endocrine - Ca and phosphate homeostasis Flashcards
Bone cell type for production of matrix
Osteoblast
Circulating forms of calcium
Ionized - 50%
Protein-bound - 40%
Complexed with anion - 10%
Bone cell type for resorption of matrix
Osteoclasts
Hormones and minerals found in bones
PTH Vit D Calcitonin Calcium Phosphorus
Predominant parenchymal cell type and a primary endocrine cell of parathyroid gland
Chief/principal cell
Larger, mitochondria-rich, eosinophilic cell type of parathyroid gland
Oxyphil cell
Major regulator of calcium and phosphorus metabolism
PTH
The most important effect of PTH is to increase/decrease plasma calcium level
Increase plasma calcium level
The most important effect of PTH is to increase plasma Ca level by
Stimulate bone resorption
Increase renal tubular reabsorption
Stimulate renal 1,25 dihydroxy- D synthesis
PTH decrease /increase plasma phosphate
Decrease plasma phosphate
PTH decrease plasma phosphate by
Inhibiting renal tubular phosphate reabsorption
Parathyroid cell type that secretes PTH
Chief cell
Primary target of PTH
Bone
Kidneys
PTH receptors
PTH1R (hPTH/PTHrP)
PTH2R
CPTH
Pty receptor that bonds both PTH and PTHrP
PTH1R
PTH receptor that activates adenylyl cyclase and PLC
PTH1R
PTH receptor that is abundant in bones (osteoblasts) and kidneys (prox and distal convoluted tubules)
PTH1R
PTH receptor that does not bind to PTHrP
PTH2R
PTH receptor that is found in brain, placenta and pancreas
PTH2R
PTH receptor that reacts with the carboxylate terminal rather than amino terminal of PTH
CPTH
Primary stimulating signal of PTH
Low circulating Ca level
Low circulating Ca level is sensed by principal cells thru
Ca-sensing receptor (CaSR)
High Mg level inhibits PTH
True
PTH stimulation
Phosphodieasterase inhibitors Epinephrine Dopamine Histamine Lithium Thiazides diuretics
PTH inhibition
A-adrenergic agonists
Prostaglandins
Aluminum
Chromogranin
Mechanism of action of PTH in kidneys
Stimulates Ca reabsorption
Inhibits Pi reabsorption
Stimulates conversion to 1,25 dihydroxy vitamin D
Vit D3
Cholecalciferol
Vit D synthesis
7-dehydrocholesterol -(skin UV light)- cholecalciferol - (liver vitD 25-hydroxylase)- 25hydroxycholecalciferol -(kidney 1a-hydroxylase)- 1,25dihydroxyvitamin D
Rate limiting enzyme in vit d synthesis
1a-hydroxylase (CYP1a)
Secosteroid (class of steroid with 1 open cholesterol ring)
Vit D3
Ergocalciferol, secosteroid produced in plants. Enters the liver for hydroxylation via portal circulation and chylomicrons
Vit D2
Facilitates absorption of Ca in duodenum and jejunum
Vit d
Percentage of active vit d that circulates as free steroid
0.4%.
Other binds to DBP from liver
What kind of receptor is vit D receptor
Nuclear receptor
Low Ca stimulates renal 1a-hydroxylase thru increased PTH
High Ca inhibits 1a-hydroxylase thru CaSR in proximal tubule
Very active vit D preparation
Calcitriol
Effect of calcitonin to phosphate and Ca level
Decrease Ca and decrease phosphate
Effect of PTH to phosphate and Ca level
Increase Ca
Decrease phosphate
Effect of vitD to phosphate and Ca level
Increase Ca
Increase phosphate
Bone remodeling is regulated by
PTH
Calcitonin is produce by what cell
Parafollicular C cell
Calcitonin is regulated by
CaSR and high Ca level
Calcitonin is primarily inactivated in what organ
Kidney
Inhibits bone resorption
Calcitonin
As decreases Ca and Pi
Useful histo chemical marker for MEdullary thyroid Ca
Calcitonin
Calcitonin is expressed in
Osteoclast (inhibits bone resorption)
Nephrons (inhibits Ca and Pi reabsorption)
Major stimulus of calcitonin
Hypercalcemia
Normal calcitonin plasma level
10-20pg/mL
Any increase In plasma Ca by 1mg/dl will result to 2-10fold acute rise in calcitonin
Calcitonin release is stimulated by
Vit D
Ingestion of food due to GASTRIN
Inhibitors of calcitonin
Low vit D
Somatostatin
Calcitonin excess does not produce hypocalcemia (MTC).
Calcitonin deficiency does not produce hypercalcemia (post total thyroidectomy for thyroid Ca )
Calcitonin plays a very minimal or negligible physiologic role in Ca and phosphate homeostasis
Hyperparathyroidism is an excessive production of PTH that is usually due to single adenoma. It has high/low Ca and high/low Pi.
High Ca and low Pi
High Ca and low Pi in hyperparathyroidism is due to
Bone demineralization
High GI Ca absorption
High renal Ca reabsorption
Hypoparathyroidism is due to PTH and vitD deficiency. It has high/low Ca and high/low Pi.
Low Ca and high Pi
The low Ca and high Pi in hypoparathyroidism is due to
Impaired GI Ca absorption
Decreased renal reabsorption
Decreased bone Ca mobilization
Bone is not affected in hypoparathyroidism
True
Rare familial disorder charac by tissue resistance to PTH.
Pseudo hypoparathyroidism
There is high PTH secretion, low Ca and congenital defects of skeleton.
Pseudo hyperparathyroidism
Mg and Ca in vit D deficiency
Low mg and Ca
VitD deficiency leads to defective bone mineralization in adults
Osteomalacia
VitD deficiency leads to defective bone mineralization in children
Rickets
VitD deficiency leads to secondary increase in PTH
Osteoporosis
Results in bone deformities due to increase bone resorption ff by increase bone formation.
It has high alkaline phosphatase, osteocalcin and urinary hydroxyproline.
It produces pain, bone deformation and bone weakness.
Paget’s disease
As in chronic renal disease with high Pi and low Ca due to high PTH and low vit D
Renal osteodystrophy
