Unit 6 - PTH, Ca Regulation, and Bone Flashcards Preview

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Flashcards in Unit 6 - PTH, Ca Regulation, and Bone Deck (46)
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1

what is the total Ca in body and the components?

1 kg in body
-99% in skeleton
-1% (10 g) in ECF and muscles)
--0.1% (1 g) in plasma, and half is ionized

2

what form of Ca is tightly regulated?

ionized Ca

3

what happens to Ca measurements if albumin is higher than normal?

total Ca++ may be high and false positive for hypercalcemia
-ionized portion may be normal
-correction factors are applied if this is the case

4

what happens to albumin under acidic conditions? alkalemia?

albumin in plasma binds less Ca++, causing a true increase in ionized Ca
-if alkalemia, then albumin binds more, and true decrease in ionized Ca

5

what is familial hypercalcemic hypocalcuria?

FHH; [Ca++] is normally high, without any symptoms
-genetic defect in Ca sensors causes increased Ca reabsorption
-urine Ca++ is low, and the PTH secretion curve is normal (it just shifts over to the right)

6

what are symptoms if there is high Ca (>12 mg/dL) for
-general
-neuro
-cardiac
-renal

-fatigue, apathy, anorexia, delirum, coma
-headache, ICP, muscle weakness; high Ca increases membrane polarization and decreased neural responses
-bradycardia, short Q-T interval
-polydipsia, polyuria, HTN, calculi

7

what are symptoms if there is low Ca (<7 mg/dL) for
-general
-neuro
-cardiac
-skeletal

-learning regardation, apnea (children)
-tetany; low Ca reduces membrane polarization and increases hypersensitivity
-long Q-T interval, decreased CO
-Ca/PO4 deficiency causes rickets or osteomalacia

8

how much of ingested daily Ca is excreted into feces?

over 80%

9

what role does the kidney have in Ca?

enormous role in filtering 10x the average daily intake, and recapturing all but 175 mg

10

what 3 systems are most important in regulating Ca balance? what amount do they take care of?

-intestines (absorb 500 mg/day, secrete 325 mg/day to feces)
-renal tubules (filter 10,000 mg/day, reabsorb 9825 mg/day, excrete 175 mg/day in urine)
-skeleton (constant turnover between formation and resorption of about 280 mg/day)

11

what role does the bone have in Ca?

repository and buffer of Ca
-active, with daily turnover of 280 mg/day

12

what happens if dietary intake of Ca, or absorption, is poor? in the long run?

kidneys increase reabsorption of filtered Ca
-in long run, if kidneys don't work well, the bone reservoir increases resorption, causing net loss of bone mass and density

13

what are the 2 targets for PTH? what does it do?

1. kidney (rapid)
-increase reabsorption of Ca in distal tubule
-increase 1,25-(OH)2-D3 (active form) synthesis
-decrease PO4 reabsorption in proximal tubule

2. bone cells (slow)
-increase osteoclastic resorption via osteoblast receptors to increase Ca and PO4 in ECF and plasma
-increase osteocytic osteolysis (rapid; in osteocytes)

14

what happens to osteoblasts when PTH is present?

osteoblasts secrete paracrine RANK-L
-when in contact with monocyte lineage cells, causes maturation into multi-nucleated osteoclasts that resorb bone on its surfaces
-release more Ca, PO4

15

what happens to Ca and where in the kidney tubules when PTH activates it?

1. only 9% is actually controlled by PTH concentration, in distal convoluted tubule (increases active transport of Ca reabsorption)
2. 30% is passive diffusion in loop of Henle
3. 60% is active transport in proximal tubule

16

what is the effect of PTH on PO4 in kidney tubules?

reabsorption is reduced when plasma PTH increase, and vice versa
-this reduces serum PO4 (although there is increased bone resorption of PO4 too)

17

how does vit D help in Ca transport in kidney?

increases calbindin/Ca++ transport and efflux at basal side of distal convoluted tubule

18

what are the 4 targets of vitamin D?

1. intestine (Ca++ and PO4 absorption increases)
2. bone (stimulates osteoclastic resorption via receptors on osteoblasts to increase Ca++ and PO4 released into ESF and plasma
3. parathyroid gland (decrease PTH secretion for negative feedback)
4. distal tubule of kidney (increases Ca and PO4 reabsorption

19

what does calcitriol do to the intestines?

increases active and passive transport of Ca and PO4 into blood by increasing synthesis of calbindin transporter

20

is increased PO4 in plasma good or bad?

it's undesirable, so when PTH and vit D increase absorption in intestines, and vit D increases it in distal tubules, PTH will decrease reabsorption in distal tubules

21

what happens in primary hyperparathyroidism? treatment?

adenoma in parathyroid gland secretes excess PTH, causing kidneys to increase Ca reabosption, increase serum Ca++, and excrete PO4
-increases alkaline phosphatase (marker for high bone turnover)
-increases urinary Ca excretion (b/c chronically high serum Ca eventually increases Ca excretion)
-treated by removing nodule, and leaving behind 3 normal ones
("stones, bones, and groans")

22

what happens in secondary hyperparathyroidism?

hypocalcemia is primary
-low vit D, renal failure, diet problems)
-renal osteo dystrophy

23

what happens in humoral hypercalcemia if malignancy?

hypercalcemia b/c PTH-rp mimics natural PTH (although real PTH is low b/c inhibited by hypercalcemia)
-high alkaline phosphatase b/c more bone turnover
-will have normal serum albumin (b/c Ca is ionized and unbound)

24

what happens in hypoparathyroidism?

hypocalcemia, due to surgical damage to parathyroid gland or genetics
-low PTH

25

what happens in pseudohypoparathyroidism?

hypocalcemia due to genetic defect in G-PRO in PTH receptor in kidney
-so high PTH, but just can't exert effect

26

what happens to PO4 in chronic kidney failure?

PO4 excretion is reduced, and hyperphosphatemia results

27

how much Pi is in the body?

2.5-4.5 mg/dL, as 1/3rd of total
-10-20% of Pi is protein bound, and not very rigidly maintained (30% diurnal variations)

28

how are collagen matrix made and mineralized?

pre-collagen triple-helix molecules (tropocollagen) are made by the osteoblast, then polymerized extracellularly to make fibrils and "osteoid matrix" that eventually mineralizes into lateral binding pattern

29

what is the "osteoid" area of bone? what is it used for?

between layer of osteoblasts and mineralizing matrix
-thickness of "not-yet mineralized" collagen is measure of state of health of skeleton, and availability of Ca and PO4

30

what do osteoblasts do signal-wise?

does most of the signaling in bone
-have receptors for PTH, vit D, estrogen, and many paracrine and growth factors
-signal osteoclasts to mature and activate to resorb bone

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