Parathyroid Hormone

Dr. Shaikh Mujeeb AhmedAssistant ProfessorAlMaarefa College

ENDO BLOCK 412

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

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 PO4

3-)– Parathyroid hormone (PTH)– Calcitonin– Vitamin D

Ca++ homeostasis & Ca++ balance• Ca++ homeostasis

– 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 PO4

3- 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 PO4

3- from the stable pool of bone minerals in bone itself.

PTH’s chronic effect is to promote localizeddissolution of bone to release Ca2+ into plasma.

• Stimulate osteoclast• Both Ca2+ & PO4

3- 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 PO4

3-

• Activation of Vit. D• PTH indirectly promotes Ca++ & PO4

3-

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.

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.

p. 730

1 High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.

1 High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.

CALCITONIN inhibitsosteoclasts, thus decreasingblood Ca2+ level.

2

1 High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.

Low level of Ca2+ in bloodstimulates parathyroid gland chief cells to release more PTH.

CALCITONIN inhibitsosteoclasts, thus decreasingblood Ca2+ level.

3

2

1 High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.

Low level of Ca2+ in bloodstimulates parathyroid gland chief cells to release more PTH.

CALCITONIN inhibitsosteoclasts, thus decreasingblood Ca2+ level.

PARATHYROID HORMONE (PTH)promotes release of Ca2+ frombone extracellular matrix intoblood and slows loss of Ca2+ in urine, thus increasing bloodCa2+ level.

3

4 2

1

PTH also stimulatesthe kidneys to releaseCALCITRIOL.

High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.

Low level of Ca2+ in bloodstimulates parathyroid gland chief cells to release more PTH.

CALCITONIN inhibitsosteoclasts, thus decreasingblood Ca2+ level.

PARATHYROID HORMONE (PTH)promotes release of Ca2+ frombone extracellular matrix intoblood and slows loss of Ca2+ in urine, thus increasing bloodCa2+ level.

3

4 25

1

CALCITRIOL stimulatesincreased absorption ofCa2+ from foods, whichincreases blood Ca2+ level.

PTH also stimulatesthe kidneys to releaseCALCITRIOL.

High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.

Low level of Ca2+ in bloodstimulates parathyroid gland chief cells to release more PTH.

CALCITONIN inhibitsosteoclasts, thus decreasingblood Ca2+ level.

PARATHYROID HORMONE (PTH)promotes release of Ca2+ frombone extracellular matrix intoblood and slows loss of Ca2+ in urine, thus increasing bloodCa2+ level.

3

4 25

6

30

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