Parathyroid Hormone and Calcium Homeostasis

~0.1%

What approximate percentage of total body calcium is located in the extracellular fluid?

Bone

Besides extracellular fluid and cells, where is the majority of total body calcium stored?

Not nearly as well regulated as calcium concentration

How does the regulation of total body phosphate compare to the regulation of calcium concentration?

<1%

What approximate percentage of total body phosphate is found in the extracellular fluid?

85%

What percentage of total body phosphate is stored in bones?

~41%

Approximately what percentage of calcium in plasma is bound to proteins and thus non-diffusible?

~9%

Roughly what proportion of plasma calcium is combined with anionic substances such as citrate and phosphate?

50%

What percentage of calcium in plasma is ionized and diffusible?

1.2 mmol/L

What is the normal concentration of ionized calcium (iCa) in plasma?

Ionized and diffusible form

Which form of calcium in the body is most important for physiological functions?

HPO4= (hydrogen phosphate) & H2PO4− (dihydrogen phosphate)

In what two main forms does inorganic phosphate exist in plasma and interstitial fluid?

Increase in H2PO4- and Decrease in HPO4=

How do the proportions of HPO4= and H2PO4− change when the pH of the extracellular fluid becomes acidic?

Opposite occurs when alkaline

What happens to the levels of HPO4= and H2PO4− when the pH of the extracellular fluid becomes alkaline?

mg of phosphorus per dL of blood

In what unit is the total quantity of inorganic phosphate in extracellular fluids typically expressed?

3-4 mg/dL

What is the average range of inorganic phosphorus in blood?

Not cause major immediate effects

How do changes in phosphate levels generally affect the body in the short term?

Extreme immediate effects

How do slight changes in extracellular fluid calcium levels generally affect the body?

Nervous system progressively excitable → carpopedal spasm → tetany; QT prolongation

What are the key immediate effects of hypocalcemia on the nervous system and cardiac function?

Depress nervous system → sluggish CNS reflexes; shortened QT, constipation

What are the major immediate effects of hypercalcemia on the nervous system, cardiac function, and the gastrointestinal system?

Poorly absorbed

How well is calcium and phosphate absorbed in the intestines?

Only 10% excreted

What is the approximate percentage of filtered calcium and phosphate that is excreted by the kidneys?

90% reabsorbed in PCT, Loop of Henle, early DCT

Where in the nephron is the majority of filtered calcium and phosphate reabsorbed?

Cortical (compact) & trabecular (spongy)

What are the two general types of bone?

Hard outer layer (denser)

Describe the general structure and density of cortical bone.

80%

What percentage of total bone mass does cortical bone constitute?

Thick in shaft of long bones

Where in long bones is cortical bone particularly thick?

Interior (porous)

Describe the general structure of trabecular bone.

20%

What percentage of total bone mass does trabecular bone represent?

Ends of long bones, near joints, interior of vertebrae

Where are the primary locations of trabecular bone?

Hematopoiesis

What important process occurs in the spaces between trabeculae?

Higher bone turnover rate than cortical bone

How does the bone turnover rate of trabecular bone compare to that of cortical bone?

30% Organic 70% Inorganic

What are the approximate proportions of organic and inorganic components in the bone matrix?

Collagen Fiber (90-95%)

What is the main organic component of the bone matrix?

Hydroxyapatite

What is the primary inorganic component of bone?

Collagen Fiber and Calcium Salts

Which components of bone provide it with great tensile and compressional strength?

Osteoblasts

Which type of bone cell is responsible for secreting collagen monomers and proteoglycans?

Collagen fibers

What is formed when collagen monomers and proteoglycans polymerize?

Osteoid

What is the unmineralized organic matrix of bone called?

Osteocytes (quiescent stage)

What are osteoblasts called once they become embedded in the bone matrix?

Calcium salts

What precipitates to form hydroxyapatite crystals in bone calcification?

Pyrophosphate

What substance inhibits hydroxyapatite crystallization?

Amorphous salt and Hydroxyapatite crystals

What are the two main forms of calcium found in bone?

Amorphous salt

Which form of bone calcium is more readily mobilizable and in equilibrium with ECF calcium ions?

0.4-1.0%

What approximate percentage of total bone calcium is considered exchangeable?

Rapid buffering mechanism

What role does the exchangeable calcium in bone play in calcium homeostasis?

Osteoblasts

Which type of bone cell is responsible for forming new bone?

Outer surfaces of bones and trabecular cavities

Where are osteoblasts primarily found?

Osteoclasts

Which type of bone cell is responsible for the resorption of bone?

Large, phagocytic, multinucleated cells

Describe the key characteristics of osteoclasts.

Derivatives of monocytes or monocyte-like cells

From what type of cell do osteoclasts originate?

Proteolytic enzymes and Citric and lactic acid

What are the two main mechanisms by which osteoclasts resorb bone matrix and salts?

PTH (parathyroid hormone)

What hormone primarily regulates the activity of osteoclasts?

Osteoblasts

Which cells signal osteoclast precursors to form mature osteoclasts?

Receptor activator for nuclear factor κB ligand (RANKL) and Macrophage colony-stimulating factor

What are the two key osteoblast proteins involved in signaling osteoclast maturation?

Adjacent osteoblasts

To which cells does PTH bind to stimulate RANKL production?

Preosteoclast

On which cells does RANKL bind to promote the formation of mature osteoclasts?

Osteoprotegerin (OPG)

What cytokine produced by osteoblasts inhibits bone resorption by acting as a decoy receptor for RANKL?

Bone mass remains constant

What is the normal balance between bone deposition and resorption in adults (excluding growing bones)?

Osteocytes

Which bone cells are involved in the initial phase of bone remodeling by eating away bone?

~3 weeks

Approximately how long does it take for osteocytes to create a tunnel during bone remodeling?

Osteoblasts

Which cells invade the tunnel created by osteocytes and lay down new bone?

Lamellae

In what structural arrangement is new bone laid down in the tunnel during remodeling?

Haversian canal

What is the central channel within an osteon that contains blood vessels?

Osteon or Haversian system

What is the structural unit of compact bone, consisting of lamellae and a central canal?

7-dehydrocholesterol

What is the precursor molecule in the skin that is converted to previtamin D3 upon UV exposure?

Previtamin D3

What is the immediate product of 7-dehydrocholesterol conversion in the skin?

Vitamin D3 (cholecalciferol)

What is formed from previtamin D3 in the skin?

Liver

In which organ does the first hydroxylation of vitamin D3 occur?

Calcidiol (25-hydroxyvitamin D or 25(OH)D)

What is the product of the liver's hydroxylation of vitamin D3?

25-hydroxylase enzyme

Which enzyme in the liver catalyzes the conversion of vitamin D3 to calcidiol?

Strong feedback effect mechanism

How is the liver's conversion of vitamin D3 to calcidiol regulated?

Kidney

In which organ does the second hydroxylation of calcidiol occur to form the active form of vitamin D?

Calcitriol (1,25-dihydroxyvitamin D or 1,25(OH)2D)

What is the biologically active form of vitamin D?

1α-hydroxylase enzyme

Which enzyme in the kidney catalyzes the conversion of calcidiol to calcitriol?

PTH

What hormone is required for the kidney's conversion of calcidiol to calcitriol?

Kidneys

Where is calcitriol inactivated?

24-hydroxylase enzyme

Which enzyme is responsible for the inactivation of calcitriol in the kidneys?

Intestinal calcium & phosphate absorption

What is a primary action of vitamin D on the intestines?

Renal calcium & phosphate reabsorption

What is a key action of vitamin D on the kidneys?

Bone resorption

What effect can extreme quantities of vitamin D have on bone?

Bone calcification

What effect can small quantities of vitamin D have on bone?

4

How many parathyroid glands are typically located posterior to the thyroid gland?

Difficult to locate during operation

What is a common challenge regarding the parathyroid glands during surgery?

No major abnormalities

What is the usual consequence of removing half of the parathyroid glands?

Transient hypoparathyroidism

What typically occurs if 3 out of 4 parathyroid glands are removed?

Hypertrophy

What can happen to a small remaining amount of parathyroid tissue after significant removal?

Chief cells

Which type of cell in the parathyroid glands secretes the majority of PTH?

Oxyphil cells

What is the other type of cell found in the parathyroid glands besides chief cells?

Unknown function; modified or depleted chief cells

What is currently understood about the function of oxyphil cells?

Pre-pro-PTH (110 AA)

What is the initial form of parathyroid hormone synthesized on ribosomes, and how many amino acids does it contain?

ER and Golgi

In which cellular organelles is pre-pro-PTH cleaved into pro-PTH?

Pro-PTH (90 AA)

What is the intermediate form of parathyroid hormone, and how many amino acids does it have?

Intact PTH (84 AA)

What is the mature, secreted form of parathyroid hormone, and how many amino acids does it contain?

Secretory granules

Where is intact PTH finally packaged before secretion?

Few minutes

What is the approximate serum half-life of PTH?

Activation of already existing cells (mainly osteocytes)

What is the primary cellular mechanism of the rapid phase of PTH action on bone?

Osteolysis

What term describes the PTH-mediated removal of calcium phosphate salts from the amorphous bone salts?

Bone fluid → osteocytic membrane → ECF

Describe the movement of calcium ions during the rapid phase of PTH action on bone.

Activation & proliferation of osteoclasts

What is the main cellular event during the slow phase of PTH action on bone?

Activated osteoblasts and osteocytes

Which cells send secondary signals to osteoclasts via RANKL during the slow phase of PTH action?