Physiology Block 3 Week 15 12 Calcium Flashcards
Functions of Calcium Ion
Extracellular:
- maintenance of normal ion product for mineralization
- cofactor for prothrombin factors
- maintenance of plasma membrane stability and permeability
Cellular:
- skeletal and cardiac muscle contraction
- cellular secretion
- neural excitation and light transmission
- regulation of membrane ion transport
- enzyme regulation (gluconeogenesis, glycogenolysis)
- cell growth and division
Calcium Absorption/Secretion
35% absorbed in small intestine
Calcitrol 1, 25 (OH) 2D of vitamin D pathway–stimulates calcium and phosphate absorption
25% of calcium intake is secreted into GI tract
NET CALCIUM ABSORPTION = 10% of intake
Calcium Deposition/Resorption
1 kg Ca2+ stored in bone–metabolically active
Parathyroid Hormone (PTH) stimulates resorption–reclamation of calcium (and phosphate) from bone
Deposition–calcium and phosphorus stored in bone
Continual exchange (bone turnover) helps to maintain healthy bone
Resorption > Deposition = net loss of bone calcium and phosphorus = osteoporosis
Estrogen is anti-resorptive; at menopause, women have less estrogen and have a higher incidence of osteoporosis
Calcium Filtration/Reabsorption
99.9% calcium filtered in kidney
Parathyroid Hormone stimulates reabsorption–critical to minimize loss of calcium and phosphate ions at proximal tubule
How is calcium transported in the blood?
50% ionized (free, dissolved)–biologically active
Circulates bound to albumin
Small amount complexed to anions (CaCl2)
Important in patients with hypoalbuminuria
Negative Feedback of Parathyroid Hormone
Synthesized and Secreted by the chief cells from 4 parathyroid glands (glands behind thyroid)
- stimulates bone resorption of calcium and phosphate
- stimulates production of 1,25(OH)2D (converted from 25OHD3)–>increases calcium absorption in GI tract and REabsorption in kidneys
-inhibited by increases in extracellular Ca2+
Decreases in calcium releases PTH from inhibition, allowing resorption (bone breakdown) to restore plasma calcium levels
Negative Feedback of Calcitonin
No importance in humans
Secreted from P,arafolicular Cells of Thyroid
Used as anti-resorptive therapy
–if plasma calcium is VERY high, calcitonin is stimulated and inhibits bone resorption (bone break down)
Calcium Inhibition of Parathyroid Hormone Secretion
Calcium Receptor is a G-Protein coupled Receptor
If calcium is low, the receptor is unloaded, and PTH is secreted from the chief cells of the parathyroid gland
What happens to the feedback loop if plasma calcium is too high (hypercalcemia)?
If there is too much calcium, there will be an inhibition of PTH secretion from parathyroid cells
PTH stimulates bone resorption (bone breakdown)
During hypercalcemia, PTH is inhibited, preventing bone breakdown
Effect of plasma calcium concentration on PTH and Calcitonin
(Hypercalcemic) High Calcium:
- PTH inhibited
- high calcitonin
Low Calcium:
- PTH inhibition relieved = PTH released
- low calcitonin
Chronic Hypocalcemia:
-small changes in calcium concentration result in 100 inc in PTH concentration
What will happen to bone calcium content with long term decreases in calcium intake?
What is the hormonal mechanism involved?
100% increase in PTH
PTH increases bone resorption (bone breakdown)
Leads to osteoporosis
Role of Vitamin D in controlling plasma Calcium Concentration
D3 = cholecalciferol; D2 = ergocalciferol
Vitamin D intake (diet and supplementation)
–liberated from the skin (UV light)
Liver converts to 25OHD3
–reflection of Vit D intake and stores in body
Kidney = REGULATORY STEP
PTH stimulates enzyme 1-hydroxylase to convert 25OHD3 to 1, 25(OH)2D3 = CALCITRIOL
Calcitriol stimulates calcium and phosphate absorption in small intestine
- -increases plasma Ca2+ levels
- -inhibits PTH when Ca2+ levels are high
Does 1-hydroxylase activity alter:
- plasma 1, 25(OH)2D3?
- plasma 25OHD concentration?
25OHD concentration 100-1000x > 1,25(OH)2D3
Only a small portion of 25OHD is actually activated to 1,25(OH)2D3
1-hydroxylase activity:
- can increase or decrease plasma 1,25(OH)2D
- does NOT alter plasma 25OHD because is in excess
Clinical Interpretation of serum 25OHD
Index of Vitamin D Stores (intake/absorption)
–not altered by changes in 1-hydroxylase activity
Clinical Interpretation of serum 1,25(OH)2D3
Index of renal 1-hydroxylase activity