes are treated.

Normal Level of Vitamin D: 30 to 80 ng/ml.

  • Normal Level of Vitamin D: 30 to 80 ng/ml.
  • Estimated parameter - Total 25 hydroxyvitamin D.
    • Sum of 25 hydroxyvitamin D2 and D3.
      • Functionally both are the same.
Vitamin D2Vitamin D3
Ergocalciferol
Artificially synthesized.
Double bond is present in the side chain.
Cholecalciferol 
Naturally formed.
  • 1,25 dihydroxy cholecalciferol - Has a short half-life.
    • Have short term fluctuations.
    • So not used as an estimating parameter. 
  • 25 hydroxy vitamin D has a longer half-life.
    • Not subjected to short term fluctuations. 

Significance of 1,25 Dihydroxy Vitamin D

Used in the estimation of

  • Chronic Kidney Disease:
    • Leads to hyperphosphatemia.
    • Also, as 1 alpha hydroxylase is present in kidneys it is also inhibited.
    • This indicates - low levels of 1,25 dihydroxycholecalciferol. 
    • Hence, measuring its levels is helpful rather than 25 hydroxyvitamin D. Leading to:
      • Hypocalcemia - activates PTH.
      • Hyperphosphatemia 
      • Secondary hyperparathyroidism 
    • 2 causes of hyperparathyroidism 
      • Vitamin D deficiency 
      • Chronic kidney disease
  • The secondary hyperparathyroidism causes - Renal osteodystrophy.
    • There may be pathological fractures.
    • Measure ALT levels to identify Secondary hyperparathyroidism. 
      • If High, the result is positive. 
      • Should be treated soon.
    • Treatment includes: 
      • Dialysis 
        • Calci mimicking drugs - Cinacalcet and etelcalcetide.
      • Mimics calcium 
      • Binds to calcium sensing receptors.
      • Inhibits PTH.

Important Information

  • Care should be taken with Calci mimicking drugs. 
  • May lead to more PTH inhibition - A dynamic Bone disease. 
    • Cause pathological fractures. 
  • Doses should be titrated by estimating ALT levels.
    • High ALT - Increase the dose - Signifies secondary hyperparathyroidism. 
    • Low ALT - Decrease the dose - May signify a dynamic bone disease. 
  • Hypoparathyroidism - Less 1,25 dihydroxyvitamin D. 
  • Sarcoidosis (Granulomatous disease) - High 1,25 dihydroxyvitamin D.

One Liners

  1. Active form of Vitamin D is 1,25 dihydroxy cholecalciferol.
  2. Rate Limiting enzyme of vitamin D synthesis 1 alpha hydroxylase. 
  3. 1 alpha hydroxylase is stimulated by PTH.
  4. Normal serum vitamin D is 30 to 80 ng/ml.

Q. True about vitamin D action is.

  1. It decreases calcium absorption along Intestine.
  2. It stimulates osteoblasts indirectly. 
  3. It stimulates osteoclasts directly.
  4. It increases serum calcium and phosphate. 

Q. True about vitamin D Synthesis and regulations all except

  1. 1 alpha hydroxylase is the rate Limiting enzyme.
  2. 1 alpha hydroxylase is stimulated by PTH.
  3. 1 alpha hydroxylase is directly inhibited by high phosphate. 
  4. 1 alpha hydroxylase is directly inhibited by High calcium.

Q. 1,25 Dihydroxy Vitamin D is increased in

  1. Chronic kidney disease 
  2. Hypoparathyroidism 
  3. Pseudohypoparathyroidism 
  4. Sarcoidosis

Q. True about vitamin D deficiency is.

  1. High calcium
  2. High phosphorus 
  3. High PTH
  4. Low ALT

Explanation

  • Vitamin D deficiency:
    • Normal calcium
    • Hypophosphatemia 
    • High PTH
    • High ALP

Q. A known patient with chronic kidney disease presents with low serum calcium and high serum phosphorus. Which of the following is true?

  1. His 1,25 DHCC is expected to be High.
  2. His PTH is expected to be low.
  3. Cinacalcet is recommended. 
  4. His ALP is expected to be low.

Important Information

Secondary Hyperthyroidism - Causes

  • Vitamin D deficiency - Hypocalcemia. 
  • Chronic kidney disease - Hyperphosphatemia. 
  • Cushing's disease 
    • Glucocorticoids inhibit osteoclasts - Source of serum calcium.
    • No source for serum calcium - Hypocalcemia. 
    • PTH increases - Secondary hyperparathyroidism. 
    • Leads to osteoporosis in Cushing’s disease 

And that is everything you need to know about fat-soluble vitamins to scale up your Biochemistry preparation. For more interesting and informative posts, keep following our blog! 


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