The Endocrine System, Doctor why do I need calcium and Vitamin D? What is Cholecalcepherol? Why is my Calcium levels abnormal and what does it mean?

Dear patients
Thank you for your most interesting questions and thank you for trusting me to manage you health.
This is an interesting question. To answer these question we need to talk about Calcium, phosphate and magnesium in the Human Body.

Calcium content of the body depends on the balance between the intestinal calcium from diet and the calcium lost in your faeces (shit) and urine (pee).

Intestinal (GUT) uptake and loss


The amount of calcium that is absorbed is dependent on

1. Amount of calcium (Ca2+) available. 
• Acid pH increases calcium and alkalinity promotes complex formation and diminishes absorption. 
• The following reduce your calcium absorption:
• Uncooked beans - phytates and
• Oxalytes - chocolate, nuts and berries - and tea
2. Active Vitamin D

Kidney

The kidney filters 250mmol of Calcium each day, 95% are reabsorbed in the tubules. The majority is taken up in the proximal tubules without hormonal regulation, while fine adjustment is required to the amount reabsorbed in the distal tubules under the influence of PARATHYROID HORMONE - PTH

Plasma Calcium:

Calcium is present in 3 forms in the plasma - Ionised calcium, Bound to proteins, and complexed (citrates, phosphate and bicarbonate) 

Ionised calcium is the physiologically active fraction - the important part - that effects the neuromuscular excitability and PTH secretion. The distribution of calcium in its various forms is affected by the plasma pH:

• pH increases - decreases plasma calcium
• pH decreases - increases plasma calcium

There are other factors that affect plasma calcium concentration, such as plasma albumin, bone flux that may be altered in trauma and cancer, calcium precipitation. Calcium precipitation is important in kidney failure where there is an excess of phosphate and calcium to be deposited in the tissues. Similarly the increased levels of fatty acids resulting from the action of lipases in pancreatitis will also result in calcium being deposited in tissues.

PTH - Parathyroid hormone - Free ionised calcium is the principal regulator of PTH secretion. Hypermagnesemia - too much magnesium - inhibits PTH secretion while low levels inhibit PTH release. Not too much Magnesium or too little magnesium - it needs to be just right. Like Magnesium - so does the levels of active vitamin D need to be just right - negative feedback mechanism.

• BONE: PTH stimulates osteoclast activity, the increase in bone resorption causing an increase in plasma calcium and phosphate - Vitamin D has a permissive role in this effect.
• KIDNEY: PTH stimulates cAMP increase distal tube reabsorption of Calcium and decreases phosphate in the proximal tubule. PTH also stimulates the conversion to active Vitamin D

Vitamin D (D3, Cholecalciferol)

Vitamin D (D3, Cholecalciferol) - is obtain from plants and sunlight - UV exposure. 90% is obtained from photoconversion. The physiologically active metabolite is derived from renal formation regulated by PTH. Vitamin D active is increase by PTH and decreased by Phosphate. Decrease in plasma Calcium will increase PTH that converts vitamin D3 to Cholecalcepherol or active Vitamin D3.

Increased vitamin D3 levels are required in growth, pregnancy, lactation. This may be why Growth Hormone (for Growth) and Estrogen E2 (for pregnancy and lactation) also stimulate the formation of active Vitamin D3. 

What are the actions of active Active Vitamin D3 - 1,25-(OH)2D3?


actions of active Active Vitamin D3 - 1,25-(OH)2D3:
Active Vitamin D3 - 1,25-(OH)2D3 Increases Small intestine absorption of dietary calcium, through calcium binding protein in the intestine (enterocyte) - stimulating the absorption of calcium across the brush boarder.

Active Vitamin D3 - 1,25-(OH)2D3 stimulates the number and the activity of osteoclasts, this mobilises calcium and phosphate from the bone - if there is PTH. Vitamin D3 is also required for normal bone mineralisation. 


Active Vitamin D3 - 1,25-(OH)2D3 acts on the DISTAL renal tubule enhancing the calcium and phosphate retension. 


Plasma Active Vitamin D3 is elevated in primary hyperparathyroidism, absorptive hypercalciuria, Sarcoidosis. 


Active Vitamin D3 - 1,25-(OH)2D3 is reduced in hypoparathyroidism, liver disease or liver cirrhosis, renal failure, hypercalcemia of malignancy and immobilisation, drug use 0 phenytoin, lack of sunlight, Vitamin D dependent rickets type I.


Calcitonin:
Calcitonin increases renal clearence of calcium and phosphate. Calcitonin is stimulated by high calcium and calcitonin is inhibited by the decrease in calcium.  Calcitonin strongly inhibits osteoclastic bone resorption.

Thyroid hormone influence the rate of calcium removal from the bone - so as expected the marginal hypercalcemia is expected in 20% of the cases in thyrotoxicosis, and hypocalcemia is expected when you initially start receiving treatment for you hyperthyroidism.

Adrenocortical Steroids Addisons disease is associated with hypercalcemia. increase glucocorticosteroids impairs bone growth and reduces the uptake of both calcium and phosphate from the intestine, the renal excretion of calcium. 


Laboratory investigation for calcium Metabolism requires that the following blood test be done: Plasma calcium, albumin, urea, phosphate, alkaline phosphate (AP)

Remember that your doctor will have to correct the calcium values read - for example:

• calcium = 1.89 mmol/L (2.15 to 2.55)
• albumin = 22 g/L (30 to 50)

The correction is 

• (40g/l - 22g/l albumin) x 0.02 + 1.89
• (18 x 0.02) + 1 .89 Ca 2+ 
• 2.25 mmol/l Ca2+

1. Collect blood samples without a tourniquet, otherwise the local hemoconcentration of albumin will elevate the calcium value.
2. fasting levels are preferred - after meals the calcium value may be elevated
3. There are different values for outpatient and inpatients - compare the calcium values to the correct population 
4. Repeat the test of the values are elevated

Phosphates have limited value - elevated in hyperparathyroidism and reduced in hypoparathyroidism, phosphates have limited value

1. Hypophosphathemia may occure in the present of cancers or malignancy when PTH-like substances are secreted. 
2. Hypercalcemia due to any cause is shown to increase the secretion of phosphates.
3. Half of all patients with hyperparathyroidism may have normal phosphates

Plasma alkaline phosphatase -  a raise in AP in conjunction with a plasma calcium abnormality is suggestive of:

1. Increase osteoblast activity - primary hyperparathyroidism, malignancy of the bone (primary or secondary cancer), secondary hyperparathyroidism
2. Liver involvement due to metastases from malignancy
3. There are numerous causes of a raised AP, including growth, pregnancy and liver disease

Plasma Urea - Renal failure gives hypocalcemia with hyperphosphatemia. Similarly prolonged hypercalcemia may cause renal damage.

Plasma parathyroid hormone - PTH - is difficult to measure the active N-terminal fragment from the inactive C-terminal fragment. 

1. Primary hyperparathyroidism may be associated with an increased or normal PTH level. 
2. Renal failure is associated with increased PTH. The increased PTH is due to a increased secretion of calcium by the kidney and a decreased ionised calcium. There is also a rise in inactive C-terminal fragment PTH 
3. Hypercalcemia of malignancy is associated with increased circulating levels of PTH
1. Hypercalcemia of pregnancy
2. Coexistence of  renal failure
3. Coexistence of primary hyperparathyroidism

Vitamin D Levels

These are now able to be tested in most good labs.

HYPERCALCEMIA:

Hypercalcemia may be classified as an increase intake, increased plasma albumin, increased bone resorption, increased renal reabsorption. The commonest causes of hypercalcemia are malignancy (carcinoma, lymphoma, multiple myeloma, leukemia); primary hyperparathyroidism, Vitamin D toxicity, using too much calcium supplementation. 

• increase calcium intake, - Vitamin D Access, sarcoidosis, milk alkali syndrome, hyperalimentation - imbalance of IV therapy
• increased plasma albumin, - Dehydration, prolonged application of a tourniquet  
• increased bone resorption of calcium, -  Malignancy, hyperparathyroidism, renal failure, thyrotoxicosis, immobilisation
• increased renal reabsorption of calcium - Thiazide diuretics, familial hypocalciuric hypercalcemia, Addisons disease. 

It is difficult to differentiate between hypercalcemia from Malignancy and Hypercalcemia from primary hyperparathyroidism:

•  hypercalcemia from Malignancy - Calcium above 3,5mmol/l, weeks or months, rapid increase of calcium, there generally would not be kidney stones, steroid suppression test would suppress calcium, and plasma PTH would be low
• Hypercalcemia from primary hyperparathyroidism - calcium would be below 3,5 mmol/l, months or years, slow increase in calcium, renal calculi would be common, no response to the steroid suppression test and PTH would be elevated

CASE EXAMPLES -

CASE - VITAMIN D EXCESS
A 59 year old female complaining of polyuria (urinating or peeing alot) and nocturia (urinating or peeing at night). She had a long history of taking natural self-prescribed multivitamins.

• Calcium 3.21  mmol/l (2,15-2,55)
• PO4      2.01  mmol/l (0.60-1.25)
• Alb           43 g/l         (30-120)
• Urea     12.0 mmol/l    (3.0-8.0)

1. Increased Vitamin D3, increased gut absorption of calcium and posphate, increased free ionised calcium.  
2. Increased calcium, decreased PTH, and decreased phosphate excretion, that increased plasma phosphate

Prolonged hypercalcemia may be associated with a high plasma urea due to:

1. renal insufficiency due to deposit of calcium around the tubules - nephrocalcinosis
2. dehydration - hypercalcemia interferes with the action of ADH and therefore renal concentration mechanism, producing polyuria

CASE - SARCOIDOSIS

Sarcoid tissue is capable of forming active Vitamin D3  - extra-renal production of Vitamin D3 - this explains this patients sensitivity to sunlight and Vitamin D supplements. The LAB pattern was the same as the CASE - VITAMIN D EXCESS.

Sarcoidosis

Low calcium: Hypocalcemia - when there is a low calcium level consider primary hypopathyroidism. You must consider Cancer if you have increase calcium levels.

Essential Information About Vitamin D

Pagets Disease

Vitamin D Prevents Cancer: Is It True?

Vitamin D and Cardiovascular Disease Prevention

Hypercalcemia: Review of Most Important Points

Hypocalcemia: Most Important Points