Parathyroid Gland Introduction .
[1]. Human beings have four parathyroid glands, which are situated on the posterior surface of upper and lower poles of thyroid gland .
[2]. Parathyroid glands are very small in size, measuring about 6 mm long, 3 mm wide and 2 mm thick, with dark brown color.
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| Parathyroid glands on the posterior surface of thyroid gland . |
Histology of Parathyroid Glands .
[1]. Each parathyroid gland is made up of chief cells and oxyphil cells.
[2]. Chief cells secrete parathormone.
[3]. Oxyphil cells are the degenerated chief cells and their function is known. However, these cells may secrete parathormone during pathological condition called parathyroid adenoma.
[4]. The number of oxyphil cells increases after puberty.
Parathormone .
[1]. Parathormone secreted by parathyroid gland is essential for the maintenance of blood calcium level within a very narrow critical level.
[2]. Maintenance of blood calcium level is necessary because calcium is an important inorganic ion for many physiological functions .
Source of Secretion of Parathormone .
Parathormone (PTH) is secreted by the chief cells of the parathyroid glands.
Chemistry of Parathormone .
Parathormone is protein in nature, having 84 amino acids. Its molecular weight is 9,500.
Half-life and Plasma Level of Parathormone .
[1]. Parathormone has a half-life of 10 minutes.
[2]. Normal plasma level of PTH is about 1.5 to 5.5 ng/dL.
Synthesis of Parathormone .
[1]. Parathormone is synthesized from the precursor called prepro-PTH containing 115 amino acids.
[2]. First, the prepro-PTH enters the endoplasmic reticulum of chief cells of parathyroid glands. There it is converted into a prohormone called pro-PTH, which contains 96 amino acids.
[3]. Pro-PTH enters the Golgi apparatus, where it is converted into PTH.
Metabolism of Parathormone .
[1]. Sixty to seventy percent of PTH is degraded by Kupffer cells of liver, by means of proteolysis.
[2]. Degradation of about 20% to 30% PTH occurs in kidneys and to a lesser extent in other organs.
Actions of Parathormone .
[1]. PTH plays an important role in maintaining blood calcium level.
[2]. It also controls blood phosphate level.
Actions of PTH on Blood Calcium level .
[1]. Primary action of PTH is to maintain the blood calcium level within the critical range of 9 to 11 mg/dL.
[2]. The blood calcium level has to be maintained critically because, it is very important for many of the activities in the body.
[3]. PTH maintains blood calcium level by acting on:
1. Bones .
2. Kidney .
3. Gastrointestinal tract.
1. On Bone .
[1]. Parathormone enhances the resorption of calcium from the bones (osteoclastic activity) by acting on osteoblasts and osteoclasts of the bone.
[2]. Resorption of calcium from bones occurs in two phases:
i. Rapid phase .
ii. Slow phase.
Rapid phase .
[1]. Rapid phase occurs within minutes after the release of PTH from parathyroid glands.
[2]. Immediately after reaching the bone, PTH gets attached with the receptors on the cell membrane of osteoblasts and osteocytes.
[3]. The hormone-receptor complex increases the permeability of membranes of these cells for calcium ions.
[4]. It accelerates the calcium pump mechanism, so that calcium ions move out of these bone cells and enter the blood at a faster rate.
Slow phase .
[1]. Slow phase of calcium resorption from bone is due to the activation of osteoclasts by PTH.
[2]. When osteoclasts are activated, some substances such as proteolytic enzymes, citric acid and lactic acid are released from lysosomes of these cells.
[3]. All these substances digest or dissolve the organic matrix of the bone, releasing the calcium ions. [4]. The calcium ions slowly enter the blood. PTH increases calcium resorption from bone by stimulating the proliferation of osteoclasts also.
2. On Kidney .
[1]. PTH increases the reabsorption of calcium from the renal tubules along with magnesium ions and hydrogen ions.
[2]. It increases calcium reabsorption mainly from distal convoluted tubule and proximal part of collecting duct.
[3]. PTH also increases the formation of 1,25- dihydroxycholecalciferol (activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys .
3. On Gastrointestinal Tract .
[1]. PTH increases the absorption of calcium ions from the GI tract indirectly.
[2]. It increases the formation of 1,25- dihydroxycholecalciferol in the kidneys. This vitamin, in turn increases the absorption of calcium from GI tract.
[3]. Thus, the activated vitamin D is very essential for the absorption of calcium from the GI tract. And PTH is essential for the formation of activated vitamin D.
Role of PTH in the activation of vitamin D .
[1]. Vitamin D is very essential for calcium absorption from the GI tract. But vitamin D itself is not an active substance.
[2]. Instead, vitamin D has to be converted into 1, 25-dihydroxycholecalciferol in the liver and kidney in the presence of PTH.
[3]. The 1,25-dihydroxycholecalciferol is the active product.
Activation of vitamin D .
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| activation of vitamin D . |
[1]. There are various forms of vitamin D. But, the most important one is vitamin D3. It is also known as cholecalciferol.
[2]. Vitamin D3 is synthesized in the skin from 7-dehydrocholesterol, by the action of ultraviolet rays from the sunlight. It is also obtained from dietary sources.
[3]. The activation of vitamin D3 occurs in two steps .
1. Cholecalciferol (vitamin D3) is converted into 25- hydroxycholecalciferol in the liver. This process is limited and is inhibited by 25-hydroxycholecalciferol itself by feedback mechanism.
This inhibition is essential for two reasons :-
i. Regulation of the amount of active vitamin D
ii. Storage of vitamin D for months together. If vitamin D3 is converted into 25-hydroxycholecalciferol, it remains in the body only for 2 to 5 days. But vitamin D3 is stored in liver for several months.
2. 25-hydroxycholecalciferol is converted into 1,25- dihydroxycholecalciferol (calcitriol) in kidney. It is the active form of vitamin D3. This step needs the presence of PTH.
Role of Calcium Ion in Regulating 1, 25-Dihydroxycholecalciferol .
[1]. When blood calcium level increases, it inhibits the formation of 1,25-dihydroxycholecalciferol.
[2]. The mechanism involved in the inhibition of the formation of 1,25-dihydroxycholecalciferol is as follows:
i. Increase in calcium ion concentration directly suppresses the conversion of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol. This effect is very mild
ii. Increase in calcium ion concentration decreases the PTH secretion, which in turn suppresses the conversion of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol.
1. This regulates the calcium ion concentration of plasma itself indirectly, i.e. when the PTH synthesis is inhibited, the conversion of 25-hydroxycholecalciferol into 1,25-hydroxycholecalciferol is also inhibited.
2. Lack of 1,25-dihydroxycholecalciferol, decreases the absorption of calcium ions from the intestine, from the bones and from the renal tubules as well. This makes the calcium level in the plasma to fall back to normal.
Actions of 1, 25-Dihydroxycholecalciferol .
1. It increases the absorption of calcium from the intestine, by increasing the formation of calcium binding proteins in the intestinal epithelial cells.
[1a]. These proteins act as carrier proteins for facilitated diffusion, by which the calcium ions are transported.
[1b]. The proteins remain in the cells for several weeks after 1,25-dihydroxycholecalciferol has been removed from the body, thus causing a prolonged effect on calcium absorption
2. It increases the synthesis of calcium-induced ATPase in the intestinal epithelium .
3. It increases the synthesis of alkaline phosphatase in the intestinal epithelium .
4. It increases the absorption of phosphate from intestine along with calcium.
Actions of Parathormone on Blood Phosphate level .
1. PTH decreases blood level of phosphate by increasing its urinary excretion.
2. It also acts on bone and GI tract.
1. On Bone .
Along with calcium resorption, PTH also increases phosphate absorption from the bones.
2. On Kidney .
Phosphaturic action .
[1]. It is the effect of PTH by which phosphate is excreted through urine.
[2]. PTH increases phosphate excretion by inhibiting reabsorption of phosphate from renal tubules.
[3]. It acts mainly on proximal convoluted tubule.
3. On Gastrointestinal Tract .
Parathormone increases the absorption of phosphate from GI tract through calcitriol.
Sequence of events .
[1]. PTH converts 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol (calcitriol: active form of vitamin D3) in kidney
[2]. Calcitriol increases the synthesis of calcium induced ATPase in the intestinal epithelium
[3]. ATPase increases the synthesis of alkaline phosphatase
[4]. Alkaline phosphatase increases the absorption of phosphate from intestine along with calcium.
Mode of Action of Parathormone .
Parathormone Receptors .
[1]. Parathormone receptors (PTH receptors) are of three types, PTHR1, PTHR2 and PTHR3, which are G protein coupled receptors.
[2]. PTHR1 is physiologically more important than the other two types.
[3]. PTHR1 mediates the actions of PTH and PTH-related protein . Role of PTHR2 and PTHR3 is not known clearly.
[4]. On the target cells, PTH binds with PTHR1 which is coupled to G protein and forms hormone-receptor complex.
[5]. Hormone-receptor complex causes formation of cAMP, which acts as a second messenger for the hormone.
Regulation of Parathormone Secretion .
[1]. Blood level of calcium is the main factor regulating the secretion of PTH.
[2]. Blood phosphate level also regulates PTH secretion.
Blood Level of Calcium .
[1]. Parathormone secretion is inversely proportional to blood calcium level. Increase in blood calcium level decreases PTH secretion.
[2]. Conditions when PTH secretion decreases are:
1. Excess quantities of calcium in the diet .
2. Increased vitamin D in the diet .
3. Increased resorption of calcium from the bones caused by some other factors such as bone diseases.
On the other hand, decrease in calcium ion concentration of blood increases PTH secretion, as in the case of rickets, pregnancy and in lactation.
Blood Level of Phosphate .
[1]. PTH secretion is directly proportional to blood phosphate level.
[2]. Whenever the blood level of phosphate increases, it combines with ionized calcium to form calcium hydrogen phosphate.
[3]. This decreases ionized calcium level in blood which stimulates PTH secretion.
Calcitonin .
Source of Secretion of Calcitonin .
[1]. Calcitonin is secreted by the parafollicular cells or clear cells (C cells), situated amongst the follicles in thyroid gland.
[2]. In lower animals, the parafollicular cells are derived from ultimobranchial glands, which develop from fifth pharyngeal pouches.
[3]. In human being, the ultimobranchial glands and fifth pharyngeal pouches are rudimentary and their cells are incorporated with fourth pharyngeal pouches and distributed amongst the follicles of thyroid gland.
[4]. Recently, calcitonin is found in brain, prostate and bronchial cells of lungs. However, the physiological role of calcitonin from non-thyroid tissues is not known.
Chemistry and Synthesis of Calcitonin .
[1]. Calcitonin is a polypeptide chain with 32 amino acids.
[2]. Its molecular weight is about 3,400.
[3]. It is synthesized from procalcitonin.
Plasma Level and Half-life of Calcitonin .
[1]. Plasma level of calcitonin is 1 to 2 ng/dL.
[2]. It has a halflife of 5 to 10 minutes.
Metabolism of Calcitonin .
Calcitonin is degraded and excreted by liver and kidney.
Action of Calcitonin .
1. On Blood Calcium Level .
[1]. Calcitonin plays an important role in controlling the blood calcium level.
[2]. It decreases the blood calcium level and thereby counteracts parathormone.
[3]. Calcitonin reduces the blood calcium level by acting on bones, kidneys and intestine.
i. On bones .
[1]. Calcitonin stimulates osteoblastic activity and facilitates the deposition of calcium on bones.
[2]. At the same time, it suppresses the activity of osteoclasts and inhibits the resorption of calcium from bones. It inhibits even the development of new osteoclasts in bones.
ii. On kidney .
Calcitonin increases excretion of calcium through urine by inhibiting the reabsorption from the renal tubules.
iii. On intestine .
Calcitonin prevents the absorption of calcium from intestine into the blood.
2. On Blood Phosphate Level .
[1]. With respect to calcium, calcitonin is an antagonist to PTH. But it has similar actions of PTH with respect to phosphate.
[2]. It decreases the blood level of phosphate by acting on bones and kidneys.
i. On bones .
Calcitonin inhibits the resorption of phosphate from bone and stimulates the deposition of phosphate on bones.
ii. On kidney .
Calcitonin increases the excretion of phosphate through urine, by inhibiting the reabsorption from renal tubules.
Regulation of Calcitonin Secretion .
[1]. High calcium content in plasma stimulates the calcitonin secretion through a calcium receptor in parafollicular cells.
[2]. Gastrin also is known to stimulate the release of calcitonin.
Calcium Metabolism .
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| calcium metabolism . |
Importance of Calcium .
Calcium is very essential for many activities in the body such as: 1. Bone and teeth formation 2. Neuronal activity 3. Skeletal muscle activity 4. Cardiac activity 5. Smooth muscle activity 6. Secretory activity of the glands 7. Cell division and growth 8. Coagulation of blood.
Normal Value .
[1]. In a normal young healthy adult, there is about 1,100 g of calcium in the body.
[2]. It forms about 1.5% of total body weight. 99% of calcium is present in the bones and teeth and the rest is present in the plasma.
[3]. Normal blood calcium level ranges between 9 and 11 mg/dL.
Types of Calcium .
Calcium in Plasma .
Calcium is present in three forms in plasma:
i. Ionized or diffusible calcium:
1. Found freely in plasma and forms about 50% of plasma calcium.
2. It is essential for vital functions such as neuronal activity, muscle contraction, cardiac activity, secretions in the glands, blood coagulation, etc.
ii. Non-ionized or non-diffusible calcium:
1. Present in non-ionic form such as calcium bicarbonate.
2. It is about 8% to 10% of plasma calcium
iii. Calcium bound to albumin:
1. Forms about 40% to 42% of plasma calcium.
Calcium in Bones .
[1]. Calcium is constantly removed from bone and deposited in bone.
[2]. Bone calcium is present in two forms:
i. Rapidly exchangeable calcium or exchangeable calcium : Available in small quantity in bone and helps to maintain the plasma calcium level .
ii. Slowly exchangeable calcium or stable calcium : Available in large quantity in bones and helps in bone remodeling.
Source of Calcium .
1. Dietary Source .
[1]. Calcium is available in several foodstuffs.
[2]. Percentage of calcium in different food substance is:
1. Whole milk = 10%
2. Low fat milk = 18%
3. Cheese = 27%
4. Other dairy products = 17%
5. Vegetables = 7%
6. Other substances such as meat, egg, grains, sugar, coffee, tea, chocolate, etc. = 21%
2. From Bones .
Besides dietary calcium, blood also gets calcium from bone by resorption.
Daily requirement of Calcium .
1. 1 to 3 years = 500 mg
2. 4 to 8 years = 800 mg
3. 9 to 18 years = 1,300 mg
4. 19 to 50 years = 1,000 mg
5. 51 years and above = 1,200 mg
6. Pregnant ladies and lactating mothers = 1,300 mg .
Absorption & Excretion of Calcium .
[1]. Calcium taken through dietary sources is absorbed from GI tract into blood and distributed to various parts of the body.
[2]. Depending upon the blood level, the calcium is either deposited in the bone or removed from the bone (resorption).
[3]. Calcium is excreted from the body through urine and feces.
Absorption from Gastrointestinal Tract .
[1]. Calcium is absorbed from duodenum by carrier mediated active transport and from the rest of the small intestine, by facilitated diffusion.
[2]. Vitamin D is essential for the absorption of calcium from GI tract.
Excretion .
[1]. While passing through the kidney, large quantity of calcium is filtered in the glomerulus.
[2]. From the filtrate, 98% to 99% of calcium is reabsorbed from renal tubules into the blood.
[3]. Only a small quantity is excreted through urine.
[4]. Most of the filtered calcium is reabsorbed in the distal convoluted tubules and proximal part of collecting duct.
[5]. In distal convoluted tubule, parathormone increases the reabsorption.
[6]. In collecting duct, vitamin D increases the reabsorption and calcitonin decreases reabsorption.
[7]. About 1,000 mg of calcium is excreted daily. Out of this, 900 mg is excreted through feces and 100 mg through urine.
Regulation of Blood Calcium Level .
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| Regulation of blood calcium level |
Blood calcium level is regulated mainly by three hormones :
1. Parathormone .
2. 1,25-dihydroxycholecalciferol (calcitriol) .
3. Calcitonin.
1. Parathormone .
Parathormone is a protein hormone secreted by parathyroid gland and its main function is to increase the blood calcium level by mobilizing calcium from bone (resorption) .
2. 1,25-dihydroxycholecalciferol – Calcitriol .
[1]. Calcitriol is a steroid hormone synthesized in kidney.
[2]. It is the activated form of vitamin D.
[3]. Its main action is to increase the blood calcium level by increasing the calcium absorption from the small intestine .
3. Calcitonin .
[1]. Calcitonin secreted by parafollicular cells of thyroid gland.
[2]. Thyroid gland is a calcium-lowering hormone.
[3]. It reduces the blood calcium level mainly by decreasing bone resorption .
Effects of Other Hormones .
In addition to the above mentioned three hormones, growth hormone and glucocorticoids also influence the calcium level.
1. Growth hormone .
[1]. Growth hormone increases the blood calcium level by increasing the intestinal calcium absorption. [2]. It is also suggested that it increases the urinary excretion of calcium. However, this action is only transient.
2. Glucocorticoids .
Glucocorticoids (cortisol) decrease blood calcium by inhibiting intestinal absorption and increasing the renal excretion of calcium.
Phosphate Metabolism .
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| Effect of hormones on blood phosphate level . |
[1]. Phosphorus (P) is an essential mineral that is required by every cell in the body for normal function. [2]. Phosphorus is present in many food substances, such as peas, dried beans, nuts, milk, cheese and butter.
[3]. Inorganic phosphorus (Pi) is in the form of the phosphate (PO4 ).
[4]. The majority of the phosphorus in the body is found as phosphate.
[5]. Phosphorus is also the body’s source of phosphate.
[6]. In body, phosphate is the most abundant intracellular anion.
Importance of Phosphate .
1. Phosphate is an important component of many organic substances such as, ATP, DNA, RNA and many intermediates of metabolic pathways .
2. Along with calcium, it forms an important constituent of bone and teeth .
3. It forms a buffer in the maintenance of acid-base balance.
Normal Value .
[1]. Total amount of phosphate in the body is 500 to 800 g.
[2]. Though it is present in every cell of the body, 85% to 90% of body’s phosphate is found in the bones and teeth.
[3]. Normal plasma level of phosphate is 4 mg/dL.
Regulation of Phosphate Level .
[1]. Phosphorus is taken through dietary sources.
[2]. It is absorbed from GI tract into blood. It is also resorbed from bone.
[3]. From blood it is distributed to various parts of the body. While passing through the kidney, large quantity of phosphate is excreted through urine.
[4]. Blood phosphate level is regulated mainly by three hormones:
1. Parathormone .
2. Calcitonin .
3. 1,25-dihydroxycholecalciferol (calcitriol).
1. Parathormone .
[1]. Parathormone stimulates resorption of phosphate from bone and increases its urinary excretion.
[2]. It also increases the absorption of phosphate from gastrointestinal tract through calcitriol.
[3]. The overall action of parathormone decreases the plasma level of phosphate.
2. Calcitonin .
Calcitonin also decreases the plasma level of phosphate by inhibiting bone resorption and stimulating the urinary excretion.
3. 1,25-Dihydroxycholecalciferol – Calcitriol .
Calcitriol hormone increases absorption of phosphate from small intestine .
Effects of Other Hormones .
In addition to the above mentioned three hormones, growth hormone and glucocorticoids also influence the phosphate level.
1. Growth hormone .
Growth hormone increases the blood phosphate level by increasing the intestinal phosphate absorption.
2. Glucocorticoids .
Glucocorticoids (cortisol) decreases blood phosphate by inhibiting intestinal absorption and increasing the renal excretion of phosphate.
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