Phys of Ca-Regulating Hormones (Fan) Flashcards
physiologic roles of Ca
Bonne growth/remodeling Secretion (excitation coupled) Contraction Action Potentials Cofactors for Enzymes Secondary messangers
What age does out total body calcium peak? Significance?
25; risk of osteoporosis increases with age
Describe the distribution of Ca in the body
99% in bone
1& Intracellular
.1% extracell (inc plasma)
Describe the distribution of Ca in the blood
Free > proteins bound»_space; anion bound
What is the normal mM/L for Ca in the blood
10 mg/dl or 2.5 mM/L
hypocalcemia is defined as …
hypercalcemia is defined as …
10/5 mg/dl
When ECF [Ca++] falls below normal, the nervous system becomes (less or more excitable)
How far below normal does Ca have to fall for this to happen
more
<50% of nml
What happens when [Ca++] falls below 50% of nml
muscle spontaneously discharge impulses → tetanic muscle contraction
TETANY
WHat effect does severe hypocalcemia have on cardiac muscle?
long QT and arrhythmias
How is Ca excreted
feces»_space; urine
*but kidneys do have a large capacity to excrete urine by reducing tubular reabs (55% filtered and ~90% reabs)
PTH is secreted by …
chief cells of the parathyroid gland
WHat produces calcitonin
C cells in thyroid gland
structual diff of PTH and calcitonin
PTH = 84 aa and Calcitonin = 32 aa
PTH (↓ or ↑) Ca in blood by…
↑ Ca by …
↑ release from bone
↑ reabs/↓secretion from kidney
PTH (↓ or ↑) PO4 in blood by…
↓PO4 by ↑excretion/↓reabs via kidneys
How long after PTH infusion will Ca/PO4 levels change
immediately
Describe how PTH effects Ca and PO4 is exchange between the bone fluid and ECF
- ↑formation and activity of ostoclast →↑bone reabs → ↑Ca and ↑PO4 released into bone fluid
- ↑ activity of Ca pump on osteocyte and blast membranes and ↑ permeability of their membranes → movement of Ca from bone fluid into ECF
Describe the effect of PTH on osteoclasts
PTH bind PTHR1 on osteoblasts → ↑RANKL and ↓OPG on osteoblasts → RANKL bind RANK in osteoclast precursor → activation of osteoclasts gene trcpt and diff → mature osteoclast → ↑bone reabs → ↑Ca in plasma
OPG is secreted by ____ and its effect is to _____
secreted by osteoblasts to inhibit osteoclast formation/bone reabsoption
effect of PTH on OPG production
↓
What stimulates OPG production
estrogen
effect of LOW dose PTH on osteoclasrs
↑ osteoblast prolif/differentiation and ↓ apoptosis of osteoblasts → ↑bone formation
(via PTHR on osteoblasts)
Describe effect of PTH on renal kidney
inc reabs of Ca by 10-15% → 99% of Ca that is filtered is reabsorbed and only 1% is excreted
How much Ca is filtered at the glomerulus? Why is some not freely filtered?
55% bc the other 40% is bound to plasma proteins and is not filterable
T or F: it take a big inc or dec in Ca levels to see an response in PTH or calcitonin levels
F: small change!!!
Changes in ECF [Ca] are sensed by…
GPCR on parathyroid chief cells to ↑or↑ PTH secretion
↑Ca are sensed by Ca sensing receptor
↓Ca are sensed by Relaxed Ca sensor
Effect of ↑PTH on vit D
PTH is needed to convert 25-vit D to 1,25-vit D
Calcitonin ↑ or ↓ Ca levels? PO4 levels?
How
↓Ca and ↓PO4
inhibit osteoclasts → ↓bone reabs
inhibits reabs of Ca in kidney
Function of Calcitonin
protects against Ca loss from skeleton during periods of Ca mobilization (pregnancy, lactation, being a child)
Calcitonin is used pharmacologically to treat
osteoporosis
Describe Vit D synthesis
Cholecalciferol (UV rxn) or Ergocalciferol (diet) go to liver → liver makes 25(OH)vitD → kidney converts it to 1,25(OH)2vitD (if PTH is there/low Ca)
Describe the effects of vit D in the body
↑ Ca absorption in GI
↓ Ca reabs in kidney
↑ bone resorption
↓ PTH synthesis (feedback)
Where does the control of vit D synthesis occur? Explain
kidney:
- if high Ca, 24alpha-hydroxylase is active and converts 25(OH)vitD to inactive 24,25(OH2)vitD
- also active by 1,25vitD (feedback), FGF23
-if Ca low + PTH, 1alpha-hydroxylase is active and converts 25(OH)vitD to 1, 25(OH)2vitD
______ in skin is converted to Cholecalciferol via UV light
7-dehydrocholesterol (provitamin D)
A slight dec in [Ca] below normal, causes increased formation of _____
1,25(OH2)D
complex precipitate of Ca and PO4
hydroxyapatite
What determines whether Ca or PO4 are laid down or resorbed from bone?
product of their concentrations
NOT on their individual concs*
Ca x PO4 > solubility product →
bone deposition
Ca x PO4 < solubility product →
bone reaorption
inc in Ca or PO4 in the ECF would …
inc bone mineralization/deposition
normal levels of PO4 in blood
4 mg/dl or 1.3 mM
levels of PO4 in children are (lower or higher). why?>
higher, due to active bone growth!!
Describe the distribution of PO4 in the body
Bone (85%) > ICF (14%) > ECF <(0.1%)
Describe the distribution of PO4 in the blood
Free (55%) > CATION bound (35%) > PROTEIN bound (10%)
**the ppt slide was wrong!!
How is PO4 excreted
Urine > feces
*kidney clearance more imp for maintaining PO4 balance
Describe the changes in PO4 metabolism with renal failure
↓renal Cx → ↑ Sr PO4 (→ ↑bone mineralization → ↓Ca → ↑PTH → ↑ VitD ??) → ↑bone resorption
+ deposition of Ca in vasculature
FGF23 is produced in ____
bone
FGF 23 is secreted into blood in response to …
↑PO4
↑ Vit D
↑ PTH
FGF23 acts in kidneys to…
↓ expression of Na-PO4 co-transporter (↓reabs) and dec vitD synthesis
→ ↓PO4 (→ ↑bone resorption and ↑Ca)
