Parathyroid & calcitonin hormones

BONE PHYSIOLOGY

OSTEOBLAST Bone-forming cellsSecrete collagen forming a matrix then calcifiesOSTEOCYTESSurrounded by calcified matrix OSTEOCLASTMultinuclear cellsErode and resorb previously formed boneRelease of Ca and PO4 into the ECFBreakdown of Collagen into its constituent amino acids

THE PARATHYROIDS

Smallest endocrine glands in the body2 pairs of glands- typical Two Types of Cell1.CHIEF CELLS:Most numerousSeen and identified even at birthSecrete the PTH2. OXYPHIL CELLS:After pubertyFunction not certain

THE PARATHYROIDSROLE OF PTHRegulation of the serum calcium concentrationAction on the three tissuesBone, kidney & Intestine.No known pituitary regulating hormone Direct action unlike (adrenal, gonads and thyroid )

AWS

MECHANISM OF ACTION OF PTH (Bone & KidneyActivation of adenyl cyclase increase formation of cyclic AMPcAMP increases the permeability of osteoclasts, osteocytes, and osteoblasts to the bone fluidOsteoblast pump the Ca into the ECFThe pump is stimulated by 1,25 -(OH)2 D3NOTE: PTH serve as a trophic hormone for the conversion of 25 (OH)D3 to 1,25- (OH)2 D3

Kidney Failure- cant convert 25-hyroxyVitaminD3 into the active form. Therefore, no calcium is reabsorbed. Blood calcium levels decrease and there is over secretion of PTH.

REGULATION OF PTHThe parathyroid cells rely on a G-protein-coupled membrane receptor designated the calcium-sensing receptor (CASR), to regulate PTH secretion by sensing extracellular calcium levelsIncreased PTH secretion leads to an increase in serum calcium levels by increasing bone resorption and enhancing renal calcium reabsorption.PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, catecholamines, hypomagnesemia.

HYPOPARATHYROIDISM

Mild (tingling in the hands, fingers, and around the mouth) severe muscle cramps leading all the way to tetany .CAUSESIdiopathic hypoparathyroidism, hypoplasia or absence of parathyroid tissueAccidental removal of the glands

TREATMENT OF HYPOPARATHYROIDISM

Vitamin D and calcium supplementsParathyroid Gland Transplantation

HYPERPATATHYROIDISM

Condition of too much PTH activity. Primary hyperparathyroidism increased parathyroid cell proliferation PTH secretion which is independent of calcium levels.

CLINICAL FEATURES

Kidney stones, painful bones, Osteopenia, osteoporosis,. Peptic ulcer disease & pancreatitis

HYPERPATATHYROIDISMBony errosion & fracture

PARATHYROID CARCINOMA1% of cases of primary hyperparathyroidism15% of patients have lymph node metastases and 33% have distant metastases at presentation.E.g. bone scan with ribs metastasis

TREATMENT OF HYPERPARATHYROIDISM

Bisphosphonates.Surgery if any of following;

CALCITONINBIOSYNTHESISOF CALCITONIN

Calcitonin is formed by the proteolytic cleavage of a larger prepropeptide, which is the product of the CALC1 gene (CALCA).

CALCITONIN RECEPTOR

The calcitonin receptor, found on osteoclasts and in kidney and regions of the brain.This a G protein-coupled receptor, which is coupled by Gs to adenylyl cyclase and thereby to the generation of cAMP in target cells.

PHYSIOLOGY OF CALCITONIN

Calcitonin lowers blood Ca2+ levels in following ways:Inhibits Ca2+ absorption by the intestines.Inhibits osteoclast activity in bones.Inhibits phosphate reabsorption by the kidney tubules.Calcitonin increases tubular reabsorption of Ca2+, leading to decreased rates of its loss in urine.

USES OF CALCITONIN

Salmon calcitonin is used for the treatment of:Postmenopausal osteoporosisHypercalcaemia Pagets diseaseBone metastases

USES OF CALCITONINDIAGNOSTIC diagnostically as a tumor marker for a form of thyroid cancer (medullary thyroid adenocarcinoma), in which high calcitonin levels may be present and elevated levels after surgery may indicate recurrence.

Interactions of PTH and Calcitonin