Calcium and Phosphate Flashcards
Calcium and phosphate levels are regulated by PTH and vitamin D via interaction of what 3 target organs?
Bone, intestine, kidney
What type of cells in the parathyroid gland release PTH after stimulation by low serum calcium?
Chief cells
Cushingnoid syndromes and glucocorticoid therapy lead to an increase or decrease in PTH secretion?
Increase
Increased plasma calcium has a negative feedback loop leading to a decrease in Ca and PO4 via what 2 things?
Calcitonin release Inhibition of bone resorption and tubular resorption
Does excess calcitonin produce hypocalcemia?
No
Does a deficiency in calcitonin lead to dramatic hypercalcemia?
No
Once the inactive form of vitamin D enters the body from the diet/ skin, it undergoes 2 steps of activation. Where in the body do these steps occur and what happens?
1st activation: addition of OH to carbon 25 in liver 2nd activation: addition of OH to carbon 1 in kidney
What is the active form of vitamin D?
1,25- dihydroxycholecalciferol
How does vitamin D act with PTH in the bones, leading to resorption, remodeling, and mobilization of calcium and phosphate?
Synergistic
Vitamin D promotes calcium and phosphate reabsorption in what parts of the kidney?
Calcium in DCT Phosphate in PCT
Vitamin D increases calcium absorption by the small intestine by increasing expression of what molecule?
Calbindin (Calcium crosses apical membrane via diffusion then binds to calbindin to be pumped across basolateral membrane by Ca-ATPase)
What does chronic vitamin D intake lead to?
Decreased PTH secretion
Where is the majority of calcium held?
99% in crystalline form in teeth and bone (Of remaining 1%- 0.9% in soft tissue and 0.1% in ECF) (Half of portion in ECF is in ionized active form)
What is meant by the fact that calcium is in equilibrium with the bone pool?
Amount removed from ECF for bone formation = amount returned to ECF by bone resorption (This favors bone remodeling)
Any amount of calcium absorbed by the GI tract must also be what?
Excreted via stool/ urine
What is necessary for metabolic pathways of fuel provision, high energy trasfer/ storage, cofactors, and 2nd messengers?
Phosphate
Muscle weakness, cardiac/ respiratory arrest, and loss of RBC integrity results from what?
Phosphate depletion
How is phosphate distributed within the body?
85% in bones/ teeth, 15% in muscles
(Within cells > 80% in mitochondria)
(Excretion via kidney/ urine > feces)
What area of bone are the following things located?
Stable pool?
Labile pool?
Osteocytic-osteoblastic bone membrane?
Stable pool- mineralized bone (superficial layer)
Labile pool- bone fluid
Osteocytic-osteoblastic bone membrane- canaliculi
What property of the osteocytic-osteoblastic bone membrane allows for a large influx of Ca between bone fluid and plasma even with a small net movement of Ca?
Large SA
How does the stable Ca pool contribute to Ca and PO4 release into ECF?
Resorption = PTH induced slow breakdown of bone crystal
How does the labile Ca pool contribute to Ca and PO4 release into ECF?
Osteolytic osteolysis = fast release into ECF
What hormone contributes to osteoblast regulation of osteoclast function to increase plasma Ca/ PO4?
PTH
PTH contributes to increased Ca and PO4 in the blood first by recruitment and differentiation of what type of cells?
Stromal cells within stable pool of Ca
What do stromal cells differentiate into?
Osteoblasts via Runx2 (transcription factor)
Once differentiated osteoblasts are targeted by PTH, what 3 things are releaed?
Monocyte colony stimulaing factor
RANKL
OPG
What is the role of monocyte colony factor?
Preosteoclast differentiation
What contributes to the clustering and fusion of preosteoclasts to then form a mature osteoclast?
RANKL
(Mature osteoclasts then settle on resorption cavity of bone)
What is the role of OPG in PTH stimulation of increased plasma Ca/ PO4?
Binds to RANK on osteoclasts = bone breakdown (via HCL/ hydrolytic enzymes) = release of Ca and PO4 into blood
How does PTH affects the kidney by inhibiting PO4 reabsorption and contributing to the phosphaturic effect?
Elimination of PO4 via cAMP
How does PTH affect the kidney with respect to activation of vitamin D?
Stimulates 1-alpha-hydroylase
What disease is defined a mutation in transcription factor Runx2 that leads to abnormal bone formation (clavicles, fontanels, teeth)?
Cleidocranial dysplasia
“Stones, bones and groans” and complications of osteoporosis, osteomalacia, kidney stones, muscle weakness, and decreased muscle excitability is indicative of what disease?
Primary hyperparathyroidism (PTH secreting adenoma)
What disease is typically a consequence of thyroid surgery (ex. tx of cancer or Grave’s)?
Hypoparathyroidism
Complications caused by hypocalcemia and leading to tetany, hyperreflexia, spontaneous twitching, muscle cramps, and convulsions are indicative of what disease?
Hypoparathyroidism
What disease is described as malignant cells in the breast and lung which secrete PTH related peptide (PTH-rp) that binds to the PTH receptor and has similar actions as PTH?
Humoral hypercalcemia of malignancy
Albright’s hereditary osteodystrophy is aka?
Pseudohypoparathyroidism
Pseudohypoparathyroidism is an autosomal disorder with defective what?
Gs in kidney and bone
Pt who is short, obese, has a short neck, and shortened 4th metatarsals and metacarpals likely has what condition?
Pseudohypoparathyroidism
A vitamin D deficiency in children vs adults presents as what?
Children = Rickets
Adults = osteomalacia
In Rickets disease, there is insufficient vitamin D, Ca, and PO4 to mineralize growing bone. What effect will this have on growth?
Growth failure and skeletal abnormalities
Why do you see hypocalcemia in Rickets disease?
Decreased Ca and PO4 absorption in gut (secondary to vit D deficiency)
Will a pt with Rickets have elevated or low levels of PTH?
Elevated
Complications of tetany, muscle weakness, and greenstick fractures are indicative of what condition?
Rickets
What are the causes of hypocalcemic tetany and hypocalcemia seen with osteomalacia? (4)
Dietary deficiency, intestinal surgery, malabsorption, renal failure
(malabsorption can be caused by malabsorption syndrome or Celiac disease)
Complications of softened/ weakened bones and frequent fractures are indicative of what condition?
Osteomalacia