Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College Parathyroid Hormone ENDO BLOCK 412 Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College

Lecture Objectives At the end of this lecture the student should be able to Describe the role of calcium in the body Enumerate the factors affecting plasma calcium Describe the mechanisms controlling plasma Ca++ concentration Describe the chemical nature, source and actions of parathyroid hormone Describe the chemical nature, source and actions of calcitonin hormone Describe the role of vit.D in regulation of Ca++ conc. Describe Pathophysiology of hypo & hyperparathyroidism Describe the effects of Vit.D deficiency

Bound to plasma protein (50%) Calcium Distribution Total Body Ca++ Body fluid (1%) ECF (0.1%) Free form (50%) Bound to plasma protein (50%) ICF in soft tissues (0.9%) Skeleton & teeth (99%)

Vital role of Ca++ Neuromuscular excitability Excitation contraction coupling in cardiac, smooth & skeletal muscle Stimulus secretion coupling Excitation secretion coupling Maintenance of tight junctions between cells Clotting of blood

Endocrine Control of Calcium Metabolism Three hormones regulate plasma concentration of Ca2+ (and PO43-) Parathyroid hormone (PTH) Calcitonin Vitamin D

Ca++ homeostasis & Ca++ balance Ca++ adjustment on Minute to minute basis Exchange between bone and ECF Ca++ balance Slowly responding adjustment Ca++ intake Vs Ca++ excretion Parathyroid hormone (PTH) the principal regulator of Ca++ metabolism , acts directly or indirectly on all three of these effector sites.

Parathyroid hormone secreted by the parathyroid glands, four rice grainsized glands located on the back surface of the thyroid gland, one in each corner

Cont… PTH is essential for life The overall effect is increase plasma Ca++ Complete absence of PTH ensues death within few days. It acts on bone, kidneys and intestine PTH acts to lower plasma PO43- conc.

PTH raises plasma Ca2+ by withdrawing Ca2+ from the bone bank. induces a fast Ca2+ efflux into the plasma from the small labile pool of Ca2+ in the bone fluid. Second, by stimulating bone dissolution, it promotes a slow transfer into the plasma of both Ca2+ and PO43- from the stable pool of bone minerals in bone itself.

Both Ca2+ & PO43- are released in plasma PTH’s chronic effect is to promote localized dissolution of bone to release Ca2+ into plasma. Stimulate osteoclast Both Ca2+ & PO43- are released in plasma PTH deals with PO4 by its action on kidneys

PTH acts on the kidneys to conserve Ca2+ and eliminate PO43- Absorb more Ca++ Decrease reabsorption of PO43- an inverse relationship exists between the plasma concentrations of Ca2+ and PO43- Activation of Vit. D PTH indirectly promotes Ca++ & PO43- absorption from the intestine by helping Vit.D

Regulation of PTH secretion PTH secretion increases when plasma Ca2 falls and decreases when plasma Ca2 rises. this relationship forms a simple negative- feedback loop for controlling PTH secretion

Calcitonin Polypeptide hormone produced by C cells of thyroid gland Decreases plasma Ca ++ levels on a short-term basis calcitonin decreases Ca ++ movement from the bone fluid into the plasma. Second, on a long-term basis calcitonin decreases bone resorption by inhibiting the activity of osteoclasts via the cAMP pathway. Calcitonin also inhibits Ca ++ and PO43- reabsorption from the nephron

ACTIONS OF CALCITONIN ON BONE Decresaed osteoclastic number Decreased osteoclastic activity Actions are proportional to baseline rate of bone turnover

VITAMIN D cholecalciferol, or vitamin D, a steroid like compound essential for Ca++ absorption in the intestine. Activated by the addition of two (-OH) groups. The first reaction occurs in the liver & the second in kidneys. The active form of vit.D is 1,25-(OH)2- vitamin D3 also known as calcitriol.

Figure 19.26: Activation of vitamin D.

Figure 19.27: Interactions between PTH and vitamin D in controlling plasma calcium. Fig. 19-27, p. 736

Disorder of parathyroid hormone PTH hypersecretion – hyperparathyroidism Characterized by hypercalcemia & hypophosphatemia Clinical features: Muscle weakness Decrease alertness, poor memory & depression Cardiac disturbances Mobilization of Ca2+ & PO43- from skeletal store may results in thinning of bone, fractures, skeletal deformities Increase incidence of Kidney stones

Hyperparathyroidism Bones Stones Abdominal groans

PTH hyposecretion Hypoparathyroidism Inadvertent removal of parathyroid gland Hypocalcemia and hyperphospatemia Increased neuromuscular excitability Muscle cramps twitches Tingling and pins and needle sensation Irritability & paranoia

SIGNS AND SYMPTOMS OF HYPOPARATHYROIDISM Positive Chvostek’s (facial muscle twitch) sign Positive Trousseau’s (carpal spasm) sign Delayed cardiac repolarization with prolongation of the QT interval Paresthesia Tetany

Hypocalcemic tetany

VITAMIN D DEFICIENCY Decrease Ca++ absorption from intestine. PTH increases plasma Ca++ from bone Demineralization of bones - softening Rickets in children Osteomalacia in adult.

Comparison of normal and osteoporotic bone. Note the reduced density of osteoporotic trabecular bone compared to normal trabecular bone. p. 730

1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. 3 2 1 CALCITRIOL stimulates increased absorption of Ca2+ from foods, which increases blood Ca2+ level. PTH also stimulates the kidneys to release CALCITRIOL. High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 5 6 1 PTH also stimulates the kidneys to release CALCITRIOL. High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 5 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. 2

References Human physiology, Lauralee Sherwood, seventh edition. Text book physiology by Guyton &Hall,11th edition. Text book of physiology by Linda .S .Costanzo third edition