Calcium and Phosphate Homeostasis Flashcards
Where is most of the body’s Calcium found?
Bones and teeth
What is the biologically active form of Calcium?
Free, ionized
Decreased calcium levels in the plasma
Hypocalcemia
Increased calcium levels in the plasma
Hypercalcemia
What are some signs of hypocalcemia?
Muscle twitching, hyperreflexia, muscle cramps and tingling and numbness
What does hypocalcemia do to the membrane excitability?
It increases membrane excitability (spontaneous APs) by reducing the activation threshold of sodium channels
What are 3 things that can change the calcium concentration in the plasma?
Changes in plasma protein concentration
Changes in anion concentration
Acid-base abnormalities
If there is an increase in plasma protein, what does that do to the calcium concentration?
Increases total Calcium
If there is an increase in an anion (ex. phosphate), what does that do to the calcium concentration?
Decreases ionized Calcium
Alters ionized concentration of calcium by changing fraction of calcium bound to albumin
Acid-base abnormalities
If less calcium is bound to albumin, what does that do to ionized calcium levels in the plasma?
Increases them (acidemia)
If more calcium is bound to albumin, what does that do to ionized calcium levels in the plasma?
Decreases them (Alkalemia)
What are the 3 main hormones that control calcium and phosphate homeostasis?
PTH, Vitamin D and Calcitonin
In order to maintain calcium balance, what must the kidney do?
Excrete the same amount of calcium that the GI tract absorbed
What is the optimal level of calcium in the ECF?
10 mg/ml
Phosphate concentration is _____ related to calcium concentrations
Inversely
Only 50% of calcium is ionized, what is the percentage of phosphate that is ionized?
84%
What cells in the parathyroid synthesize and secrete PTH?
Chief cells
If there is LOW calcium plasma levels, what will be secreted MORE?
PTH
What inhibits PTH synthesis and secretion?
Hypercalcemia
What senses calcium plasma levels?
CaSR receptors
If there is low calcium, PTH will increase. What are its main actions?
Increase bone resorption
Increase Calcium reabsorption from kidneys
Increase Calcium reabsorption from intestines
What type of hormone is Vitamin D?
Steroid hormone
What is the action of Vitamin D on calcium and phosphate concentrations?
INCREASE
How does Vitamin D promote bone mineralization?
Increases CaXPi
What activates 1alpha-hydroxylase to form the active version of Vitamin D?
Low calcium and low phosphate
High PTH
Where is Vitamin D synthesis?
Kidney tubule
What activates CYP1alpha gene?
Increased PTH
What suppresses the CYP1alpha gene using what mechanism?
Increased calcium suppresses it using CaSR
The CYP1alpha gene codes for what?
1alpha-hydroxylase which activates Vitamin D
Short term, what does PTH do to bone?
Bone formation
Long term, what does PTH do to bone?
Bone resorption (degradation)
What helps PTH synergistically stimulate osteoclast activity for bone resorption?
Vitamin D
HOW does PTH increase bone resorption?
Increases RANKL release from osteoblasts and decreases OPG
HOW does Vitamin D increase bone resorption?
Increases RANKL
Osteoblasts release RankL, how does that result in bone resorption?
It binds RANK receptors on osteoclasts and activates them
Where are PTH receptors located for bone remodeling?
On osteoBlasts
What activates the thyroid gland to release calcitonin?
Increased Calcium levels
What does Calcitonin do?
Stimulates bone formation and decreases the reuptake of calcium in the kidney
For bone formation, where are calcitonin receptors?
On osteoClasts to reduce their activity
Increased PTH which results in increased Ca
- stones, bones and groans
Primary hyperparathyroidism
Primary hyperparathyroidism
Increased PTH, Ca, Vitamin D
Decreased Pi
Decreased Ca which causes an increased PTH
Secondary hyperparathyroidism
Secondary hyperparathyroidism
Increased PTH
Decreased Ca, Vitamin D
Decreased PTH which causes decreased calcium
Hypoparathyroidism
Hypoparathyroidism
Decreased PTH, Ca, Vitamin D
Increased Pi
Autosomal dominant disorder that causes PTH resistance
- short, short neck, obese, short fingers
Albright hereditary osteodystrophy
Albright hereditary osteodystropy
Increased PTH, Pi
Decreased Ca, Vitamin D
Tumors that produce PTHrP that will bind the same receptor as PTH
Humerol hypercalcemia of malignancy
Humerol hypercalcemia of malignancy
Increased PTHrP, Ca
Decreased PTH, Pi, vitamin D
Autosomal dominant disorder that causes mutations in CaSR in the parathyroid glands and kidney
Familial hypocalciuric hypercalcemia (FHH)
Familial hypocalciuric hypercalcemia
Increased serum calcium
Decreased urine calcium
Vitamin D deficiency disorders?
Rickets and Osteomalacia
Growth failure and skeletal deformities in children
Rickets - vitamin D deficiency
Bone tenderness, fracture, bending and softening in adults
Osteomalacia
Type 1 rickets is due to?
Decreased 1alpha-hydroxylase