Bone Physiology

Question 1

Total circulating calcium

Answer 1

8.5 to 10.5 mg/dL

50% circulates as free or ionized Ca
45% is bound to albumin.
5% in complexes

** free, ionized calcium is important for physiologic processes or in pathophysiologic settings**

Question 2

➢ If the serum albumin level declines as a result of hepatic cirrhosis or the nephrotic
syndrome, the total serum calcium also declines,

Answer 2

but the ionized serum calcium concentration remains normal.

✓ To correct for protein changes adjusts:
the total serum Ca (in mg/dL) upward by 0.8 times the deficit in serum ALB (g/dL)

Question 3

Intestinal Calcium Absorption

Answer 3

• About 300 mg of the total is absorbed.
• About 150 mg of calcium per day is secreted.
• Thus, net absorption of calcium is approximately 15% of intake.
• 1/The efficiency of calcium absorption is regulated by the active form
of vitamin D, 1,25-di hydroxy vitamin D (1,25[OH]2VitD) .
2/PTH indirectly.

Question 4

• Pathologic increases in serum calcium (i.e., hypercalcemia) can be caused by increases in
circulating 1,25(OH)2VitD ……………. or by excessive calcium intake……………

Answer 4

in sarcoidosis

milk-alkali syndrome

Question 5

Renal calcium handling

Answer 5

The filtered load of calcium by the kidneys is about 10,000 mg per day.
• About 9000 mg (90%) is reabsorbed proximally by
– The proximal convoluted tubule
– The thick ascending limb of Henle loop (Ca Sensing Receptor)
➢ )This 90% is absorbed in conjunction/competition with sodium and chloride reabsorption and is
not subject to regulation by PTH)

• The remaining 10% (1000 mg) that arrives at the distal tubule is subject to
regulation by PTH.
• About 150 mg of calcium is excreted by the kidney in the final urine.
• (98.5%) is reabsorbed at proximal and distal sites

Question 6

Effects of PTH

Answer 6

PTH targets three organs, two directly and one indirectly:-
• The kidney:
– Calcium reabsorption in the distal tubule
– PTH also inhibits phosphate and bicarbonate reabsorption by the proximal
tubules
– PTH also stimulates the production of the active form of vitamin D,
1,25(OH)2D by the renal tubules

• The skeleton:
– PTH can mobilize calcium immediately from the skeleton (rapid)
– It also stimulates the activity of osteoblasts

• The intestine, which PTH affects indirectly.(by vit D)

Question 7

• The absence of PTH effect on kidney :-

Answer 7

produces hypercalciuria and nephrolithiasis in hypoparathyroidism.

Question 8

Sensing biomechanical strain

Answer 8

Osteocytes

Question 9

پايروفوسفات خارج خلوي ،تثبيط ……………كةد ، خوةيشي تشبيط كريةد من قبل ………

Answer 9

تمعدن

ALP

Question 10

Bone resorption stimulated by

Answer 10

RANKL
IL1+6

Question 11

What stimulates osteoblasts

Answer 11

PTH
Vit D
BMPs
IGF
Wnts
Inhibiting sclerostin by PTH

Question 12

Anti bone resorptive agents, such as:-

Answer 12

estrogens
estrogen-like drugs,
bisphosphonates,
RANKL inhibitors.

Question 13

Vit D deficiency causes

Answer 13

Hypocalcemia
Osteomalacia
Rickets
Osteoporosis
Intestinal malabsorption

Question 14

👆Calcium intake leads to

Answer 14

👇PTH ……>👆Wasting Ca from DCT ………>👆Hypercalciuria+nephrolithiasis+nephrocalcinosis

Question 15

may lead to hyperphosphatemia:-

((Intracellular-Extracellular Phosphate Fluxes))

Answer 15

metabolic acidosis
crush injury
tumor lysis syndrome

Question 16

……………shifts phosphate into cells

Answer 16

Glucose

Question 17

FGF23 effects on P
(Sensitive to P concentrations in blood 🩸 )

Answer 17

1/determined by phosphate concentrations, stimulates bone matrix mineralization independently of calcium.
2/ increase its renal excretion
3/suppresses 1,25 vitamin D levels.
4/suppresses PTH.
5/decrease intestinal phosphate absorption indirectly.
6/inhibits erythropoietin-mediated synthesis of RBCs.

Question 18

Causes hypophosphatemia

Answer 18

1/Osteoblastic metastases in prostate and breast cancers

2/hungry bone syndrome after parathyroidectomy

Question 19

Autosomal dominant hypophosphatemic rickets = (ADHR).

Answer 19

Mutation in the o-glycosylation site of FGF23, stabilize and thereby increase its bioactivity.

Question 20

is also the factor responsible for most paraneoplastic hypophosphatemic
syndromes, also referred to as tumor-induced osteomalacia (TIO)

Answer 20

FGF23

Question 21

FGF23 gene expression is stimulated by

Answer 21

1,25(OH)2D
phosphate-regulating neutral endopeptidase
X-linked (PHEX),

gene mutation cause X-linked hypophosphatemia (XLH).

Question 22

deficiency is often unrecognized because its symptoms
are nonspecific: weakness, respirator dependence, diffuse neurologic syndromes
(including seizures), and cardiovascular collapse.

Answer 22

weakness
respirator dependence
diffuse neurologic syndromes including seizures
cardiovascular collapse.

Question 23

• Many instances of magnesium deficiency are caused by ………….

widely available in normal diets and about ………….of what is ingested is absorbed

Answer 23

Excessive renal losses

one third

Question 24

Milk-Alkali syndrome

Answer 24

Ingestion of very large quantities of calcium carbonate or other calcium-containing
antacids
• Triad of hypercalcemia, metabolic alkalosis, and acute kidney injury
كالسيوم،كلية،الكالوز
• Calcium intake in patients typically exceeds 4 g/day