The parathyroid glands secrete parathyroid hormone (PTH) which regulates calcium levels in the blood. PTH increases blood calcium levels by mobilizing calcium from bone, increasing calcium absorption in the gut, and decreasing calcium excretion by the kidneys. PTH also decreases blood phosphate levels by inhibiting its reabsorption by the kidneys. The secretion of PTH is regulated by calcium levels in the blood, with low calcium stimulating PTH secretion and high calcium inhibiting it, forming a negative feedback loop to maintain blood calcium homeostasis.
The parathyroid glands secrete parathyroid hormone (PTH) which regulates calcium levels in the blood. PTH increases blood calcium levels by mobilizing calcium from bone, increasing calcium absorption in the gut, and decreasing calcium excretion by the kidneys. PTH also decreases blood phosphate levels by inhibiting its reabsorption by the kidneys. The secretion of PTH is regulated by calcium levels in the blood, with low calcium stimulating PTH secretion and high calcium inhibiting it, forming a negative feedback loop to maintain blood calcium homeostasis.
The parathyroid glands secrete parathyroid hormone (PTH) which regulates calcium levels in the blood. PTH increases blood calcium levels by mobilizing calcium from bone, increasing calcium absorption in the gut, and decreasing calcium excretion by the kidneys. PTH also decreases blood phosphate levels by inhibiting its reabsorption by the kidneys. The secretion of PTH is regulated by calcium levels in the blood, with low calcium stimulating PTH secretion and high calcium inhibiting it, forming a negative feedback loop to maintain blood calcium homeostasis.
The parathyroid glands secrete parathyroid hormone (PTH) which regulates calcium levels in the blood. PTH increases blood calcium levels by mobilizing calcium from bone, increasing calcium absorption in the gut, and decreasing calcium excretion by the kidneys. PTH also decreases blood phosphate levels by inhibiting its reabsorption by the kidneys. The secretion of PTH is regulated by calcium levels in the blood, with low calcium stimulating PTH secretion and high calcium inhibiting it, forming a negative feedback loop to maintain blood calcium homeostasis.
Download as PPTX, PDF, TXT or read online from Scribd
Download as pptx, pdf, or txt
You are on page 1/ 28
PARATHYROIDS AND CALCIUM
METABOLISM presented by
Dr. EGBEJIMI AYEBATONBRA MICHAEL
B.Med sc. Human Physio, MBBS, (NDU)
06/28/2021 Parathyroids and calcium metabolism 1
INTRODUCTION • The parathyroid glands are usually 4 in number, which are situated on the posterior surface of upper and lower poles of thyroid gland (i.e) a superior and an inferior pair • Parathyroid glands are very small in size, yellowish-brown in colour each measuring about 6 mm long, 3 mm wide and 2 mm thick • Each parathyroid gland is made up of chief cells and oxyphil cells • Chief cells; secrete parathormone (parathyroid hormone) • They have abundant glycogen, Golgi apparatus and few clusters of secretory granules
06/28/2021 Parathyroids and calcium metabolism 2
• Oxyphil cells; Are the degenerated chief cells
First appears at puberty
Distinguished by its larger and lighter staining (numerous mitochondria) Believed to be modified or depleted chief cells that no longer secrete hormone
• N/B ; Parathyroid hormone(PTH) is the only hormone secreted by the
parathyroid gland
06/28/2021 Parathyroids and calcium metabolism 3
INTRODUCTION CONTD • Parathormone is a protein hormone having 84 amino acids • Its molecular weight is 9,500 • Half life is less than 20min • normal plasma level of PTH is about 1.5 to 5.5 ng/dL • Ectopic locations occurs rarely in the neck and mediastinum • Their blood supply is from thyroid arteries 06/28/2021 Parathyroids and calcium metabolism 4 Parathyroid Glands
06/28/2021 Parathyroids and calcium metabolism 5
06/28/2021 Parathyroids and calcium metabolism 6 FUNCTIONS OF PARATHYROID HORMONE • PTH is the single most important hormone in the control of calcium levels of the blood • It promotes the rise in blood calcium levels by acting on the bone, kidneys and intestine 1) Mobilization of calcium from bone causing an increase in osteoblastic activity 2) Absorbs calcium from GIT in the presence of vitamin D 3) Decreases excretion of calcium by kidneys by increasing renal threshold leading to decrease in urinary loss of calcium 4) Has a phosphaturic action; causing phosphate excretion in urine by decreasing tubular reabsorption , thereby increasing serum calcium
06/28/2021 Parathyroids and calcium metabolism 7
Synthesis and Release of PTH • Synthesized on the ribosomes in the form of a preprohormone,(prepro-PTH) • Prepro-PTH is transported to ER • Where it is cleaved to a prohormone • Pro-PTH is transported to Golgi apparatus further cleaved to form PTH • Finally packaged in secretory granules in the cytoplasm of cell 06/28/2021 Parathyroids and calcium metabolism 8 Metabolism
• 60% to 70% of PTH is degraded by Kupffer cells of liver, by means of
proteolysis.
• Degradation of about 20% to 30% PTH occurs in kidneys
06/28/2021 Parathyroids and calcium metabolism 9
PTH Actions • Primary action of PTH is to maintain the blood calcium level within the critical range of 9 to 11 mg/dL. (10mg/dl) • The blood calcium level has to be maintained critically because it is very important for many of the activities in the body • Its paramount effect is to increase plasma Ca2+ levels by • Stimulating bone resorption • Renal tubular Ca2+ reabsorption • And 1,25 – (OH)2D3 synthesis • PTH decrease plasma phosphate concentration • By Inhibiting renal tubular phosphate reabsorption 06/28/2021 Parathyroids and calcium metabolism 10 Mechanism of PTH Actions • PTH action is initiated by binding to a plasma cell membrane receptors • Parathormone receptors (PTH receptors) are of three types, PTHR1, PTHR2 and PTHR3, • PTHR1 is physiologically more important than the other two types. • PTHR1 mediates the actions of PTH and PTH-related protein • Role of PTHR2 and PTHR3 is not known clearly. • On the target cells, PTH binds with PTHR1 which is coupled to G protein and forms hormone-receptor complex. • Hormone-receptor complex causes formation of cAMP, which acts as a second messenger for the hormone. 06/28/2021 Parathyroids and calcium metabolism 11 Effects of PTH: • The overall effect of PTH is • To increase plasma calcium and decrease plasma phosphate • By acting on 3 major target organs • Bone • Kidney • GIT
06/28/2021 Parathyroids and calcium metabolism 12
Calcium and Phosphate Absorption From the Bone • PTH accelerates removal of calcium and phosphate from bone by acting on osteoblasts and osteoclasts of the bone. • Resorption of calcium from bones occurs in two phases • Rapid phase • Slow phase
06/28/2021 Parathyroids and calcium metabolism 13
Rapid Phase of Calcium and Phosphate Absorption • Rapid phase occurs within minutes after the release of PTH from parathyroid glands • PTH gets attached with the receptors on the cell membrane of osteoblasts and osteocytes. • The hormone-receptor complex increases the permeability of membranes of these cells for calcium ions. It accelerates the calcium pump mechanism, so that calcium ions move out of these bone cells and enter the blood at a faster rate • PTH stimulates osteolysis • Note: bone fluid & osteocytic membrane 06/28/2021 Parathyroids and calcium metabolism 14 Rapid Phase of Calcium and Phosphate Absorption
• PTH stimulates osteolysis
• By increaseing calcium permeability of the osteocytic membrane • osteolysis occurs without absorption of bone’s fibrous and gel matrix
06/28/2021 Parathyroids and calcium metabolism 15
Slow Phase of Calcium and Phosphate Absorption • PTH activates the osteoclasts • Requires several days or even weeks to become fully developed • PTH also stimulates the formation of new osteoclasts • Osteoclasts reabsorb bone itself • Not merely reabsorption of calcium phosphate salt from the bone
06/28/2021 Parathyroids and calcium metabolism 16
Slow Phase of Calcium and Phosphate Absorption • Osteoclasts do not have membrane receptor proteins for PTH • It is believed that activated osteoblasts and osteocytes • Send a secondary but unknown signal to the osteoclasts • Causing them to set their usual task of bone reabsorption • After few months, osteoclastic resorption of bone can lead to weakened bones and secondary stimulation of the osteoblasts that attempt to correct the weakened state
06/28/2021 Parathyroids and calcium metabolism 17
Slow Phase of Calcium and Phosphate Absorption • When osteoclasts are activated, some substances such as proteolytic enzymes, citric acid and lactic acid are released from lysosomes of these cells. All these substances digest or dissolve the organic matrix of the bone, releasing the calcium ions. • PTH also induces increase in acid Phosphatase, carbonic anhydrase and accumulation of lactic acid and citric acid • The resultant lowering of pH contributes to the resorptive process 06/28/2021 Parathyroids and calcium metabolism 18 Effect of PTH in Kidneys • PTH increase the reabsorption of calcium from the distal convoluted tubules, collecting tubules and proximal part of collecting ducts
• PTH also increases the formation of 1,25-
dihydroxycholecalciferol (activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys
06/28/2021 Parathyroids and calcium metabolism 19
Effect of PTH in Kidneys • PTH inhibits the reabsorption of phosphates in the proximal tubules • PTH also inhibits the reabsorption of Na+, and HCO3- in the proximal tubules • Without PTH either none or almost none of the 1,25(OH)2-d3is formed
06/28/2021 Parathyroids and calcium metabolism 20
Schematic diagram showing activation of vitamin D
06/28/2021 Parathyroids and calcium metabolism 21
Effects of PTH in GIT
• PTH greatly enhances both calcium and phosphate
absorption from the intestines • By increasing the formation of 1,25(OH)2-D3 in the kidneys
06/28/2021 Parathyroids and calcium metabolism 22
Effects of PTH in Other Tissues/organs • Alteration in the function of • CNS, • CVS, • Muscles • Peripheral nerves and of • Other endocrine glands • Are seen in states of PTH excess or deficiency
06/28/2021 Parathyroids and calcium metabolism 23
Regulation of PTH Secretion • The dominant regulator of parathyroid gland activity is plasma calcium level
• The regulation is done via a negative feed back fashion
• It is actually the ionized fraction of plasma calcium that regulates PTH
secretion
06/28/2021 Parathyroids and calcium metabolism 24
Regulation of PTH Secretion • Hypocalcaemia increases PTH • Synthesis, stores, and secretory rate • And ultimately stimulates growth of the gland • Despite the close physiological relation of phosphate to calcium, No direct effect of phosphate on the parathyroid gland • However a rise in plasma phosphate cause a fall in ionized calcium levels which in turn stimulates PTH secretion • 1,25- (OH)2 D3 inhibits synthesis of PTH and decrease PTH secretion • Phosphadiesterase inhibitors, epinephrine, dopamine and histamine All stimulate PTH secretion
06/28/2021 Parathyroids and calcium metabolism 25
ACTIONS OF PARATHORMONE ON BLOOD PHOSPHATE LEVEL • PTH decreases blood level of phosphate by increasing its urinary excretion. • 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
• PTH increases phosphate excretion by inhibiting reabsorption of phosphate from renal tubules. • It acts mainly on proximal convoluted tubule.
3. On Gastrointestinal Tract • Parathormone increases the absorption of phosphate from GI tract 06/28/2021 Parathyroids and calcium metabolism 26 Disorders of parathyroid glands • Two types: I. Hypoparathyroidism II. Hyperparathyroidism • Hyposecretion of PTH is called hypoparathyroidism.It leads to hypocalcemia (decrease in blood calcium level). • Causes for Hypoparathyroidism 1. Surgical removal of parathyroid glands i.e (parathyroidectomy) 2. Removal of parathyroid glands during surgical removal of thyroid gland (thyroidectomy) 3. Autoimmune disease 4. Deficiency of receptors for PTH in the target cells. • In this, the PTH secretion is normal or increased but the hormone cannot act on the target cells. This condition is called pseudohypoparathyroidism 06/28/2021 Parathyroids and calcium metabolism 27 06/28/2021 Parathyroids and calcium metabolism 28
