Calcium and Phosphate Homeostasis
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- Why are we worried about regulating Ca and Phosphate?
- Because low Calcium levels can cause increased nerve excitability, tetani, and death (because the diaphragm stays contracted and you can't breathe). Therefore, gotta regulate Ca2+ tightly.
- What are 3 main functions of Ca?
-
1. Muscle contraction, release of NT/hormones,
2. Constituent of bones
3. Alters nerve excitability - What are 3 main functions of phosphate?
-
1. Acts as a buffer
2. Very important in ATP
3. Phosphorylates/activates things. - Where do we regulate calcium, intracelluarly or extra?
- Extracellular.
- What process and movements does calcium undergo normally?
-
1. Deposition/resorption - bone
2. Filtration/reabsorption - kidney
3. Secretion/absorption from GI -
How much calcium exchanges w/
-BONES
-KIDNEY
-GI TRACT
in the normal course of a day? -
-500mg is deposited/resorpted
-10,000 filtered; 9850 reabsorbd
-300 absbd from GI, 150 secreted - How much (mass) of Ca is in the extracellular fluid normally?
- 900 mg
- What Ca rocesses can we regulate and move around for ea. organ?
-
1. Bone Resorption
2. Kidney Reabsorption
3. Absorption from GI - What occurs in bone metabolism, and what cells do the work?
-
Deposition - osteoblasts
Resorption - osteoclasts - What hormone regulates bone resorption?
- Parathyroid hormones - they increase plasma [Ca]
- What stimulates the release of parathyroid hormone?
- low plasma calcium
- Molecularly, what type of hormones are Parathyroid and Calcitonin?
- PEPTIDE hormones.. therefore, they don't need a carrier, and they do need a surface receptor.
- What's Parathyroid hormone's net effect on blood Calcium and phosphate levels?
-
Increased Ca
Decreased phosphate - What's Calcitonin's net effect on blood Calcium and phosphate levels?
- Not EXACTLY opposite PTH; decreased plasma Ca, but decreased PO4 too.
- What would happen if Ca and PO4 both increased in plasma?
- They would precipitate and make crystals. (bad)
- So, what happens when plasma Ca is increased?
- Your parafollicular cells in the thyroid increase calcitonin levels to tone down Ca levels.
- Other than calcitonin and parathyroid hormone, what effects plasma calcium levels?
- 1, 25 dihydroxycholecaciferol - aka, Vitamin D3.
- What pathway stimulates Vit D3 release?
- Decreased plasma Calcium, which increases PTH release, which increases 1-alpha-hydroxylase from the kidney.
- What does 1-alpha-hydroxylase do?
- Increases secretion of active Vit D3.
- How does Vit D3 alter blood calcium?
- By PROMOTING pth activity (bone resorption) and increasing plasma calcium.
- What's Vit D3'hormone's net effect on blood Calcium and phosphate levels?
-
Calcium -> increased
PO4 -> increased - What molecule does Vitamin D3 come from originally?
- Cholesterol
- How do you become Vitamin D3 deficient?
- From Rickets desease.
-
How do you get ricket's disease?
(2 ways) -
1. Lack of sunlight and vitamin d3.
2. Liver/kidney disease - Wait a sec, the net effect of Vitamin D3 is to increase BOTH phosphate and calcium !?
- Well, it only happens by the action of PTH, which also decreases phosphate, so no precipitation occurs. (whew, no crystals!)
- What is osteoporosis?
- Loss ofbone.
- What increases osteoclast production?
- Cytokines.
- What inhibits cytokines?
- Estrogen
- So why do females in menopause get osteoporosis?
- Because they have less estrogen, so more cytokines are around to increase osteoclast production.
- What do osteoclasts do?
- break down bone.
- Why don't men get osteoporosis when they're old? (2 reasons)
-
1. Their testosterone levels don't drop off as dramatically.
2. They have more bone to begin with. - What is Rickets?
- a lack of vitamin D3
-
What is rickets called in
-Children
-Adults -
Children: rickets
Adults: Osteomalacia - What is rickets a result of?
-
1. Decreased sunlight
2. Decreased diet
3. Kidney/liver disease - What are the results of Ricket's?
-
-Decreased Calcium/PO3 in plasma
-Decreased bone mineralization.