The Parathyroid Gland and Calcium Homeostasis Flashcards
What cells in the parathyroid gland are responsible for secreting PTH?
chief cells
What are the actions of PTH?
- increase in calcium concentration (absorption from bone and decreased excretion from kidneys)
- decrease in phosphate concentration (increased renal excretion)
- release of calcium and phosphate from bones into bloodstream
- absorption of calcium and phosphate from contents of intestines (by vitamin D pathway)
- conservation of calcium and increase in phosphate excretion by kidneys
What are the effects of dysregulation of the parathyroid glands?
- excess activity = hypercalcaemia (rapid release of calcium and salt from bones)
- rickets, pregnancy, lactation
- reduced activity = hypocalcaemia (with tetany - involuntary contraction of the muscles
- high Ca2+ or Vit D conc in diet, other bone resorption factors (eg. disuse)
Describe the synthesis of PTH
- ribosomes form a preprohormone and undergoes intracellular processing and cleaved to produce mature hormone
- mature hormone undergoes processing in the golgi and is packaged into secretory vesicles and exocytosed into the blood
How does cAMP mediate the effects of PTH?
- secretion of PTH causes increase in cAMP in osteocytes and osteoclasts in bone
- stimulates osteoclastic secretion of enzymes and acids for bone resorption and formation of calcitriol (mediates Ca2+ increase) in kidneys
Describe the effect that PTH has on bone
triggers release of calcium and phosphate from bone
2 phases:
- rapid phase: begins in minutes, lasts hours, osteocytes liberate calcium and phosphate, no breakdown of bone
- slow phase: lasts days/weeks, osteoclasts proliferate and increase resorption of bone to liberate calcium and phosphate
Describe the cellular mechanism of PTH induced bone resorption
- PTH binds to receptors on osteoblasts
- triggers a cascade of reactions which activate osteoclasts (due interaction of RANKL with increased expression of RANK receptors on lining cells)
- osteoclasts resorb bone allowing release of factors stored in matrix
- this recruits osteoblasts to the resorbed area to produce new bone matrix and promote mineralisation
Describe the effect that PTH has on the kidneys
- increased tubular reabsorption of Ca2+
- decreased phosphate tubular reabsorption
- increased reabsorption of magnesium and hydrogen ions
- decreased reabsorption of sodium, potassium and amino acids
- stimulation of more active forms of Vit D to increase Ca2+ absorption
Why is PTH mediated conversion of Vit D3 to 25-hydroxycholecalciferol important?
compound is stable over a wide range of D3 intake so no toxic build up, and very reduced level required for deficiency
conserves vit D storage in the liver as it can last for a few weeks and vit D can last for months
Describe the actions of Vit D and cellular mechanism
- 1,25-D and Vit D increase of reabsorption of Ca2+ and phosphate into ECF in intestines, kidneys and bones
- binds to receptor in nuclei of cells and forms complex with retinoid X receptor
- complex binds to DNA to activate transcription
Describe the hormonal effect of Vit D in intestines
- 1,25-D promotes intestinal absorption of calcium by forming calbindin (Ca2+ binding protein) in intestinal epithelial cell brush border
- Ca2+ moves through basolateral membrane by facilitated diffusion
- rate of Ca2+ absorption directly proportional to quantity of calbindin
What affect does Vit D have on bone?
- high vit d = resorption of bone
- low vit d = reduces/no reabsorption of bone due to normal affect of PTH being reduced
- small vit d quantities = bone calcification (increases Ca2+ and phosphate absorption from intestines)
- can increase mineralisation in absence of increased absorption of Ca2+ and phosphate
How is ECF Ca2+ concentration changes deteced?
- CSR (calcium sensing receptor) in parathyroid cell membranes
- stimulation from increased Ca2+ activates phospholipase C which increases inositol 1,4,5-triphosphate and diacylglycerol formation causing release of calcium from intracellular stores
- decreases PTH secretion
What is the effect of Ca2+ on calcitonin?
- increased ECF Ca2+ stimulates calcitonin secretion
- does this by providing hormonal feedback (weak)
- immediate effect = decrease resorption by osteoclasts (favours bone deposition)
- prolonged effect = decreased formation of osteoclasts but osteoblasts also reduce so transient effect
Describe the action of calcium in the body
- excitation-contraction coupling in muscle
- excitation-secretion coupling at axon terminals and in endocrine and exocrine glands
- blood coagulation
- intracellular second messenger
