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.
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.
Synthesis of Active form of Vitamin D
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
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.
1,25 dihydroxy cholecalciferol inhibits 1 alpha hydroxylase as a feedback mechanism.
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 D2
Vitamin 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
Active form of Vitamin D is 1,25 dihydroxy cholecalciferol.
Rate Limiting enzyme of vitamin D synthesis 1 alpha hydroxylase.
1 alpha hydroxylase is stimulated by PTH.
Normal serum vitamin D is 30 to 80 ng/ml.
Q. True about vitamin D action is.
It decreases calcium absorption along Intestine.
It stimulates osteoblasts indirectly.
It stimulates osteoclasts directly.
It increases serum calcium and phosphate.
Q. True about vitamin D Synthesis and regulations all except
1 alpha hydroxylase is the rate Limiting enzyme.
1 alpha hydroxylase is stimulated by PTH.
1 alpha hydroxylase is directly inhibited by high phosphate.
1 alpha hydroxylase is directly inhibited by High calcium.
Q. 1,25 Dihydroxy Vitamin D is increased in
Chronic kidney disease
Hypoparathyroidism
Pseudohypoparathyroidism
Sarcoidosis
Q. True about vitamin D deficiency is.
High calcium
High phosphorus
High PTH
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?
His 1,25 DHCC is expected to be High.
His PTH is expected to be low.
Cinacalcet is recommended.
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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