Calcium and Phosphate regulation

1
Calcium and Phosphate regulation

• JP Slovak

2
Ca

• Structure of bones and teeth
• Contraction of muscle tissue
• Maintains membrane potential in some neurons
• Second messenger
• Role in exocytosis

3
Phosphate

• Structure of bones and teeth
• Activates enzymes
• Buffer in blood
• ATP
• Component of nucleic acids
• Component of phospholipids
• Metabolism of glucose

4
Calcium Homeostasis

• Precisely regulated
• ½ is free in plasma
• 40 bound to protein
• 10 occurs in other compounds
• Free Ca important for many processes
• Ca obtained in diet
• Absorbed through small intestine
• Deposited in bone or excreted
• Bone serves as sink

5
Calcium Homeostasis

• Coop between bones teeth and intestines
• Kidney can prevent loss
• Intestine can secrete
• Maintained by 3 hormones
• PTH
• CT
• 1,25-DHC

6
Phosphate Homeostasis

• 80 of phosphate in skeleton
• The rest is in essential molecules
• Rare as a limiting factor
• Excess can cause problems more often
• In plasma 90 is free
• 10 bound to proteins
• Interrelated to Ca regulation

7
Interrelationship of Ca and Phosphate

• Ca x P k
• k can differ according to state
• k higher in growing mammals
• Changes in Ca or P accomplished by bone
  resorption or formation and absorption and
  excretion
• Osteoblasts and osteoclasts

8
(No Transcript)
9
Endocrine regulation

• PTH
• Hypercalcemic factor
• Release stimulated by low Ca
• Not influenced by P levels
• Works on bone
• CT
• Hypocalcemic factor
• Release related to plasma Ca levels
• 1, 25-DHC
• Stimulates absorption of Ca by gut lumen
• Also influences PTH action on bone and kidney

10
Parathyroid

• Chief cells
• Cuboidal
• Granular (PTH)
• Possible neural influence
• Oxyphils
• Many mitochondria
• 1 of population
• Unknown function
• PTH
• 84 aa
• 34 aa for biologic activity
• PreprPTH 115 aa ?proPTH(90aa)?PTH
• Packaged in vesicles until release
• 20 min half life in cattle and rats

11
Regulation of PTH

• Low Ca ? increase PTH
• Increase Ca ? inhibit PTH
• Cells contain receptors
• G protein coupled receptor
• Vitamin D inhibits PTH secretion
• Parathyroidectomy
• Ca decreases ? violent convulsions
• Low calcium induced tetany
• If continued causes asphyxiation

12
Roles of PTH

• Stimulation of osteoclasts
• Renal reabsorption of Ca
• Renal excretion of P
• Intestinal absorption of Ca
• Control of 1,25 DHC synthesis

13
Calcitonin

• Released from C cells in thyroid
• Entire molecule needed for action
• 32 aa
• Prohormone 136 aa
• 1,25 DHC
• 7-DHC?cholecalciferol?25 HC(liver)?1,25
  DHC(kidney)

14
(No Transcript)
15
Interaction of PTH, CT and 1,25 DHC

• Post prandial hypercalcemia
• Rapid growth, pregnancy and lactation
• Ca and P in bone
• PTH stimulates osteoclasts
• 1. Increase in PG
• 2. Increase in cyclic AMP
• 3. Release of lysosomal enzymes from OC
• 4. Resorb bone
• 5. Increased Ca and P in plasma
• CT may inhibit AC

16

• Ca and P in kidney
• PTH causes reabsorption
• PTH increases formation of 1,25 DHC
• Estrogens enhance formation of 1,25 DHC
• Androgens and estrogens
• Stimulate osteoblast activity
• Glucocorticoids
• Cause Ca loss
• Reduce intestinal absorption and kidney
  reabsorption
• GH
• IGF1 stimulates osteoblast activity
• Hence increased osteoclast activity

17
Disorders

• Hypercalcemia
• Primary
• Increased levels of PTH
• Parathyroid adenoma(90)
• Very few synptoms
• Hypercaluria, nausea, anorexic
• Hypocalcemia
• Reduction in PTH
• Abnormal development of parathyroids

18

• Osteoporosis
• Decalcification
• Increased brittleness
• 1.2 mil fractures a year
• Type 1
• Occur in women after menopause
• Type 2
• Later in life
• Both men and women
• ERT, exercise, Ca supplements
• Pagets disease
• Increased osteoclast activity
• Western europe and mediterranean
• Bones become brittle