Regualtion Of Calcium And Phosphate Flashcards
What are the signs of hypercalcemia?
Decreased QT interval, hyporeflexia, polyuria, poludipsia
What does hypocalcemia do to the membrane potential?
Reduces activation threshold of Na+ channels. These are Ca+ dependent Na+ channels. Ca2+ normally inhibits them.
What does hypercalcemia due to the membrane potential?
Increase activation threshold (more negative), makes it harder to elicit an action potential
What does academia do to free ionized calcium levels?
Increases free ionized calcium concentration due to less Ca2+ bound to albumin
What does alkalemia due to free ionized Ca2+ levels?
Decrease free ionized Ca2+.
What three hormones regulate Ca2+?
PTH, Calcitonin, Vit. D,
What is the relationship between Phosphate and Calcium concentrations?
Inverse.
Increase in extracellular Ca2+ concentration inhibits PTH release via what molecular sensor?
CaSR. Inhibits PTH gene expression and PTH exocytosis.
What are the actions of PTH?
Increase serum calcium and decrease serum phosphate.
What are the actions of PTH on bone, kidney, and intestine?
Bone-> incrase resorption
Kidney-> decrease phosphate reabsorption, increase Ca2+ reabsorption, increase urinary cAMP
Intestine-> increase Ca2+ absorption via Vit D.
What is the second messenger for PTH?
CAMP
PTH stimulates what gene expression in response to low calcium concentration?
CYP1-alpha. This increases the activity of 1 alpha-hydroxylase.
what cell type of bone are PTH receptors located on?
Osteoblasts
What are the short term and long term actions of PTH on bone?
Short term-> bone formation via direct action on osteoblast.
Long term-> increase bone resorption via indirect action of osteoclasts mediated by cytokines released from osteoblasts.
Vit D and PTH both have what effect on bone?
Bone resorption.
- but Vit D increases phosphate reabsorption and PTH decreases it*
What is the primary mediator of osteoclast formation?
RANKL ( receptor activator for NF-kappaB ligand)
What is Osteoprotegrin?
Soluble protein produced by osteoblasts, decoy receptor for RANKL. Inhibits RANKL/RANK interaction.
What is the mechanism of action of PTH on the proximal tubule in relation to phosphate?
Decrease uptake by inhibiting the Na+/phosphate cotransporter on the basolateral membrane. This will also cause the increase in cAMP in the urine.
What are the actions of Vit D on the kidney?
Ca2+ and phosphate reabsorption
What is the mechanism of action of Vit D on the intestine for Calcium reabsorption?
- Increase phosphate reabsorption via the Na/ phosphate cotransporter (luminal side).
- Increase Na/ Ca antiporter on the basolateral side.
- Also incrase active transport of Ca on basolateral side.
-Actions are is Calbindin protein
Where does PTH stimulate Ca2+ reabsoprtion in the kidney?
Distal Tubule.
What are the actions of calcitonin on bone and kidney?
- inhibits bone resorption thus decreasing Ca2+ and phosphate levels.
- major stimulus for release in increased serum Ca2+.
What is the effect of estradiol -17beta on Ca2+ and phosphate in the blood?
-stimulates intestinal Ca2+ absorption and renal tubular Ca2+ reabsorption.
What is estrogens effect on osteoblasts and osteoclasts?
-Stimulates osteoblasts survival and osteoclast apoptosis
What are the effects of adrenal glucocorticoids on Ca2+ regulation?
-Promote bone resorption and renal Ca2+ wasting. Also inhibit intestinal Ca2+ absorption.
What are the findings for PTH, Ca2+, Pi, and Vit D levels for Primary hyperparathyroidism?
PTH- high Ca2+- high Pi- low Vit D- high -also increased bone resorption.
What are the levels of PTH, Ca2+, Pi, and Vit D for Secondary hyperparathyroidism (Renal cause and Vit D deficiency)?
Renal: PTH- high Ca2+- low ( due to Ca2+ completing with phospahte) Pi- high Vit D- low Vit D deficiency: PTH-high Ca2+- low Pi- low Vit D- low
What are the levels of PTH, Ca2+, Pi, Vit D in Hypoparathyroidism?
PTH- low
Ca2+- low
Pi- high
Vit D- low
What is the etiology of Albright hereditary osteodystropy?
-Inherited autosomal dominant disorder, Gs for PTH in bone and kidney is defective.
What are the levels of PTH, Ca2+, Pi, Vit D in Albright hereditary osteodystropy?
PTH- high
Ca2+- low
Pi- high
Vit D- low
What is the etiology of Humoral hypercalcemia of malignancy?
PTH-related peptide,produced by a tumor, can bind to the same receptor as PTH and stimulate it.
What are the levels of PTH, Ca2+, Pi, and Vit D in humoral hypercalcemia of malignancy?
PTH- low
Ca2+- high
Pi- low
Vit D- low
What is the etiology of familial hypocalcuiric hypercalcemia?
Autosomal dominant disorder. Mutation that inactivates CaSR and leads to increased release of PTH
What are the levels of serum Ca2+, urine Ca2+, in familial hypocalcuiric hypercalcemia?
Serum calcium- increased
Urine calcium- decreased
What is the cause of Rickets?
- Insufficient amount of Ca2+ and Pi are available to mineralize growing bone.
- Characterized by growth failure and skeletal deformities
What is osteomalacia?
New bone fails to mineralize. Characterized by bending and softening of weight-bearing bones.
What is the deficiency in vitamin D-dependent rickets type 1?
1 alpha- hydroxylase
What is the deficiency in vitamin D-dependent rickets type 2?
Vitamin D receptor.
What are the symptoms of hypocalcemia?
- Hyperflexia, spontaneous twitching, tingling, numbness.
- positive Chvostek sign and trousseau sign
