Endocrine - Bone, Ca, & Hormones - COX Flashcards
What three forms does plasma calcium exist in? What is the main form? What is the biologically active form?
Complexed with organic compounds
Protein bound - most common
Ionized - biologically active form
What symptoms are seen with low Ca levels? High Ca levels?
Low Ca - excitability of cells - titanic convulsions
High Ca - death due to muscle paralysis and coma
What three hormones regulate plasma calcium levels? Which two have a major role? Which has a minor role?
PTH & Vit. D - major role
Calcitonin - minor role
Where is PTH produced? Is it a protein or steroid hormone?
Produced by chief cells in parathyroid gland
Peptide hormone
What portion of PTH contains the biological activity of the hormone? What region is primarily responsible for receptor binding?
N-terminal
Region 25-34
What form of PTH is synthesized? Where is it processed? Is it stored?
Synthesized as preproPTH
Processing in ER and golgi
Stored in secretory vesicles
What are the three fates of PTH once it is put into secretory vesicles?
Transportation into storage
Degradation
Immediate Secretion
How do low plasma Ca+2 levels affect PTH?
Increased PTH synthesis by increasing size and number of chief cells
How does Vit D play a role in regulating PTH expression?
PTH gene contains several vit. D response elements (VDRE)
When vit D is bound to there, PTH expression is decreased
How do chief cells of the parathyroid gland know where to make PTH or not?
By detecting plasma Ca
What type of calcium receptor is on the parathyroid chief cells? How does signaling differ when Ca is bound vs when Ca is not bound?
Ca bound (high plasma Ca) - stimulates phospholipase C which increases IP3, inhibiting adenylate cyclase, decrease cAMP - PTH release REDUCED Ca not bound (low plasma Ca) - Decreasing IP3 production, which increases CAMP - PTH release INCREASED
How is PTH secretion related to calcium concentration?
Inversely proportional
Is PTH secretion ever fully suppressed?
No, some PTH is always being released
What ionized Ca concentration must be reached to achieve maximal rate of PTH secretion? What is the typical set-point?
1.1 mmol/L
Set-point - 1.3 mmol/L
How long can maximal PTH secretion be sustained for? What?
1.5 hours
Parathyroid glands have very fer storage granules
What three ways for PTH act on the system to increase Ca+2 concentration? Which is most rapid? Which has largest effect/impact?
Reduce renal excretion - most rapid
Increase intestinal reabsorption
Increase rate of bone dissolution - largest effect
In a prolonged dietary deficiency of Ca2+, what gets sacrificed?
Bone (bone density)
Besides having a direct effect on production of osteoclasts, what other cell does PTH and vit. D act on to increase osteoclast activity? Through what?
Osteoblasts
They increase OAF (osteoclast activating factors) which stimulates osteoclast activity
What is the counter-ion to Ca?
Phosphate
How does PTH affect plasma phosphate levels? How?
Increases renal clearance of phosphate
What are mild symptoms of hypoparathyroidism? Severe symptoms?
Mild - muscle cramps and tetany
Severe - muscle paralysis, convulsions, and death
What are the two usualy, yet rare, causes of hypoparathyroidism?
Autoimmune
Accidental removal during surgery
What is pseudohypoparathyroidism? Where does the problem occur? What are 4 phsyical findings seen?
PTH is produced but receptor defect leads to low Ca and high PO4 levels
Short stature, Mental retardation, short metatarsals, short tarsals
What is the most common cause of primary hyperparathyroidism? What is seen on blood work? What are symptoms?
Parathyroid ademona
Elevated Ca and PTH, decreased PO4
Kidney stones, nephrocalcinosis, frequent UTIs, decrease renal function
What is the most common cause of secondary hyperparthyroidism? Why?
Progressive renal failure
Lack of renal vitamin D synthesis leads to hyperplasia and hypersecretion of PTH
In the skin exposed to sunlight, 7-dehydrocholesterol is converted to what?
Vit D3
What binds vit. D3, moving it from skin/intestine into blood stream?
Vitamin D-binding proteins
What is the major form of vitamin D in the blood? Where is it converted to active form? By what? What else is need?
25(OH)-D3 major form in blood
Converted to 1,25(OH)2-D3 in kidney by 1alpha-hydroxylase
Require: NADPH, MG2+, oxygen
High levels of 1,25(OH)2-D3 inhibit what? Increase activity of what? Producing what?
Inhibit 1 alpha-hydroxylase
Increase activity of 24-hydroxylase
Produces inactive 24,25(OH)2-D3
What hormone receptor family is 1,25(OH)2-D3 receptor a member of?
Steroid receptor family
What DNA bind-domain does 1,25(OH)2-D3 have?
Zinc Finger
What is seen in Rickets (non-genetic)? Cause?
Low plasma calcium and PO4, high bone demineralization due to vit. D deficiency Poor nutrition (low vit D)
What are the two types of genetic Rickets? Differentiate them
Type I - defect in conversion of 25(Oh)-D3 to 1,25(OH2)-D3 due to mutation of 1 alpha-hydroxylase problem
Type II - autosomal recessive due to single amino acid change in zinc finger, creating non-function vit. D receptor
What is vit. D deficiency in adults called?
Osteomalacia
What are two causes of osteomalacia?
Decreased Vit D intake
Loss of renal parenchyma - leading to increased PTH, increase bone reabsorption
What are symptoms of loss of renal parenchyma in osteomalacia known as? What is the treatment?
Renal osteodystrophy
Treat with vit. D
What is calcintonin secreted from?
Parafollicular cells of thyroid gland
What activity does calcitonin suppress?
Osteoclast activity suppressed, promoting renal excretion of Ca and Phosphate
