05a: Calcium and Parathyroid Flashcards
List the three hormones primarily involved in Ca metabolism regulation
- PTH
- 1,25-DHCC (Dihydroxycholecalciferol)
- Calcitonin
T/F: 1,25-DHCC is a steroid hormone.
True
1,25-DHCC is derived from (X) that primarily functions to (increase/decrease):
X = vitamin D
Increase;
Ca absorption from intestine
A (high/low) Ca concentration increases (X) cell excitability. This leads to the condition (Y) tetany.
Low;
X = nerve and muscle
Y = hypocalcemic
A (high/low) Ca concentration can cause cardiac arrhythmia and (over-excites/depresses) neuromuscular excitability
High;
Depresses
(X)% of Ca is in the skeleton. Normal plasma calcium concentration is:
X = 99
10 mg/dL
(X)%, of plasma Ca is bound to plasma proteins. The rest is ultrafiltrable, which means it’s either (Y) or (Z).
X = 40 Y = complexed with anions (PO4) Z = free, ionized
T/F: Ca that’s complexed with anions (such as PO4) is the biologically active form.
False - free, ionized Ca is
T/F: Person taking in 1.0 g Ca means that 0.9 g of it will be absorbed by gut.
False - only 0.5 g
T/F: Person taking in 1.0 g Ca means that net gain is about 0.2 g.
True - 0.175 g
Net gain of Ca in body is offset by (gain/loss) of (X) in (Y) organ/system. This maintains Ca balance.
(Equal) loss;
X = Ca
Y = kidney
List the main sites of important Ca regulation.
- Bones
- Kidney
- GI
T/F: Most of the Ca in bones is in a rapidly exchangeable pool.
False - only 500 of 25,000 mmol are
(X)% of Ca is reabosrbed in kidney.
X = 98
Ca reabsorption in GI tract is via (X) channel/transporter/ATPas.
X = Ca-dependent ATPase
Bone is a(n) (X) matrix, impregnated with (Y).
X = collagenous Y = hydroxyapatites (Ca phosphates)
Bone is both (cellular/acellular) and (well/poorly)-vascularized.
Cellular; well-vascularized
The outer layer of (X) bone is (more/less) metabolically active than the inner layer of (Y) bone.
X = compact
Less
Y = spongy/trabecular
(X) cells form bone by secreting (Y).
X = osteoblasts Y = collagen
(X) cells are surrounded by bone matrix and send long processes that ramify throughout bone. They formed from (Y) cells.
X = osteocytes; Y = osteoblasts (differentiation)
The “bone membrane” separates (X) and (Y) compartments.
X = mineralized bone matrix Y = ECF (and rest of body)
Bone membrane: what are the components?
- Endosteum
- Periosteum
- Osteocytes
Bone resorption is carried out by (X) cells, derived from (Y) cells.
X = osteoclasts Y = monocyte precursors
Osteoclasts secrete (X) that dissolve (Y) from underlying bone.
X = acids and proteases Y = mineral crystals and protein matrix
T/F: Osteoclasts and osteoblasts continually communicate with each other via endocrine factors/hormones.
False - paracrine factors
Bone: The cytoplasmic processes of (X) cells extend deep into bone and connect to those of (Y) cells via (gap/tight) junctions.
X = osteoblasts; Y = osteocytes
Gap
UV light acts on (X) compound in skin to produce vitamin D3. Where is vitamin D3 taken?
X = 7-dehydrocholesterol
Liver
Vit D synthesis: liver modifies vitamin D3 via (X), forming (Y).
X = hydroxylation Y = 25OH-D3
The major biologically active form of vitamin D is (X). The final step in its formation occurs in (Y).
X = 1,25-(OH)2-D3 Y = kidney (proximal tubule)
Vit D synthesis: Instead of (X) modification, the kidney could modify 25OH-D3 via (Y), to promote degradation.
X = hydroxylation at 1-position Y = hydroxylation at 24-position
List the overall, general goals/functions of 1,25-(OH)2-D3.
Provide Ca and phosphate to ECF for bone mineralization
Vit D deficiency in children causes (X), and in adults causes (Y).
X = rickets Y = osteomalacia
1,25-(OH)2-D3 acts primarily by binding (X) receptor, which (increases/decreases) production of (Y).
X = nuclear (VDR, Vitamin D Receptor)
Increases;
Y = CaBP; and Ca and P transporters
T/F: Vitamin D Receptor is only present in Ca-regulating tissues.
False - wide variety of other tissues as well
One method in treating psoriasis uses the mechanism of 1,25-(OH)2-D3 (stimulation/inhibition) of (X) process in cells containing (Y).
Inhibition
X = cell proliferation
Y = VDR
1,25-(OH)2-D3 (increases/decreases) Ca absorption in GI tract by inducing (increase/decrease):
Increases; Increase; 1. ECaC (epithelial channels) 2. Calbindin 3. Ca/Na exchangers; Ca pumps
T/F: 1,25-(OH)2-D3 directly promotes Ca deposition in bone.
False - acts indirectly by increasing plasma Ca and P absorption (their supersaturating levels will promote mineralization)
T/F: 1,25-(OH)2-D3 acts indirectly to promote osteoclastic activity and bone resorption.
True
1,25-(OH)2-D3 acts in synergy with (X), either one being far less effective in (Y) function in absence of the other.
X = PTH Y = mobilizing Ca stores
1,25-(OH)2-D3 acts on proximal nephron to (increase/decrease) (X).
Increase;
X = Na-dependent phosphate transporter (thus, increases phosphate reuptake)
1,25-(OH)2-D3 acts on distal nephron to (increase/decrease) (X).
Increase;
X = ECaC and Calbindin (thus, Ca reabsorption)
High plasma concentrations of (X) inhibit 1,25-(OH)2-D3 synthesis (neg-feedback). Specifically, they inhibit (Y).
X = Ca and P; and 1,25-(OH)2-D3 Y = 1a-hydroxylase
Synthesis of 1a-hydroxylase enzyme is prompted by (high/low) levels of PTH and (high/low) levels of P.
High; low
1,25-(OH)2-D3 feedback/regulation: (X) stimulates (Y) enzyme to produce (Z), leading to degradative pathway.
X = 1,25-(OH)2-D3 Y = 24-hydroxylase Z = 24,25-(OH)2-D3
(X) cells in the parathyroid make PTH. The hormone is synthesized as (Y) and undergoes (Z) modification to become “mature” PTH.
X = chief/principal Y = pre-pro-hormone Z = cleavage
T/F: Half-life of intact PTH is about 30 min.
False - 5 min
T/F: PTH is rapidly cleaved/degraded in peripheral tissues.
False - in Kupfer cells in liver
Primary signal that stimulates PTH secretion is (X).
X = low circulating Ca levels
Ca Sensing Receptor (CaSR) is found in (X) cells. It functions to:
X = parathyroid chief
Monitor extracellular Ca levels
By default, PTH is (secreted/stored) in/from (X) cells until (Y).
Secreted;
X = chief
Y = high Ca levels bind CaSR, which activates pathway to inhibit PTH secretion
T/F: Like 1,25-(OH)2-D3, PTH acts to increase serum Ca and PO4.
False - increase serum Ca, but decrease serum PO4
PTH acts by activating (X) receptor, leading to (production/cleavage) of (Y).
X = G-protein
Production
X = cAMP and IP3
List the 5 general actions of PTH.
- Increase bone resoprtion/Ca mobilization
- Increase Ca reabsorption (kidney)
- Decrease plasma PO4
- Increase 1,25-(OH)2-D3 production
- Increase osteoclast and osteoblast formation
PTH will (increase/decrease) serum PO4 via which mechanism?
Decrease;
Increase urine PO4 excretion (decreases proximal tubule reabsorption)
T/F: PTH acts directly on intestine to increase Ca reabsorption.
False - indirect by stimulating 1,25-(OH)2-D3 formation
Bone: (X) compounds stimulate the expression of RANKL on surface of (Y) cells. This interacts with (Z).
X = PTH and 1,25-(OH)2-D3 Y = osteoblasts Z = RANK (receptor) on (pre)osteoclasts
T/F: Increasing RANKL expression on osteoblasts will decrease bone resorption.
False - RANKL activates osteoclasts (via binding RANK receptor)
(X) hormones are important regulators of bone resorption. They enhance (Y) production, which acts as decoy by binding/blocking (RANK/RANKL).
X = estrogens Y = Osteoprotegerin (OPG)
RANKL (prevents RANK activation)
T/F: PTH has a short-term anabolic effect, by increasing osteoblast activity.
True (but limited)
Pulsatile injections of (X) is used clinically to treat osteoporosis. The pulsatile nature functions to sidestep (Y).
X = PTH Y = osteoblast apoptosis (via prolonged PTH stimulation)
Specific action of PTH on proximal nephron: (increase/decrease) (X) activity, which (increases/decreases) (Y) formation and excretion.
Increase;
X = AC
Increases;
Y = cAMP (thus, phosphate)
(High/low) urinary levels of (X) is often used as an index of excess PTH secretion.
High;
X = cAMP
Severe (increases/decreases) in Mg levels inhibit PTH production.
Both!
PTH regulation: (X) acts directly on parathyroid to decrease PTH secretion.
X = Ca
PTH regulation: (X) acts directly on parathyroid to decrease PTH precursor production.
X = 1,25-(OH)2-D3
Chronic kidney disease likely leads to (hyper/hypo)-parathyroidism. Why?
Hyperparathyroidism (due to low 1,25-(OH)2-D3 formation and low Ca reabsorption)
Parathyroidectomy will lead to (increase/decrease) in plasma concentrations of (X).
Increase (X = PO4); Decrease (X = Ca)
T/F: PTH is essential for life.
True
You’d expect to see Ca-containing stones in PTH (deficiency/excess).
Excess
PTH-related peptide (PTHrP) is found in plasma of some patients. What are its actions? Serum PTH levels would (increase/decrease) in presence PTHrP.
All same physiological actions of PTH;
Decrease (result of hypercalcemia)
Calcitonin is produced by (X) cells in presence of (high/low) levels of (Y).
X = parafollicular cells (in thyroid)
High;
Y = Ca
Calcitonin (increases/decreases) Ca permeability in osteoclasts/osteoblasts, thus (increasing/decreasing) plasma Ca and PO4.
Decreases;
decreasing
The biological activity of PTH is dictated mainly by the (X) portion of the molecule.
X = N-terminal
The main circulating form of vitamin D3 is (X). And most is (bound/unbound).
X = 25-hydroxyvitamin D3
Bound (to Vit DBP)
T/F: High PTH levels may lead to osteomalacia.
False - PTH stimulates 1a-hydroxylase
High plasma FGF23 would (stimulate/inhibit) 1a-hydroxylase and (increases/decreases) chance of osteomalacia.
Inhibit;
increases
